1
Systematic Review
The effectiveness of non-pharmacological interventions on fatigue in children and adolescents with cancer a systematic review
First Reviewer
Chi-Wen Chang RN PhD candidate School of Nursing National Yang-Ming University and Instructor School of Nursing Chang Gung University Taipei Taiwan R OC Taiwan A collaborating centre of the Joanna Briggs Institute Email cwchangmailcguedutw Second Reviewer Pei-Fan Mu RN PhD Professor and Deputy Academic Dean School of Nursing National Yang-Ming University Taipei Taiwan R OC Taiwan Joanna Briggs Institute Collaborating Centre
Third Reviewer Shiann-Tarng Jou Assistant professor Visiting Staff Department of Pediatrics National Taiwan University Hospital Taipei Taiwan R OC
Fourth Reviewer Tai-Ting Wong Division of Pediatric Neurosurgery Department of Neurosurgery Neurological Institute Veterans General Hospital Taipei Taiwan R OC
Fifth Reviewer Yu-Chih Chen RN PhD Director Department of Nursing Taipei Veterans General Hospital amp Adjunct Associate Professor School of Nursing National Taipei University of Nursing and Health Sciences Taipei Medical University and National Defense Medical Center
Contact Reviewer Pei-Fan Mu RN PhD Professor and Deputy Academic Dean School of Nursing National Yang-Ming University Taipei Taiwan R OC Taiwan Joanna Briggs Institute Collaborating Centre
Executive Summary Background Fatigue is one of the most distressing and prevalent symptoms reported by
pediatric oncology patients With the increase in cancer survival rate how to control
childrenrsquos cancer-related fatigue during treatments or the coexisting period with the
disease to further increase their quality of life has become the focus of medical teams
who provide care to children with cancer
634
2
Objectives The objective of this systematic review was to determine the best available
evidence concerning the effectiveness of non-pharmacological interventions on fatigue in
children and adolescents with cancer
Search strategy The search strategy aimed to find studies published between 1960 and
2010 in either the English or Chinese languages Reference lists of studies that met the
inclusion criteria were also searched for additional studies
Types of studies This review included randomised controlled trials and
quasi-experimental studies that examined the effectiveness of non-pharmacological
interventions for fatigue in children and adolescents with cancer
Types of participants Children and adolescents aged from 1 to 18 years old with
cancer either during or after the chemotherapy The types of cancer included were Acute
lymphoblastic leukemia Acute myeloid leukemia lymphoma and solid tumors
Types of interventions This review considered studies that examine
non-pharmacological interventions on fatigue for children and adolescents with cancer
including activity enhancement (exercise physical activity) psychosocial interventions
cognitive behavioral therapy stress management relaxation nutrition consultation
massage and educational interventions The intervention descriptions included the length
frequency setting and intervention providers
Types of outcome measures The outcome measures considered fatigue scores
assessment
Types of setting The review focused on studies that conducted either in a hospital or a
community setting
Data collection and synthesisThe data were extracted using the standardised data
635
3
extraction tool from the Joanna Briggs Institute-Meta-Analysis of Statistics Assessment
and Review Instrument
Results
The review included a total of six studies - five English-language papers and one
Chinese-language paper Meta-analysis did not show statistically significant impact on
the effectiveness of exercise interventions in reducing fatigue in children and adolescents
with cancer The impact of the exercise interventions on general fatigue did however
indicate a statistically significant difference (p = 001 95 Confidence Interval -135 to
-017)
Conclusions
The results of this systematic review show that exercise interventions can effectively
reduce the level of general fatigue of children six to 18 years No strong conclusions
can be made for the use of massage therapy or health education measures as there
was only one article for each of these interventions
Implications for practice The review provides an evidenced-based guide to future priorities for clinical practice
Exercise intervention could reduce the level of general fatigue of children who ages are
six to 18 In particular exercise intervention for fatigue are feasible and safe
Implications for research There is still a lack of rigorous research on this specific topic Further research requires
more rigorous study design and reporting of menthdologic issues such as randomized
controlled trials using concealment of allocation Other non-pharmacological
interventions should be also examined including cognitive behavioral therapy stress
management relaxation support groups massage therapy in this area
636
4
Keywords non-pharmacological intervention fatigue children adolescents cancer
exercise cognitive systematic review
BACKGROUND
The Clinical Practice Guidelines in Oncology of the National Comprehensive Cancer
Network (NCCN) in the USA define cancer-related fatigue as ldquoa distressing persistent
subjective sense of physical emotional andor cognitive tiredness or exhaustion related
to cancer or cancer treatments that is not proportional to recent activity and interferes
with daily functionrdquo(pFT-1)1 When children suffer from cancer fatigue is not only the most
consistently reported symptom by children with cancer but also one of the most
persistent and uncomfortable symptoms 2
The incidence of cancer in children is high across the world As an example the
incidence in the USA for children aged 0-14 years is approximately 129 per million with
an estimated projection of 8200 newly diagnosed cases per year3 In Taiwan
approximately 550-600 children are diagnosed with cancer every year4 According to the
estimation of group proportions the incidence of childhood cancer in Taiwan and the
United States are similar 5 In addition malignant tumor has become the second leading
causes of death for children and adolescents aged 1-14 years in Taiwan3 and US6
Although cancer has been one of the major illnesses threatening the life of children the
progress made in medical technology has led to a significant improvement in the
treatment of children and adolescents with cancer over the past three decades7
especially the increase in their survival rate Statistics have indicated that the five-year
637
5
survival rate of children with cancer has exceeded 756 however the treatments of
cancer tend to rely on aggressive chemotherapies which force children to face a long
treatment process as well as various physical and mental symptoms8 Fatigue is one of
the common symptoms affecting children during treatments Children may feel persistent
fatigue even after they complete cancer treatments9
To date the causes and mechanism of cancer-related fatigue are still unclear However
the theories concerning the causes of fatigue have been proposed Common theories
include Integrated Fatigue Model10 Psychobiological Entropy Model11 Energy Analysis
Model12
Piper et al (1987) 10 proposed the Integrated Fatigue Model which is one of the most
frequently cited fatigue models at present They suggest that fatigue is the tiredness felt
by individuals as a result of the influence of body rhythm which makes individuals
experience different degrees of discomfort In this model fatigue can be measured by
biochemical indicators such as cytokines interferon and tumor necrosis factors as well
as with a self-report fatigue scale
The term ldquoIntegratedrdquo refers to a combination of features including perception physics
biochemistry and behavior all of which affect level of fatigue and in turn influence
fatigue patterns including diseases treatments activitiesrests environment symptoms
social activities life events individual internal factors and other aspects of the patients
life
The second theory is the Psychobiological Entropy Model11 is the most complete fatigue
638
6
theory at present This model suggests that the main cause of fatigue is a lack of energy
The physical ability of patients is reduced because of the symptoms caused by diseases
or treatments and thus patients experience emotion-related fatigue and the reduction in
functional status as a result In addition the symptoms caused by reoccurring diseases
or treatments may be harmful to physical conditions even more and lead to disability
eventually In this model any treatment program that can address the decline in activity
can alleviate fatigue symptoms is said to improve fatigue Therefore Psychobiological
Entropy Model not only provides a more direct detection of clinical patterns but also for
providing measures of care within a fatigue model
The third model is the Energy Analysis Model12 which suggests that the pathological
change of individual physical status becomes the barrier of energy conversion When the
supply of energy in individuals is low or the demand is high a lack of energy results and
the individuals feel fatigue Energy is generated by the oxygenation in blood The
correction factors of energy reaction are cancer treatments symptom distress and
emotional disorders Concepts in the fatigue model include energy sources energy
transformations energy expenditures and energy response modifiers The relationships
among these concepts are dynamic and intercorrelated with each other From the Energy
Analysis Mode point of view the physiological mechanism of fatigue includes some
objective indicators such as body weight and hemglobulin
In terms of the causes of fatigue Ekti Genc amp Conk (2008) 2 indicated that illnesses
treatments and stage of disease can cause fatigue NCCN (2011) 1 points out that many
conditions are related to fatigue including pain emotional pain anaemia sleep disorders
639
7
nutritional deficiencies activity reduction side effects of drugs (antihistamine drugs
anti-vomiting drugs and anti-anxiety drugs) and others In a study on children
adolescents parents and relevant medical and nursing staffs Hinds and
Hockenberry-Eaton (2001) 13 proposed four factors causing the fatigue of children with
cancer which are 1) environmental factors treatment setting events or situations that
place demands on the patient such as appointments inpatient stay long waiting time
altered routines that lack clear beginnings and endings of each day and decision making
and information exchange 2) personalbehavioral factors the negative faith of children
with illness 3) culturalfamilyother factors emotions concerns the hope of friends and
family ability to participate in activities and restricted activities 4) treatment-related
factors the invasive inspections experienced by children with illness insufficient time for
physical strength recovery between the repeated courses of treatments or the side
effects caused by treatments (infection pain and decrease in complete blood count) It
can be inferred that the causes of fatigue are complicated and multifaceted
Fatigue is a complex and multidimensional condition 10 therefore fatigue is subject to
different definitions and there are different measurement tools Aaronson et alrsquos14
review the literature of fatigue summarised the characteristics of fatigue measurement
including the following(1) Subjective quantification of fatigue can be determined with the
Lee and colleagues (1991) Visual Analog Scale for Fatigue (VASF)(2) Subjective
distress This item simply asks the rater to report to what degree fatigue has caused
distress (3) The effect of fatigue on activities of daily living (4) Correlates of fatigue
such as sleep and depression to assess when measuring fatigue (5) key biological
parameters such as cytokines interferon and tumor necrosis factor
640
8
Fatigue can be also measured with unidimensional or multidimensional scales The first
type of fatigue scale is not suitable for studies focusing on fatigue because they are too
long if the aim is to only assess fatigue Furthermore they only allow for a limited number
of possible responses Unidimensional scales also are not suitable for the in-depth study
of fatigue because they assess only one aspect of fatigue15
In recent years fatigue in children with cancer has received some attention and
measurement tools have gradually been developed - such as1) Checklist individual
strength (CIS) The items are scored on 7-point Likert scales (with 1 indicating best and
7 worst function) 2) The Child Fatigue Scale (CFS) is a 2-part questionnaire that asks for
a yes or no (frequency) response and a 5-point rating of the intensity of any yes
responses ranging from not at all to a lot The Fatigue Scale for 7-12 year Olds (FS-C)
is provide a fatigue intensity score higher scores indicating higher fatigue The Fatigue
Scale for 13-18 year Olds (FS-A) measure adolescent cancer patientsrsquo perceptions of
the intensity of their fatigue on a daily or weekly basis higher scores indicating higher
fatigue 3) The Fatigue Scale Parent Version (FS-P) measures the parentsrsquo perception
of their childrsquos fatigue intensity on a five-point Likert-type scale higher scores indicating
higher fatigue 4) The Fatigue Scale Staff Version (FS-S ) measures the staffrsquos
perceptions of the patientrsquos fatigue intensity during the past 24 hours Intensity ratings are
on a four-point Likert-type scale with higher scores indicating more intense fatigue
symptoms 5) The Pediatric Quality of life Multidimensional Fatigue Scale (Peds
QL-MFS)Higher scores (0 to 100) indicate less fatigue( Appendix IV)
Besides disturbing physical and mental functions and status fatigue also affects the
641
9
quality of life 15 of children with cancer and impacts their daily life16 among all different
types of cancer progress and childrsquos ages However as opposed to the fatigue of adults
the fatigue of children tends to be neglected and left untreated17 by medical and nursing
staffs
In terms of the management approach to cancer-related fatigue Ekti Gene (2008) 2
suggests that strategies could include pharmacologic and non-pharmacologic measures
NCCN (2011) 1 indicated in the Clinical Practice Guidelines in Oncology that during
aggressive treatments during long-term follow-up treatments or in the terminal phase of
cancer the intervening measures for cancer-related fatigue can be divided into
pharmacologic and non-pharmacologic measures Non-pharmacologic measures include
activity enhancement psychosocial interventions (eg cognitive behavioral therapy
(CBT) stress management relaxation support groups) attention-restoring therapy and
nutrition consultation As for the effectiveness of pharmacological measures the
effectiveness is still uncertain However there is evidence to suggest that
methylphenidate may be effective in treating cancer-related fatigue1 Whiting et al
(2001)18 included 36 randomized controlled trials and 8 controlled trails to assess the
effectiveness of the pharmacological and non-pharmacological interventions used in the
treatment or management of chronic fatigue syndrome in adults or children Results
showed insufficient evidence on the effectiveness of the pharmacological supplements
complementaryalternative and other interventions In addition the evidence of
pharmacological treatments of immunoglobulin and hydrocortisone were also
inconclusive However interventions such as cognitive behavioral therapy and graded
exercise therapy have shown promising results
642
10
The efficacy of pharmacological treatments for cancer-related fatigue has not been
established6 therefore there is a need to provide evidence-based findings of the
effectiveness of non-pharmacological interventions to support nursing intervention to
release the childrsquos cancer-related fatigue To date most studies have investigated the
effectiveness of non-pharmacological treatments on cancer-related fatigue of
adults20and to date there is no systematic review in relation to cancer-related fatigue of
children However as children are not a smaller version of adults it is inappropriate to
extrapolate the results of adults onto children Therefore there is a need to establish the
effectiveness of non-pharmacological intervention on the cancer-related fatigue of
children
Given the increase in childhood cancer survival rate the importance of decreasing
childrenrsquos cancer-related fatigue during treatments and so increase their quality of life has
become a focus of their medical teams The role of nurses during care intervention is to
confirm the major symptoms of children with illness and effectively treat each symptom to
increase the childrenrsquos quality of life21 Moreover the USA based NCCN also indicated in
the Care Standard for the Treatment of Cancer-related Fatigue of Children and
Adolescents that treatments for fatigue should be included in the health care teams and
the children and their family should be informed of relevant information The definition of
non-pharmacological interventions for childrenrsquos cancer ndashrelated fatigue include activity
enhancement (exercise physical activity) psychosocial interventions cognitive
behavioral therapy (CBT) stress management relaxation nutrition consultation
massage and educational interventions
643
11
The Cochrane Library of Systematic Reviews and The Joanna Briggs Institute Library of
Systematic Reviews were initially searched to ensure that systematic reviews on this
subject were not already published or being undertaken This initial search prior to the
commencement of the review did not yield any results
This systematic review has examined the effectiveness of non-pharmacologic
interventions on the cancer-related fatigue of children in hope of finding scientific
evidence that can support or refute such measures on children The results of this study
may serve as a reference for professional caregivers children with cancer and their
families or to be put into practice during the clinical care of children with cancer
Definition of terms
FatigueFatigue as a distressing persistent subjective sense of physical emotional
andor cognitive tiredness or exhaustion related to cancer or cancer treatments
that is not proportional to recent activity and interferes with daily function1 There
are various scales and measurements of the degree of fatiguewe have elected to
use the study authors own definitions of fatigue rather than applying a single
pre-set definition of the condition
Non-pharmacological interventionsReferring to reduce fatigue that does not involve
drugsNon-pharmacologic measures include activity enhancement psychosocial
interventions (eg cognitive behavioral therapy stress management relaxation
support groups) attention-restoring therapy and nutrition consultation1
ChemotherapyTreatment with drugs that kill cancer cells 1
644
12
Review QuestionsObjectives
Review Objective
The objective of this systematic review was to critically appraise synthesize and
present the best available evidence concerning the effects of non-pharmacological
interventions fatigue in children and adolescents with cancer
Review Question
The following specific question was addressed in this review
What is the effectiveness of non-pharmacological interventions on fatigue in
children and adolescents with cancer aged from one to 18 years
Criteria for Considering Studies for this Review
Types of studies
This review included randomised controlled trials (RCTs) and quasi-experimental
studies that examine the effectiveness of non-pharmacological intervention for fatigue in
children and adolescents with cancer
Types of participants
Children and adolescents aged from one to 18 years old experiencing fatigue
associated with cancer either during or after the chemotherapy or maintenance stage of
chemotherapy or survive stage The types of cancer to be included in this systematic
review will be ALL (Acute lymphoblastic leukemia) AML (Acute myeloid leukemia)
lymphoma and solid tumors
Exclusion criteria for Types of participants
645
13
newborn infants under 1 years of age
participants who do not have a specific diagnosis of cancer
participants who have received immunoglobulin or hydrocortisone
treatment
If participants have received immunoglobulin or hydrocortisone treatment may
inference the effectiveness of non-pharmacological interventions on fatigue
Types of intervention
This review considered studies that examine non-pharmacological interventions on
fatigue for children and adolescents with cancer including activity enhancement
(exercise physical activity) psychosocial interventions CBT stress management
relaxation nutrition consultation massage and educational interventions The
interventions descriptive included the length frequency setting and intervention
providers eg Nurse Psychologist Dietician
Exclusion criteria for types of interventions only pharmacological interventions were
tested
Types of outcome measures
The outcome measures considered were fatigue scores The literature demonstrates that
differences of opinion exist regarding the most valid and reliable method of measuring
cancer-related fatigue Therefore studies that used any validated scale for
cancer-related fatigue were considered for inclusion Currently commonly used scales to
measure fatigue include Checklist Individual Strength (CIS) Child Fatigue Scale (CFS)
The Fatigue Scale for 7-12 year Olds (FS-C) The Fatigue Scale for 13-18 year Olds
646
14
(FS-A)and Pediatric Quality of life Multidimensional Fatigue Scale (Peds QL-MFS)
Types of settings
Both hospital and community settings
Search Strategy
Before undertaking this systematic review the Cochrane Library Joanna Briggs Institute
Library of Systematic Reviews and CINAHL were searched and no systematic reviews on
this topic were found or identified as underway
The search strategy aimed to find both published and unpublished studies
A three-step search strategy was utilized in each component of this review An initial
limited search of CINAHL and MEDLINE was undertaken followed by an analysis of the
text words contained in the title and abstract and of the index terms used to describe the
article A second search using all identified keywords and index terms was undertaken
Lastly the reference lists of all identified reports and articles were searched for additional
studies
Types of languages
1 English
2 Chinese
The following databases were searched to identify keywords contained in the title and
abstract and relevant MeSH headings and descriptor terms
The Cochrane Library PsycINFO 1990 ndash 2010
647
15
Ovid MEDLINE 1966 ndash 2010 CINAHL Plus with Full Text 1960 ndash2010 EMBASE ProQuest Dissertations amp theses 1990-2010 Electronic theses and dissertations system 1956(abstract)1990(full text)-2010 MEDNAR Index to Taiwan periodical literature 1970-2010 Electronic thesis and dissertation system (Chinese) 1990-2010
Keyword search terms
1Types of studies experimental study random quasi-experimental study實驗性研究隨
機類實驗性研究
2 Types of participants childchildren adolescents pediatric cancer and oncology兒童
青少年兒科癌症腫瘤
3 Types of interventions non-pharmacological interventions massage exercise fitness
physical activity cognitive behavioral stress management energy conservation
sleep therapy relaxation distraction and psycho-education非藥物性處置按摩運動
身體活動認知行為壓力處置能量保存睡眠治療放鬆轉移注意力衛教
4 Types of outcome measures fatigue cancer-related fatigue loss of energy levels of
tiredness tired side effect symptoms疲憊癌性疲憊疲倦合併症症狀
Methods of the Review
Assessment of methodological quality Papers selected for retrieval were assessed by two independent reviewers for
methodological validity prior to inclusion in the review using the standardised critical
appraisal instruments (Appendix I) from the JBI-SUMARI (Joanna Briggs Institute
Systems for the Unified Management Assessment and Review of Information package)
Any disagreements that arise between the reviewers were resolved through discussion
648
16
with a third reviewer
Data extraction Data was extracted from papers included in the review using standardised data
extraction tool (Appendix II) from the JBI-SUMARI Details of eligible studies were
extracted and summarised independently by two reviewers
Data Synthesis
All data analysissynthesis were made using the JBI-SUMARI The studies were
assessed for clinical heterogeneity by considering the settings populations interventions
and outcomes Where possible these binary outcomes were analyzed by calculation of
the Odds Ratio with the 95 CI The weighted mean difference was calculated if the
pooled studies have used the same scale for continuous data The standardized mean
difference was calculated for continuous data measuring the same outcome on a
different scale In studies where statistical pooling of results was inappropriate the
findings were considered for inclusion as a narrative summary
Results The findings from the systematic review are presented first Followed by the results from
the meta-analysis component of this review
Description of studies From database search and hand search a total of 76 papers were identified Thirty
papers were then excluded because they did not meet the inclusion criteria Forty-six
full text were retrieved for further consideration for inclusion Of the 30 excluded reasons
for exclusion were follows 11articles were duplicated eight articles did not meet
649
17
participant inclusion criteria eight articles did not meet outcome criteria and nine articles
were correlation studies or discussion papers others articles were unclear reporting In
total after sorting six papers have been included in this article Figure 1 displays the
process used to identify relevant articles for inclusion in the systematic review
Figure 1 Stages of searching and inclusionexclusion of references for the review
Potentially relevant English-language and Chinese- language Studies Identified
Electronically and hand search (n=76)
Duplicate (n= 11) Papers excluded after evaluation of abstract (n=19)
Papers retrieved for detailed examination (N=46)
Papers excluded after review of full paper
(n=40)
Papers assessed for methodological
quality (n=6)
Papers included in systematic review
(n=6)
Methodological Quality
Of the six included articles 2722232425 two articles were RCT design224 with score 7 out
of 10 each paper from Critical Appraisal Checklist and four articles used
650
18
quasi-experimental design7222425 with socre 5 to 6 out of 10 because the quality of
the whole papers is still acceptable therefore these six articles were accepted after
primary reviewer and secondary reviewerrsquos decision
Randomisation
In two RCT articles224 one study24 used to a computer-generated program operated by
the St Jude Protocol and Data Management System to randomize the sample Another
study2 didnrsquot address how randomization was done
Allocation concealment
No studies reported allocation concealment
Intention-to-treat analysis
One quasi-experimental design7 stated Intention-to-treat analysis
Adequate follow up
The follow-up periods included 2or 3 days24 7 days2 4 week7 one month25 6 week25 12
week2216 week23 and 1 year23
Baseline comparability of groups
Three 22425 of six studies had baseline comparability in terms of age sex diagnosis
race institution duration of illness
Blinded outcome assessment
No studies used blinded outcome assessment The researchers including study team
patients staff and families were not blinded to the patientrsquos group assignment
Characteristics of included studies
651
19
There were six studies related to interventions designed to cancer-related fatigue for
pediatric patients than there are for adults There are a total of six including five
English-language papers 27222324 and one Chinese-language paper 25 ranging in year of
publication from 2007 to 2009
Patient characteristics
The research subjects of four papers included both school-aged children and
adolescents 7222324 one papers involved mainly adolescents25 and one paper sampled
only school-aged children 2 the range in ages was between six-18 years The number of
patients included in the samples ranged from nine to 60 The sources of case data were
from both outpatients and hospitalized children The types of cancer included acute
lymphoblastic leukemia (ALL) solid tumors acute myeloid leukemia (AML) and
lymphoma Overall ALL was the most commonly studied cancer type The stage of the
disease varied in these reports some patients were in the maintenance stage of
chemotherapy25 some had just received their first round of chemotherapy224 some had
completed two courses of treatments lasting 4-8 weeks each 7 and some had entered
the survivor stage 2223
Countries
Two RCTrsquos 2 24 were conducted in the USA There were four quasi-experimental design
studiesThree studies conducted in the USA7 22 23 and one in Taiwan25
Intervention types
652
20
The interventions included exercise training programs 2225 physical activity 2324
massage therapy 7 and health education 223 exercise training and physical activity as
an intervention method given in three different settings home 22 25 community 23 or
hospital 24 The studies used different types of exercise interventions including
home-based aerobic exercise use a Video Compact Disc 25 use of a bicycle-style
exerciser 24 aerobics2223 and various types of physical activities2 and strength-building
exercises 2223 The intensity of the exercise varied and often included gradual warm-up
exercises a period of main exercise and a cool down period For these studies2023 the
target exercise intensity was a heart rate of gt90 of the maximum heart rate (HR max) or
the increase in the percentage of heart rate reserve ( HRR) of 40-60
The number of weeks for the exercisephysical activity interventions duration including
2-4 days 24 6 weeks25 12 weeks22 and 16 weeks23 The frequency of exercise ranged
from 2-3 times per week to twice a day Typical duration of exercise ranged from 10 to 45
minutes There are three papers using exercise interventions based on ACSM (American
College of Sports Medicine) 2225 recommendations and one of these used an Activity
pyramid from the ACSM to determine intensity 24
One article did not clarify the type of exercise intervention or the reasons for their choices
23 In addition there was an article focusing on massage therapy 7 as an intervention in
this study the experimental group received four weeks of massage therapy either in the
clinic or in the patientrsquos room the therapy was applied by a professional masseur and
targeted the back legs arms chest stomach and face of the children However the
frequency of massage sessions per week and the duration of the massages were not
653
21
given There is another article about intervention measures combine health education
and physical activity 2 In this study patients were informed about the following (1) health
education patients received daily education about chemotherapy-related fatigue and
information from a health education manual written by the author (2) encouragement for
children to engage in activities such as listening to music drawing and reading and (3)
physical activity which involved walking along the corridors of the ward for 10-15 minutes
These health education measures were presented for 45-60 minutes a day for a total of
seven days The study design for non-pharmacological interventions used control groups
that included primarily people who had received standard treatment or people who did
not receive an exercise intervention
Outcome measures
Five measurement tools were used in this group of seven papers concerning childrenrsquos
fatigue (Appendix IV) Because those studies included both school-age children and
adolescents the following descriptions will be differentiated by age Fatigue
measurements for school-aged children with cancer include the following the Child
Fatigue Scale (CFS) 7 a scale that measures the frequency and intensity of fatigue and
the Fatigue Scale for 7-12 year Olds (FS-C) 224 a scale that can be used to evaluate the
intensity of fatigue On the other hand fatigue measurements for adolescent cancer
patients include the following the Fatigue Scale for 13-18-year-olds (FS-A) 24 a measure
that can help evaluate fatigue levels the Pediatric Quality of Life Multidimensional
Fatigue Scale (Peds QL-MFS) 2325 a tool that can be divided into three sub-scales to
understand the general cognitive and sleep rest components of fatigue and finally the
CIS-20 for school-age children and adolescents 22 a scale that measures four levels of
654
22
fatigue namely subjective experience attention motivation and physical activity Two
studies used the Peds QL-MFS scale to measure fatigue2325
Meta-analysis results Two studies of the included papers failed to provide sufficient raw data they could not be
included in the meta-analysis Hinds et al 24 did not include post-test data Genc et al 2
provided no pre-test data PostWhite et al7 reported that fatigue after the health
education intervention was not statistically different but they presented the results
without presenting fatigue-related data Therefore the meta-analysis included three
studies 222325
The heterogeneity of studies was analyzed with Chi square statistics and no statistical
significance was found Therefore the data was combined in meta-analysis according to
exercise intervention on fatigue In addition there were three articles using the Peds
QL-MFS as a research tool to examine childrenrsquos improvements in fatigue Among these
Keats 22 and Chiang 24 present the effectiveness of exercise interventions using three
subscales Therefore the meta-analysis also analysis of the effects of these exercise
intervention measures on three subscales of Peds QL-MFS general fatigue sleep rest
fatigue and cognitive fatigue
The effectiveness of exercise intervention for fatigue We analyzed the exercise intervention effect on fatigue A total of 2 studies 22 23 were
included Takken et al 22 used community-based exercise training program to reduce
fatigue of children 6 to 14 years (mean 93y) of age who survived ALL Fatigue
measurement by Checklist Individual Strength (CIS) after 12-week of training fatigue
655
23
show no significant differences between pre (meanplusmnSD 415plusmn147) and post training
(meanplusmnSD368plusmn217) but fatigue change from baseline mean reduction of 11
Keats et al23 although used community-based physical activity program to reduce fatigue
for adolescents 14 to 18 years of age (mean162 y) with cancer (Lymphoma leukemia CNS
tumor germ cell tumor) Studies used fatigue by PedsQLMFS Results show general fatigue
from baseline to 8 weeks and to 3 months follow up significantly improves General
fatigue sleeprest fatigue and total fatigue from baseline to 3 months follow up showed
significant improvements Sleeprest fatigue and total fatigue at 1 years followed up were
significant improvements
Figure 2 shows the overall effect of exercise intervention in children and adolescents with
cancers with a focus on improving fatigue Due to the lower heterogeneity (p>005) the
fixed effects model was used to pool the data for meta-analysis (Overall effect size=
-006 95 Confidence Interval (CI) -070 to 058) A result did not indicate a statistically
significant difference (p = 087)
656
24
Figure2 Meta-analysis results of exercise intervention on fatigue
In addition Keats23 and Chiang25 used the three sub-scales of Peds QL-MFS to
determine the general cognitive and sleep rest components of fatigue The following
present the effectiveness of exercise interventions using three subscales including
general fatigue sleep rest fatigue and cognitive fatigue 2325
Chiang et al 25 used a 6- week home-based aerobic exercise intervention to reduce
fatigue of children 7 to 18 years (mean age at experimental group was 1088 y in control
group was 1247 y) of age who with acute lymphoblastic leukemia Fatigue measurement
by Peds QL-MFS after training For intent-to ndash treat analysis the findings indicated that
there are no intervention effects and time differences by any items on the subscale of
fatigue For per-protocol analysis general fatigue( meanplusmnSD 422plusmn402) was the only
subscale that was significantly lower for children who received the exercise intervention
than those in control group at follow-up assessment (one month after the completion of
intervention)
Keats et al23 although used community-based physical activity program to reduce fatigue
for adolescents 14 to 18 years of age (mean162 y) with cancer (Lymphoma leukemia
CNS tumor germ cell tumor) Both studies used fatigue by PedsQLMFS Results show
general fatigue from baseline to 8 weeks and to 3 months follow up significantly improves
657
25
General fatigue sleeprest fatigue and total fatigue from baseline to 3 months follow up
showed significant improvements Sleeprest fatigue and total fatigue at 1 years followed
up were significant improvements
The effectiveness of exercise intervention for general fatigue
The impact of the exercise interventions upon levels of general fatigue was also analysed
The heterogeneity was low (p>005) Therefore the fixed effects model was used to
examine the effectiveness The effect size is -076 indicating a statistically significant
difference (p = 001 95 CI -135 to -017 Fig 3) The evidence suggests that exercise
intervention can reduce general fatigue in children with cancer
Fig 3 Meta-analysis results of exercise intervention for general fatigue
The effectiveness of exercise intervention for sleep rest fatigue
The following is the result of the meta-analysis of the effectiveness of exercise
interventions on sleep rest fatigue First the heterogeneity test was conducted with P gt
005 representing small heterogeneity and the fixed effects model was used Fig 4
shows the effect size is -035 indicating no statistically significant differences (p = 023
95 CI-092 to 022 Fig 4)
658
26
Fig 4 Meta-analysis results of exercise intervention for sleep rest fatigue
The effectiveness of exercise intervention for cognitive fatigue Lastly the following data reports the results of meta-analysis of the effectiveness of
exercise interventions for cognitive fatigue The heterogeneity was p>005 then the
fixed effects model was used The effect size is -035 indicating no statistically significant
differences (p = 024 95 CI-092 023 Fig 5)
Fig 5 Meta-analysis results of exercise intervention for cognitive fatigue
Narrative presentation of remaining included studies
Three studies were not included in meta-analysis Post-White et al7 one of the aims in
this study was to examine the effect of massage therapy on fatigue in children with
cancer The study was a quasi-experimental design Twenty-three childrenparent dyads
were enrolled 17completed all data points Children with cancer ages 7 to 18 years
received at least 2 identical cycles of chemotherapy and one parent participated in the
2-period crossover design in which 4 weekly massage sessions (MT) alternated with 4
659
27
weekly quiet-time (QT) control sessions There were no significant changes in fatigue in
children over the 4-week MT or QT conditions either independently (change over time) or
when we compared fatigue by condition
The lack of effect of massage on fatigue may be the difficulty some children had in
differentiating fatigue from being relaxed underscores the challenge of measuring fatigue
in children Some children interpreted being tired or relaxed as having greater fatigue
because they felt like lying around and sleeping or felt unmotivated to do their usual
activities all measures of fatigue in the instrument used in the study
Hinds et al24conducted a prospective two-site randomized controlled pilot study to
assess the feasibility of an enhanced physical activity (EPA) intervention in hospitalized
children and adolescents receiving treatment for a solid tumor or for acute myeloid
leukemia (AML) Twenty-nine patients (25 with a solid tumor and 4 with AML) participated
age range from 736 to 1816 (mean 1248 y) The EPA intervention selected was
pedaling a stationary bicycle-style exerciser (Chattanooga Peddler Deluxe Bio-Teck
Medical Memphis TN) for 30 minutes twice daily for 2 to 4 days of hospitalization The
mixed model analysis revealed no significant differences in patient reports of fatigue
between the two study arms or over time
Genc et al2 conducted a RCT involving children with cancer who are 7 to 12 years of age
and receiving chemotherapy treatment to determine the impact of educational
intervention by nurses on decreasing the fatigue syndrome The research sample was
composed of a total of 60 children with cancer with 30 children being included in the
660
28
experimental group (mean age 923)and 30 children included in the control group (mean
age 937) with their mothers In the experimental group after the 7th to 10th day of the
chemotherapy treatment throughout a week the researcher conducted the nursing
interventions every day for 45 to 60 minutes In the control group routine nursing
interventions were carried out The experimental group received education about the
fatigue with the chemotherapy and fatigue handbook was given which was developed by
the authors Children and mothers were consulted for including activities that could
decrease fatigue which were described as effective interventions A statistically
significant difference was found between the Fatigue Scale-Child mean scores of the
experimental (2723) and the control group (4213) The results suggest that fatigue of
children with cancer can be reduced by implementing appropriate nursing interventions
(t=567 Plt00)
Discussion The purpose of this systematic review was to determine the effectiveness of
non-pharmacological interventions specifically targeting fatigue for children and
adolescents with cancer undergoing chemotherapy or after receiving chemotherapy
Included articles about the effectiveness of non-pharmacological interventions for
children and adolescents with cancer were published between the years of 2007 and
2009 Although interventions for cancer fatigue for adults have been extensively studied
it can be seen from either the title of the paper or related content that an intervention
study on children was a pilot study or a feasibility study Representing a field in its early
stage these studies show that the fatigue issues with young cancer patients have only
recently been taken seriously
661
29
The results of our meta-analysis include measurement of the four performance indicators
fatigue and general fatigue sleep rest fatigue and cognitive fatigue The results show
that there is a statistically significant difference only in the domain of general fatigue
using an exercise intervention for children with cancer can improve the degree of fatigue
with the effect size reaching 0671 Other results do not indicate significant differences
The reasons may include the following
1 Characteristics of the cancer The exhaustion from cancer occurs not only during cancer treatment but also in during
long-term survival a time during which patients may continue to be affected by this
symptom 8 26 Therefore when using intervention measures to improve fatigue
circumstances should be considered such as the process of the treatment and the course
or stage of the disease Because cancer patients will experience different forms of
treatment or courses of treatment the disease itself or treatment differences should be
considered in the choice of intervention Even chemotherapy drugs should be taken into
consideration For example a period of general steroid treatment can increase patientsrsquo
fatigue In those studies of children with cancer few studies looked solely at one type of
cancer most studies included a variety of cancer patients Furthermore most studies do
not clearly explain the stage of the disease or course of treatment and most do not
include treatment variables in the control group Moreover children with cancer may
have different levels of physical function
2 Research design The sample size Currently there are few studies with large sample size and a rigorous
RCT design due to the small number of papers available for analysis The sample size
included in our studyrsquos data analysis is between 20 and 42 people this small sample size
will affect the power available to evaluate outcome variables
Although most of the non-pharmacological interventions still use exercise and physical
activity and these studies overall show better results for fatigue as compared with
controls more research is still needed to further confirm the efficacy of these findings
662
30
The dropout rate in the evaluated research varies a great deal ranging from 5 to 45
these dropout rates may result from the characteristics of the research subjects or the
lengthy time involved in participating in these studies The research data with a high
turnover rate might not reflect the actual outcomes of participation in exercise and the
quality of the research contained in articles with high subject turnover rates may be
lower
Exercise doses and time The exercise doses needed to reduce fatigue cannot be
determined additionally the amount of exercise completed by the patient is also
inconsistent interventions vary between 2-3 times per week and two times a day and
exercise duration varies between 10 and 45 minutes each time Furthermore the study
interventions vary in length between a couple of days and a long period of 16 weeks The
data collection times are different some were measured 12 weeks after the intervention
began some were measured during the 6 weeks of intervention some were measured
three months after the intervention was finished and some were measured after one
year
In addition disease-related symptoms decrease childrenrsquos willingness to participate in
exercise interventions inappropriate exercise intervention programs may actually
increase childrens fatigue In addition the children in the study are still developing
physically it is important to consider ways to design an interesting exercise intervention
to increase the compliance of patients in order to improve the effectiveness Although
intervention programs in the hospital or in a community sports center can improve the
effectiveness because they provide supervision the feasibility of these programs is
questionable However if the program is home-based the children need to be
supervised by parents in order to improve their compliance in doing the exercises
Furthermore regarding the nature of the intervention the results from this study indicate
that the researched non-pharmacological interventions include the following exercise
training programs physical activity massage therapy and health education interventions
However according to the National Comprehensive Cancer Network 1 clinical guidelines
663
31
for cancer non-drug measures for cancer fatigue can be separated into five categories
(1) activity enhancement (2) psychosocial interventions such as cognitive behavioral
therapy (CBT) stress management relaxation techniques and support groups (3)
attention-restoring therapy (4) nutritional consultation and (5) cognitive behavioral
therapy specifically targeting sleep disturbance Researchers have also suggested that
psychosocial interventions should be included in the future research for children with
cancer-related fatigue 22
(2) The measurement tools in the study The assessment of fatigue can be
one-dimensional or multidimensional One-dimensional assessment can help understand
the severity of fatigue symptoms however multidimensional scales are often more
credible Therefore when measuring cancer-related fatigue researchers should consider
whether there is a uniform definition of fatigue or a standardized tool for measuring
fatigue in order to facilitate further systematic meta-analyses and further develop the
clinical care guidelines
Limitations of the review The present review has some potential limitations First the low methodological quality
may influence the result Although exercise intervention seems promising quality of the
RCTs was generally quite low Future studies require better design and reporting if
methodological issues to establish evidence-based nonpharmcologic intervention
Second the identified studies covered only a limited types of nonpharmcological
intervention especially in exercise intervention The guidelines for cancer-related fatigue
in NCCN (2011)1 referred to more interventions than the ones included in this review
such as cognitive behavioral therapy and nutrition consultation Thirdly the small sample
size and effect size could be potentially having led to underpowered approach for
detecting the effects on fatigue Therefore we recommend that as research continues to
grow a re-analysis can be undertaken Fourthly Combining data in meta analysis from
664
32
studies where the ages were quite different is a potential source of heterogeneity and
may affect the interpretation of the results
Conclusion At present clinical treatment is widely used for cancer patients However child and
adolescent cancer patients often experience various side effects which cause short-term
or long-term discomfort both physically and psychologically In particular with the
increasing cure rate cancer related fatigue during or after treatment has become an
important issue This study result provided positive effect of exercise intervention on
general fatigue
Implications for practice The results of this systematic review and meta-analysis show that exercise interventions
can effectively improve the level of general fatigue In particular although the articles
were self-reported feasibility studies their results all indicate that exercise interventions
for fatigue are feasible and safe there was no conclusion to be made for the use of
massage therapy or health education measures because there was only one article for
each of these interventions
Recommendations for practice
Cancer-related fatigue is one of the most severe and frequent symptoms by pediatric
oncology children and adolescent suffered during treatment and the symptom existed
even after treatment has ended Until now no golden standard of treatment to fatigue is
established The findings call for more attention to how to reduce patientrsquos levels of
fatigue Based on the available information evaluated in this review the following
recommendations for practice are provided
665
33
bull For children aged 7 to 18 who has cancer (eg Lymphoma leukemia CNS tumor
germ cell tumor) an effective progressive aerobic exercise program is recommended to
be at least 2-3 times per week 20 to 45 minute for each session and last for 6-16 weeks
in order to reduce their general fatigue (tiredness physically weakness) In addition
adults should be involved in accompanying children while they are performing physical
exercise of which should be able to improve the adherence rate (level 2 ) ( Grade of
recommendation A)
bull For children aged 7 to 18 who has cancer (eg Lymphoma leukemia CNS tumor
germ cell tumor) an progressive aerobic exercise program will not be effective to reduce
their sleep andor rest (sleeping or resting a lot) or cognitive fatigue (problems with
thinking quickly or problems with remembering) (level 2 ) ( Grade of recommendation C)
bull Nursing interventions in educating treatment of fatigue include information about
activity nutrition energy preservation consulting and providing a useful fatigue
handbook will benefit those children who are 7 to 12 years have a new diagnosis of ALL
AML or lymphoma and receive for the first time after being diagnosed a 7- to 10-day
chemotherapy treatment (level 2) ( Grade of recommendation A)
bull A 4-week massage therapy program (the therapists massage childrenrsquos back legs
arms stomachchest and face) is not effective for children who are aged 7 to 18 and
have acute lymphoblastic leukemia brain tumors lymphoma rhabdomyosarcoma
Wilms tumor or Ewing sarcoma(level 2)( Grade of recommendation C)
bull Using a 12-week aerobic and strength exercise (45-min exercise sessions twice a
week) is not effective for children who are aged 6-14 and survived acute lymphoblaststic
leukemia age from 6 to 14(level 2) ( Grade of recommendation C)
bull Using a physical activity intervention (30minutestwice daily for 2-4days) is not
effective for children who are 7 to 18 years of age with soild tumor or AML(level 2)
( Grade of recommendation C)
666
34
Implications for research According to this systematic review and meta-analysis results there are suggestions to
improve the effectiveness of future research on non-pharmacological interventions for
children and young peoplersquos cancer-related fatigue
As the majority of included non-pharmacological interventions for the fatigue of cancer
patients consist of exercise programs future research should also consider various
non-pharmacological interventions in order to understand the effectiveness of different
methods
Regarding the exercise intervention methods and studies should consider multiple
factors including the age or personal condition of the subject the disease stage and the
amount of daily activities Studies should use design prescriptions (eg frequency
intensity duration and type of exercise) and consider the adherence to the measures in
order to enhance the study strength
In measuring the results of non-pharmacological interventions there should be standard
definitions or standard measurement tools to facilitate the following systematic review
and meta-analysis that can subsequently be developed into clinical care guidelines
Reviewing the effectiveness of the current non-pharmacological management of children
and adolescent cancer patients there is still a lack of rigorous RCT research Limited by
the characteristics of cancer there is still a lack of large sample sizes
Potential conflicts of interest There is no conflict of interest
Acknowledgements
Thank you to Dr Rie Konno Research Fellow Joanna Briggs Institute for her help in
assessing studies
667
35
References 1 National Comprehensive Cancer Network( NCCN) in USA NCCN clinical practice
guideline in oncology cancer-related fatigue 2011 2 Ekti Genc R amp Conk Z Impact of effective nursing interventions to the fatigue
syndrome in children who receive chemotherapy Cancer Nursing 200831(4)312-317
3 Childhood Cancer Foundation of ROC (2009March) The classification of diseases
and age sex statistical tables of case Childhood Cancer Foundation of ROC newsletter103105-106
4 Department of Health Executive Yuan ROC (TAIWAN)(2009 March 20)2009 cause of death statistic Health and National Health Insurance Annual Statistics Information Service 2010 June 28Available httpwwwdohgovtwstatisticdatavital statists9898health statistic--lifepdf
5 Chang TK (2007December 8) Common childhood cancer and its treatment Status
Childhood Cancer Foundation of ROC (TAIWAN) 2010 September 23 Available httpwwwccfrocorgtwchildchild_events_readphpe_id=45
6 Hockenberry MJ amp Wilson D Wongs nursing care of infants and children (8th ed) St
Louis MO Mosby 2007
7 Post-White J Fitzgerald M Savik K Hooke MC Hannahan AB amp Sencer SF
Massage therapy for children with cancer Journal of Pediatric Oncology Nursing 2009 26(1)16-28
8Chiang YC Yeh CH Wang WKamp Yang CP The experience of cancer-related fatigue
in Taiwanese children European Journal of Cancer Care 2009 18(1)43-49 9Langeveld NE Grootenhuis M A Voute P A de Haan RJ amp van den Bos C No excess
fatigue in young adult survivors of childhood cancer European Journal of Cancer 200339(2)204-214
10Piper BF Lindsey AM amp Dodd MJ Fatigue mechanisms in cancer patients
developing nursing theory Oncology Nursing Forum 1987 14(6)17-23 11Nail LM amp Winningham ML Fatigue In S L Groenwald M H Forgge M Goodman
amp C H Yarbro (Eds) Cancer Nursing Principles and practice (4 th ed) Boston Jones and Bartlett1997
12Irvine D Vincent L Graydon JE Bubela N amp Thompson L The prevalence and
correlates of fatigue in patients receiving treatment with chemotherapy and
668
36
radiotherapy A comparison with the fatigue experienced by healthy individuals Cancer Nursing 199417(5)367-378
13Hinds PS amp Hockenberry-Eaton M Developing a research program on fatigue in
children and adloescents diagnosed with cancer Journal of Pediatric Oncology Nursing 200118(2)3-12
14Aaronson LS Teel CS Cassmeyer V Neuberger GB Pallikkathayil L Pierce J Press
AN Williams DP amp Wingate A Defining and measuring fatigue Journal of Nursing scholarship 1999 31(1)45-50
15Yeh CH Wang CH Chiang YC Lin Lamp Chien LC Assessment of symptoms reported
by 10- to 18-year-old cancer patients in Taiwan 2009 38(5)738-746 16 Okuyama T Akechi T Kugaya A Okamura H Shima Yamp Maruguchi M
Development and validation of the cancer fatigue scale a brief three-dimensional self-rating scale for assessment of fatigue in cancer patients Journal of Pain amp Symptom Management 2000 19(1) 5-14
17Gibson F Mulhall AB Richardson A Edwards JL Ream E amp Sepion BJ A
phenomenologic study of fatigue in adolescents receiving treatment for cancer Oncology Nursing Forum200532(3)651-660
18Wolfe J Grier HE Klar N Levin SB Ellenbogen JMamp Salem-Schatz S et al
Symptoms and suffering at the end of life in children with cancer New England Journal of Medicine 2000342(5)326-333
19Whiting P Bagnall AM Sowden AJ Cornell JE Mulrow CD amp Ramirez G
Interventions for the treatment and management of chronic fatigue syndrome a systematic review JAMA the Journal of the American Medical Association 2001286(11)1360-1368
20 Kangas M Bovbjerg DHamp Montgomery G H Cancer-related fatigue a systematic
and meta-analytic review of non-pharmacological therapies for cancer patients Psychological Bulletin 2008134 (5)700-741
21Williams PD Schmideskamp J Ridder EL amp Williams AR Symptom monitoring and
dependent care during cancer treatment in children pilot study Cancer Nursing 200629(3)188-197
22Takken T van der Torre P Zwerink M Hulzebos EH Bierings M Helders PJMamp van
der Net J Development feasibility and efficacy of a community-based exercise training
669
37
program in pediatric cancer survivors Psycho-Oncology 200918(4)440-448
23Keats MR amp Culos-Reed SN A community-based physical activity program for
adolescents with cancer (project TREK) program feasibility and preliminary findings
Pediatric hematology and oncology 200830(4) 272-280
24Hinds PS Hockenberry M Rai SN Zhang L Razzouk B I Cremer L McCarthy K amp
Rodriguez-Galindo C Clinical field testing of an enhanced-activity intervention in
hospitalized children with cancer Journal of Pain amp Symptom Management 2007
33(6)686-697
25Chiang YC The effects of ldquo a home-based aerobic exercise interventionrdquo on fatigue
and cardiorespiratory fitness in children with acute lymphoblastic leukemia during the
maintenance stage of chemotherapy Unpublished thesis Taiwan Tao-Yuan 2007
26Langeveld N Ubbink M amp Smets E I dont have any energy The experience of
fatigue in young adult survivors of childhood cancer European journal of oncology
nursing 20004(1)20-28
27 Kisner C Colby L Therapeutic exercise Foundations and techniques 2nd ed Philadelphia PAFA Davies 2007
670
38
Appendix I JBI Critical Appraisal Checklist for Experimental studies
Author__________ Year_________ Record Number__________________
Questions 1 to 4 must be answered ldquoyesrdquo for study to be included in the metashyanalysis
1 Were the participants randomized to study groups
Yes No Not clear
2 Other than research intervention were participants in each groups treated the same
Yes No Not clear
3 Were the outcomes measured in the same manner for all participants
Yes No Not clear
4 Were groups comparable at entry
Yes No Not clear
5 Was randomization of participants blinded
Yes No Not clear
6 Were those assessing outcome blinded to treatment allocation (if outcome not objective such as survival or length of hospitalization)
Yes No Not clear
7 Was allocation to treatment groups concealed from the allocator
Yes No Not clear
8 Was an appropriate statistical analysis used
671
39
Yes No Not clear
9 Were outcomes measured in a reliable way
Yes No Not clear
10 Was there adequate followshyup of participants
Yes No Not clear
Summary
TOTAL
Yes No Not clear
DECISION
Use Reject
Narrative summary only Further information needed
COMMENTS
672
40
Appendix II JBI Data Extraction Tool for Quantitative Studies Authors and Year
Journal Title
Record NumberArticle Reference No
Reviewer
Method
Settings
Participants
Number of participants
Group A Group B Group C
Control Intervention 1 Intervention 2
Interventions
Group A
Control
Group B
Intervention 1
Group C
Intervention 2
Outcome measures
Definition
673
41
Other outcome measures
Outcome description ScaleMeasure
Results
Dichotomous Data
Outcome Control Group
Numbertotal number
Treatment Group
Numbertotal number
Continuous Data
Authorrsquos Conclusions
Comments
Outcome Control Group
Mean amp SD
Treatment Group
Mean amp SD
674
43
Appendix III Details of included studies (N=6)(2720212223) RefNo Author(s)
(years) Title Study question Research
method Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
22 Takken T van der Torre P Zwerink M Hulzebos E H Bierings M Helders P J Mamp van der Net J (2009)
Development feasibility and efficacy of a community-based exercise training program in pediatric cancer survivors
To develop a 12-week home-based exercise training program (comprising aerobic and strength exercises) for children who survived ALL and to study itrsquos feasibility and efficacy
Pre-post test design
No comparsion group
Survived ALL(N=9)ages 6-14 years
1anthropometry 2 muscle strength 3functional mobility 4cardio-pulmonary
exercise test 5Fatigue
1 Feasibility questionnaire 2 anthropometry electronic scale and a wallmounted stadiometerHarpenden skin fold calipers 3 muscle strength handheld dynamometer 4functional mobility Timed Up
and Go test (TUG) 5cardio-pulmonary exercise test electronically braked cycle ergometer 6Fatigue(mean)CSI-20 (subjective experience of fatigueconcentrationmotivationphysical activity)
112-week exercise training program
2 Patients were assessed before (T0) and after (T1) 12 weeks of training
1 muscle strength execapacity functional moand fatigue showed nosignificant differences between pre(meanplusmnSD415plusmn147) and post training(meanplusmnSD3687)
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
7 Post-White J Fitzgerald M Savik K Hooke M C Hannahan A B amp Sencer S F (2009)
Massage therapy for children with cancer
To determine whether 4 weekly sessions of massage compared with 4 quiet-time control conditions would reduce anxiety cortisol levels fatigue nausea and pain in children with cancer undergoing chemotherapy and would reduce anxiety fatigue and mood disturbance in a parent
2-period crossover design (Randomized)
quiet-time
control
sessions
Children with cancer 1 to 18 years of age Twenty-three childrenparent dyads were enrolled 17 completed all data points
children 1relaxation 2symptoms 3 fatigue
parents
1anxiety 2 fatigue
children 1relaxation (heart and respiratory rates blood pressure and salivary cortisol level)
2symptoms (pain nausea anxiety 3 fatigue 1-2y3-6yLansky Play Performance Scale (PPS) 7-13y
1 4 weekly massage (MT) sessions alternated with 4 weekly quiet-time(QT) control sessions
2 children included presession and postsession vital signs (heart rate respiratory rate blood pressure) and self-report (parent proxy report for age 1-2 years) of pain nausea and anxiety Fatigue was measured before sessions 1 and 4 and at each follow-up Parent measures
included anxiety fatigue and mood states
1Massage was moreeffective than quiet tireducing heart rate inchildren anxiety in cless than age 14 yeaparent anxiety 2There were no sign
changes in blood pcortisol pain naufatigue (no state d
3 Children reported tmassage helped thebetter lessened theirand worries and hadlasting effects than q
675
44
14-18yChild Fatigue Scale (CFS) (frequency
intensity) 2 parents anxiety and fatigue
676
45
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
24 Hinds P S Hockenberry M Rai S N Zhang L Razzouk B I Cremer L McCarthy K amp Rodriguez-Galindo C (2007)
Clinical field testing of an enhanced-activity intervention in hospitalized children with cancer
To determine the feasibility of an
enhanced physical activity EPA intervention in children and adolescents hospitalized to receive chemotherapy for a solid tumor or AML and to assess the sleep and fatigue outcomes of the intervention using two different statistical approaches to analyze the longitudinal symptom data
randomized prospective two-site and two-group pilot study
Standard care Twenty nine patients (25 with a solid tumor and 4 with AML)ages 7-18 years
1 sleep duration 2 sleep efficiency 3 fatigue
1sleep duration sleep efficiency The
Wrist Actigraph The Daily Sleep Diary-Parent 2 fatigue (mean) The Fatigue Scale(FS-C) for 7-12 (intensity) The Fatigue Scale(FS-A) for 13-18 The Fatigue Scale Parent Version (FS-P) The Fatigue Scale Staff Version (FS-S)
1enhanced physical activity (EPA) (hospital-based 30 minutes
twice daily for 2-4 days) 2 T0On the day of admission
(Day 0 or baseline)patient and parents completed the fatigue instruments and a team member applied the actigraph Patients wore the wrist actigraph T1 from Day 0 to 2 or 3 consecutive days (Days 0e3) In addition the patient same parent and staff nurses completed the daily sleep and fatigue reports in the late afternoons of Days 1-3
1 ANOVA model slesignificantly more the experimental athe control arm whdifferences from bsleep efficiency vaaveraged and com
2 The patient-reported mean fatigue scoresarms were higher amadolescents than for
3 The mixed model anarevealed no significandifferences in patientfatigue between
the two study arms otime( no final result iSD only give mixed result)
677
46
23 Keats M
R amp Culos-Reed S N (2008)
A community-based physical activity program for adolescents with cancer (project TREK) program feasibility and preliminary findings
To examine the
feasibility of a
theoretically-based
physical activity (PA)
intervention in
adolescents with
cancerand
examination of the
impact of the
program on
participant QOL
including social
emotional and
physical
well-being(including fatigue)
Repeat measures longitudinal design
No comparsion group
10 adolescents(Lymphoma(4)leukemia(4)CNS tumor(1)germ cell tumor(1)) ages 14-18 years
1physical fitness 2quality of life (QOL) 3PA behavior 4fatigue
1 Feasibility was assessed by participant recruitment attendance and adherence
2physical fitness Fitnessgram 3quality of life (QOL) Pediatric Quality of Life Inventory (PedsQL) 4PA behavior leisure score index (LSI) 5fatigue (mean) pediatric Quality of life
Multidimensional Fatigue Scale (Peds QL-MFS)
(Generalsleepcognitive fatigue)
116week physical activity (PA)
2 total PA physical fitness and overall QOL was assessed at 5 different intervals T0 preintervention (baseline) T1midintervention (after the
first 8 wk) T2 postintervention
(16 wk) T3 3-months
postintervention T4 1-year poststudy
initiation
1 from baseline -wkssig Improvementstotal PA physfitness and Qgeneral fatigue(meanplusmnSD 796plusmn135)
2 from baseline to 3FUsig Improvin general fatigue(meanplusmnSD824plusmn131)slefatigue(meanplusmnSD755plusmn191)totafatigue(meanplusmnSD778plusmn150)
3at 1 years FUsImprovements in sleeprest fatigue(meanplusmnSD725plusmn203)total (meanplusmnSD 763plusmn
678
47
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
2 Gene R E amp Conk Z (2008)
Impact of Effective Nursing Interventions to the Fatigue Syndrome in Children Who Receive Chemotherapy
1 to examine the effects of an effective nursing intervention to the fatigue syndrome of children 7 to 12 years of age who receive chemotherapy 2Tto examine the relationship between fatigue and demographic variables (age sex) diagnoses ([ALL AML] lymphoma) and therapy-related variables (eg level of hemoglobin
experimental randomized controlled study
Routine nursing care
A total of 60 children who are 7-12 years of age(a new diagnosis of ALL AML or lymphoma and receiving for the first time after being diagnosed a 7- to 10-day chemotherapy treatment )
fatigue The Fatigue Scale(FS-C) for 7-12 (intensity)
The Fatigue Scale Parent Version (FS-P)
1 effective nursing interventions(45- 60mdaya week)education about the fatigue with the chemotherapy and fatigue handbook 2 T1 After a 7-day period the children
and parent were evaluated with the Fatigue Scale
1The difference betwthe 2 mean values wafound to be statisticallsignificant 2 statistically significadifference was found between the Fatigue Scale-Child mean scothe experimental (272the control group (4213)children
679
48
25 Chiang et
al(2007)
The effects of ldquo a home ndashbased aerobic exercise interventionrdquo on fatigue and cardiorespiratory fitness in children with Acute Lymphoblastic Leukemia during the maintenance stage of chemotherapy
To examine the effect of ldquo a home ndashbased aerobic exercise interventionrdquo on fatigue and cardiorespiratory fitness in children with Acute Lymphoblastic Leukemia during the maintenance stage of chemotherapy
Quasi-experi -mental
Routine
nursing care
14 pediatric oncology patients in the experimental group and 10 in control group who were matched by age and sex ages7-18 years
1Cardiorespiratory fitness
2Fatigue
1Cardiorespiratory fitness Physical Activity Recall
VO2maxHR peak 6MWT
2 Fatigue PedsQL-MFS(Generalsleepcognitive fatigue)
1A six-week home-based aerobic exercise intervention 2 8 time points T0 baseline T1-T6 every week during the
intervention(6 weeks) T7 post intervention T8 follow-up (one month after
the end of the home-based exercise program)
1 For intent-to ndash treatthe findings indicated are no intervention efftime differences by anon the subscale of fat2 For per-protocol angeneral fatigue( mean422plusmn402) was the osubscale that was siglower for children whothe exercise interventthose in control groupfollow-up assessmentmonth after the compintervention) 3 The VO2peak are significantly improvingexperimental group atbaseline- and post-intassessment The VO2was significantly highechildren who were in experimental group thcontrol subjects at post-intervention assefor the per-protocol an
680
49
Appendix IV Instrument used to measure fatigue
Name Instrument
developers
Description Used in
age in
ref
Reliability
Consistency of
instrument
Checklist Individual Strength
(CIS)22
Vercoulen et
al1996
20 items using 7-point Likert scale of
fatigue To measure four aspects of
fatiguesubjective experience
contractionmotivation physical
Activity
6-14 Not reported
Child Fatigue Scale (CFS)7 Hockenberry
et al2003
14 items 2 part questionnaire frequency
(yes or no) 5-point Likert scale of the
intensity of any yes responses
7-13
14-18 α073-o84
The Fatigue Scale for 7-12
year Olds (FS-C)224
Hockenberry
et al
14 items provide a fatigue intensity score
5-point Likert scale
7-12 αo84
The Fatigue Scale for 13-18
year Olds (FS-A)24
Hockenberry
et al
14 items provide a fatigue intensity score
5-point Likert scale
13-18 α076-o96
Pediatric Quality of life
Multidimensional Fatigue
Scale (Peds QL-MFS)2325
Varni2002 18 items to measure three aspects of
fatigueGeneralsleepcognitive
14-18 Not reported
681
50
Appendix V Excluded studies and reasons for exclusion
Baggott C Dodd M Kennedy C Marina N Miaskowski C Multiple Symptoms in Pediatric Oncology
Patients A Systematic Review Journal of Pediatric Oncology Nursing 2009 Nov-Dec 27(6)
325-339
Reason for exclusion Not outcome of interest
Barlow JH Ellard DR Psycho-educational interventions for children with chronic disease parents and
siblings an overview of the research evidence base Care Health amp Development 2004 Nov
30(6)637-45
Reason for exclusion Not outcome of interest
Bedider S Moyer CA Randomized controlled trials of pediatric massage A review Evid Based
Complement Alternat Med 2007 Mar 4(1)23-34 Epub 2006 Nov 3
Reason for exclusion Not outcome of interest
de Nijs EJ Ros W Grijpdonck MH Nursing intervention for fatigue during the treatment for cancer Cancer
Nursing 2008 31(3)191-206
Reason for exclusion Not population of interest
Edwards JL Gibson F Richardson A Sepion B Ream E Fatigue in adolescents with and following a
cancer diagnosis developing an evidence base for practice European Journal of Cancer 2003
Dec 39(18)2671-80
Reason for exclusion Not experimental or quasi-experimental study
Hinds PS Hockenberry-Eatan M Developing a research program on fatigue in children and adolescents
diagnosed with cancer Journal of Pediatric Oncology Nursing 2001 Mar-Apr 18(2 Suppl
1)3-12
Reason for exclusion Not experimental or quasi-experimental study
Hockenberry-Eaton M Hinds PS Alcoser P ONeill JB Euell K Howard V Gattuso J Taylor J Fatigue in
Children and Adolescents With Cancer Journal of Pediatric Oncology Nursing 1998 July
15(3)172-182
Reason for exclusion Not experimental or quasi-experimental study
Jean-Pierre P Mustian K Kohli S Roscoe JA Hickok JT Morrow GR Community-based clinical oncology
research trials for cancer-related fatigue The Journal of Supportive Oncology 2006 Nov-Dec
4(10)511-6
682
51
Reason for exclusion Not population of interest
Kangas M Bovbjerg DH Montgomery GH Cancer-Related Fatigue A Systematic and Meta-Analytic
Review of Non-Pharmacological Therapies for Cancer Patients Psychological Bulletin 2008 Sep
134(5)700-41
Reason for exclusion Not population of interest
Lotfi-Jam K Carey M Jefford M Schofield P Charleson C Aranda S Nonpharmacologic strategies for
managing common chemotherapy adverse effects A systematic review Journal of Clinical
Oncology 2008 Dec 1 26(34)5618-29 Epub 2008 Nov 3
Reason for exclusion Not outcome of interest
Marchese VG Chiarello LA Lange BJ Effects of physical therapy intervention for children with acute
lymphoblastic leukemia Pediatr Blood Cancer 2004 Feb42(2)127-33
Reason for exclusion Not outcome of interest
Meeske KA Siegel SE Globe DR Mack WJ Bernstein L Prevalence and correlates of fatigue in
long-term survivors of childhood leukemia Journal of Clinical Oncology 2005 Aug 20
23(24)5501-10
Reason for exclusion Not intervention study
Minton O Richardson A Sharpe M Hotopf Stone P A systematic review and meta-analysis of the
pharmacological treatment of cancer-related fatigue J Natl Cancer Inst 2008 Aug 20
100(16)1155-66 Epub 2008 Aug 11
Reason for exclusion Not population and intervention of interest
Mustian KM Morrow GR Carroll JK Figueroa-Moseley CD Pascal JP Williams GC Integrative
nonpharmacologic behavioral interventions for the management of Cancer-Related fatigue The
Oncologist 2007 12(1)52-67
Reason for exclusion Not population of interest
Neill J Belan I Ried K Effectiveness of non-pharmacological interventions for fatigue in adults with
multiple sclerosis rheumatoid arthritis or systemic lupus erythematosus a systematic review
Journal of Advanced Nursing 2006 Dec 56(6)617-35
Reason for exclusion Not population of interest
Rheingans JI A systematic review of nonpharmacologic adjunctive therapies for symptom management
Journal of Pediatric Oncology Nursing 2007 24(2) 81-94
683
52
Reason for exclusion Not outcome of interest
Rheingans JI Pediatric oncology nursesrsquo management of patients symptoms Journal of Pediatric
Oncology Nursing 2008 Nov 25(6) 303-11
Reason for exclusion Not outcome of interest
San Juan AF Fleck SJ Chamorro-Vintildea C Mateacute-Muntildeoz JL Moral S Peacuterez M Cardona C Del Valle MF
Hernaacutendez M Ramiacuterez M Madero L Lucia A Effects of an intrahospital exercise program
intervention for children with leukemia Medicine amp Science in Sports amp Exercise 2007 Jan
39(1)13-21
Reason for exclusion Not outcome of interest
Sanford SD Okuma JO Pan J Srivastava DK West N Farr L Hinds PS Gender differences in sleep
fatigue and daytime activity in a pediatric oncology sample receiving dexamethasone Journal of
Pediatric Psychology 2008 Apr 33(3)298-306 Epub 2007 Nov 17
Reason for exclusion Not experimental or quasi-experimental study
Schmitz KH Holtzman J Courneya KS Macircsse LC Duval S Kane R Controlled physical activity trials in
cancer survivors a systematic review and meta-analysis Cancer Epidemiol Biomarkers Prev
2005 Jul 14(7)1588-95
Reason for exclusion Not population of interest
van Brussel M Takken T Lucia A van der Net J Helders PJ Is physical fitness decreased in survivors of
childhood leukemia A systematic review Leukemia 2005 Jan 19(1)13-7
Reason for exclusion Not population of interest
Whiting P Bagnall AM Snowden AJ Cornell JE Mulrow CD Ramirez G Interventions for the treatment
and management of chronic fatigue syndrome JAMA 2001 Sep 19 286(11)1360-8
Reason for exclusion Not intervention of interest
Whitsett SF Gudmundsdottir M Davies B McCarthy P Friedman D Chemotherapy-related fatigue in
childhood cancer correlates consequences and coping strategies Journal of Pediatric
Oncology Nursing 2008 Mar-Apr 25(2)86-96 Epub 2008 Feb 29
Reason for exclusion Not experimental or quasi-experimental study
Winner C Muumlller C Hoffmann C Boos J Rosenbaum D Physical activity and childhood cancer Pediatr
Blood Cancer 2010 Apr 54(4)501-10
Reason for exclusion Not research study
684
53
Wu M Hsu L Zhang B Shen N Lu H Li S The experiences of cancer-related fatigue among Chinese
children with leukaemia A phenomenological study Journal of Nursing Studies 2010 Jan
47(1)49-59 Epub 2009 Aug 25
Reason for exclusion Not experimental or quasi-experimental study
Yeh CH Chiang YC Lin L Yang CP Chien LC Weaver MA Chuang HL Clinical factors associated with
fatigue over time in paediatric oncology patients receiving chemotherapy British Journal of
Cancer 2008 Jul 8 99(1)23-9 Epub 2008 Jun 24
Reason for exclusion Not experimental or quasi-experimental study
685
2
Objectives The objective of this systematic review was to determine the best available
evidence concerning the effectiveness of non-pharmacological interventions on fatigue in
children and adolescents with cancer
Search strategy The search strategy aimed to find studies published between 1960 and
2010 in either the English or Chinese languages Reference lists of studies that met the
inclusion criteria were also searched for additional studies
Types of studies This review included randomised controlled trials and
quasi-experimental studies that examined the effectiveness of non-pharmacological
interventions for fatigue in children and adolescents with cancer
Types of participants Children and adolescents aged from 1 to 18 years old with
cancer either during or after the chemotherapy The types of cancer included were Acute
lymphoblastic leukemia Acute myeloid leukemia lymphoma and solid tumors
Types of interventions This review considered studies that examine
non-pharmacological interventions on fatigue for children and adolescents with cancer
including activity enhancement (exercise physical activity) psychosocial interventions
cognitive behavioral therapy stress management relaxation nutrition consultation
massage and educational interventions The intervention descriptions included the length
frequency setting and intervention providers
Types of outcome measures The outcome measures considered fatigue scores
assessment
Types of setting The review focused on studies that conducted either in a hospital or a
community setting
Data collection and synthesisThe data were extracted using the standardised data
635
3
extraction tool from the Joanna Briggs Institute-Meta-Analysis of Statistics Assessment
and Review Instrument
Results
The review included a total of six studies - five English-language papers and one
Chinese-language paper Meta-analysis did not show statistically significant impact on
the effectiveness of exercise interventions in reducing fatigue in children and adolescents
with cancer The impact of the exercise interventions on general fatigue did however
indicate a statistically significant difference (p = 001 95 Confidence Interval -135 to
-017)
Conclusions
The results of this systematic review show that exercise interventions can effectively
reduce the level of general fatigue of children six to 18 years No strong conclusions
can be made for the use of massage therapy or health education measures as there
was only one article for each of these interventions
Implications for practice The review provides an evidenced-based guide to future priorities for clinical practice
Exercise intervention could reduce the level of general fatigue of children who ages are
six to 18 In particular exercise intervention for fatigue are feasible and safe
Implications for research There is still a lack of rigorous research on this specific topic Further research requires
more rigorous study design and reporting of menthdologic issues such as randomized
controlled trials using concealment of allocation Other non-pharmacological
interventions should be also examined including cognitive behavioral therapy stress
management relaxation support groups massage therapy in this area
636
4
Keywords non-pharmacological intervention fatigue children adolescents cancer
exercise cognitive systematic review
BACKGROUND
The Clinical Practice Guidelines in Oncology of the National Comprehensive Cancer
Network (NCCN) in the USA define cancer-related fatigue as ldquoa distressing persistent
subjective sense of physical emotional andor cognitive tiredness or exhaustion related
to cancer or cancer treatments that is not proportional to recent activity and interferes
with daily functionrdquo(pFT-1)1 When children suffer from cancer fatigue is not only the most
consistently reported symptom by children with cancer but also one of the most
persistent and uncomfortable symptoms 2
The incidence of cancer in children is high across the world As an example the
incidence in the USA for children aged 0-14 years is approximately 129 per million with
an estimated projection of 8200 newly diagnosed cases per year3 In Taiwan
approximately 550-600 children are diagnosed with cancer every year4 According to the
estimation of group proportions the incidence of childhood cancer in Taiwan and the
United States are similar 5 In addition malignant tumor has become the second leading
causes of death for children and adolescents aged 1-14 years in Taiwan3 and US6
Although cancer has been one of the major illnesses threatening the life of children the
progress made in medical technology has led to a significant improvement in the
treatment of children and adolescents with cancer over the past three decades7
especially the increase in their survival rate Statistics have indicated that the five-year
637
5
survival rate of children with cancer has exceeded 756 however the treatments of
cancer tend to rely on aggressive chemotherapies which force children to face a long
treatment process as well as various physical and mental symptoms8 Fatigue is one of
the common symptoms affecting children during treatments Children may feel persistent
fatigue even after they complete cancer treatments9
To date the causes and mechanism of cancer-related fatigue are still unclear However
the theories concerning the causes of fatigue have been proposed Common theories
include Integrated Fatigue Model10 Psychobiological Entropy Model11 Energy Analysis
Model12
Piper et al (1987) 10 proposed the Integrated Fatigue Model which is one of the most
frequently cited fatigue models at present They suggest that fatigue is the tiredness felt
by individuals as a result of the influence of body rhythm which makes individuals
experience different degrees of discomfort In this model fatigue can be measured by
biochemical indicators such as cytokines interferon and tumor necrosis factors as well
as with a self-report fatigue scale
The term ldquoIntegratedrdquo refers to a combination of features including perception physics
biochemistry and behavior all of which affect level of fatigue and in turn influence
fatigue patterns including diseases treatments activitiesrests environment symptoms
social activities life events individual internal factors and other aspects of the patients
life
The second theory is the Psychobiological Entropy Model11 is the most complete fatigue
638
6
theory at present This model suggests that the main cause of fatigue is a lack of energy
The physical ability of patients is reduced because of the symptoms caused by diseases
or treatments and thus patients experience emotion-related fatigue and the reduction in
functional status as a result In addition the symptoms caused by reoccurring diseases
or treatments may be harmful to physical conditions even more and lead to disability
eventually In this model any treatment program that can address the decline in activity
can alleviate fatigue symptoms is said to improve fatigue Therefore Psychobiological
Entropy Model not only provides a more direct detection of clinical patterns but also for
providing measures of care within a fatigue model
The third model is the Energy Analysis Model12 which suggests that the pathological
change of individual physical status becomes the barrier of energy conversion When the
supply of energy in individuals is low or the demand is high a lack of energy results and
the individuals feel fatigue Energy is generated by the oxygenation in blood The
correction factors of energy reaction are cancer treatments symptom distress and
emotional disorders Concepts in the fatigue model include energy sources energy
transformations energy expenditures and energy response modifiers The relationships
among these concepts are dynamic and intercorrelated with each other From the Energy
Analysis Mode point of view the physiological mechanism of fatigue includes some
objective indicators such as body weight and hemglobulin
In terms of the causes of fatigue Ekti Genc amp Conk (2008) 2 indicated that illnesses
treatments and stage of disease can cause fatigue NCCN (2011) 1 points out that many
conditions are related to fatigue including pain emotional pain anaemia sleep disorders
639
7
nutritional deficiencies activity reduction side effects of drugs (antihistamine drugs
anti-vomiting drugs and anti-anxiety drugs) and others In a study on children
adolescents parents and relevant medical and nursing staffs Hinds and
Hockenberry-Eaton (2001) 13 proposed four factors causing the fatigue of children with
cancer which are 1) environmental factors treatment setting events or situations that
place demands on the patient such as appointments inpatient stay long waiting time
altered routines that lack clear beginnings and endings of each day and decision making
and information exchange 2) personalbehavioral factors the negative faith of children
with illness 3) culturalfamilyother factors emotions concerns the hope of friends and
family ability to participate in activities and restricted activities 4) treatment-related
factors the invasive inspections experienced by children with illness insufficient time for
physical strength recovery between the repeated courses of treatments or the side
effects caused by treatments (infection pain and decrease in complete blood count) It
can be inferred that the causes of fatigue are complicated and multifaceted
Fatigue is a complex and multidimensional condition 10 therefore fatigue is subject to
different definitions and there are different measurement tools Aaronson et alrsquos14
review the literature of fatigue summarised the characteristics of fatigue measurement
including the following(1) Subjective quantification of fatigue can be determined with the
Lee and colleagues (1991) Visual Analog Scale for Fatigue (VASF)(2) Subjective
distress This item simply asks the rater to report to what degree fatigue has caused
distress (3) The effect of fatigue on activities of daily living (4) Correlates of fatigue
such as sleep and depression to assess when measuring fatigue (5) key biological
parameters such as cytokines interferon and tumor necrosis factor
640
8
Fatigue can be also measured with unidimensional or multidimensional scales The first
type of fatigue scale is not suitable for studies focusing on fatigue because they are too
long if the aim is to only assess fatigue Furthermore they only allow for a limited number
of possible responses Unidimensional scales also are not suitable for the in-depth study
of fatigue because they assess only one aspect of fatigue15
In recent years fatigue in children with cancer has received some attention and
measurement tools have gradually been developed - such as1) Checklist individual
strength (CIS) The items are scored on 7-point Likert scales (with 1 indicating best and
7 worst function) 2) The Child Fatigue Scale (CFS) is a 2-part questionnaire that asks for
a yes or no (frequency) response and a 5-point rating of the intensity of any yes
responses ranging from not at all to a lot The Fatigue Scale for 7-12 year Olds (FS-C)
is provide a fatigue intensity score higher scores indicating higher fatigue The Fatigue
Scale for 13-18 year Olds (FS-A) measure adolescent cancer patientsrsquo perceptions of
the intensity of their fatigue on a daily or weekly basis higher scores indicating higher
fatigue 3) The Fatigue Scale Parent Version (FS-P) measures the parentsrsquo perception
of their childrsquos fatigue intensity on a five-point Likert-type scale higher scores indicating
higher fatigue 4) The Fatigue Scale Staff Version (FS-S ) measures the staffrsquos
perceptions of the patientrsquos fatigue intensity during the past 24 hours Intensity ratings are
on a four-point Likert-type scale with higher scores indicating more intense fatigue
symptoms 5) The Pediatric Quality of life Multidimensional Fatigue Scale (Peds
QL-MFS)Higher scores (0 to 100) indicate less fatigue( Appendix IV)
Besides disturbing physical and mental functions and status fatigue also affects the
641
9
quality of life 15 of children with cancer and impacts their daily life16 among all different
types of cancer progress and childrsquos ages However as opposed to the fatigue of adults
the fatigue of children tends to be neglected and left untreated17 by medical and nursing
staffs
In terms of the management approach to cancer-related fatigue Ekti Gene (2008) 2
suggests that strategies could include pharmacologic and non-pharmacologic measures
NCCN (2011) 1 indicated in the Clinical Practice Guidelines in Oncology that during
aggressive treatments during long-term follow-up treatments or in the terminal phase of
cancer the intervening measures for cancer-related fatigue can be divided into
pharmacologic and non-pharmacologic measures Non-pharmacologic measures include
activity enhancement psychosocial interventions (eg cognitive behavioral therapy
(CBT) stress management relaxation support groups) attention-restoring therapy and
nutrition consultation As for the effectiveness of pharmacological measures the
effectiveness is still uncertain However there is evidence to suggest that
methylphenidate may be effective in treating cancer-related fatigue1 Whiting et al
(2001)18 included 36 randomized controlled trials and 8 controlled trails to assess the
effectiveness of the pharmacological and non-pharmacological interventions used in the
treatment or management of chronic fatigue syndrome in adults or children Results
showed insufficient evidence on the effectiveness of the pharmacological supplements
complementaryalternative and other interventions In addition the evidence of
pharmacological treatments of immunoglobulin and hydrocortisone were also
inconclusive However interventions such as cognitive behavioral therapy and graded
exercise therapy have shown promising results
642
10
The efficacy of pharmacological treatments for cancer-related fatigue has not been
established6 therefore there is a need to provide evidence-based findings of the
effectiveness of non-pharmacological interventions to support nursing intervention to
release the childrsquos cancer-related fatigue To date most studies have investigated the
effectiveness of non-pharmacological treatments on cancer-related fatigue of
adults20and to date there is no systematic review in relation to cancer-related fatigue of
children However as children are not a smaller version of adults it is inappropriate to
extrapolate the results of adults onto children Therefore there is a need to establish the
effectiveness of non-pharmacological intervention on the cancer-related fatigue of
children
Given the increase in childhood cancer survival rate the importance of decreasing
childrenrsquos cancer-related fatigue during treatments and so increase their quality of life has
become a focus of their medical teams The role of nurses during care intervention is to
confirm the major symptoms of children with illness and effectively treat each symptom to
increase the childrenrsquos quality of life21 Moreover the USA based NCCN also indicated in
the Care Standard for the Treatment of Cancer-related Fatigue of Children and
Adolescents that treatments for fatigue should be included in the health care teams and
the children and their family should be informed of relevant information The definition of
non-pharmacological interventions for childrenrsquos cancer ndashrelated fatigue include activity
enhancement (exercise physical activity) psychosocial interventions cognitive
behavioral therapy (CBT) stress management relaxation nutrition consultation
massage and educational interventions
643
11
The Cochrane Library of Systematic Reviews and The Joanna Briggs Institute Library of
Systematic Reviews were initially searched to ensure that systematic reviews on this
subject were not already published or being undertaken This initial search prior to the
commencement of the review did not yield any results
This systematic review has examined the effectiveness of non-pharmacologic
interventions on the cancer-related fatigue of children in hope of finding scientific
evidence that can support or refute such measures on children The results of this study
may serve as a reference for professional caregivers children with cancer and their
families or to be put into practice during the clinical care of children with cancer
Definition of terms
FatigueFatigue as a distressing persistent subjective sense of physical emotional
andor cognitive tiredness or exhaustion related to cancer or cancer treatments
that is not proportional to recent activity and interferes with daily function1 There
are various scales and measurements of the degree of fatiguewe have elected to
use the study authors own definitions of fatigue rather than applying a single
pre-set definition of the condition
Non-pharmacological interventionsReferring to reduce fatigue that does not involve
drugsNon-pharmacologic measures include activity enhancement psychosocial
interventions (eg cognitive behavioral therapy stress management relaxation
support groups) attention-restoring therapy and nutrition consultation1
ChemotherapyTreatment with drugs that kill cancer cells 1
644
12
Review QuestionsObjectives
Review Objective
The objective of this systematic review was to critically appraise synthesize and
present the best available evidence concerning the effects of non-pharmacological
interventions fatigue in children and adolescents with cancer
Review Question
The following specific question was addressed in this review
What is the effectiveness of non-pharmacological interventions on fatigue in
children and adolescents with cancer aged from one to 18 years
Criteria for Considering Studies for this Review
Types of studies
This review included randomised controlled trials (RCTs) and quasi-experimental
studies that examine the effectiveness of non-pharmacological intervention for fatigue in
children and adolescents with cancer
Types of participants
Children and adolescents aged from one to 18 years old experiencing fatigue
associated with cancer either during or after the chemotherapy or maintenance stage of
chemotherapy or survive stage The types of cancer to be included in this systematic
review will be ALL (Acute lymphoblastic leukemia) AML (Acute myeloid leukemia)
lymphoma and solid tumors
Exclusion criteria for Types of participants
645
13
newborn infants under 1 years of age
participants who do not have a specific diagnosis of cancer
participants who have received immunoglobulin or hydrocortisone
treatment
If participants have received immunoglobulin or hydrocortisone treatment may
inference the effectiveness of non-pharmacological interventions on fatigue
Types of intervention
This review considered studies that examine non-pharmacological interventions on
fatigue for children and adolescents with cancer including activity enhancement
(exercise physical activity) psychosocial interventions CBT stress management
relaxation nutrition consultation massage and educational interventions The
interventions descriptive included the length frequency setting and intervention
providers eg Nurse Psychologist Dietician
Exclusion criteria for types of interventions only pharmacological interventions were
tested
Types of outcome measures
The outcome measures considered were fatigue scores The literature demonstrates that
differences of opinion exist regarding the most valid and reliable method of measuring
cancer-related fatigue Therefore studies that used any validated scale for
cancer-related fatigue were considered for inclusion Currently commonly used scales to
measure fatigue include Checklist Individual Strength (CIS) Child Fatigue Scale (CFS)
The Fatigue Scale for 7-12 year Olds (FS-C) The Fatigue Scale for 13-18 year Olds
646
14
(FS-A)and Pediatric Quality of life Multidimensional Fatigue Scale (Peds QL-MFS)
Types of settings
Both hospital and community settings
Search Strategy
Before undertaking this systematic review the Cochrane Library Joanna Briggs Institute
Library of Systematic Reviews and CINAHL were searched and no systematic reviews on
this topic were found or identified as underway
The search strategy aimed to find both published and unpublished studies
A three-step search strategy was utilized in each component of this review An initial
limited search of CINAHL and MEDLINE was undertaken followed by an analysis of the
text words contained in the title and abstract and of the index terms used to describe the
article A second search using all identified keywords and index terms was undertaken
Lastly the reference lists of all identified reports and articles were searched for additional
studies
Types of languages
1 English
2 Chinese
The following databases were searched to identify keywords contained in the title and
abstract and relevant MeSH headings and descriptor terms
The Cochrane Library PsycINFO 1990 ndash 2010
647
15
Ovid MEDLINE 1966 ndash 2010 CINAHL Plus with Full Text 1960 ndash2010 EMBASE ProQuest Dissertations amp theses 1990-2010 Electronic theses and dissertations system 1956(abstract)1990(full text)-2010 MEDNAR Index to Taiwan periodical literature 1970-2010 Electronic thesis and dissertation system (Chinese) 1990-2010
Keyword search terms
1Types of studies experimental study random quasi-experimental study實驗性研究隨
機類實驗性研究
2 Types of participants childchildren adolescents pediatric cancer and oncology兒童
青少年兒科癌症腫瘤
3 Types of interventions non-pharmacological interventions massage exercise fitness
physical activity cognitive behavioral stress management energy conservation
sleep therapy relaxation distraction and psycho-education非藥物性處置按摩運動
身體活動認知行為壓力處置能量保存睡眠治療放鬆轉移注意力衛教
4 Types of outcome measures fatigue cancer-related fatigue loss of energy levels of
tiredness tired side effect symptoms疲憊癌性疲憊疲倦合併症症狀
Methods of the Review
Assessment of methodological quality Papers selected for retrieval were assessed by two independent reviewers for
methodological validity prior to inclusion in the review using the standardised critical
appraisal instruments (Appendix I) from the JBI-SUMARI (Joanna Briggs Institute
Systems for the Unified Management Assessment and Review of Information package)
Any disagreements that arise between the reviewers were resolved through discussion
648
16
with a third reviewer
Data extraction Data was extracted from papers included in the review using standardised data
extraction tool (Appendix II) from the JBI-SUMARI Details of eligible studies were
extracted and summarised independently by two reviewers
Data Synthesis
All data analysissynthesis were made using the JBI-SUMARI The studies were
assessed for clinical heterogeneity by considering the settings populations interventions
and outcomes Where possible these binary outcomes were analyzed by calculation of
the Odds Ratio with the 95 CI The weighted mean difference was calculated if the
pooled studies have used the same scale for continuous data The standardized mean
difference was calculated for continuous data measuring the same outcome on a
different scale In studies where statistical pooling of results was inappropriate the
findings were considered for inclusion as a narrative summary
Results The findings from the systematic review are presented first Followed by the results from
the meta-analysis component of this review
Description of studies From database search and hand search a total of 76 papers were identified Thirty
papers were then excluded because they did not meet the inclusion criteria Forty-six
full text were retrieved for further consideration for inclusion Of the 30 excluded reasons
for exclusion were follows 11articles were duplicated eight articles did not meet
649
17
participant inclusion criteria eight articles did not meet outcome criteria and nine articles
were correlation studies or discussion papers others articles were unclear reporting In
total after sorting six papers have been included in this article Figure 1 displays the
process used to identify relevant articles for inclusion in the systematic review
Figure 1 Stages of searching and inclusionexclusion of references for the review
Potentially relevant English-language and Chinese- language Studies Identified
Electronically and hand search (n=76)
Duplicate (n= 11) Papers excluded after evaluation of abstract (n=19)
Papers retrieved for detailed examination (N=46)
Papers excluded after review of full paper
(n=40)
Papers assessed for methodological
quality (n=6)
Papers included in systematic review
(n=6)
Methodological Quality
Of the six included articles 2722232425 two articles were RCT design224 with score 7 out
of 10 each paper from Critical Appraisal Checklist and four articles used
650
18
quasi-experimental design7222425 with socre 5 to 6 out of 10 because the quality of
the whole papers is still acceptable therefore these six articles were accepted after
primary reviewer and secondary reviewerrsquos decision
Randomisation
In two RCT articles224 one study24 used to a computer-generated program operated by
the St Jude Protocol and Data Management System to randomize the sample Another
study2 didnrsquot address how randomization was done
Allocation concealment
No studies reported allocation concealment
Intention-to-treat analysis
One quasi-experimental design7 stated Intention-to-treat analysis
Adequate follow up
The follow-up periods included 2or 3 days24 7 days2 4 week7 one month25 6 week25 12
week2216 week23 and 1 year23
Baseline comparability of groups
Three 22425 of six studies had baseline comparability in terms of age sex diagnosis
race institution duration of illness
Blinded outcome assessment
No studies used blinded outcome assessment The researchers including study team
patients staff and families were not blinded to the patientrsquos group assignment
Characteristics of included studies
651
19
There were six studies related to interventions designed to cancer-related fatigue for
pediatric patients than there are for adults There are a total of six including five
English-language papers 27222324 and one Chinese-language paper 25 ranging in year of
publication from 2007 to 2009
Patient characteristics
The research subjects of four papers included both school-aged children and
adolescents 7222324 one papers involved mainly adolescents25 and one paper sampled
only school-aged children 2 the range in ages was between six-18 years The number of
patients included in the samples ranged from nine to 60 The sources of case data were
from both outpatients and hospitalized children The types of cancer included acute
lymphoblastic leukemia (ALL) solid tumors acute myeloid leukemia (AML) and
lymphoma Overall ALL was the most commonly studied cancer type The stage of the
disease varied in these reports some patients were in the maintenance stage of
chemotherapy25 some had just received their first round of chemotherapy224 some had
completed two courses of treatments lasting 4-8 weeks each 7 and some had entered
the survivor stage 2223
Countries
Two RCTrsquos 2 24 were conducted in the USA There were four quasi-experimental design
studiesThree studies conducted in the USA7 22 23 and one in Taiwan25
Intervention types
652
20
The interventions included exercise training programs 2225 physical activity 2324
massage therapy 7 and health education 223 exercise training and physical activity as
an intervention method given in three different settings home 22 25 community 23 or
hospital 24 The studies used different types of exercise interventions including
home-based aerobic exercise use a Video Compact Disc 25 use of a bicycle-style
exerciser 24 aerobics2223 and various types of physical activities2 and strength-building
exercises 2223 The intensity of the exercise varied and often included gradual warm-up
exercises a period of main exercise and a cool down period For these studies2023 the
target exercise intensity was a heart rate of gt90 of the maximum heart rate (HR max) or
the increase in the percentage of heart rate reserve ( HRR) of 40-60
The number of weeks for the exercisephysical activity interventions duration including
2-4 days 24 6 weeks25 12 weeks22 and 16 weeks23 The frequency of exercise ranged
from 2-3 times per week to twice a day Typical duration of exercise ranged from 10 to 45
minutes There are three papers using exercise interventions based on ACSM (American
College of Sports Medicine) 2225 recommendations and one of these used an Activity
pyramid from the ACSM to determine intensity 24
One article did not clarify the type of exercise intervention or the reasons for their choices
23 In addition there was an article focusing on massage therapy 7 as an intervention in
this study the experimental group received four weeks of massage therapy either in the
clinic or in the patientrsquos room the therapy was applied by a professional masseur and
targeted the back legs arms chest stomach and face of the children However the
frequency of massage sessions per week and the duration of the massages were not
653
21
given There is another article about intervention measures combine health education
and physical activity 2 In this study patients were informed about the following (1) health
education patients received daily education about chemotherapy-related fatigue and
information from a health education manual written by the author (2) encouragement for
children to engage in activities such as listening to music drawing and reading and (3)
physical activity which involved walking along the corridors of the ward for 10-15 minutes
These health education measures were presented for 45-60 minutes a day for a total of
seven days The study design for non-pharmacological interventions used control groups
that included primarily people who had received standard treatment or people who did
not receive an exercise intervention
Outcome measures
Five measurement tools were used in this group of seven papers concerning childrenrsquos
fatigue (Appendix IV) Because those studies included both school-age children and
adolescents the following descriptions will be differentiated by age Fatigue
measurements for school-aged children with cancer include the following the Child
Fatigue Scale (CFS) 7 a scale that measures the frequency and intensity of fatigue and
the Fatigue Scale for 7-12 year Olds (FS-C) 224 a scale that can be used to evaluate the
intensity of fatigue On the other hand fatigue measurements for adolescent cancer
patients include the following the Fatigue Scale for 13-18-year-olds (FS-A) 24 a measure
that can help evaluate fatigue levels the Pediatric Quality of Life Multidimensional
Fatigue Scale (Peds QL-MFS) 2325 a tool that can be divided into three sub-scales to
understand the general cognitive and sleep rest components of fatigue and finally the
CIS-20 for school-age children and adolescents 22 a scale that measures four levels of
654
22
fatigue namely subjective experience attention motivation and physical activity Two
studies used the Peds QL-MFS scale to measure fatigue2325
Meta-analysis results Two studies of the included papers failed to provide sufficient raw data they could not be
included in the meta-analysis Hinds et al 24 did not include post-test data Genc et al 2
provided no pre-test data PostWhite et al7 reported that fatigue after the health
education intervention was not statistically different but they presented the results
without presenting fatigue-related data Therefore the meta-analysis included three
studies 222325
The heterogeneity of studies was analyzed with Chi square statistics and no statistical
significance was found Therefore the data was combined in meta-analysis according to
exercise intervention on fatigue In addition there were three articles using the Peds
QL-MFS as a research tool to examine childrenrsquos improvements in fatigue Among these
Keats 22 and Chiang 24 present the effectiveness of exercise interventions using three
subscales Therefore the meta-analysis also analysis of the effects of these exercise
intervention measures on three subscales of Peds QL-MFS general fatigue sleep rest
fatigue and cognitive fatigue
The effectiveness of exercise intervention for fatigue We analyzed the exercise intervention effect on fatigue A total of 2 studies 22 23 were
included Takken et al 22 used community-based exercise training program to reduce
fatigue of children 6 to 14 years (mean 93y) of age who survived ALL Fatigue
measurement by Checklist Individual Strength (CIS) after 12-week of training fatigue
655
23
show no significant differences between pre (meanplusmnSD 415plusmn147) and post training
(meanplusmnSD368plusmn217) but fatigue change from baseline mean reduction of 11
Keats et al23 although used community-based physical activity program to reduce fatigue
for adolescents 14 to 18 years of age (mean162 y) with cancer (Lymphoma leukemia CNS
tumor germ cell tumor) Studies used fatigue by PedsQLMFS Results show general fatigue
from baseline to 8 weeks and to 3 months follow up significantly improves General
fatigue sleeprest fatigue and total fatigue from baseline to 3 months follow up showed
significant improvements Sleeprest fatigue and total fatigue at 1 years followed up were
significant improvements
Figure 2 shows the overall effect of exercise intervention in children and adolescents with
cancers with a focus on improving fatigue Due to the lower heterogeneity (p>005) the
fixed effects model was used to pool the data for meta-analysis (Overall effect size=
-006 95 Confidence Interval (CI) -070 to 058) A result did not indicate a statistically
significant difference (p = 087)
656
24
Figure2 Meta-analysis results of exercise intervention on fatigue
In addition Keats23 and Chiang25 used the three sub-scales of Peds QL-MFS to
determine the general cognitive and sleep rest components of fatigue The following
present the effectiveness of exercise interventions using three subscales including
general fatigue sleep rest fatigue and cognitive fatigue 2325
Chiang et al 25 used a 6- week home-based aerobic exercise intervention to reduce
fatigue of children 7 to 18 years (mean age at experimental group was 1088 y in control
group was 1247 y) of age who with acute lymphoblastic leukemia Fatigue measurement
by Peds QL-MFS after training For intent-to ndash treat analysis the findings indicated that
there are no intervention effects and time differences by any items on the subscale of
fatigue For per-protocol analysis general fatigue( meanplusmnSD 422plusmn402) was the only
subscale that was significantly lower for children who received the exercise intervention
than those in control group at follow-up assessment (one month after the completion of
intervention)
Keats et al23 although used community-based physical activity program to reduce fatigue
for adolescents 14 to 18 years of age (mean162 y) with cancer (Lymphoma leukemia
CNS tumor germ cell tumor) Both studies used fatigue by PedsQLMFS Results show
general fatigue from baseline to 8 weeks and to 3 months follow up significantly improves
657
25
General fatigue sleeprest fatigue and total fatigue from baseline to 3 months follow up
showed significant improvements Sleeprest fatigue and total fatigue at 1 years followed
up were significant improvements
The effectiveness of exercise intervention for general fatigue
The impact of the exercise interventions upon levels of general fatigue was also analysed
The heterogeneity was low (p>005) Therefore the fixed effects model was used to
examine the effectiveness The effect size is -076 indicating a statistically significant
difference (p = 001 95 CI -135 to -017 Fig 3) The evidence suggests that exercise
intervention can reduce general fatigue in children with cancer
Fig 3 Meta-analysis results of exercise intervention for general fatigue
The effectiveness of exercise intervention for sleep rest fatigue
The following is the result of the meta-analysis of the effectiveness of exercise
interventions on sleep rest fatigue First the heterogeneity test was conducted with P gt
005 representing small heterogeneity and the fixed effects model was used Fig 4
shows the effect size is -035 indicating no statistically significant differences (p = 023
95 CI-092 to 022 Fig 4)
658
26
Fig 4 Meta-analysis results of exercise intervention for sleep rest fatigue
The effectiveness of exercise intervention for cognitive fatigue Lastly the following data reports the results of meta-analysis of the effectiveness of
exercise interventions for cognitive fatigue The heterogeneity was p>005 then the
fixed effects model was used The effect size is -035 indicating no statistically significant
differences (p = 024 95 CI-092 023 Fig 5)
Fig 5 Meta-analysis results of exercise intervention for cognitive fatigue
Narrative presentation of remaining included studies
Three studies were not included in meta-analysis Post-White et al7 one of the aims in
this study was to examine the effect of massage therapy on fatigue in children with
cancer The study was a quasi-experimental design Twenty-three childrenparent dyads
were enrolled 17completed all data points Children with cancer ages 7 to 18 years
received at least 2 identical cycles of chemotherapy and one parent participated in the
2-period crossover design in which 4 weekly massage sessions (MT) alternated with 4
659
27
weekly quiet-time (QT) control sessions There were no significant changes in fatigue in
children over the 4-week MT or QT conditions either independently (change over time) or
when we compared fatigue by condition
The lack of effect of massage on fatigue may be the difficulty some children had in
differentiating fatigue from being relaxed underscores the challenge of measuring fatigue
in children Some children interpreted being tired or relaxed as having greater fatigue
because they felt like lying around and sleeping or felt unmotivated to do their usual
activities all measures of fatigue in the instrument used in the study
Hinds et al24conducted a prospective two-site randomized controlled pilot study to
assess the feasibility of an enhanced physical activity (EPA) intervention in hospitalized
children and adolescents receiving treatment for a solid tumor or for acute myeloid
leukemia (AML) Twenty-nine patients (25 with a solid tumor and 4 with AML) participated
age range from 736 to 1816 (mean 1248 y) The EPA intervention selected was
pedaling a stationary bicycle-style exerciser (Chattanooga Peddler Deluxe Bio-Teck
Medical Memphis TN) for 30 minutes twice daily for 2 to 4 days of hospitalization The
mixed model analysis revealed no significant differences in patient reports of fatigue
between the two study arms or over time
Genc et al2 conducted a RCT involving children with cancer who are 7 to 12 years of age
and receiving chemotherapy treatment to determine the impact of educational
intervention by nurses on decreasing the fatigue syndrome The research sample was
composed of a total of 60 children with cancer with 30 children being included in the
660
28
experimental group (mean age 923)and 30 children included in the control group (mean
age 937) with their mothers In the experimental group after the 7th to 10th day of the
chemotherapy treatment throughout a week the researcher conducted the nursing
interventions every day for 45 to 60 minutes In the control group routine nursing
interventions were carried out The experimental group received education about the
fatigue with the chemotherapy and fatigue handbook was given which was developed by
the authors Children and mothers were consulted for including activities that could
decrease fatigue which were described as effective interventions A statistically
significant difference was found between the Fatigue Scale-Child mean scores of the
experimental (2723) and the control group (4213) The results suggest that fatigue of
children with cancer can be reduced by implementing appropriate nursing interventions
(t=567 Plt00)
Discussion The purpose of this systematic review was to determine the effectiveness of
non-pharmacological interventions specifically targeting fatigue for children and
adolescents with cancer undergoing chemotherapy or after receiving chemotherapy
Included articles about the effectiveness of non-pharmacological interventions for
children and adolescents with cancer were published between the years of 2007 and
2009 Although interventions for cancer fatigue for adults have been extensively studied
it can be seen from either the title of the paper or related content that an intervention
study on children was a pilot study or a feasibility study Representing a field in its early
stage these studies show that the fatigue issues with young cancer patients have only
recently been taken seriously
661
29
The results of our meta-analysis include measurement of the four performance indicators
fatigue and general fatigue sleep rest fatigue and cognitive fatigue The results show
that there is a statistically significant difference only in the domain of general fatigue
using an exercise intervention for children with cancer can improve the degree of fatigue
with the effect size reaching 0671 Other results do not indicate significant differences
The reasons may include the following
1 Characteristics of the cancer The exhaustion from cancer occurs not only during cancer treatment but also in during
long-term survival a time during which patients may continue to be affected by this
symptom 8 26 Therefore when using intervention measures to improve fatigue
circumstances should be considered such as the process of the treatment and the course
or stage of the disease Because cancer patients will experience different forms of
treatment or courses of treatment the disease itself or treatment differences should be
considered in the choice of intervention Even chemotherapy drugs should be taken into
consideration For example a period of general steroid treatment can increase patientsrsquo
fatigue In those studies of children with cancer few studies looked solely at one type of
cancer most studies included a variety of cancer patients Furthermore most studies do
not clearly explain the stage of the disease or course of treatment and most do not
include treatment variables in the control group Moreover children with cancer may
have different levels of physical function
2 Research design The sample size Currently there are few studies with large sample size and a rigorous
RCT design due to the small number of papers available for analysis The sample size
included in our studyrsquos data analysis is between 20 and 42 people this small sample size
will affect the power available to evaluate outcome variables
Although most of the non-pharmacological interventions still use exercise and physical
activity and these studies overall show better results for fatigue as compared with
controls more research is still needed to further confirm the efficacy of these findings
662
30
The dropout rate in the evaluated research varies a great deal ranging from 5 to 45
these dropout rates may result from the characteristics of the research subjects or the
lengthy time involved in participating in these studies The research data with a high
turnover rate might not reflect the actual outcomes of participation in exercise and the
quality of the research contained in articles with high subject turnover rates may be
lower
Exercise doses and time The exercise doses needed to reduce fatigue cannot be
determined additionally the amount of exercise completed by the patient is also
inconsistent interventions vary between 2-3 times per week and two times a day and
exercise duration varies between 10 and 45 minutes each time Furthermore the study
interventions vary in length between a couple of days and a long period of 16 weeks The
data collection times are different some were measured 12 weeks after the intervention
began some were measured during the 6 weeks of intervention some were measured
three months after the intervention was finished and some were measured after one
year
In addition disease-related symptoms decrease childrenrsquos willingness to participate in
exercise interventions inappropriate exercise intervention programs may actually
increase childrens fatigue In addition the children in the study are still developing
physically it is important to consider ways to design an interesting exercise intervention
to increase the compliance of patients in order to improve the effectiveness Although
intervention programs in the hospital or in a community sports center can improve the
effectiveness because they provide supervision the feasibility of these programs is
questionable However if the program is home-based the children need to be
supervised by parents in order to improve their compliance in doing the exercises
Furthermore regarding the nature of the intervention the results from this study indicate
that the researched non-pharmacological interventions include the following exercise
training programs physical activity massage therapy and health education interventions
However according to the National Comprehensive Cancer Network 1 clinical guidelines
663
31
for cancer non-drug measures for cancer fatigue can be separated into five categories
(1) activity enhancement (2) psychosocial interventions such as cognitive behavioral
therapy (CBT) stress management relaxation techniques and support groups (3)
attention-restoring therapy (4) nutritional consultation and (5) cognitive behavioral
therapy specifically targeting sleep disturbance Researchers have also suggested that
psychosocial interventions should be included in the future research for children with
cancer-related fatigue 22
(2) The measurement tools in the study The assessment of fatigue can be
one-dimensional or multidimensional One-dimensional assessment can help understand
the severity of fatigue symptoms however multidimensional scales are often more
credible Therefore when measuring cancer-related fatigue researchers should consider
whether there is a uniform definition of fatigue or a standardized tool for measuring
fatigue in order to facilitate further systematic meta-analyses and further develop the
clinical care guidelines
Limitations of the review The present review has some potential limitations First the low methodological quality
may influence the result Although exercise intervention seems promising quality of the
RCTs was generally quite low Future studies require better design and reporting if
methodological issues to establish evidence-based nonpharmcologic intervention
Second the identified studies covered only a limited types of nonpharmcological
intervention especially in exercise intervention The guidelines for cancer-related fatigue
in NCCN (2011)1 referred to more interventions than the ones included in this review
such as cognitive behavioral therapy and nutrition consultation Thirdly the small sample
size and effect size could be potentially having led to underpowered approach for
detecting the effects on fatigue Therefore we recommend that as research continues to
grow a re-analysis can be undertaken Fourthly Combining data in meta analysis from
664
32
studies where the ages were quite different is a potential source of heterogeneity and
may affect the interpretation of the results
Conclusion At present clinical treatment is widely used for cancer patients However child and
adolescent cancer patients often experience various side effects which cause short-term
or long-term discomfort both physically and psychologically In particular with the
increasing cure rate cancer related fatigue during or after treatment has become an
important issue This study result provided positive effect of exercise intervention on
general fatigue
Implications for practice The results of this systematic review and meta-analysis show that exercise interventions
can effectively improve the level of general fatigue In particular although the articles
were self-reported feasibility studies their results all indicate that exercise interventions
for fatigue are feasible and safe there was no conclusion to be made for the use of
massage therapy or health education measures because there was only one article for
each of these interventions
Recommendations for practice
Cancer-related fatigue is one of the most severe and frequent symptoms by pediatric
oncology children and adolescent suffered during treatment and the symptom existed
even after treatment has ended Until now no golden standard of treatment to fatigue is
established The findings call for more attention to how to reduce patientrsquos levels of
fatigue Based on the available information evaluated in this review the following
recommendations for practice are provided
665
33
bull For children aged 7 to 18 who has cancer (eg Lymphoma leukemia CNS tumor
germ cell tumor) an effective progressive aerobic exercise program is recommended to
be at least 2-3 times per week 20 to 45 minute for each session and last for 6-16 weeks
in order to reduce their general fatigue (tiredness physically weakness) In addition
adults should be involved in accompanying children while they are performing physical
exercise of which should be able to improve the adherence rate (level 2 ) ( Grade of
recommendation A)
bull For children aged 7 to 18 who has cancer (eg Lymphoma leukemia CNS tumor
germ cell tumor) an progressive aerobic exercise program will not be effective to reduce
their sleep andor rest (sleeping or resting a lot) or cognitive fatigue (problems with
thinking quickly or problems with remembering) (level 2 ) ( Grade of recommendation C)
bull Nursing interventions in educating treatment of fatigue include information about
activity nutrition energy preservation consulting and providing a useful fatigue
handbook will benefit those children who are 7 to 12 years have a new diagnosis of ALL
AML or lymphoma and receive for the first time after being diagnosed a 7- to 10-day
chemotherapy treatment (level 2) ( Grade of recommendation A)
bull A 4-week massage therapy program (the therapists massage childrenrsquos back legs
arms stomachchest and face) is not effective for children who are aged 7 to 18 and
have acute lymphoblastic leukemia brain tumors lymphoma rhabdomyosarcoma
Wilms tumor or Ewing sarcoma(level 2)( Grade of recommendation C)
bull Using a 12-week aerobic and strength exercise (45-min exercise sessions twice a
week) is not effective for children who are aged 6-14 and survived acute lymphoblaststic
leukemia age from 6 to 14(level 2) ( Grade of recommendation C)
bull Using a physical activity intervention (30minutestwice daily for 2-4days) is not
effective for children who are 7 to 18 years of age with soild tumor or AML(level 2)
( Grade of recommendation C)
666
34
Implications for research According to this systematic review and meta-analysis results there are suggestions to
improve the effectiveness of future research on non-pharmacological interventions for
children and young peoplersquos cancer-related fatigue
As the majority of included non-pharmacological interventions for the fatigue of cancer
patients consist of exercise programs future research should also consider various
non-pharmacological interventions in order to understand the effectiveness of different
methods
Regarding the exercise intervention methods and studies should consider multiple
factors including the age or personal condition of the subject the disease stage and the
amount of daily activities Studies should use design prescriptions (eg frequency
intensity duration and type of exercise) and consider the adherence to the measures in
order to enhance the study strength
In measuring the results of non-pharmacological interventions there should be standard
definitions or standard measurement tools to facilitate the following systematic review
and meta-analysis that can subsequently be developed into clinical care guidelines
Reviewing the effectiveness of the current non-pharmacological management of children
and adolescent cancer patients there is still a lack of rigorous RCT research Limited by
the characteristics of cancer there is still a lack of large sample sizes
Potential conflicts of interest There is no conflict of interest
Acknowledgements
Thank you to Dr Rie Konno Research Fellow Joanna Briggs Institute for her help in
assessing studies
667
35
References 1 National Comprehensive Cancer Network( NCCN) in USA NCCN clinical practice
guideline in oncology cancer-related fatigue 2011 2 Ekti Genc R amp Conk Z Impact of effective nursing interventions to the fatigue
syndrome in children who receive chemotherapy Cancer Nursing 200831(4)312-317
3 Childhood Cancer Foundation of ROC (2009March) The classification of diseases
and age sex statistical tables of case Childhood Cancer Foundation of ROC newsletter103105-106
4 Department of Health Executive Yuan ROC (TAIWAN)(2009 March 20)2009 cause of death statistic Health and National Health Insurance Annual Statistics Information Service 2010 June 28Available httpwwwdohgovtwstatisticdatavital statists9898health statistic--lifepdf
5 Chang TK (2007December 8) Common childhood cancer and its treatment Status
Childhood Cancer Foundation of ROC (TAIWAN) 2010 September 23 Available httpwwwccfrocorgtwchildchild_events_readphpe_id=45
6 Hockenberry MJ amp Wilson D Wongs nursing care of infants and children (8th ed) St
Louis MO Mosby 2007
7 Post-White J Fitzgerald M Savik K Hooke MC Hannahan AB amp Sencer SF
Massage therapy for children with cancer Journal of Pediatric Oncology Nursing 2009 26(1)16-28
8Chiang YC Yeh CH Wang WKamp Yang CP The experience of cancer-related fatigue
in Taiwanese children European Journal of Cancer Care 2009 18(1)43-49 9Langeveld NE Grootenhuis M A Voute P A de Haan RJ amp van den Bos C No excess
fatigue in young adult survivors of childhood cancer European Journal of Cancer 200339(2)204-214
10Piper BF Lindsey AM amp Dodd MJ Fatigue mechanisms in cancer patients
developing nursing theory Oncology Nursing Forum 1987 14(6)17-23 11Nail LM amp Winningham ML Fatigue In S L Groenwald M H Forgge M Goodman
amp C H Yarbro (Eds) Cancer Nursing Principles and practice (4 th ed) Boston Jones and Bartlett1997
12Irvine D Vincent L Graydon JE Bubela N amp Thompson L The prevalence and
correlates of fatigue in patients receiving treatment with chemotherapy and
668
36
radiotherapy A comparison with the fatigue experienced by healthy individuals Cancer Nursing 199417(5)367-378
13Hinds PS amp Hockenberry-Eaton M Developing a research program on fatigue in
children and adloescents diagnosed with cancer Journal of Pediatric Oncology Nursing 200118(2)3-12
14Aaronson LS Teel CS Cassmeyer V Neuberger GB Pallikkathayil L Pierce J Press
AN Williams DP amp Wingate A Defining and measuring fatigue Journal of Nursing scholarship 1999 31(1)45-50
15Yeh CH Wang CH Chiang YC Lin Lamp Chien LC Assessment of symptoms reported
by 10- to 18-year-old cancer patients in Taiwan 2009 38(5)738-746 16 Okuyama T Akechi T Kugaya A Okamura H Shima Yamp Maruguchi M
Development and validation of the cancer fatigue scale a brief three-dimensional self-rating scale for assessment of fatigue in cancer patients Journal of Pain amp Symptom Management 2000 19(1) 5-14
17Gibson F Mulhall AB Richardson A Edwards JL Ream E amp Sepion BJ A
phenomenologic study of fatigue in adolescents receiving treatment for cancer Oncology Nursing Forum200532(3)651-660
18Wolfe J Grier HE Klar N Levin SB Ellenbogen JMamp Salem-Schatz S et al
Symptoms and suffering at the end of life in children with cancer New England Journal of Medicine 2000342(5)326-333
19Whiting P Bagnall AM Sowden AJ Cornell JE Mulrow CD amp Ramirez G
Interventions for the treatment and management of chronic fatigue syndrome a systematic review JAMA the Journal of the American Medical Association 2001286(11)1360-1368
20 Kangas M Bovbjerg DHamp Montgomery G H Cancer-related fatigue a systematic
and meta-analytic review of non-pharmacological therapies for cancer patients Psychological Bulletin 2008134 (5)700-741
21Williams PD Schmideskamp J Ridder EL amp Williams AR Symptom monitoring and
dependent care during cancer treatment in children pilot study Cancer Nursing 200629(3)188-197
22Takken T van der Torre P Zwerink M Hulzebos EH Bierings M Helders PJMamp van
der Net J Development feasibility and efficacy of a community-based exercise training
669
37
program in pediatric cancer survivors Psycho-Oncology 200918(4)440-448
23Keats MR amp Culos-Reed SN A community-based physical activity program for
adolescents with cancer (project TREK) program feasibility and preliminary findings
Pediatric hematology and oncology 200830(4) 272-280
24Hinds PS Hockenberry M Rai SN Zhang L Razzouk B I Cremer L McCarthy K amp
Rodriguez-Galindo C Clinical field testing of an enhanced-activity intervention in
hospitalized children with cancer Journal of Pain amp Symptom Management 2007
33(6)686-697
25Chiang YC The effects of ldquo a home-based aerobic exercise interventionrdquo on fatigue
and cardiorespiratory fitness in children with acute lymphoblastic leukemia during the
maintenance stage of chemotherapy Unpublished thesis Taiwan Tao-Yuan 2007
26Langeveld N Ubbink M amp Smets E I dont have any energy The experience of
fatigue in young adult survivors of childhood cancer European journal of oncology
nursing 20004(1)20-28
27 Kisner C Colby L Therapeutic exercise Foundations and techniques 2nd ed Philadelphia PAFA Davies 2007
670
38
Appendix I JBI Critical Appraisal Checklist for Experimental studies
Author__________ Year_________ Record Number__________________
Questions 1 to 4 must be answered ldquoyesrdquo for study to be included in the metashyanalysis
1 Were the participants randomized to study groups
Yes No Not clear
2 Other than research intervention were participants in each groups treated the same
Yes No Not clear
3 Were the outcomes measured in the same manner for all participants
Yes No Not clear
4 Were groups comparable at entry
Yes No Not clear
5 Was randomization of participants blinded
Yes No Not clear
6 Were those assessing outcome blinded to treatment allocation (if outcome not objective such as survival or length of hospitalization)
Yes No Not clear
7 Was allocation to treatment groups concealed from the allocator
Yes No Not clear
8 Was an appropriate statistical analysis used
671
39
Yes No Not clear
9 Were outcomes measured in a reliable way
Yes No Not clear
10 Was there adequate followshyup of participants
Yes No Not clear
Summary
TOTAL
Yes No Not clear
DECISION
Use Reject
Narrative summary only Further information needed
COMMENTS
672
40
Appendix II JBI Data Extraction Tool for Quantitative Studies Authors and Year
Journal Title
Record NumberArticle Reference No
Reviewer
Method
Settings
Participants
Number of participants
Group A Group B Group C
Control Intervention 1 Intervention 2
Interventions
Group A
Control
Group B
Intervention 1
Group C
Intervention 2
Outcome measures
Definition
673
41
Other outcome measures
Outcome description ScaleMeasure
Results
Dichotomous Data
Outcome Control Group
Numbertotal number
Treatment Group
Numbertotal number
Continuous Data
Authorrsquos Conclusions
Comments
Outcome Control Group
Mean amp SD
Treatment Group
Mean amp SD
674
43
Appendix III Details of included studies (N=6)(2720212223) RefNo Author(s)
(years) Title Study question Research
method Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
22 Takken T van der Torre P Zwerink M Hulzebos E H Bierings M Helders P J Mamp van der Net J (2009)
Development feasibility and efficacy of a community-based exercise training program in pediatric cancer survivors
To develop a 12-week home-based exercise training program (comprising aerobic and strength exercises) for children who survived ALL and to study itrsquos feasibility and efficacy
Pre-post test design
No comparsion group
Survived ALL(N=9)ages 6-14 years
1anthropometry 2 muscle strength 3functional mobility 4cardio-pulmonary
exercise test 5Fatigue
1 Feasibility questionnaire 2 anthropometry electronic scale and a wallmounted stadiometerHarpenden skin fold calipers 3 muscle strength handheld dynamometer 4functional mobility Timed Up
and Go test (TUG) 5cardio-pulmonary exercise test electronically braked cycle ergometer 6Fatigue(mean)CSI-20 (subjective experience of fatigueconcentrationmotivationphysical activity)
112-week exercise training program
2 Patients were assessed before (T0) and after (T1) 12 weeks of training
1 muscle strength execapacity functional moand fatigue showed nosignificant differences between pre(meanplusmnSD415plusmn147) and post training(meanplusmnSD3687)
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
7 Post-White J Fitzgerald M Savik K Hooke M C Hannahan A B amp Sencer S F (2009)
Massage therapy for children with cancer
To determine whether 4 weekly sessions of massage compared with 4 quiet-time control conditions would reduce anxiety cortisol levels fatigue nausea and pain in children with cancer undergoing chemotherapy and would reduce anxiety fatigue and mood disturbance in a parent
2-period crossover design (Randomized)
quiet-time
control
sessions
Children with cancer 1 to 18 years of age Twenty-three childrenparent dyads were enrolled 17 completed all data points
children 1relaxation 2symptoms 3 fatigue
parents
1anxiety 2 fatigue
children 1relaxation (heart and respiratory rates blood pressure and salivary cortisol level)
2symptoms (pain nausea anxiety 3 fatigue 1-2y3-6yLansky Play Performance Scale (PPS) 7-13y
1 4 weekly massage (MT) sessions alternated with 4 weekly quiet-time(QT) control sessions
2 children included presession and postsession vital signs (heart rate respiratory rate blood pressure) and self-report (parent proxy report for age 1-2 years) of pain nausea and anxiety Fatigue was measured before sessions 1 and 4 and at each follow-up Parent measures
included anxiety fatigue and mood states
1Massage was moreeffective than quiet tireducing heart rate inchildren anxiety in cless than age 14 yeaparent anxiety 2There were no sign
changes in blood pcortisol pain naufatigue (no state d
3 Children reported tmassage helped thebetter lessened theirand worries and hadlasting effects than q
675
44
14-18yChild Fatigue Scale (CFS) (frequency
intensity) 2 parents anxiety and fatigue
676
45
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
24 Hinds P S Hockenberry M Rai S N Zhang L Razzouk B I Cremer L McCarthy K amp Rodriguez-Galindo C (2007)
Clinical field testing of an enhanced-activity intervention in hospitalized children with cancer
To determine the feasibility of an
enhanced physical activity EPA intervention in children and adolescents hospitalized to receive chemotherapy for a solid tumor or AML and to assess the sleep and fatigue outcomes of the intervention using two different statistical approaches to analyze the longitudinal symptom data
randomized prospective two-site and two-group pilot study
Standard care Twenty nine patients (25 with a solid tumor and 4 with AML)ages 7-18 years
1 sleep duration 2 sleep efficiency 3 fatigue
1sleep duration sleep efficiency The
Wrist Actigraph The Daily Sleep Diary-Parent 2 fatigue (mean) The Fatigue Scale(FS-C) for 7-12 (intensity) The Fatigue Scale(FS-A) for 13-18 The Fatigue Scale Parent Version (FS-P) The Fatigue Scale Staff Version (FS-S)
1enhanced physical activity (EPA) (hospital-based 30 minutes
twice daily for 2-4 days) 2 T0On the day of admission
(Day 0 or baseline)patient and parents completed the fatigue instruments and a team member applied the actigraph Patients wore the wrist actigraph T1 from Day 0 to 2 or 3 consecutive days (Days 0e3) In addition the patient same parent and staff nurses completed the daily sleep and fatigue reports in the late afternoons of Days 1-3
1 ANOVA model slesignificantly more the experimental athe control arm whdifferences from bsleep efficiency vaaveraged and com
2 The patient-reported mean fatigue scoresarms were higher amadolescents than for
3 The mixed model anarevealed no significandifferences in patientfatigue between
the two study arms otime( no final result iSD only give mixed result)
677
46
23 Keats M
R amp Culos-Reed S N (2008)
A community-based physical activity program for adolescents with cancer (project TREK) program feasibility and preliminary findings
To examine the
feasibility of a
theoretically-based
physical activity (PA)
intervention in
adolescents with
cancerand
examination of the
impact of the
program on
participant QOL
including social
emotional and
physical
well-being(including fatigue)
Repeat measures longitudinal design
No comparsion group
10 adolescents(Lymphoma(4)leukemia(4)CNS tumor(1)germ cell tumor(1)) ages 14-18 years
1physical fitness 2quality of life (QOL) 3PA behavior 4fatigue
1 Feasibility was assessed by participant recruitment attendance and adherence
2physical fitness Fitnessgram 3quality of life (QOL) Pediatric Quality of Life Inventory (PedsQL) 4PA behavior leisure score index (LSI) 5fatigue (mean) pediatric Quality of life
Multidimensional Fatigue Scale (Peds QL-MFS)
(Generalsleepcognitive fatigue)
116week physical activity (PA)
2 total PA physical fitness and overall QOL was assessed at 5 different intervals T0 preintervention (baseline) T1midintervention (after the
first 8 wk) T2 postintervention
(16 wk) T3 3-months
postintervention T4 1-year poststudy
initiation
1 from baseline -wkssig Improvementstotal PA physfitness and Qgeneral fatigue(meanplusmnSD 796plusmn135)
2 from baseline to 3FUsig Improvin general fatigue(meanplusmnSD824plusmn131)slefatigue(meanplusmnSD755plusmn191)totafatigue(meanplusmnSD778plusmn150)
3at 1 years FUsImprovements in sleeprest fatigue(meanplusmnSD725plusmn203)total (meanplusmnSD 763plusmn
678
47
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
2 Gene R E amp Conk Z (2008)
Impact of Effective Nursing Interventions to the Fatigue Syndrome in Children Who Receive Chemotherapy
1 to examine the effects of an effective nursing intervention to the fatigue syndrome of children 7 to 12 years of age who receive chemotherapy 2Tto examine the relationship between fatigue and demographic variables (age sex) diagnoses ([ALL AML] lymphoma) and therapy-related variables (eg level of hemoglobin
experimental randomized controlled study
Routine nursing care
A total of 60 children who are 7-12 years of age(a new diagnosis of ALL AML or lymphoma and receiving for the first time after being diagnosed a 7- to 10-day chemotherapy treatment )
fatigue The Fatigue Scale(FS-C) for 7-12 (intensity)
The Fatigue Scale Parent Version (FS-P)
1 effective nursing interventions(45- 60mdaya week)education about the fatigue with the chemotherapy and fatigue handbook 2 T1 After a 7-day period the children
and parent were evaluated with the Fatigue Scale
1The difference betwthe 2 mean values wafound to be statisticallsignificant 2 statistically significadifference was found between the Fatigue Scale-Child mean scothe experimental (272the control group (4213)children
679
48
25 Chiang et
al(2007)
The effects of ldquo a home ndashbased aerobic exercise interventionrdquo on fatigue and cardiorespiratory fitness in children with Acute Lymphoblastic Leukemia during the maintenance stage of chemotherapy
To examine the effect of ldquo a home ndashbased aerobic exercise interventionrdquo on fatigue and cardiorespiratory fitness in children with Acute Lymphoblastic Leukemia during the maintenance stage of chemotherapy
Quasi-experi -mental
Routine
nursing care
14 pediatric oncology patients in the experimental group and 10 in control group who were matched by age and sex ages7-18 years
1Cardiorespiratory fitness
2Fatigue
1Cardiorespiratory fitness Physical Activity Recall
VO2maxHR peak 6MWT
2 Fatigue PedsQL-MFS(Generalsleepcognitive fatigue)
1A six-week home-based aerobic exercise intervention 2 8 time points T0 baseline T1-T6 every week during the
intervention(6 weeks) T7 post intervention T8 follow-up (one month after
the end of the home-based exercise program)
1 For intent-to ndash treatthe findings indicated are no intervention efftime differences by anon the subscale of fat2 For per-protocol angeneral fatigue( mean422plusmn402) was the osubscale that was siglower for children whothe exercise interventthose in control groupfollow-up assessmentmonth after the compintervention) 3 The VO2peak are significantly improvingexperimental group atbaseline- and post-intassessment The VO2was significantly highechildren who were in experimental group thcontrol subjects at post-intervention assefor the per-protocol an
680
49
Appendix IV Instrument used to measure fatigue
Name Instrument
developers
Description Used in
age in
ref
Reliability
Consistency of
instrument
Checklist Individual Strength
(CIS)22
Vercoulen et
al1996
20 items using 7-point Likert scale of
fatigue To measure four aspects of
fatiguesubjective experience
contractionmotivation physical
Activity
6-14 Not reported
Child Fatigue Scale (CFS)7 Hockenberry
et al2003
14 items 2 part questionnaire frequency
(yes or no) 5-point Likert scale of the
intensity of any yes responses
7-13
14-18 α073-o84
The Fatigue Scale for 7-12
year Olds (FS-C)224
Hockenberry
et al
14 items provide a fatigue intensity score
5-point Likert scale
7-12 αo84
The Fatigue Scale for 13-18
year Olds (FS-A)24
Hockenberry
et al
14 items provide a fatigue intensity score
5-point Likert scale
13-18 α076-o96
Pediatric Quality of life
Multidimensional Fatigue
Scale (Peds QL-MFS)2325
Varni2002 18 items to measure three aspects of
fatigueGeneralsleepcognitive
14-18 Not reported
681
50
Appendix V Excluded studies and reasons for exclusion
Baggott C Dodd M Kennedy C Marina N Miaskowski C Multiple Symptoms in Pediatric Oncology
Patients A Systematic Review Journal of Pediatric Oncology Nursing 2009 Nov-Dec 27(6)
325-339
Reason for exclusion Not outcome of interest
Barlow JH Ellard DR Psycho-educational interventions for children with chronic disease parents and
siblings an overview of the research evidence base Care Health amp Development 2004 Nov
30(6)637-45
Reason for exclusion Not outcome of interest
Bedider S Moyer CA Randomized controlled trials of pediatric massage A review Evid Based
Complement Alternat Med 2007 Mar 4(1)23-34 Epub 2006 Nov 3
Reason for exclusion Not outcome of interest
de Nijs EJ Ros W Grijpdonck MH Nursing intervention for fatigue during the treatment for cancer Cancer
Nursing 2008 31(3)191-206
Reason for exclusion Not population of interest
Edwards JL Gibson F Richardson A Sepion B Ream E Fatigue in adolescents with and following a
cancer diagnosis developing an evidence base for practice European Journal of Cancer 2003
Dec 39(18)2671-80
Reason for exclusion Not experimental or quasi-experimental study
Hinds PS Hockenberry-Eatan M Developing a research program on fatigue in children and adolescents
diagnosed with cancer Journal of Pediatric Oncology Nursing 2001 Mar-Apr 18(2 Suppl
1)3-12
Reason for exclusion Not experimental or quasi-experimental study
Hockenberry-Eaton M Hinds PS Alcoser P ONeill JB Euell K Howard V Gattuso J Taylor J Fatigue in
Children and Adolescents With Cancer Journal of Pediatric Oncology Nursing 1998 July
15(3)172-182
Reason for exclusion Not experimental or quasi-experimental study
Jean-Pierre P Mustian K Kohli S Roscoe JA Hickok JT Morrow GR Community-based clinical oncology
research trials for cancer-related fatigue The Journal of Supportive Oncology 2006 Nov-Dec
4(10)511-6
682
51
Reason for exclusion Not population of interest
Kangas M Bovbjerg DH Montgomery GH Cancer-Related Fatigue A Systematic and Meta-Analytic
Review of Non-Pharmacological Therapies for Cancer Patients Psychological Bulletin 2008 Sep
134(5)700-41
Reason for exclusion Not population of interest
Lotfi-Jam K Carey M Jefford M Schofield P Charleson C Aranda S Nonpharmacologic strategies for
managing common chemotherapy adverse effects A systematic review Journal of Clinical
Oncology 2008 Dec 1 26(34)5618-29 Epub 2008 Nov 3
Reason for exclusion Not outcome of interest
Marchese VG Chiarello LA Lange BJ Effects of physical therapy intervention for children with acute
lymphoblastic leukemia Pediatr Blood Cancer 2004 Feb42(2)127-33
Reason for exclusion Not outcome of interest
Meeske KA Siegel SE Globe DR Mack WJ Bernstein L Prevalence and correlates of fatigue in
long-term survivors of childhood leukemia Journal of Clinical Oncology 2005 Aug 20
23(24)5501-10
Reason for exclusion Not intervention study
Minton O Richardson A Sharpe M Hotopf Stone P A systematic review and meta-analysis of the
pharmacological treatment of cancer-related fatigue J Natl Cancer Inst 2008 Aug 20
100(16)1155-66 Epub 2008 Aug 11
Reason for exclusion Not population and intervention of interest
Mustian KM Morrow GR Carroll JK Figueroa-Moseley CD Pascal JP Williams GC Integrative
nonpharmacologic behavioral interventions for the management of Cancer-Related fatigue The
Oncologist 2007 12(1)52-67
Reason for exclusion Not population of interest
Neill J Belan I Ried K Effectiveness of non-pharmacological interventions for fatigue in adults with
multiple sclerosis rheumatoid arthritis or systemic lupus erythematosus a systematic review
Journal of Advanced Nursing 2006 Dec 56(6)617-35
Reason for exclusion Not population of interest
Rheingans JI A systematic review of nonpharmacologic adjunctive therapies for symptom management
Journal of Pediatric Oncology Nursing 2007 24(2) 81-94
683
52
Reason for exclusion Not outcome of interest
Rheingans JI Pediatric oncology nursesrsquo management of patients symptoms Journal of Pediatric
Oncology Nursing 2008 Nov 25(6) 303-11
Reason for exclusion Not outcome of interest
San Juan AF Fleck SJ Chamorro-Vintildea C Mateacute-Muntildeoz JL Moral S Peacuterez M Cardona C Del Valle MF
Hernaacutendez M Ramiacuterez M Madero L Lucia A Effects of an intrahospital exercise program
intervention for children with leukemia Medicine amp Science in Sports amp Exercise 2007 Jan
39(1)13-21
Reason for exclusion Not outcome of interest
Sanford SD Okuma JO Pan J Srivastava DK West N Farr L Hinds PS Gender differences in sleep
fatigue and daytime activity in a pediatric oncology sample receiving dexamethasone Journal of
Pediatric Psychology 2008 Apr 33(3)298-306 Epub 2007 Nov 17
Reason for exclusion Not experimental or quasi-experimental study
Schmitz KH Holtzman J Courneya KS Macircsse LC Duval S Kane R Controlled physical activity trials in
cancer survivors a systematic review and meta-analysis Cancer Epidemiol Biomarkers Prev
2005 Jul 14(7)1588-95
Reason for exclusion Not population of interest
van Brussel M Takken T Lucia A van der Net J Helders PJ Is physical fitness decreased in survivors of
childhood leukemia A systematic review Leukemia 2005 Jan 19(1)13-7
Reason for exclusion Not population of interest
Whiting P Bagnall AM Snowden AJ Cornell JE Mulrow CD Ramirez G Interventions for the treatment
and management of chronic fatigue syndrome JAMA 2001 Sep 19 286(11)1360-8
Reason for exclusion Not intervention of interest
Whitsett SF Gudmundsdottir M Davies B McCarthy P Friedman D Chemotherapy-related fatigue in
childhood cancer correlates consequences and coping strategies Journal of Pediatric
Oncology Nursing 2008 Mar-Apr 25(2)86-96 Epub 2008 Feb 29
Reason for exclusion Not experimental or quasi-experimental study
Winner C Muumlller C Hoffmann C Boos J Rosenbaum D Physical activity and childhood cancer Pediatr
Blood Cancer 2010 Apr 54(4)501-10
Reason for exclusion Not research study
684
53
Wu M Hsu L Zhang B Shen N Lu H Li S The experiences of cancer-related fatigue among Chinese
children with leukaemia A phenomenological study Journal of Nursing Studies 2010 Jan
47(1)49-59 Epub 2009 Aug 25
Reason for exclusion Not experimental or quasi-experimental study
Yeh CH Chiang YC Lin L Yang CP Chien LC Weaver MA Chuang HL Clinical factors associated with
fatigue over time in paediatric oncology patients receiving chemotherapy British Journal of
Cancer 2008 Jul 8 99(1)23-9 Epub 2008 Jun 24
Reason for exclusion Not experimental or quasi-experimental study
685
3
extraction tool from the Joanna Briggs Institute-Meta-Analysis of Statistics Assessment
and Review Instrument
Results
The review included a total of six studies - five English-language papers and one
Chinese-language paper Meta-analysis did not show statistically significant impact on
the effectiveness of exercise interventions in reducing fatigue in children and adolescents
with cancer The impact of the exercise interventions on general fatigue did however
indicate a statistically significant difference (p = 001 95 Confidence Interval -135 to
-017)
Conclusions
The results of this systematic review show that exercise interventions can effectively
reduce the level of general fatigue of children six to 18 years No strong conclusions
can be made for the use of massage therapy or health education measures as there
was only one article for each of these interventions
Implications for practice The review provides an evidenced-based guide to future priorities for clinical practice
Exercise intervention could reduce the level of general fatigue of children who ages are
six to 18 In particular exercise intervention for fatigue are feasible and safe
Implications for research There is still a lack of rigorous research on this specific topic Further research requires
more rigorous study design and reporting of menthdologic issues such as randomized
controlled trials using concealment of allocation Other non-pharmacological
interventions should be also examined including cognitive behavioral therapy stress
management relaxation support groups massage therapy in this area
636
4
Keywords non-pharmacological intervention fatigue children adolescents cancer
exercise cognitive systematic review
BACKGROUND
The Clinical Practice Guidelines in Oncology of the National Comprehensive Cancer
Network (NCCN) in the USA define cancer-related fatigue as ldquoa distressing persistent
subjective sense of physical emotional andor cognitive tiredness or exhaustion related
to cancer or cancer treatments that is not proportional to recent activity and interferes
with daily functionrdquo(pFT-1)1 When children suffer from cancer fatigue is not only the most
consistently reported symptom by children with cancer but also one of the most
persistent and uncomfortable symptoms 2
The incidence of cancer in children is high across the world As an example the
incidence in the USA for children aged 0-14 years is approximately 129 per million with
an estimated projection of 8200 newly diagnosed cases per year3 In Taiwan
approximately 550-600 children are diagnosed with cancer every year4 According to the
estimation of group proportions the incidence of childhood cancer in Taiwan and the
United States are similar 5 In addition malignant tumor has become the second leading
causes of death for children and adolescents aged 1-14 years in Taiwan3 and US6
Although cancer has been one of the major illnesses threatening the life of children the
progress made in medical technology has led to a significant improvement in the
treatment of children and adolescents with cancer over the past three decades7
especially the increase in their survival rate Statistics have indicated that the five-year
637
5
survival rate of children with cancer has exceeded 756 however the treatments of
cancer tend to rely on aggressive chemotherapies which force children to face a long
treatment process as well as various physical and mental symptoms8 Fatigue is one of
the common symptoms affecting children during treatments Children may feel persistent
fatigue even after they complete cancer treatments9
To date the causes and mechanism of cancer-related fatigue are still unclear However
the theories concerning the causes of fatigue have been proposed Common theories
include Integrated Fatigue Model10 Psychobiological Entropy Model11 Energy Analysis
Model12
Piper et al (1987) 10 proposed the Integrated Fatigue Model which is one of the most
frequently cited fatigue models at present They suggest that fatigue is the tiredness felt
by individuals as a result of the influence of body rhythm which makes individuals
experience different degrees of discomfort In this model fatigue can be measured by
biochemical indicators such as cytokines interferon and tumor necrosis factors as well
as with a self-report fatigue scale
The term ldquoIntegratedrdquo refers to a combination of features including perception physics
biochemistry and behavior all of which affect level of fatigue and in turn influence
fatigue patterns including diseases treatments activitiesrests environment symptoms
social activities life events individual internal factors and other aspects of the patients
life
The second theory is the Psychobiological Entropy Model11 is the most complete fatigue
638
6
theory at present This model suggests that the main cause of fatigue is a lack of energy
The physical ability of patients is reduced because of the symptoms caused by diseases
or treatments and thus patients experience emotion-related fatigue and the reduction in
functional status as a result In addition the symptoms caused by reoccurring diseases
or treatments may be harmful to physical conditions even more and lead to disability
eventually In this model any treatment program that can address the decline in activity
can alleviate fatigue symptoms is said to improve fatigue Therefore Psychobiological
Entropy Model not only provides a more direct detection of clinical patterns but also for
providing measures of care within a fatigue model
The third model is the Energy Analysis Model12 which suggests that the pathological
change of individual physical status becomes the barrier of energy conversion When the
supply of energy in individuals is low or the demand is high a lack of energy results and
the individuals feel fatigue Energy is generated by the oxygenation in blood The
correction factors of energy reaction are cancer treatments symptom distress and
emotional disorders Concepts in the fatigue model include energy sources energy
transformations energy expenditures and energy response modifiers The relationships
among these concepts are dynamic and intercorrelated with each other From the Energy
Analysis Mode point of view the physiological mechanism of fatigue includes some
objective indicators such as body weight and hemglobulin
In terms of the causes of fatigue Ekti Genc amp Conk (2008) 2 indicated that illnesses
treatments and stage of disease can cause fatigue NCCN (2011) 1 points out that many
conditions are related to fatigue including pain emotional pain anaemia sleep disorders
639
7
nutritional deficiencies activity reduction side effects of drugs (antihistamine drugs
anti-vomiting drugs and anti-anxiety drugs) and others In a study on children
adolescents parents and relevant medical and nursing staffs Hinds and
Hockenberry-Eaton (2001) 13 proposed four factors causing the fatigue of children with
cancer which are 1) environmental factors treatment setting events or situations that
place demands on the patient such as appointments inpatient stay long waiting time
altered routines that lack clear beginnings and endings of each day and decision making
and information exchange 2) personalbehavioral factors the negative faith of children
with illness 3) culturalfamilyother factors emotions concerns the hope of friends and
family ability to participate in activities and restricted activities 4) treatment-related
factors the invasive inspections experienced by children with illness insufficient time for
physical strength recovery between the repeated courses of treatments or the side
effects caused by treatments (infection pain and decrease in complete blood count) It
can be inferred that the causes of fatigue are complicated and multifaceted
Fatigue is a complex and multidimensional condition 10 therefore fatigue is subject to
different definitions and there are different measurement tools Aaronson et alrsquos14
review the literature of fatigue summarised the characteristics of fatigue measurement
including the following(1) Subjective quantification of fatigue can be determined with the
Lee and colleagues (1991) Visual Analog Scale for Fatigue (VASF)(2) Subjective
distress This item simply asks the rater to report to what degree fatigue has caused
distress (3) The effect of fatigue on activities of daily living (4) Correlates of fatigue
such as sleep and depression to assess when measuring fatigue (5) key biological
parameters such as cytokines interferon and tumor necrosis factor
640
8
Fatigue can be also measured with unidimensional or multidimensional scales The first
type of fatigue scale is not suitable for studies focusing on fatigue because they are too
long if the aim is to only assess fatigue Furthermore they only allow for a limited number
of possible responses Unidimensional scales also are not suitable for the in-depth study
of fatigue because they assess only one aspect of fatigue15
In recent years fatigue in children with cancer has received some attention and
measurement tools have gradually been developed - such as1) Checklist individual
strength (CIS) The items are scored on 7-point Likert scales (with 1 indicating best and
7 worst function) 2) The Child Fatigue Scale (CFS) is a 2-part questionnaire that asks for
a yes or no (frequency) response and a 5-point rating of the intensity of any yes
responses ranging from not at all to a lot The Fatigue Scale for 7-12 year Olds (FS-C)
is provide a fatigue intensity score higher scores indicating higher fatigue The Fatigue
Scale for 13-18 year Olds (FS-A) measure adolescent cancer patientsrsquo perceptions of
the intensity of their fatigue on a daily or weekly basis higher scores indicating higher
fatigue 3) The Fatigue Scale Parent Version (FS-P) measures the parentsrsquo perception
of their childrsquos fatigue intensity on a five-point Likert-type scale higher scores indicating
higher fatigue 4) The Fatigue Scale Staff Version (FS-S ) measures the staffrsquos
perceptions of the patientrsquos fatigue intensity during the past 24 hours Intensity ratings are
on a four-point Likert-type scale with higher scores indicating more intense fatigue
symptoms 5) The Pediatric Quality of life Multidimensional Fatigue Scale (Peds
QL-MFS)Higher scores (0 to 100) indicate less fatigue( Appendix IV)
Besides disturbing physical and mental functions and status fatigue also affects the
641
9
quality of life 15 of children with cancer and impacts their daily life16 among all different
types of cancer progress and childrsquos ages However as opposed to the fatigue of adults
the fatigue of children tends to be neglected and left untreated17 by medical and nursing
staffs
In terms of the management approach to cancer-related fatigue Ekti Gene (2008) 2
suggests that strategies could include pharmacologic and non-pharmacologic measures
NCCN (2011) 1 indicated in the Clinical Practice Guidelines in Oncology that during
aggressive treatments during long-term follow-up treatments or in the terminal phase of
cancer the intervening measures for cancer-related fatigue can be divided into
pharmacologic and non-pharmacologic measures Non-pharmacologic measures include
activity enhancement psychosocial interventions (eg cognitive behavioral therapy
(CBT) stress management relaxation support groups) attention-restoring therapy and
nutrition consultation As for the effectiveness of pharmacological measures the
effectiveness is still uncertain However there is evidence to suggest that
methylphenidate may be effective in treating cancer-related fatigue1 Whiting et al
(2001)18 included 36 randomized controlled trials and 8 controlled trails to assess the
effectiveness of the pharmacological and non-pharmacological interventions used in the
treatment or management of chronic fatigue syndrome in adults or children Results
showed insufficient evidence on the effectiveness of the pharmacological supplements
complementaryalternative and other interventions In addition the evidence of
pharmacological treatments of immunoglobulin and hydrocortisone were also
inconclusive However interventions such as cognitive behavioral therapy and graded
exercise therapy have shown promising results
642
10
The efficacy of pharmacological treatments for cancer-related fatigue has not been
established6 therefore there is a need to provide evidence-based findings of the
effectiveness of non-pharmacological interventions to support nursing intervention to
release the childrsquos cancer-related fatigue To date most studies have investigated the
effectiveness of non-pharmacological treatments on cancer-related fatigue of
adults20and to date there is no systematic review in relation to cancer-related fatigue of
children However as children are not a smaller version of adults it is inappropriate to
extrapolate the results of adults onto children Therefore there is a need to establish the
effectiveness of non-pharmacological intervention on the cancer-related fatigue of
children
Given the increase in childhood cancer survival rate the importance of decreasing
childrenrsquos cancer-related fatigue during treatments and so increase their quality of life has
become a focus of their medical teams The role of nurses during care intervention is to
confirm the major symptoms of children with illness and effectively treat each symptom to
increase the childrenrsquos quality of life21 Moreover the USA based NCCN also indicated in
the Care Standard for the Treatment of Cancer-related Fatigue of Children and
Adolescents that treatments for fatigue should be included in the health care teams and
the children and their family should be informed of relevant information The definition of
non-pharmacological interventions for childrenrsquos cancer ndashrelated fatigue include activity
enhancement (exercise physical activity) psychosocial interventions cognitive
behavioral therapy (CBT) stress management relaxation nutrition consultation
massage and educational interventions
643
11
The Cochrane Library of Systematic Reviews and The Joanna Briggs Institute Library of
Systematic Reviews were initially searched to ensure that systematic reviews on this
subject were not already published or being undertaken This initial search prior to the
commencement of the review did not yield any results
This systematic review has examined the effectiveness of non-pharmacologic
interventions on the cancer-related fatigue of children in hope of finding scientific
evidence that can support or refute such measures on children The results of this study
may serve as a reference for professional caregivers children with cancer and their
families or to be put into practice during the clinical care of children with cancer
Definition of terms
FatigueFatigue as a distressing persistent subjective sense of physical emotional
andor cognitive tiredness or exhaustion related to cancer or cancer treatments
that is not proportional to recent activity and interferes with daily function1 There
are various scales and measurements of the degree of fatiguewe have elected to
use the study authors own definitions of fatigue rather than applying a single
pre-set definition of the condition
Non-pharmacological interventionsReferring to reduce fatigue that does not involve
drugsNon-pharmacologic measures include activity enhancement psychosocial
interventions (eg cognitive behavioral therapy stress management relaxation
support groups) attention-restoring therapy and nutrition consultation1
ChemotherapyTreatment with drugs that kill cancer cells 1
644
12
Review QuestionsObjectives
Review Objective
The objective of this systematic review was to critically appraise synthesize and
present the best available evidence concerning the effects of non-pharmacological
interventions fatigue in children and adolescents with cancer
Review Question
The following specific question was addressed in this review
What is the effectiveness of non-pharmacological interventions on fatigue in
children and adolescents with cancer aged from one to 18 years
Criteria for Considering Studies for this Review
Types of studies
This review included randomised controlled trials (RCTs) and quasi-experimental
studies that examine the effectiveness of non-pharmacological intervention for fatigue in
children and adolescents with cancer
Types of participants
Children and adolescents aged from one to 18 years old experiencing fatigue
associated with cancer either during or after the chemotherapy or maintenance stage of
chemotherapy or survive stage The types of cancer to be included in this systematic
review will be ALL (Acute lymphoblastic leukemia) AML (Acute myeloid leukemia)
lymphoma and solid tumors
Exclusion criteria for Types of participants
645
13
newborn infants under 1 years of age
participants who do not have a specific diagnosis of cancer
participants who have received immunoglobulin or hydrocortisone
treatment
If participants have received immunoglobulin or hydrocortisone treatment may
inference the effectiveness of non-pharmacological interventions on fatigue
Types of intervention
This review considered studies that examine non-pharmacological interventions on
fatigue for children and adolescents with cancer including activity enhancement
(exercise physical activity) psychosocial interventions CBT stress management
relaxation nutrition consultation massage and educational interventions The
interventions descriptive included the length frequency setting and intervention
providers eg Nurse Psychologist Dietician
Exclusion criteria for types of interventions only pharmacological interventions were
tested
Types of outcome measures
The outcome measures considered were fatigue scores The literature demonstrates that
differences of opinion exist regarding the most valid and reliable method of measuring
cancer-related fatigue Therefore studies that used any validated scale for
cancer-related fatigue were considered for inclusion Currently commonly used scales to
measure fatigue include Checklist Individual Strength (CIS) Child Fatigue Scale (CFS)
The Fatigue Scale for 7-12 year Olds (FS-C) The Fatigue Scale for 13-18 year Olds
646
14
(FS-A)and Pediatric Quality of life Multidimensional Fatigue Scale (Peds QL-MFS)
Types of settings
Both hospital and community settings
Search Strategy
Before undertaking this systematic review the Cochrane Library Joanna Briggs Institute
Library of Systematic Reviews and CINAHL were searched and no systematic reviews on
this topic were found or identified as underway
The search strategy aimed to find both published and unpublished studies
A three-step search strategy was utilized in each component of this review An initial
limited search of CINAHL and MEDLINE was undertaken followed by an analysis of the
text words contained in the title and abstract and of the index terms used to describe the
article A second search using all identified keywords and index terms was undertaken
Lastly the reference lists of all identified reports and articles were searched for additional
studies
Types of languages
1 English
2 Chinese
The following databases were searched to identify keywords contained in the title and
abstract and relevant MeSH headings and descriptor terms
The Cochrane Library PsycINFO 1990 ndash 2010
647
15
Ovid MEDLINE 1966 ndash 2010 CINAHL Plus with Full Text 1960 ndash2010 EMBASE ProQuest Dissertations amp theses 1990-2010 Electronic theses and dissertations system 1956(abstract)1990(full text)-2010 MEDNAR Index to Taiwan periodical literature 1970-2010 Electronic thesis and dissertation system (Chinese) 1990-2010
Keyword search terms
1Types of studies experimental study random quasi-experimental study實驗性研究隨
機類實驗性研究
2 Types of participants childchildren adolescents pediatric cancer and oncology兒童
青少年兒科癌症腫瘤
3 Types of interventions non-pharmacological interventions massage exercise fitness
physical activity cognitive behavioral stress management energy conservation
sleep therapy relaxation distraction and psycho-education非藥物性處置按摩運動
身體活動認知行為壓力處置能量保存睡眠治療放鬆轉移注意力衛教
4 Types of outcome measures fatigue cancer-related fatigue loss of energy levels of
tiredness tired side effect symptoms疲憊癌性疲憊疲倦合併症症狀
Methods of the Review
Assessment of methodological quality Papers selected for retrieval were assessed by two independent reviewers for
methodological validity prior to inclusion in the review using the standardised critical
appraisal instruments (Appendix I) from the JBI-SUMARI (Joanna Briggs Institute
Systems for the Unified Management Assessment and Review of Information package)
Any disagreements that arise between the reviewers were resolved through discussion
648
16
with a third reviewer
Data extraction Data was extracted from papers included in the review using standardised data
extraction tool (Appendix II) from the JBI-SUMARI Details of eligible studies were
extracted and summarised independently by two reviewers
Data Synthesis
All data analysissynthesis were made using the JBI-SUMARI The studies were
assessed for clinical heterogeneity by considering the settings populations interventions
and outcomes Where possible these binary outcomes were analyzed by calculation of
the Odds Ratio with the 95 CI The weighted mean difference was calculated if the
pooled studies have used the same scale for continuous data The standardized mean
difference was calculated for continuous data measuring the same outcome on a
different scale In studies where statistical pooling of results was inappropriate the
findings were considered for inclusion as a narrative summary
Results The findings from the systematic review are presented first Followed by the results from
the meta-analysis component of this review
Description of studies From database search and hand search a total of 76 papers were identified Thirty
papers were then excluded because they did not meet the inclusion criteria Forty-six
full text were retrieved for further consideration for inclusion Of the 30 excluded reasons
for exclusion were follows 11articles were duplicated eight articles did not meet
649
17
participant inclusion criteria eight articles did not meet outcome criteria and nine articles
were correlation studies or discussion papers others articles were unclear reporting In
total after sorting six papers have been included in this article Figure 1 displays the
process used to identify relevant articles for inclusion in the systematic review
Figure 1 Stages of searching and inclusionexclusion of references for the review
Potentially relevant English-language and Chinese- language Studies Identified
Electronically and hand search (n=76)
Duplicate (n= 11) Papers excluded after evaluation of abstract (n=19)
Papers retrieved for detailed examination (N=46)
Papers excluded after review of full paper
(n=40)
Papers assessed for methodological
quality (n=6)
Papers included in systematic review
(n=6)
Methodological Quality
Of the six included articles 2722232425 two articles were RCT design224 with score 7 out
of 10 each paper from Critical Appraisal Checklist and four articles used
650
18
quasi-experimental design7222425 with socre 5 to 6 out of 10 because the quality of
the whole papers is still acceptable therefore these six articles were accepted after
primary reviewer and secondary reviewerrsquos decision
Randomisation
In two RCT articles224 one study24 used to a computer-generated program operated by
the St Jude Protocol and Data Management System to randomize the sample Another
study2 didnrsquot address how randomization was done
Allocation concealment
No studies reported allocation concealment
Intention-to-treat analysis
One quasi-experimental design7 stated Intention-to-treat analysis
Adequate follow up
The follow-up periods included 2or 3 days24 7 days2 4 week7 one month25 6 week25 12
week2216 week23 and 1 year23
Baseline comparability of groups
Three 22425 of six studies had baseline comparability in terms of age sex diagnosis
race institution duration of illness
Blinded outcome assessment
No studies used blinded outcome assessment The researchers including study team
patients staff and families were not blinded to the patientrsquos group assignment
Characteristics of included studies
651
19
There were six studies related to interventions designed to cancer-related fatigue for
pediatric patients than there are for adults There are a total of six including five
English-language papers 27222324 and one Chinese-language paper 25 ranging in year of
publication from 2007 to 2009
Patient characteristics
The research subjects of four papers included both school-aged children and
adolescents 7222324 one papers involved mainly adolescents25 and one paper sampled
only school-aged children 2 the range in ages was between six-18 years The number of
patients included in the samples ranged from nine to 60 The sources of case data were
from both outpatients and hospitalized children The types of cancer included acute
lymphoblastic leukemia (ALL) solid tumors acute myeloid leukemia (AML) and
lymphoma Overall ALL was the most commonly studied cancer type The stage of the
disease varied in these reports some patients were in the maintenance stage of
chemotherapy25 some had just received their first round of chemotherapy224 some had
completed two courses of treatments lasting 4-8 weeks each 7 and some had entered
the survivor stage 2223
Countries
Two RCTrsquos 2 24 were conducted in the USA There were four quasi-experimental design
studiesThree studies conducted in the USA7 22 23 and one in Taiwan25
Intervention types
652
20
The interventions included exercise training programs 2225 physical activity 2324
massage therapy 7 and health education 223 exercise training and physical activity as
an intervention method given in three different settings home 22 25 community 23 or
hospital 24 The studies used different types of exercise interventions including
home-based aerobic exercise use a Video Compact Disc 25 use of a bicycle-style
exerciser 24 aerobics2223 and various types of physical activities2 and strength-building
exercises 2223 The intensity of the exercise varied and often included gradual warm-up
exercises a period of main exercise and a cool down period For these studies2023 the
target exercise intensity was a heart rate of gt90 of the maximum heart rate (HR max) or
the increase in the percentage of heart rate reserve ( HRR) of 40-60
The number of weeks for the exercisephysical activity interventions duration including
2-4 days 24 6 weeks25 12 weeks22 and 16 weeks23 The frequency of exercise ranged
from 2-3 times per week to twice a day Typical duration of exercise ranged from 10 to 45
minutes There are three papers using exercise interventions based on ACSM (American
College of Sports Medicine) 2225 recommendations and one of these used an Activity
pyramid from the ACSM to determine intensity 24
One article did not clarify the type of exercise intervention or the reasons for their choices
23 In addition there was an article focusing on massage therapy 7 as an intervention in
this study the experimental group received four weeks of massage therapy either in the
clinic or in the patientrsquos room the therapy was applied by a professional masseur and
targeted the back legs arms chest stomach and face of the children However the
frequency of massage sessions per week and the duration of the massages were not
653
21
given There is another article about intervention measures combine health education
and physical activity 2 In this study patients were informed about the following (1) health
education patients received daily education about chemotherapy-related fatigue and
information from a health education manual written by the author (2) encouragement for
children to engage in activities such as listening to music drawing and reading and (3)
physical activity which involved walking along the corridors of the ward for 10-15 minutes
These health education measures were presented for 45-60 minutes a day for a total of
seven days The study design for non-pharmacological interventions used control groups
that included primarily people who had received standard treatment or people who did
not receive an exercise intervention
Outcome measures
Five measurement tools were used in this group of seven papers concerning childrenrsquos
fatigue (Appendix IV) Because those studies included both school-age children and
adolescents the following descriptions will be differentiated by age Fatigue
measurements for school-aged children with cancer include the following the Child
Fatigue Scale (CFS) 7 a scale that measures the frequency and intensity of fatigue and
the Fatigue Scale for 7-12 year Olds (FS-C) 224 a scale that can be used to evaluate the
intensity of fatigue On the other hand fatigue measurements for adolescent cancer
patients include the following the Fatigue Scale for 13-18-year-olds (FS-A) 24 a measure
that can help evaluate fatigue levels the Pediatric Quality of Life Multidimensional
Fatigue Scale (Peds QL-MFS) 2325 a tool that can be divided into three sub-scales to
understand the general cognitive and sleep rest components of fatigue and finally the
CIS-20 for school-age children and adolescents 22 a scale that measures four levels of
654
22
fatigue namely subjective experience attention motivation and physical activity Two
studies used the Peds QL-MFS scale to measure fatigue2325
Meta-analysis results Two studies of the included papers failed to provide sufficient raw data they could not be
included in the meta-analysis Hinds et al 24 did not include post-test data Genc et al 2
provided no pre-test data PostWhite et al7 reported that fatigue after the health
education intervention was not statistically different but they presented the results
without presenting fatigue-related data Therefore the meta-analysis included three
studies 222325
The heterogeneity of studies was analyzed with Chi square statistics and no statistical
significance was found Therefore the data was combined in meta-analysis according to
exercise intervention on fatigue In addition there were three articles using the Peds
QL-MFS as a research tool to examine childrenrsquos improvements in fatigue Among these
Keats 22 and Chiang 24 present the effectiveness of exercise interventions using three
subscales Therefore the meta-analysis also analysis of the effects of these exercise
intervention measures on three subscales of Peds QL-MFS general fatigue sleep rest
fatigue and cognitive fatigue
The effectiveness of exercise intervention for fatigue We analyzed the exercise intervention effect on fatigue A total of 2 studies 22 23 were
included Takken et al 22 used community-based exercise training program to reduce
fatigue of children 6 to 14 years (mean 93y) of age who survived ALL Fatigue
measurement by Checklist Individual Strength (CIS) after 12-week of training fatigue
655
23
show no significant differences between pre (meanplusmnSD 415plusmn147) and post training
(meanplusmnSD368plusmn217) but fatigue change from baseline mean reduction of 11
Keats et al23 although used community-based physical activity program to reduce fatigue
for adolescents 14 to 18 years of age (mean162 y) with cancer (Lymphoma leukemia CNS
tumor germ cell tumor) Studies used fatigue by PedsQLMFS Results show general fatigue
from baseline to 8 weeks and to 3 months follow up significantly improves General
fatigue sleeprest fatigue and total fatigue from baseline to 3 months follow up showed
significant improvements Sleeprest fatigue and total fatigue at 1 years followed up were
significant improvements
Figure 2 shows the overall effect of exercise intervention in children and adolescents with
cancers with a focus on improving fatigue Due to the lower heterogeneity (p>005) the
fixed effects model was used to pool the data for meta-analysis (Overall effect size=
-006 95 Confidence Interval (CI) -070 to 058) A result did not indicate a statistically
significant difference (p = 087)
656
24
Figure2 Meta-analysis results of exercise intervention on fatigue
In addition Keats23 and Chiang25 used the three sub-scales of Peds QL-MFS to
determine the general cognitive and sleep rest components of fatigue The following
present the effectiveness of exercise interventions using three subscales including
general fatigue sleep rest fatigue and cognitive fatigue 2325
Chiang et al 25 used a 6- week home-based aerobic exercise intervention to reduce
fatigue of children 7 to 18 years (mean age at experimental group was 1088 y in control
group was 1247 y) of age who with acute lymphoblastic leukemia Fatigue measurement
by Peds QL-MFS after training For intent-to ndash treat analysis the findings indicated that
there are no intervention effects and time differences by any items on the subscale of
fatigue For per-protocol analysis general fatigue( meanplusmnSD 422plusmn402) was the only
subscale that was significantly lower for children who received the exercise intervention
than those in control group at follow-up assessment (one month after the completion of
intervention)
Keats et al23 although used community-based physical activity program to reduce fatigue
for adolescents 14 to 18 years of age (mean162 y) with cancer (Lymphoma leukemia
CNS tumor germ cell tumor) Both studies used fatigue by PedsQLMFS Results show
general fatigue from baseline to 8 weeks and to 3 months follow up significantly improves
657
25
General fatigue sleeprest fatigue and total fatigue from baseline to 3 months follow up
showed significant improvements Sleeprest fatigue and total fatigue at 1 years followed
up were significant improvements
The effectiveness of exercise intervention for general fatigue
The impact of the exercise interventions upon levels of general fatigue was also analysed
The heterogeneity was low (p>005) Therefore the fixed effects model was used to
examine the effectiveness The effect size is -076 indicating a statistically significant
difference (p = 001 95 CI -135 to -017 Fig 3) The evidence suggests that exercise
intervention can reduce general fatigue in children with cancer
Fig 3 Meta-analysis results of exercise intervention for general fatigue
The effectiveness of exercise intervention for sleep rest fatigue
The following is the result of the meta-analysis of the effectiveness of exercise
interventions on sleep rest fatigue First the heterogeneity test was conducted with P gt
005 representing small heterogeneity and the fixed effects model was used Fig 4
shows the effect size is -035 indicating no statistically significant differences (p = 023
95 CI-092 to 022 Fig 4)
658
26
Fig 4 Meta-analysis results of exercise intervention for sleep rest fatigue
The effectiveness of exercise intervention for cognitive fatigue Lastly the following data reports the results of meta-analysis of the effectiveness of
exercise interventions for cognitive fatigue The heterogeneity was p>005 then the
fixed effects model was used The effect size is -035 indicating no statistically significant
differences (p = 024 95 CI-092 023 Fig 5)
Fig 5 Meta-analysis results of exercise intervention for cognitive fatigue
Narrative presentation of remaining included studies
Three studies were not included in meta-analysis Post-White et al7 one of the aims in
this study was to examine the effect of massage therapy on fatigue in children with
cancer The study was a quasi-experimental design Twenty-three childrenparent dyads
were enrolled 17completed all data points Children with cancer ages 7 to 18 years
received at least 2 identical cycles of chemotherapy and one parent participated in the
2-period crossover design in which 4 weekly massage sessions (MT) alternated with 4
659
27
weekly quiet-time (QT) control sessions There were no significant changes in fatigue in
children over the 4-week MT or QT conditions either independently (change over time) or
when we compared fatigue by condition
The lack of effect of massage on fatigue may be the difficulty some children had in
differentiating fatigue from being relaxed underscores the challenge of measuring fatigue
in children Some children interpreted being tired or relaxed as having greater fatigue
because they felt like lying around and sleeping or felt unmotivated to do their usual
activities all measures of fatigue in the instrument used in the study
Hinds et al24conducted a prospective two-site randomized controlled pilot study to
assess the feasibility of an enhanced physical activity (EPA) intervention in hospitalized
children and adolescents receiving treatment for a solid tumor or for acute myeloid
leukemia (AML) Twenty-nine patients (25 with a solid tumor and 4 with AML) participated
age range from 736 to 1816 (mean 1248 y) The EPA intervention selected was
pedaling a stationary bicycle-style exerciser (Chattanooga Peddler Deluxe Bio-Teck
Medical Memphis TN) for 30 minutes twice daily for 2 to 4 days of hospitalization The
mixed model analysis revealed no significant differences in patient reports of fatigue
between the two study arms or over time
Genc et al2 conducted a RCT involving children with cancer who are 7 to 12 years of age
and receiving chemotherapy treatment to determine the impact of educational
intervention by nurses on decreasing the fatigue syndrome The research sample was
composed of a total of 60 children with cancer with 30 children being included in the
660
28
experimental group (mean age 923)and 30 children included in the control group (mean
age 937) with their mothers In the experimental group after the 7th to 10th day of the
chemotherapy treatment throughout a week the researcher conducted the nursing
interventions every day for 45 to 60 minutes In the control group routine nursing
interventions were carried out The experimental group received education about the
fatigue with the chemotherapy and fatigue handbook was given which was developed by
the authors Children and mothers were consulted for including activities that could
decrease fatigue which were described as effective interventions A statistically
significant difference was found between the Fatigue Scale-Child mean scores of the
experimental (2723) and the control group (4213) The results suggest that fatigue of
children with cancer can be reduced by implementing appropriate nursing interventions
(t=567 Plt00)
Discussion The purpose of this systematic review was to determine the effectiveness of
non-pharmacological interventions specifically targeting fatigue for children and
adolescents with cancer undergoing chemotherapy or after receiving chemotherapy
Included articles about the effectiveness of non-pharmacological interventions for
children and adolescents with cancer were published between the years of 2007 and
2009 Although interventions for cancer fatigue for adults have been extensively studied
it can be seen from either the title of the paper or related content that an intervention
study on children was a pilot study or a feasibility study Representing a field in its early
stage these studies show that the fatigue issues with young cancer patients have only
recently been taken seriously
661
29
The results of our meta-analysis include measurement of the four performance indicators
fatigue and general fatigue sleep rest fatigue and cognitive fatigue The results show
that there is a statistically significant difference only in the domain of general fatigue
using an exercise intervention for children with cancer can improve the degree of fatigue
with the effect size reaching 0671 Other results do not indicate significant differences
The reasons may include the following
1 Characteristics of the cancer The exhaustion from cancer occurs not only during cancer treatment but also in during
long-term survival a time during which patients may continue to be affected by this
symptom 8 26 Therefore when using intervention measures to improve fatigue
circumstances should be considered such as the process of the treatment and the course
or stage of the disease Because cancer patients will experience different forms of
treatment or courses of treatment the disease itself or treatment differences should be
considered in the choice of intervention Even chemotherapy drugs should be taken into
consideration For example a period of general steroid treatment can increase patientsrsquo
fatigue In those studies of children with cancer few studies looked solely at one type of
cancer most studies included a variety of cancer patients Furthermore most studies do
not clearly explain the stage of the disease or course of treatment and most do not
include treatment variables in the control group Moreover children with cancer may
have different levels of physical function
2 Research design The sample size Currently there are few studies with large sample size and a rigorous
RCT design due to the small number of papers available for analysis The sample size
included in our studyrsquos data analysis is between 20 and 42 people this small sample size
will affect the power available to evaluate outcome variables
Although most of the non-pharmacological interventions still use exercise and physical
activity and these studies overall show better results for fatigue as compared with
controls more research is still needed to further confirm the efficacy of these findings
662
30
The dropout rate in the evaluated research varies a great deal ranging from 5 to 45
these dropout rates may result from the characteristics of the research subjects or the
lengthy time involved in participating in these studies The research data with a high
turnover rate might not reflect the actual outcomes of participation in exercise and the
quality of the research contained in articles with high subject turnover rates may be
lower
Exercise doses and time The exercise doses needed to reduce fatigue cannot be
determined additionally the amount of exercise completed by the patient is also
inconsistent interventions vary between 2-3 times per week and two times a day and
exercise duration varies between 10 and 45 minutes each time Furthermore the study
interventions vary in length between a couple of days and a long period of 16 weeks The
data collection times are different some were measured 12 weeks after the intervention
began some were measured during the 6 weeks of intervention some were measured
three months after the intervention was finished and some were measured after one
year
In addition disease-related symptoms decrease childrenrsquos willingness to participate in
exercise interventions inappropriate exercise intervention programs may actually
increase childrens fatigue In addition the children in the study are still developing
physically it is important to consider ways to design an interesting exercise intervention
to increase the compliance of patients in order to improve the effectiveness Although
intervention programs in the hospital or in a community sports center can improve the
effectiveness because they provide supervision the feasibility of these programs is
questionable However if the program is home-based the children need to be
supervised by parents in order to improve their compliance in doing the exercises
Furthermore regarding the nature of the intervention the results from this study indicate
that the researched non-pharmacological interventions include the following exercise
training programs physical activity massage therapy and health education interventions
However according to the National Comprehensive Cancer Network 1 clinical guidelines
663
31
for cancer non-drug measures for cancer fatigue can be separated into five categories
(1) activity enhancement (2) psychosocial interventions such as cognitive behavioral
therapy (CBT) stress management relaxation techniques and support groups (3)
attention-restoring therapy (4) nutritional consultation and (5) cognitive behavioral
therapy specifically targeting sleep disturbance Researchers have also suggested that
psychosocial interventions should be included in the future research for children with
cancer-related fatigue 22
(2) The measurement tools in the study The assessment of fatigue can be
one-dimensional or multidimensional One-dimensional assessment can help understand
the severity of fatigue symptoms however multidimensional scales are often more
credible Therefore when measuring cancer-related fatigue researchers should consider
whether there is a uniform definition of fatigue or a standardized tool for measuring
fatigue in order to facilitate further systematic meta-analyses and further develop the
clinical care guidelines
Limitations of the review The present review has some potential limitations First the low methodological quality
may influence the result Although exercise intervention seems promising quality of the
RCTs was generally quite low Future studies require better design and reporting if
methodological issues to establish evidence-based nonpharmcologic intervention
Second the identified studies covered only a limited types of nonpharmcological
intervention especially in exercise intervention The guidelines for cancer-related fatigue
in NCCN (2011)1 referred to more interventions than the ones included in this review
such as cognitive behavioral therapy and nutrition consultation Thirdly the small sample
size and effect size could be potentially having led to underpowered approach for
detecting the effects on fatigue Therefore we recommend that as research continues to
grow a re-analysis can be undertaken Fourthly Combining data in meta analysis from
664
32
studies where the ages were quite different is a potential source of heterogeneity and
may affect the interpretation of the results
Conclusion At present clinical treatment is widely used for cancer patients However child and
adolescent cancer patients often experience various side effects which cause short-term
or long-term discomfort both physically and psychologically In particular with the
increasing cure rate cancer related fatigue during or after treatment has become an
important issue This study result provided positive effect of exercise intervention on
general fatigue
Implications for practice The results of this systematic review and meta-analysis show that exercise interventions
can effectively improve the level of general fatigue In particular although the articles
were self-reported feasibility studies their results all indicate that exercise interventions
for fatigue are feasible and safe there was no conclusion to be made for the use of
massage therapy or health education measures because there was only one article for
each of these interventions
Recommendations for practice
Cancer-related fatigue is one of the most severe and frequent symptoms by pediatric
oncology children and adolescent suffered during treatment and the symptom existed
even after treatment has ended Until now no golden standard of treatment to fatigue is
established The findings call for more attention to how to reduce patientrsquos levels of
fatigue Based on the available information evaluated in this review the following
recommendations for practice are provided
665
33
bull For children aged 7 to 18 who has cancer (eg Lymphoma leukemia CNS tumor
germ cell tumor) an effective progressive aerobic exercise program is recommended to
be at least 2-3 times per week 20 to 45 minute for each session and last for 6-16 weeks
in order to reduce their general fatigue (tiredness physically weakness) In addition
adults should be involved in accompanying children while they are performing physical
exercise of which should be able to improve the adherence rate (level 2 ) ( Grade of
recommendation A)
bull For children aged 7 to 18 who has cancer (eg Lymphoma leukemia CNS tumor
germ cell tumor) an progressive aerobic exercise program will not be effective to reduce
their sleep andor rest (sleeping or resting a lot) or cognitive fatigue (problems with
thinking quickly or problems with remembering) (level 2 ) ( Grade of recommendation C)
bull Nursing interventions in educating treatment of fatigue include information about
activity nutrition energy preservation consulting and providing a useful fatigue
handbook will benefit those children who are 7 to 12 years have a new diagnosis of ALL
AML or lymphoma and receive for the first time after being diagnosed a 7- to 10-day
chemotherapy treatment (level 2) ( Grade of recommendation A)
bull A 4-week massage therapy program (the therapists massage childrenrsquos back legs
arms stomachchest and face) is not effective for children who are aged 7 to 18 and
have acute lymphoblastic leukemia brain tumors lymphoma rhabdomyosarcoma
Wilms tumor or Ewing sarcoma(level 2)( Grade of recommendation C)
bull Using a 12-week aerobic and strength exercise (45-min exercise sessions twice a
week) is not effective for children who are aged 6-14 and survived acute lymphoblaststic
leukemia age from 6 to 14(level 2) ( Grade of recommendation C)
bull Using a physical activity intervention (30minutestwice daily for 2-4days) is not
effective for children who are 7 to 18 years of age with soild tumor or AML(level 2)
( Grade of recommendation C)
666
34
Implications for research According to this systematic review and meta-analysis results there are suggestions to
improve the effectiveness of future research on non-pharmacological interventions for
children and young peoplersquos cancer-related fatigue
As the majority of included non-pharmacological interventions for the fatigue of cancer
patients consist of exercise programs future research should also consider various
non-pharmacological interventions in order to understand the effectiveness of different
methods
Regarding the exercise intervention methods and studies should consider multiple
factors including the age or personal condition of the subject the disease stage and the
amount of daily activities Studies should use design prescriptions (eg frequency
intensity duration and type of exercise) and consider the adherence to the measures in
order to enhance the study strength
In measuring the results of non-pharmacological interventions there should be standard
definitions or standard measurement tools to facilitate the following systematic review
and meta-analysis that can subsequently be developed into clinical care guidelines
Reviewing the effectiveness of the current non-pharmacological management of children
and adolescent cancer patients there is still a lack of rigorous RCT research Limited by
the characteristics of cancer there is still a lack of large sample sizes
Potential conflicts of interest There is no conflict of interest
Acknowledgements
Thank you to Dr Rie Konno Research Fellow Joanna Briggs Institute for her help in
assessing studies
667
35
References 1 National Comprehensive Cancer Network( NCCN) in USA NCCN clinical practice
guideline in oncology cancer-related fatigue 2011 2 Ekti Genc R amp Conk Z Impact of effective nursing interventions to the fatigue
syndrome in children who receive chemotherapy Cancer Nursing 200831(4)312-317
3 Childhood Cancer Foundation of ROC (2009March) The classification of diseases
and age sex statistical tables of case Childhood Cancer Foundation of ROC newsletter103105-106
4 Department of Health Executive Yuan ROC (TAIWAN)(2009 March 20)2009 cause of death statistic Health and National Health Insurance Annual Statistics Information Service 2010 June 28Available httpwwwdohgovtwstatisticdatavital statists9898health statistic--lifepdf
5 Chang TK (2007December 8) Common childhood cancer and its treatment Status
Childhood Cancer Foundation of ROC (TAIWAN) 2010 September 23 Available httpwwwccfrocorgtwchildchild_events_readphpe_id=45
6 Hockenberry MJ amp Wilson D Wongs nursing care of infants and children (8th ed) St
Louis MO Mosby 2007
7 Post-White J Fitzgerald M Savik K Hooke MC Hannahan AB amp Sencer SF
Massage therapy for children with cancer Journal of Pediatric Oncology Nursing 2009 26(1)16-28
8Chiang YC Yeh CH Wang WKamp Yang CP The experience of cancer-related fatigue
in Taiwanese children European Journal of Cancer Care 2009 18(1)43-49 9Langeveld NE Grootenhuis M A Voute P A de Haan RJ amp van den Bos C No excess
fatigue in young adult survivors of childhood cancer European Journal of Cancer 200339(2)204-214
10Piper BF Lindsey AM amp Dodd MJ Fatigue mechanisms in cancer patients
developing nursing theory Oncology Nursing Forum 1987 14(6)17-23 11Nail LM amp Winningham ML Fatigue In S L Groenwald M H Forgge M Goodman
amp C H Yarbro (Eds) Cancer Nursing Principles and practice (4 th ed) Boston Jones and Bartlett1997
12Irvine D Vincent L Graydon JE Bubela N amp Thompson L The prevalence and
correlates of fatigue in patients receiving treatment with chemotherapy and
668
36
radiotherapy A comparison with the fatigue experienced by healthy individuals Cancer Nursing 199417(5)367-378
13Hinds PS amp Hockenberry-Eaton M Developing a research program on fatigue in
children and adloescents diagnosed with cancer Journal of Pediatric Oncology Nursing 200118(2)3-12
14Aaronson LS Teel CS Cassmeyer V Neuberger GB Pallikkathayil L Pierce J Press
AN Williams DP amp Wingate A Defining and measuring fatigue Journal of Nursing scholarship 1999 31(1)45-50
15Yeh CH Wang CH Chiang YC Lin Lamp Chien LC Assessment of symptoms reported
by 10- to 18-year-old cancer patients in Taiwan 2009 38(5)738-746 16 Okuyama T Akechi T Kugaya A Okamura H Shima Yamp Maruguchi M
Development and validation of the cancer fatigue scale a brief three-dimensional self-rating scale for assessment of fatigue in cancer patients Journal of Pain amp Symptom Management 2000 19(1) 5-14
17Gibson F Mulhall AB Richardson A Edwards JL Ream E amp Sepion BJ A
phenomenologic study of fatigue in adolescents receiving treatment for cancer Oncology Nursing Forum200532(3)651-660
18Wolfe J Grier HE Klar N Levin SB Ellenbogen JMamp Salem-Schatz S et al
Symptoms and suffering at the end of life in children with cancer New England Journal of Medicine 2000342(5)326-333
19Whiting P Bagnall AM Sowden AJ Cornell JE Mulrow CD amp Ramirez G
Interventions for the treatment and management of chronic fatigue syndrome a systematic review JAMA the Journal of the American Medical Association 2001286(11)1360-1368
20 Kangas M Bovbjerg DHamp Montgomery G H Cancer-related fatigue a systematic
and meta-analytic review of non-pharmacological therapies for cancer patients Psychological Bulletin 2008134 (5)700-741
21Williams PD Schmideskamp J Ridder EL amp Williams AR Symptom monitoring and
dependent care during cancer treatment in children pilot study Cancer Nursing 200629(3)188-197
22Takken T van der Torre P Zwerink M Hulzebos EH Bierings M Helders PJMamp van
der Net J Development feasibility and efficacy of a community-based exercise training
669
37
program in pediatric cancer survivors Psycho-Oncology 200918(4)440-448
23Keats MR amp Culos-Reed SN A community-based physical activity program for
adolescents with cancer (project TREK) program feasibility and preliminary findings
Pediatric hematology and oncology 200830(4) 272-280
24Hinds PS Hockenberry M Rai SN Zhang L Razzouk B I Cremer L McCarthy K amp
Rodriguez-Galindo C Clinical field testing of an enhanced-activity intervention in
hospitalized children with cancer Journal of Pain amp Symptom Management 2007
33(6)686-697
25Chiang YC The effects of ldquo a home-based aerobic exercise interventionrdquo on fatigue
and cardiorespiratory fitness in children with acute lymphoblastic leukemia during the
maintenance stage of chemotherapy Unpublished thesis Taiwan Tao-Yuan 2007
26Langeveld N Ubbink M amp Smets E I dont have any energy The experience of
fatigue in young adult survivors of childhood cancer European journal of oncology
nursing 20004(1)20-28
27 Kisner C Colby L Therapeutic exercise Foundations and techniques 2nd ed Philadelphia PAFA Davies 2007
670
38
Appendix I JBI Critical Appraisal Checklist for Experimental studies
Author__________ Year_________ Record Number__________________
Questions 1 to 4 must be answered ldquoyesrdquo for study to be included in the metashyanalysis
1 Were the participants randomized to study groups
Yes No Not clear
2 Other than research intervention were participants in each groups treated the same
Yes No Not clear
3 Were the outcomes measured in the same manner for all participants
Yes No Not clear
4 Were groups comparable at entry
Yes No Not clear
5 Was randomization of participants blinded
Yes No Not clear
6 Were those assessing outcome blinded to treatment allocation (if outcome not objective such as survival or length of hospitalization)
Yes No Not clear
7 Was allocation to treatment groups concealed from the allocator
Yes No Not clear
8 Was an appropriate statistical analysis used
671
39
Yes No Not clear
9 Were outcomes measured in a reliable way
Yes No Not clear
10 Was there adequate followshyup of participants
Yes No Not clear
Summary
TOTAL
Yes No Not clear
DECISION
Use Reject
Narrative summary only Further information needed
COMMENTS
672
40
Appendix II JBI Data Extraction Tool for Quantitative Studies Authors and Year
Journal Title
Record NumberArticle Reference No
Reviewer
Method
Settings
Participants
Number of participants
Group A Group B Group C
Control Intervention 1 Intervention 2
Interventions
Group A
Control
Group B
Intervention 1
Group C
Intervention 2
Outcome measures
Definition
673
41
Other outcome measures
Outcome description ScaleMeasure
Results
Dichotomous Data
Outcome Control Group
Numbertotal number
Treatment Group
Numbertotal number
Continuous Data
Authorrsquos Conclusions
Comments
Outcome Control Group
Mean amp SD
Treatment Group
Mean amp SD
674
43
Appendix III Details of included studies (N=6)(2720212223) RefNo Author(s)
(years) Title Study question Research
method Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
22 Takken T van der Torre P Zwerink M Hulzebos E H Bierings M Helders P J Mamp van der Net J (2009)
Development feasibility and efficacy of a community-based exercise training program in pediatric cancer survivors
To develop a 12-week home-based exercise training program (comprising aerobic and strength exercises) for children who survived ALL and to study itrsquos feasibility and efficacy
Pre-post test design
No comparsion group
Survived ALL(N=9)ages 6-14 years
1anthropometry 2 muscle strength 3functional mobility 4cardio-pulmonary
exercise test 5Fatigue
1 Feasibility questionnaire 2 anthropometry electronic scale and a wallmounted stadiometerHarpenden skin fold calipers 3 muscle strength handheld dynamometer 4functional mobility Timed Up
and Go test (TUG) 5cardio-pulmonary exercise test electronically braked cycle ergometer 6Fatigue(mean)CSI-20 (subjective experience of fatigueconcentrationmotivationphysical activity)
112-week exercise training program
2 Patients were assessed before (T0) and after (T1) 12 weeks of training
1 muscle strength execapacity functional moand fatigue showed nosignificant differences between pre(meanplusmnSD415plusmn147) and post training(meanplusmnSD3687)
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
7 Post-White J Fitzgerald M Savik K Hooke M C Hannahan A B amp Sencer S F (2009)
Massage therapy for children with cancer
To determine whether 4 weekly sessions of massage compared with 4 quiet-time control conditions would reduce anxiety cortisol levels fatigue nausea and pain in children with cancer undergoing chemotherapy and would reduce anxiety fatigue and mood disturbance in a parent
2-period crossover design (Randomized)
quiet-time
control
sessions
Children with cancer 1 to 18 years of age Twenty-three childrenparent dyads were enrolled 17 completed all data points
children 1relaxation 2symptoms 3 fatigue
parents
1anxiety 2 fatigue
children 1relaxation (heart and respiratory rates blood pressure and salivary cortisol level)
2symptoms (pain nausea anxiety 3 fatigue 1-2y3-6yLansky Play Performance Scale (PPS) 7-13y
1 4 weekly massage (MT) sessions alternated with 4 weekly quiet-time(QT) control sessions
2 children included presession and postsession vital signs (heart rate respiratory rate blood pressure) and self-report (parent proxy report for age 1-2 years) of pain nausea and anxiety Fatigue was measured before sessions 1 and 4 and at each follow-up Parent measures
included anxiety fatigue and mood states
1Massage was moreeffective than quiet tireducing heart rate inchildren anxiety in cless than age 14 yeaparent anxiety 2There were no sign
changes in blood pcortisol pain naufatigue (no state d
3 Children reported tmassage helped thebetter lessened theirand worries and hadlasting effects than q
675
44
14-18yChild Fatigue Scale (CFS) (frequency
intensity) 2 parents anxiety and fatigue
676
45
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
24 Hinds P S Hockenberry M Rai S N Zhang L Razzouk B I Cremer L McCarthy K amp Rodriguez-Galindo C (2007)
Clinical field testing of an enhanced-activity intervention in hospitalized children with cancer
To determine the feasibility of an
enhanced physical activity EPA intervention in children and adolescents hospitalized to receive chemotherapy for a solid tumor or AML and to assess the sleep and fatigue outcomes of the intervention using two different statistical approaches to analyze the longitudinal symptom data
randomized prospective two-site and two-group pilot study
Standard care Twenty nine patients (25 with a solid tumor and 4 with AML)ages 7-18 years
1 sleep duration 2 sleep efficiency 3 fatigue
1sleep duration sleep efficiency The
Wrist Actigraph The Daily Sleep Diary-Parent 2 fatigue (mean) The Fatigue Scale(FS-C) for 7-12 (intensity) The Fatigue Scale(FS-A) for 13-18 The Fatigue Scale Parent Version (FS-P) The Fatigue Scale Staff Version (FS-S)
1enhanced physical activity (EPA) (hospital-based 30 minutes
twice daily for 2-4 days) 2 T0On the day of admission
(Day 0 or baseline)patient and parents completed the fatigue instruments and a team member applied the actigraph Patients wore the wrist actigraph T1 from Day 0 to 2 or 3 consecutive days (Days 0e3) In addition the patient same parent and staff nurses completed the daily sleep and fatigue reports in the late afternoons of Days 1-3
1 ANOVA model slesignificantly more the experimental athe control arm whdifferences from bsleep efficiency vaaveraged and com
2 The patient-reported mean fatigue scoresarms were higher amadolescents than for
3 The mixed model anarevealed no significandifferences in patientfatigue between
the two study arms otime( no final result iSD only give mixed result)
677
46
23 Keats M
R amp Culos-Reed S N (2008)
A community-based physical activity program for adolescents with cancer (project TREK) program feasibility and preliminary findings
To examine the
feasibility of a
theoretically-based
physical activity (PA)
intervention in
adolescents with
cancerand
examination of the
impact of the
program on
participant QOL
including social
emotional and
physical
well-being(including fatigue)
Repeat measures longitudinal design
No comparsion group
10 adolescents(Lymphoma(4)leukemia(4)CNS tumor(1)germ cell tumor(1)) ages 14-18 years
1physical fitness 2quality of life (QOL) 3PA behavior 4fatigue
1 Feasibility was assessed by participant recruitment attendance and adherence
2physical fitness Fitnessgram 3quality of life (QOL) Pediatric Quality of Life Inventory (PedsQL) 4PA behavior leisure score index (LSI) 5fatigue (mean) pediatric Quality of life
Multidimensional Fatigue Scale (Peds QL-MFS)
(Generalsleepcognitive fatigue)
116week physical activity (PA)
2 total PA physical fitness and overall QOL was assessed at 5 different intervals T0 preintervention (baseline) T1midintervention (after the
first 8 wk) T2 postintervention
(16 wk) T3 3-months
postintervention T4 1-year poststudy
initiation
1 from baseline -wkssig Improvementstotal PA physfitness and Qgeneral fatigue(meanplusmnSD 796plusmn135)
2 from baseline to 3FUsig Improvin general fatigue(meanplusmnSD824plusmn131)slefatigue(meanplusmnSD755plusmn191)totafatigue(meanplusmnSD778plusmn150)
3at 1 years FUsImprovements in sleeprest fatigue(meanplusmnSD725plusmn203)total (meanplusmnSD 763plusmn
678
47
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
2 Gene R E amp Conk Z (2008)
Impact of Effective Nursing Interventions to the Fatigue Syndrome in Children Who Receive Chemotherapy
1 to examine the effects of an effective nursing intervention to the fatigue syndrome of children 7 to 12 years of age who receive chemotherapy 2Tto examine the relationship between fatigue and demographic variables (age sex) diagnoses ([ALL AML] lymphoma) and therapy-related variables (eg level of hemoglobin
experimental randomized controlled study
Routine nursing care
A total of 60 children who are 7-12 years of age(a new diagnosis of ALL AML or lymphoma and receiving for the first time after being diagnosed a 7- to 10-day chemotherapy treatment )
fatigue The Fatigue Scale(FS-C) for 7-12 (intensity)
The Fatigue Scale Parent Version (FS-P)
1 effective nursing interventions(45- 60mdaya week)education about the fatigue with the chemotherapy and fatigue handbook 2 T1 After a 7-day period the children
and parent were evaluated with the Fatigue Scale
1The difference betwthe 2 mean values wafound to be statisticallsignificant 2 statistically significadifference was found between the Fatigue Scale-Child mean scothe experimental (272the control group (4213)children
679
48
25 Chiang et
al(2007)
The effects of ldquo a home ndashbased aerobic exercise interventionrdquo on fatigue and cardiorespiratory fitness in children with Acute Lymphoblastic Leukemia during the maintenance stage of chemotherapy
To examine the effect of ldquo a home ndashbased aerobic exercise interventionrdquo on fatigue and cardiorespiratory fitness in children with Acute Lymphoblastic Leukemia during the maintenance stage of chemotherapy
Quasi-experi -mental
Routine
nursing care
14 pediatric oncology patients in the experimental group and 10 in control group who were matched by age and sex ages7-18 years
1Cardiorespiratory fitness
2Fatigue
1Cardiorespiratory fitness Physical Activity Recall
VO2maxHR peak 6MWT
2 Fatigue PedsQL-MFS(Generalsleepcognitive fatigue)
1A six-week home-based aerobic exercise intervention 2 8 time points T0 baseline T1-T6 every week during the
intervention(6 weeks) T7 post intervention T8 follow-up (one month after
the end of the home-based exercise program)
1 For intent-to ndash treatthe findings indicated are no intervention efftime differences by anon the subscale of fat2 For per-protocol angeneral fatigue( mean422plusmn402) was the osubscale that was siglower for children whothe exercise interventthose in control groupfollow-up assessmentmonth after the compintervention) 3 The VO2peak are significantly improvingexperimental group atbaseline- and post-intassessment The VO2was significantly highechildren who were in experimental group thcontrol subjects at post-intervention assefor the per-protocol an
680
49
Appendix IV Instrument used to measure fatigue
Name Instrument
developers
Description Used in
age in
ref
Reliability
Consistency of
instrument
Checklist Individual Strength
(CIS)22
Vercoulen et
al1996
20 items using 7-point Likert scale of
fatigue To measure four aspects of
fatiguesubjective experience
contractionmotivation physical
Activity
6-14 Not reported
Child Fatigue Scale (CFS)7 Hockenberry
et al2003
14 items 2 part questionnaire frequency
(yes or no) 5-point Likert scale of the
intensity of any yes responses
7-13
14-18 α073-o84
The Fatigue Scale for 7-12
year Olds (FS-C)224
Hockenberry
et al
14 items provide a fatigue intensity score
5-point Likert scale
7-12 αo84
The Fatigue Scale for 13-18
year Olds (FS-A)24
Hockenberry
et al
14 items provide a fatigue intensity score
5-point Likert scale
13-18 α076-o96
Pediatric Quality of life
Multidimensional Fatigue
Scale (Peds QL-MFS)2325
Varni2002 18 items to measure three aspects of
fatigueGeneralsleepcognitive
14-18 Not reported
681
50
Appendix V Excluded studies and reasons for exclusion
Baggott C Dodd M Kennedy C Marina N Miaskowski C Multiple Symptoms in Pediatric Oncology
Patients A Systematic Review Journal of Pediatric Oncology Nursing 2009 Nov-Dec 27(6)
325-339
Reason for exclusion Not outcome of interest
Barlow JH Ellard DR Psycho-educational interventions for children with chronic disease parents and
siblings an overview of the research evidence base Care Health amp Development 2004 Nov
30(6)637-45
Reason for exclusion Not outcome of interest
Bedider S Moyer CA Randomized controlled trials of pediatric massage A review Evid Based
Complement Alternat Med 2007 Mar 4(1)23-34 Epub 2006 Nov 3
Reason for exclusion Not outcome of interest
de Nijs EJ Ros W Grijpdonck MH Nursing intervention for fatigue during the treatment for cancer Cancer
Nursing 2008 31(3)191-206
Reason for exclusion Not population of interest
Edwards JL Gibson F Richardson A Sepion B Ream E Fatigue in adolescents with and following a
cancer diagnosis developing an evidence base for practice European Journal of Cancer 2003
Dec 39(18)2671-80
Reason for exclusion Not experimental or quasi-experimental study
Hinds PS Hockenberry-Eatan M Developing a research program on fatigue in children and adolescents
diagnosed with cancer Journal of Pediatric Oncology Nursing 2001 Mar-Apr 18(2 Suppl
1)3-12
Reason for exclusion Not experimental or quasi-experimental study
Hockenberry-Eaton M Hinds PS Alcoser P ONeill JB Euell K Howard V Gattuso J Taylor J Fatigue in
Children and Adolescents With Cancer Journal of Pediatric Oncology Nursing 1998 July
15(3)172-182
Reason for exclusion Not experimental or quasi-experimental study
Jean-Pierre P Mustian K Kohli S Roscoe JA Hickok JT Morrow GR Community-based clinical oncology
research trials for cancer-related fatigue The Journal of Supportive Oncology 2006 Nov-Dec
4(10)511-6
682
51
Reason for exclusion Not population of interest
Kangas M Bovbjerg DH Montgomery GH Cancer-Related Fatigue A Systematic and Meta-Analytic
Review of Non-Pharmacological Therapies for Cancer Patients Psychological Bulletin 2008 Sep
134(5)700-41
Reason for exclusion Not population of interest
Lotfi-Jam K Carey M Jefford M Schofield P Charleson C Aranda S Nonpharmacologic strategies for
managing common chemotherapy adverse effects A systematic review Journal of Clinical
Oncology 2008 Dec 1 26(34)5618-29 Epub 2008 Nov 3
Reason for exclusion Not outcome of interest
Marchese VG Chiarello LA Lange BJ Effects of physical therapy intervention for children with acute
lymphoblastic leukemia Pediatr Blood Cancer 2004 Feb42(2)127-33
Reason for exclusion Not outcome of interest
Meeske KA Siegel SE Globe DR Mack WJ Bernstein L Prevalence and correlates of fatigue in
long-term survivors of childhood leukemia Journal of Clinical Oncology 2005 Aug 20
23(24)5501-10
Reason for exclusion Not intervention study
Minton O Richardson A Sharpe M Hotopf Stone P A systematic review and meta-analysis of the
pharmacological treatment of cancer-related fatigue J Natl Cancer Inst 2008 Aug 20
100(16)1155-66 Epub 2008 Aug 11
Reason for exclusion Not population and intervention of interest
Mustian KM Morrow GR Carroll JK Figueroa-Moseley CD Pascal JP Williams GC Integrative
nonpharmacologic behavioral interventions for the management of Cancer-Related fatigue The
Oncologist 2007 12(1)52-67
Reason for exclusion Not population of interest
Neill J Belan I Ried K Effectiveness of non-pharmacological interventions for fatigue in adults with
multiple sclerosis rheumatoid arthritis or systemic lupus erythematosus a systematic review
Journal of Advanced Nursing 2006 Dec 56(6)617-35
Reason for exclusion Not population of interest
Rheingans JI A systematic review of nonpharmacologic adjunctive therapies for symptom management
Journal of Pediatric Oncology Nursing 2007 24(2) 81-94
683
52
Reason for exclusion Not outcome of interest
Rheingans JI Pediatric oncology nursesrsquo management of patients symptoms Journal of Pediatric
Oncology Nursing 2008 Nov 25(6) 303-11
Reason for exclusion Not outcome of interest
San Juan AF Fleck SJ Chamorro-Vintildea C Mateacute-Muntildeoz JL Moral S Peacuterez M Cardona C Del Valle MF
Hernaacutendez M Ramiacuterez M Madero L Lucia A Effects of an intrahospital exercise program
intervention for children with leukemia Medicine amp Science in Sports amp Exercise 2007 Jan
39(1)13-21
Reason for exclusion Not outcome of interest
Sanford SD Okuma JO Pan J Srivastava DK West N Farr L Hinds PS Gender differences in sleep
fatigue and daytime activity in a pediatric oncology sample receiving dexamethasone Journal of
Pediatric Psychology 2008 Apr 33(3)298-306 Epub 2007 Nov 17
Reason for exclusion Not experimental or quasi-experimental study
Schmitz KH Holtzman J Courneya KS Macircsse LC Duval S Kane R Controlled physical activity trials in
cancer survivors a systematic review and meta-analysis Cancer Epidemiol Biomarkers Prev
2005 Jul 14(7)1588-95
Reason for exclusion Not population of interest
van Brussel M Takken T Lucia A van der Net J Helders PJ Is physical fitness decreased in survivors of
childhood leukemia A systematic review Leukemia 2005 Jan 19(1)13-7
Reason for exclusion Not population of interest
Whiting P Bagnall AM Snowden AJ Cornell JE Mulrow CD Ramirez G Interventions for the treatment
and management of chronic fatigue syndrome JAMA 2001 Sep 19 286(11)1360-8
Reason for exclusion Not intervention of interest
Whitsett SF Gudmundsdottir M Davies B McCarthy P Friedman D Chemotherapy-related fatigue in
childhood cancer correlates consequences and coping strategies Journal of Pediatric
Oncology Nursing 2008 Mar-Apr 25(2)86-96 Epub 2008 Feb 29
Reason for exclusion Not experimental or quasi-experimental study
Winner C Muumlller C Hoffmann C Boos J Rosenbaum D Physical activity and childhood cancer Pediatr
Blood Cancer 2010 Apr 54(4)501-10
Reason for exclusion Not research study
684
53
Wu M Hsu L Zhang B Shen N Lu H Li S The experiences of cancer-related fatigue among Chinese
children with leukaemia A phenomenological study Journal of Nursing Studies 2010 Jan
47(1)49-59 Epub 2009 Aug 25
Reason for exclusion Not experimental or quasi-experimental study
Yeh CH Chiang YC Lin L Yang CP Chien LC Weaver MA Chuang HL Clinical factors associated with
fatigue over time in paediatric oncology patients receiving chemotherapy British Journal of
Cancer 2008 Jul 8 99(1)23-9 Epub 2008 Jun 24
Reason for exclusion Not experimental or quasi-experimental study
685
4
Keywords non-pharmacological intervention fatigue children adolescents cancer
exercise cognitive systematic review
BACKGROUND
The Clinical Practice Guidelines in Oncology of the National Comprehensive Cancer
Network (NCCN) in the USA define cancer-related fatigue as ldquoa distressing persistent
subjective sense of physical emotional andor cognitive tiredness or exhaustion related
to cancer or cancer treatments that is not proportional to recent activity and interferes
with daily functionrdquo(pFT-1)1 When children suffer from cancer fatigue is not only the most
consistently reported symptom by children with cancer but also one of the most
persistent and uncomfortable symptoms 2
The incidence of cancer in children is high across the world As an example the
incidence in the USA for children aged 0-14 years is approximately 129 per million with
an estimated projection of 8200 newly diagnosed cases per year3 In Taiwan
approximately 550-600 children are diagnosed with cancer every year4 According to the
estimation of group proportions the incidence of childhood cancer in Taiwan and the
United States are similar 5 In addition malignant tumor has become the second leading
causes of death for children and adolescents aged 1-14 years in Taiwan3 and US6
Although cancer has been one of the major illnesses threatening the life of children the
progress made in medical technology has led to a significant improvement in the
treatment of children and adolescents with cancer over the past three decades7
especially the increase in their survival rate Statistics have indicated that the five-year
637
5
survival rate of children with cancer has exceeded 756 however the treatments of
cancer tend to rely on aggressive chemotherapies which force children to face a long
treatment process as well as various physical and mental symptoms8 Fatigue is one of
the common symptoms affecting children during treatments Children may feel persistent
fatigue even after they complete cancer treatments9
To date the causes and mechanism of cancer-related fatigue are still unclear However
the theories concerning the causes of fatigue have been proposed Common theories
include Integrated Fatigue Model10 Psychobiological Entropy Model11 Energy Analysis
Model12
Piper et al (1987) 10 proposed the Integrated Fatigue Model which is one of the most
frequently cited fatigue models at present They suggest that fatigue is the tiredness felt
by individuals as a result of the influence of body rhythm which makes individuals
experience different degrees of discomfort In this model fatigue can be measured by
biochemical indicators such as cytokines interferon and tumor necrosis factors as well
as with a self-report fatigue scale
The term ldquoIntegratedrdquo refers to a combination of features including perception physics
biochemistry and behavior all of which affect level of fatigue and in turn influence
fatigue patterns including diseases treatments activitiesrests environment symptoms
social activities life events individual internal factors and other aspects of the patients
life
The second theory is the Psychobiological Entropy Model11 is the most complete fatigue
638
6
theory at present This model suggests that the main cause of fatigue is a lack of energy
The physical ability of patients is reduced because of the symptoms caused by diseases
or treatments and thus patients experience emotion-related fatigue and the reduction in
functional status as a result In addition the symptoms caused by reoccurring diseases
or treatments may be harmful to physical conditions even more and lead to disability
eventually In this model any treatment program that can address the decline in activity
can alleviate fatigue symptoms is said to improve fatigue Therefore Psychobiological
Entropy Model not only provides a more direct detection of clinical patterns but also for
providing measures of care within a fatigue model
The third model is the Energy Analysis Model12 which suggests that the pathological
change of individual physical status becomes the barrier of energy conversion When the
supply of energy in individuals is low or the demand is high a lack of energy results and
the individuals feel fatigue Energy is generated by the oxygenation in blood The
correction factors of energy reaction are cancer treatments symptom distress and
emotional disorders Concepts in the fatigue model include energy sources energy
transformations energy expenditures and energy response modifiers The relationships
among these concepts are dynamic and intercorrelated with each other From the Energy
Analysis Mode point of view the physiological mechanism of fatigue includes some
objective indicators such as body weight and hemglobulin
In terms of the causes of fatigue Ekti Genc amp Conk (2008) 2 indicated that illnesses
treatments and stage of disease can cause fatigue NCCN (2011) 1 points out that many
conditions are related to fatigue including pain emotional pain anaemia sleep disorders
639
7
nutritional deficiencies activity reduction side effects of drugs (antihistamine drugs
anti-vomiting drugs and anti-anxiety drugs) and others In a study on children
adolescents parents and relevant medical and nursing staffs Hinds and
Hockenberry-Eaton (2001) 13 proposed four factors causing the fatigue of children with
cancer which are 1) environmental factors treatment setting events or situations that
place demands on the patient such as appointments inpatient stay long waiting time
altered routines that lack clear beginnings and endings of each day and decision making
and information exchange 2) personalbehavioral factors the negative faith of children
with illness 3) culturalfamilyother factors emotions concerns the hope of friends and
family ability to participate in activities and restricted activities 4) treatment-related
factors the invasive inspections experienced by children with illness insufficient time for
physical strength recovery between the repeated courses of treatments or the side
effects caused by treatments (infection pain and decrease in complete blood count) It
can be inferred that the causes of fatigue are complicated and multifaceted
Fatigue is a complex and multidimensional condition 10 therefore fatigue is subject to
different definitions and there are different measurement tools Aaronson et alrsquos14
review the literature of fatigue summarised the characteristics of fatigue measurement
including the following(1) Subjective quantification of fatigue can be determined with the
Lee and colleagues (1991) Visual Analog Scale for Fatigue (VASF)(2) Subjective
distress This item simply asks the rater to report to what degree fatigue has caused
distress (3) The effect of fatigue on activities of daily living (4) Correlates of fatigue
such as sleep and depression to assess when measuring fatigue (5) key biological
parameters such as cytokines interferon and tumor necrosis factor
640
8
Fatigue can be also measured with unidimensional or multidimensional scales The first
type of fatigue scale is not suitable for studies focusing on fatigue because they are too
long if the aim is to only assess fatigue Furthermore they only allow for a limited number
of possible responses Unidimensional scales also are not suitable for the in-depth study
of fatigue because they assess only one aspect of fatigue15
In recent years fatigue in children with cancer has received some attention and
measurement tools have gradually been developed - such as1) Checklist individual
strength (CIS) The items are scored on 7-point Likert scales (with 1 indicating best and
7 worst function) 2) The Child Fatigue Scale (CFS) is a 2-part questionnaire that asks for
a yes or no (frequency) response and a 5-point rating of the intensity of any yes
responses ranging from not at all to a lot The Fatigue Scale for 7-12 year Olds (FS-C)
is provide a fatigue intensity score higher scores indicating higher fatigue The Fatigue
Scale for 13-18 year Olds (FS-A) measure adolescent cancer patientsrsquo perceptions of
the intensity of their fatigue on a daily or weekly basis higher scores indicating higher
fatigue 3) The Fatigue Scale Parent Version (FS-P) measures the parentsrsquo perception
of their childrsquos fatigue intensity on a five-point Likert-type scale higher scores indicating
higher fatigue 4) The Fatigue Scale Staff Version (FS-S ) measures the staffrsquos
perceptions of the patientrsquos fatigue intensity during the past 24 hours Intensity ratings are
on a four-point Likert-type scale with higher scores indicating more intense fatigue
symptoms 5) The Pediatric Quality of life Multidimensional Fatigue Scale (Peds
QL-MFS)Higher scores (0 to 100) indicate less fatigue( Appendix IV)
Besides disturbing physical and mental functions and status fatigue also affects the
641
9
quality of life 15 of children with cancer and impacts their daily life16 among all different
types of cancer progress and childrsquos ages However as opposed to the fatigue of adults
the fatigue of children tends to be neglected and left untreated17 by medical and nursing
staffs
In terms of the management approach to cancer-related fatigue Ekti Gene (2008) 2
suggests that strategies could include pharmacologic and non-pharmacologic measures
NCCN (2011) 1 indicated in the Clinical Practice Guidelines in Oncology that during
aggressive treatments during long-term follow-up treatments or in the terminal phase of
cancer the intervening measures for cancer-related fatigue can be divided into
pharmacologic and non-pharmacologic measures Non-pharmacologic measures include
activity enhancement psychosocial interventions (eg cognitive behavioral therapy
(CBT) stress management relaxation support groups) attention-restoring therapy and
nutrition consultation As for the effectiveness of pharmacological measures the
effectiveness is still uncertain However there is evidence to suggest that
methylphenidate may be effective in treating cancer-related fatigue1 Whiting et al
(2001)18 included 36 randomized controlled trials and 8 controlled trails to assess the
effectiveness of the pharmacological and non-pharmacological interventions used in the
treatment or management of chronic fatigue syndrome in adults or children Results
showed insufficient evidence on the effectiveness of the pharmacological supplements
complementaryalternative and other interventions In addition the evidence of
pharmacological treatments of immunoglobulin and hydrocortisone were also
inconclusive However interventions such as cognitive behavioral therapy and graded
exercise therapy have shown promising results
642
10
The efficacy of pharmacological treatments for cancer-related fatigue has not been
established6 therefore there is a need to provide evidence-based findings of the
effectiveness of non-pharmacological interventions to support nursing intervention to
release the childrsquos cancer-related fatigue To date most studies have investigated the
effectiveness of non-pharmacological treatments on cancer-related fatigue of
adults20and to date there is no systematic review in relation to cancer-related fatigue of
children However as children are not a smaller version of adults it is inappropriate to
extrapolate the results of adults onto children Therefore there is a need to establish the
effectiveness of non-pharmacological intervention on the cancer-related fatigue of
children
Given the increase in childhood cancer survival rate the importance of decreasing
childrenrsquos cancer-related fatigue during treatments and so increase their quality of life has
become a focus of their medical teams The role of nurses during care intervention is to
confirm the major symptoms of children with illness and effectively treat each symptom to
increase the childrenrsquos quality of life21 Moreover the USA based NCCN also indicated in
the Care Standard for the Treatment of Cancer-related Fatigue of Children and
Adolescents that treatments for fatigue should be included in the health care teams and
the children and their family should be informed of relevant information The definition of
non-pharmacological interventions for childrenrsquos cancer ndashrelated fatigue include activity
enhancement (exercise physical activity) psychosocial interventions cognitive
behavioral therapy (CBT) stress management relaxation nutrition consultation
massage and educational interventions
643
11
The Cochrane Library of Systematic Reviews and The Joanna Briggs Institute Library of
Systematic Reviews were initially searched to ensure that systematic reviews on this
subject were not already published or being undertaken This initial search prior to the
commencement of the review did not yield any results
This systematic review has examined the effectiveness of non-pharmacologic
interventions on the cancer-related fatigue of children in hope of finding scientific
evidence that can support or refute such measures on children The results of this study
may serve as a reference for professional caregivers children with cancer and their
families or to be put into practice during the clinical care of children with cancer
Definition of terms
FatigueFatigue as a distressing persistent subjective sense of physical emotional
andor cognitive tiredness or exhaustion related to cancer or cancer treatments
that is not proportional to recent activity and interferes with daily function1 There
are various scales and measurements of the degree of fatiguewe have elected to
use the study authors own definitions of fatigue rather than applying a single
pre-set definition of the condition
Non-pharmacological interventionsReferring to reduce fatigue that does not involve
drugsNon-pharmacologic measures include activity enhancement psychosocial
interventions (eg cognitive behavioral therapy stress management relaxation
support groups) attention-restoring therapy and nutrition consultation1
ChemotherapyTreatment with drugs that kill cancer cells 1
644
12
Review QuestionsObjectives
Review Objective
The objective of this systematic review was to critically appraise synthesize and
present the best available evidence concerning the effects of non-pharmacological
interventions fatigue in children and adolescents with cancer
Review Question
The following specific question was addressed in this review
What is the effectiveness of non-pharmacological interventions on fatigue in
children and adolescents with cancer aged from one to 18 years
Criteria for Considering Studies for this Review
Types of studies
This review included randomised controlled trials (RCTs) and quasi-experimental
studies that examine the effectiveness of non-pharmacological intervention for fatigue in
children and adolescents with cancer
Types of participants
Children and adolescents aged from one to 18 years old experiencing fatigue
associated with cancer either during or after the chemotherapy or maintenance stage of
chemotherapy or survive stage The types of cancer to be included in this systematic
review will be ALL (Acute lymphoblastic leukemia) AML (Acute myeloid leukemia)
lymphoma and solid tumors
Exclusion criteria for Types of participants
645
13
newborn infants under 1 years of age
participants who do not have a specific diagnosis of cancer
participants who have received immunoglobulin or hydrocortisone
treatment
If participants have received immunoglobulin or hydrocortisone treatment may
inference the effectiveness of non-pharmacological interventions on fatigue
Types of intervention
This review considered studies that examine non-pharmacological interventions on
fatigue for children and adolescents with cancer including activity enhancement
(exercise physical activity) psychosocial interventions CBT stress management
relaxation nutrition consultation massage and educational interventions The
interventions descriptive included the length frequency setting and intervention
providers eg Nurse Psychologist Dietician
Exclusion criteria for types of interventions only pharmacological interventions were
tested
Types of outcome measures
The outcome measures considered were fatigue scores The literature demonstrates that
differences of opinion exist regarding the most valid and reliable method of measuring
cancer-related fatigue Therefore studies that used any validated scale for
cancer-related fatigue were considered for inclusion Currently commonly used scales to
measure fatigue include Checklist Individual Strength (CIS) Child Fatigue Scale (CFS)
The Fatigue Scale for 7-12 year Olds (FS-C) The Fatigue Scale for 13-18 year Olds
646
14
(FS-A)and Pediatric Quality of life Multidimensional Fatigue Scale (Peds QL-MFS)
Types of settings
Both hospital and community settings
Search Strategy
Before undertaking this systematic review the Cochrane Library Joanna Briggs Institute
Library of Systematic Reviews and CINAHL were searched and no systematic reviews on
this topic were found or identified as underway
The search strategy aimed to find both published and unpublished studies
A three-step search strategy was utilized in each component of this review An initial
limited search of CINAHL and MEDLINE was undertaken followed by an analysis of the
text words contained in the title and abstract and of the index terms used to describe the
article A second search using all identified keywords and index terms was undertaken
Lastly the reference lists of all identified reports and articles were searched for additional
studies
Types of languages
1 English
2 Chinese
The following databases were searched to identify keywords contained in the title and
abstract and relevant MeSH headings and descriptor terms
The Cochrane Library PsycINFO 1990 ndash 2010
647
15
Ovid MEDLINE 1966 ndash 2010 CINAHL Plus with Full Text 1960 ndash2010 EMBASE ProQuest Dissertations amp theses 1990-2010 Electronic theses and dissertations system 1956(abstract)1990(full text)-2010 MEDNAR Index to Taiwan periodical literature 1970-2010 Electronic thesis and dissertation system (Chinese) 1990-2010
Keyword search terms
1Types of studies experimental study random quasi-experimental study實驗性研究隨
機類實驗性研究
2 Types of participants childchildren adolescents pediatric cancer and oncology兒童
青少年兒科癌症腫瘤
3 Types of interventions non-pharmacological interventions massage exercise fitness
physical activity cognitive behavioral stress management energy conservation
sleep therapy relaxation distraction and psycho-education非藥物性處置按摩運動
身體活動認知行為壓力處置能量保存睡眠治療放鬆轉移注意力衛教
4 Types of outcome measures fatigue cancer-related fatigue loss of energy levels of
tiredness tired side effect symptoms疲憊癌性疲憊疲倦合併症症狀
Methods of the Review
Assessment of methodological quality Papers selected for retrieval were assessed by two independent reviewers for
methodological validity prior to inclusion in the review using the standardised critical
appraisal instruments (Appendix I) from the JBI-SUMARI (Joanna Briggs Institute
Systems for the Unified Management Assessment and Review of Information package)
Any disagreements that arise between the reviewers were resolved through discussion
648
16
with a third reviewer
Data extraction Data was extracted from papers included in the review using standardised data
extraction tool (Appendix II) from the JBI-SUMARI Details of eligible studies were
extracted and summarised independently by two reviewers
Data Synthesis
All data analysissynthesis were made using the JBI-SUMARI The studies were
assessed for clinical heterogeneity by considering the settings populations interventions
and outcomes Where possible these binary outcomes were analyzed by calculation of
the Odds Ratio with the 95 CI The weighted mean difference was calculated if the
pooled studies have used the same scale for continuous data The standardized mean
difference was calculated for continuous data measuring the same outcome on a
different scale In studies where statistical pooling of results was inappropriate the
findings were considered for inclusion as a narrative summary
Results The findings from the systematic review are presented first Followed by the results from
the meta-analysis component of this review
Description of studies From database search and hand search a total of 76 papers were identified Thirty
papers were then excluded because they did not meet the inclusion criteria Forty-six
full text were retrieved for further consideration for inclusion Of the 30 excluded reasons
for exclusion were follows 11articles were duplicated eight articles did not meet
649
17
participant inclusion criteria eight articles did not meet outcome criteria and nine articles
were correlation studies or discussion papers others articles were unclear reporting In
total after sorting six papers have been included in this article Figure 1 displays the
process used to identify relevant articles for inclusion in the systematic review
Figure 1 Stages of searching and inclusionexclusion of references for the review
Potentially relevant English-language and Chinese- language Studies Identified
Electronically and hand search (n=76)
Duplicate (n= 11) Papers excluded after evaluation of abstract (n=19)
Papers retrieved for detailed examination (N=46)
Papers excluded after review of full paper
(n=40)
Papers assessed for methodological
quality (n=6)
Papers included in systematic review
(n=6)
Methodological Quality
Of the six included articles 2722232425 two articles were RCT design224 with score 7 out
of 10 each paper from Critical Appraisal Checklist and four articles used
650
18
quasi-experimental design7222425 with socre 5 to 6 out of 10 because the quality of
the whole papers is still acceptable therefore these six articles were accepted after
primary reviewer and secondary reviewerrsquos decision
Randomisation
In two RCT articles224 one study24 used to a computer-generated program operated by
the St Jude Protocol and Data Management System to randomize the sample Another
study2 didnrsquot address how randomization was done
Allocation concealment
No studies reported allocation concealment
Intention-to-treat analysis
One quasi-experimental design7 stated Intention-to-treat analysis
Adequate follow up
The follow-up periods included 2or 3 days24 7 days2 4 week7 one month25 6 week25 12
week2216 week23 and 1 year23
Baseline comparability of groups
Three 22425 of six studies had baseline comparability in terms of age sex diagnosis
race institution duration of illness
Blinded outcome assessment
No studies used blinded outcome assessment The researchers including study team
patients staff and families were not blinded to the patientrsquos group assignment
Characteristics of included studies
651
19
There were six studies related to interventions designed to cancer-related fatigue for
pediatric patients than there are for adults There are a total of six including five
English-language papers 27222324 and one Chinese-language paper 25 ranging in year of
publication from 2007 to 2009
Patient characteristics
The research subjects of four papers included both school-aged children and
adolescents 7222324 one papers involved mainly adolescents25 and one paper sampled
only school-aged children 2 the range in ages was between six-18 years The number of
patients included in the samples ranged from nine to 60 The sources of case data were
from both outpatients and hospitalized children The types of cancer included acute
lymphoblastic leukemia (ALL) solid tumors acute myeloid leukemia (AML) and
lymphoma Overall ALL was the most commonly studied cancer type The stage of the
disease varied in these reports some patients were in the maintenance stage of
chemotherapy25 some had just received their first round of chemotherapy224 some had
completed two courses of treatments lasting 4-8 weeks each 7 and some had entered
the survivor stage 2223
Countries
Two RCTrsquos 2 24 were conducted in the USA There were four quasi-experimental design
studiesThree studies conducted in the USA7 22 23 and one in Taiwan25
Intervention types
652
20
The interventions included exercise training programs 2225 physical activity 2324
massage therapy 7 and health education 223 exercise training and physical activity as
an intervention method given in three different settings home 22 25 community 23 or
hospital 24 The studies used different types of exercise interventions including
home-based aerobic exercise use a Video Compact Disc 25 use of a bicycle-style
exerciser 24 aerobics2223 and various types of physical activities2 and strength-building
exercises 2223 The intensity of the exercise varied and often included gradual warm-up
exercises a period of main exercise and a cool down period For these studies2023 the
target exercise intensity was a heart rate of gt90 of the maximum heart rate (HR max) or
the increase in the percentage of heart rate reserve ( HRR) of 40-60
The number of weeks for the exercisephysical activity interventions duration including
2-4 days 24 6 weeks25 12 weeks22 and 16 weeks23 The frequency of exercise ranged
from 2-3 times per week to twice a day Typical duration of exercise ranged from 10 to 45
minutes There are three papers using exercise interventions based on ACSM (American
College of Sports Medicine) 2225 recommendations and one of these used an Activity
pyramid from the ACSM to determine intensity 24
One article did not clarify the type of exercise intervention or the reasons for their choices
23 In addition there was an article focusing on massage therapy 7 as an intervention in
this study the experimental group received four weeks of massage therapy either in the
clinic or in the patientrsquos room the therapy was applied by a professional masseur and
targeted the back legs arms chest stomach and face of the children However the
frequency of massage sessions per week and the duration of the massages were not
653
21
given There is another article about intervention measures combine health education
and physical activity 2 In this study patients were informed about the following (1) health
education patients received daily education about chemotherapy-related fatigue and
information from a health education manual written by the author (2) encouragement for
children to engage in activities such as listening to music drawing and reading and (3)
physical activity which involved walking along the corridors of the ward for 10-15 minutes
These health education measures were presented for 45-60 minutes a day for a total of
seven days The study design for non-pharmacological interventions used control groups
that included primarily people who had received standard treatment or people who did
not receive an exercise intervention
Outcome measures
Five measurement tools were used in this group of seven papers concerning childrenrsquos
fatigue (Appendix IV) Because those studies included both school-age children and
adolescents the following descriptions will be differentiated by age Fatigue
measurements for school-aged children with cancer include the following the Child
Fatigue Scale (CFS) 7 a scale that measures the frequency and intensity of fatigue and
the Fatigue Scale for 7-12 year Olds (FS-C) 224 a scale that can be used to evaluate the
intensity of fatigue On the other hand fatigue measurements for adolescent cancer
patients include the following the Fatigue Scale for 13-18-year-olds (FS-A) 24 a measure
that can help evaluate fatigue levels the Pediatric Quality of Life Multidimensional
Fatigue Scale (Peds QL-MFS) 2325 a tool that can be divided into three sub-scales to
understand the general cognitive and sleep rest components of fatigue and finally the
CIS-20 for school-age children and adolescents 22 a scale that measures four levels of
654
22
fatigue namely subjective experience attention motivation and physical activity Two
studies used the Peds QL-MFS scale to measure fatigue2325
Meta-analysis results Two studies of the included papers failed to provide sufficient raw data they could not be
included in the meta-analysis Hinds et al 24 did not include post-test data Genc et al 2
provided no pre-test data PostWhite et al7 reported that fatigue after the health
education intervention was not statistically different but they presented the results
without presenting fatigue-related data Therefore the meta-analysis included three
studies 222325
The heterogeneity of studies was analyzed with Chi square statistics and no statistical
significance was found Therefore the data was combined in meta-analysis according to
exercise intervention on fatigue In addition there were three articles using the Peds
QL-MFS as a research tool to examine childrenrsquos improvements in fatigue Among these
Keats 22 and Chiang 24 present the effectiveness of exercise interventions using three
subscales Therefore the meta-analysis also analysis of the effects of these exercise
intervention measures on three subscales of Peds QL-MFS general fatigue sleep rest
fatigue and cognitive fatigue
The effectiveness of exercise intervention for fatigue We analyzed the exercise intervention effect on fatigue A total of 2 studies 22 23 were
included Takken et al 22 used community-based exercise training program to reduce
fatigue of children 6 to 14 years (mean 93y) of age who survived ALL Fatigue
measurement by Checklist Individual Strength (CIS) after 12-week of training fatigue
655
23
show no significant differences between pre (meanplusmnSD 415plusmn147) and post training
(meanplusmnSD368plusmn217) but fatigue change from baseline mean reduction of 11
Keats et al23 although used community-based physical activity program to reduce fatigue
for adolescents 14 to 18 years of age (mean162 y) with cancer (Lymphoma leukemia CNS
tumor germ cell tumor) Studies used fatigue by PedsQLMFS Results show general fatigue
from baseline to 8 weeks and to 3 months follow up significantly improves General
fatigue sleeprest fatigue and total fatigue from baseline to 3 months follow up showed
significant improvements Sleeprest fatigue and total fatigue at 1 years followed up were
significant improvements
Figure 2 shows the overall effect of exercise intervention in children and adolescents with
cancers with a focus on improving fatigue Due to the lower heterogeneity (p>005) the
fixed effects model was used to pool the data for meta-analysis (Overall effect size=
-006 95 Confidence Interval (CI) -070 to 058) A result did not indicate a statistically
significant difference (p = 087)
656
24
Figure2 Meta-analysis results of exercise intervention on fatigue
In addition Keats23 and Chiang25 used the three sub-scales of Peds QL-MFS to
determine the general cognitive and sleep rest components of fatigue The following
present the effectiveness of exercise interventions using three subscales including
general fatigue sleep rest fatigue and cognitive fatigue 2325
Chiang et al 25 used a 6- week home-based aerobic exercise intervention to reduce
fatigue of children 7 to 18 years (mean age at experimental group was 1088 y in control
group was 1247 y) of age who with acute lymphoblastic leukemia Fatigue measurement
by Peds QL-MFS after training For intent-to ndash treat analysis the findings indicated that
there are no intervention effects and time differences by any items on the subscale of
fatigue For per-protocol analysis general fatigue( meanplusmnSD 422plusmn402) was the only
subscale that was significantly lower for children who received the exercise intervention
than those in control group at follow-up assessment (one month after the completion of
intervention)
Keats et al23 although used community-based physical activity program to reduce fatigue
for adolescents 14 to 18 years of age (mean162 y) with cancer (Lymphoma leukemia
CNS tumor germ cell tumor) Both studies used fatigue by PedsQLMFS Results show
general fatigue from baseline to 8 weeks and to 3 months follow up significantly improves
657
25
General fatigue sleeprest fatigue and total fatigue from baseline to 3 months follow up
showed significant improvements Sleeprest fatigue and total fatigue at 1 years followed
up were significant improvements
The effectiveness of exercise intervention for general fatigue
The impact of the exercise interventions upon levels of general fatigue was also analysed
The heterogeneity was low (p>005) Therefore the fixed effects model was used to
examine the effectiveness The effect size is -076 indicating a statistically significant
difference (p = 001 95 CI -135 to -017 Fig 3) The evidence suggests that exercise
intervention can reduce general fatigue in children with cancer
Fig 3 Meta-analysis results of exercise intervention for general fatigue
The effectiveness of exercise intervention for sleep rest fatigue
The following is the result of the meta-analysis of the effectiveness of exercise
interventions on sleep rest fatigue First the heterogeneity test was conducted with P gt
005 representing small heterogeneity and the fixed effects model was used Fig 4
shows the effect size is -035 indicating no statistically significant differences (p = 023
95 CI-092 to 022 Fig 4)
658
26
Fig 4 Meta-analysis results of exercise intervention for sleep rest fatigue
The effectiveness of exercise intervention for cognitive fatigue Lastly the following data reports the results of meta-analysis of the effectiveness of
exercise interventions for cognitive fatigue The heterogeneity was p>005 then the
fixed effects model was used The effect size is -035 indicating no statistically significant
differences (p = 024 95 CI-092 023 Fig 5)
Fig 5 Meta-analysis results of exercise intervention for cognitive fatigue
Narrative presentation of remaining included studies
Three studies were not included in meta-analysis Post-White et al7 one of the aims in
this study was to examine the effect of massage therapy on fatigue in children with
cancer The study was a quasi-experimental design Twenty-three childrenparent dyads
were enrolled 17completed all data points Children with cancer ages 7 to 18 years
received at least 2 identical cycles of chemotherapy and one parent participated in the
2-period crossover design in which 4 weekly massage sessions (MT) alternated with 4
659
27
weekly quiet-time (QT) control sessions There were no significant changes in fatigue in
children over the 4-week MT or QT conditions either independently (change over time) or
when we compared fatigue by condition
The lack of effect of massage on fatigue may be the difficulty some children had in
differentiating fatigue from being relaxed underscores the challenge of measuring fatigue
in children Some children interpreted being tired or relaxed as having greater fatigue
because they felt like lying around and sleeping or felt unmotivated to do their usual
activities all measures of fatigue in the instrument used in the study
Hinds et al24conducted a prospective two-site randomized controlled pilot study to
assess the feasibility of an enhanced physical activity (EPA) intervention in hospitalized
children and adolescents receiving treatment for a solid tumor or for acute myeloid
leukemia (AML) Twenty-nine patients (25 with a solid tumor and 4 with AML) participated
age range from 736 to 1816 (mean 1248 y) The EPA intervention selected was
pedaling a stationary bicycle-style exerciser (Chattanooga Peddler Deluxe Bio-Teck
Medical Memphis TN) for 30 minutes twice daily for 2 to 4 days of hospitalization The
mixed model analysis revealed no significant differences in patient reports of fatigue
between the two study arms or over time
Genc et al2 conducted a RCT involving children with cancer who are 7 to 12 years of age
and receiving chemotherapy treatment to determine the impact of educational
intervention by nurses on decreasing the fatigue syndrome The research sample was
composed of a total of 60 children with cancer with 30 children being included in the
660
28
experimental group (mean age 923)and 30 children included in the control group (mean
age 937) with their mothers In the experimental group after the 7th to 10th day of the
chemotherapy treatment throughout a week the researcher conducted the nursing
interventions every day for 45 to 60 minutes In the control group routine nursing
interventions were carried out The experimental group received education about the
fatigue with the chemotherapy and fatigue handbook was given which was developed by
the authors Children and mothers were consulted for including activities that could
decrease fatigue which were described as effective interventions A statistically
significant difference was found between the Fatigue Scale-Child mean scores of the
experimental (2723) and the control group (4213) The results suggest that fatigue of
children with cancer can be reduced by implementing appropriate nursing interventions
(t=567 Plt00)
Discussion The purpose of this systematic review was to determine the effectiveness of
non-pharmacological interventions specifically targeting fatigue for children and
adolescents with cancer undergoing chemotherapy or after receiving chemotherapy
Included articles about the effectiveness of non-pharmacological interventions for
children and adolescents with cancer were published between the years of 2007 and
2009 Although interventions for cancer fatigue for adults have been extensively studied
it can be seen from either the title of the paper or related content that an intervention
study on children was a pilot study or a feasibility study Representing a field in its early
stage these studies show that the fatigue issues with young cancer patients have only
recently been taken seriously
661
29
The results of our meta-analysis include measurement of the four performance indicators
fatigue and general fatigue sleep rest fatigue and cognitive fatigue The results show
that there is a statistically significant difference only in the domain of general fatigue
using an exercise intervention for children with cancer can improve the degree of fatigue
with the effect size reaching 0671 Other results do not indicate significant differences
The reasons may include the following
1 Characteristics of the cancer The exhaustion from cancer occurs not only during cancer treatment but also in during
long-term survival a time during which patients may continue to be affected by this
symptom 8 26 Therefore when using intervention measures to improve fatigue
circumstances should be considered such as the process of the treatment and the course
or stage of the disease Because cancer patients will experience different forms of
treatment or courses of treatment the disease itself or treatment differences should be
considered in the choice of intervention Even chemotherapy drugs should be taken into
consideration For example a period of general steroid treatment can increase patientsrsquo
fatigue In those studies of children with cancer few studies looked solely at one type of
cancer most studies included a variety of cancer patients Furthermore most studies do
not clearly explain the stage of the disease or course of treatment and most do not
include treatment variables in the control group Moreover children with cancer may
have different levels of physical function
2 Research design The sample size Currently there are few studies with large sample size and a rigorous
RCT design due to the small number of papers available for analysis The sample size
included in our studyrsquos data analysis is between 20 and 42 people this small sample size
will affect the power available to evaluate outcome variables
Although most of the non-pharmacological interventions still use exercise and physical
activity and these studies overall show better results for fatigue as compared with
controls more research is still needed to further confirm the efficacy of these findings
662
30
The dropout rate in the evaluated research varies a great deal ranging from 5 to 45
these dropout rates may result from the characteristics of the research subjects or the
lengthy time involved in participating in these studies The research data with a high
turnover rate might not reflect the actual outcomes of participation in exercise and the
quality of the research contained in articles with high subject turnover rates may be
lower
Exercise doses and time The exercise doses needed to reduce fatigue cannot be
determined additionally the amount of exercise completed by the patient is also
inconsistent interventions vary between 2-3 times per week and two times a day and
exercise duration varies between 10 and 45 minutes each time Furthermore the study
interventions vary in length between a couple of days and a long period of 16 weeks The
data collection times are different some were measured 12 weeks after the intervention
began some were measured during the 6 weeks of intervention some were measured
three months after the intervention was finished and some were measured after one
year
In addition disease-related symptoms decrease childrenrsquos willingness to participate in
exercise interventions inappropriate exercise intervention programs may actually
increase childrens fatigue In addition the children in the study are still developing
physically it is important to consider ways to design an interesting exercise intervention
to increase the compliance of patients in order to improve the effectiveness Although
intervention programs in the hospital or in a community sports center can improve the
effectiveness because they provide supervision the feasibility of these programs is
questionable However if the program is home-based the children need to be
supervised by parents in order to improve their compliance in doing the exercises
Furthermore regarding the nature of the intervention the results from this study indicate
that the researched non-pharmacological interventions include the following exercise
training programs physical activity massage therapy and health education interventions
However according to the National Comprehensive Cancer Network 1 clinical guidelines
663
31
for cancer non-drug measures for cancer fatigue can be separated into five categories
(1) activity enhancement (2) psychosocial interventions such as cognitive behavioral
therapy (CBT) stress management relaxation techniques and support groups (3)
attention-restoring therapy (4) nutritional consultation and (5) cognitive behavioral
therapy specifically targeting sleep disturbance Researchers have also suggested that
psychosocial interventions should be included in the future research for children with
cancer-related fatigue 22
(2) The measurement tools in the study The assessment of fatigue can be
one-dimensional or multidimensional One-dimensional assessment can help understand
the severity of fatigue symptoms however multidimensional scales are often more
credible Therefore when measuring cancer-related fatigue researchers should consider
whether there is a uniform definition of fatigue or a standardized tool for measuring
fatigue in order to facilitate further systematic meta-analyses and further develop the
clinical care guidelines
Limitations of the review The present review has some potential limitations First the low methodological quality
may influence the result Although exercise intervention seems promising quality of the
RCTs was generally quite low Future studies require better design and reporting if
methodological issues to establish evidence-based nonpharmcologic intervention
Second the identified studies covered only a limited types of nonpharmcological
intervention especially in exercise intervention The guidelines for cancer-related fatigue
in NCCN (2011)1 referred to more interventions than the ones included in this review
such as cognitive behavioral therapy and nutrition consultation Thirdly the small sample
size and effect size could be potentially having led to underpowered approach for
detecting the effects on fatigue Therefore we recommend that as research continues to
grow a re-analysis can be undertaken Fourthly Combining data in meta analysis from
664
32
studies where the ages were quite different is a potential source of heterogeneity and
may affect the interpretation of the results
Conclusion At present clinical treatment is widely used for cancer patients However child and
adolescent cancer patients often experience various side effects which cause short-term
or long-term discomfort both physically and psychologically In particular with the
increasing cure rate cancer related fatigue during or after treatment has become an
important issue This study result provided positive effect of exercise intervention on
general fatigue
Implications for practice The results of this systematic review and meta-analysis show that exercise interventions
can effectively improve the level of general fatigue In particular although the articles
were self-reported feasibility studies their results all indicate that exercise interventions
for fatigue are feasible and safe there was no conclusion to be made for the use of
massage therapy or health education measures because there was only one article for
each of these interventions
Recommendations for practice
Cancer-related fatigue is one of the most severe and frequent symptoms by pediatric
oncology children and adolescent suffered during treatment and the symptom existed
even after treatment has ended Until now no golden standard of treatment to fatigue is
established The findings call for more attention to how to reduce patientrsquos levels of
fatigue Based on the available information evaluated in this review the following
recommendations for practice are provided
665
33
bull For children aged 7 to 18 who has cancer (eg Lymphoma leukemia CNS tumor
germ cell tumor) an effective progressive aerobic exercise program is recommended to
be at least 2-3 times per week 20 to 45 minute for each session and last for 6-16 weeks
in order to reduce their general fatigue (tiredness physically weakness) In addition
adults should be involved in accompanying children while they are performing physical
exercise of which should be able to improve the adherence rate (level 2 ) ( Grade of
recommendation A)
bull For children aged 7 to 18 who has cancer (eg Lymphoma leukemia CNS tumor
germ cell tumor) an progressive aerobic exercise program will not be effective to reduce
their sleep andor rest (sleeping or resting a lot) or cognitive fatigue (problems with
thinking quickly or problems with remembering) (level 2 ) ( Grade of recommendation C)
bull Nursing interventions in educating treatment of fatigue include information about
activity nutrition energy preservation consulting and providing a useful fatigue
handbook will benefit those children who are 7 to 12 years have a new diagnosis of ALL
AML or lymphoma and receive for the first time after being diagnosed a 7- to 10-day
chemotherapy treatment (level 2) ( Grade of recommendation A)
bull A 4-week massage therapy program (the therapists massage childrenrsquos back legs
arms stomachchest and face) is not effective for children who are aged 7 to 18 and
have acute lymphoblastic leukemia brain tumors lymphoma rhabdomyosarcoma
Wilms tumor or Ewing sarcoma(level 2)( Grade of recommendation C)
bull Using a 12-week aerobic and strength exercise (45-min exercise sessions twice a
week) is not effective for children who are aged 6-14 and survived acute lymphoblaststic
leukemia age from 6 to 14(level 2) ( Grade of recommendation C)
bull Using a physical activity intervention (30minutestwice daily for 2-4days) is not
effective for children who are 7 to 18 years of age with soild tumor or AML(level 2)
( Grade of recommendation C)
666
34
Implications for research According to this systematic review and meta-analysis results there are suggestions to
improve the effectiveness of future research on non-pharmacological interventions for
children and young peoplersquos cancer-related fatigue
As the majority of included non-pharmacological interventions for the fatigue of cancer
patients consist of exercise programs future research should also consider various
non-pharmacological interventions in order to understand the effectiveness of different
methods
Regarding the exercise intervention methods and studies should consider multiple
factors including the age or personal condition of the subject the disease stage and the
amount of daily activities Studies should use design prescriptions (eg frequency
intensity duration and type of exercise) and consider the adherence to the measures in
order to enhance the study strength
In measuring the results of non-pharmacological interventions there should be standard
definitions or standard measurement tools to facilitate the following systematic review
and meta-analysis that can subsequently be developed into clinical care guidelines
Reviewing the effectiveness of the current non-pharmacological management of children
and adolescent cancer patients there is still a lack of rigorous RCT research Limited by
the characteristics of cancer there is still a lack of large sample sizes
Potential conflicts of interest There is no conflict of interest
Acknowledgements
Thank you to Dr Rie Konno Research Fellow Joanna Briggs Institute for her help in
assessing studies
667
35
References 1 National Comprehensive Cancer Network( NCCN) in USA NCCN clinical practice
guideline in oncology cancer-related fatigue 2011 2 Ekti Genc R amp Conk Z Impact of effective nursing interventions to the fatigue
syndrome in children who receive chemotherapy Cancer Nursing 200831(4)312-317
3 Childhood Cancer Foundation of ROC (2009March) The classification of diseases
and age sex statistical tables of case Childhood Cancer Foundation of ROC newsletter103105-106
4 Department of Health Executive Yuan ROC (TAIWAN)(2009 March 20)2009 cause of death statistic Health and National Health Insurance Annual Statistics Information Service 2010 June 28Available httpwwwdohgovtwstatisticdatavital statists9898health statistic--lifepdf
5 Chang TK (2007December 8) Common childhood cancer and its treatment Status
Childhood Cancer Foundation of ROC (TAIWAN) 2010 September 23 Available httpwwwccfrocorgtwchildchild_events_readphpe_id=45
6 Hockenberry MJ amp Wilson D Wongs nursing care of infants and children (8th ed) St
Louis MO Mosby 2007
7 Post-White J Fitzgerald M Savik K Hooke MC Hannahan AB amp Sencer SF
Massage therapy for children with cancer Journal of Pediatric Oncology Nursing 2009 26(1)16-28
8Chiang YC Yeh CH Wang WKamp Yang CP The experience of cancer-related fatigue
in Taiwanese children European Journal of Cancer Care 2009 18(1)43-49 9Langeveld NE Grootenhuis M A Voute P A de Haan RJ amp van den Bos C No excess
fatigue in young adult survivors of childhood cancer European Journal of Cancer 200339(2)204-214
10Piper BF Lindsey AM amp Dodd MJ Fatigue mechanisms in cancer patients
developing nursing theory Oncology Nursing Forum 1987 14(6)17-23 11Nail LM amp Winningham ML Fatigue In S L Groenwald M H Forgge M Goodman
amp C H Yarbro (Eds) Cancer Nursing Principles and practice (4 th ed) Boston Jones and Bartlett1997
12Irvine D Vincent L Graydon JE Bubela N amp Thompson L The prevalence and
correlates of fatigue in patients receiving treatment with chemotherapy and
668
36
radiotherapy A comparison with the fatigue experienced by healthy individuals Cancer Nursing 199417(5)367-378
13Hinds PS amp Hockenberry-Eaton M Developing a research program on fatigue in
children and adloescents diagnosed with cancer Journal of Pediatric Oncology Nursing 200118(2)3-12
14Aaronson LS Teel CS Cassmeyer V Neuberger GB Pallikkathayil L Pierce J Press
AN Williams DP amp Wingate A Defining and measuring fatigue Journal of Nursing scholarship 1999 31(1)45-50
15Yeh CH Wang CH Chiang YC Lin Lamp Chien LC Assessment of symptoms reported
by 10- to 18-year-old cancer patients in Taiwan 2009 38(5)738-746 16 Okuyama T Akechi T Kugaya A Okamura H Shima Yamp Maruguchi M
Development and validation of the cancer fatigue scale a brief three-dimensional self-rating scale for assessment of fatigue in cancer patients Journal of Pain amp Symptom Management 2000 19(1) 5-14
17Gibson F Mulhall AB Richardson A Edwards JL Ream E amp Sepion BJ A
phenomenologic study of fatigue in adolescents receiving treatment for cancer Oncology Nursing Forum200532(3)651-660
18Wolfe J Grier HE Klar N Levin SB Ellenbogen JMamp Salem-Schatz S et al
Symptoms and suffering at the end of life in children with cancer New England Journal of Medicine 2000342(5)326-333
19Whiting P Bagnall AM Sowden AJ Cornell JE Mulrow CD amp Ramirez G
Interventions for the treatment and management of chronic fatigue syndrome a systematic review JAMA the Journal of the American Medical Association 2001286(11)1360-1368
20 Kangas M Bovbjerg DHamp Montgomery G H Cancer-related fatigue a systematic
and meta-analytic review of non-pharmacological therapies for cancer patients Psychological Bulletin 2008134 (5)700-741
21Williams PD Schmideskamp J Ridder EL amp Williams AR Symptom monitoring and
dependent care during cancer treatment in children pilot study Cancer Nursing 200629(3)188-197
22Takken T van der Torre P Zwerink M Hulzebos EH Bierings M Helders PJMamp van
der Net J Development feasibility and efficacy of a community-based exercise training
669
37
program in pediatric cancer survivors Psycho-Oncology 200918(4)440-448
23Keats MR amp Culos-Reed SN A community-based physical activity program for
adolescents with cancer (project TREK) program feasibility and preliminary findings
Pediatric hematology and oncology 200830(4) 272-280
24Hinds PS Hockenberry M Rai SN Zhang L Razzouk B I Cremer L McCarthy K amp
Rodriguez-Galindo C Clinical field testing of an enhanced-activity intervention in
hospitalized children with cancer Journal of Pain amp Symptom Management 2007
33(6)686-697
25Chiang YC The effects of ldquo a home-based aerobic exercise interventionrdquo on fatigue
and cardiorespiratory fitness in children with acute lymphoblastic leukemia during the
maintenance stage of chemotherapy Unpublished thesis Taiwan Tao-Yuan 2007
26Langeveld N Ubbink M amp Smets E I dont have any energy The experience of
fatigue in young adult survivors of childhood cancer European journal of oncology
nursing 20004(1)20-28
27 Kisner C Colby L Therapeutic exercise Foundations and techniques 2nd ed Philadelphia PAFA Davies 2007
670
38
Appendix I JBI Critical Appraisal Checklist for Experimental studies
Author__________ Year_________ Record Number__________________
Questions 1 to 4 must be answered ldquoyesrdquo for study to be included in the metashyanalysis
1 Were the participants randomized to study groups
Yes No Not clear
2 Other than research intervention were participants in each groups treated the same
Yes No Not clear
3 Were the outcomes measured in the same manner for all participants
Yes No Not clear
4 Were groups comparable at entry
Yes No Not clear
5 Was randomization of participants blinded
Yes No Not clear
6 Were those assessing outcome blinded to treatment allocation (if outcome not objective such as survival or length of hospitalization)
Yes No Not clear
7 Was allocation to treatment groups concealed from the allocator
Yes No Not clear
8 Was an appropriate statistical analysis used
671
39
Yes No Not clear
9 Were outcomes measured in a reliable way
Yes No Not clear
10 Was there adequate followshyup of participants
Yes No Not clear
Summary
TOTAL
Yes No Not clear
DECISION
Use Reject
Narrative summary only Further information needed
COMMENTS
672
40
Appendix II JBI Data Extraction Tool for Quantitative Studies Authors and Year
Journal Title
Record NumberArticle Reference No
Reviewer
Method
Settings
Participants
Number of participants
Group A Group B Group C
Control Intervention 1 Intervention 2
Interventions
Group A
Control
Group B
Intervention 1
Group C
Intervention 2
Outcome measures
Definition
673
41
Other outcome measures
Outcome description ScaleMeasure
Results
Dichotomous Data
Outcome Control Group
Numbertotal number
Treatment Group
Numbertotal number
Continuous Data
Authorrsquos Conclusions
Comments
Outcome Control Group
Mean amp SD
Treatment Group
Mean amp SD
674
43
Appendix III Details of included studies (N=6)(2720212223) RefNo Author(s)
(years) Title Study question Research
method Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
22 Takken T van der Torre P Zwerink M Hulzebos E H Bierings M Helders P J Mamp van der Net J (2009)
Development feasibility and efficacy of a community-based exercise training program in pediatric cancer survivors
To develop a 12-week home-based exercise training program (comprising aerobic and strength exercises) for children who survived ALL and to study itrsquos feasibility and efficacy
Pre-post test design
No comparsion group
Survived ALL(N=9)ages 6-14 years
1anthropometry 2 muscle strength 3functional mobility 4cardio-pulmonary
exercise test 5Fatigue
1 Feasibility questionnaire 2 anthropometry electronic scale and a wallmounted stadiometerHarpenden skin fold calipers 3 muscle strength handheld dynamometer 4functional mobility Timed Up
and Go test (TUG) 5cardio-pulmonary exercise test electronically braked cycle ergometer 6Fatigue(mean)CSI-20 (subjective experience of fatigueconcentrationmotivationphysical activity)
112-week exercise training program
2 Patients were assessed before (T0) and after (T1) 12 weeks of training
1 muscle strength execapacity functional moand fatigue showed nosignificant differences between pre(meanplusmnSD415plusmn147) and post training(meanplusmnSD3687)
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
7 Post-White J Fitzgerald M Savik K Hooke M C Hannahan A B amp Sencer S F (2009)
Massage therapy for children with cancer
To determine whether 4 weekly sessions of massage compared with 4 quiet-time control conditions would reduce anxiety cortisol levels fatigue nausea and pain in children with cancer undergoing chemotherapy and would reduce anxiety fatigue and mood disturbance in a parent
2-period crossover design (Randomized)
quiet-time
control
sessions
Children with cancer 1 to 18 years of age Twenty-three childrenparent dyads were enrolled 17 completed all data points
children 1relaxation 2symptoms 3 fatigue
parents
1anxiety 2 fatigue
children 1relaxation (heart and respiratory rates blood pressure and salivary cortisol level)
2symptoms (pain nausea anxiety 3 fatigue 1-2y3-6yLansky Play Performance Scale (PPS) 7-13y
1 4 weekly massage (MT) sessions alternated with 4 weekly quiet-time(QT) control sessions
2 children included presession and postsession vital signs (heart rate respiratory rate blood pressure) and self-report (parent proxy report for age 1-2 years) of pain nausea and anxiety Fatigue was measured before sessions 1 and 4 and at each follow-up Parent measures
included anxiety fatigue and mood states
1Massage was moreeffective than quiet tireducing heart rate inchildren anxiety in cless than age 14 yeaparent anxiety 2There were no sign
changes in blood pcortisol pain naufatigue (no state d
3 Children reported tmassage helped thebetter lessened theirand worries and hadlasting effects than q
675
44
14-18yChild Fatigue Scale (CFS) (frequency
intensity) 2 parents anxiety and fatigue
676
45
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
24 Hinds P S Hockenberry M Rai S N Zhang L Razzouk B I Cremer L McCarthy K amp Rodriguez-Galindo C (2007)
Clinical field testing of an enhanced-activity intervention in hospitalized children with cancer
To determine the feasibility of an
enhanced physical activity EPA intervention in children and adolescents hospitalized to receive chemotherapy for a solid tumor or AML and to assess the sleep and fatigue outcomes of the intervention using two different statistical approaches to analyze the longitudinal symptom data
randomized prospective two-site and two-group pilot study
Standard care Twenty nine patients (25 with a solid tumor and 4 with AML)ages 7-18 years
1 sleep duration 2 sleep efficiency 3 fatigue
1sleep duration sleep efficiency The
Wrist Actigraph The Daily Sleep Diary-Parent 2 fatigue (mean) The Fatigue Scale(FS-C) for 7-12 (intensity) The Fatigue Scale(FS-A) for 13-18 The Fatigue Scale Parent Version (FS-P) The Fatigue Scale Staff Version (FS-S)
1enhanced physical activity (EPA) (hospital-based 30 minutes
twice daily for 2-4 days) 2 T0On the day of admission
(Day 0 or baseline)patient and parents completed the fatigue instruments and a team member applied the actigraph Patients wore the wrist actigraph T1 from Day 0 to 2 or 3 consecutive days (Days 0e3) In addition the patient same parent and staff nurses completed the daily sleep and fatigue reports in the late afternoons of Days 1-3
1 ANOVA model slesignificantly more the experimental athe control arm whdifferences from bsleep efficiency vaaveraged and com
2 The patient-reported mean fatigue scoresarms were higher amadolescents than for
3 The mixed model anarevealed no significandifferences in patientfatigue between
the two study arms otime( no final result iSD only give mixed result)
677
46
23 Keats M
R amp Culos-Reed S N (2008)
A community-based physical activity program for adolescents with cancer (project TREK) program feasibility and preliminary findings
To examine the
feasibility of a
theoretically-based
physical activity (PA)
intervention in
adolescents with
cancerand
examination of the
impact of the
program on
participant QOL
including social
emotional and
physical
well-being(including fatigue)
Repeat measures longitudinal design
No comparsion group
10 adolescents(Lymphoma(4)leukemia(4)CNS tumor(1)germ cell tumor(1)) ages 14-18 years
1physical fitness 2quality of life (QOL) 3PA behavior 4fatigue
1 Feasibility was assessed by participant recruitment attendance and adherence
2physical fitness Fitnessgram 3quality of life (QOL) Pediatric Quality of Life Inventory (PedsQL) 4PA behavior leisure score index (LSI) 5fatigue (mean) pediatric Quality of life
Multidimensional Fatigue Scale (Peds QL-MFS)
(Generalsleepcognitive fatigue)
116week physical activity (PA)
2 total PA physical fitness and overall QOL was assessed at 5 different intervals T0 preintervention (baseline) T1midintervention (after the
first 8 wk) T2 postintervention
(16 wk) T3 3-months
postintervention T4 1-year poststudy
initiation
1 from baseline -wkssig Improvementstotal PA physfitness and Qgeneral fatigue(meanplusmnSD 796plusmn135)
2 from baseline to 3FUsig Improvin general fatigue(meanplusmnSD824plusmn131)slefatigue(meanplusmnSD755plusmn191)totafatigue(meanplusmnSD778plusmn150)
3at 1 years FUsImprovements in sleeprest fatigue(meanplusmnSD725plusmn203)total (meanplusmnSD 763plusmn
678
47
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
2 Gene R E amp Conk Z (2008)
Impact of Effective Nursing Interventions to the Fatigue Syndrome in Children Who Receive Chemotherapy
1 to examine the effects of an effective nursing intervention to the fatigue syndrome of children 7 to 12 years of age who receive chemotherapy 2Tto examine the relationship between fatigue and demographic variables (age sex) diagnoses ([ALL AML] lymphoma) and therapy-related variables (eg level of hemoglobin
experimental randomized controlled study
Routine nursing care
A total of 60 children who are 7-12 years of age(a new diagnosis of ALL AML or lymphoma and receiving for the first time after being diagnosed a 7- to 10-day chemotherapy treatment )
fatigue The Fatigue Scale(FS-C) for 7-12 (intensity)
The Fatigue Scale Parent Version (FS-P)
1 effective nursing interventions(45- 60mdaya week)education about the fatigue with the chemotherapy and fatigue handbook 2 T1 After a 7-day period the children
and parent were evaluated with the Fatigue Scale
1The difference betwthe 2 mean values wafound to be statisticallsignificant 2 statistically significadifference was found between the Fatigue Scale-Child mean scothe experimental (272the control group (4213)children
679
48
25 Chiang et
al(2007)
The effects of ldquo a home ndashbased aerobic exercise interventionrdquo on fatigue and cardiorespiratory fitness in children with Acute Lymphoblastic Leukemia during the maintenance stage of chemotherapy
To examine the effect of ldquo a home ndashbased aerobic exercise interventionrdquo on fatigue and cardiorespiratory fitness in children with Acute Lymphoblastic Leukemia during the maintenance stage of chemotherapy
Quasi-experi -mental
Routine
nursing care
14 pediatric oncology patients in the experimental group and 10 in control group who were matched by age and sex ages7-18 years
1Cardiorespiratory fitness
2Fatigue
1Cardiorespiratory fitness Physical Activity Recall
VO2maxHR peak 6MWT
2 Fatigue PedsQL-MFS(Generalsleepcognitive fatigue)
1A six-week home-based aerobic exercise intervention 2 8 time points T0 baseline T1-T6 every week during the
intervention(6 weeks) T7 post intervention T8 follow-up (one month after
the end of the home-based exercise program)
1 For intent-to ndash treatthe findings indicated are no intervention efftime differences by anon the subscale of fat2 For per-protocol angeneral fatigue( mean422plusmn402) was the osubscale that was siglower for children whothe exercise interventthose in control groupfollow-up assessmentmonth after the compintervention) 3 The VO2peak are significantly improvingexperimental group atbaseline- and post-intassessment The VO2was significantly highechildren who were in experimental group thcontrol subjects at post-intervention assefor the per-protocol an
680
49
Appendix IV Instrument used to measure fatigue
Name Instrument
developers
Description Used in
age in
ref
Reliability
Consistency of
instrument
Checklist Individual Strength
(CIS)22
Vercoulen et
al1996
20 items using 7-point Likert scale of
fatigue To measure four aspects of
fatiguesubjective experience
contractionmotivation physical
Activity
6-14 Not reported
Child Fatigue Scale (CFS)7 Hockenberry
et al2003
14 items 2 part questionnaire frequency
(yes or no) 5-point Likert scale of the
intensity of any yes responses
7-13
14-18 α073-o84
The Fatigue Scale for 7-12
year Olds (FS-C)224
Hockenberry
et al
14 items provide a fatigue intensity score
5-point Likert scale
7-12 αo84
The Fatigue Scale for 13-18
year Olds (FS-A)24
Hockenberry
et al
14 items provide a fatigue intensity score
5-point Likert scale
13-18 α076-o96
Pediatric Quality of life
Multidimensional Fatigue
Scale (Peds QL-MFS)2325
Varni2002 18 items to measure three aspects of
fatigueGeneralsleepcognitive
14-18 Not reported
681
50
Appendix V Excluded studies and reasons for exclusion
Baggott C Dodd M Kennedy C Marina N Miaskowski C Multiple Symptoms in Pediatric Oncology
Patients A Systematic Review Journal of Pediatric Oncology Nursing 2009 Nov-Dec 27(6)
325-339
Reason for exclusion Not outcome of interest
Barlow JH Ellard DR Psycho-educational interventions for children with chronic disease parents and
siblings an overview of the research evidence base Care Health amp Development 2004 Nov
30(6)637-45
Reason for exclusion Not outcome of interest
Bedider S Moyer CA Randomized controlled trials of pediatric massage A review Evid Based
Complement Alternat Med 2007 Mar 4(1)23-34 Epub 2006 Nov 3
Reason for exclusion Not outcome of interest
de Nijs EJ Ros W Grijpdonck MH Nursing intervention for fatigue during the treatment for cancer Cancer
Nursing 2008 31(3)191-206
Reason for exclusion Not population of interest
Edwards JL Gibson F Richardson A Sepion B Ream E Fatigue in adolescents with and following a
cancer diagnosis developing an evidence base for practice European Journal of Cancer 2003
Dec 39(18)2671-80
Reason for exclusion Not experimental or quasi-experimental study
Hinds PS Hockenberry-Eatan M Developing a research program on fatigue in children and adolescents
diagnosed with cancer Journal of Pediatric Oncology Nursing 2001 Mar-Apr 18(2 Suppl
1)3-12
Reason for exclusion Not experimental or quasi-experimental study
Hockenberry-Eaton M Hinds PS Alcoser P ONeill JB Euell K Howard V Gattuso J Taylor J Fatigue in
Children and Adolescents With Cancer Journal of Pediatric Oncology Nursing 1998 July
15(3)172-182
Reason for exclusion Not experimental or quasi-experimental study
Jean-Pierre P Mustian K Kohli S Roscoe JA Hickok JT Morrow GR Community-based clinical oncology
research trials for cancer-related fatigue The Journal of Supportive Oncology 2006 Nov-Dec
4(10)511-6
682
51
Reason for exclusion Not population of interest
Kangas M Bovbjerg DH Montgomery GH Cancer-Related Fatigue A Systematic and Meta-Analytic
Review of Non-Pharmacological Therapies for Cancer Patients Psychological Bulletin 2008 Sep
134(5)700-41
Reason for exclusion Not population of interest
Lotfi-Jam K Carey M Jefford M Schofield P Charleson C Aranda S Nonpharmacologic strategies for
managing common chemotherapy adverse effects A systematic review Journal of Clinical
Oncology 2008 Dec 1 26(34)5618-29 Epub 2008 Nov 3
Reason for exclusion Not outcome of interest
Marchese VG Chiarello LA Lange BJ Effects of physical therapy intervention for children with acute
lymphoblastic leukemia Pediatr Blood Cancer 2004 Feb42(2)127-33
Reason for exclusion Not outcome of interest
Meeske KA Siegel SE Globe DR Mack WJ Bernstein L Prevalence and correlates of fatigue in
long-term survivors of childhood leukemia Journal of Clinical Oncology 2005 Aug 20
23(24)5501-10
Reason for exclusion Not intervention study
Minton O Richardson A Sharpe M Hotopf Stone P A systematic review and meta-analysis of the
pharmacological treatment of cancer-related fatigue J Natl Cancer Inst 2008 Aug 20
100(16)1155-66 Epub 2008 Aug 11
Reason for exclusion Not population and intervention of interest
Mustian KM Morrow GR Carroll JK Figueroa-Moseley CD Pascal JP Williams GC Integrative
nonpharmacologic behavioral interventions for the management of Cancer-Related fatigue The
Oncologist 2007 12(1)52-67
Reason for exclusion Not population of interest
Neill J Belan I Ried K Effectiveness of non-pharmacological interventions for fatigue in adults with
multiple sclerosis rheumatoid arthritis or systemic lupus erythematosus a systematic review
Journal of Advanced Nursing 2006 Dec 56(6)617-35
Reason for exclusion Not population of interest
Rheingans JI A systematic review of nonpharmacologic adjunctive therapies for symptom management
Journal of Pediatric Oncology Nursing 2007 24(2) 81-94
683
52
Reason for exclusion Not outcome of interest
Rheingans JI Pediatric oncology nursesrsquo management of patients symptoms Journal of Pediatric
Oncology Nursing 2008 Nov 25(6) 303-11
Reason for exclusion Not outcome of interest
San Juan AF Fleck SJ Chamorro-Vintildea C Mateacute-Muntildeoz JL Moral S Peacuterez M Cardona C Del Valle MF
Hernaacutendez M Ramiacuterez M Madero L Lucia A Effects of an intrahospital exercise program
intervention for children with leukemia Medicine amp Science in Sports amp Exercise 2007 Jan
39(1)13-21
Reason for exclusion Not outcome of interest
Sanford SD Okuma JO Pan J Srivastava DK West N Farr L Hinds PS Gender differences in sleep
fatigue and daytime activity in a pediatric oncology sample receiving dexamethasone Journal of
Pediatric Psychology 2008 Apr 33(3)298-306 Epub 2007 Nov 17
Reason for exclusion Not experimental or quasi-experimental study
Schmitz KH Holtzman J Courneya KS Macircsse LC Duval S Kane R Controlled physical activity trials in
cancer survivors a systematic review and meta-analysis Cancer Epidemiol Biomarkers Prev
2005 Jul 14(7)1588-95
Reason for exclusion Not population of interest
van Brussel M Takken T Lucia A van der Net J Helders PJ Is physical fitness decreased in survivors of
childhood leukemia A systematic review Leukemia 2005 Jan 19(1)13-7
Reason for exclusion Not population of interest
Whiting P Bagnall AM Snowden AJ Cornell JE Mulrow CD Ramirez G Interventions for the treatment
and management of chronic fatigue syndrome JAMA 2001 Sep 19 286(11)1360-8
Reason for exclusion Not intervention of interest
Whitsett SF Gudmundsdottir M Davies B McCarthy P Friedman D Chemotherapy-related fatigue in
childhood cancer correlates consequences and coping strategies Journal of Pediatric
Oncology Nursing 2008 Mar-Apr 25(2)86-96 Epub 2008 Feb 29
Reason for exclusion Not experimental or quasi-experimental study
Winner C Muumlller C Hoffmann C Boos J Rosenbaum D Physical activity and childhood cancer Pediatr
Blood Cancer 2010 Apr 54(4)501-10
Reason for exclusion Not research study
684
53
Wu M Hsu L Zhang B Shen N Lu H Li S The experiences of cancer-related fatigue among Chinese
children with leukaemia A phenomenological study Journal of Nursing Studies 2010 Jan
47(1)49-59 Epub 2009 Aug 25
Reason for exclusion Not experimental or quasi-experimental study
Yeh CH Chiang YC Lin L Yang CP Chien LC Weaver MA Chuang HL Clinical factors associated with
fatigue over time in paediatric oncology patients receiving chemotherapy British Journal of
Cancer 2008 Jul 8 99(1)23-9 Epub 2008 Jun 24
Reason for exclusion Not experimental or quasi-experimental study
685
5
survival rate of children with cancer has exceeded 756 however the treatments of
cancer tend to rely on aggressive chemotherapies which force children to face a long
treatment process as well as various physical and mental symptoms8 Fatigue is one of
the common symptoms affecting children during treatments Children may feel persistent
fatigue even after they complete cancer treatments9
To date the causes and mechanism of cancer-related fatigue are still unclear However
the theories concerning the causes of fatigue have been proposed Common theories
include Integrated Fatigue Model10 Psychobiological Entropy Model11 Energy Analysis
Model12
Piper et al (1987) 10 proposed the Integrated Fatigue Model which is one of the most
frequently cited fatigue models at present They suggest that fatigue is the tiredness felt
by individuals as a result of the influence of body rhythm which makes individuals
experience different degrees of discomfort In this model fatigue can be measured by
biochemical indicators such as cytokines interferon and tumor necrosis factors as well
as with a self-report fatigue scale
The term ldquoIntegratedrdquo refers to a combination of features including perception physics
biochemistry and behavior all of which affect level of fatigue and in turn influence
fatigue patterns including diseases treatments activitiesrests environment symptoms
social activities life events individual internal factors and other aspects of the patients
life
The second theory is the Psychobiological Entropy Model11 is the most complete fatigue
638
6
theory at present This model suggests that the main cause of fatigue is a lack of energy
The physical ability of patients is reduced because of the symptoms caused by diseases
or treatments and thus patients experience emotion-related fatigue and the reduction in
functional status as a result In addition the symptoms caused by reoccurring diseases
or treatments may be harmful to physical conditions even more and lead to disability
eventually In this model any treatment program that can address the decline in activity
can alleviate fatigue symptoms is said to improve fatigue Therefore Psychobiological
Entropy Model not only provides a more direct detection of clinical patterns but also for
providing measures of care within a fatigue model
The third model is the Energy Analysis Model12 which suggests that the pathological
change of individual physical status becomes the barrier of energy conversion When the
supply of energy in individuals is low or the demand is high a lack of energy results and
the individuals feel fatigue Energy is generated by the oxygenation in blood The
correction factors of energy reaction are cancer treatments symptom distress and
emotional disorders Concepts in the fatigue model include energy sources energy
transformations energy expenditures and energy response modifiers The relationships
among these concepts are dynamic and intercorrelated with each other From the Energy
Analysis Mode point of view the physiological mechanism of fatigue includes some
objective indicators such as body weight and hemglobulin
In terms of the causes of fatigue Ekti Genc amp Conk (2008) 2 indicated that illnesses
treatments and stage of disease can cause fatigue NCCN (2011) 1 points out that many
conditions are related to fatigue including pain emotional pain anaemia sleep disorders
639
7
nutritional deficiencies activity reduction side effects of drugs (antihistamine drugs
anti-vomiting drugs and anti-anxiety drugs) and others In a study on children
adolescents parents and relevant medical and nursing staffs Hinds and
Hockenberry-Eaton (2001) 13 proposed four factors causing the fatigue of children with
cancer which are 1) environmental factors treatment setting events or situations that
place demands on the patient such as appointments inpatient stay long waiting time
altered routines that lack clear beginnings and endings of each day and decision making
and information exchange 2) personalbehavioral factors the negative faith of children
with illness 3) culturalfamilyother factors emotions concerns the hope of friends and
family ability to participate in activities and restricted activities 4) treatment-related
factors the invasive inspections experienced by children with illness insufficient time for
physical strength recovery between the repeated courses of treatments or the side
effects caused by treatments (infection pain and decrease in complete blood count) It
can be inferred that the causes of fatigue are complicated and multifaceted
Fatigue is a complex and multidimensional condition 10 therefore fatigue is subject to
different definitions and there are different measurement tools Aaronson et alrsquos14
review the literature of fatigue summarised the characteristics of fatigue measurement
including the following(1) Subjective quantification of fatigue can be determined with the
Lee and colleagues (1991) Visual Analog Scale for Fatigue (VASF)(2) Subjective
distress This item simply asks the rater to report to what degree fatigue has caused
distress (3) The effect of fatigue on activities of daily living (4) Correlates of fatigue
such as sleep and depression to assess when measuring fatigue (5) key biological
parameters such as cytokines interferon and tumor necrosis factor
640
8
Fatigue can be also measured with unidimensional or multidimensional scales The first
type of fatigue scale is not suitable for studies focusing on fatigue because they are too
long if the aim is to only assess fatigue Furthermore they only allow for a limited number
of possible responses Unidimensional scales also are not suitable for the in-depth study
of fatigue because they assess only one aspect of fatigue15
In recent years fatigue in children with cancer has received some attention and
measurement tools have gradually been developed - such as1) Checklist individual
strength (CIS) The items are scored on 7-point Likert scales (with 1 indicating best and
7 worst function) 2) The Child Fatigue Scale (CFS) is a 2-part questionnaire that asks for
a yes or no (frequency) response and a 5-point rating of the intensity of any yes
responses ranging from not at all to a lot The Fatigue Scale for 7-12 year Olds (FS-C)
is provide a fatigue intensity score higher scores indicating higher fatigue The Fatigue
Scale for 13-18 year Olds (FS-A) measure adolescent cancer patientsrsquo perceptions of
the intensity of their fatigue on a daily or weekly basis higher scores indicating higher
fatigue 3) The Fatigue Scale Parent Version (FS-P) measures the parentsrsquo perception
of their childrsquos fatigue intensity on a five-point Likert-type scale higher scores indicating
higher fatigue 4) The Fatigue Scale Staff Version (FS-S ) measures the staffrsquos
perceptions of the patientrsquos fatigue intensity during the past 24 hours Intensity ratings are
on a four-point Likert-type scale with higher scores indicating more intense fatigue
symptoms 5) The Pediatric Quality of life Multidimensional Fatigue Scale (Peds
QL-MFS)Higher scores (0 to 100) indicate less fatigue( Appendix IV)
Besides disturbing physical and mental functions and status fatigue also affects the
641
9
quality of life 15 of children with cancer and impacts their daily life16 among all different
types of cancer progress and childrsquos ages However as opposed to the fatigue of adults
the fatigue of children tends to be neglected and left untreated17 by medical and nursing
staffs
In terms of the management approach to cancer-related fatigue Ekti Gene (2008) 2
suggests that strategies could include pharmacologic and non-pharmacologic measures
NCCN (2011) 1 indicated in the Clinical Practice Guidelines in Oncology that during
aggressive treatments during long-term follow-up treatments or in the terminal phase of
cancer the intervening measures for cancer-related fatigue can be divided into
pharmacologic and non-pharmacologic measures Non-pharmacologic measures include
activity enhancement psychosocial interventions (eg cognitive behavioral therapy
(CBT) stress management relaxation support groups) attention-restoring therapy and
nutrition consultation As for the effectiveness of pharmacological measures the
effectiveness is still uncertain However there is evidence to suggest that
methylphenidate may be effective in treating cancer-related fatigue1 Whiting et al
(2001)18 included 36 randomized controlled trials and 8 controlled trails to assess the
effectiveness of the pharmacological and non-pharmacological interventions used in the
treatment or management of chronic fatigue syndrome in adults or children Results
showed insufficient evidence on the effectiveness of the pharmacological supplements
complementaryalternative and other interventions In addition the evidence of
pharmacological treatments of immunoglobulin and hydrocortisone were also
inconclusive However interventions such as cognitive behavioral therapy and graded
exercise therapy have shown promising results
642
10
The efficacy of pharmacological treatments for cancer-related fatigue has not been
established6 therefore there is a need to provide evidence-based findings of the
effectiveness of non-pharmacological interventions to support nursing intervention to
release the childrsquos cancer-related fatigue To date most studies have investigated the
effectiveness of non-pharmacological treatments on cancer-related fatigue of
adults20and to date there is no systematic review in relation to cancer-related fatigue of
children However as children are not a smaller version of adults it is inappropriate to
extrapolate the results of adults onto children Therefore there is a need to establish the
effectiveness of non-pharmacological intervention on the cancer-related fatigue of
children
Given the increase in childhood cancer survival rate the importance of decreasing
childrenrsquos cancer-related fatigue during treatments and so increase their quality of life has
become a focus of their medical teams The role of nurses during care intervention is to
confirm the major symptoms of children with illness and effectively treat each symptom to
increase the childrenrsquos quality of life21 Moreover the USA based NCCN also indicated in
the Care Standard for the Treatment of Cancer-related Fatigue of Children and
Adolescents that treatments for fatigue should be included in the health care teams and
the children and their family should be informed of relevant information The definition of
non-pharmacological interventions for childrenrsquos cancer ndashrelated fatigue include activity
enhancement (exercise physical activity) psychosocial interventions cognitive
behavioral therapy (CBT) stress management relaxation nutrition consultation
massage and educational interventions
643
11
The Cochrane Library of Systematic Reviews and The Joanna Briggs Institute Library of
Systematic Reviews were initially searched to ensure that systematic reviews on this
subject were not already published or being undertaken This initial search prior to the
commencement of the review did not yield any results
This systematic review has examined the effectiveness of non-pharmacologic
interventions on the cancer-related fatigue of children in hope of finding scientific
evidence that can support or refute such measures on children The results of this study
may serve as a reference for professional caregivers children with cancer and their
families or to be put into practice during the clinical care of children with cancer
Definition of terms
FatigueFatigue as a distressing persistent subjective sense of physical emotional
andor cognitive tiredness or exhaustion related to cancer or cancer treatments
that is not proportional to recent activity and interferes with daily function1 There
are various scales and measurements of the degree of fatiguewe have elected to
use the study authors own definitions of fatigue rather than applying a single
pre-set definition of the condition
Non-pharmacological interventionsReferring to reduce fatigue that does not involve
drugsNon-pharmacologic measures include activity enhancement psychosocial
interventions (eg cognitive behavioral therapy stress management relaxation
support groups) attention-restoring therapy and nutrition consultation1
ChemotherapyTreatment with drugs that kill cancer cells 1
644
12
Review QuestionsObjectives
Review Objective
The objective of this systematic review was to critically appraise synthesize and
present the best available evidence concerning the effects of non-pharmacological
interventions fatigue in children and adolescents with cancer
Review Question
The following specific question was addressed in this review
What is the effectiveness of non-pharmacological interventions on fatigue in
children and adolescents with cancer aged from one to 18 years
Criteria for Considering Studies for this Review
Types of studies
This review included randomised controlled trials (RCTs) and quasi-experimental
studies that examine the effectiveness of non-pharmacological intervention for fatigue in
children and adolescents with cancer
Types of participants
Children and adolescents aged from one to 18 years old experiencing fatigue
associated with cancer either during or after the chemotherapy or maintenance stage of
chemotherapy or survive stage The types of cancer to be included in this systematic
review will be ALL (Acute lymphoblastic leukemia) AML (Acute myeloid leukemia)
lymphoma and solid tumors
Exclusion criteria for Types of participants
645
13
newborn infants under 1 years of age
participants who do not have a specific diagnosis of cancer
participants who have received immunoglobulin or hydrocortisone
treatment
If participants have received immunoglobulin or hydrocortisone treatment may
inference the effectiveness of non-pharmacological interventions on fatigue
Types of intervention
This review considered studies that examine non-pharmacological interventions on
fatigue for children and adolescents with cancer including activity enhancement
(exercise physical activity) psychosocial interventions CBT stress management
relaxation nutrition consultation massage and educational interventions The
interventions descriptive included the length frequency setting and intervention
providers eg Nurse Psychologist Dietician
Exclusion criteria for types of interventions only pharmacological interventions were
tested
Types of outcome measures
The outcome measures considered were fatigue scores The literature demonstrates that
differences of opinion exist regarding the most valid and reliable method of measuring
cancer-related fatigue Therefore studies that used any validated scale for
cancer-related fatigue were considered for inclusion Currently commonly used scales to
measure fatigue include Checklist Individual Strength (CIS) Child Fatigue Scale (CFS)
The Fatigue Scale for 7-12 year Olds (FS-C) The Fatigue Scale for 13-18 year Olds
646
14
(FS-A)and Pediatric Quality of life Multidimensional Fatigue Scale (Peds QL-MFS)
Types of settings
Both hospital and community settings
Search Strategy
Before undertaking this systematic review the Cochrane Library Joanna Briggs Institute
Library of Systematic Reviews and CINAHL were searched and no systematic reviews on
this topic were found or identified as underway
The search strategy aimed to find both published and unpublished studies
A three-step search strategy was utilized in each component of this review An initial
limited search of CINAHL and MEDLINE was undertaken followed by an analysis of the
text words contained in the title and abstract and of the index terms used to describe the
article A second search using all identified keywords and index terms was undertaken
Lastly the reference lists of all identified reports and articles were searched for additional
studies
Types of languages
1 English
2 Chinese
The following databases were searched to identify keywords contained in the title and
abstract and relevant MeSH headings and descriptor terms
The Cochrane Library PsycINFO 1990 ndash 2010
647
15
Ovid MEDLINE 1966 ndash 2010 CINAHL Plus with Full Text 1960 ndash2010 EMBASE ProQuest Dissertations amp theses 1990-2010 Electronic theses and dissertations system 1956(abstract)1990(full text)-2010 MEDNAR Index to Taiwan periodical literature 1970-2010 Electronic thesis and dissertation system (Chinese) 1990-2010
Keyword search terms
1Types of studies experimental study random quasi-experimental study實驗性研究隨
機類實驗性研究
2 Types of participants childchildren adolescents pediatric cancer and oncology兒童
青少年兒科癌症腫瘤
3 Types of interventions non-pharmacological interventions massage exercise fitness
physical activity cognitive behavioral stress management energy conservation
sleep therapy relaxation distraction and psycho-education非藥物性處置按摩運動
身體活動認知行為壓力處置能量保存睡眠治療放鬆轉移注意力衛教
4 Types of outcome measures fatigue cancer-related fatigue loss of energy levels of
tiredness tired side effect symptoms疲憊癌性疲憊疲倦合併症症狀
Methods of the Review
Assessment of methodological quality Papers selected for retrieval were assessed by two independent reviewers for
methodological validity prior to inclusion in the review using the standardised critical
appraisal instruments (Appendix I) from the JBI-SUMARI (Joanna Briggs Institute
Systems for the Unified Management Assessment and Review of Information package)
Any disagreements that arise between the reviewers were resolved through discussion
648
16
with a third reviewer
Data extraction Data was extracted from papers included in the review using standardised data
extraction tool (Appendix II) from the JBI-SUMARI Details of eligible studies were
extracted and summarised independently by two reviewers
Data Synthesis
All data analysissynthesis were made using the JBI-SUMARI The studies were
assessed for clinical heterogeneity by considering the settings populations interventions
and outcomes Where possible these binary outcomes were analyzed by calculation of
the Odds Ratio with the 95 CI The weighted mean difference was calculated if the
pooled studies have used the same scale for continuous data The standardized mean
difference was calculated for continuous data measuring the same outcome on a
different scale In studies where statistical pooling of results was inappropriate the
findings were considered for inclusion as a narrative summary
Results The findings from the systematic review are presented first Followed by the results from
the meta-analysis component of this review
Description of studies From database search and hand search a total of 76 papers were identified Thirty
papers were then excluded because they did not meet the inclusion criteria Forty-six
full text were retrieved for further consideration for inclusion Of the 30 excluded reasons
for exclusion were follows 11articles were duplicated eight articles did not meet
649
17
participant inclusion criteria eight articles did not meet outcome criteria and nine articles
were correlation studies or discussion papers others articles were unclear reporting In
total after sorting six papers have been included in this article Figure 1 displays the
process used to identify relevant articles for inclusion in the systematic review
Figure 1 Stages of searching and inclusionexclusion of references for the review
Potentially relevant English-language and Chinese- language Studies Identified
Electronically and hand search (n=76)
Duplicate (n= 11) Papers excluded after evaluation of abstract (n=19)
Papers retrieved for detailed examination (N=46)
Papers excluded after review of full paper
(n=40)
Papers assessed for methodological
quality (n=6)
Papers included in systematic review
(n=6)
Methodological Quality
Of the six included articles 2722232425 two articles were RCT design224 with score 7 out
of 10 each paper from Critical Appraisal Checklist and four articles used
650
18
quasi-experimental design7222425 with socre 5 to 6 out of 10 because the quality of
the whole papers is still acceptable therefore these six articles were accepted after
primary reviewer and secondary reviewerrsquos decision
Randomisation
In two RCT articles224 one study24 used to a computer-generated program operated by
the St Jude Protocol and Data Management System to randomize the sample Another
study2 didnrsquot address how randomization was done
Allocation concealment
No studies reported allocation concealment
Intention-to-treat analysis
One quasi-experimental design7 stated Intention-to-treat analysis
Adequate follow up
The follow-up periods included 2or 3 days24 7 days2 4 week7 one month25 6 week25 12
week2216 week23 and 1 year23
Baseline comparability of groups
Three 22425 of six studies had baseline comparability in terms of age sex diagnosis
race institution duration of illness
Blinded outcome assessment
No studies used blinded outcome assessment The researchers including study team
patients staff and families were not blinded to the patientrsquos group assignment
Characteristics of included studies
651
19
There were six studies related to interventions designed to cancer-related fatigue for
pediatric patients than there are for adults There are a total of six including five
English-language papers 27222324 and one Chinese-language paper 25 ranging in year of
publication from 2007 to 2009
Patient characteristics
The research subjects of four papers included both school-aged children and
adolescents 7222324 one papers involved mainly adolescents25 and one paper sampled
only school-aged children 2 the range in ages was between six-18 years The number of
patients included in the samples ranged from nine to 60 The sources of case data were
from both outpatients and hospitalized children The types of cancer included acute
lymphoblastic leukemia (ALL) solid tumors acute myeloid leukemia (AML) and
lymphoma Overall ALL was the most commonly studied cancer type The stage of the
disease varied in these reports some patients were in the maintenance stage of
chemotherapy25 some had just received their first round of chemotherapy224 some had
completed two courses of treatments lasting 4-8 weeks each 7 and some had entered
the survivor stage 2223
Countries
Two RCTrsquos 2 24 were conducted in the USA There were four quasi-experimental design
studiesThree studies conducted in the USA7 22 23 and one in Taiwan25
Intervention types
652
20
The interventions included exercise training programs 2225 physical activity 2324
massage therapy 7 and health education 223 exercise training and physical activity as
an intervention method given in three different settings home 22 25 community 23 or
hospital 24 The studies used different types of exercise interventions including
home-based aerobic exercise use a Video Compact Disc 25 use of a bicycle-style
exerciser 24 aerobics2223 and various types of physical activities2 and strength-building
exercises 2223 The intensity of the exercise varied and often included gradual warm-up
exercises a period of main exercise and a cool down period For these studies2023 the
target exercise intensity was a heart rate of gt90 of the maximum heart rate (HR max) or
the increase in the percentage of heart rate reserve ( HRR) of 40-60
The number of weeks for the exercisephysical activity interventions duration including
2-4 days 24 6 weeks25 12 weeks22 and 16 weeks23 The frequency of exercise ranged
from 2-3 times per week to twice a day Typical duration of exercise ranged from 10 to 45
minutes There are three papers using exercise interventions based on ACSM (American
College of Sports Medicine) 2225 recommendations and one of these used an Activity
pyramid from the ACSM to determine intensity 24
One article did not clarify the type of exercise intervention or the reasons for their choices
23 In addition there was an article focusing on massage therapy 7 as an intervention in
this study the experimental group received four weeks of massage therapy either in the
clinic or in the patientrsquos room the therapy was applied by a professional masseur and
targeted the back legs arms chest stomach and face of the children However the
frequency of massage sessions per week and the duration of the massages were not
653
21
given There is another article about intervention measures combine health education
and physical activity 2 In this study patients were informed about the following (1) health
education patients received daily education about chemotherapy-related fatigue and
information from a health education manual written by the author (2) encouragement for
children to engage in activities such as listening to music drawing and reading and (3)
physical activity which involved walking along the corridors of the ward for 10-15 minutes
These health education measures were presented for 45-60 minutes a day for a total of
seven days The study design for non-pharmacological interventions used control groups
that included primarily people who had received standard treatment or people who did
not receive an exercise intervention
Outcome measures
Five measurement tools were used in this group of seven papers concerning childrenrsquos
fatigue (Appendix IV) Because those studies included both school-age children and
adolescents the following descriptions will be differentiated by age Fatigue
measurements for school-aged children with cancer include the following the Child
Fatigue Scale (CFS) 7 a scale that measures the frequency and intensity of fatigue and
the Fatigue Scale for 7-12 year Olds (FS-C) 224 a scale that can be used to evaluate the
intensity of fatigue On the other hand fatigue measurements for adolescent cancer
patients include the following the Fatigue Scale for 13-18-year-olds (FS-A) 24 a measure
that can help evaluate fatigue levels the Pediatric Quality of Life Multidimensional
Fatigue Scale (Peds QL-MFS) 2325 a tool that can be divided into three sub-scales to
understand the general cognitive and sleep rest components of fatigue and finally the
CIS-20 for school-age children and adolescents 22 a scale that measures four levels of
654
22
fatigue namely subjective experience attention motivation and physical activity Two
studies used the Peds QL-MFS scale to measure fatigue2325
Meta-analysis results Two studies of the included papers failed to provide sufficient raw data they could not be
included in the meta-analysis Hinds et al 24 did not include post-test data Genc et al 2
provided no pre-test data PostWhite et al7 reported that fatigue after the health
education intervention was not statistically different but they presented the results
without presenting fatigue-related data Therefore the meta-analysis included three
studies 222325
The heterogeneity of studies was analyzed with Chi square statistics and no statistical
significance was found Therefore the data was combined in meta-analysis according to
exercise intervention on fatigue In addition there were three articles using the Peds
QL-MFS as a research tool to examine childrenrsquos improvements in fatigue Among these
Keats 22 and Chiang 24 present the effectiveness of exercise interventions using three
subscales Therefore the meta-analysis also analysis of the effects of these exercise
intervention measures on three subscales of Peds QL-MFS general fatigue sleep rest
fatigue and cognitive fatigue
The effectiveness of exercise intervention for fatigue We analyzed the exercise intervention effect on fatigue A total of 2 studies 22 23 were
included Takken et al 22 used community-based exercise training program to reduce
fatigue of children 6 to 14 years (mean 93y) of age who survived ALL Fatigue
measurement by Checklist Individual Strength (CIS) after 12-week of training fatigue
655
23
show no significant differences between pre (meanplusmnSD 415plusmn147) and post training
(meanplusmnSD368plusmn217) but fatigue change from baseline mean reduction of 11
Keats et al23 although used community-based physical activity program to reduce fatigue
for adolescents 14 to 18 years of age (mean162 y) with cancer (Lymphoma leukemia CNS
tumor germ cell tumor) Studies used fatigue by PedsQLMFS Results show general fatigue
from baseline to 8 weeks and to 3 months follow up significantly improves General
fatigue sleeprest fatigue and total fatigue from baseline to 3 months follow up showed
significant improvements Sleeprest fatigue and total fatigue at 1 years followed up were
significant improvements
Figure 2 shows the overall effect of exercise intervention in children and adolescents with
cancers with a focus on improving fatigue Due to the lower heterogeneity (p>005) the
fixed effects model was used to pool the data for meta-analysis (Overall effect size=
-006 95 Confidence Interval (CI) -070 to 058) A result did not indicate a statistically
significant difference (p = 087)
656
24
Figure2 Meta-analysis results of exercise intervention on fatigue
In addition Keats23 and Chiang25 used the three sub-scales of Peds QL-MFS to
determine the general cognitive and sleep rest components of fatigue The following
present the effectiveness of exercise interventions using three subscales including
general fatigue sleep rest fatigue and cognitive fatigue 2325
Chiang et al 25 used a 6- week home-based aerobic exercise intervention to reduce
fatigue of children 7 to 18 years (mean age at experimental group was 1088 y in control
group was 1247 y) of age who with acute lymphoblastic leukemia Fatigue measurement
by Peds QL-MFS after training For intent-to ndash treat analysis the findings indicated that
there are no intervention effects and time differences by any items on the subscale of
fatigue For per-protocol analysis general fatigue( meanplusmnSD 422plusmn402) was the only
subscale that was significantly lower for children who received the exercise intervention
than those in control group at follow-up assessment (one month after the completion of
intervention)
Keats et al23 although used community-based physical activity program to reduce fatigue
for adolescents 14 to 18 years of age (mean162 y) with cancer (Lymphoma leukemia
CNS tumor germ cell tumor) Both studies used fatigue by PedsQLMFS Results show
general fatigue from baseline to 8 weeks and to 3 months follow up significantly improves
657
25
General fatigue sleeprest fatigue and total fatigue from baseline to 3 months follow up
showed significant improvements Sleeprest fatigue and total fatigue at 1 years followed
up were significant improvements
The effectiveness of exercise intervention for general fatigue
The impact of the exercise interventions upon levels of general fatigue was also analysed
The heterogeneity was low (p>005) Therefore the fixed effects model was used to
examine the effectiveness The effect size is -076 indicating a statistically significant
difference (p = 001 95 CI -135 to -017 Fig 3) The evidence suggests that exercise
intervention can reduce general fatigue in children with cancer
Fig 3 Meta-analysis results of exercise intervention for general fatigue
The effectiveness of exercise intervention for sleep rest fatigue
The following is the result of the meta-analysis of the effectiveness of exercise
interventions on sleep rest fatigue First the heterogeneity test was conducted with P gt
005 representing small heterogeneity and the fixed effects model was used Fig 4
shows the effect size is -035 indicating no statistically significant differences (p = 023
95 CI-092 to 022 Fig 4)
658
26
Fig 4 Meta-analysis results of exercise intervention for sleep rest fatigue
The effectiveness of exercise intervention for cognitive fatigue Lastly the following data reports the results of meta-analysis of the effectiveness of
exercise interventions for cognitive fatigue The heterogeneity was p>005 then the
fixed effects model was used The effect size is -035 indicating no statistically significant
differences (p = 024 95 CI-092 023 Fig 5)
Fig 5 Meta-analysis results of exercise intervention for cognitive fatigue
Narrative presentation of remaining included studies
Three studies were not included in meta-analysis Post-White et al7 one of the aims in
this study was to examine the effect of massage therapy on fatigue in children with
cancer The study was a quasi-experimental design Twenty-three childrenparent dyads
were enrolled 17completed all data points Children with cancer ages 7 to 18 years
received at least 2 identical cycles of chemotherapy and one parent participated in the
2-period crossover design in which 4 weekly massage sessions (MT) alternated with 4
659
27
weekly quiet-time (QT) control sessions There were no significant changes in fatigue in
children over the 4-week MT or QT conditions either independently (change over time) or
when we compared fatigue by condition
The lack of effect of massage on fatigue may be the difficulty some children had in
differentiating fatigue from being relaxed underscores the challenge of measuring fatigue
in children Some children interpreted being tired or relaxed as having greater fatigue
because they felt like lying around and sleeping or felt unmotivated to do their usual
activities all measures of fatigue in the instrument used in the study
Hinds et al24conducted a prospective two-site randomized controlled pilot study to
assess the feasibility of an enhanced physical activity (EPA) intervention in hospitalized
children and adolescents receiving treatment for a solid tumor or for acute myeloid
leukemia (AML) Twenty-nine patients (25 with a solid tumor and 4 with AML) participated
age range from 736 to 1816 (mean 1248 y) The EPA intervention selected was
pedaling a stationary bicycle-style exerciser (Chattanooga Peddler Deluxe Bio-Teck
Medical Memphis TN) for 30 minutes twice daily for 2 to 4 days of hospitalization The
mixed model analysis revealed no significant differences in patient reports of fatigue
between the two study arms or over time
Genc et al2 conducted a RCT involving children with cancer who are 7 to 12 years of age
and receiving chemotherapy treatment to determine the impact of educational
intervention by nurses on decreasing the fatigue syndrome The research sample was
composed of a total of 60 children with cancer with 30 children being included in the
660
28
experimental group (mean age 923)and 30 children included in the control group (mean
age 937) with their mothers In the experimental group after the 7th to 10th day of the
chemotherapy treatment throughout a week the researcher conducted the nursing
interventions every day for 45 to 60 minutes In the control group routine nursing
interventions were carried out The experimental group received education about the
fatigue with the chemotherapy and fatigue handbook was given which was developed by
the authors Children and mothers were consulted for including activities that could
decrease fatigue which were described as effective interventions A statistically
significant difference was found between the Fatigue Scale-Child mean scores of the
experimental (2723) and the control group (4213) The results suggest that fatigue of
children with cancer can be reduced by implementing appropriate nursing interventions
(t=567 Plt00)
Discussion The purpose of this systematic review was to determine the effectiveness of
non-pharmacological interventions specifically targeting fatigue for children and
adolescents with cancer undergoing chemotherapy or after receiving chemotherapy
Included articles about the effectiveness of non-pharmacological interventions for
children and adolescents with cancer were published between the years of 2007 and
2009 Although interventions for cancer fatigue for adults have been extensively studied
it can be seen from either the title of the paper or related content that an intervention
study on children was a pilot study or a feasibility study Representing a field in its early
stage these studies show that the fatigue issues with young cancer patients have only
recently been taken seriously
661
29
The results of our meta-analysis include measurement of the four performance indicators
fatigue and general fatigue sleep rest fatigue and cognitive fatigue The results show
that there is a statistically significant difference only in the domain of general fatigue
using an exercise intervention for children with cancer can improve the degree of fatigue
with the effect size reaching 0671 Other results do not indicate significant differences
The reasons may include the following
1 Characteristics of the cancer The exhaustion from cancer occurs not only during cancer treatment but also in during
long-term survival a time during which patients may continue to be affected by this
symptom 8 26 Therefore when using intervention measures to improve fatigue
circumstances should be considered such as the process of the treatment and the course
or stage of the disease Because cancer patients will experience different forms of
treatment or courses of treatment the disease itself or treatment differences should be
considered in the choice of intervention Even chemotherapy drugs should be taken into
consideration For example a period of general steroid treatment can increase patientsrsquo
fatigue In those studies of children with cancer few studies looked solely at one type of
cancer most studies included a variety of cancer patients Furthermore most studies do
not clearly explain the stage of the disease or course of treatment and most do not
include treatment variables in the control group Moreover children with cancer may
have different levels of physical function
2 Research design The sample size Currently there are few studies with large sample size and a rigorous
RCT design due to the small number of papers available for analysis The sample size
included in our studyrsquos data analysis is between 20 and 42 people this small sample size
will affect the power available to evaluate outcome variables
Although most of the non-pharmacological interventions still use exercise and physical
activity and these studies overall show better results for fatigue as compared with
controls more research is still needed to further confirm the efficacy of these findings
662
30
The dropout rate in the evaluated research varies a great deal ranging from 5 to 45
these dropout rates may result from the characteristics of the research subjects or the
lengthy time involved in participating in these studies The research data with a high
turnover rate might not reflect the actual outcomes of participation in exercise and the
quality of the research contained in articles with high subject turnover rates may be
lower
Exercise doses and time The exercise doses needed to reduce fatigue cannot be
determined additionally the amount of exercise completed by the patient is also
inconsistent interventions vary between 2-3 times per week and two times a day and
exercise duration varies between 10 and 45 minutes each time Furthermore the study
interventions vary in length between a couple of days and a long period of 16 weeks The
data collection times are different some were measured 12 weeks after the intervention
began some were measured during the 6 weeks of intervention some were measured
three months after the intervention was finished and some were measured after one
year
In addition disease-related symptoms decrease childrenrsquos willingness to participate in
exercise interventions inappropriate exercise intervention programs may actually
increase childrens fatigue In addition the children in the study are still developing
physically it is important to consider ways to design an interesting exercise intervention
to increase the compliance of patients in order to improve the effectiveness Although
intervention programs in the hospital or in a community sports center can improve the
effectiveness because they provide supervision the feasibility of these programs is
questionable However if the program is home-based the children need to be
supervised by parents in order to improve their compliance in doing the exercises
Furthermore regarding the nature of the intervention the results from this study indicate
that the researched non-pharmacological interventions include the following exercise
training programs physical activity massage therapy and health education interventions
However according to the National Comprehensive Cancer Network 1 clinical guidelines
663
31
for cancer non-drug measures for cancer fatigue can be separated into five categories
(1) activity enhancement (2) psychosocial interventions such as cognitive behavioral
therapy (CBT) stress management relaxation techniques and support groups (3)
attention-restoring therapy (4) nutritional consultation and (5) cognitive behavioral
therapy specifically targeting sleep disturbance Researchers have also suggested that
psychosocial interventions should be included in the future research for children with
cancer-related fatigue 22
(2) The measurement tools in the study The assessment of fatigue can be
one-dimensional or multidimensional One-dimensional assessment can help understand
the severity of fatigue symptoms however multidimensional scales are often more
credible Therefore when measuring cancer-related fatigue researchers should consider
whether there is a uniform definition of fatigue or a standardized tool for measuring
fatigue in order to facilitate further systematic meta-analyses and further develop the
clinical care guidelines
Limitations of the review The present review has some potential limitations First the low methodological quality
may influence the result Although exercise intervention seems promising quality of the
RCTs was generally quite low Future studies require better design and reporting if
methodological issues to establish evidence-based nonpharmcologic intervention
Second the identified studies covered only a limited types of nonpharmcological
intervention especially in exercise intervention The guidelines for cancer-related fatigue
in NCCN (2011)1 referred to more interventions than the ones included in this review
such as cognitive behavioral therapy and nutrition consultation Thirdly the small sample
size and effect size could be potentially having led to underpowered approach for
detecting the effects on fatigue Therefore we recommend that as research continues to
grow a re-analysis can be undertaken Fourthly Combining data in meta analysis from
664
32
studies where the ages were quite different is a potential source of heterogeneity and
may affect the interpretation of the results
Conclusion At present clinical treatment is widely used for cancer patients However child and
adolescent cancer patients often experience various side effects which cause short-term
or long-term discomfort both physically and psychologically In particular with the
increasing cure rate cancer related fatigue during or after treatment has become an
important issue This study result provided positive effect of exercise intervention on
general fatigue
Implications for practice The results of this systematic review and meta-analysis show that exercise interventions
can effectively improve the level of general fatigue In particular although the articles
were self-reported feasibility studies their results all indicate that exercise interventions
for fatigue are feasible and safe there was no conclusion to be made for the use of
massage therapy or health education measures because there was only one article for
each of these interventions
Recommendations for practice
Cancer-related fatigue is one of the most severe and frequent symptoms by pediatric
oncology children and adolescent suffered during treatment and the symptom existed
even after treatment has ended Until now no golden standard of treatment to fatigue is
established The findings call for more attention to how to reduce patientrsquos levels of
fatigue Based on the available information evaluated in this review the following
recommendations for practice are provided
665
33
bull For children aged 7 to 18 who has cancer (eg Lymphoma leukemia CNS tumor
germ cell tumor) an effective progressive aerobic exercise program is recommended to
be at least 2-3 times per week 20 to 45 minute for each session and last for 6-16 weeks
in order to reduce their general fatigue (tiredness physically weakness) In addition
adults should be involved in accompanying children while they are performing physical
exercise of which should be able to improve the adherence rate (level 2 ) ( Grade of
recommendation A)
bull For children aged 7 to 18 who has cancer (eg Lymphoma leukemia CNS tumor
germ cell tumor) an progressive aerobic exercise program will not be effective to reduce
their sleep andor rest (sleeping or resting a lot) or cognitive fatigue (problems with
thinking quickly or problems with remembering) (level 2 ) ( Grade of recommendation C)
bull Nursing interventions in educating treatment of fatigue include information about
activity nutrition energy preservation consulting and providing a useful fatigue
handbook will benefit those children who are 7 to 12 years have a new diagnosis of ALL
AML or lymphoma and receive for the first time after being diagnosed a 7- to 10-day
chemotherapy treatment (level 2) ( Grade of recommendation A)
bull A 4-week massage therapy program (the therapists massage childrenrsquos back legs
arms stomachchest and face) is not effective for children who are aged 7 to 18 and
have acute lymphoblastic leukemia brain tumors lymphoma rhabdomyosarcoma
Wilms tumor or Ewing sarcoma(level 2)( Grade of recommendation C)
bull Using a 12-week aerobic and strength exercise (45-min exercise sessions twice a
week) is not effective for children who are aged 6-14 and survived acute lymphoblaststic
leukemia age from 6 to 14(level 2) ( Grade of recommendation C)
bull Using a physical activity intervention (30minutestwice daily for 2-4days) is not
effective for children who are 7 to 18 years of age with soild tumor or AML(level 2)
( Grade of recommendation C)
666
34
Implications for research According to this systematic review and meta-analysis results there are suggestions to
improve the effectiveness of future research on non-pharmacological interventions for
children and young peoplersquos cancer-related fatigue
As the majority of included non-pharmacological interventions for the fatigue of cancer
patients consist of exercise programs future research should also consider various
non-pharmacological interventions in order to understand the effectiveness of different
methods
Regarding the exercise intervention methods and studies should consider multiple
factors including the age or personal condition of the subject the disease stage and the
amount of daily activities Studies should use design prescriptions (eg frequency
intensity duration and type of exercise) and consider the adherence to the measures in
order to enhance the study strength
In measuring the results of non-pharmacological interventions there should be standard
definitions or standard measurement tools to facilitate the following systematic review
and meta-analysis that can subsequently be developed into clinical care guidelines
Reviewing the effectiveness of the current non-pharmacological management of children
and adolescent cancer patients there is still a lack of rigorous RCT research Limited by
the characteristics of cancer there is still a lack of large sample sizes
Potential conflicts of interest There is no conflict of interest
Acknowledgements
Thank you to Dr Rie Konno Research Fellow Joanna Briggs Institute for her help in
assessing studies
667
35
References 1 National Comprehensive Cancer Network( NCCN) in USA NCCN clinical practice
guideline in oncology cancer-related fatigue 2011 2 Ekti Genc R amp Conk Z Impact of effective nursing interventions to the fatigue
syndrome in children who receive chemotherapy Cancer Nursing 200831(4)312-317
3 Childhood Cancer Foundation of ROC (2009March) The classification of diseases
and age sex statistical tables of case Childhood Cancer Foundation of ROC newsletter103105-106
4 Department of Health Executive Yuan ROC (TAIWAN)(2009 March 20)2009 cause of death statistic Health and National Health Insurance Annual Statistics Information Service 2010 June 28Available httpwwwdohgovtwstatisticdatavital statists9898health statistic--lifepdf
5 Chang TK (2007December 8) Common childhood cancer and its treatment Status
Childhood Cancer Foundation of ROC (TAIWAN) 2010 September 23 Available httpwwwccfrocorgtwchildchild_events_readphpe_id=45
6 Hockenberry MJ amp Wilson D Wongs nursing care of infants and children (8th ed) St
Louis MO Mosby 2007
7 Post-White J Fitzgerald M Savik K Hooke MC Hannahan AB amp Sencer SF
Massage therapy for children with cancer Journal of Pediatric Oncology Nursing 2009 26(1)16-28
8Chiang YC Yeh CH Wang WKamp Yang CP The experience of cancer-related fatigue
in Taiwanese children European Journal of Cancer Care 2009 18(1)43-49 9Langeveld NE Grootenhuis M A Voute P A de Haan RJ amp van den Bos C No excess
fatigue in young adult survivors of childhood cancer European Journal of Cancer 200339(2)204-214
10Piper BF Lindsey AM amp Dodd MJ Fatigue mechanisms in cancer patients
developing nursing theory Oncology Nursing Forum 1987 14(6)17-23 11Nail LM amp Winningham ML Fatigue In S L Groenwald M H Forgge M Goodman
amp C H Yarbro (Eds) Cancer Nursing Principles and practice (4 th ed) Boston Jones and Bartlett1997
12Irvine D Vincent L Graydon JE Bubela N amp Thompson L The prevalence and
correlates of fatigue in patients receiving treatment with chemotherapy and
668
36
radiotherapy A comparison with the fatigue experienced by healthy individuals Cancer Nursing 199417(5)367-378
13Hinds PS amp Hockenberry-Eaton M Developing a research program on fatigue in
children and adloescents diagnosed with cancer Journal of Pediatric Oncology Nursing 200118(2)3-12
14Aaronson LS Teel CS Cassmeyer V Neuberger GB Pallikkathayil L Pierce J Press
AN Williams DP amp Wingate A Defining and measuring fatigue Journal of Nursing scholarship 1999 31(1)45-50
15Yeh CH Wang CH Chiang YC Lin Lamp Chien LC Assessment of symptoms reported
by 10- to 18-year-old cancer patients in Taiwan 2009 38(5)738-746 16 Okuyama T Akechi T Kugaya A Okamura H Shima Yamp Maruguchi M
Development and validation of the cancer fatigue scale a brief three-dimensional self-rating scale for assessment of fatigue in cancer patients Journal of Pain amp Symptom Management 2000 19(1) 5-14
17Gibson F Mulhall AB Richardson A Edwards JL Ream E amp Sepion BJ A
phenomenologic study of fatigue in adolescents receiving treatment for cancer Oncology Nursing Forum200532(3)651-660
18Wolfe J Grier HE Klar N Levin SB Ellenbogen JMamp Salem-Schatz S et al
Symptoms and suffering at the end of life in children with cancer New England Journal of Medicine 2000342(5)326-333
19Whiting P Bagnall AM Sowden AJ Cornell JE Mulrow CD amp Ramirez G
Interventions for the treatment and management of chronic fatigue syndrome a systematic review JAMA the Journal of the American Medical Association 2001286(11)1360-1368
20 Kangas M Bovbjerg DHamp Montgomery G H Cancer-related fatigue a systematic
and meta-analytic review of non-pharmacological therapies for cancer patients Psychological Bulletin 2008134 (5)700-741
21Williams PD Schmideskamp J Ridder EL amp Williams AR Symptom monitoring and
dependent care during cancer treatment in children pilot study Cancer Nursing 200629(3)188-197
22Takken T van der Torre P Zwerink M Hulzebos EH Bierings M Helders PJMamp van
der Net J Development feasibility and efficacy of a community-based exercise training
669
37
program in pediatric cancer survivors Psycho-Oncology 200918(4)440-448
23Keats MR amp Culos-Reed SN A community-based physical activity program for
adolescents with cancer (project TREK) program feasibility and preliminary findings
Pediatric hematology and oncology 200830(4) 272-280
24Hinds PS Hockenberry M Rai SN Zhang L Razzouk B I Cremer L McCarthy K amp
Rodriguez-Galindo C Clinical field testing of an enhanced-activity intervention in
hospitalized children with cancer Journal of Pain amp Symptom Management 2007
33(6)686-697
25Chiang YC The effects of ldquo a home-based aerobic exercise interventionrdquo on fatigue
and cardiorespiratory fitness in children with acute lymphoblastic leukemia during the
maintenance stage of chemotherapy Unpublished thesis Taiwan Tao-Yuan 2007
26Langeveld N Ubbink M amp Smets E I dont have any energy The experience of
fatigue in young adult survivors of childhood cancer European journal of oncology
nursing 20004(1)20-28
27 Kisner C Colby L Therapeutic exercise Foundations and techniques 2nd ed Philadelphia PAFA Davies 2007
670
38
Appendix I JBI Critical Appraisal Checklist for Experimental studies
Author__________ Year_________ Record Number__________________
Questions 1 to 4 must be answered ldquoyesrdquo for study to be included in the metashyanalysis
1 Were the participants randomized to study groups
Yes No Not clear
2 Other than research intervention were participants in each groups treated the same
Yes No Not clear
3 Were the outcomes measured in the same manner for all participants
Yes No Not clear
4 Were groups comparable at entry
Yes No Not clear
5 Was randomization of participants blinded
Yes No Not clear
6 Were those assessing outcome blinded to treatment allocation (if outcome not objective such as survival or length of hospitalization)
Yes No Not clear
7 Was allocation to treatment groups concealed from the allocator
Yes No Not clear
8 Was an appropriate statistical analysis used
671
39
Yes No Not clear
9 Were outcomes measured in a reliable way
Yes No Not clear
10 Was there adequate followshyup of participants
Yes No Not clear
Summary
TOTAL
Yes No Not clear
DECISION
Use Reject
Narrative summary only Further information needed
COMMENTS
672
40
Appendix II JBI Data Extraction Tool for Quantitative Studies Authors and Year
Journal Title
Record NumberArticle Reference No
Reviewer
Method
Settings
Participants
Number of participants
Group A Group B Group C
Control Intervention 1 Intervention 2
Interventions
Group A
Control
Group B
Intervention 1
Group C
Intervention 2
Outcome measures
Definition
673
41
Other outcome measures
Outcome description ScaleMeasure
Results
Dichotomous Data
Outcome Control Group
Numbertotal number
Treatment Group
Numbertotal number
Continuous Data
Authorrsquos Conclusions
Comments
Outcome Control Group
Mean amp SD
Treatment Group
Mean amp SD
674
43
Appendix III Details of included studies (N=6)(2720212223) RefNo Author(s)
(years) Title Study question Research
method Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
22 Takken T van der Torre P Zwerink M Hulzebos E H Bierings M Helders P J Mamp van der Net J (2009)
Development feasibility and efficacy of a community-based exercise training program in pediatric cancer survivors
To develop a 12-week home-based exercise training program (comprising aerobic and strength exercises) for children who survived ALL and to study itrsquos feasibility and efficacy
Pre-post test design
No comparsion group
Survived ALL(N=9)ages 6-14 years
1anthropometry 2 muscle strength 3functional mobility 4cardio-pulmonary
exercise test 5Fatigue
1 Feasibility questionnaire 2 anthropometry electronic scale and a wallmounted stadiometerHarpenden skin fold calipers 3 muscle strength handheld dynamometer 4functional mobility Timed Up
and Go test (TUG) 5cardio-pulmonary exercise test electronically braked cycle ergometer 6Fatigue(mean)CSI-20 (subjective experience of fatigueconcentrationmotivationphysical activity)
112-week exercise training program
2 Patients were assessed before (T0) and after (T1) 12 weeks of training
1 muscle strength execapacity functional moand fatigue showed nosignificant differences between pre(meanplusmnSD415plusmn147) and post training(meanplusmnSD3687)
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
7 Post-White J Fitzgerald M Savik K Hooke M C Hannahan A B amp Sencer S F (2009)
Massage therapy for children with cancer
To determine whether 4 weekly sessions of massage compared with 4 quiet-time control conditions would reduce anxiety cortisol levels fatigue nausea and pain in children with cancer undergoing chemotherapy and would reduce anxiety fatigue and mood disturbance in a parent
2-period crossover design (Randomized)
quiet-time
control
sessions
Children with cancer 1 to 18 years of age Twenty-three childrenparent dyads were enrolled 17 completed all data points
children 1relaxation 2symptoms 3 fatigue
parents
1anxiety 2 fatigue
children 1relaxation (heart and respiratory rates blood pressure and salivary cortisol level)
2symptoms (pain nausea anxiety 3 fatigue 1-2y3-6yLansky Play Performance Scale (PPS) 7-13y
1 4 weekly massage (MT) sessions alternated with 4 weekly quiet-time(QT) control sessions
2 children included presession and postsession vital signs (heart rate respiratory rate blood pressure) and self-report (parent proxy report for age 1-2 years) of pain nausea and anxiety Fatigue was measured before sessions 1 and 4 and at each follow-up Parent measures
included anxiety fatigue and mood states
1Massage was moreeffective than quiet tireducing heart rate inchildren anxiety in cless than age 14 yeaparent anxiety 2There were no sign
changes in blood pcortisol pain naufatigue (no state d
3 Children reported tmassage helped thebetter lessened theirand worries and hadlasting effects than q
675
44
14-18yChild Fatigue Scale (CFS) (frequency
intensity) 2 parents anxiety and fatigue
676
45
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
24 Hinds P S Hockenberry M Rai S N Zhang L Razzouk B I Cremer L McCarthy K amp Rodriguez-Galindo C (2007)
Clinical field testing of an enhanced-activity intervention in hospitalized children with cancer
To determine the feasibility of an
enhanced physical activity EPA intervention in children and adolescents hospitalized to receive chemotherapy for a solid tumor or AML and to assess the sleep and fatigue outcomes of the intervention using two different statistical approaches to analyze the longitudinal symptom data
randomized prospective two-site and two-group pilot study
Standard care Twenty nine patients (25 with a solid tumor and 4 with AML)ages 7-18 years
1 sleep duration 2 sleep efficiency 3 fatigue
1sleep duration sleep efficiency The
Wrist Actigraph The Daily Sleep Diary-Parent 2 fatigue (mean) The Fatigue Scale(FS-C) for 7-12 (intensity) The Fatigue Scale(FS-A) for 13-18 The Fatigue Scale Parent Version (FS-P) The Fatigue Scale Staff Version (FS-S)
1enhanced physical activity (EPA) (hospital-based 30 minutes
twice daily for 2-4 days) 2 T0On the day of admission
(Day 0 or baseline)patient and parents completed the fatigue instruments and a team member applied the actigraph Patients wore the wrist actigraph T1 from Day 0 to 2 or 3 consecutive days (Days 0e3) In addition the patient same parent and staff nurses completed the daily sleep and fatigue reports in the late afternoons of Days 1-3
1 ANOVA model slesignificantly more the experimental athe control arm whdifferences from bsleep efficiency vaaveraged and com
2 The patient-reported mean fatigue scoresarms were higher amadolescents than for
3 The mixed model anarevealed no significandifferences in patientfatigue between
the two study arms otime( no final result iSD only give mixed result)
677
46
23 Keats M
R amp Culos-Reed S N (2008)
A community-based physical activity program for adolescents with cancer (project TREK) program feasibility and preliminary findings
To examine the
feasibility of a
theoretically-based
physical activity (PA)
intervention in
adolescents with
cancerand
examination of the
impact of the
program on
participant QOL
including social
emotional and
physical
well-being(including fatigue)
Repeat measures longitudinal design
No comparsion group
10 adolescents(Lymphoma(4)leukemia(4)CNS tumor(1)germ cell tumor(1)) ages 14-18 years
1physical fitness 2quality of life (QOL) 3PA behavior 4fatigue
1 Feasibility was assessed by participant recruitment attendance and adherence
2physical fitness Fitnessgram 3quality of life (QOL) Pediatric Quality of Life Inventory (PedsQL) 4PA behavior leisure score index (LSI) 5fatigue (mean) pediatric Quality of life
Multidimensional Fatigue Scale (Peds QL-MFS)
(Generalsleepcognitive fatigue)
116week physical activity (PA)
2 total PA physical fitness and overall QOL was assessed at 5 different intervals T0 preintervention (baseline) T1midintervention (after the
first 8 wk) T2 postintervention
(16 wk) T3 3-months
postintervention T4 1-year poststudy
initiation
1 from baseline -wkssig Improvementstotal PA physfitness and Qgeneral fatigue(meanplusmnSD 796plusmn135)
2 from baseline to 3FUsig Improvin general fatigue(meanplusmnSD824plusmn131)slefatigue(meanplusmnSD755plusmn191)totafatigue(meanplusmnSD778plusmn150)
3at 1 years FUsImprovements in sleeprest fatigue(meanplusmnSD725plusmn203)total (meanplusmnSD 763plusmn
678
47
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
2 Gene R E amp Conk Z (2008)
Impact of Effective Nursing Interventions to the Fatigue Syndrome in Children Who Receive Chemotherapy
1 to examine the effects of an effective nursing intervention to the fatigue syndrome of children 7 to 12 years of age who receive chemotherapy 2Tto examine the relationship between fatigue and demographic variables (age sex) diagnoses ([ALL AML] lymphoma) and therapy-related variables (eg level of hemoglobin
experimental randomized controlled study
Routine nursing care
A total of 60 children who are 7-12 years of age(a new diagnosis of ALL AML or lymphoma and receiving for the first time after being diagnosed a 7- to 10-day chemotherapy treatment )
fatigue The Fatigue Scale(FS-C) for 7-12 (intensity)
The Fatigue Scale Parent Version (FS-P)
1 effective nursing interventions(45- 60mdaya week)education about the fatigue with the chemotherapy and fatigue handbook 2 T1 After a 7-day period the children
and parent were evaluated with the Fatigue Scale
1The difference betwthe 2 mean values wafound to be statisticallsignificant 2 statistically significadifference was found between the Fatigue Scale-Child mean scothe experimental (272the control group (4213)children
679
48
25 Chiang et
al(2007)
The effects of ldquo a home ndashbased aerobic exercise interventionrdquo on fatigue and cardiorespiratory fitness in children with Acute Lymphoblastic Leukemia during the maintenance stage of chemotherapy
To examine the effect of ldquo a home ndashbased aerobic exercise interventionrdquo on fatigue and cardiorespiratory fitness in children with Acute Lymphoblastic Leukemia during the maintenance stage of chemotherapy
Quasi-experi -mental
Routine
nursing care
14 pediatric oncology patients in the experimental group and 10 in control group who were matched by age and sex ages7-18 years
1Cardiorespiratory fitness
2Fatigue
1Cardiorespiratory fitness Physical Activity Recall
VO2maxHR peak 6MWT
2 Fatigue PedsQL-MFS(Generalsleepcognitive fatigue)
1A six-week home-based aerobic exercise intervention 2 8 time points T0 baseline T1-T6 every week during the
intervention(6 weeks) T7 post intervention T8 follow-up (one month after
the end of the home-based exercise program)
1 For intent-to ndash treatthe findings indicated are no intervention efftime differences by anon the subscale of fat2 For per-protocol angeneral fatigue( mean422plusmn402) was the osubscale that was siglower for children whothe exercise interventthose in control groupfollow-up assessmentmonth after the compintervention) 3 The VO2peak are significantly improvingexperimental group atbaseline- and post-intassessment The VO2was significantly highechildren who were in experimental group thcontrol subjects at post-intervention assefor the per-protocol an
680
49
Appendix IV Instrument used to measure fatigue
Name Instrument
developers
Description Used in
age in
ref
Reliability
Consistency of
instrument
Checklist Individual Strength
(CIS)22
Vercoulen et
al1996
20 items using 7-point Likert scale of
fatigue To measure four aspects of
fatiguesubjective experience
contractionmotivation physical
Activity
6-14 Not reported
Child Fatigue Scale (CFS)7 Hockenberry
et al2003
14 items 2 part questionnaire frequency
(yes or no) 5-point Likert scale of the
intensity of any yes responses
7-13
14-18 α073-o84
The Fatigue Scale for 7-12
year Olds (FS-C)224
Hockenberry
et al
14 items provide a fatigue intensity score
5-point Likert scale
7-12 αo84
The Fatigue Scale for 13-18
year Olds (FS-A)24
Hockenberry
et al
14 items provide a fatigue intensity score
5-point Likert scale
13-18 α076-o96
Pediatric Quality of life
Multidimensional Fatigue
Scale (Peds QL-MFS)2325
Varni2002 18 items to measure three aspects of
fatigueGeneralsleepcognitive
14-18 Not reported
681
50
Appendix V Excluded studies and reasons for exclusion
Baggott C Dodd M Kennedy C Marina N Miaskowski C Multiple Symptoms in Pediatric Oncology
Patients A Systematic Review Journal of Pediatric Oncology Nursing 2009 Nov-Dec 27(6)
325-339
Reason for exclusion Not outcome of interest
Barlow JH Ellard DR Psycho-educational interventions for children with chronic disease parents and
siblings an overview of the research evidence base Care Health amp Development 2004 Nov
30(6)637-45
Reason for exclusion Not outcome of interest
Bedider S Moyer CA Randomized controlled trials of pediatric massage A review Evid Based
Complement Alternat Med 2007 Mar 4(1)23-34 Epub 2006 Nov 3
Reason for exclusion Not outcome of interest
de Nijs EJ Ros W Grijpdonck MH Nursing intervention for fatigue during the treatment for cancer Cancer
Nursing 2008 31(3)191-206
Reason for exclusion Not population of interest
Edwards JL Gibson F Richardson A Sepion B Ream E Fatigue in adolescents with and following a
cancer diagnosis developing an evidence base for practice European Journal of Cancer 2003
Dec 39(18)2671-80
Reason for exclusion Not experimental or quasi-experimental study
Hinds PS Hockenberry-Eatan M Developing a research program on fatigue in children and adolescents
diagnosed with cancer Journal of Pediatric Oncology Nursing 2001 Mar-Apr 18(2 Suppl
1)3-12
Reason for exclusion Not experimental or quasi-experimental study
Hockenberry-Eaton M Hinds PS Alcoser P ONeill JB Euell K Howard V Gattuso J Taylor J Fatigue in
Children and Adolescents With Cancer Journal of Pediatric Oncology Nursing 1998 July
15(3)172-182
Reason for exclusion Not experimental or quasi-experimental study
Jean-Pierre P Mustian K Kohli S Roscoe JA Hickok JT Morrow GR Community-based clinical oncology
research trials for cancer-related fatigue The Journal of Supportive Oncology 2006 Nov-Dec
4(10)511-6
682
51
Reason for exclusion Not population of interest
Kangas M Bovbjerg DH Montgomery GH Cancer-Related Fatigue A Systematic and Meta-Analytic
Review of Non-Pharmacological Therapies for Cancer Patients Psychological Bulletin 2008 Sep
134(5)700-41
Reason for exclusion Not population of interest
Lotfi-Jam K Carey M Jefford M Schofield P Charleson C Aranda S Nonpharmacologic strategies for
managing common chemotherapy adverse effects A systematic review Journal of Clinical
Oncology 2008 Dec 1 26(34)5618-29 Epub 2008 Nov 3
Reason for exclusion Not outcome of interest
Marchese VG Chiarello LA Lange BJ Effects of physical therapy intervention for children with acute
lymphoblastic leukemia Pediatr Blood Cancer 2004 Feb42(2)127-33
Reason for exclusion Not outcome of interest
Meeske KA Siegel SE Globe DR Mack WJ Bernstein L Prevalence and correlates of fatigue in
long-term survivors of childhood leukemia Journal of Clinical Oncology 2005 Aug 20
23(24)5501-10
Reason for exclusion Not intervention study
Minton O Richardson A Sharpe M Hotopf Stone P A systematic review and meta-analysis of the
pharmacological treatment of cancer-related fatigue J Natl Cancer Inst 2008 Aug 20
100(16)1155-66 Epub 2008 Aug 11
Reason for exclusion Not population and intervention of interest
Mustian KM Morrow GR Carroll JK Figueroa-Moseley CD Pascal JP Williams GC Integrative
nonpharmacologic behavioral interventions for the management of Cancer-Related fatigue The
Oncologist 2007 12(1)52-67
Reason for exclusion Not population of interest
Neill J Belan I Ried K Effectiveness of non-pharmacological interventions for fatigue in adults with
multiple sclerosis rheumatoid arthritis or systemic lupus erythematosus a systematic review
Journal of Advanced Nursing 2006 Dec 56(6)617-35
Reason for exclusion Not population of interest
Rheingans JI A systematic review of nonpharmacologic adjunctive therapies for symptom management
Journal of Pediatric Oncology Nursing 2007 24(2) 81-94
683
52
Reason for exclusion Not outcome of interest
Rheingans JI Pediatric oncology nursesrsquo management of patients symptoms Journal of Pediatric
Oncology Nursing 2008 Nov 25(6) 303-11
Reason for exclusion Not outcome of interest
San Juan AF Fleck SJ Chamorro-Vintildea C Mateacute-Muntildeoz JL Moral S Peacuterez M Cardona C Del Valle MF
Hernaacutendez M Ramiacuterez M Madero L Lucia A Effects of an intrahospital exercise program
intervention for children with leukemia Medicine amp Science in Sports amp Exercise 2007 Jan
39(1)13-21
Reason for exclusion Not outcome of interest
Sanford SD Okuma JO Pan J Srivastava DK West N Farr L Hinds PS Gender differences in sleep
fatigue and daytime activity in a pediatric oncology sample receiving dexamethasone Journal of
Pediatric Psychology 2008 Apr 33(3)298-306 Epub 2007 Nov 17
Reason for exclusion Not experimental or quasi-experimental study
Schmitz KH Holtzman J Courneya KS Macircsse LC Duval S Kane R Controlled physical activity trials in
cancer survivors a systematic review and meta-analysis Cancer Epidemiol Biomarkers Prev
2005 Jul 14(7)1588-95
Reason for exclusion Not population of interest
van Brussel M Takken T Lucia A van der Net J Helders PJ Is physical fitness decreased in survivors of
childhood leukemia A systematic review Leukemia 2005 Jan 19(1)13-7
Reason for exclusion Not population of interest
Whiting P Bagnall AM Snowden AJ Cornell JE Mulrow CD Ramirez G Interventions for the treatment
and management of chronic fatigue syndrome JAMA 2001 Sep 19 286(11)1360-8
Reason for exclusion Not intervention of interest
Whitsett SF Gudmundsdottir M Davies B McCarthy P Friedman D Chemotherapy-related fatigue in
childhood cancer correlates consequences and coping strategies Journal of Pediatric
Oncology Nursing 2008 Mar-Apr 25(2)86-96 Epub 2008 Feb 29
Reason for exclusion Not experimental or quasi-experimental study
Winner C Muumlller C Hoffmann C Boos J Rosenbaum D Physical activity and childhood cancer Pediatr
Blood Cancer 2010 Apr 54(4)501-10
Reason for exclusion Not research study
684
53
Wu M Hsu L Zhang B Shen N Lu H Li S The experiences of cancer-related fatigue among Chinese
children with leukaemia A phenomenological study Journal of Nursing Studies 2010 Jan
47(1)49-59 Epub 2009 Aug 25
Reason for exclusion Not experimental or quasi-experimental study
Yeh CH Chiang YC Lin L Yang CP Chien LC Weaver MA Chuang HL Clinical factors associated with
fatigue over time in paediatric oncology patients receiving chemotherapy British Journal of
Cancer 2008 Jul 8 99(1)23-9 Epub 2008 Jun 24
Reason for exclusion Not experimental or quasi-experimental study
685
6
theory at present This model suggests that the main cause of fatigue is a lack of energy
The physical ability of patients is reduced because of the symptoms caused by diseases
or treatments and thus patients experience emotion-related fatigue and the reduction in
functional status as a result In addition the symptoms caused by reoccurring diseases
or treatments may be harmful to physical conditions even more and lead to disability
eventually In this model any treatment program that can address the decline in activity
can alleviate fatigue symptoms is said to improve fatigue Therefore Psychobiological
Entropy Model not only provides a more direct detection of clinical patterns but also for
providing measures of care within a fatigue model
The third model is the Energy Analysis Model12 which suggests that the pathological
change of individual physical status becomes the barrier of energy conversion When the
supply of energy in individuals is low or the demand is high a lack of energy results and
the individuals feel fatigue Energy is generated by the oxygenation in blood The
correction factors of energy reaction are cancer treatments symptom distress and
emotional disorders Concepts in the fatigue model include energy sources energy
transformations energy expenditures and energy response modifiers The relationships
among these concepts are dynamic and intercorrelated with each other From the Energy
Analysis Mode point of view the physiological mechanism of fatigue includes some
objective indicators such as body weight and hemglobulin
In terms of the causes of fatigue Ekti Genc amp Conk (2008) 2 indicated that illnesses
treatments and stage of disease can cause fatigue NCCN (2011) 1 points out that many
conditions are related to fatigue including pain emotional pain anaemia sleep disorders
639
7
nutritional deficiencies activity reduction side effects of drugs (antihistamine drugs
anti-vomiting drugs and anti-anxiety drugs) and others In a study on children
adolescents parents and relevant medical and nursing staffs Hinds and
Hockenberry-Eaton (2001) 13 proposed four factors causing the fatigue of children with
cancer which are 1) environmental factors treatment setting events or situations that
place demands on the patient such as appointments inpatient stay long waiting time
altered routines that lack clear beginnings and endings of each day and decision making
and information exchange 2) personalbehavioral factors the negative faith of children
with illness 3) culturalfamilyother factors emotions concerns the hope of friends and
family ability to participate in activities and restricted activities 4) treatment-related
factors the invasive inspections experienced by children with illness insufficient time for
physical strength recovery between the repeated courses of treatments or the side
effects caused by treatments (infection pain and decrease in complete blood count) It
can be inferred that the causes of fatigue are complicated and multifaceted
Fatigue is a complex and multidimensional condition 10 therefore fatigue is subject to
different definitions and there are different measurement tools Aaronson et alrsquos14
review the literature of fatigue summarised the characteristics of fatigue measurement
including the following(1) Subjective quantification of fatigue can be determined with the
Lee and colleagues (1991) Visual Analog Scale for Fatigue (VASF)(2) Subjective
distress This item simply asks the rater to report to what degree fatigue has caused
distress (3) The effect of fatigue on activities of daily living (4) Correlates of fatigue
such as sleep and depression to assess when measuring fatigue (5) key biological
parameters such as cytokines interferon and tumor necrosis factor
640
8
Fatigue can be also measured with unidimensional or multidimensional scales The first
type of fatigue scale is not suitable for studies focusing on fatigue because they are too
long if the aim is to only assess fatigue Furthermore they only allow for a limited number
of possible responses Unidimensional scales also are not suitable for the in-depth study
of fatigue because they assess only one aspect of fatigue15
In recent years fatigue in children with cancer has received some attention and
measurement tools have gradually been developed - such as1) Checklist individual
strength (CIS) The items are scored on 7-point Likert scales (with 1 indicating best and
7 worst function) 2) The Child Fatigue Scale (CFS) is a 2-part questionnaire that asks for
a yes or no (frequency) response and a 5-point rating of the intensity of any yes
responses ranging from not at all to a lot The Fatigue Scale for 7-12 year Olds (FS-C)
is provide a fatigue intensity score higher scores indicating higher fatigue The Fatigue
Scale for 13-18 year Olds (FS-A) measure adolescent cancer patientsrsquo perceptions of
the intensity of their fatigue on a daily or weekly basis higher scores indicating higher
fatigue 3) The Fatigue Scale Parent Version (FS-P) measures the parentsrsquo perception
of their childrsquos fatigue intensity on a five-point Likert-type scale higher scores indicating
higher fatigue 4) The Fatigue Scale Staff Version (FS-S ) measures the staffrsquos
perceptions of the patientrsquos fatigue intensity during the past 24 hours Intensity ratings are
on a four-point Likert-type scale with higher scores indicating more intense fatigue
symptoms 5) The Pediatric Quality of life Multidimensional Fatigue Scale (Peds
QL-MFS)Higher scores (0 to 100) indicate less fatigue( Appendix IV)
Besides disturbing physical and mental functions and status fatigue also affects the
641
9
quality of life 15 of children with cancer and impacts their daily life16 among all different
types of cancer progress and childrsquos ages However as opposed to the fatigue of adults
the fatigue of children tends to be neglected and left untreated17 by medical and nursing
staffs
In terms of the management approach to cancer-related fatigue Ekti Gene (2008) 2
suggests that strategies could include pharmacologic and non-pharmacologic measures
NCCN (2011) 1 indicated in the Clinical Practice Guidelines in Oncology that during
aggressive treatments during long-term follow-up treatments or in the terminal phase of
cancer the intervening measures for cancer-related fatigue can be divided into
pharmacologic and non-pharmacologic measures Non-pharmacologic measures include
activity enhancement psychosocial interventions (eg cognitive behavioral therapy
(CBT) stress management relaxation support groups) attention-restoring therapy and
nutrition consultation As for the effectiveness of pharmacological measures the
effectiveness is still uncertain However there is evidence to suggest that
methylphenidate may be effective in treating cancer-related fatigue1 Whiting et al
(2001)18 included 36 randomized controlled trials and 8 controlled trails to assess the
effectiveness of the pharmacological and non-pharmacological interventions used in the
treatment or management of chronic fatigue syndrome in adults or children Results
showed insufficient evidence on the effectiveness of the pharmacological supplements
complementaryalternative and other interventions In addition the evidence of
pharmacological treatments of immunoglobulin and hydrocortisone were also
inconclusive However interventions such as cognitive behavioral therapy and graded
exercise therapy have shown promising results
642
10
The efficacy of pharmacological treatments for cancer-related fatigue has not been
established6 therefore there is a need to provide evidence-based findings of the
effectiveness of non-pharmacological interventions to support nursing intervention to
release the childrsquos cancer-related fatigue To date most studies have investigated the
effectiveness of non-pharmacological treatments on cancer-related fatigue of
adults20and to date there is no systematic review in relation to cancer-related fatigue of
children However as children are not a smaller version of adults it is inappropriate to
extrapolate the results of adults onto children Therefore there is a need to establish the
effectiveness of non-pharmacological intervention on the cancer-related fatigue of
children
Given the increase in childhood cancer survival rate the importance of decreasing
childrenrsquos cancer-related fatigue during treatments and so increase their quality of life has
become a focus of their medical teams The role of nurses during care intervention is to
confirm the major symptoms of children with illness and effectively treat each symptom to
increase the childrenrsquos quality of life21 Moreover the USA based NCCN also indicated in
the Care Standard for the Treatment of Cancer-related Fatigue of Children and
Adolescents that treatments for fatigue should be included in the health care teams and
the children and their family should be informed of relevant information The definition of
non-pharmacological interventions for childrenrsquos cancer ndashrelated fatigue include activity
enhancement (exercise physical activity) psychosocial interventions cognitive
behavioral therapy (CBT) stress management relaxation nutrition consultation
massage and educational interventions
643
11
The Cochrane Library of Systematic Reviews and The Joanna Briggs Institute Library of
Systematic Reviews were initially searched to ensure that systematic reviews on this
subject were not already published or being undertaken This initial search prior to the
commencement of the review did not yield any results
This systematic review has examined the effectiveness of non-pharmacologic
interventions on the cancer-related fatigue of children in hope of finding scientific
evidence that can support or refute such measures on children The results of this study
may serve as a reference for professional caregivers children with cancer and their
families or to be put into practice during the clinical care of children with cancer
Definition of terms
FatigueFatigue as a distressing persistent subjective sense of physical emotional
andor cognitive tiredness or exhaustion related to cancer or cancer treatments
that is not proportional to recent activity and interferes with daily function1 There
are various scales and measurements of the degree of fatiguewe have elected to
use the study authors own definitions of fatigue rather than applying a single
pre-set definition of the condition
Non-pharmacological interventionsReferring to reduce fatigue that does not involve
drugsNon-pharmacologic measures include activity enhancement psychosocial
interventions (eg cognitive behavioral therapy stress management relaxation
support groups) attention-restoring therapy and nutrition consultation1
ChemotherapyTreatment with drugs that kill cancer cells 1
644
12
Review QuestionsObjectives
Review Objective
The objective of this systematic review was to critically appraise synthesize and
present the best available evidence concerning the effects of non-pharmacological
interventions fatigue in children and adolescents with cancer
Review Question
The following specific question was addressed in this review
What is the effectiveness of non-pharmacological interventions on fatigue in
children and adolescents with cancer aged from one to 18 years
Criteria for Considering Studies for this Review
Types of studies
This review included randomised controlled trials (RCTs) and quasi-experimental
studies that examine the effectiveness of non-pharmacological intervention for fatigue in
children and adolescents with cancer
Types of participants
Children and adolescents aged from one to 18 years old experiencing fatigue
associated with cancer either during or after the chemotherapy or maintenance stage of
chemotherapy or survive stage The types of cancer to be included in this systematic
review will be ALL (Acute lymphoblastic leukemia) AML (Acute myeloid leukemia)
lymphoma and solid tumors
Exclusion criteria for Types of participants
645
13
newborn infants under 1 years of age
participants who do not have a specific diagnosis of cancer
participants who have received immunoglobulin or hydrocortisone
treatment
If participants have received immunoglobulin or hydrocortisone treatment may
inference the effectiveness of non-pharmacological interventions on fatigue
Types of intervention
This review considered studies that examine non-pharmacological interventions on
fatigue for children and adolescents with cancer including activity enhancement
(exercise physical activity) psychosocial interventions CBT stress management
relaxation nutrition consultation massage and educational interventions The
interventions descriptive included the length frequency setting and intervention
providers eg Nurse Psychologist Dietician
Exclusion criteria for types of interventions only pharmacological interventions were
tested
Types of outcome measures
The outcome measures considered were fatigue scores The literature demonstrates that
differences of opinion exist regarding the most valid and reliable method of measuring
cancer-related fatigue Therefore studies that used any validated scale for
cancer-related fatigue were considered for inclusion Currently commonly used scales to
measure fatigue include Checklist Individual Strength (CIS) Child Fatigue Scale (CFS)
The Fatigue Scale for 7-12 year Olds (FS-C) The Fatigue Scale for 13-18 year Olds
646
14
(FS-A)and Pediatric Quality of life Multidimensional Fatigue Scale (Peds QL-MFS)
Types of settings
Both hospital and community settings
Search Strategy
Before undertaking this systematic review the Cochrane Library Joanna Briggs Institute
Library of Systematic Reviews and CINAHL were searched and no systematic reviews on
this topic were found or identified as underway
The search strategy aimed to find both published and unpublished studies
A three-step search strategy was utilized in each component of this review An initial
limited search of CINAHL and MEDLINE was undertaken followed by an analysis of the
text words contained in the title and abstract and of the index terms used to describe the
article A second search using all identified keywords and index terms was undertaken
Lastly the reference lists of all identified reports and articles were searched for additional
studies
Types of languages
1 English
2 Chinese
The following databases were searched to identify keywords contained in the title and
abstract and relevant MeSH headings and descriptor terms
The Cochrane Library PsycINFO 1990 ndash 2010
647
15
Ovid MEDLINE 1966 ndash 2010 CINAHL Plus with Full Text 1960 ndash2010 EMBASE ProQuest Dissertations amp theses 1990-2010 Electronic theses and dissertations system 1956(abstract)1990(full text)-2010 MEDNAR Index to Taiwan periodical literature 1970-2010 Electronic thesis and dissertation system (Chinese) 1990-2010
Keyword search terms
1Types of studies experimental study random quasi-experimental study實驗性研究隨
機類實驗性研究
2 Types of participants childchildren adolescents pediatric cancer and oncology兒童
青少年兒科癌症腫瘤
3 Types of interventions non-pharmacological interventions massage exercise fitness
physical activity cognitive behavioral stress management energy conservation
sleep therapy relaxation distraction and psycho-education非藥物性處置按摩運動
身體活動認知行為壓力處置能量保存睡眠治療放鬆轉移注意力衛教
4 Types of outcome measures fatigue cancer-related fatigue loss of energy levels of
tiredness tired side effect symptoms疲憊癌性疲憊疲倦合併症症狀
Methods of the Review
Assessment of methodological quality Papers selected for retrieval were assessed by two independent reviewers for
methodological validity prior to inclusion in the review using the standardised critical
appraisal instruments (Appendix I) from the JBI-SUMARI (Joanna Briggs Institute
Systems for the Unified Management Assessment and Review of Information package)
Any disagreements that arise between the reviewers were resolved through discussion
648
16
with a third reviewer
Data extraction Data was extracted from papers included in the review using standardised data
extraction tool (Appendix II) from the JBI-SUMARI Details of eligible studies were
extracted and summarised independently by two reviewers
Data Synthesis
All data analysissynthesis were made using the JBI-SUMARI The studies were
assessed for clinical heterogeneity by considering the settings populations interventions
and outcomes Where possible these binary outcomes were analyzed by calculation of
the Odds Ratio with the 95 CI The weighted mean difference was calculated if the
pooled studies have used the same scale for continuous data The standardized mean
difference was calculated for continuous data measuring the same outcome on a
different scale In studies where statistical pooling of results was inappropriate the
findings were considered for inclusion as a narrative summary
Results The findings from the systematic review are presented first Followed by the results from
the meta-analysis component of this review
Description of studies From database search and hand search a total of 76 papers were identified Thirty
papers were then excluded because they did not meet the inclusion criteria Forty-six
full text were retrieved for further consideration for inclusion Of the 30 excluded reasons
for exclusion were follows 11articles were duplicated eight articles did not meet
649
17
participant inclusion criteria eight articles did not meet outcome criteria and nine articles
were correlation studies or discussion papers others articles were unclear reporting In
total after sorting six papers have been included in this article Figure 1 displays the
process used to identify relevant articles for inclusion in the systematic review
Figure 1 Stages of searching and inclusionexclusion of references for the review
Potentially relevant English-language and Chinese- language Studies Identified
Electronically and hand search (n=76)
Duplicate (n= 11) Papers excluded after evaluation of abstract (n=19)
Papers retrieved for detailed examination (N=46)
Papers excluded after review of full paper
(n=40)
Papers assessed for methodological
quality (n=6)
Papers included in systematic review
(n=6)
Methodological Quality
Of the six included articles 2722232425 two articles were RCT design224 with score 7 out
of 10 each paper from Critical Appraisal Checklist and four articles used
650
18
quasi-experimental design7222425 with socre 5 to 6 out of 10 because the quality of
the whole papers is still acceptable therefore these six articles were accepted after
primary reviewer and secondary reviewerrsquos decision
Randomisation
In two RCT articles224 one study24 used to a computer-generated program operated by
the St Jude Protocol and Data Management System to randomize the sample Another
study2 didnrsquot address how randomization was done
Allocation concealment
No studies reported allocation concealment
Intention-to-treat analysis
One quasi-experimental design7 stated Intention-to-treat analysis
Adequate follow up
The follow-up periods included 2or 3 days24 7 days2 4 week7 one month25 6 week25 12
week2216 week23 and 1 year23
Baseline comparability of groups
Three 22425 of six studies had baseline comparability in terms of age sex diagnosis
race institution duration of illness
Blinded outcome assessment
No studies used blinded outcome assessment The researchers including study team
patients staff and families were not blinded to the patientrsquos group assignment
Characteristics of included studies
651
19
There were six studies related to interventions designed to cancer-related fatigue for
pediatric patients than there are for adults There are a total of six including five
English-language papers 27222324 and one Chinese-language paper 25 ranging in year of
publication from 2007 to 2009
Patient characteristics
The research subjects of four papers included both school-aged children and
adolescents 7222324 one papers involved mainly adolescents25 and one paper sampled
only school-aged children 2 the range in ages was between six-18 years The number of
patients included in the samples ranged from nine to 60 The sources of case data were
from both outpatients and hospitalized children The types of cancer included acute
lymphoblastic leukemia (ALL) solid tumors acute myeloid leukemia (AML) and
lymphoma Overall ALL was the most commonly studied cancer type The stage of the
disease varied in these reports some patients were in the maintenance stage of
chemotherapy25 some had just received their first round of chemotherapy224 some had
completed two courses of treatments lasting 4-8 weeks each 7 and some had entered
the survivor stage 2223
Countries
Two RCTrsquos 2 24 were conducted in the USA There were four quasi-experimental design
studiesThree studies conducted in the USA7 22 23 and one in Taiwan25
Intervention types
652
20
The interventions included exercise training programs 2225 physical activity 2324
massage therapy 7 and health education 223 exercise training and physical activity as
an intervention method given in three different settings home 22 25 community 23 or
hospital 24 The studies used different types of exercise interventions including
home-based aerobic exercise use a Video Compact Disc 25 use of a bicycle-style
exerciser 24 aerobics2223 and various types of physical activities2 and strength-building
exercises 2223 The intensity of the exercise varied and often included gradual warm-up
exercises a period of main exercise and a cool down period For these studies2023 the
target exercise intensity was a heart rate of gt90 of the maximum heart rate (HR max) or
the increase in the percentage of heart rate reserve ( HRR) of 40-60
The number of weeks for the exercisephysical activity interventions duration including
2-4 days 24 6 weeks25 12 weeks22 and 16 weeks23 The frequency of exercise ranged
from 2-3 times per week to twice a day Typical duration of exercise ranged from 10 to 45
minutes There are three papers using exercise interventions based on ACSM (American
College of Sports Medicine) 2225 recommendations and one of these used an Activity
pyramid from the ACSM to determine intensity 24
One article did not clarify the type of exercise intervention or the reasons for their choices
23 In addition there was an article focusing on massage therapy 7 as an intervention in
this study the experimental group received four weeks of massage therapy either in the
clinic or in the patientrsquos room the therapy was applied by a professional masseur and
targeted the back legs arms chest stomach and face of the children However the
frequency of massage sessions per week and the duration of the massages were not
653
21
given There is another article about intervention measures combine health education
and physical activity 2 In this study patients were informed about the following (1) health
education patients received daily education about chemotherapy-related fatigue and
information from a health education manual written by the author (2) encouragement for
children to engage in activities such as listening to music drawing and reading and (3)
physical activity which involved walking along the corridors of the ward for 10-15 minutes
These health education measures were presented for 45-60 minutes a day for a total of
seven days The study design for non-pharmacological interventions used control groups
that included primarily people who had received standard treatment or people who did
not receive an exercise intervention
Outcome measures
Five measurement tools were used in this group of seven papers concerning childrenrsquos
fatigue (Appendix IV) Because those studies included both school-age children and
adolescents the following descriptions will be differentiated by age Fatigue
measurements for school-aged children with cancer include the following the Child
Fatigue Scale (CFS) 7 a scale that measures the frequency and intensity of fatigue and
the Fatigue Scale for 7-12 year Olds (FS-C) 224 a scale that can be used to evaluate the
intensity of fatigue On the other hand fatigue measurements for adolescent cancer
patients include the following the Fatigue Scale for 13-18-year-olds (FS-A) 24 a measure
that can help evaluate fatigue levels the Pediatric Quality of Life Multidimensional
Fatigue Scale (Peds QL-MFS) 2325 a tool that can be divided into three sub-scales to
understand the general cognitive and sleep rest components of fatigue and finally the
CIS-20 for school-age children and adolescents 22 a scale that measures four levels of
654
22
fatigue namely subjective experience attention motivation and physical activity Two
studies used the Peds QL-MFS scale to measure fatigue2325
Meta-analysis results Two studies of the included papers failed to provide sufficient raw data they could not be
included in the meta-analysis Hinds et al 24 did not include post-test data Genc et al 2
provided no pre-test data PostWhite et al7 reported that fatigue after the health
education intervention was not statistically different but they presented the results
without presenting fatigue-related data Therefore the meta-analysis included three
studies 222325
The heterogeneity of studies was analyzed with Chi square statistics and no statistical
significance was found Therefore the data was combined in meta-analysis according to
exercise intervention on fatigue In addition there were three articles using the Peds
QL-MFS as a research tool to examine childrenrsquos improvements in fatigue Among these
Keats 22 and Chiang 24 present the effectiveness of exercise interventions using three
subscales Therefore the meta-analysis also analysis of the effects of these exercise
intervention measures on three subscales of Peds QL-MFS general fatigue sleep rest
fatigue and cognitive fatigue
The effectiveness of exercise intervention for fatigue We analyzed the exercise intervention effect on fatigue A total of 2 studies 22 23 were
included Takken et al 22 used community-based exercise training program to reduce
fatigue of children 6 to 14 years (mean 93y) of age who survived ALL Fatigue
measurement by Checklist Individual Strength (CIS) after 12-week of training fatigue
655
23
show no significant differences between pre (meanplusmnSD 415plusmn147) and post training
(meanplusmnSD368plusmn217) but fatigue change from baseline mean reduction of 11
Keats et al23 although used community-based physical activity program to reduce fatigue
for adolescents 14 to 18 years of age (mean162 y) with cancer (Lymphoma leukemia CNS
tumor germ cell tumor) Studies used fatigue by PedsQLMFS Results show general fatigue
from baseline to 8 weeks and to 3 months follow up significantly improves General
fatigue sleeprest fatigue and total fatigue from baseline to 3 months follow up showed
significant improvements Sleeprest fatigue and total fatigue at 1 years followed up were
significant improvements
Figure 2 shows the overall effect of exercise intervention in children and adolescents with
cancers with a focus on improving fatigue Due to the lower heterogeneity (p>005) the
fixed effects model was used to pool the data for meta-analysis (Overall effect size=
-006 95 Confidence Interval (CI) -070 to 058) A result did not indicate a statistically
significant difference (p = 087)
656
24
Figure2 Meta-analysis results of exercise intervention on fatigue
In addition Keats23 and Chiang25 used the three sub-scales of Peds QL-MFS to
determine the general cognitive and sleep rest components of fatigue The following
present the effectiveness of exercise interventions using three subscales including
general fatigue sleep rest fatigue and cognitive fatigue 2325
Chiang et al 25 used a 6- week home-based aerobic exercise intervention to reduce
fatigue of children 7 to 18 years (mean age at experimental group was 1088 y in control
group was 1247 y) of age who with acute lymphoblastic leukemia Fatigue measurement
by Peds QL-MFS after training For intent-to ndash treat analysis the findings indicated that
there are no intervention effects and time differences by any items on the subscale of
fatigue For per-protocol analysis general fatigue( meanplusmnSD 422plusmn402) was the only
subscale that was significantly lower for children who received the exercise intervention
than those in control group at follow-up assessment (one month after the completion of
intervention)
Keats et al23 although used community-based physical activity program to reduce fatigue
for adolescents 14 to 18 years of age (mean162 y) with cancer (Lymphoma leukemia
CNS tumor germ cell tumor) Both studies used fatigue by PedsQLMFS Results show
general fatigue from baseline to 8 weeks and to 3 months follow up significantly improves
657
25
General fatigue sleeprest fatigue and total fatigue from baseline to 3 months follow up
showed significant improvements Sleeprest fatigue and total fatigue at 1 years followed
up were significant improvements
The effectiveness of exercise intervention for general fatigue
The impact of the exercise interventions upon levels of general fatigue was also analysed
The heterogeneity was low (p>005) Therefore the fixed effects model was used to
examine the effectiveness The effect size is -076 indicating a statistically significant
difference (p = 001 95 CI -135 to -017 Fig 3) The evidence suggests that exercise
intervention can reduce general fatigue in children with cancer
Fig 3 Meta-analysis results of exercise intervention for general fatigue
The effectiveness of exercise intervention for sleep rest fatigue
The following is the result of the meta-analysis of the effectiveness of exercise
interventions on sleep rest fatigue First the heterogeneity test was conducted with P gt
005 representing small heterogeneity and the fixed effects model was used Fig 4
shows the effect size is -035 indicating no statistically significant differences (p = 023
95 CI-092 to 022 Fig 4)
658
26
Fig 4 Meta-analysis results of exercise intervention for sleep rest fatigue
The effectiveness of exercise intervention for cognitive fatigue Lastly the following data reports the results of meta-analysis of the effectiveness of
exercise interventions for cognitive fatigue The heterogeneity was p>005 then the
fixed effects model was used The effect size is -035 indicating no statistically significant
differences (p = 024 95 CI-092 023 Fig 5)
Fig 5 Meta-analysis results of exercise intervention for cognitive fatigue
Narrative presentation of remaining included studies
Three studies were not included in meta-analysis Post-White et al7 one of the aims in
this study was to examine the effect of massage therapy on fatigue in children with
cancer The study was a quasi-experimental design Twenty-three childrenparent dyads
were enrolled 17completed all data points Children with cancer ages 7 to 18 years
received at least 2 identical cycles of chemotherapy and one parent participated in the
2-period crossover design in which 4 weekly massage sessions (MT) alternated with 4
659
27
weekly quiet-time (QT) control sessions There were no significant changes in fatigue in
children over the 4-week MT or QT conditions either independently (change over time) or
when we compared fatigue by condition
The lack of effect of massage on fatigue may be the difficulty some children had in
differentiating fatigue from being relaxed underscores the challenge of measuring fatigue
in children Some children interpreted being tired or relaxed as having greater fatigue
because they felt like lying around and sleeping or felt unmotivated to do their usual
activities all measures of fatigue in the instrument used in the study
Hinds et al24conducted a prospective two-site randomized controlled pilot study to
assess the feasibility of an enhanced physical activity (EPA) intervention in hospitalized
children and adolescents receiving treatment for a solid tumor or for acute myeloid
leukemia (AML) Twenty-nine patients (25 with a solid tumor and 4 with AML) participated
age range from 736 to 1816 (mean 1248 y) The EPA intervention selected was
pedaling a stationary bicycle-style exerciser (Chattanooga Peddler Deluxe Bio-Teck
Medical Memphis TN) for 30 minutes twice daily for 2 to 4 days of hospitalization The
mixed model analysis revealed no significant differences in patient reports of fatigue
between the two study arms or over time
Genc et al2 conducted a RCT involving children with cancer who are 7 to 12 years of age
and receiving chemotherapy treatment to determine the impact of educational
intervention by nurses on decreasing the fatigue syndrome The research sample was
composed of a total of 60 children with cancer with 30 children being included in the
660
28
experimental group (mean age 923)and 30 children included in the control group (mean
age 937) with their mothers In the experimental group after the 7th to 10th day of the
chemotherapy treatment throughout a week the researcher conducted the nursing
interventions every day for 45 to 60 minutes In the control group routine nursing
interventions were carried out The experimental group received education about the
fatigue with the chemotherapy and fatigue handbook was given which was developed by
the authors Children and mothers were consulted for including activities that could
decrease fatigue which were described as effective interventions A statistically
significant difference was found between the Fatigue Scale-Child mean scores of the
experimental (2723) and the control group (4213) The results suggest that fatigue of
children with cancer can be reduced by implementing appropriate nursing interventions
(t=567 Plt00)
Discussion The purpose of this systematic review was to determine the effectiveness of
non-pharmacological interventions specifically targeting fatigue for children and
adolescents with cancer undergoing chemotherapy or after receiving chemotherapy
Included articles about the effectiveness of non-pharmacological interventions for
children and adolescents with cancer were published between the years of 2007 and
2009 Although interventions for cancer fatigue for adults have been extensively studied
it can be seen from either the title of the paper or related content that an intervention
study on children was a pilot study or a feasibility study Representing a field in its early
stage these studies show that the fatigue issues with young cancer patients have only
recently been taken seriously
661
29
The results of our meta-analysis include measurement of the four performance indicators
fatigue and general fatigue sleep rest fatigue and cognitive fatigue The results show
that there is a statistically significant difference only in the domain of general fatigue
using an exercise intervention for children with cancer can improve the degree of fatigue
with the effect size reaching 0671 Other results do not indicate significant differences
The reasons may include the following
1 Characteristics of the cancer The exhaustion from cancer occurs not only during cancer treatment but also in during
long-term survival a time during which patients may continue to be affected by this
symptom 8 26 Therefore when using intervention measures to improve fatigue
circumstances should be considered such as the process of the treatment and the course
or stage of the disease Because cancer patients will experience different forms of
treatment or courses of treatment the disease itself or treatment differences should be
considered in the choice of intervention Even chemotherapy drugs should be taken into
consideration For example a period of general steroid treatment can increase patientsrsquo
fatigue In those studies of children with cancer few studies looked solely at one type of
cancer most studies included a variety of cancer patients Furthermore most studies do
not clearly explain the stage of the disease or course of treatment and most do not
include treatment variables in the control group Moreover children with cancer may
have different levels of physical function
2 Research design The sample size Currently there are few studies with large sample size and a rigorous
RCT design due to the small number of papers available for analysis The sample size
included in our studyrsquos data analysis is between 20 and 42 people this small sample size
will affect the power available to evaluate outcome variables
Although most of the non-pharmacological interventions still use exercise and physical
activity and these studies overall show better results for fatigue as compared with
controls more research is still needed to further confirm the efficacy of these findings
662
30
The dropout rate in the evaluated research varies a great deal ranging from 5 to 45
these dropout rates may result from the characteristics of the research subjects or the
lengthy time involved in participating in these studies The research data with a high
turnover rate might not reflect the actual outcomes of participation in exercise and the
quality of the research contained in articles with high subject turnover rates may be
lower
Exercise doses and time The exercise doses needed to reduce fatigue cannot be
determined additionally the amount of exercise completed by the patient is also
inconsistent interventions vary between 2-3 times per week and two times a day and
exercise duration varies between 10 and 45 minutes each time Furthermore the study
interventions vary in length between a couple of days and a long period of 16 weeks The
data collection times are different some were measured 12 weeks after the intervention
began some were measured during the 6 weeks of intervention some were measured
three months after the intervention was finished and some were measured after one
year
In addition disease-related symptoms decrease childrenrsquos willingness to participate in
exercise interventions inappropriate exercise intervention programs may actually
increase childrens fatigue In addition the children in the study are still developing
physically it is important to consider ways to design an interesting exercise intervention
to increase the compliance of patients in order to improve the effectiveness Although
intervention programs in the hospital or in a community sports center can improve the
effectiveness because they provide supervision the feasibility of these programs is
questionable However if the program is home-based the children need to be
supervised by parents in order to improve their compliance in doing the exercises
Furthermore regarding the nature of the intervention the results from this study indicate
that the researched non-pharmacological interventions include the following exercise
training programs physical activity massage therapy and health education interventions
However according to the National Comprehensive Cancer Network 1 clinical guidelines
663
31
for cancer non-drug measures for cancer fatigue can be separated into five categories
(1) activity enhancement (2) psychosocial interventions such as cognitive behavioral
therapy (CBT) stress management relaxation techniques and support groups (3)
attention-restoring therapy (4) nutritional consultation and (5) cognitive behavioral
therapy specifically targeting sleep disturbance Researchers have also suggested that
psychosocial interventions should be included in the future research for children with
cancer-related fatigue 22
(2) The measurement tools in the study The assessment of fatigue can be
one-dimensional or multidimensional One-dimensional assessment can help understand
the severity of fatigue symptoms however multidimensional scales are often more
credible Therefore when measuring cancer-related fatigue researchers should consider
whether there is a uniform definition of fatigue or a standardized tool for measuring
fatigue in order to facilitate further systematic meta-analyses and further develop the
clinical care guidelines
Limitations of the review The present review has some potential limitations First the low methodological quality
may influence the result Although exercise intervention seems promising quality of the
RCTs was generally quite low Future studies require better design and reporting if
methodological issues to establish evidence-based nonpharmcologic intervention
Second the identified studies covered only a limited types of nonpharmcological
intervention especially in exercise intervention The guidelines for cancer-related fatigue
in NCCN (2011)1 referred to more interventions than the ones included in this review
such as cognitive behavioral therapy and nutrition consultation Thirdly the small sample
size and effect size could be potentially having led to underpowered approach for
detecting the effects on fatigue Therefore we recommend that as research continues to
grow a re-analysis can be undertaken Fourthly Combining data in meta analysis from
664
32
studies where the ages were quite different is a potential source of heterogeneity and
may affect the interpretation of the results
Conclusion At present clinical treatment is widely used for cancer patients However child and
adolescent cancer patients often experience various side effects which cause short-term
or long-term discomfort both physically and psychologically In particular with the
increasing cure rate cancer related fatigue during or after treatment has become an
important issue This study result provided positive effect of exercise intervention on
general fatigue
Implications for practice The results of this systematic review and meta-analysis show that exercise interventions
can effectively improve the level of general fatigue In particular although the articles
were self-reported feasibility studies their results all indicate that exercise interventions
for fatigue are feasible and safe there was no conclusion to be made for the use of
massage therapy or health education measures because there was only one article for
each of these interventions
Recommendations for practice
Cancer-related fatigue is one of the most severe and frequent symptoms by pediatric
oncology children and adolescent suffered during treatment and the symptom existed
even after treatment has ended Until now no golden standard of treatment to fatigue is
established The findings call for more attention to how to reduce patientrsquos levels of
fatigue Based on the available information evaluated in this review the following
recommendations for practice are provided
665
33
bull For children aged 7 to 18 who has cancer (eg Lymphoma leukemia CNS tumor
germ cell tumor) an effective progressive aerobic exercise program is recommended to
be at least 2-3 times per week 20 to 45 minute for each session and last for 6-16 weeks
in order to reduce their general fatigue (tiredness physically weakness) In addition
adults should be involved in accompanying children while they are performing physical
exercise of which should be able to improve the adherence rate (level 2 ) ( Grade of
recommendation A)
bull For children aged 7 to 18 who has cancer (eg Lymphoma leukemia CNS tumor
germ cell tumor) an progressive aerobic exercise program will not be effective to reduce
their sleep andor rest (sleeping or resting a lot) or cognitive fatigue (problems with
thinking quickly or problems with remembering) (level 2 ) ( Grade of recommendation C)
bull Nursing interventions in educating treatment of fatigue include information about
activity nutrition energy preservation consulting and providing a useful fatigue
handbook will benefit those children who are 7 to 12 years have a new diagnosis of ALL
AML or lymphoma and receive for the first time after being diagnosed a 7- to 10-day
chemotherapy treatment (level 2) ( Grade of recommendation A)
bull A 4-week massage therapy program (the therapists massage childrenrsquos back legs
arms stomachchest and face) is not effective for children who are aged 7 to 18 and
have acute lymphoblastic leukemia brain tumors lymphoma rhabdomyosarcoma
Wilms tumor or Ewing sarcoma(level 2)( Grade of recommendation C)
bull Using a 12-week aerobic and strength exercise (45-min exercise sessions twice a
week) is not effective for children who are aged 6-14 and survived acute lymphoblaststic
leukemia age from 6 to 14(level 2) ( Grade of recommendation C)
bull Using a physical activity intervention (30minutestwice daily for 2-4days) is not
effective for children who are 7 to 18 years of age with soild tumor or AML(level 2)
( Grade of recommendation C)
666
34
Implications for research According to this systematic review and meta-analysis results there are suggestions to
improve the effectiveness of future research on non-pharmacological interventions for
children and young peoplersquos cancer-related fatigue
As the majority of included non-pharmacological interventions for the fatigue of cancer
patients consist of exercise programs future research should also consider various
non-pharmacological interventions in order to understand the effectiveness of different
methods
Regarding the exercise intervention methods and studies should consider multiple
factors including the age or personal condition of the subject the disease stage and the
amount of daily activities Studies should use design prescriptions (eg frequency
intensity duration and type of exercise) and consider the adherence to the measures in
order to enhance the study strength
In measuring the results of non-pharmacological interventions there should be standard
definitions or standard measurement tools to facilitate the following systematic review
and meta-analysis that can subsequently be developed into clinical care guidelines
Reviewing the effectiveness of the current non-pharmacological management of children
and adolescent cancer patients there is still a lack of rigorous RCT research Limited by
the characteristics of cancer there is still a lack of large sample sizes
Potential conflicts of interest There is no conflict of interest
Acknowledgements
Thank you to Dr Rie Konno Research Fellow Joanna Briggs Institute for her help in
assessing studies
667
35
References 1 National Comprehensive Cancer Network( NCCN) in USA NCCN clinical practice
guideline in oncology cancer-related fatigue 2011 2 Ekti Genc R amp Conk Z Impact of effective nursing interventions to the fatigue
syndrome in children who receive chemotherapy Cancer Nursing 200831(4)312-317
3 Childhood Cancer Foundation of ROC (2009March) The classification of diseases
and age sex statistical tables of case Childhood Cancer Foundation of ROC newsletter103105-106
4 Department of Health Executive Yuan ROC (TAIWAN)(2009 March 20)2009 cause of death statistic Health and National Health Insurance Annual Statistics Information Service 2010 June 28Available httpwwwdohgovtwstatisticdatavital statists9898health statistic--lifepdf
5 Chang TK (2007December 8) Common childhood cancer and its treatment Status
Childhood Cancer Foundation of ROC (TAIWAN) 2010 September 23 Available httpwwwccfrocorgtwchildchild_events_readphpe_id=45
6 Hockenberry MJ amp Wilson D Wongs nursing care of infants and children (8th ed) St
Louis MO Mosby 2007
7 Post-White J Fitzgerald M Savik K Hooke MC Hannahan AB amp Sencer SF
Massage therapy for children with cancer Journal of Pediatric Oncology Nursing 2009 26(1)16-28
8Chiang YC Yeh CH Wang WKamp Yang CP The experience of cancer-related fatigue
in Taiwanese children European Journal of Cancer Care 2009 18(1)43-49 9Langeveld NE Grootenhuis M A Voute P A de Haan RJ amp van den Bos C No excess
fatigue in young adult survivors of childhood cancer European Journal of Cancer 200339(2)204-214
10Piper BF Lindsey AM amp Dodd MJ Fatigue mechanisms in cancer patients
developing nursing theory Oncology Nursing Forum 1987 14(6)17-23 11Nail LM amp Winningham ML Fatigue In S L Groenwald M H Forgge M Goodman
amp C H Yarbro (Eds) Cancer Nursing Principles and practice (4 th ed) Boston Jones and Bartlett1997
12Irvine D Vincent L Graydon JE Bubela N amp Thompson L The prevalence and
correlates of fatigue in patients receiving treatment with chemotherapy and
668
36
radiotherapy A comparison with the fatigue experienced by healthy individuals Cancer Nursing 199417(5)367-378
13Hinds PS amp Hockenberry-Eaton M Developing a research program on fatigue in
children and adloescents diagnosed with cancer Journal of Pediatric Oncology Nursing 200118(2)3-12
14Aaronson LS Teel CS Cassmeyer V Neuberger GB Pallikkathayil L Pierce J Press
AN Williams DP amp Wingate A Defining and measuring fatigue Journal of Nursing scholarship 1999 31(1)45-50
15Yeh CH Wang CH Chiang YC Lin Lamp Chien LC Assessment of symptoms reported
by 10- to 18-year-old cancer patients in Taiwan 2009 38(5)738-746 16 Okuyama T Akechi T Kugaya A Okamura H Shima Yamp Maruguchi M
Development and validation of the cancer fatigue scale a brief three-dimensional self-rating scale for assessment of fatigue in cancer patients Journal of Pain amp Symptom Management 2000 19(1) 5-14
17Gibson F Mulhall AB Richardson A Edwards JL Ream E amp Sepion BJ A
phenomenologic study of fatigue in adolescents receiving treatment for cancer Oncology Nursing Forum200532(3)651-660
18Wolfe J Grier HE Klar N Levin SB Ellenbogen JMamp Salem-Schatz S et al
Symptoms and suffering at the end of life in children with cancer New England Journal of Medicine 2000342(5)326-333
19Whiting P Bagnall AM Sowden AJ Cornell JE Mulrow CD amp Ramirez G
Interventions for the treatment and management of chronic fatigue syndrome a systematic review JAMA the Journal of the American Medical Association 2001286(11)1360-1368
20 Kangas M Bovbjerg DHamp Montgomery G H Cancer-related fatigue a systematic
and meta-analytic review of non-pharmacological therapies for cancer patients Psychological Bulletin 2008134 (5)700-741
21Williams PD Schmideskamp J Ridder EL amp Williams AR Symptom monitoring and
dependent care during cancer treatment in children pilot study Cancer Nursing 200629(3)188-197
22Takken T van der Torre P Zwerink M Hulzebos EH Bierings M Helders PJMamp van
der Net J Development feasibility and efficacy of a community-based exercise training
669
37
program in pediatric cancer survivors Psycho-Oncology 200918(4)440-448
23Keats MR amp Culos-Reed SN A community-based physical activity program for
adolescents with cancer (project TREK) program feasibility and preliminary findings
Pediatric hematology and oncology 200830(4) 272-280
24Hinds PS Hockenberry M Rai SN Zhang L Razzouk B I Cremer L McCarthy K amp
Rodriguez-Galindo C Clinical field testing of an enhanced-activity intervention in
hospitalized children with cancer Journal of Pain amp Symptom Management 2007
33(6)686-697
25Chiang YC The effects of ldquo a home-based aerobic exercise interventionrdquo on fatigue
and cardiorespiratory fitness in children with acute lymphoblastic leukemia during the
maintenance stage of chemotherapy Unpublished thesis Taiwan Tao-Yuan 2007
26Langeveld N Ubbink M amp Smets E I dont have any energy The experience of
fatigue in young adult survivors of childhood cancer European journal of oncology
nursing 20004(1)20-28
27 Kisner C Colby L Therapeutic exercise Foundations and techniques 2nd ed Philadelphia PAFA Davies 2007
670
38
Appendix I JBI Critical Appraisal Checklist for Experimental studies
Author__________ Year_________ Record Number__________________
Questions 1 to 4 must be answered ldquoyesrdquo for study to be included in the metashyanalysis
1 Were the participants randomized to study groups
Yes No Not clear
2 Other than research intervention were participants in each groups treated the same
Yes No Not clear
3 Were the outcomes measured in the same manner for all participants
Yes No Not clear
4 Were groups comparable at entry
Yes No Not clear
5 Was randomization of participants blinded
Yes No Not clear
6 Were those assessing outcome blinded to treatment allocation (if outcome not objective such as survival or length of hospitalization)
Yes No Not clear
7 Was allocation to treatment groups concealed from the allocator
Yes No Not clear
8 Was an appropriate statistical analysis used
671
39
Yes No Not clear
9 Were outcomes measured in a reliable way
Yes No Not clear
10 Was there adequate followshyup of participants
Yes No Not clear
Summary
TOTAL
Yes No Not clear
DECISION
Use Reject
Narrative summary only Further information needed
COMMENTS
672
40
Appendix II JBI Data Extraction Tool for Quantitative Studies Authors and Year
Journal Title
Record NumberArticle Reference No
Reviewer
Method
Settings
Participants
Number of participants
Group A Group B Group C
Control Intervention 1 Intervention 2
Interventions
Group A
Control
Group B
Intervention 1
Group C
Intervention 2
Outcome measures
Definition
673
41
Other outcome measures
Outcome description ScaleMeasure
Results
Dichotomous Data
Outcome Control Group
Numbertotal number
Treatment Group
Numbertotal number
Continuous Data
Authorrsquos Conclusions
Comments
Outcome Control Group
Mean amp SD
Treatment Group
Mean amp SD
674
43
Appendix III Details of included studies (N=6)(2720212223) RefNo Author(s)
(years) Title Study question Research
method Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
22 Takken T van der Torre P Zwerink M Hulzebos E H Bierings M Helders P J Mamp van der Net J (2009)
Development feasibility and efficacy of a community-based exercise training program in pediatric cancer survivors
To develop a 12-week home-based exercise training program (comprising aerobic and strength exercises) for children who survived ALL and to study itrsquos feasibility and efficacy
Pre-post test design
No comparsion group
Survived ALL(N=9)ages 6-14 years
1anthropometry 2 muscle strength 3functional mobility 4cardio-pulmonary
exercise test 5Fatigue
1 Feasibility questionnaire 2 anthropometry electronic scale and a wallmounted stadiometerHarpenden skin fold calipers 3 muscle strength handheld dynamometer 4functional mobility Timed Up
and Go test (TUG) 5cardio-pulmonary exercise test electronically braked cycle ergometer 6Fatigue(mean)CSI-20 (subjective experience of fatigueconcentrationmotivationphysical activity)
112-week exercise training program
2 Patients were assessed before (T0) and after (T1) 12 weeks of training
1 muscle strength execapacity functional moand fatigue showed nosignificant differences between pre(meanplusmnSD415plusmn147) and post training(meanplusmnSD3687)
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
7 Post-White J Fitzgerald M Savik K Hooke M C Hannahan A B amp Sencer S F (2009)
Massage therapy for children with cancer
To determine whether 4 weekly sessions of massage compared with 4 quiet-time control conditions would reduce anxiety cortisol levels fatigue nausea and pain in children with cancer undergoing chemotherapy and would reduce anxiety fatigue and mood disturbance in a parent
2-period crossover design (Randomized)
quiet-time
control
sessions
Children with cancer 1 to 18 years of age Twenty-three childrenparent dyads were enrolled 17 completed all data points
children 1relaxation 2symptoms 3 fatigue
parents
1anxiety 2 fatigue
children 1relaxation (heart and respiratory rates blood pressure and salivary cortisol level)
2symptoms (pain nausea anxiety 3 fatigue 1-2y3-6yLansky Play Performance Scale (PPS) 7-13y
1 4 weekly massage (MT) sessions alternated with 4 weekly quiet-time(QT) control sessions
2 children included presession and postsession vital signs (heart rate respiratory rate blood pressure) and self-report (parent proxy report for age 1-2 years) of pain nausea and anxiety Fatigue was measured before sessions 1 and 4 and at each follow-up Parent measures
included anxiety fatigue and mood states
1Massage was moreeffective than quiet tireducing heart rate inchildren anxiety in cless than age 14 yeaparent anxiety 2There were no sign
changes in blood pcortisol pain naufatigue (no state d
3 Children reported tmassage helped thebetter lessened theirand worries and hadlasting effects than q
675
44
14-18yChild Fatigue Scale (CFS) (frequency
intensity) 2 parents anxiety and fatigue
676
45
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
24 Hinds P S Hockenberry M Rai S N Zhang L Razzouk B I Cremer L McCarthy K amp Rodriguez-Galindo C (2007)
Clinical field testing of an enhanced-activity intervention in hospitalized children with cancer
To determine the feasibility of an
enhanced physical activity EPA intervention in children and adolescents hospitalized to receive chemotherapy for a solid tumor or AML and to assess the sleep and fatigue outcomes of the intervention using two different statistical approaches to analyze the longitudinal symptom data
randomized prospective two-site and two-group pilot study
Standard care Twenty nine patients (25 with a solid tumor and 4 with AML)ages 7-18 years
1 sleep duration 2 sleep efficiency 3 fatigue
1sleep duration sleep efficiency The
Wrist Actigraph The Daily Sleep Diary-Parent 2 fatigue (mean) The Fatigue Scale(FS-C) for 7-12 (intensity) The Fatigue Scale(FS-A) for 13-18 The Fatigue Scale Parent Version (FS-P) The Fatigue Scale Staff Version (FS-S)
1enhanced physical activity (EPA) (hospital-based 30 minutes
twice daily for 2-4 days) 2 T0On the day of admission
(Day 0 or baseline)patient and parents completed the fatigue instruments and a team member applied the actigraph Patients wore the wrist actigraph T1 from Day 0 to 2 or 3 consecutive days (Days 0e3) In addition the patient same parent and staff nurses completed the daily sleep and fatigue reports in the late afternoons of Days 1-3
1 ANOVA model slesignificantly more the experimental athe control arm whdifferences from bsleep efficiency vaaveraged and com
2 The patient-reported mean fatigue scoresarms were higher amadolescents than for
3 The mixed model anarevealed no significandifferences in patientfatigue between
the two study arms otime( no final result iSD only give mixed result)
677
46
23 Keats M
R amp Culos-Reed S N (2008)
A community-based physical activity program for adolescents with cancer (project TREK) program feasibility and preliminary findings
To examine the
feasibility of a
theoretically-based
physical activity (PA)
intervention in
adolescents with
cancerand
examination of the
impact of the
program on
participant QOL
including social
emotional and
physical
well-being(including fatigue)
Repeat measures longitudinal design
No comparsion group
10 adolescents(Lymphoma(4)leukemia(4)CNS tumor(1)germ cell tumor(1)) ages 14-18 years
1physical fitness 2quality of life (QOL) 3PA behavior 4fatigue
1 Feasibility was assessed by participant recruitment attendance and adherence
2physical fitness Fitnessgram 3quality of life (QOL) Pediatric Quality of Life Inventory (PedsQL) 4PA behavior leisure score index (LSI) 5fatigue (mean) pediatric Quality of life
Multidimensional Fatigue Scale (Peds QL-MFS)
(Generalsleepcognitive fatigue)
116week physical activity (PA)
2 total PA physical fitness and overall QOL was assessed at 5 different intervals T0 preintervention (baseline) T1midintervention (after the
first 8 wk) T2 postintervention
(16 wk) T3 3-months
postintervention T4 1-year poststudy
initiation
1 from baseline -wkssig Improvementstotal PA physfitness and Qgeneral fatigue(meanplusmnSD 796plusmn135)
2 from baseline to 3FUsig Improvin general fatigue(meanplusmnSD824plusmn131)slefatigue(meanplusmnSD755plusmn191)totafatigue(meanplusmnSD778plusmn150)
3at 1 years FUsImprovements in sleeprest fatigue(meanplusmnSD725plusmn203)total (meanplusmnSD 763plusmn
678
47
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
2 Gene R E amp Conk Z (2008)
Impact of Effective Nursing Interventions to the Fatigue Syndrome in Children Who Receive Chemotherapy
1 to examine the effects of an effective nursing intervention to the fatigue syndrome of children 7 to 12 years of age who receive chemotherapy 2Tto examine the relationship between fatigue and demographic variables (age sex) diagnoses ([ALL AML] lymphoma) and therapy-related variables (eg level of hemoglobin
experimental randomized controlled study
Routine nursing care
A total of 60 children who are 7-12 years of age(a new diagnosis of ALL AML or lymphoma and receiving for the first time after being diagnosed a 7- to 10-day chemotherapy treatment )
fatigue The Fatigue Scale(FS-C) for 7-12 (intensity)
The Fatigue Scale Parent Version (FS-P)
1 effective nursing interventions(45- 60mdaya week)education about the fatigue with the chemotherapy and fatigue handbook 2 T1 After a 7-day period the children
and parent were evaluated with the Fatigue Scale
1The difference betwthe 2 mean values wafound to be statisticallsignificant 2 statistically significadifference was found between the Fatigue Scale-Child mean scothe experimental (272the control group (4213)children
679
48
25 Chiang et
al(2007)
The effects of ldquo a home ndashbased aerobic exercise interventionrdquo on fatigue and cardiorespiratory fitness in children with Acute Lymphoblastic Leukemia during the maintenance stage of chemotherapy
To examine the effect of ldquo a home ndashbased aerobic exercise interventionrdquo on fatigue and cardiorespiratory fitness in children with Acute Lymphoblastic Leukemia during the maintenance stage of chemotherapy
Quasi-experi -mental
Routine
nursing care
14 pediatric oncology patients in the experimental group and 10 in control group who were matched by age and sex ages7-18 years
1Cardiorespiratory fitness
2Fatigue
1Cardiorespiratory fitness Physical Activity Recall
VO2maxHR peak 6MWT
2 Fatigue PedsQL-MFS(Generalsleepcognitive fatigue)
1A six-week home-based aerobic exercise intervention 2 8 time points T0 baseline T1-T6 every week during the
intervention(6 weeks) T7 post intervention T8 follow-up (one month after
the end of the home-based exercise program)
1 For intent-to ndash treatthe findings indicated are no intervention efftime differences by anon the subscale of fat2 For per-protocol angeneral fatigue( mean422plusmn402) was the osubscale that was siglower for children whothe exercise interventthose in control groupfollow-up assessmentmonth after the compintervention) 3 The VO2peak are significantly improvingexperimental group atbaseline- and post-intassessment The VO2was significantly highechildren who were in experimental group thcontrol subjects at post-intervention assefor the per-protocol an
680
49
Appendix IV Instrument used to measure fatigue
Name Instrument
developers
Description Used in
age in
ref
Reliability
Consistency of
instrument
Checklist Individual Strength
(CIS)22
Vercoulen et
al1996
20 items using 7-point Likert scale of
fatigue To measure four aspects of
fatiguesubjective experience
contractionmotivation physical
Activity
6-14 Not reported
Child Fatigue Scale (CFS)7 Hockenberry
et al2003
14 items 2 part questionnaire frequency
(yes or no) 5-point Likert scale of the
intensity of any yes responses
7-13
14-18 α073-o84
The Fatigue Scale for 7-12
year Olds (FS-C)224
Hockenberry
et al
14 items provide a fatigue intensity score
5-point Likert scale
7-12 αo84
The Fatigue Scale for 13-18
year Olds (FS-A)24
Hockenberry
et al
14 items provide a fatigue intensity score
5-point Likert scale
13-18 α076-o96
Pediatric Quality of life
Multidimensional Fatigue
Scale (Peds QL-MFS)2325
Varni2002 18 items to measure three aspects of
fatigueGeneralsleepcognitive
14-18 Not reported
681
50
Appendix V Excluded studies and reasons for exclusion
Baggott C Dodd M Kennedy C Marina N Miaskowski C Multiple Symptoms in Pediatric Oncology
Patients A Systematic Review Journal of Pediatric Oncology Nursing 2009 Nov-Dec 27(6)
325-339
Reason for exclusion Not outcome of interest
Barlow JH Ellard DR Psycho-educational interventions for children with chronic disease parents and
siblings an overview of the research evidence base Care Health amp Development 2004 Nov
30(6)637-45
Reason for exclusion Not outcome of interest
Bedider S Moyer CA Randomized controlled trials of pediatric massage A review Evid Based
Complement Alternat Med 2007 Mar 4(1)23-34 Epub 2006 Nov 3
Reason for exclusion Not outcome of interest
de Nijs EJ Ros W Grijpdonck MH Nursing intervention for fatigue during the treatment for cancer Cancer
Nursing 2008 31(3)191-206
Reason for exclusion Not population of interest
Edwards JL Gibson F Richardson A Sepion B Ream E Fatigue in adolescents with and following a
cancer diagnosis developing an evidence base for practice European Journal of Cancer 2003
Dec 39(18)2671-80
Reason for exclusion Not experimental or quasi-experimental study
Hinds PS Hockenberry-Eatan M Developing a research program on fatigue in children and adolescents
diagnosed with cancer Journal of Pediatric Oncology Nursing 2001 Mar-Apr 18(2 Suppl
1)3-12
Reason for exclusion Not experimental or quasi-experimental study
Hockenberry-Eaton M Hinds PS Alcoser P ONeill JB Euell K Howard V Gattuso J Taylor J Fatigue in
Children and Adolescents With Cancer Journal of Pediatric Oncology Nursing 1998 July
15(3)172-182
Reason for exclusion Not experimental or quasi-experimental study
Jean-Pierre P Mustian K Kohli S Roscoe JA Hickok JT Morrow GR Community-based clinical oncology
research trials for cancer-related fatigue The Journal of Supportive Oncology 2006 Nov-Dec
4(10)511-6
682
51
Reason for exclusion Not population of interest
Kangas M Bovbjerg DH Montgomery GH Cancer-Related Fatigue A Systematic and Meta-Analytic
Review of Non-Pharmacological Therapies for Cancer Patients Psychological Bulletin 2008 Sep
134(5)700-41
Reason for exclusion Not population of interest
Lotfi-Jam K Carey M Jefford M Schofield P Charleson C Aranda S Nonpharmacologic strategies for
managing common chemotherapy adverse effects A systematic review Journal of Clinical
Oncology 2008 Dec 1 26(34)5618-29 Epub 2008 Nov 3
Reason for exclusion Not outcome of interest
Marchese VG Chiarello LA Lange BJ Effects of physical therapy intervention for children with acute
lymphoblastic leukemia Pediatr Blood Cancer 2004 Feb42(2)127-33
Reason for exclusion Not outcome of interest
Meeske KA Siegel SE Globe DR Mack WJ Bernstein L Prevalence and correlates of fatigue in
long-term survivors of childhood leukemia Journal of Clinical Oncology 2005 Aug 20
23(24)5501-10
Reason for exclusion Not intervention study
Minton O Richardson A Sharpe M Hotopf Stone P A systematic review and meta-analysis of the
pharmacological treatment of cancer-related fatigue J Natl Cancer Inst 2008 Aug 20
100(16)1155-66 Epub 2008 Aug 11
Reason for exclusion Not population and intervention of interest
Mustian KM Morrow GR Carroll JK Figueroa-Moseley CD Pascal JP Williams GC Integrative
nonpharmacologic behavioral interventions for the management of Cancer-Related fatigue The
Oncologist 2007 12(1)52-67
Reason for exclusion Not population of interest
Neill J Belan I Ried K Effectiveness of non-pharmacological interventions for fatigue in adults with
multiple sclerosis rheumatoid arthritis or systemic lupus erythematosus a systematic review
Journal of Advanced Nursing 2006 Dec 56(6)617-35
Reason for exclusion Not population of interest
Rheingans JI A systematic review of nonpharmacologic adjunctive therapies for symptom management
Journal of Pediatric Oncology Nursing 2007 24(2) 81-94
683
52
Reason for exclusion Not outcome of interest
Rheingans JI Pediatric oncology nursesrsquo management of patients symptoms Journal of Pediatric
Oncology Nursing 2008 Nov 25(6) 303-11
Reason for exclusion Not outcome of interest
San Juan AF Fleck SJ Chamorro-Vintildea C Mateacute-Muntildeoz JL Moral S Peacuterez M Cardona C Del Valle MF
Hernaacutendez M Ramiacuterez M Madero L Lucia A Effects of an intrahospital exercise program
intervention for children with leukemia Medicine amp Science in Sports amp Exercise 2007 Jan
39(1)13-21
Reason for exclusion Not outcome of interest
Sanford SD Okuma JO Pan J Srivastava DK West N Farr L Hinds PS Gender differences in sleep
fatigue and daytime activity in a pediatric oncology sample receiving dexamethasone Journal of
Pediatric Psychology 2008 Apr 33(3)298-306 Epub 2007 Nov 17
Reason for exclusion Not experimental or quasi-experimental study
Schmitz KH Holtzman J Courneya KS Macircsse LC Duval S Kane R Controlled physical activity trials in
cancer survivors a systematic review and meta-analysis Cancer Epidemiol Biomarkers Prev
2005 Jul 14(7)1588-95
Reason for exclusion Not population of interest
van Brussel M Takken T Lucia A van der Net J Helders PJ Is physical fitness decreased in survivors of
childhood leukemia A systematic review Leukemia 2005 Jan 19(1)13-7
Reason for exclusion Not population of interest
Whiting P Bagnall AM Snowden AJ Cornell JE Mulrow CD Ramirez G Interventions for the treatment
and management of chronic fatigue syndrome JAMA 2001 Sep 19 286(11)1360-8
Reason for exclusion Not intervention of interest
Whitsett SF Gudmundsdottir M Davies B McCarthy P Friedman D Chemotherapy-related fatigue in
childhood cancer correlates consequences and coping strategies Journal of Pediatric
Oncology Nursing 2008 Mar-Apr 25(2)86-96 Epub 2008 Feb 29
Reason for exclusion Not experimental or quasi-experimental study
Winner C Muumlller C Hoffmann C Boos J Rosenbaum D Physical activity and childhood cancer Pediatr
Blood Cancer 2010 Apr 54(4)501-10
Reason for exclusion Not research study
684
53
Wu M Hsu L Zhang B Shen N Lu H Li S The experiences of cancer-related fatigue among Chinese
children with leukaemia A phenomenological study Journal of Nursing Studies 2010 Jan
47(1)49-59 Epub 2009 Aug 25
Reason for exclusion Not experimental or quasi-experimental study
Yeh CH Chiang YC Lin L Yang CP Chien LC Weaver MA Chuang HL Clinical factors associated with
fatigue over time in paediatric oncology patients receiving chemotherapy British Journal of
Cancer 2008 Jul 8 99(1)23-9 Epub 2008 Jun 24
Reason for exclusion Not experimental or quasi-experimental study
685
7
nutritional deficiencies activity reduction side effects of drugs (antihistamine drugs
anti-vomiting drugs and anti-anxiety drugs) and others In a study on children
adolescents parents and relevant medical and nursing staffs Hinds and
Hockenberry-Eaton (2001) 13 proposed four factors causing the fatigue of children with
cancer which are 1) environmental factors treatment setting events or situations that
place demands on the patient such as appointments inpatient stay long waiting time
altered routines that lack clear beginnings and endings of each day and decision making
and information exchange 2) personalbehavioral factors the negative faith of children
with illness 3) culturalfamilyother factors emotions concerns the hope of friends and
family ability to participate in activities and restricted activities 4) treatment-related
factors the invasive inspections experienced by children with illness insufficient time for
physical strength recovery between the repeated courses of treatments or the side
effects caused by treatments (infection pain and decrease in complete blood count) It
can be inferred that the causes of fatigue are complicated and multifaceted
Fatigue is a complex and multidimensional condition 10 therefore fatigue is subject to
different definitions and there are different measurement tools Aaronson et alrsquos14
review the literature of fatigue summarised the characteristics of fatigue measurement
including the following(1) Subjective quantification of fatigue can be determined with the
Lee and colleagues (1991) Visual Analog Scale for Fatigue (VASF)(2) Subjective
distress This item simply asks the rater to report to what degree fatigue has caused
distress (3) The effect of fatigue on activities of daily living (4) Correlates of fatigue
such as sleep and depression to assess when measuring fatigue (5) key biological
parameters such as cytokines interferon and tumor necrosis factor
640
8
Fatigue can be also measured with unidimensional or multidimensional scales The first
type of fatigue scale is not suitable for studies focusing on fatigue because they are too
long if the aim is to only assess fatigue Furthermore they only allow for a limited number
of possible responses Unidimensional scales also are not suitable for the in-depth study
of fatigue because they assess only one aspect of fatigue15
In recent years fatigue in children with cancer has received some attention and
measurement tools have gradually been developed - such as1) Checklist individual
strength (CIS) The items are scored on 7-point Likert scales (with 1 indicating best and
7 worst function) 2) The Child Fatigue Scale (CFS) is a 2-part questionnaire that asks for
a yes or no (frequency) response and a 5-point rating of the intensity of any yes
responses ranging from not at all to a lot The Fatigue Scale for 7-12 year Olds (FS-C)
is provide a fatigue intensity score higher scores indicating higher fatigue The Fatigue
Scale for 13-18 year Olds (FS-A) measure adolescent cancer patientsrsquo perceptions of
the intensity of their fatigue on a daily or weekly basis higher scores indicating higher
fatigue 3) The Fatigue Scale Parent Version (FS-P) measures the parentsrsquo perception
of their childrsquos fatigue intensity on a five-point Likert-type scale higher scores indicating
higher fatigue 4) The Fatigue Scale Staff Version (FS-S ) measures the staffrsquos
perceptions of the patientrsquos fatigue intensity during the past 24 hours Intensity ratings are
on a four-point Likert-type scale with higher scores indicating more intense fatigue
symptoms 5) The Pediatric Quality of life Multidimensional Fatigue Scale (Peds
QL-MFS)Higher scores (0 to 100) indicate less fatigue( Appendix IV)
Besides disturbing physical and mental functions and status fatigue also affects the
641
9
quality of life 15 of children with cancer and impacts their daily life16 among all different
types of cancer progress and childrsquos ages However as opposed to the fatigue of adults
the fatigue of children tends to be neglected and left untreated17 by medical and nursing
staffs
In terms of the management approach to cancer-related fatigue Ekti Gene (2008) 2
suggests that strategies could include pharmacologic and non-pharmacologic measures
NCCN (2011) 1 indicated in the Clinical Practice Guidelines in Oncology that during
aggressive treatments during long-term follow-up treatments or in the terminal phase of
cancer the intervening measures for cancer-related fatigue can be divided into
pharmacologic and non-pharmacologic measures Non-pharmacologic measures include
activity enhancement psychosocial interventions (eg cognitive behavioral therapy
(CBT) stress management relaxation support groups) attention-restoring therapy and
nutrition consultation As for the effectiveness of pharmacological measures the
effectiveness is still uncertain However there is evidence to suggest that
methylphenidate may be effective in treating cancer-related fatigue1 Whiting et al
(2001)18 included 36 randomized controlled trials and 8 controlled trails to assess the
effectiveness of the pharmacological and non-pharmacological interventions used in the
treatment or management of chronic fatigue syndrome in adults or children Results
showed insufficient evidence on the effectiveness of the pharmacological supplements
complementaryalternative and other interventions In addition the evidence of
pharmacological treatments of immunoglobulin and hydrocortisone were also
inconclusive However interventions such as cognitive behavioral therapy and graded
exercise therapy have shown promising results
642
10
The efficacy of pharmacological treatments for cancer-related fatigue has not been
established6 therefore there is a need to provide evidence-based findings of the
effectiveness of non-pharmacological interventions to support nursing intervention to
release the childrsquos cancer-related fatigue To date most studies have investigated the
effectiveness of non-pharmacological treatments on cancer-related fatigue of
adults20and to date there is no systematic review in relation to cancer-related fatigue of
children However as children are not a smaller version of adults it is inappropriate to
extrapolate the results of adults onto children Therefore there is a need to establish the
effectiveness of non-pharmacological intervention on the cancer-related fatigue of
children
Given the increase in childhood cancer survival rate the importance of decreasing
childrenrsquos cancer-related fatigue during treatments and so increase their quality of life has
become a focus of their medical teams The role of nurses during care intervention is to
confirm the major symptoms of children with illness and effectively treat each symptom to
increase the childrenrsquos quality of life21 Moreover the USA based NCCN also indicated in
the Care Standard for the Treatment of Cancer-related Fatigue of Children and
Adolescents that treatments for fatigue should be included in the health care teams and
the children and their family should be informed of relevant information The definition of
non-pharmacological interventions for childrenrsquos cancer ndashrelated fatigue include activity
enhancement (exercise physical activity) psychosocial interventions cognitive
behavioral therapy (CBT) stress management relaxation nutrition consultation
massage and educational interventions
643
11
The Cochrane Library of Systematic Reviews and The Joanna Briggs Institute Library of
Systematic Reviews were initially searched to ensure that systematic reviews on this
subject were not already published or being undertaken This initial search prior to the
commencement of the review did not yield any results
This systematic review has examined the effectiveness of non-pharmacologic
interventions on the cancer-related fatigue of children in hope of finding scientific
evidence that can support or refute such measures on children The results of this study
may serve as a reference for professional caregivers children with cancer and their
families or to be put into practice during the clinical care of children with cancer
Definition of terms
FatigueFatigue as a distressing persistent subjective sense of physical emotional
andor cognitive tiredness or exhaustion related to cancer or cancer treatments
that is not proportional to recent activity and interferes with daily function1 There
are various scales and measurements of the degree of fatiguewe have elected to
use the study authors own definitions of fatigue rather than applying a single
pre-set definition of the condition
Non-pharmacological interventionsReferring to reduce fatigue that does not involve
drugsNon-pharmacologic measures include activity enhancement psychosocial
interventions (eg cognitive behavioral therapy stress management relaxation
support groups) attention-restoring therapy and nutrition consultation1
ChemotherapyTreatment with drugs that kill cancer cells 1
644
12
Review QuestionsObjectives
Review Objective
The objective of this systematic review was to critically appraise synthesize and
present the best available evidence concerning the effects of non-pharmacological
interventions fatigue in children and adolescents with cancer
Review Question
The following specific question was addressed in this review
What is the effectiveness of non-pharmacological interventions on fatigue in
children and adolescents with cancer aged from one to 18 years
Criteria for Considering Studies for this Review
Types of studies
This review included randomised controlled trials (RCTs) and quasi-experimental
studies that examine the effectiveness of non-pharmacological intervention for fatigue in
children and adolescents with cancer
Types of participants
Children and adolescents aged from one to 18 years old experiencing fatigue
associated with cancer either during or after the chemotherapy or maintenance stage of
chemotherapy or survive stage The types of cancer to be included in this systematic
review will be ALL (Acute lymphoblastic leukemia) AML (Acute myeloid leukemia)
lymphoma and solid tumors
Exclusion criteria for Types of participants
645
13
newborn infants under 1 years of age
participants who do not have a specific diagnosis of cancer
participants who have received immunoglobulin or hydrocortisone
treatment
If participants have received immunoglobulin or hydrocortisone treatment may
inference the effectiveness of non-pharmacological interventions on fatigue
Types of intervention
This review considered studies that examine non-pharmacological interventions on
fatigue for children and adolescents with cancer including activity enhancement
(exercise physical activity) psychosocial interventions CBT stress management
relaxation nutrition consultation massage and educational interventions The
interventions descriptive included the length frequency setting and intervention
providers eg Nurse Psychologist Dietician
Exclusion criteria for types of interventions only pharmacological interventions were
tested
Types of outcome measures
The outcome measures considered were fatigue scores The literature demonstrates that
differences of opinion exist regarding the most valid and reliable method of measuring
cancer-related fatigue Therefore studies that used any validated scale for
cancer-related fatigue were considered for inclusion Currently commonly used scales to
measure fatigue include Checklist Individual Strength (CIS) Child Fatigue Scale (CFS)
The Fatigue Scale for 7-12 year Olds (FS-C) The Fatigue Scale for 13-18 year Olds
646
14
(FS-A)and Pediatric Quality of life Multidimensional Fatigue Scale (Peds QL-MFS)
Types of settings
Both hospital and community settings
Search Strategy
Before undertaking this systematic review the Cochrane Library Joanna Briggs Institute
Library of Systematic Reviews and CINAHL were searched and no systematic reviews on
this topic were found or identified as underway
The search strategy aimed to find both published and unpublished studies
A three-step search strategy was utilized in each component of this review An initial
limited search of CINAHL and MEDLINE was undertaken followed by an analysis of the
text words contained in the title and abstract and of the index terms used to describe the
article A second search using all identified keywords and index terms was undertaken
Lastly the reference lists of all identified reports and articles were searched for additional
studies
Types of languages
1 English
2 Chinese
The following databases were searched to identify keywords contained in the title and
abstract and relevant MeSH headings and descriptor terms
The Cochrane Library PsycINFO 1990 ndash 2010
647
15
Ovid MEDLINE 1966 ndash 2010 CINAHL Plus with Full Text 1960 ndash2010 EMBASE ProQuest Dissertations amp theses 1990-2010 Electronic theses and dissertations system 1956(abstract)1990(full text)-2010 MEDNAR Index to Taiwan periodical literature 1970-2010 Electronic thesis and dissertation system (Chinese) 1990-2010
Keyword search terms
1Types of studies experimental study random quasi-experimental study實驗性研究隨
機類實驗性研究
2 Types of participants childchildren adolescents pediatric cancer and oncology兒童
青少年兒科癌症腫瘤
3 Types of interventions non-pharmacological interventions massage exercise fitness
physical activity cognitive behavioral stress management energy conservation
sleep therapy relaxation distraction and psycho-education非藥物性處置按摩運動
身體活動認知行為壓力處置能量保存睡眠治療放鬆轉移注意力衛教
4 Types of outcome measures fatigue cancer-related fatigue loss of energy levels of
tiredness tired side effect symptoms疲憊癌性疲憊疲倦合併症症狀
Methods of the Review
Assessment of methodological quality Papers selected for retrieval were assessed by two independent reviewers for
methodological validity prior to inclusion in the review using the standardised critical
appraisal instruments (Appendix I) from the JBI-SUMARI (Joanna Briggs Institute
Systems for the Unified Management Assessment and Review of Information package)
Any disagreements that arise between the reviewers were resolved through discussion
648
16
with a third reviewer
Data extraction Data was extracted from papers included in the review using standardised data
extraction tool (Appendix II) from the JBI-SUMARI Details of eligible studies were
extracted and summarised independently by two reviewers
Data Synthesis
All data analysissynthesis were made using the JBI-SUMARI The studies were
assessed for clinical heterogeneity by considering the settings populations interventions
and outcomes Where possible these binary outcomes were analyzed by calculation of
the Odds Ratio with the 95 CI The weighted mean difference was calculated if the
pooled studies have used the same scale for continuous data The standardized mean
difference was calculated for continuous data measuring the same outcome on a
different scale In studies where statistical pooling of results was inappropriate the
findings were considered for inclusion as a narrative summary
Results The findings from the systematic review are presented first Followed by the results from
the meta-analysis component of this review
Description of studies From database search and hand search a total of 76 papers were identified Thirty
papers were then excluded because they did not meet the inclusion criteria Forty-six
full text were retrieved for further consideration for inclusion Of the 30 excluded reasons
for exclusion were follows 11articles were duplicated eight articles did not meet
649
17
participant inclusion criteria eight articles did not meet outcome criteria and nine articles
were correlation studies or discussion papers others articles were unclear reporting In
total after sorting six papers have been included in this article Figure 1 displays the
process used to identify relevant articles for inclusion in the systematic review
Figure 1 Stages of searching and inclusionexclusion of references for the review
Potentially relevant English-language and Chinese- language Studies Identified
Electronically and hand search (n=76)
Duplicate (n= 11) Papers excluded after evaluation of abstract (n=19)
Papers retrieved for detailed examination (N=46)
Papers excluded after review of full paper
(n=40)
Papers assessed for methodological
quality (n=6)
Papers included in systematic review
(n=6)
Methodological Quality
Of the six included articles 2722232425 two articles were RCT design224 with score 7 out
of 10 each paper from Critical Appraisal Checklist and four articles used
650
18
quasi-experimental design7222425 with socre 5 to 6 out of 10 because the quality of
the whole papers is still acceptable therefore these six articles were accepted after
primary reviewer and secondary reviewerrsquos decision
Randomisation
In two RCT articles224 one study24 used to a computer-generated program operated by
the St Jude Protocol and Data Management System to randomize the sample Another
study2 didnrsquot address how randomization was done
Allocation concealment
No studies reported allocation concealment
Intention-to-treat analysis
One quasi-experimental design7 stated Intention-to-treat analysis
Adequate follow up
The follow-up periods included 2or 3 days24 7 days2 4 week7 one month25 6 week25 12
week2216 week23 and 1 year23
Baseline comparability of groups
Three 22425 of six studies had baseline comparability in terms of age sex diagnosis
race institution duration of illness
Blinded outcome assessment
No studies used blinded outcome assessment The researchers including study team
patients staff and families were not blinded to the patientrsquos group assignment
Characteristics of included studies
651
19
There were six studies related to interventions designed to cancer-related fatigue for
pediatric patients than there are for adults There are a total of six including five
English-language papers 27222324 and one Chinese-language paper 25 ranging in year of
publication from 2007 to 2009
Patient characteristics
The research subjects of four papers included both school-aged children and
adolescents 7222324 one papers involved mainly adolescents25 and one paper sampled
only school-aged children 2 the range in ages was between six-18 years The number of
patients included in the samples ranged from nine to 60 The sources of case data were
from both outpatients and hospitalized children The types of cancer included acute
lymphoblastic leukemia (ALL) solid tumors acute myeloid leukemia (AML) and
lymphoma Overall ALL was the most commonly studied cancer type The stage of the
disease varied in these reports some patients were in the maintenance stage of
chemotherapy25 some had just received their first round of chemotherapy224 some had
completed two courses of treatments lasting 4-8 weeks each 7 and some had entered
the survivor stage 2223
Countries
Two RCTrsquos 2 24 were conducted in the USA There were four quasi-experimental design
studiesThree studies conducted in the USA7 22 23 and one in Taiwan25
Intervention types
652
20
The interventions included exercise training programs 2225 physical activity 2324
massage therapy 7 and health education 223 exercise training and physical activity as
an intervention method given in three different settings home 22 25 community 23 or
hospital 24 The studies used different types of exercise interventions including
home-based aerobic exercise use a Video Compact Disc 25 use of a bicycle-style
exerciser 24 aerobics2223 and various types of physical activities2 and strength-building
exercises 2223 The intensity of the exercise varied and often included gradual warm-up
exercises a period of main exercise and a cool down period For these studies2023 the
target exercise intensity was a heart rate of gt90 of the maximum heart rate (HR max) or
the increase in the percentage of heart rate reserve ( HRR) of 40-60
The number of weeks for the exercisephysical activity interventions duration including
2-4 days 24 6 weeks25 12 weeks22 and 16 weeks23 The frequency of exercise ranged
from 2-3 times per week to twice a day Typical duration of exercise ranged from 10 to 45
minutes There are three papers using exercise interventions based on ACSM (American
College of Sports Medicine) 2225 recommendations and one of these used an Activity
pyramid from the ACSM to determine intensity 24
One article did not clarify the type of exercise intervention or the reasons for their choices
23 In addition there was an article focusing on massage therapy 7 as an intervention in
this study the experimental group received four weeks of massage therapy either in the
clinic or in the patientrsquos room the therapy was applied by a professional masseur and
targeted the back legs arms chest stomach and face of the children However the
frequency of massage sessions per week and the duration of the massages were not
653
21
given There is another article about intervention measures combine health education
and physical activity 2 In this study patients were informed about the following (1) health
education patients received daily education about chemotherapy-related fatigue and
information from a health education manual written by the author (2) encouragement for
children to engage in activities such as listening to music drawing and reading and (3)
physical activity which involved walking along the corridors of the ward for 10-15 minutes
These health education measures were presented for 45-60 minutes a day for a total of
seven days The study design for non-pharmacological interventions used control groups
that included primarily people who had received standard treatment or people who did
not receive an exercise intervention
Outcome measures
Five measurement tools were used in this group of seven papers concerning childrenrsquos
fatigue (Appendix IV) Because those studies included both school-age children and
adolescents the following descriptions will be differentiated by age Fatigue
measurements for school-aged children with cancer include the following the Child
Fatigue Scale (CFS) 7 a scale that measures the frequency and intensity of fatigue and
the Fatigue Scale for 7-12 year Olds (FS-C) 224 a scale that can be used to evaluate the
intensity of fatigue On the other hand fatigue measurements for adolescent cancer
patients include the following the Fatigue Scale for 13-18-year-olds (FS-A) 24 a measure
that can help evaluate fatigue levels the Pediatric Quality of Life Multidimensional
Fatigue Scale (Peds QL-MFS) 2325 a tool that can be divided into three sub-scales to
understand the general cognitive and sleep rest components of fatigue and finally the
CIS-20 for school-age children and adolescents 22 a scale that measures four levels of
654
22
fatigue namely subjective experience attention motivation and physical activity Two
studies used the Peds QL-MFS scale to measure fatigue2325
Meta-analysis results Two studies of the included papers failed to provide sufficient raw data they could not be
included in the meta-analysis Hinds et al 24 did not include post-test data Genc et al 2
provided no pre-test data PostWhite et al7 reported that fatigue after the health
education intervention was not statistically different but they presented the results
without presenting fatigue-related data Therefore the meta-analysis included three
studies 222325
The heterogeneity of studies was analyzed with Chi square statistics and no statistical
significance was found Therefore the data was combined in meta-analysis according to
exercise intervention on fatigue In addition there were three articles using the Peds
QL-MFS as a research tool to examine childrenrsquos improvements in fatigue Among these
Keats 22 and Chiang 24 present the effectiveness of exercise interventions using three
subscales Therefore the meta-analysis also analysis of the effects of these exercise
intervention measures on three subscales of Peds QL-MFS general fatigue sleep rest
fatigue and cognitive fatigue
The effectiveness of exercise intervention for fatigue We analyzed the exercise intervention effect on fatigue A total of 2 studies 22 23 were
included Takken et al 22 used community-based exercise training program to reduce
fatigue of children 6 to 14 years (mean 93y) of age who survived ALL Fatigue
measurement by Checklist Individual Strength (CIS) after 12-week of training fatigue
655
23
show no significant differences between pre (meanplusmnSD 415plusmn147) and post training
(meanplusmnSD368plusmn217) but fatigue change from baseline mean reduction of 11
Keats et al23 although used community-based physical activity program to reduce fatigue
for adolescents 14 to 18 years of age (mean162 y) with cancer (Lymphoma leukemia CNS
tumor germ cell tumor) Studies used fatigue by PedsQLMFS Results show general fatigue
from baseline to 8 weeks and to 3 months follow up significantly improves General
fatigue sleeprest fatigue and total fatigue from baseline to 3 months follow up showed
significant improvements Sleeprest fatigue and total fatigue at 1 years followed up were
significant improvements
Figure 2 shows the overall effect of exercise intervention in children and adolescents with
cancers with a focus on improving fatigue Due to the lower heterogeneity (p>005) the
fixed effects model was used to pool the data for meta-analysis (Overall effect size=
-006 95 Confidence Interval (CI) -070 to 058) A result did not indicate a statistically
significant difference (p = 087)
656
24
Figure2 Meta-analysis results of exercise intervention on fatigue
In addition Keats23 and Chiang25 used the three sub-scales of Peds QL-MFS to
determine the general cognitive and sleep rest components of fatigue The following
present the effectiveness of exercise interventions using three subscales including
general fatigue sleep rest fatigue and cognitive fatigue 2325
Chiang et al 25 used a 6- week home-based aerobic exercise intervention to reduce
fatigue of children 7 to 18 years (mean age at experimental group was 1088 y in control
group was 1247 y) of age who with acute lymphoblastic leukemia Fatigue measurement
by Peds QL-MFS after training For intent-to ndash treat analysis the findings indicated that
there are no intervention effects and time differences by any items on the subscale of
fatigue For per-protocol analysis general fatigue( meanplusmnSD 422plusmn402) was the only
subscale that was significantly lower for children who received the exercise intervention
than those in control group at follow-up assessment (one month after the completion of
intervention)
Keats et al23 although used community-based physical activity program to reduce fatigue
for adolescents 14 to 18 years of age (mean162 y) with cancer (Lymphoma leukemia
CNS tumor germ cell tumor) Both studies used fatigue by PedsQLMFS Results show
general fatigue from baseline to 8 weeks and to 3 months follow up significantly improves
657
25
General fatigue sleeprest fatigue and total fatigue from baseline to 3 months follow up
showed significant improvements Sleeprest fatigue and total fatigue at 1 years followed
up were significant improvements
The effectiveness of exercise intervention for general fatigue
The impact of the exercise interventions upon levels of general fatigue was also analysed
The heterogeneity was low (p>005) Therefore the fixed effects model was used to
examine the effectiveness The effect size is -076 indicating a statistically significant
difference (p = 001 95 CI -135 to -017 Fig 3) The evidence suggests that exercise
intervention can reduce general fatigue in children with cancer
Fig 3 Meta-analysis results of exercise intervention for general fatigue
The effectiveness of exercise intervention for sleep rest fatigue
The following is the result of the meta-analysis of the effectiveness of exercise
interventions on sleep rest fatigue First the heterogeneity test was conducted with P gt
005 representing small heterogeneity and the fixed effects model was used Fig 4
shows the effect size is -035 indicating no statistically significant differences (p = 023
95 CI-092 to 022 Fig 4)
658
26
Fig 4 Meta-analysis results of exercise intervention for sleep rest fatigue
The effectiveness of exercise intervention for cognitive fatigue Lastly the following data reports the results of meta-analysis of the effectiveness of
exercise interventions for cognitive fatigue The heterogeneity was p>005 then the
fixed effects model was used The effect size is -035 indicating no statistically significant
differences (p = 024 95 CI-092 023 Fig 5)
Fig 5 Meta-analysis results of exercise intervention for cognitive fatigue
Narrative presentation of remaining included studies
Three studies were not included in meta-analysis Post-White et al7 one of the aims in
this study was to examine the effect of massage therapy on fatigue in children with
cancer The study was a quasi-experimental design Twenty-three childrenparent dyads
were enrolled 17completed all data points Children with cancer ages 7 to 18 years
received at least 2 identical cycles of chemotherapy and one parent participated in the
2-period crossover design in which 4 weekly massage sessions (MT) alternated with 4
659
27
weekly quiet-time (QT) control sessions There were no significant changes in fatigue in
children over the 4-week MT or QT conditions either independently (change over time) or
when we compared fatigue by condition
The lack of effect of massage on fatigue may be the difficulty some children had in
differentiating fatigue from being relaxed underscores the challenge of measuring fatigue
in children Some children interpreted being tired or relaxed as having greater fatigue
because they felt like lying around and sleeping or felt unmotivated to do their usual
activities all measures of fatigue in the instrument used in the study
Hinds et al24conducted a prospective two-site randomized controlled pilot study to
assess the feasibility of an enhanced physical activity (EPA) intervention in hospitalized
children and adolescents receiving treatment for a solid tumor or for acute myeloid
leukemia (AML) Twenty-nine patients (25 with a solid tumor and 4 with AML) participated
age range from 736 to 1816 (mean 1248 y) The EPA intervention selected was
pedaling a stationary bicycle-style exerciser (Chattanooga Peddler Deluxe Bio-Teck
Medical Memphis TN) for 30 minutes twice daily for 2 to 4 days of hospitalization The
mixed model analysis revealed no significant differences in patient reports of fatigue
between the two study arms or over time
Genc et al2 conducted a RCT involving children with cancer who are 7 to 12 years of age
and receiving chemotherapy treatment to determine the impact of educational
intervention by nurses on decreasing the fatigue syndrome The research sample was
composed of a total of 60 children with cancer with 30 children being included in the
660
28
experimental group (mean age 923)and 30 children included in the control group (mean
age 937) with their mothers In the experimental group after the 7th to 10th day of the
chemotherapy treatment throughout a week the researcher conducted the nursing
interventions every day for 45 to 60 minutes In the control group routine nursing
interventions were carried out The experimental group received education about the
fatigue with the chemotherapy and fatigue handbook was given which was developed by
the authors Children and mothers were consulted for including activities that could
decrease fatigue which were described as effective interventions A statistically
significant difference was found between the Fatigue Scale-Child mean scores of the
experimental (2723) and the control group (4213) The results suggest that fatigue of
children with cancer can be reduced by implementing appropriate nursing interventions
(t=567 Plt00)
Discussion The purpose of this systematic review was to determine the effectiveness of
non-pharmacological interventions specifically targeting fatigue for children and
adolescents with cancer undergoing chemotherapy or after receiving chemotherapy
Included articles about the effectiveness of non-pharmacological interventions for
children and adolescents with cancer were published between the years of 2007 and
2009 Although interventions for cancer fatigue for adults have been extensively studied
it can be seen from either the title of the paper or related content that an intervention
study on children was a pilot study or a feasibility study Representing a field in its early
stage these studies show that the fatigue issues with young cancer patients have only
recently been taken seriously
661
29
The results of our meta-analysis include measurement of the four performance indicators
fatigue and general fatigue sleep rest fatigue and cognitive fatigue The results show
that there is a statistically significant difference only in the domain of general fatigue
using an exercise intervention for children with cancer can improve the degree of fatigue
with the effect size reaching 0671 Other results do not indicate significant differences
The reasons may include the following
1 Characteristics of the cancer The exhaustion from cancer occurs not only during cancer treatment but also in during
long-term survival a time during which patients may continue to be affected by this
symptom 8 26 Therefore when using intervention measures to improve fatigue
circumstances should be considered such as the process of the treatment and the course
or stage of the disease Because cancer patients will experience different forms of
treatment or courses of treatment the disease itself or treatment differences should be
considered in the choice of intervention Even chemotherapy drugs should be taken into
consideration For example a period of general steroid treatment can increase patientsrsquo
fatigue In those studies of children with cancer few studies looked solely at one type of
cancer most studies included a variety of cancer patients Furthermore most studies do
not clearly explain the stage of the disease or course of treatment and most do not
include treatment variables in the control group Moreover children with cancer may
have different levels of physical function
2 Research design The sample size Currently there are few studies with large sample size and a rigorous
RCT design due to the small number of papers available for analysis The sample size
included in our studyrsquos data analysis is between 20 and 42 people this small sample size
will affect the power available to evaluate outcome variables
Although most of the non-pharmacological interventions still use exercise and physical
activity and these studies overall show better results for fatigue as compared with
controls more research is still needed to further confirm the efficacy of these findings
662
30
The dropout rate in the evaluated research varies a great deal ranging from 5 to 45
these dropout rates may result from the characteristics of the research subjects or the
lengthy time involved in participating in these studies The research data with a high
turnover rate might not reflect the actual outcomes of participation in exercise and the
quality of the research contained in articles with high subject turnover rates may be
lower
Exercise doses and time The exercise doses needed to reduce fatigue cannot be
determined additionally the amount of exercise completed by the patient is also
inconsistent interventions vary between 2-3 times per week and two times a day and
exercise duration varies between 10 and 45 minutes each time Furthermore the study
interventions vary in length between a couple of days and a long period of 16 weeks The
data collection times are different some were measured 12 weeks after the intervention
began some were measured during the 6 weeks of intervention some were measured
three months after the intervention was finished and some were measured after one
year
In addition disease-related symptoms decrease childrenrsquos willingness to participate in
exercise interventions inappropriate exercise intervention programs may actually
increase childrens fatigue In addition the children in the study are still developing
physically it is important to consider ways to design an interesting exercise intervention
to increase the compliance of patients in order to improve the effectiveness Although
intervention programs in the hospital or in a community sports center can improve the
effectiveness because they provide supervision the feasibility of these programs is
questionable However if the program is home-based the children need to be
supervised by parents in order to improve their compliance in doing the exercises
Furthermore regarding the nature of the intervention the results from this study indicate
that the researched non-pharmacological interventions include the following exercise
training programs physical activity massage therapy and health education interventions
However according to the National Comprehensive Cancer Network 1 clinical guidelines
663
31
for cancer non-drug measures for cancer fatigue can be separated into five categories
(1) activity enhancement (2) psychosocial interventions such as cognitive behavioral
therapy (CBT) stress management relaxation techniques and support groups (3)
attention-restoring therapy (4) nutritional consultation and (5) cognitive behavioral
therapy specifically targeting sleep disturbance Researchers have also suggested that
psychosocial interventions should be included in the future research for children with
cancer-related fatigue 22
(2) The measurement tools in the study The assessment of fatigue can be
one-dimensional or multidimensional One-dimensional assessment can help understand
the severity of fatigue symptoms however multidimensional scales are often more
credible Therefore when measuring cancer-related fatigue researchers should consider
whether there is a uniform definition of fatigue or a standardized tool for measuring
fatigue in order to facilitate further systematic meta-analyses and further develop the
clinical care guidelines
Limitations of the review The present review has some potential limitations First the low methodological quality
may influence the result Although exercise intervention seems promising quality of the
RCTs was generally quite low Future studies require better design and reporting if
methodological issues to establish evidence-based nonpharmcologic intervention
Second the identified studies covered only a limited types of nonpharmcological
intervention especially in exercise intervention The guidelines for cancer-related fatigue
in NCCN (2011)1 referred to more interventions than the ones included in this review
such as cognitive behavioral therapy and nutrition consultation Thirdly the small sample
size and effect size could be potentially having led to underpowered approach for
detecting the effects on fatigue Therefore we recommend that as research continues to
grow a re-analysis can be undertaken Fourthly Combining data in meta analysis from
664
32
studies where the ages were quite different is a potential source of heterogeneity and
may affect the interpretation of the results
Conclusion At present clinical treatment is widely used for cancer patients However child and
adolescent cancer patients often experience various side effects which cause short-term
or long-term discomfort both physically and psychologically In particular with the
increasing cure rate cancer related fatigue during or after treatment has become an
important issue This study result provided positive effect of exercise intervention on
general fatigue
Implications for practice The results of this systematic review and meta-analysis show that exercise interventions
can effectively improve the level of general fatigue In particular although the articles
were self-reported feasibility studies their results all indicate that exercise interventions
for fatigue are feasible and safe there was no conclusion to be made for the use of
massage therapy or health education measures because there was only one article for
each of these interventions
Recommendations for practice
Cancer-related fatigue is one of the most severe and frequent symptoms by pediatric
oncology children and adolescent suffered during treatment and the symptom existed
even after treatment has ended Until now no golden standard of treatment to fatigue is
established The findings call for more attention to how to reduce patientrsquos levels of
fatigue Based on the available information evaluated in this review the following
recommendations for practice are provided
665
33
bull For children aged 7 to 18 who has cancer (eg Lymphoma leukemia CNS tumor
germ cell tumor) an effective progressive aerobic exercise program is recommended to
be at least 2-3 times per week 20 to 45 minute for each session and last for 6-16 weeks
in order to reduce their general fatigue (tiredness physically weakness) In addition
adults should be involved in accompanying children while they are performing physical
exercise of which should be able to improve the adherence rate (level 2 ) ( Grade of
recommendation A)
bull For children aged 7 to 18 who has cancer (eg Lymphoma leukemia CNS tumor
germ cell tumor) an progressive aerobic exercise program will not be effective to reduce
their sleep andor rest (sleeping or resting a lot) or cognitive fatigue (problems with
thinking quickly or problems with remembering) (level 2 ) ( Grade of recommendation C)
bull Nursing interventions in educating treatment of fatigue include information about
activity nutrition energy preservation consulting and providing a useful fatigue
handbook will benefit those children who are 7 to 12 years have a new diagnosis of ALL
AML or lymphoma and receive for the first time after being diagnosed a 7- to 10-day
chemotherapy treatment (level 2) ( Grade of recommendation A)
bull A 4-week massage therapy program (the therapists massage childrenrsquos back legs
arms stomachchest and face) is not effective for children who are aged 7 to 18 and
have acute lymphoblastic leukemia brain tumors lymphoma rhabdomyosarcoma
Wilms tumor or Ewing sarcoma(level 2)( Grade of recommendation C)
bull Using a 12-week aerobic and strength exercise (45-min exercise sessions twice a
week) is not effective for children who are aged 6-14 and survived acute lymphoblaststic
leukemia age from 6 to 14(level 2) ( Grade of recommendation C)
bull Using a physical activity intervention (30minutestwice daily for 2-4days) is not
effective for children who are 7 to 18 years of age with soild tumor or AML(level 2)
( Grade of recommendation C)
666
34
Implications for research According to this systematic review and meta-analysis results there are suggestions to
improve the effectiveness of future research on non-pharmacological interventions for
children and young peoplersquos cancer-related fatigue
As the majority of included non-pharmacological interventions for the fatigue of cancer
patients consist of exercise programs future research should also consider various
non-pharmacological interventions in order to understand the effectiveness of different
methods
Regarding the exercise intervention methods and studies should consider multiple
factors including the age or personal condition of the subject the disease stage and the
amount of daily activities Studies should use design prescriptions (eg frequency
intensity duration and type of exercise) and consider the adherence to the measures in
order to enhance the study strength
In measuring the results of non-pharmacological interventions there should be standard
definitions or standard measurement tools to facilitate the following systematic review
and meta-analysis that can subsequently be developed into clinical care guidelines
Reviewing the effectiveness of the current non-pharmacological management of children
and adolescent cancer patients there is still a lack of rigorous RCT research Limited by
the characteristics of cancer there is still a lack of large sample sizes
Potential conflicts of interest There is no conflict of interest
Acknowledgements
Thank you to Dr Rie Konno Research Fellow Joanna Briggs Institute for her help in
assessing studies
667
35
References 1 National Comprehensive Cancer Network( NCCN) in USA NCCN clinical practice
guideline in oncology cancer-related fatigue 2011 2 Ekti Genc R amp Conk Z Impact of effective nursing interventions to the fatigue
syndrome in children who receive chemotherapy Cancer Nursing 200831(4)312-317
3 Childhood Cancer Foundation of ROC (2009March) The classification of diseases
and age sex statistical tables of case Childhood Cancer Foundation of ROC newsletter103105-106
4 Department of Health Executive Yuan ROC (TAIWAN)(2009 March 20)2009 cause of death statistic Health and National Health Insurance Annual Statistics Information Service 2010 June 28Available httpwwwdohgovtwstatisticdatavital statists9898health statistic--lifepdf
5 Chang TK (2007December 8) Common childhood cancer and its treatment Status
Childhood Cancer Foundation of ROC (TAIWAN) 2010 September 23 Available httpwwwccfrocorgtwchildchild_events_readphpe_id=45
6 Hockenberry MJ amp Wilson D Wongs nursing care of infants and children (8th ed) St
Louis MO Mosby 2007
7 Post-White J Fitzgerald M Savik K Hooke MC Hannahan AB amp Sencer SF
Massage therapy for children with cancer Journal of Pediatric Oncology Nursing 2009 26(1)16-28
8Chiang YC Yeh CH Wang WKamp Yang CP The experience of cancer-related fatigue
in Taiwanese children European Journal of Cancer Care 2009 18(1)43-49 9Langeveld NE Grootenhuis M A Voute P A de Haan RJ amp van den Bos C No excess
fatigue in young adult survivors of childhood cancer European Journal of Cancer 200339(2)204-214
10Piper BF Lindsey AM amp Dodd MJ Fatigue mechanisms in cancer patients
developing nursing theory Oncology Nursing Forum 1987 14(6)17-23 11Nail LM amp Winningham ML Fatigue In S L Groenwald M H Forgge M Goodman
amp C H Yarbro (Eds) Cancer Nursing Principles and practice (4 th ed) Boston Jones and Bartlett1997
12Irvine D Vincent L Graydon JE Bubela N amp Thompson L The prevalence and
correlates of fatigue in patients receiving treatment with chemotherapy and
668
36
radiotherapy A comparison with the fatigue experienced by healthy individuals Cancer Nursing 199417(5)367-378
13Hinds PS amp Hockenberry-Eaton M Developing a research program on fatigue in
children and adloescents diagnosed with cancer Journal of Pediatric Oncology Nursing 200118(2)3-12
14Aaronson LS Teel CS Cassmeyer V Neuberger GB Pallikkathayil L Pierce J Press
AN Williams DP amp Wingate A Defining and measuring fatigue Journal of Nursing scholarship 1999 31(1)45-50
15Yeh CH Wang CH Chiang YC Lin Lamp Chien LC Assessment of symptoms reported
by 10- to 18-year-old cancer patients in Taiwan 2009 38(5)738-746 16 Okuyama T Akechi T Kugaya A Okamura H Shima Yamp Maruguchi M
Development and validation of the cancer fatigue scale a brief three-dimensional self-rating scale for assessment of fatigue in cancer patients Journal of Pain amp Symptom Management 2000 19(1) 5-14
17Gibson F Mulhall AB Richardson A Edwards JL Ream E amp Sepion BJ A
phenomenologic study of fatigue in adolescents receiving treatment for cancer Oncology Nursing Forum200532(3)651-660
18Wolfe J Grier HE Klar N Levin SB Ellenbogen JMamp Salem-Schatz S et al
Symptoms and suffering at the end of life in children with cancer New England Journal of Medicine 2000342(5)326-333
19Whiting P Bagnall AM Sowden AJ Cornell JE Mulrow CD amp Ramirez G
Interventions for the treatment and management of chronic fatigue syndrome a systematic review JAMA the Journal of the American Medical Association 2001286(11)1360-1368
20 Kangas M Bovbjerg DHamp Montgomery G H Cancer-related fatigue a systematic
and meta-analytic review of non-pharmacological therapies for cancer patients Psychological Bulletin 2008134 (5)700-741
21Williams PD Schmideskamp J Ridder EL amp Williams AR Symptom monitoring and
dependent care during cancer treatment in children pilot study Cancer Nursing 200629(3)188-197
22Takken T van der Torre P Zwerink M Hulzebos EH Bierings M Helders PJMamp van
der Net J Development feasibility and efficacy of a community-based exercise training
669
37
program in pediatric cancer survivors Psycho-Oncology 200918(4)440-448
23Keats MR amp Culos-Reed SN A community-based physical activity program for
adolescents with cancer (project TREK) program feasibility and preliminary findings
Pediatric hematology and oncology 200830(4) 272-280
24Hinds PS Hockenberry M Rai SN Zhang L Razzouk B I Cremer L McCarthy K amp
Rodriguez-Galindo C Clinical field testing of an enhanced-activity intervention in
hospitalized children with cancer Journal of Pain amp Symptom Management 2007
33(6)686-697
25Chiang YC The effects of ldquo a home-based aerobic exercise interventionrdquo on fatigue
and cardiorespiratory fitness in children with acute lymphoblastic leukemia during the
maintenance stage of chemotherapy Unpublished thesis Taiwan Tao-Yuan 2007
26Langeveld N Ubbink M amp Smets E I dont have any energy The experience of
fatigue in young adult survivors of childhood cancer European journal of oncology
nursing 20004(1)20-28
27 Kisner C Colby L Therapeutic exercise Foundations and techniques 2nd ed Philadelphia PAFA Davies 2007
670
38
Appendix I JBI Critical Appraisal Checklist for Experimental studies
Author__________ Year_________ Record Number__________________
Questions 1 to 4 must be answered ldquoyesrdquo for study to be included in the metashyanalysis
1 Were the participants randomized to study groups
Yes No Not clear
2 Other than research intervention were participants in each groups treated the same
Yes No Not clear
3 Were the outcomes measured in the same manner for all participants
Yes No Not clear
4 Were groups comparable at entry
Yes No Not clear
5 Was randomization of participants blinded
Yes No Not clear
6 Were those assessing outcome blinded to treatment allocation (if outcome not objective such as survival or length of hospitalization)
Yes No Not clear
7 Was allocation to treatment groups concealed from the allocator
Yes No Not clear
8 Was an appropriate statistical analysis used
671
39
Yes No Not clear
9 Were outcomes measured in a reliable way
Yes No Not clear
10 Was there adequate followshyup of participants
Yes No Not clear
Summary
TOTAL
Yes No Not clear
DECISION
Use Reject
Narrative summary only Further information needed
COMMENTS
672
40
Appendix II JBI Data Extraction Tool for Quantitative Studies Authors and Year
Journal Title
Record NumberArticle Reference No
Reviewer
Method
Settings
Participants
Number of participants
Group A Group B Group C
Control Intervention 1 Intervention 2
Interventions
Group A
Control
Group B
Intervention 1
Group C
Intervention 2
Outcome measures
Definition
673
41
Other outcome measures
Outcome description ScaleMeasure
Results
Dichotomous Data
Outcome Control Group
Numbertotal number
Treatment Group
Numbertotal number
Continuous Data
Authorrsquos Conclusions
Comments
Outcome Control Group
Mean amp SD
Treatment Group
Mean amp SD
674
43
Appendix III Details of included studies (N=6)(2720212223) RefNo Author(s)
(years) Title Study question Research
method Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
22 Takken T van der Torre P Zwerink M Hulzebos E H Bierings M Helders P J Mamp van der Net J (2009)
Development feasibility and efficacy of a community-based exercise training program in pediatric cancer survivors
To develop a 12-week home-based exercise training program (comprising aerobic and strength exercises) for children who survived ALL and to study itrsquos feasibility and efficacy
Pre-post test design
No comparsion group
Survived ALL(N=9)ages 6-14 years
1anthropometry 2 muscle strength 3functional mobility 4cardio-pulmonary
exercise test 5Fatigue
1 Feasibility questionnaire 2 anthropometry electronic scale and a wallmounted stadiometerHarpenden skin fold calipers 3 muscle strength handheld dynamometer 4functional mobility Timed Up
and Go test (TUG) 5cardio-pulmonary exercise test electronically braked cycle ergometer 6Fatigue(mean)CSI-20 (subjective experience of fatigueconcentrationmotivationphysical activity)
112-week exercise training program
2 Patients were assessed before (T0) and after (T1) 12 weeks of training
1 muscle strength execapacity functional moand fatigue showed nosignificant differences between pre(meanplusmnSD415plusmn147) and post training(meanplusmnSD3687)
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
7 Post-White J Fitzgerald M Savik K Hooke M C Hannahan A B amp Sencer S F (2009)
Massage therapy for children with cancer
To determine whether 4 weekly sessions of massage compared with 4 quiet-time control conditions would reduce anxiety cortisol levels fatigue nausea and pain in children with cancer undergoing chemotherapy and would reduce anxiety fatigue and mood disturbance in a parent
2-period crossover design (Randomized)
quiet-time
control
sessions
Children with cancer 1 to 18 years of age Twenty-three childrenparent dyads were enrolled 17 completed all data points
children 1relaxation 2symptoms 3 fatigue
parents
1anxiety 2 fatigue
children 1relaxation (heart and respiratory rates blood pressure and salivary cortisol level)
2symptoms (pain nausea anxiety 3 fatigue 1-2y3-6yLansky Play Performance Scale (PPS) 7-13y
1 4 weekly massage (MT) sessions alternated with 4 weekly quiet-time(QT) control sessions
2 children included presession and postsession vital signs (heart rate respiratory rate blood pressure) and self-report (parent proxy report for age 1-2 years) of pain nausea and anxiety Fatigue was measured before sessions 1 and 4 and at each follow-up Parent measures
included anxiety fatigue and mood states
1Massage was moreeffective than quiet tireducing heart rate inchildren anxiety in cless than age 14 yeaparent anxiety 2There were no sign
changes in blood pcortisol pain naufatigue (no state d
3 Children reported tmassage helped thebetter lessened theirand worries and hadlasting effects than q
675
44
14-18yChild Fatigue Scale (CFS) (frequency
intensity) 2 parents anxiety and fatigue
676
45
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
24 Hinds P S Hockenberry M Rai S N Zhang L Razzouk B I Cremer L McCarthy K amp Rodriguez-Galindo C (2007)
Clinical field testing of an enhanced-activity intervention in hospitalized children with cancer
To determine the feasibility of an
enhanced physical activity EPA intervention in children and adolescents hospitalized to receive chemotherapy for a solid tumor or AML and to assess the sleep and fatigue outcomes of the intervention using two different statistical approaches to analyze the longitudinal symptom data
randomized prospective two-site and two-group pilot study
Standard care Twenty nine patients (25 with a solid tumor and 4 with AML)ages 7-18 years
1 sleep duration 2 sleep efficiency 3 fatigue
1sleep duration sleep efficiency The
Wrist Actigraph The Daily Sleep Diary-Parent 2 fatigue (mean) The Fatigue Scale(FS-C) for 7-12 (intensity) The Fatigue Scale(FS-A) for 13-18 The Fatigue Scale Parent Version (FS-P) The Fatigue Scale Staff Version (FS-S)
1enhanced physical activity (EPA) (hospital-based 30 minutes
twice daily for 2-4 days) 2 T0On the day of admission
(Day 0 or baseline)patient and parents completed the fatigue instruments and a team member applied the actigraph Patients wore the wrist actigraph T1 from Day 0 to 2 or 3 consecutive days (Days 0e3) In addition the patient same parent and staff nurses completed the daily sleep and fatigue reports in the late afternoons of Days 1-3
1 ANOVA model slesignificantly more the experimental athe control arm whdifferences from bsleep efficiency vaaveraged and com
2 The patient-reported mean fatigue scoresarms were higher amadolescents than for
3 The mixed model anarevealed no significandifferences in patientfatigue between
the two study arms otime( no final result iSD only give mixed result)
677
46
23 Keats M
R amp Culos-Reed S N (2008)
A community-based physical activity program for adolescents with cancer (project TREK) program feasibility and preliminary findings
To examine the
feasibility of a
theoretically-based
physical activity (PA)
intervention in
adolescents with
cancerand
examination of the
impact of the
program on
participant QOL
including social
emotional and
physical
well-being(including fatigue)
Repeat measures longitudinal design
No comparsion group
10 adolescents(Lymphoma(4)leukemia(4)CNS tumor(1)germ cell tumor(1)) ages 14-18 years
1physical fitness 2quality of life (QOL) 3PA behavior 4fatigue
1 Feasibility was assessed by participant recruitment attendance and adherence
2physical fitness Fitnessgram 3quality of life (QOL) Pediatric Quality of Life Inventory (PedsQL) 4PA behavior leisure score index (LSI) 5fatigue (mean) pediatric Quality of life
Multidimensional Fatigue Scale (Peds QL-MFS)
(Generalsleepcognitive fatigue)
116week physical activity (PA)
2 total PA physical fitness and overall QOL was assessed at 5 different intervals T0 preintervention (baseline) T1midintervention (after the
first 8 wk) T2 postintervention
(16 wk) T3 3-months
postintervention T4 1-year poststudy
initiation
1 from baseline -wkssig Improvementstotal PA physfitness and Qgeneral fatigue(meanplusmnSD 796plusmn135)
2 from baseline to 3FUsig Improvin general fatigue(meanplusmnSD824plusmn131)slefatigue(meanplusmnSD755plusmn191)totafatigue(meanplusmnSD778plusmn150)
3at 1 years FUsImprovements in sleeprest fatigue(meanplusmnSD725plusmn203)total (meanplusmnSD 763plusmn
678
47
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
2 Gene R E amp Conk Z (2008)
Impact of Effective Nursing Interventions to the Fatigue Syndrome in Children Who Receive Chemotherapy
1 to examine the effects of an effective nursing intervention to the fatigue syndrome of children 7 to 12 years of age who receive chemotherapy 2Tto examine the relationship between fatigue and demographic variables (age sex) diagnoses ([ALL AML] lymphoma) and therapy-related variables (eg level of hemoglobin
experimental randomized controlled study
Routine nursing care
A total of 60 children who are 7-12 years of age(a new diagnosis of ALL AML or lymphoma and receiving for the first time after being diagnosed a 7- to 10-day chemotherapy treatment )
fatigue The Fatigue Scale(FS-C) for 7-12 (intensity)
The Fatigue Scale Parent Version (FS-P)
1 effective nursing interventions(45- 60mdaya week)education about the fatigue with the chemotherapy and fatigue handbook 2 T1 After a 7-day period the children
and parent were evaluated with the Fatigue Scale
1The difference betwthe 2 mean values wafound to be statisticallsignificant 2 statistically significadifference was found between the Fatigue Scale-Child mean scothe experimental (272the control group (4213)children
679
48
25 Chiang et
al(2007)
The effects of ldquo a home ndashbased aerobic exercise interventionrdquo on fatigue and cardiorespiratory fitness in children with Acute Lymphoblastic Leukemia during the maintenance stage of chemotherapy
To examine the effect of ldquo a home ndashbased aerobic exercise interventionrdquo on fatigue and cardiorespiratory fitness in children with Acute Lymphoblastic Leukemia during the maintenance stage of chemotherapy
Quasi-experi -mental
Routine
nursing care
14 pediatric oncology patients in the experimental group and 10 in control group who were matched by age and sex ages7-18 years
1Cardiorespiratory fitness
2Fatigue
1Cardiorespiratory fitness Physical Activity Recall
VO2maxHR peak 6MWT
2 Fatigue PedsQL-MFS(Generalsleepcognitive fatigue)
1A six-week home-based aerobic exercise intervention 2 8 time points T0 baseline T1-T6 every week during the
intervention(6 weeks) T7 post intervention T8 follow-up (one month after
the end of the home-based exercise program)
1 For intent-to ndash treatthe findings indicated are no intervention efftime differences by anon the subscale of fat2 For per-protocol angeneral fatigue( mean422plusmn402) was the osubscale that was siglower for children whothe exercise interventthose in control groupfollow-up assessmentmonth after the compintervention) 3 The VO2peak are significantly improvingexperimental group atbaseline- and post-intassessment The VO2was significantly highechildren who were in experimental group thcontrol subjects at post-intervention assefor the per-protocol an
680
49
Appendix IV Instrument used to measure fatigue
Name Instrument
developers
Description Used in
age in
ref
Reliability
Consistency of
instrument
Checklist Individual Strength
(CIS)22
Vercoulen et
al1996
20 items using 7-point Likert scale of
fatigue To measure four aspects of
fatiguesubjective experience
contractionmotivation physical
Activity
6-14 Not reported
Child Fatigue Scale (CFS)7 Hockenberry
et al2003
14 items 2 part questionnaire frequency
(yes or no) 5-point Likert scale of the
intensity of any yes responses
7-13
14-18 α073-o84
The Fatigue Scale for 7-12
year Olds (FS-C)224
Hockenberry
et al
14 items provide a fatigue intensity score
5-point Likert scale
7-12 αo84
The Fatigue Scale for 13-18
year Olds (FS-A)24
Hockenberry
et al
14 items provide a fatigue intensity score
5-point Likert scale
13-18 α076-o96
Pediatric Quality of life
Multidimensional Fatigue
Scale (Peds QL-MFS)2325
Varni2002 18 items to measure three aspects of
fatigueGeneralsleepcognitive
14-18 Not reported
681
50
Appendix V Excluded studies and reasons for exclusion
Baggott C Dodd M Kennedy C Marina N Miaskowski C Multiple Symptoms in Pediatric Oncology
Patients A Systematic Review Journal of Pediatric Oncology Nursing 2009 Nov-Dec 27(6)
325-339
Reason for exclusion Not outcome of interest
Barlow JH Ellard DR Psycho-educational interventions for children with chronic disease parents and
siblings an overview of the research evidence base Care Health amp Development 2004 Nov
30(6)637-45
Reason for exclusion Not outcome of interest
Bedider S Moyer CA Randomized controlled trials of pediatric massage A review Evid Based
Complement Alternat Med 2007 Mar 4(1)23-34 Epub 2006 Nov 3
Reason for exclusion Not outcome of interest
de Nijs EJ Ros W Grijpdonck MH Nursing intervention for fatigue during the treatment for cancer Cancer
Nursing 2008 31(3)191-206
Reason for exclusion Not population of interest
Edwards JL Gibson F Richardson A Sepion B Ream E Fatigue in adolescents with and following a
cancer diagnosis developing an evidence base for practice European Journal of Cancer 2003
Dec 39(18)2671-80
Reason for exclusion Not experimental or quasi-experimental study
Hinds PS Hockenberry-Eatan M Developing a research program on fatigue in children and adolescents
diagnosed with cancer Journal of Pediatric Oncology Nursing 2001 Mar-Apr 18(2 Suppl
1)3-12
Reason for exclusion Not experimental or quasi-experimental study
Hockenberry-Eaton M Hinds PS Alcoser P ONeill JB Euell K Howard V Gattuso J Taylor J Fatigue in
Children and Adolescents With Cancer Journal of Pediatric Oncology Nursing 1998 July
15(3)172-182
Reason for exclusion Not experimental or quasi-experimental study
Jean-Pierre P Mustian K Kohli S Roscoe JA Hickok JT Morrow GR Community-based clinical oncology
research trials for cancer-related fatigue The Journal of Supportive Oncology 2006 Nov-Dec
4(10)511-6
682
51
Reason for exclusion Not population of interest
Kangas M Bovbjerg DH Montgomery GH Cancer-Related Fatigue A Systematic and Meta-Analytic
Review of Non-Pharmacological Therapies for Cancer Patients Psychological Bulletin 2008 Sep
134(5)700-41
Reason for exclusion Not population of interest
Lotfi-Jam K Carey M Jefford M Schofield P Charleson C Aranda S Nonpharmacologic strategies for
managing common chemotherapy adverse effects A systematic review Journal of Clinical
Oncology 2008 Dec 1 26(34)5618-29 Epub 2008 Nov 3
Reason for exclusion Not outcome of interest
Marchese VG Chiarello LA Lange BJ Effects of physical therapy intervention for children with acute
lymphoblastic leukemia Pediatr Blood Cancer 2004 Feb42(2)127-33
Reason for exclusion Not outcome of interest
Meeske KA Siegel SE Globe DR Mack WJ Bernstein L Prevalence and correlates of fatigue in
long-term survivors of childhood leukemia Journal of Clinical Oncology 2005 Aug 20
23(24)5501-10
Reason for exclusion Not intervention study
Minton O Richardson A Sharpe M Hotopf Stone P A systematic review and meta-analysis of the
pharmacological treatment of cancer-related fatigue J Natl Cancer Inst 2008 Aug 20
100(16)1155-66 Epub 2008 Aug 11
Reason for exclusion Not population and intervention of interest
Mustian KM Morrow GR Carroll JK Figueroa-Moseley CD Pascal JP Williams GC Integrative
nonpharmacologic behavioral interventions for the management of Cancer-Related fatigue The
Oncologist 2007 12(1)52-67
Reason for exclusion Not population of interest
Neill J Belan I Ried K Effectiveness of non-pharmacological interventions for fatigue in adults with
multiple sclerosis rheumatoid arthritis or systemic lupus erythematosus a systematic review
Journal of Advanced Nursing 2006 Dec 56(6)617-35
Reason for exclusion Not population of interest
Rheingans JI A systematic review of nonpharmacologic adjunctive therapies for symptom management
Journal of Pediatric Oncology Nursing 2007 24(2) 81-94
683
52
Reason for exclusion Not outcome of interest
Rheingans JI Pediatric oncology nursesrsquo management of patients symptoms Journal of Pediatric
Oncology Nursing 2008 Nov 25(6) 303-11
Reason for exclusion Not outcome of interest
San Juan AF Fleck SJ Chamorro-Vintildea C Mateacute-Muntildeoz JL Moral S Peacuterez M Cardona C Del Valle MF
Hernaacutendez M Ramiacuterez M Madero L Lucia A Effects of an intrahospital exercise program
intervention for children with leukemia Medicine amp Science in Sports amp Exercise 2007 Jan
39(1)13-21
Reason for exclusion Not outcome of interest
Sanford SD Okuma JO Pan J Srivastava DK West N Farr L Hinds PS Gender differences in sleep
fatigue and daytime activity in a pediatric oncology sample receiving dexamethasone Journal of
Pediatric Psychology 2008 Apr 33(3)298-306 Epub 2007 Nov 17
Reason for exclusion Not experimental or quasi-experimental study
Schmitz KH Holtzman J Courneya KS Macircsse LC Duval S Kane R Controlled physical activity trials in
cancer survivors a systematic review and meta-analysis Cancer Epidemiol Biomarkers Prev
2005 Jul 14(7)1588-95
Reason for exclusion Not population of interest
van Brussel M Takken T Lucia A van der Net J Helders PJ Is physical fitness decreased in survivors of
childhood leukemia A systematic review Leukemia 2005 Jan 19(1)13-7
Reason for exclusion Not population of interest
Whiting P Bagnall AM Snowden AJ Cornell JE Mulrow CD Ramirez G Interventions for the treatment
and management of chronic fatigue syndrome JAMA 2001 Sep 19 286(11)1360-8
Reason for exclusion Not intervention of interest
Whitsett SF Gudmundsdottir M Davies B McCarthy P Friedman D Chemotherapy-related fatigue in
childhood cancer correlates consequences and coping strategies Journal of Pediatric
Oncology Nursing 2008 Mar-Apr 25(2)86-96 Epub 2008 Feb 29
Reason for exclusion Not experimental or quasi-experimental study
Winner C Muumlller C Hoffmann C Boos J Rosenbaum D Physical activity and childhood cancer Pediatr
Blood Cancer 2010 Apr 54(4)501-10
Reason for exclusion Not research study
684
53
Wu M Hsu L Zhang B Shen N Lu H Li S The experiences of cancer-related fatigue among Chinese
children with leukaemia A phenomenological study Journal of Nursing Studies 2010 Jan
47(1)49-59 Epub 2009 Aug 25
Reason for exclusion Not experimental or quasi-experimental study
Yeh CH Chiang YC Lin L Yang CP Chien LC Weaver MA Chuang HL Clinical factors associated with
fatigue over time in paediatric oncology patients receiving chemotherapy British Journal of
Cancer 2008 Jul 8 99(1)23-9 Epub 2008 Jun 24
Reason for exclusion Not experimental or quasi-experimental study
685
8
Fatigue can be also measured with unidimensional or multidimensional scales The first
type of fatigue scale is not suitable for studies focusing on fatigue because they are too
long if the aim is to only assess fatigue Furthermore they only allow for a limited number
of possible responses Unidimensional scales also are not suitable for the in-depth study
of fatigue because they assess only one aspect of fatigue15
In recent years fatigue in children with cancer has received some attention and
measurement tools have gradually been developed - such as1) Checklist individual
strength (CIS) The items are scored on 7-point Likert scales (with 1 indicating best and
7 worst function) 2) The Child Fatigue Scale (CFS) is a 2-part questionnaire that asks for
a yes or no (frequency) response and a 5-point rating of the intensity of any yes
responses ranging from not at all to a lot The Fatigue Scale for 7-12 year Olds (FS-C)
is provide a fatigue intensity score higher scores indicating higher fatigue The Fatigue
Scale for 13-18 year Olds (FS-A) measure adolescent cancer patientsrsquo perceptions of
the intensity of their fatigue on a daily or weekly basis higher scores indicating higher
fatigue 3) The Fatigue Scale Parent Version (FS-P) measures the parentsrsquo perception
of their childrsquos fatigue intensity on a five-point Likert-type scale higher scores indicating
higher fatigue 4) The Fatigue Scale Staff Version (FS-S ) measures the staffrsquos
perceptions of the patientrsquos fatigue intensity during the past 24 hours Intensity ratings are
on a four-point Likert-type scale with higher scores indicating more intense fatigue
symptoms 5) The Pediatric Quality of life Multidimensional Fatigue Scale (Peds
QL-MFS)Higher scores (0 to 100) indicate less fatigue( Appendix IV)
Besides disturbing physical and mental functions and status fatigue also affects the
641
9
quality of life 15 of children with cancer and impacts their daily life16 among all different
types of cancer progress and childrsquos ages However as opposed to the fatigue of adults
the fatigue of children tends to be neglected and left untreated17 by medical and nursing
staffs
In terms of the management approach to cancer-related fatigue Ekti Gene (2008) 2
suggests that strategies could include pharmacologic and non-pharmacologic measures
NCCN (2011) 1 indicated in the Clinical Practice Guidelines in Oncology that during
aggressive treatments during long-term follow-up treatments or in the terminal phase of
cancer the intervening measures for cancer-related fatigue can be divided into
pharmacologic and non-pharmacologic measures Non-pharmacologic measures include
activity enhancement psychosocial interventions (eg cognitive behavioral therapy
(CBT) stress management relaxation support groups) attention-restoring therapy and
nutrition consultation As for the effectiveness of pharmacological measures the
effectiveness is still uncertain However there is evidence to suggest that
methylphenidate may be effective in treating cancer-related fatigue1 Whiting et al
(2001)18 included 36 randomized controlled trials and 8 controlled trails to assess the
effectiveness of the pharmacological and non-pharmacological interventions used in the
treatment or management of chronic fatigue syndrome in adults or children Results
showed insufficient evidence on the effectiveness of the pharmacological supplements
complementaryalternative and other interventions In addition the evidence of
pharmacological treatments of immunoglobulin and hydrocortisone were also
inconclusive However interventions such as cognitive behavioral therapy and graded
exercise therapy have shown promising results
642
10
The efficacy of pharmacological treatments for cancer-related fatigue has not been
established6 therefore there is a need to provide evidence-based findings of the
effectiveness of non-pharmacological interventions to support nursing intervention to
release the childrsquos cancer-related fatigue To date most studies have investigated the
effectiveness of non-pharmacological treatments on cancer-related fatigue of
adults20and to date there is no systematic review in relation to cancer-related fatigue of
children However as children are not a smaller version of adults it is inappropriate to
extrapolate the results of adults onto children Therefore there is a need to establish the
effectiveness of non-pharmacological intervention on the cancer-related fatigue of
children
Given the increase in childhood cancer survival rate the importance of decreasing
childrenrsquos cancer-related fatigue during treatments and so increase their quality of life has
become a focus of their medical teams The role of nurses during care intervention is to
confirm the major symptoms of children with illness and effectively treat each symptom to
increase the childrenrsquos quality of life21 Moreover the USA based NCCN also indicated in
the Care Standard for the Treatment of Cancer-related Fatigue of Children and
Adolescents that treatments for fatigue should be included in the health care teams and
the children and their family should be informed of relevant information The definition of
non-pharmacological interventions for childrenrsquos cancer ndashrelated fatigue include activity
enhancement (exercise physical activity) psychosocial interventions cognitive
behavioral therapy (CBT) stress management relaxation nutrition consultation
massage and educational interventions
643
11
The Cochrane Library of Systematic Reviews and The Joanna Briggs Institute Library of
Systematic Reviews were initially searched to ensure that systematic reviews on this
subject were not already published or being undertaken This initial search prior to the
commencement of the review did not yield any results
This systematic review has examined the effectiveness of non-pharmacologic
interventions on the cancer-related fatigue of children in hope of finding scientific
evidence that can support or refute such measures on children The results of this study
may serve as a reference for professional caregivers children with cancer and their
families or to be put into practice during the clinical care of children with cancer
Definition of terms
FatigueFatigue as a distressing persistent subjective sense of physical emotional
andor cognitive tiredness or exhaustion related to cancer or cancer treatments
that is not proportional to recent activity and interferes with daily function1 There
are various scales and measurements of the degree of fatiguewe have elected to
use the study authors own definitions of fatigue rather than applying a single
pre-set definition of the condition
Non-pharmacological interventionsReferring to reduce fatigue that does not involve
drugsNon-pharmacologic measures include activity enhancement psychosocial
interventions (eg cognitive behavioral therapy stress management relaxation
support groups) attention-restoring therapy and nutrition consultation1
ChemotherapyTreatment with drugs that kill cancer cells 1
644
12
Review QuestionsObjectives
Review Objective
The objective of this systematic review was to critically appraise synthesize and
present the best available evidence concerning the effects of non-pharmacological
interventions fatigue in children and adolescents with cancer
Review Question
The following specific question was addressed in this review
What is the effectiveness of non-pharmacological interventions on fatigue in
children and adolescents with cancer aged from one to 18 years
Criteria for Considering Studies for this Review
Types of studies
This review included randomised controlled trials (RCTs) and quasi-experimental
studies that examine the effectiveness of non-pharmacological intervention for fatigue in
children and adolescents with cancer
Types of participants
Children and adolescents aged from one to 18 years old experiencing fatigue
associated with cancer either during or after the chemotherapy or maintenance stage of
chemotherapy or survive stage The types of cancer to be included in this systematic
review will be ALL (Acute lymphoblastic leukemia) AML (Acute myeloid leukemia)
lymphoma and solid tumors
Exclusion criteria for Types of participants
645
13
newborn infants under 1 years of age
participants who do not have a specific diagnosis of cancer
participants who have received immunoglobulin or hydrocortisone
treatment
If participants have received immunoglobulin or hydrocortisone treatment may
inference the effectiveness of non-pharmacological interventions on fatigue
Types of intervention
This review considered studies that examine non-pharmacological interventions on
fatigue for children and adolescents with cancer including activity enhancement
(exercise physical activity) psychosocial interventions CBT stress management
relaxation nutrition consultation massage and educational interventions The
interventions descriptive included the length frequency setting and intervention
providers eg Nurse Psychologist Dietician
Exclusion criteria for types of interventions only pharmacological interventions were
tested
Types of outcome measures
The outcome measures considered were fatigue scores The literature demonstrates that
differences of opinion exist regarding the most valid and reliable method of measuring
cancer-related fatigue Therefore studies that used any validated scale for
cancer-related fatigue were considered for inclusion Currently commonly used scales to
measure fatigue include Checklist Individual Strength (CIS) Child Fatigue Scale (CFS)
The Fatigue Scale for 7-12 year Olds (FS-C) The Fatigue Scale for 13-18 year Olds
646
14
(FS-A)and Pediatric Quality of life Multidimensional Fatigue Scale (Peds QL-MFS)
Types of settings
Both hospital and community settings
Search Strategy
Before undertaking this systematic review the Cochrane Library Joanna Briggs Institute
Library of Systematic Reviews and CINAHL were searched and no systematic reviews on
this topic were found or identified as underway
The search strategy aimed to find both published and unpublished studies
A three-step search strategy was utilized in each component of this review An initial
limited search of CINAHL and MEDLINE was undertaken followed by an analysis of the
text words contained in the title and abstract and of the index terms used to describe the
article A second search using all identified keywords and index terms was undertaken
Lastly the reference lists of all identified reports and articles were searched for additional
studies
Types of languages
1 English
2 Chinese
The following databases were searched to identify keywords contained in the title and
abstract and relevant MeSH headings and descriptor terms
The Cochrane Library PsycINFO 1990 ndash 2010
647
15
Ovid MEDLINE 1966 ndash 2010 CINAHL Plus with Full Text 1960 ndash2010 EMBASE ProQuest Dissertations amp theses 1990-2010 Electronic theses and dissertations system 1956(abstract)1990(full text)-2010 MEDNAR Index to Taiwan periodical literature 1970-2010 Electronic thesis and dissertation system (Chinese) 1990-2010
Keyword search terms
1Types of studies experimental study random quasi-experimental study實驗性研究隨
機類實驗性研究
2 Types of participants childchildren adolescents pediatric cancer and oncology兒童
青少年兒科癌症腫瘤
3 Types of interventions non-pharmacological interventions massage exercise fitness
physical activity cognitive behavioral stress management energy conservation
sleep therapy relaxation distraction and psycho-education非藥物性處置按摩運動
身體活動認知行為壓力處置能量保存睡眠治療放鬆轉移注意力衛教
4 Types of outcome measures fatigue cancer-related fatigue loss of energy levels of
tiredness tired side effect symptoms疲憊癌性疲憊疲倦合併症症狀
Methods of the Review
Assessment of methodological quality Papers selected for retrieval were assessed by two independent reviewers for
methodological validity prior to inclusion in the review using the standardised critical
appraisal instruments (Appendix I) from the JBI-SUMARI (Joanna Briggs Institute
Systems for the Unified Management Assessment and Review of Information package)
Any disagreements that arise between the reviewers were resolved through discussion
648
16
with a third reviewer
Data extraction Data was extracted from papers included in the review using standardised data
extraction tool (Appendix II) from the JBI-SUMARI Details of eligible studies were
extracted and summarised independently by two reviewers
Data Synthesis
All data analysissynthesis were made using the JBI-SUMARI The studies were
assessed for clinical heterogeneity by considering the settings populations interventions
and outcomes Where possible these binary outcomes were analyzed by calculation of
the Odds Ratio with the 95 CI The weighted mean difference was calculated if the
pooled studies have used the same scale for continuous data The standardized mean
difference was calculated for continuous data measuring the same outcome on a
different scale In studies where statistical pooling of results was inappropriate the
findings were considered for inclusion as a narrative summary
Results The findings from the systematic review are presented first Followed by the results from
the meta-analysis component of this review
Description of studies From database search and hand search a total of 76 papers were identified Thirty
papers were then excluded because they did not meet the inclusion criteria Forty-six
full text were retrieved for further consideration for inclusion Of the 30 excluded reasons
for exclusion were follows 11articles were duplicated eight articles did not meet
649
17
participant inclusion criteria eight articles did not meet outcome criteria and nine articles
were correlation studies or discussion papers others articles were unclear reporting In
total after sorting six papers have been included in this article Figure 1 displays the
process used to identify relevant articles for inclusion in the systematic review
Figure 1 Stages of searching and inclusionexclusion of references for the review
Potentially relevant English-language and Chinese- language Studies Identified
Electronically and hand search (n=76)
Duplicate (n= 11) Papers excluded after evaluation of abstract (n=19)
Papers retrieved for detailed examination (N=46)
Papers excluded after review of full paper
(n=40)
Papers assessed for methodological
quality (n=6)
Papers included in systematic review
(n=6)
Methodological Quality
Of the six included articles 2722232425 two articles were RCT design224 with score 7 out
of 10 each paper from Critical Appraisal Checklist and four articles used
650
18
quasi-experimental design7222425 with socre 5 to 6 out of 10 because the quality of
the whole papers is still acceptable therefore these six articles were accepted after
primary reviewer and secondary reviewerrsquos decision
Randomisation
In two RCT articles224 one study24 used to a computer-generated program operated by
the St Jude Protocol and Data Management System to randomize the sample Another
study2 didnrsquot address how randomization was done
Allocation concealment
No studies reported allocation concealment
Intention-to-treat analysis
One quasi-experimental design7 stated Intention-to-treat analysis
Adequate follow up
The follow-up periods included 2or 3 days24 7 days2 4 week7 one month25 6 week25 12
week2216 week23 and 1 year23
Baseline comparability of groups
Three 22425 of six studies had baseline comparability in terms of age sex diagnosis
race institution duration of illness
Blinded outcome assessment
No studies used blinded outcome assessment The researchers including study team
patients staff and families were not blinded to the patientrsquos group assignment
Characteristics of included studies
651
19
There were six studies related to interventions designed to cancer-related fatigue for
pediatric patients than there are for adults There are a total of six including five
English-language papers 27222324 and one Chinese-language paper 25 ranging in year of
publication from 2007 to 2009
Patient characteristics
The research subjects of four papers included both school-aged children and
adolescents 7222324 one papers involved mainly adolescents25 and one paper sampled
only school-aged children 2 the range in ages was between six-18 years The number of
patients included in the samples ranged from nine to 60 The sources of case data were
from both outpatients and hospitalized children The types of cancer included acute
lymphoblastic leukemia (ALL) solid tumors acute myeloid leukemia (AML) and
lymphoma Overall ALL was the most commonly studied cancer type The stage of the
disease varied in these reports some patients were in the maintenance stage of
chemotherapy25 some had just received their first round of chemotherapy224 some had
completed two courses of treatments lasting 4-8 weeks each 7 and some had entered
the survivor stage 2223
Countries
Two RCTrsquos 2 24 were conducted in the USA There were four quasi-experimental design
studiesThree studies conducted in the USA7 22 23 and one in Taiwan25
Intervention types
652
20
The interventions included exercise training programs 2225 physical activity 2324
massage therapy 7 and health education 223 exercise training and physical activity as
an intervention method given in three different settings home 22 25 community 23 or
hospital 24 The studies used different types of exercise interventions including
home-based aerobic exercise use a Video Compact Disc 25 use of a bicycle-style
exerciser 24 aerobics2223 and various types of physical activities2 and strength-building
exercises 2223 The intensity of the exercise varied and often included gradual warm-up
exercises a period of main exercise and a cool down period For these studies2023 the
target exercise intensity was a heart rate of gt90 of the maximum heart rate (HR max) or
the increase in the percentage of heart rate reserve ( HRR) of 40-60
The number of weeks for the exercisephysical activity interventions duration including
2-4 days 24 6 weeks25 12 weeks22 and 16 weeks23 The frequency of exercise ranged
from 2-3 times per week to twice a day Typical duration of exercise ranged from 10 to 45
minutes There are three papers using exercise interventions based on ACSM (American
College of Sports Medicine) 2225 recommendations and one of these used an Activity
pyramid from the ACSM to determine intensity 24
One article did not clarify the type of exercise intervention or the reasons for their choices
23 In addition there was an article focusing on massage therapy 7 as an intervention in
this study the experimental group received four weeks of massage therapy either in the
clinic or in the patientrsquos room the therapy was applied by a professional masseur and
targeted the back legs arms chest stomach and face of the children However the
frequency of massage sessions per week and the duration of the massages were not
653
21
given There is another article about intervention measures combine health education
and physical activity 2 In this study patients were informed about the following (1) health
education patients received daily education about chemotherapy-related fatigue and
information from a health education manual written by the author (2) encouragement for
children to engage in activities such as listening to music drawing and reading and (3)
physical activity which involved walking along the corridors of the ward for 10-15 minutes
These health education measures were presented for 45-60 minutes a day for a total of
seven days The study design for non-pharmacological interventions used control groups
that included primarily people who had received standard treatment or people who did
not receive an exercise intervention
Outcome measures
Five measurement tools were used in this group of seven papers concerning childrenrsquos
fatigue (Appendix IV) Because those studies included both school-age children and
adolescents the following descriptions will be differentiated by age Fatigue
measurements for school-aged children with cancer include the following the Child
Fatigue Scale (CFS) 7 a scale that measures the frequency and intensity of fatigue and
the Fatigue Scale for 7-12 year Olds (FS-C) 224 a scale that can be used to evaluate the
intensity of fatigue On the other hand fatigue measurements for adolescent cancer
patients include the following the Fatigue Scale for 13-18-year-olds (FS-A) 24 a measure
that can help evaluate fatigue levels the Pediatric Quality of Life Multidimensional
Fatigue Scale (Peds QL-MFS) 2325 a tool that can be divided into three sub-scales to
understand the general cognitive and sleep rest components of fatigue and finally the
CIS-20 for school-age children and adolescents 22 a scale that measures four levels of
654
22
fatigue namely subjective experience attention motivation and physical activity Two
studies used the Peds QL-MFS scale to measure fatigue2325
Meta-analysis results Two studies of the included papers failed to provide sufficient raw data they could not be
included in the meta-analysis Hinds et al 24 did not include post-test data Genc et al 2
provided no pre-test data PostWhite et al7 reported that fatigue after the health
education intervention was not statistically different but they presented the results
without presenting fatigue-related data Therefore the meta-analysis included three
studies 222325
The heterogeneity of studies was analyzed with Chi square statistics and no statistical
significance was found Therefore the data was combined in meta-analysis according to
exercise intervention on fatigue In addition there were three articles using the Peds
QL-MFS as a research tool to examine childrenrsquos improvements in fatigue Among these
Keats 22 and Chiang 24 present the effectiveness of exercise interventions using three
subscales Therefore the meta-analysis also analysis of the effects of these exercise
intervention measures on three subscales of Peds QL-MFS general fatigue sleep rest
fatigue and cognitive fatigue
The effectiveness of exercise intervention for fatigue We analyzed the exercise intervention effect on fatigue A total of 2 studies 22 23 were
included Takken et al 22 used community-based exercise training program to reduce
fatigue of children 6 to 14 years (mean 93y) of age who survived ALL Fatigue
measurement by Checklist Individual Strength (CIS) after 12-week of training fatigue
655
23
show no significant differences between pre (meanplusmnSD 415plusmn147) and post training
(meanplusmnSD368plusmn217) but fatigue change from baseline mean reduction of 11
Keats et al23 although used community-based physical activity program to reduce fatigue
for adolescents 14 to 18 years of age (mean162 y) with cancer (Lymphoma leukemia CNS
tumor germ cell tumor) Studies used fatigue by PedsQLMFS Results show general fatigue
from baseline to 8 weeks and to 3 months follow up significantly improves General
fatigue sleeprest fatigue and total fatigue from baseline to 3 months follow up showed
significant improvements Sleeprest fatigue and total fatigue at 1 years followed up were
significant improvements
Figure 2 shows the overall effect of exercise intervention in children and adolescents with
cancers with a focus on improving fatigue Due to the lower heterogeneity (p>005) the
fixed effects model was used to pool the data for meta-analysis (Overall effect size=
-006 95 Confidence Interval (CI) -070 to 058) A result did not indicate a statistically
significant difference (p = 087)
656
24
Figure2 Meta-analysis results of exercise intervention on fatigue
In addition Keats23 and Chiang25 used the three sub-scales of Peds QL-MFS to
determine the general cognitive and sleep rest components of fatigue The following
present the effectiveness of exercise interventions using three subscales including
general fatigue sleep rest fatigue and cognitive fatigue 2325
Chiang et al 25 used a 6- week home-based aerobic exercise intervention to reduce
fatigue of children 7 to 18 years (mean age at experimental group was 1088 y in control
group was 1247 y) of age who with acute lymphoblastic leukemia Fatigue measurement
by Peds QL-MFS after training For intent-to ndash treat analysis the findings indicated that
there are no intervention effects and time differences by any items on the subscale of
fatigue For per-protocol analysis general fatigue( meanplusmnSD 422plusmn402) was the only
subscale that was significantly lower for children who received the exercise intervention
than those in control group at follow-up assessment (one month after the completion of
intervention)
Keats et al23 although used community-based physical activity program to reduce fatigue
for adolescents 14 to 18 years of age (mean162 y) with cancer (Lymphoma leukemia
CNS tumor germ cell tumor) Both studies used fatigue by PedsQLMFS Results show
general fatigue from baseline to 8 weeks and to 3 months follow up significantly improves
657
25
General fatigue sleeprest fatigue and total fatigue from baseline to 3 months follow up
showed significant improvements Sleeprest fatigue and total fatigue at 1 years followed
up were significant improvements
The effectiveness of exercise intervention for general fatigue
The impact of the exercise interventions upon levels of general fatigue was also analysed
The heterogeneity was low (p>005) Therefore the fixed effects model was used to
examine the effectiveness The effect size is -076 indicating a statistically significant
difference (p = 001 95 CI -135 to -017 Fig 3) The evidence suggests that exercise
intervention can reduce general fatigue in children with cancer
Fig 3 Meta-analysis results of exercise intervention for general fatigue
The effectiveness of exercise intervention for sleep rest fatigue
The following is the result of the meta-analysis of the effectiveness of exercise
interventions on sleep rest fatigue First the heterogeneity test was conducted with P gt
005 representing small heterogeneity and the fixed effects model was used Fig 4
shows the effect size is -035 indicating no statistically significant differences (p = 023
95 CI-092 to 022 Fig 4)
658
26
Fig 4 Meta-analysis results of exercise intervention for sleep rest fatigue
The effectiveness of exercise intervention for cognitive fatigue Lastly the following data reports the results of meta-analysis of the effectiveness of
exercise interventions for cognitive fatigue The heterogeneity was p>005 then the
fixed effects model was used The effect size is -035 indicating no statistically significant
differences (p = 024 95 CI-092 023 Fig 5)
Fig 5 Meta-analysis results of exercise intervention for cognitive fatigue
Narrative presentation of remaining included studies
Three studies were not included in meta-analysis Post-White et al7 one of the aims in
this study was to examine the effect of massage therapy on fatigue in children with
cancer The study was a quasi-experimental design Twenty-three childrenparent dyads
were enrolled 17completed all data points Children with cancer ages 7 to 18 years
received at least 2 identical cycles of chemotherapy and one parent participated in the
2-period crossover design in which 4 weekly massage sessions (MT) alternated with 4
659
27
weekly quiet-time (QT) control sessions There were no significant changes in fatigue in
children over the 4-week MT or QT conditions either independently (change over time) or
when we compared fatigue by condition
The lack of effect of massage on fatigue may be the difficulty some children had in
differentiating fatigue from being relaxed underscores the challenge of measuring fatigue
in children Some children interpreted being tired or relaxed as having greater fatigue
because they felt like lying around and sleeping or felt unmotivated to do their usual
activities all measures of fatigue in the instrument used in the study
Hinds et al24conducted a prospective two-site randomized controlled pilot study to
assess the feasibility of an enhanced physical activity (EPA) intervention in hospitalized
children and adolescents receiving treatment for a solid tumor or for acute myeloid
leukemia (AML) Twenty-nine patients (25 with a solid tumor and 4 with AML) participated
age range from 736 to 1816 (mean 1248 y) The EPA intervention selected was
pedaling a stationary bicycle-style exerciser (Chattanooga Peddler Deluxe Bio-Teck
Medical Memphis TN) for 30 minutes twice daily for 2 to 4 days of hospitalization The
mixed model analysis revealed no significant differences in patient reports of fatigue
between the two study arms or over time
Genc et al2 conducted a RCT involving children with cancer who are 7 to 12 years of age
and receiving chemotherapy treatment to determine the impact of educational
intervention by nurses on decreasing the fatigue syndrome The research sample was
composed of a total of 60 children with cancer with 30 children being included in the
660
28
experimental group (mean age 923)and 30 children included in the control group (mean
age 937) with their mothers In the experimental group after the 7th to 10th day of the
chemotherapy treatment throughout a week the researcher conducted the nursing
interventions every day for 45 to 60 minutes In the control group routine nursing
interventions were carried out The experimental group received education about the
fatigue with the chemotherapy and fatigue handbook was given which was developed by
the authors Children and mothers were consulted for including activities that could
decrease fatigue which were described as effective interventions A statistically
significant difference was found between the Fatigue Scale-Child mean scores of the
experimental (2723) and the control group (4213) The results suggest that fatigue of
children with cancer can be reduced by implementing appropriate nursing interventions
(t=567 Plt00)
Discussion The purpose of this systematic review was to determine the effectiveness of
non-pharmacological interventions specifically targeting fatigue for children and
adolescents with cancer undergoing chemotherapy or after receiving chemotherapy
Included articles about the effectiveness of non-pharmacological interventions for
children and adolescents with cancer were published between the years of 2007 and
2009 Although interventions for cancer fatigue for adults have been extensively studied
it can be seen from either the title of the paper or related content that an intervention
study on children was a pilot study or a feasibility study Representing a field in its early
stage these studies show that the fatigue issues with young cancer patients have only
recently been taken seriously
661
29
The results of our meta-analysis include measurement of the four performance indicators
fatigue and general fatigue sleep rest fatigue and cognitive fatigue The results show
that there is a statistically significant difference only in the domain of general fatigue
using an exercise intervention for children with cancer can improve the degree of fatigue
with the effect size reaching 0671 Other results do not indicate significant differences
The reasons may include the following
1 Characteristics of the cancer The exhaustion from cancer occurs not only during cancer treatment but also in during
long-term survival a time during which patients may continue to be affected by this
symptom 8 26 Therefore when using intervention measures to improve fatigue
circumstances should be considered such as the process of the treatment and the course
or stage of the disease Because cancer patients will experience different forms of
treatment or courses of treatment the disease itself or treatment differences should be
considered in the choice of intervention Even chemotherapy drugs should be taken into
consideration For example a period of general steroid treatment can increase patientsrsquo
fatigue In those studies of children with cancer few studies looked solely at one type of
cancer most studies included a variety of cancer patients Furthermore most studies do
not clearly explain the stage of the disease or course of treatment and most do not
include treatment variables in the control group Moreover children with cancer may
have different levels of physical function
2 Research design The sample size Currently there are few studies with large sample size and a rigorous
RCT design due to the small number of papers available for analysis The sample size
included in our studyrsquos data analysis is between 20 and 42 people this small sample size
will affect the power available to evaluate outcome variables
Although most of the non-pharmacological interventions still use exercise and physical
activity and these studies overall show better results for fatigue as compared with
controls more research is still needed to further confirm the efficacy of these findings
662
30
The dropout rate in the evaluated research varies a great deal ranging from 5 to 45
these dropout rates may result from the characteristics of the research subjects or the
lengthy time involved in participating in these studies The research data with a high
turnover rate might not reflect the actual outcomes of participation in exercise and the
quality of the research contained in articles with high subject turnover rates may be
lower
Exercise doses and time The exercise doses needed to reduce fatigue cannot be
determined additionally the amount of exercise completed by the patient is also
inconsistent interventions vary between 2-3 times per week and two times a day and
exercise duration varies between 10 and 45 minutes each time Furthermore the study
interventions vary in length between a couple of days and a long period of 16 weeks The
data collection times are different some were measured 12 weeks after the intervention
began some were measured during the 6 weeks of intervention some were measured
three months after the intervention was finished and some were measured after one
year
In addition disease-related symptoms decrease childrenrsquos willingness to participate in
exercise interventions inappropriate exercise intervention programs may actually
increase childrens fatigue In addition the children in the study are still developing
physically it is important to consider ways to design an interesting exercise intervention
to increase the compliance of patients in order to improve the effectiveness Although
intervention programs in the hospital or in a community sports center can improve the
effectiveness because they provide supervision the feasibility of these programs is
questionable However if the program is home-based the children need to be
supervised by parents in order to improve their compliance in doing the exercises
Furthermore regarding the nature of the intervention the results from this study indicate
that the researched non-pharmacological interventions include the following exercise
training programs physical activity massage therapy and health education interventions
However according to the National Comprehensive Cancer Network 1 clinical guidelines
663
31
for cancer non-drug measures for cancer fatigue can be separated into five categories
(1) activity enhancement (2) psychosocial interventions such as cognitive behavioral
therapy (CBT) stress management relaxation techniques and support groups (3)
attention-restoring therapy (4) nutritional consultation and (5) cognitive behavioral
therapy specifically targeting sleep disturbance Researchers have also suggested that
psychosocial interventions should be included in the future research for children with
cancer-related fatigue 22
(2) The measurement tools in the study The assessment of fatigue can be
one-dimensional or multidimensional One-dimensional assessment can help understand
the severity of fatigue symptoms however multidimensional scales are often more
credible Therefore when measuring cancer-related fatigue researchers should consider
whether there is a uniform definition of fatigue or a standardized tool for measuring
fatigue in order to facilitate further systematic meta-analyses and further develop the
clinical care guidelines
Limitations of the review The present review has some potential limitations First the low methodological quality
may influence the result Although exercise intervention seems promising quality of the
RCTs was generally quite low Future studies require better design and reporting if
methodological issues to establish evidence-based nonpharmcologic intervention
Second the identified studies covered only a limited types of nonpharmcological
intervention especially in exercise intervention The guidelines for cancer-related fatigue
in NCCN (2011)1 referred to more interventions than the ones included in this review
such as cognitive behavioral therapy and nutrition consultation Thirdly the small sample
size and effect size could be potentially having led to underpowered approach for
detecting the effects on fatigue Therefore we recommend that as research continues to
grow a re-analysis can be undertaken Fourthly Combining data in meta analysis from
664
32
studies where the ages were quite different is a potential source of heterogeneity and
may affect the interpretation of the results
Conclusion At present clinical treatment is widely used for cancer patients However child and
adolescent cancer patients often experience various side effects which cause short-term
or long-term discomfort both physically and psychologically In particular with the
increasing cure rate cancer related fatigue during or after treatment has become an
important issue This study result provided positive effect of exercise intervention on
general fatigue
Implications for practice The results of this systematic review and meta-analysis show that exercise interventions
can effectively improve the level of general fatigue In particular although the articles
were self-reported feasibility studies their results all indicate that exercise interventions
for fatigue are feasible and safe there was no conclusion to be made for the use of
massage therapy or health education measures because there was only one article for
each of these interventions
Recommendations for practice
Cancer-related fatigue is one of the most severe and frequent symptoms by pediatric
oncology children and adolescent suffered during treatment and the symptom existed
even after treatment has ended Until now no golden standard of treatment to fatigue is
established The findings call for more attention to how to reduce patientrsquos levels of
fatigue Based on the available information evaluated in this review the following
recommendations for practice are provided
665
33
bull For children aged 7 to 18 who has cancer (eg Lymphoma leukemia CNS tumor
germ cell tumor) an effective progressive aerobic exercise program is recommended to
be at least 2-3 times per week 20 to 45 minute for each session and last for 6-16 weeks
in order to reduce their general fatigue (tiredness physically weakness) In addition
adults should be involved in accompanying children while they are performing physical
exercise of which should be able to improve the adherence rate (level 2 ) ( Grade of
recommendation A)
bull For children aged 7 to 18 who has cancer (eg Lymphoma leukemia CNS tumor
germ cell tumor) an progressive aerobic exercise program will not be effective to reduce
their sleep andor rest (sleeping or resting a lot) or cognitive fatigue (problems with
thinking quickly or problems with remembering) (level 2 ) ( Grade of recommendation C)
bull Nursing interventions in educating treatment of fatigue include information about
activity nutrition energy preservation consulting and providing a useful fatigue
handbook will benefit those children who are 7 to 12 years have a new diagnosis of ALL
AML or lymphoma and receive for the first time after being diagnosed a 7- to 10-day
chemotherapy treatment (level 2) ( Grade of recommendation A)
bull A 4-week massage therapy program (the therapists massage childrenrsquos back legs
arms stomachchest and face) is not effective for children who are aged 7 to 18 and
have acute lymphoblastic leukemia brain tumors lymphoma rhabdomyosarcoma
Wilms tumor or Ewing sarcoma(level 2)( Grade of recommendation C)
bull Using a 12-week aerobic and strength exercise (45-min exercise sessions twice a
week) is not effective for children who are aged 6-14 and survived acute lymphoblaststic
leukemia age from 6 to 14(level 2) ( Grade of recommendation C)
bull Using a physical activity intervention (30minutestwice daily for 2-4days) is not
effective for children who are 7 to 18 years of age with soild tumor or AML(level 2)
( Grade of recommendation C)
666
34
Implications for research According to this systematic review and meta-analysis results there are suggestions to
improve the effectiveness of future research on non-pharmacological interventions for
children and young peoplersquos cancer-related fatigue
As the majority of included non-pharmacological interventions for the fatigue of cancer
patients consist of exercise programs future research should also consider various
non-pharmacological interventions in order to understand the effectiveness of different
methods
Regarding the exercise intervention methods and studies should consider multiple
factors including the age or personal condition of the subject the disease stage and the
amount of daily activities Studies should use design prescriptions (eg frequency
intensity duration and type of exercise) and consider the adherence to the measures in
order to enhance the study strength
In measuring the results of non-pharmacological interventions there should be standard
definitions or standard measurement tools to facilitate the following systematic review
and meta-analysis that can subsequently be developed into clinical care guidelines
Reviewing the effectiveness of the current non-pharmacological management of children
and adolescent cancer patients there is still a lack of rigorous RCT research Limited by
the characteristics of cancer there is still a lack of large sample sizes
Potential conflicts of interest There is no conflict of interest
Acknowledgements
Thank you to Dr Rie Konno Research Fellow Joanna Briggs Institute for her help in
assessing studies
667
35
References 1 National Comprehensive Cancer Network( NCCN) in USA NCCN clinical practice
guideline in oncology cancer-related fatigue 2011 2 Ekti Genc R amp Conk Z Impact of effective nursing interventions to the fatigue
syndrome in children who receive chemotherapy Cancer Nursing 200831(4)312-317
3 Childhood Cancer Foundation of ROC (2009March) The classification of diseases
and age sex statistical tables of case Childhood Cancer Foundation of ROC newsletter103105-106
4 Department of Health Executive Yuan ROC (TAIWAN)(2009 March 20)2009 cause of death statistic Health and National Health Insurance Annual Statistics Information Service 2010 June 28Available httpwwwdohgovtwstatisticdatavital statists9898health statistic--lifepdf
5 Chang TK (2007December 8) Common childhood cancer and its treatment Status
Childhood Cancer Foundation of ROC (TAIWAN) 2010 September 23 Available httpwwwccfrocorgtwchildchild_events_readphpe_id=45
6 Hockenberry MJ amp Wilson D Wongs nursing care of infants and children (8th ed) St
Louis MO Mosby 2007
7 Post-White J Fitzgerald M Savik K Hooke MC Hannahan AB amp Sencer SF
Massage therapy for children with cancer Journal of Pediatric Oncology Nursing 2009 26(1)16-28
8Chiang YC Yeh CH Wang WKamp Yang CP The experience of cancer-related fatigue
in Taiwanese children European Journal of Cancer Care 2009 18(1)43-49 9Langeveld NE Grootenhuis M A Voute P A de Haan RJ amp van den Bos C No excess
fatigue in young adult survivors of childhood cancer European Journal of Cancer 200339(2)204-214
10Piper BF Lindsey AM amp Dodd MJ Fatigue mechanisms in cancer patients
developing nursing theory Oncology Nursing Forum 1987 14(6)17-23 11Nail LM amp Winningham ML Fatigue In S L Groenwald M H Forgge M Goodman
amp C H Yarbro (Eds) Cancer Nursing Principles and practice (4 th ed) Boston Jones and Bartlett1997
12Irvine D Vincent L Graydon JE Bubela N amp Thompson L The prevalence and
correlates of fatigue in patients receiving treatment with chemotherapy and
668
36
radiotherapy A comparison with the fatigue experienced by healthy individuals Cancer Nursing 199417(5)367-378
13Hinds PS amp Hockenberry-Eaton M Developing a research program on fatigue in
children and adloescents diagnosed with cancer Journal of Pediatric Oncology Nursing 200118(2)3-12
14Aaronson LS Teel CS Cassmeyer V Neuberger GB Pallikkathayil L Pierce J Press
AN Williams DP amp Wingate A Defining and measuring fatigue Journal of Nursing scholarship 1999 31(1)45-50
15Yeh CH Wang CH Chiang YC Lin Lamp Chien LC Assessment of symptoms reported
by 10- to 18-year-old cancer patients in Taiwan 2009 38(5)738-746 16 Okuyama T Akechi T Kugaya A Okamura H Shima Yamp Maruguchi M
Development and validation of the cancer fatigue scale a brief three-dimensional self-rating scale for assessment of fatigue in cancer patients Journal of Pain amp Symptom Management 2000 19(1) 5-14
17Gibson F Mulhall AB Richardson A Edwards JL Ream E amp Sepion BJ A
phenomenologic study of fatigue in adolescents receiving treatment for cancer Oncology Nursing Forum200532(3)651-660
18Wolfe J Grier HE Klar N Levin SB Ellenbogen JMamp Salem-Schatz S et al
Symptoms and suffering at the end of life in children with cancer New England Journal of Medicine 2000342(5)326-333
19Whiting P Bagnall AM Sowden AJ Cornell JE Mulrow CD amp Ramirez G
Interventions for the treatment and management of chronic fatigue syndrome a systematic review JAMA the Journal of the American Medical Association 2001286(11)1360-1368
20 Kangas M Bovbjerg DHamp Montgomery G H Cancer-related fatigue a systematic
and meta-analytic review of non-pharmacological therapies for cancer patients Psychological Bulletin 2008134 (5)700-741
21Williams PD Schmideskamp J Ridder EL amp Williams AR Symptom monitoring and
dependent care during cancer treatment in children pilot study Cancer Nursing 200629(3)188-197
22Takken T van der Torre P Zwerink M Hulzebos EH Bierings M Helders PJMamp van
der Net J Development feasibility and efficacy of a community-based exercise training
669
37
program in pediatric cancer survivors Psycho-Oncology 200918(4)440-448
23Keats MR amp Culos-Reed SN A community-based physical activity program for
adolescents with cancer (project TREK) program feasibility and preliminary findings
Pediatric hematology and oncology 200830(4) 272-280
24Hinds PS Hockenberry M Rai SN Zhang L Razzouk B I Cremer L McCarthy K amp
Rodriguez-Galindo C Clinical field testing of an enhanced-activity intervention in
hospitalized children with cancer Journal of Pain amp Symptom Management 2007
33(6)686-697
25Chiang YC The effects of ldquo a home-based aerobic exercise interventionrdquo on fatigue
and cardiorespiratory fitness in children with acute lymphoblastic leukemia during the
maintenance stage of chemotherapy Unpublished thesis Taiwan Tao-Yuan 2007
26Langeveld N Ubbink M amp Smets E I dont have any energy The experience of
fatigue in young adult survivors of childhood cancer European journal of oncology
nursing 20004(1)20-28
27 Kisner C Colby L Therapeutic exercise Foundations and techniques 2nd ed Philadelphia PAFA Davies 2007
670
38
Appendix I JBI Critical Appraisal Checklist for Experimental studies
Author__________ Year_________ Record Number__________________
Questions 1 to 4 must be answered ldquoyesrdquo for study to be included in the metashyanalysis
1 Were the participants randomized to study groups
Yes No Not clear
2 Other than research intervention were participants in each groups treated the same
Yes No Not clear
3 Were the outcomes measured in the same manner for all participants
Yes No Not clear
4 Were groups comparable at entry
Yes No Not clear
5 Was randomization of participants blinded
Yes No Not clear
6 Were those assessing outcome blinded to treatment allocation (if outcome not objective such as survival or length of hospitalization)
Yes No Not clear
7 Was allocation to treatment groups concealed from the allocator
Yes No Not clear
8 Was an appropriate statistical analysis used
671
39
Yes No Not clear
9 Were outcomes measured in a reliable way
Yes No Not clear
10 Was there adequate followshyup of participants
Yes No Not clear
Summary
TOTAL
Yes No Not clear
DECISION
Use Reject
Narrative summary only Further information needed
COMMENTS
672
40
Appendix II JBI Data Extraction Tool for Quantitative Studies Authors and Year
Journal Title
Record NumberArticle Reference No
Reviewer
Method
Settings
Participants
Number of participants
Group A Group B Group C
Control Intervention 1 Intervention 2
Interventions
Group A
Control
Group B
Intervention 1
Group C
Intervention 2
Outcome measures
Definition
673
41
Other outcome measures
Outcome description ScaleMeasure
Results
Dichotomous Data
Outcome Control Group
Numbertotal number
Treatment Group
Numbertotal number
Continuous Data
Authorrsquos Conclusions
Comments
Outcome Control Group
Mean amp SD
Treatment Group
Mean amp SD
674
43
Appendix III Details of included studies (N=6)(2720212223) RefNo Author(s)
(years) Title Study question Research
method Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
22 Takken T van der Torre P Zwerink M Hulzebos E H Bierings M Helders P J Mamp van der Net J (2009)
Development feasibility and efficacy of a community-based exercise training program in pediatric cancer survivors
To develop a 12-week home-based exercise training program (comprising aerobic and strength exercises) for children who survived ALL and to study itrsquos feasibility and efficacy
Pre-post test design
No comparsion group
Survived ALL(N=9)ages 6-14 years
1anthropometry 2 muscle strength 3functional mobility 4cardio-pulmonary
exercise test 5Fatigue
1 Feasibility questionnaire 2 anthropometry electronic scale and a wallmounted stadiometerHarpenden skin fold calipers 3 muscle strength handheld dynamometer 4functional mobility Timed Up
and Go test (TUG) 5cardio-pulmonary exercise test electronically braked cycle ergometer 6Fatigue(mean)CSI-20 (subjective experience of fatigueconcentrationmotivationphysical activity)
112-week exercise training program
2 Patients were assessed before (T0) and after (T1) 12 weeks of training
1 muscle strength execapacity functional moand fatigue showed nosignificant differences between pre(meanplusmnSD415plusmn147) and post training(meanplusmnSD3687)
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
7 Post-White J Fitzgerald M Savik K Hooke M C Hannahan A B amp Sencer S F (2009)
Massage therapy for children with cancer
To determine whether 4 weekly sessions of massage compared with 4 quiet-time control conditions would reduce anxiety cortisol levels fatigue nausea and pain in children with cancer undergoing chemotherapy and would reduce anxiety fatigue and mood disturbance in a parent
2-period crossover design (Randomized)
quiet-time
control
sessions
Children with cancer 1 to 18 years of age Twenty-three childrenparent dyads were enrolled 17 completed all data points
children 1relaxation 2symptoms 3 fatigue
parents
1anxiety 2 fatigue
children 1relaxation (heart and respiratory rates blood pressure and salivary cortisol level)
2symptoms (pain nausea anxiety 3 fatigue 1-2y3-6yLansky Play Performance Scale (PPS) 7-13y
1 4 weekly massage (MT) sessions alternated with 4 weekly quiet-time(QT) control sessions
2 children included presession and postsession vital signs (heart rate respiratory rate blood pressure) and self-report (parent proxy report for age 1-2 years) of pain nausea and anxiety Fatigue was measured before sessions 1 and 4 and at each follow-up Parent measures
included anxiety fatigue and mood states
1Massage was moreeffective than quiet tireducing heart rate inchildren anxiety in cless than age 14 yeaparent anxiety 2There were no sign
changes in blood pcortisol pain naufatigue (no state d
3 Children reported tmassage helped thebetter lessened theirand worries and hadlasting effects than q
675
44
14-18yChild Fatigue Scale (CFS) (frequency
intensity) 2 parents anxiety and fatigue
676
45
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
24 Hinds P S Hockenberry M Rai S N Zhang L Razzouk B I Cremer L McCarthy K amp Rodriguez-Galindo C (2007)
Clinical field testing of an enhanced-activity intervention in hospitalized children with cancer
To determine the feasibility of an
enhanced physical activity EPA intervention in children and adolescents hospitalized to receive chemotherapy for a solid tumor or AML and to assess the sleep and fatigue outcomes of the intervention using two different statistical approaches to analyze the longitudinal symptom data
randomized prospective two-site and two-group pilot study
Standard care Twenty nine patients (25 with a solid tumor and 4 with AML)ages 7-18 years
1 sleep duration 2 sleep efficiency 3 fatigue
1sleep duration sleep efficiency The
Wrist Actigraph The Daily Sleep Diary-Parent 2 fatigue (mean) The Fatigue Scale(FS-C) for 7-12 (intensity) The Fatigue Scale(FS-A) for 13-18 The Fatigue Scale Parent Version (FS-P) The Fatigue Scale Staff Version (FS-S)
1enhanced physical activity (EPA) (hospital-based 30 minutes
twice daily for 2-4 days) 2 T0On the day of admission
(Day 0 or baseline)patient and parents completed the fatigue instruments and a team member applied the actigraph Patients wore the wrist actigraph T1 from Day 0 to 2 or 3 consecutive days (Days 0e3) In addition the patient same parent and staff nurses completed the daily sleep and fatigue reports in the late afternoons of Days 1-3
1 ANOVA model slesignificantly more the experimental athe control arm whdifferences from bsleep efficiency vaaveraged and com
2 The patient-reported mean fatigue scoresarms were higher amadolescents than for
3 The mixed model anarevealed no significandifferences in patientfatigue between
the two study arms otime( no final result iSD only give mixed result)
677
46
23 Keats M
R amp Culos-Reed S N (2008)
A community-based physical activity program for adolescents with cancer (project TREK) program feasibility and preliminary findings
To examine the
feasibility of a
theoretically-based
physical activity (PA)
intervention in
adolescents with
cancerand
examination of the
impact of the
program on
participant QOL
including social
emotional and
physical
well-being(including fatigue)
Repeat measures longitudinal design
No comparsion group
10 adolescents(Lymphoma(4)leukemia(4)CNS tumor(1)germ cell tumor(1)) ages 14-18 years
1physical fitness 2quality of life (QOL) 3PA behavior 4fatigue
1 Feasibility was assessed by participant recruitment attendance and adherence
2physical fitness Fitnessgram 3quality of life (QOL) Pediatric Quality of Life Inventory (PedsQL) 4PA behavior leisure score index (LSI) 5fatigue (mean) pediatric Quality of life
Multidimensional Fatigue Scale (Peds QL-MFS)
(Generalsleepcognitive fatigue)
116week physical activity (PA)
2 total PA physical fitness and overall QOL was assessed at 5 different intervals T0 preintervention (baseline) T1midintervention (after the
first 8 wk) T2 postintervention
(16 wk) T3 3-months
postintervention T4 1-year poststudy
initiation
1 from baseline -wkssig Improvementstotal PA physfitness and Qgeneral fatigue(meanplusmnSD 796plusmn135)
2 from baseline to 3FUsig Improvin general fatigue(meanplusmnSD824plusmn131)slefatigue(meanplusmnSD755plusmn191)totafatigue(meanplusmnSD778plusmn150)
3at 1 years FUsImprovements in sleeprest fatigue(meanplusmnSD725plusmn203)total (meanplusmnSD 763plusmn
678
47
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
2 Gene R E amp Conk Z (2008)
Impact of Effective Nursing Interventions to the Fatigue Syndrome in Children Who Receive Chemotherapy
1 to examine the effects of an effective nursing intervention to the fatigue syndrome of children 7 to 12 years of age who receive chemotherapy 2Tto examine the relationship between fatigue and demographic variables (age sex) diagnoses ([ALL AML] lymphoma) and therapy-related variables (eg level of hemoglobin
experimental randomized controlled study
Routine nursing care
A total of 60 children who are 7-12 years of age(a new diagnosis of ALL AML or lymphoma and receiving for the first time after being diagnosed a 7- to 10-day chemotherapy treatment )
fatigue The Fatigue Scale(FS-C) for 7-12 (intensity)
The Fatigue Scale Parent Version (FS-P)
1 effective nursing interventions(45- 60mdaya week)education about the fatigue with the chemotherapy and fatigue handbook 2 T1 After a 7-day period the children
and parent were evaluated with the Fatigue Scale
1The difference betwthe 2 mean values wafound to be statisticallsignificant 2 statistically significadifference was found between the Fatigue Scale-Child mean scothe experimental (272the control group (4213)children
679
48
25 Chiang et
al(2007)
The effects of ldquo a home ndashbased aerobic exercise interventionrdquo on fatigue and cardiorespiratory fitness in children with Acute Lymphoblastic Leukemia during the maintenance stage of chemotherapy
To examine the effect of ldquo a home ndashbased aerobic exercise interventionrdquo on fatigue and cardiorespiratory fitness in children with Acute Lymphoblastic Leukemia during the maintenance stage of chemotherapy
Quasi-experi -mental
Routine
nursing care
14 pediatric oncology patients in the experimental group and 10 in control group who were matched by age and sex ages7-18 years
1Cardiorespiratory fitness
2Fatigue
1Cardiorespiratory fitness Physical Activity Recall
VO2maxHR peak 6MWT
2 Fatigue PedsQL-MFS(Generalsleepcognitive fatigue)
1A six-week home-based aerobic exercise intervention 2 8 time points T0 baseline T1-T6 every week during the
intervention(6 weeks) T7 post intervention T8 follow-up (one month after
the end of the home-based exercise program)
1 For intent-to ndash treatthe findings indicated are no intervention efftime differences by anon the subscale of fat2 For per-protocol angeneral fatigue( mean422plusmn402) was the osubscale that was siglower for children whothe exercise interventthose in control groupfollow-up assessmentmonth after the compintervention) 3 The VO2peak are significantly improvingexperimental group atbaseline- and post-intassessment The VO2was significantly highechildren who were in experimental group thcontrol subjects at post-intervention assefor the per-protocol an
680
49
Appendix IV Instrument used to measure fatigue
Name Instrument
developers
Description Used in
age in
ref
Reliability
Consistency of
instrument
Checklist Individual Strength
(CIS)22
Vercoulen et
al1996
20 items using 7-point Likert scale of
fatigue To measure four aspects of
fatiguesubjective experience
contractionmotivation physical
Activity
6-14 Not reported
Child Fatigue Scale (CFS)7 Hockenberry
et al2003
14 items 2 part questionnaire frequency
(yes or no) 5-point Likert scale of the
intensity of any yes responses
7-13
14-18 α073-o84
The Fatigue Scale for 7-12
year Olds (FS-C)224
Hockenberry
et al
14 items provide a fatigue intensity score
5-point Likert scale
7-12 αo84
The Fatigue Scale for 13-18
year Olds (FS-A)24
Hockenberry
et al
14 items provide a fatigue intensity score
5-point Likert scale
13-18 α076-o96
Pediatric Quality of life
Multidimensional Fatigue
Scale (Peds QL-MFS)2325
Varni2002 18 items to measure three aspects of
fatigueGeneralsleepcognitive
14-18 Not reported
681
50
Appendix V Excluded studies and reasons for exclusion
Baggott C Dodd M Kennedy C Marina N Miaskowski C Multiple Symptoms in Pediatric Oncology
Patients A Systematic Review Journal of Pediatric Oncology Nursing 2009 Nov-Dec 27(6)
325-339
Reason for exclusion Not outcome of interest
Barlow JH Ellard DR Psycho-educational interventions for children with chronic disease parents and
siblings an overview of the research evidence base Care Health amp Development 2004 Nov
30(6)637-45
Reason for exclusion Not outcome of interest
Bedider S Moyer CA Randomized controlled trials of pediatric massage A review Evid Based
Complement Alternat Med 2007 Mar 4(1)23-34 Epub 2006 Nov 3
Reason for exclusion Not outcome of interest
de Nijs EJ Ros W Grijpdonck MH Nursing intervention for fatigue during the treatment for cancer Cancer
Nursing 2008 31(3)191-206
Reason for exclusion Not population of interest
Edwards JL Gibson F Richardson A Sepion B Ream E Fatigue in adolescents with and following a
cancer diagnosis developing an evidence base for practice European Journal of Cancer 2003
Dec 39(18)2671-80
Reason for exclusion Not experimental or quasi-experimental study
Hinds PS Hockenberry-Eatan M Developing a research program on fatigue in children and adolescents
diagnosed with cancer Journal of Pediatric Oncology Nursing 2001 Mar-Apr 18(2 Suppl
1)3-12
Reason for exclusion Not experimental or quasi-experimental study
Hockenberry-Eaton M Hinds PS Alcoser P ONeill JB Euell K Howard V Gattuso J Taylor J Fatigue in
Children and Adolescents With Cancer Journal of Pediatric Oncology Nursing 1998 July
15(3)172-182
Reason for exclusion Not experimental or quasi-experimental study
Jean-Pierre P Mustian K Kohli S Roscoe JA Hickok JT Morrow GR Community-based clinical oncology
research trials for cancer-related fatigue The Journal of Supportive Oncology 2006 Nov-Dec
4(10)511-6
682
51
Reason for exclusion Not population of interest
Kangas M Bovbjerg DH Montgomery GH Cancer-Related Fatigue A Systematic and Meta-Analytic
Review of Non-Pharmacological Therapies for Cancer Patients Psychological Bulletin 2008 Sep
134(5)700-41
Reason for exclusion Not population of interest
Lotfi-Jam K Carey M Jefford M Schofield P Charleson C Aranda S Nonpharmacologic strategies for
managing common chemotherapy adverse effects A systematic review Journal of Clinical
Oncology 2008 Dec 1 26(34)5618-29 Epub 2008 Nov 3
Reason for exclusion Not outcome of interest
Marchese VG Chiarello LA Lange BJ Effects of physical therapy intervention for children with acute
lymphoblastic leukemia Pediatr Blood Cancer 2004 Feb42(2)127-33
Reason for exclusion Not outcome of interest
Meeske KA Siegel SE Globe DR Mack WJ Bernstein L Prevalence and correlates of fatigue in
long-term survivors of childhood leukemia Journal of Clinical Oncology 2005 Aug 20
23(24)5501-10
Reason for exclusion Not intervention study
Minton O Richardson A Sharpe M Hotopf Stone P A systematic review and meta-analysis of the
pharmacological treatment of cancer-related fatigue J Natl Cancer Inst 2008 Aug 20
100(16)1155-66 Epub 2008 Aug 11
Reason for exclusion Not population and intervention of interest
Mustian KM Morrow GR Carroll JK Figueroa-Moseley CD Pascal JP Williams GC Integrative
nonpharmacologic behavioral interventions for the management of Cancer-Related fatigue The
Oncologist 2007 12(1)52-67
Reason for exclusion Not population of interest
Neill J Belan I Ried K Effectiveness of non-pharmacological interventions for fatigue in adults with
multiple sclerosis rheumatoid arthritis or systemic lupus erythematosus a systematic review
Journal of Advanced Nursing 2006 Dec 56(6)617-35
Reason for exclusion Not population of interest
Rheingans JI A systematic review of nonpharmacologic adjunctive therapies for symptom management
Journal of Pediatric Oncology Nursing 2007 24(2) 81-94
683
52
Reason for exclusion Not outcome of interest
Rheingans JI Pediatric oncology nursesrsquo management of patients symptoms Journal of Pediatric
Oncology Nursing 2008 Nov 25(6) 303-11
Reason for exclusion Not outcome of interest
San Juan AF Fleck SJ Chamorro-Vintildea C Mateacute-Muntildeoz JL Moral S Peacuterez M Cardona C Del Valle MF
Hernaacutendez M Ramiacuterez M Madero L Lucia A Effects of an intrahospital exercise program
intervention for children with leukemia Medicine amp Science in Sports amp Exercise 2007 Jan
39(1)13-21
Reason for exclusion Not outcome of interest
Sanford SD Okuma JO Pan J Srivastava DK West N Farr L Hinds PS Gender differences in sleep
fatigue and daytime activity in a pediatric oncology sample receiving dexamethasone Journal of
Pediatric Psychology 2008 Apr 33(3)298-306 Epub 2007 Nov 17
Reason for exclusion Not experimental or quasi-experimental study
Schmitz KH Holtzman J Courneya KS Macircsse LC Duval S Kane R Controlled physical activity trials in
cancer survivors a systematic review and meta-analysis Cancer Epidemiol Biomarkers Prev
2005 Jul 14(7)1588-95
Reason for exclusion Not population of interest
van Brussel M Takken T Lucia A van der Net J Helders PJ Is physical fitness decreased in survivors of
childhood leukemia A systematic review Leukemia 2005 Jan 19(1)13-7
Reason for exclusion Not population of interest
Whiting P Bagnall AM Snowden AJ Cornell JE Mulrow CD Ramirez G Interventions for the treatment
and management of chronic fatigue syndrome JAMA 2001 Sep 19 286(11)1360-8
Reason for exclusion Not intervention of interest
Whitsett SF Gudmundsdottir M Davies B McCarthy P Friedman D Chemotherapy-related fatigue in
childhood cancer correlates consequences and coping strategies Journal of Pediatric
Oncology Nursing 2008 Mar-Apr 25(2)86-96 Epub 2008 Feb 29
Reason for exclusion Not experimental or quasi-experimental study
Winner C Muumlller C Hoffmann C Boos J Rosenbaum D Physical activity and childhood cancer Pediatr
Blood Cancer 2010 Apr 54(4)501-10
Reason for exclusion Not research study
684
53
Wu M Hsu L Zhang B Shen N Lu H Li S The experiences of cancer-related fatigue among Chinese
children with leukaemia A phenomenological study Journal of Nursing Studies 2010 Jan
47(1)49-59 Epub 2009 Aug 25
Reason for exclusion Not experimental or quasi-experimental study
Yeh CH Chiang YC Lin L Yang CP Chien LC Weaver MA Chuang HL Clinical factors associated with
fatigue over time in paediatric oncology patients receiving chemotherapy British Journal of
Cancer 2008 Jul 8 99(1)23-9 Epub 2008 Jun 24
Reason for exclusion Not experimental or quasi-experimental study
685
9
quality of life 15 of children with cancer and impacts their daily life16 among all different
types of cancer progress and childrsquos ages However as opposed to the fatigue of adults
the fatigue of children tends to be neglected and left untreated17 by medical and nursing
staffs
In terms of the management approach to cancer-related fatigue Ekti Gene (2008) 2
suggests that strategies could include pharmacologic and non-pharmacologic measures
NCCN (2011) 1 indicated in the Clinical Practice Guidelines in Oncology that during
aggressive treatments during long-term follow-up treatments or in the terminal phase of
cancer the intervening measures for cancer-related fatigue can be divided into
pharmacologic and non-pharmacologic measures Non-pharmacologic measures include
activity enhancement psychosocial interventions (eg cognitive behavioral therapy
(CBT) stress management relaxation support groups) attention-restoring therapy and
nutrition consultation As for the effectiveness of pharmacological measures the
effectiveness is still uncertain However there is evidence to suggest that
methylphenidate may be effective in treating cancer-related fatigue1 Whiting et al
(2001)18 included 36 randomized controlled trials and 8 controlled trails to assess the
effectiveness of the pharmacological and non-pharmacological interventions used in the
treatment or management of chronic fatigue syndrome in adults or children Results
showed insufficient evidence on the effectiveness of the pharmacological supplements
complementaryalternative and other interventions In addition the evidence of
pharmacological treatments of immunoglobulin and hydrocortisone were also
inconclusive However interventions such as cognitive behavioral therapy and graded
exercise therapy have shown promising results
642
10
The efficacy of pharmacological treatments for cancer-related fatigue has not been
established6 therefore there is a need to provide evidence-based findings of the
effectiveness of non-pharmacological interventions to support nursing intervention to
release the childrsquos cancer-related fatigue To date most studies have investigated the
effectiveness of non-pharmacological treatments on cancer-related fatigue of
adults20and to date there is no systematic review in relation to cancer-related fatigue of
children However as children are not a smaller version of adults it is inappropriate to
extrapolate the results of adults onto children Therefore there is a need to establish the
effectiveness of non-pharmacological intervention on the cancer-related fatigue of
children
Given the increase in childhood cancer survival rate the importance of decreasing
childrenrsquos cancer-related fatigue during treatments and so increase their quality of life has
become a focus of their medical teams The role of nurses during care intervention is to
confirm the major symptoms of children with illness and effectively treat each symptom to
increase the childrenrsquos quality of life21 Moreover the USA based NCCN also indicated in
the Care Standard for the Treatment of Cancer-related Fatigue of Children and
Adolescents that treatments for fatigue should be included in the health care teams and
the children and their family should be informed of relevant information The definition of
non-pharmacological interventions for childrenrsquos cancer ndashrelated fatigue include activity
enhancement (exercise physical activity) psychosocial interventions cognitive
behavioral therapy (CBT) stress management relaxation nutrition consultation
massage and educational interventions
643
11
The Cochrane Library of Systematic Reviews and The Joanna Briggs Institute Library of
Systematic Reviews were initially searched to ensure that systematic reviews on this
subject were not already published or being undertaken This initial search prior to the
commencement of the review did not yield any results
This systematic review has examined the effectiveness of non-pharmacologic
interventions on the cancer-related fatigue of children in hope of finding scientific
evidence that can support or refute such measures on children The results of this study
may serve as a reference for professional caregivers children with cancer and their
families or to be put into practice during the clinical care of children with cancer
Definition of terms
FatigueFatigue as a distressing persistent subjective sense of physical emotional
andor cognitive tiredness or exhaustion related to cancer or cancer treatments
that is not proportional to recent activity and interferes with daily function1 There
are various scales and measurements of the degree of fatiguewe have elected to
use the study authors own definitions of fatigue rather than applying a single
pre-set definition of the condition
Non-pharmacological interventionsReferring to reduce fatigue that does not involve
drugsNon-pharmacologic measures include activity enhancement psychosocial
interventions (eg cognitive behavioral therapy stress management relaxation
support groups) attention-restoring therapy and nutrition consultation1
ChemotherapyTreatment with drugs that kill cancer cells 1
644
12
Review QuestionsObjectives
Review Objective
The objective of this systematic review was to critically appraise synthesize and
present the best available evidence concerning the effects of non-pharmacological
interventions fatigue in children and adolescents with cancer
Review Question
The following specific question was addressed in this review
What is the effectiveness of non-pharmacological interventions on fatigue in
children and adolescents with cancer aged from one to 18 years
Criteria for Considering Studies for this Review
Types of studies
This review included randomised controlled trials (RCTs) and quasi-experimental
studies that examine the effectiveness of non-pharmacological intervention for fatigue in
children and adolescents with cancer
Types of participants
Children and adolescents aged from one to 18 years old experiencing fatigue
associated with cancer either during or after the chemotherapy or maintenance stage of
chemotherapy or survive stage The types of cancer to be included in this systematic
review will be ALL (Acute lymphoblastic leukemia) AML (Acute myeloid leukemia)
lymphoma and solid tumors
Exclusion criteria for Types of participants
645
13
newborn infants under 1 years of age
participants who do not have a specific diagnosis of cancer
participants who have received immunoglobulin or hydrocortisone
treatment
If participants have received immunoglobulin or hydrocortisone treatment may
inference the effectiveness of non-pharmacological interventions on fatigue
Types of intervention
This review considered studies that examine non-pharmacological interventions on
fatigue for children and adolescents with cancer including activity enhancement
(exercise physical activity) psychosocial interventions CBT stress management
relaxation nutrition consultation massage and educational interventions The
interventions descriptive included the length frequency setting and intervention
providers eg Nurse Psychologist Dietician
Exclusion criteria for types of interventions only pharmacological interventions were
tested
Types of outcome measures
The outcome measures considered were fatigue scores The literature demonstrates that
differences of opinion exist regarding the most valid and reliable method of measuring
cancer-related fatigue Therefore studies that used any validated scale for
cancer-related fatigue were considered for inclusion Currently commonly used scales to
measure fatigue include Checklist Individual Strength (CIS) Child Fatigue Scale (CFS)
The Fatigue Scale for 7-12 year Olds (FS-C) The Fatigue Scale for 13-18 year Olds
646
14
(FS-A)and Pediatric Quality of life Multidimensional Fatigue Scale (Peds QL-MFS)
Types of settings
Both hospital and community settings
Search Strategy
Before undertaking this systematic review the Cochrane Library Joanna Briggs Institute
Library of Systematic Reviews and CINAHL were searched and no systematic reviews on
this topic were found or identified as underway
The search strategy aimed to find both published and unpublished studies
A three-step search strategy was utilized in each component of this review An initial
limited search of CINAHL and MEDLINE was undertaken followed by an analysis of the
text words contained in the title and abstract and of the index terms used to describe the
article A second search using all identified keywords and index terms was undertaken
Lastly the reference lists of all identified reports and articles were searched for additional
studies
Types of languages
1 English
2 Chinese
The following databases were searched to identify keywords contained in the title and
abstract and relevant MeSH headings and descriptor terms
The Cochrane Library PsycINFO 1990 ndash 2010
647
15
Ovid MEDLINE 1966 ndash 2010 CINAHL Plus with Full Text 1960 ndash2010 EMBASE ProQuest Dissertations amp theses 1990-2010 Electronic theses and dissertations system 1956(abstract)1990(full text)-2010 MEDNAR Index to Taiwan periodical literature 1970-2010 Electronic thesis and dissertation system (Chinese) 1990-2010
Keyword search terms
1Types of studies experimental study random quasi-experimental study實驗性研究隨
機類實驗性研究
2 Types of participants childchildren adolescents pediatric cancer and oncology兒童
青少年兒科癌症腫瘤
3 Types of interventions non-pharmacological interventions massage exercise fitness
physical activity cognitive behavioral stress management energy conservation
sleep therapy relaxation distraction and psycho-education非藥物性處置按摩運動
身體活動認知行為壓力處置能量保存睡眠治療放鬆轉移注意力衛教
4 Types of outcome measures fatigue cancer-related fatigue loss of energy levels of
tiredness tired side effect symptoms疲憊癌性疲憊疲倦合併症症狀
Methods of the Review
Assessment of methodological quality Papers selected for retrieval were assessed by two independent reviewers for
methodological validity prior to inclusion in the review using the standardised critical
appraisal instruments (Appendix I) from the JBI-SUMARI (Joanna Briggs Institute
Systems for the Unified Management Assessment and Review of Information package)
Any disagreements that arise between the reviewers were resolved through discussion
648
16
with a third reviewer
Data extraction Data was extracted from papers included in the review using standardised data
extraction tool (Appendix II) from the JBI-SUMARI Details of eligible studies were
extracted and summarised independently by two reviewers
Data Synthesis
All data analysissynthesis were made using the JBI-SUMARI The studies were
assessed for clinical heterogeneity by considering the settings populations interventions
and outcomes Where possible these binary outcomes were analyzed by calculation of
the Odds Ratio with the 95 CI The weighted mean difference was calculated if the
pooled studies have used the same scale for continuous data The standardized mean
difference was calculated for continuous data measuring the same outcome on a
different scale In studies where statistical pooling of results was inappropriate the
findings were considered for inclusion as a narrative summary
Results The findings from the systematic review are presented first Followed by the results from
the meta-analysis component of this review
Description of studies From database search and hand search a total of 76 papers were identified Thirty
papers were then excluded because they did not meet the inclusion criteria Forty-six
full text were retrieved for further consideration for inclusion Of the 30 excluded reasons
for exclusion were follows 11articles were duplicated eight articles did not meet
649
17
participant inclusion criteria eight articles did not meet outcome criteria and nine articles
were correlation studies or discussion papers others articles were unclear reporting In
total after sorting six papers have been included in this article Figure 1 displays the
process used to identify relevant articles for inclusion in the systematic review
Figure 1 Stages of searching and inclusionexclusion of references for the review
Potentially relevant English-language and Chinese- language Studies Identified
Electronically and hand search (n=76)
Duplicate (n= 11) Papers excluded after evaluation of abstract (n=19)
Papers retrieved for detailed examination (N=46)
Papers excluded after review of full paper
(n=40)
Papers assessed for methodological
quality (n=6)
Papers included in systematic review
(n=6)
Methodological Quality
Of the six included articles 2722232425 two articles were RCT design224 with score 7 out
of 10 each paper from Critical Appraisal Checklist and four articles used
650
18
quasi-experimental design7222425 with socre 5 to 6 out of 10 because the quality of
the whole papers is still acceptable therefore these six articles were accepted after
primary reviewer and secondary reviewerrsquos decision
Randomisation
In two RCT articles224 one study24 used to a computer-generated program operated by
the St Jude Protocol and Data Management System to randomize the sample Another
study2 didnrsquot address how randomization was done
Allocation concealment
No studies reported allocation concealment
Intention-to-treat analysis
One quasi-experimental design7 stated Intention-to-treat analysis
Adequate follow up
The follow-up periods included 2or 3 days24 7 days2 4 week7 one month25 6 week25 12
week2216 week23 and 1 year23
Baseline comparability of groups
Three 22425 of six studies had baseline comparability in terms of age sex diagnosis
race institution duration of illness
Blinded outcome assessment
No studies used blinded outcome assessment The researchers including study team
patients staff and families were not blinded to the patientrsquos group assignment
Characteristics of included studies
651
19
There were six studies related to interventions designed to cancer-related fatigue for
pediatric patients than there are for adults There are a total of six including five
English-language papers 27222324 and one Chinese-language paper 25 ranging in year of
publication from 2007 to 2009
Patient characteristics
The research subjects of four papers included both school-aged children and
adolescents 7222324 one papers involved mainly adolescents25 and one paper sampled
only school-aged children 2 the range in ages was between six-18 years The number of
patients included in the samples ranged from nine to 60 The sources of case data were
from both outpatients and hospitalized children The types of cancer included acute
lymphoblastic leukemia (ALL) solid tumors acute myeloid leukemia (AML) and
lymphoma Overall ALL was the most commonly studied cancer type The stage of the
disease varied in these reports some patients were in the maintenance stage of
chemotherapy25 some had just received their first round of chemotherapy224 some had
completed two courses of treatments lasting 4-8 weeks each 7 and some had entered
the survivor stage 2223
Countries
Two RCTrsquos 2 24 were conducted in the USA There were four quasi-experimental design
studiesThree studies conducted in the USA7 22 23 and one in Taiwan25
Intervention types
652
20
The interventions included exercise training programs 2225 physical activity 2324
massage therapy 7 and health education 223 exercise training and physical activity as
an intervention method given in three different settings home 22 25 community 23 or
hospital 24 The studies used different types of exercise interventions including
home-based aerobic exercise use a Video Compact Disc 25 use of a bicycle-style
exerciser 24 aerobics2223 and various types of physical activities2 and strength-building
exercises 2223 The intensity of the exercise varied and often included gradual warm-up
exercises a period of main exercise and a cool down period For these studies2023 the
target exercise intensity was a heart rate of gt90 of the maximum heart rate (HR max) or
the increase in the percentage of heart rate reserve ( HRR) of 40-60
The number of weeks for the exercisephysical activity interventions duration including
2-4 days 24 6 weeks25 12 weeks22 and 16 weeks23 The frequency of exercise ranged
from 2-3 times per week to twice a day Typical duration of exercise ranged from 10 to 45
minutes There are three papers using exercise interventions based on ACSM (American
College of Sports Medicine) 2225 recommendations and one of these used an Activity
pyramid from the ACSM to determine intensity 24
One article did not clarify the type of exercise intervention or the reasons for their choices
23 In addition there was an article focusing on massage therapy 7 as an intervention in
this study the experimental group received four weeks of massage therapy either in the
clinic or in the patientrsquos room the therapy was applied by a professional masseur and
targeted the back legs arms chest stomach and face of the children However the
frequency of massage sessions per week and the duration of the massages were not
653
21
given There is another article about intervention measures combine health education
and physical activity 2 In this study patients were informed about the following (1) health
education patients received daily education about chemotherapy-related fatigue and
information from a health education manual written by the author (2) encouragement for
children to engage in activities such as listening to music drawing and reading and (3)
physical activity which involved walking along the corridors of the ward for 10-15 minutes
These health education measures were presented for 45-60 minutes a day for a total of
seven days The study design for non-pharmacological interventions used control groups
that included primarily people who had received standard treatment or people who did
not receive an exercise intervention
Outcome measures
Five measurement tools were used in this group of seven papers concerning childrenrsquos
fatigue (Appendix IV) Because those studies included both school-age children and
adolescents the following descriptions will be differentiated by age Fatigue
measurements for school-aged children with cancer include the following the Child
Fatigue Scale (CFS) 7 a scale that measures the frequency and intensity of fatigue and
the Fatigue Scale for 7-12 year Olds (FS-C) 224 a scale that can be used to evaluate the
intensity of fatigue On the other hand fatigue measurements for adolescent cancer
patients include the following the Fatigue Scale for 13-18-year-olds (FS-A) 24 a measure
that can help evaluate fatigue levels the Pediatric Quality of Life Multidimensional
Fatigue Scale (Peds QL-MFS) 2325 a tool that can be divided into three sub-scales to
understand the general cognitive and sleep rest components of fatigue and finally the
CIS-20 for school-age children and adolescents 22 a scale that measures four levels of
654
22
fatigue namely subjective experience attention motivation and physical activity Two
studies used the Peds QL-MFS scale to measure fatigue2325
Meta-analysis results Two studies of the included papers failed to provide sufficient raw data they could not be
included in the meta-analysis Hinds et al 24 did not include post-test data Genc et al 2
provided no pre-test data PostWhite et al7 reported that fatigue after the health
education intervention was not statistically different but they presented the results
without presenting fatigue-related data Therefore the meta-analysis included three
studies 222325
The heterogeneity of studies was analyzed with Chi square statistics and no statistical
significance was found Therefore the data was combined in meta-analysis according to
exercise intervention on fatigue In addition there were three articles using the Peds
QL-MFS as a research tool to examine childrenrsquos improvements in fatigue Among these
Keats 22 and Chiang 24 present the effectiveness of exercise interventions using three
subscales Therefore the meta-analysis also analysis of the effects of these exercise
intervention measures on three subscales of Peds QL-MFS general fatigue sleep rest
fatigue and cognitive fatigue
The effectiveness of exercise intervention for fatigue We analyzed the exercise intervention effect on fatigue A total of 2 studies 22 23 were
included Takken et al 22 used community-based exercise training program to reduce
fatigue of children 6 to 14 years (mean 93y) of age who survived ALL Fatigue
measurement by Checklist Individual Strength (CIS) after 12-week of training fatigue
655
23
show no significant differences between pre (meanplusmnSD 415plusmn147) and post training
(meanplusmnSD368plusmn217) but fatigue change from baseline mean reduction of 11
Keats et al23 although used community-based physical activity program to reduce fatigue
for adolescents 14 to 18 years of age (mean162 y) with cancer (Lymphoma leukemia CNS
tumor germ cell tumor) Studies used fatigue by PedsQLMFS Results show general fatigue
from baseline to 8 weeks and to 3 months follow up significantly improves General
fatigue sleeprest fatigue and total fatigue from baseline to 3 months follow up showed
significant improvements Sleeprest fatigue and total fatigue at 1 years followed up were
significant improvements
Figure 2 shows the overall effect of exercise intervention in children and adolescents with
cancers with a focus on improving fatigue Due to the lower heterogeneity (p>005) the
fixed effects model was used to pool the data for meta-analysis (Overall effect size=
-006 95 Confidence Interval (CI) -070 to 058) A result did not indicate a statistically
significant difference (p = 087)
656
24
Figure2 Meta-analysis results of exercise intervention on fatigue
In addition Keats23 and Chiang25 used the three sub-scales of Peds QL-MFS to
determine the general cognitive and sleep rest components of fatigue The following
present the effectiveness of exercise interventions using three subscales including
general fatigue sleep rest fatigue and cognitive fatigue 2325
Chiang et al 25 used a 6- week home-based aerobic exercise intervention to reduce
fatigue of children 7 to 18 years (mean age at experimental group was 1088 y in control
group was 1247 y) of age who with acute lymphoblastic leukemia Fatigue measurement
by Peds QL-MFS after training For intent-to ndash treat analysis the findings indicated that
there are no intervention effects and time differences by any items on the subscale of
fatigue For per-protocol analysis general fatigue( meanplusmnSD 422plusmn402) was the only
subscale that was significantly lower for children who received the exercise intervention
than those in control group at follow-up assessment (one month after the completion of
intervention)
Keats et al23 although used community-based physical activity program to reduce fatigue
for adolescents 14 to 18 years of age (mean162 y) with cancer (Lymphoma leukemia
CNS tumor germ cell tumor) Both studies used fatigue by PedsQLMFS Results show
general fatigue from baseline to 8 weeks and to 3 months follow up significantly improves
657
25
General fatigue sleeprest fatigue and total fatigue from baseline to 3 months follow up
showed significant improvements Sleeprest fatigue and total fatigue at 1 years followed
up were significant improvements
The effectiveness of exercise intervention for general fatigue
The impact of the exercise interventions upon levels of general fatigue was also analysed
The heterogeneity was low (p>005) Therefore the fixed effects model was used to
examine the effectiveness The effect size is -076 indicating a statistically significant
difference (p = 001 95 CI -135 to -017 Fig 3) The evidence suggests that exercise
intervention can reduce general fatigue in children with cancer
Fig 3 Meta-analysis results of exercise intervention for general fatigue
The effectiveness of exercise intervention for sleep rest fatigue
The following is the result of the meta-analysis of the effectiveness of exercise
interventions on sleep rest fatigue First the heterogeneity test was conducted with P gt
005 representing small heterogeneity and the fixed effects model was used Fig 4
shows the effect size is -035 indicating no statistically significant differences (p = 023
95 CI-092 to 022 Fig 4)
658
26
Fig 4 Meta-analysis results of exercise intervention for sleep rest fatigue
The effectiveness of exercise intervention for cognitive fatigue Lastly the following data reports the results of meta-analysis of the effectiveness of
exercise interventions for cognitive fatigue The heterogeneity was p>005 then the
fixed effects model was used The effect size is -035 indicating no statistically significant
differences (p = 024 95 CI-092 023 Fig 5)
Fig 5 Meta-analysis results of exercise intervention for cognitive fatigue
Narrative presentation of remaining included studies
Three studies were not included in meta-analysis Post-White et al7 one of the aims in
this study was to examine the effect of massage therapy on fatigue in children with
cancer The study was a quasi-experimental design Twenty-three childrenparent dyads
were enrolled 17completed all data points Children with cancer ages 7 to 18 years
received at least 2 identical cycles of chemotherapy and one parent participated in the
2-period crossover design in which 4 weekly massage sessions (MT) alternated with 4
659
27
weekly quiet-time (QT) control sessions There were no significant changes in fatigue in
children over the 4-week MT or QT conditions either independently (change over time) or
when we compared fatigue by condition
The lack of effect of massage on fatigue may be the difficulty some children had in
differentiating fatigue from being relaxed underscores the challenge of measuring fatigue
in children Some children interpreted being tired or relaxed as having greater fatigue
because they felt like lying around and sleeping or felt unmotivated to do their usual
activities all measures of fatigue in the instrument used in the study
Hinds et al24conducted a prospective two-site randomized controlled pilot study to
assess the feasibility of an enhanced physical activity (EPA) intervention in hospitalized
children and adolescents receiving treatment for a solid tumor or for acute myeloid
leukemia (AML) Twenty-nine patients (25 with a solid tumor and 4 with AML) participated
age range from 736 to 1816 (mean 1248 y) The EPA intervention selected was
pedaling a stationary bicycle-style exerciser (Chattanooga Peddler Deluxe Bio-Teck
Medical Memphis TN) for 30 minutes twice daily for 2 to 4 days of hospitalization The
mixed model analysis revealed no significant differences in patient reports of fatigue
between the two study arms or over time
Genc et al2 conducted a RCT involving children with cancer who are 7 to 12 years of age
and receiving chemotherapy treatment to determine the impact of educational
intervention by nurses on decreasing the fatigue syndrome The research sample was
composed of a total of 60 children with cancer with 30 children being included in the
660
28
experimental group (mean age 923)and 30 children included in the control group (mean
age 937) with their mothers In the experimental group after the 7th to 10th day of the
chemotherapy treatment throughout a week the researcher conducted the nursing
interventions every day for 45 to 60 minutes In the control group routine nursing
interventions were carried out The experimental group received education about the
fatigue with the chemotherapy and fatigue handbook was given which was developed by
the authors Children and mothers were consulted for including activities that could
decrease fatigue which were described as effective interventions A statistically
significant difference was found between the Fatigue Scale-Child mean scores of the
experimental (2723) and the control group (4213) The results suggest that fatigue of
children with cancer can be reduced by implementing appropriate nursing interventions
(t=567 Plt00)
Discussion The purpose of this systematic review was to determine the effectiveness of
non-pharmacological interventions specifically targeting fatigue for children and
adolescents with cancer undergoing chemotherapy or after receiving chemotherapy
Included articles about the effectiveness of non-pharmacological interventions for
children and adolescents with cancer were published between the years of 2007 and
2009 Although interventions for cancer fatigue for adults have been extensively studied
it can be seen from either the title of the paper or related content that an intervention
study on children was a pilot study or a feasibility study Representing a field in its early
stage these studies show that the fatigue issues with young cancer patients have only
recently been taken seriously
661
29
The results of our meta-analysis include measurement of the four performance indicators
fatigue and general fatigue sleep rest fatigue and cognitive fatigue The results show
that there is a statistically significant difference only in the domain of general fatigue
using an exercise intervention for children with cancer can improve the degree of fatigue
with the effect size reaching 0671 Other results do not indicate significant differences
The reasons may include the following
1 Characteristics of the cancer The exhaustion from cancer occurs not only during cancer treatment but also in during
long-term survival a time during which patients may continue to be affected by this
symptom 8 26 Therefore when using intervention measures to improve fatigue
circumstances should be considered such as the process of the treatment and the course
or stage of the disease Because cancer patients will experience different forms of
treatment or courses of treatment the disease itself or treatment differences should be
considered in the choice of intervention Even chemotherapy drugs should be taken into
consideration For example a period of general steroid treatment can increase patientsrsquo
fatigue In those studies of children with cancer few studies looked solely at one type of
cancer most studies included a variety of cancer patients Furthermore most studies do
not clearly explain the stage of the disease or course of treatment and most do not
include treatment variables in the control group Moreover children with cancer may
have different levels of physical function
2 Research design The sample size Currently there are few studies with large sample size and a rigorous
RCT design due to the small number of papers available for analysis The sample size
included in our studyrsquos data analysis is between 20 and 42 people this small sample size
will affect the power available to evaluate outcome variables
Although most of the non-pharmacological interventions still use exercise and physical
activity and these studies overall show better results for fatigue as compared with
controls more research is still needed to further confirm the efficacy of these findings
662
30
The dropout rate in the evaluated research varies a great deal ranging from 5 to 45
these dropout rates may result from the characteristics of the research subjects or the
lengthy time involved in participating in these studies The research data with a high
turnover rate might not reflect the actual outcomes of participation in exercise and the
quality of the research contained in articles with high subject turnover rates may be
lower
Exercise doses and time The exercise doses needed to reduce fatigue cannot be
determined additionally the amount of exercise completed by the patient is also
inconsistent interventions vary between 2-3 times per week and two times a day and
exercise duration varies between 10 and 45 minutes each time Furthermore the study
interventions vary in length between a couple of days and a long period of 16 weeks The
data collection times are different some were measured 12 weeks after the intervention
began some were measured during the 6 weeks of intervention some were measured
three months after the intervention was finished and some were measured after one
year
In addition disease-related symptoms decrease childrenrsquos willingness to participate in
exercise interventions inappropriate exercise intervention programs may actually
increase childrens fatigue In addition the children in the study are still developing
physically it is important to consider ways to design an interesting exercise intervention
to increase the compliance of patients in order to improve the effectiveness Although
intervention programs in the hospital or in a community sports center can improve the
effectiveness because they provide supervision the feasibility of these programs is
questionable However if the program is home-based the children need to be
supervised by parents in order to improve their compliance in doing the exercises
Furthermore regarding the nature of the intervention the results from this study indicate
that the researched non-pharmacological interventions include the following exercise
training programs physical activity massage therapy and health education interventions
However according to the National Comprehensive Cancer Network 1 clinical guidelines
663
31
for cancer non-drug measures for cancer fatigue can be separated into five categories
(1) activity enhancement (2) psychosocial interventions such as cognitive behavioral
therapy (CBT) stress management relaxation techniques and support groups (3)
attention-restoring therapy (4) nutritional consultation and (5) cognitive behavioral
therapy specifically targeting sleep disturbance Researchers have also suggested that
psychosocial interventions should be included in the future research for children with
cancer-related fatigue 22
(2) The measurement tools in the study The assessment of fatigue can be
one-dimensional or multidimensional One-dimensional assessment can help understand
the severity of fatigue symptoms however multidimensional scales are often more
credible Therefore when measuring cancer-related fatigue researchers should consider
whether there is a uniform definition of fatigue or a standardized tool for measuring
fatigue in order to facilitate further systematic meta-analyses and further develop the
clinical care guidelines
Limitations of the review The present review has some potential limitations First the low methodological quality
may influence the result Although exercise intervention seems promising quality of the
RCTs was generally quite low Future studies require better design and reporting if
methodological issues to establish evidence-based nonpharmcologic intervention
Second the identified studies covered only a limited types of nonpharmcological
intervention especially in exercise intervention The guidelines for cancer-related fatigue
in NCCN (2011)1 referred to more interventions than the ones included in this review
such as cognitive behavioral therapy and nutrition consultation Thirdly the small sample
size and effect size could be potentially having led to underpowered approach for
detecting the effects on fatigue Therefore we recommend that as research continues to
grow a re-analysis can be undertaken Fourthly Combining data in meta analysis from
664
32
studies where the ages were quite different is a potential source of heterogeneity and
may affect the interpretation of the results
Conclusion At present clinical treatment is widely used for cancer patients However child and
adolescent cancer patients often experience various side effects which cause short-term
or long-term discomfort both physically and psychologically In particular with the
increasing cure rate cancer related fatigue during or after treatment has become an
important issue This study result provided positive effect of exercise intervention on
general fatigue
Implications for practice The results of this systematic review and meta-analysis show that exercise interventions
can effectively improve the level of general fatigue In particular although the articles
were self-reported feasibility studies their results all indicate that exercise interventions
for fatigue are feasible and safe there was no conclusion to be made for the use of
massage therapy or health education measures because there was only one article for
each of these interventions
Recommendations for practice
Cancer-related fatigue is one of the most severe and frequent symptoms by pediatric
oncology children and adolescent suffered during treatment and the symptom existed
even after treatment has ended Until now no golden standard of treatment to fatigue is
established The findings call for more attention to how to reduce patientrsquos levels of
fatigue Based on the available information evaluated in this review the following
recommendations for practice are provided
665
33
bull For children aged 7 to 18 who has cancer (eg Lymphoma leukemia CNS tumor
germ cell tumor) an effective progressive aerobic exercise program is recommended to
be at least 2-3 times per week 20 to 45 minute for each session and last for 6-16 weeks
in order to reduce their general fatigue (tiredness physically weakness) In addition
adults should be involved in accompanying children while they are performing physical
exercise of which should be able to improve the adherence rate (level 2 ) ( Grade of
recommendation A)
bull For children aged 7 to 18 who has cancer (eg Lymphoma leukemia CNS tumor
germ cell tumor) an progressive aerobic exercise program will not be effective to reduce
their sleep andor rest (sleeping or resting a lot) or cognitive fatigue (problems with
thinking quickly or problems with remembering) (level 2 ) ( Grade of recommendation C)
bull Nursing interventions in educating treatment of fatigue include information about
activity nutrition energy preservation consulting and providing a useful fatigue
handbook will benefit those children who are 7 to 12 years have a new diagnosis of ALL
AML or lymphoma and receive for the first time after being diagnosed a 7- to 10-day
chemotherapy treatment (level 2) ( Grade of recommendation A)
bull A 4-week massage therapy program (the therapists massage childrenrsquos back legs
arms stomachchest and face) is not effective for children who are aged 7 to 18 and
have acute lymphoblastic leukemia brain tumors lymphoma rhabdomyosarcoma
Wilms tumor or Ewing sarcoma(level 2)( Grade of recommendation C)
bull Using a 12-week aerobic and strength exercise (45-min exercise sessions twice a
week) is not effective for children who are aged 6-14 and survived acute lymphoblaststic
leukemia age from 6 to 14(level 2) ( Grade of recommendation C)
bull Using a physical activity intervention (30minutestwice daily for 2-4days) is not
effective for children who are 7 to 18 years of age with soild tumor or AML(level 2)
( Grade of recommendation C)
666
34
Implications for research According to this systematic review and meta-analysis results there are suggestions to
improve the effectiveness of future research on non-pharmacological interventions for
children and young peoplersquos cancer-related fatigue
As the majority of included non-pharmacological interventions for the fatigue of cancer
patients consist of exercise programs future research should also consider various
non-pharmacological interventions in order to understand the effectiveness of different
methods
Regarding the exercise intervention methods and studies should consider multiple
factors including the age or personal condition of the subject the disease stage and the
amount of daily activities Studies should use design prescriptions (eg frequency
intensity duration and type of exercise) and consider the adherence to the measures in
order to enhance the study strength
In measuring the results of non-pharmacological interventions there should be standard
definitions or standard measurement tools to facilitate the following systematic review
and meta-analysis that can subsequently be developed into clinical care guidelines
Reviewing the effectiveness of the current non-pharmacological management of children
and adolescent cancer patients there is still a lack of rigorous RCT research Limited by
the characteristics of cancer there is still a lack of large sample sizes
Potential conflicts of interest There is no conflict of interest
Acknowledgements
Thank you to Dr Rie Konno Research Fellow Joanna Briggs Institute for her help in
assessing studies
667
35
References 1 National Comprehensive Cancer Network( NCCN) in USA NCCN clinical practice
guideline in oncology cancer-related fatigue 2011 2 Ekti Genc R amp Conk Z Impact of effective nursing interventions to the fatigue
syndrome in children who receive chemotherapy Cancer Nursing 200831(4)312-317
3 Childhood Cancer Foundation of ROC (2009March) The classification of diseases
and age sex statistical tables of case Childhood Cancer Foundation of ROC newsletter103105-106
4 Department of Health Executive Yuan ROC (TAIWAN)(2009 March 20)2009 cause of death statistic Health and National Health Insurance Annual Statistics Information Service 2010 June 28Available httpwwwdohgovtwstatisticdatavital statists9898health statistic--lifepdf
5 Chang TK (2007December 8) Common childhood cancer and its treatment Status
Childhood Cancer Foundation of ROC (TAIWAN) 2010 September 23 Available httpwwwccfrocorgtwchildchild_events_readphpe_id=45
6 Hockenberry MJ amp Wilson D Wongs nursing care of infants and children (8th ed) St
Louis MO Mosby 2007
7 Post-White J Fitzgerald M Savik K Hooke MC Hannahan AB amp Sencer SF
Massage therapy for children with cancer Journal of Pediatric Oncology Nursing 2009 26(1)16-28
8Chiang YC Yeh CH Wang WKamp Yang CP The experience of cancer-related fatigue
in Taiwanese children European Journal of Cancer Care 2009 18(1)43-49 9Langeveld NE Grootenhuis M A Voute P A de Haan RJ amp van den Bos C No excess
fatigue in young adult survivors of childhood cancer European Journal of Cancer 200339(2)204-214
10Piper BF Lindsey AM amp Dodd MJ Fatigue mechanisms in cancer patients
developing nursing theory Oncology Nursing Forum 1987 14(6)17-23 11Nail LM amp Winningham ML Fatigue In S L Groenwald M H Forgge M Goodman
amp C H Yarbro (Eds) Cancer Nursing Principles and practice (4 th ed) Boston Jones and Bartlett1997
12Irvine D Vincent L Graydon JE Bubela N amp Thompson L The prevalence and
correlates of fatigue in patients receiving treatment with chemotherapy and
668
36
radiotherapy A comparison with the fatigue experienced by healthy individuals Cancer Nursing 199417(5)367-378
13Hinds PS amp Hockenberry-Eaton M Developing a research program on fatigue in
children and adloescents diagnosed with cancer Journal of Pediatric Oncology Nursing 200118(2)3-12
14Aaronson LS Teel CS Cassmeyer V Neuberger GB Pallikkathayil L Pierce J Press
AN Williams DP amp Wingate A Defining and measuring fatigue Journal of Nursing scholarship 1999 31(1)45-50
15Yeh CH Wang CH Chiang YC Lin Lamp Chien LC Assessment of symptoms reported
by 10- to 18-year-old cancer patients in Taiwan 2009 38(5)738-746 16 Okuyama T Akechi T Kugaya A Okamura H Shima Yamp Maruguchi M
Development and validation of the cancer fatigue scale a brief three-dimensional self-rating scale for assessment of fatigue in cancer patients Journal of Pain amp Symptom Management 2000 19(1) 5-14
17Gibson F Mulhall AB Richardson A Edwards JL Ream E amp Sepion BJ A
phenomenologic study of fatigue in adolescents receiving treatment for cancer Oncology Nursing Forum200532(3)651-660
18Wolfe J Grier HE Klar N Levin SB Ellenbogen JMamp Salem-Schatz S et al
Symptoms and suffering at the end of life in children with cancer New England Journal of Medicine 2000342(5)326-333
19Whiting P Bagnall AM Sowden AJ Cornell JE Mulrow CD amp Ramirez G
Interventions for the treatment and management of chronic fatigue syndrome a systematic review JAMA the Journal of the American Medical Association 2001286(11)1360-1368
20 Kangas M Bovbjerg DHamp Montgomery G H Cancer-related fatigue a systematic
and meta-analytic review of non-pharmacological therapies for cancer patients Psychological Bulletin 2008134 (5)700-741
21Williams PD Schmideskamp J Ridder EL amp Williams AR Symptom monitoring and
dependent care during cancer treatment in children pilot study Cancer Nursing 200629(3)188-197
22Takken T van der Torre P Zwerink M Hulzebos EH Bierings M Helders PJMamp van
der Net J Development feasibility and efficacy of a community-based exercise training
669
37
program in pediatric cancer survivors Psycho-Oncology 200918(4)440-448
23Keats MR amp Culos-Reed SN A community-based physical activity program for
adolescents with cancer (project TREK) program feasibility and preliminary findings
Pediatric hematology and oncology 200830(4) 272-280
24Hinds PS Hockenberry M Rai SN Zhang L Razzouk B I Cremer L McCarthy K amp
Rodriguez-Galindo C Clinical field testing of an enhanced-activity intervention in
hospitalized children with cancer Journal of Pain amp Symptom Management 2007
33(6)686-697
25Chiang YC The effects of ldquo a home-based aerobic exercise interventionrdquo on fatigue
and cardiorespiratory fitness in children with acute lymphoblastic leukemia during the
maintenance stage of chemotherapy Unpublished thesis Taiwan Tao-Yuan 2007
26Langeveld N Ubbink M amp Smets E I dont have any energy The experience of
fatigue in young adult survivors of childhood cancer European journal of oncology
nursing 20004(1)20-28
27 Kisner C Colby L Therapeutic exercise Foundations and techniques 2nd ed Philadelphia PAFA Davies 2007
670
38
Appendix I JBI Critical Appraisal Checklist for Experimental studies
Author__________ Year_________ Record Number__________________
Questions 1 to 4 must be answered ldquoyesrdquo for study to be included in the metashyanalysis
1 Were the participants randomized to study groups
Yes No Not clear
2 Other than research intervention were participants in each groups treated the same
Yes No Not clear
3 Were the outcomes measured in the same manner for all participants
Yes No Not clear
4 Were groups comparable at entry
Yes No Not clear
5 Was randomization of participants blinded
Yes No Not clear
6 Were those assessing outcome blinded to treatment allocation (if outcome not objective such as survival or length of hospitalization)
Yes No Not clear
7 Was allocation to treatment groups concealed from the allocator
Yes No Not clear
8 Was an appropriate statistical analysis used
671
39
Yes No Not clear
9 Were outcomes measured in a reliable way
Yes No Not clear
10 Was there adequate followshyup of participants
Yes No Not clear
Summary
TOTAL
Yes No Not clear
DECISION
Use Reject
Narrative summary only Further information needed
COMMENTS
672
40
Appendix II JBI Data Extraction Tool for Quantitative Studies Authors and Year
Journal Title
Record NumberArticle Reference No
Reviewer
Method
Settings
Participants
Number of participants
Group A Group B Group C
Control Intervention 1 Intervention 2
Interventions
Group A
Control
Group B
Intervention 1
Group C
Intervention 2
Outcome measures
Definition
673
41
Other outcome measures
Outcome description ScaleMeasure
Results
Dichotomous Data
Outcome Control Group
Numbertotal number
Treatment Group
Numbertotal number
Continuous Data
Authorrsquos Conclusions
Comments
Outcome Control Group
Mean amp SD
Treatment Group
Mean amp SD
674
43
Appendix III Details of included studies (N=6)(2720212223) RefNo Author(s)
(years) Title Study question Research
method Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
22 Takken T van der Torre P Zwerink M Hulzebos E H Bierings M Helders P J Mamp van der Net J (2009)
Development feasibility and efficacy of a community-based exercise training program in pediatric cancer survivors
To develop a 12-week home-based exercise training program (comprising aerobic and strength exercises) for children who survived ALL and to study itrsquos feasibility and efficacy
Pre-post test design
No comparsion group
Survived ALL(N=9)ages 6-14 years
1anthropometry 2 muscle strength 3functional mobility 4cardio-pulmonary
exercise test 5Fatigue
1 Feasibility questionnaire 2 anthropometry electronic scale and a wallmounted stadiometerHarpenden skin fold calipers 3 muscle strength handheld dynamometer 4functional mobility Timed Up
and Go test (TUG) 5cardio-pulmonary exercise test electronically braked cycle ergometer 6Fatigue(mean)CSI-20 (subjective experience of fatigueconcentrationmotivationphysical activity)
112-week exercise training program
2 Patients were assessed before (T0) and after (T1) 12 weeks of training
1 muscle strength execapacity functional moand fatigue showed nosignificant differences between pre(meanplusmnSD415plusmn147) and post training(meanplusmnSD3687)
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
7 Post-White J Fitzgerald M Savik K Hooke M C Hannahan A B amp Sencer S F (2009)
Massage therapy for children with cancer
To determine whether 4 weekly sessions of massage compared with 4 quiet-time control conditions would reduce anxiety cortisol levels fatigue nausea and pain in children with cancer undergoing chemotherapy and would reduce anxiety fatigue and mood disturbance in a parent
2-period crossover design (Randomized)
quiet-time
control
sessions
Children with cancer 1 to 18 years of age Twenty-three childrenparent dyads were enrolled 17 completed all data points
children 1relaxation 2symptoms 3 fatigue
parents
1anxiety 2 fatigue
children 1relaxation (heart and respiratory rates blood pressure and salivary cortisol level)
2symptoms (pain nausea anxiety 3 fatigue 1-2y3-6yLansky Play Performance Scale (PPS) 7-13y
1 4 weekly massage (MT) sessions alternated with 4 weekly quiet-time(QT) control sessions
2 children included presession and postsession vital signs (heart rate respiratory rate blood pressure) and self-report (parent proxy report for age 1-2 years) of pain nausea and anxiety Fatigue was measured before sessions 1 and 4 and at each follow-up Parent measures
included anxiety fatigue and mood states
1Massage was moreeffective than quiet tireducing heart rate inchildren anxiety in cless than age 14 yeaparent anxiety 2There were no sign
changes in blood pcortisol pain naufatigue (no state d
3 Children reported tmassage helped thebetter lessened theirand worries and hadlasting effects than q
675
44
14-18yChild Fatigue Scale (CFS) (frequency
intensity) 2 parents anxiety and fatigue
676
45
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
24 Hinds P S Hockenberry M Rai S N Zhang L Razzouk B I Cremer L McCarthy K amp Rodriguez-Galindo C (2007)
Clinical field testing of an enhanced-activity intervention in hospitalized children with cancer
To determine the feasibility of an
enhanced physical activity EPA intervention in children and adolescents hospitalized to receive chemotherapy for a solid tumor or AML and to assess the sleep and fatigue outcomes of the intervention using two different statistical approaches to analyze the longitudinal symptom data
randomized prospective two-site and two-group pilot study
Standard care Twenty nine patients (25 with a solid tumor and 4 with AML)ages 7-18 years
1 sleep duration 2 sleep efficiency 3 fatigue
1sleep duration sleep efficiency The
Wrist Actigraph The Daily Sleep Diary-Parent 2 fatigue (mean) The Fatigue Scale(FS-C) for 7-12 (intensity) The Fatigue Scale(FS-A) for 13-18 The Fatigue Scale Parent Version (FS-P) The Fatigue Scale Staff Version (FS-S)
1enhanced physical activity (EPA) (hospital-based 30 minutes
twice daily for 2-4 days) 2 T0On the day of admission
(Day 0 or baseline)patient and parents completed the fatigue instruments and a team member applied the actigraph Patients wore the wrist actigraph T1 from Day 0 to 2 or 3 consecutive days (Days 0e3) In addition the patient same parent and staff nurses completed the daily sleep and fatigue reports in the late afternoons of Days 1-3
1 ANOVA model slesignificantly more the experimental athe control arm whdifferences from bsleep efficiency vaaveraged and com
2 The patient-reported mean fatigue scoresarms were higher amadolescents than for
3 The mixed model anarevealed no significandifferences in patientfatigue between
the two study arms otime( no final result iSD only give mixed result)
677
46
23 Keats M
R amp Culos-Reed S N (2008)
A community-based physical activity program for adolescents with cancer (project TREK) program feasibility and preliminary findings
To examine the
feasibility of a
theoretically-based
physical activity (PA)
intervention in
adolescents with
cancerand
examination of the
impact of the
program on
participant QOL
including social
emotional and
physical
well-being(including fatigue)
Repeat measures longitudinal design
No comparsion group
10 adolescents(Lymphoma(4)leukemia(4)CNS tumor(1)germ cell tumor(1)) ages 14-18 years
1physical fitness 2quality of life (QOL) 3PA behavior 4fatigue
1 Feasibility was assessed by participant recruitment attendance and adherence
2physical fitness Fitnessgram 3quality of life (QOL) Pediatric Quality of Life Inventory (PedsQL) 4PA behavior leisure score index (LSI) 5fatigue (mean) pediatric Quality of life
Multidimensional Fatigue Scale (Peds QL-MFS)
(Generalsleepcognitive fatigue)
116week physical activity (PA)
2 total PA physical fitness and overall QOL was assessed at 5 different intervals T0 preintervention (baseline) T1midintervention (after the
first 8 wk) T2 postintervention
(16 wk) T3 3-months
postintervention T4 1-year poststudy
initiation
1 from baseline -wkssig Improvementstotal PA physfitness and Qgeneral fatigue(meanplusmnSD 796plusmn135)
2 from baseline to 3FUsig Improvin general fatigue(meanplusmnSD824plusmn131)slefatigue(meanplusmnSD755plusmn191)totafatigue(meanplusmnSD778plusmn150)
3at 1 years FUsImprovements in sleeprest fatigue(meanplusmnSD725plusmn203)total (meanplusmnSD 763plusmn
678
47
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
2 Gene R E amp Conk Z (2008)
Impact of Effective Nursing Interventions to the Fatigue Syndrome in Children Who Receive Chemotherapy
1 to examine the effects of an effective nursing intervention to the fatigue syndrome of children 7 to 12 years of age who receive chemotherapy 2Tto examine the relationship between fatigue and demographic variables (age sex) diagnoses ([ALL AML] lymphoma) and therapy-related variables (eg level of hemoglobin
experimental randomized controlled study
Routine nursing care
A total of 60 children who are 7-12 years of age(a new diagnosis of ALL AML or lymphoma and receiving for the first time after being diagnosed a 7- to 10-day chemotherapy treatment )
fatigue The Fatigue Scale(FS-C) for 7-12 (intensity)
The Fatigue Scale Parent Version (FS-P)
1 effective nursing interventions(45- 60mdaya week)education about the fatigue with the chemotherapy and fatigue handbook 2 T1 After a 7-day period the children
and parent were evaluated with the Fatigue Scale
1The difference betwthe 2 mean values wafound to be statisticallsignificant 2 statistically significadifference was found between the Fatigue Scale-Child mean scothe experimental (272the control group (4213)children
679
48
25 Chiang et
al(2007)
The effects of ldquo a home ndashbased aerobic exercise interventionrdquo on fatigue and cardiorespiratory fitness in children with Acute Lymphoblastic Leukemia during the maintenance stage of chemotherapy
To examine the effect of ldquo a home ndashbased aerobic exercise interventionrdquo on fatigue and cardiorespiratory fitness in children with Acute Lymphoblastic Leukemia during the maintenance stage of chemotherapy
Quasi-experi -mental
Routine
nursing care
14 pediatric oncology patients in the experimental group and 10 in control group who were matched by age and sex ages7-18 years
1Cardiorespiratory fitness
2Fatigue
1Cardiorespiratory fitness Physical Activity Recall
VO2maxHR peak 6MWT
2 Fatigue PedsQL-MFS(Generalsleepcognitive fatigue)
1A six-week home-based aerobic exercise intervention 2 8 time points T0 baseline T1-T6 every week during the
intervention(6 weeks) T7 post intervention T8 follow-up (one month after
the end of the home-based exercise program)
1 For intent-to ndash treatthe findings indicated are no intervention efftime differences by anon the subscale of fat2 For per-protocol angeneral fatigue( mean422plusmn402) was the osubscale that was siglower for children whothe exercise interventthose in control groupfollow-up assessmentmonth after the compintervention) 3 The VO2peak are significantly improvingexperimental group atbaseline- and post-intassessment The VO2was significantly highechildren who were in experimental group thcontrol subjects at post-intervention assefor the per-protocol an
680
49
Appendix IV Instrument used to measure fatigue
Name Instrument
developers
Description Used in
age in
ref
Reliability
Consistency of
instrument
Checklist Individual Strength
(CIS)22
Vercoulen et
al1996
20 items using 7-point Likert scale of
fatigue To measure four aspects of
fatiguesubjective experience
contractionmotivation physical
Activity
6-14 Not reported
Child Fatigue Scale (CFS)7 Hockenberry
et al2003
14 items 2 part questionnaire frequency
(yes or no) 5-point Likert scale of the
intensity of any yes responses
7-13
14-18 α073-o84
The Fatigue Scale for 7-12
year Olds (FS-C)224
Hockenberry
et al
14 items provide a fatigue intensity score
5-point Likert scale
7-12 αo84
The Fatigue Scale for 13-18
year Olds (FS-A)24
Hockenberry
et al
14 items provide a fatigue intensity score
5-point Likert scale
13-18 α076-o96
Pediatric Quality of life
Multidimensional Fatigue
Scale (Peds QL-MFS)2325
Varni2002 18 items to measure three aspects of
fatigueGeneralsleepcognitive
14-18 Not reported
681
50
Appendix V Excluded studies and reasons for exclusion
Baggott C Dodd M Kennedy C Marina N Miaskowski C Multiple Symptoms in Pediatric Oncology
Patients A Systematic Review Journal of Pediatric Oncology Nursing 2009 Nov-Dec 27(6)
325-339
Reason for exclusion Not outcome of interest
Barlow JH Ellard DR Psycho-educational interventions for children with chronic disease parents and
siblings an overview of the research evidence base Care Health amp Development 2004 Nov
30(6)637-45
Reason for exclusion Not outcome of interest
Bedider S Moyer CA Randomized controlled trials of pediatric massage A review Evid Based
Complement Alternat Med 2007 Mar 4(1)23-34 Epub 2006 Nov 3
Reason for exclusion Not outcome of interest
de Nijs EJ Ros W Grijpdonck MH Nursing intervention for fatigue during the treatment for cancer Cancer
Nursing 2008 31(3)191-206
Reason for exclusion Not population of interest
Edwards JL Gibson F Richardson A Sepion B Ream E Fatigue in adolescents with and following a
cancer diagnosis developing an evidence base for practice European Journal of Cancer 2003
Dec 39(18)2671-80
Reason for exclusion Not experimental or quasi-experimental study
Hinds PS Hockenberry-Eatan M Developing a research program on fatigue in children and adolescents
diagnosed with cancer Journal of Pediatric Oncology Nursing 2001 Mar-Apr 18(2 Suppl
1)3-12
Reason for exclusion Not experimental or quasi-experimental study
Hockenberry-Eaton M Hinds PS Alcoser P ONeill JB Euell K Howard V Gattuso J Taylor J Fatigue in
Children and Adolescents With Cancer Journal of Pediatric Oncology Nursing 1998 July
15(3)172-182
Reason for exclusion Not experimental or quasi-experimental study
Jean-Pierre P Mustian K Kohli S Roscoe JA Hickok JT Morrow GR Community-based clinical oncology
research trials for cancer-related fatigue The Journal of Supportive Oncology 2006 Nov-Dec
4(10)511-6
682
51
Reason for exclusion Not population of interest
Kangas M Bovbjerg DH Montgomery GH Cancer-Related Fatigue A Systematic and Meta-Analytic
Review of Non-Pharmacological Therapies for Cancer Patients Psychological Bulletin 2008 Sep
134(5)700-41
Reason for exclusion Not population of interest
Lotfi-Jam K Carey M Jefford M Schofield P Charleson C Aranda S Nonpharmacologic strategies for
managing common chemotherapy adverse effects A systematic review Journal of Clinical
Oncology 2008 Dec 1 26(34)5618-29 Epub 2008 Nov 3
Reason for exclusion Not outcome of interest
Marchese VG Chiarello LA Lange BJ Effects of physical therapy intervention for children with acute
lymphoblastic leukemia Pediatr Blood Cancer 2004 Feb42(2)127-33
Reason for exclusion Not outcome of interest
Meeske KA Siegel SE Globe DR Mack WJ Bernstein L Prevalence and correlates of fatigue in
long-term survivors of childhood leukemia Journal of Clinical Oncology 2005 Aug 20
23(24)5501-10
Reason for exclusion Not intervention study
Minton O Richardson A Sharpe M Hotopf Stone P A systematic review and meta-analysis of the
pharmacological treatment of cancer-related fatigue J Natl Cancer Inst 2008 Aug 20
100(16)1155-66 Epub 2008 Aug 11
Reason for exclusion Not population and intervention of interest
Mustian KM Morrow GR Carroll JK Figueroa-Moseley CD Pascal JP Williams GC Integrative
nonpharmacologic behavioral interventions for the management of Cancer-Related fatigue The
Oncologist 2007 12(1)52-67
Reason for exclusion Not population of interest
Neill J Belan I Ried K Effectiveness of non-pharmacological interventions for fatigue in adults with
multiple sclerosis rheumatoid arthritis or systemic lupus erythematosus a systematic review
Journal of Advanced Nursing 2006 Dec 56(6)617-35
Reason for exclusion Not population of interest
Rheingans JI A systematic review of nonpharmacologic adjunctive therapies for symptom management
Journal of Pediatric Oncology Nursing 2007 24(2) 81-94
683
52
Reason for exclusion Not outcome of interest
Rheingans JI Pediatric oncology nursesrsquo management of patients symptoms Journal of Pediatric
Oncology Nursing 2008 Nov 25(6) 303-11
Reason for exclusion Not outcome of interest
San Juan AF Fleck SJ Chamorro-Vintildea C Mateacute-Muntildeoz JL Moral S Peacuterez M Cardona C Del Valle MF
Hernaacutendez M Ramiacuterez M Madero L Lucia A Effects of an intrahospital exercise program
intervention for children with leukemia Medicine amp Science in Sports amp Exercise 2007 Jan
39(1)13-21
Reason for exclusion Not outcome of interest
Sanford SD Okuma JO Pan J Srivastava DK West N Farr L Hinds PS Gender differences in sleep
fatigue and daytime activity in a pediatric oncology sample receiving dexamethasone Journal of
Pediatric Psychology 2008 Apr 33(3)298-306 Epub 2007 Nov 17
Reason for exclusion Not experimental or quasi-experimental study
Schmitz KH Holtzman J Courneya KS Macircsse LC Duval S Kane R Controlled physical activity trials in
cancer survivors a systematic review and meta-analysis Cancer Epidemiol Biomarkers Prev
2005 Jul 14(7)1588-95
Reason for exclusion Not population of interest
van Brussel M Takken T Lucia A van der Net J Helders PJ Is physical fitness decreased in survivors of
childhood leukemia A systematic review Leukemia 2005 Jan 19(1)13-7
Reason for exclusion Not population of interest
Whiting P Bagnall AM Snowden AJ Cornell JE Mulrow CD Ramirez G Interventions for the treatment
and management of chronic fatigue syndrome JAMA 2001 Sep 19 286(11)1360-8
Reason for exclusion Not intervention of interest
Whitsett SF Gudmundsdottir M Davies B McCarthy P Friedman D Chemotherapy-related fatigue in
childhood cancer correlates consequences and coping strategies Journal of Pediatric
Oncology Nursing 2008 Mar-Apr 25(2)86-96 Epub 2008 Feb 29
Reason for exclusion Not experimental or quasi-experimental study
Winner C Muumlller C Hoffmann C Boos J Rosenbaum D Physical activity and childhood cancer Pediatr
Blood Cancer 2010 Apr 54(4)501-10
Reason for exclusion Not research study
684
53
Wu M Hsu L Zhang B Shen N Lu H Li S The experiences of cancer-related fatigue among Chinese
children with leukaemia A phenomenological study Journal of Nursing Studies 2010 Jan
47(1)49-59 Epub 2009 Aug 25
Reason for exclusion Not experimental or quasi-experimental study
Yeh CH Chiang YC Lin L Yang CP Chien LC Weaver MA Chuang HL Clinical factors associated with
fatigue over time in paediatric oncology patients receiving chemotherapy British Journal of
Cancer 2008 Jul 8 99(1)23-9 Epub 2008 Jun 24
Reason for exclusion Not experimental or quasi-experimental study
685
10
The efficacy of pharmacological treatments for cancer-related fatigue has not been
established6 therefore there is a need to provide evidence-based findings of the
effectiveness of non-pharmacological interventions to support nursing intervention to
release the childrsquos cancer-related fatigue To date most studies have investigated the
effectiveness of non-pharmacological treatments on cancer-related fatigue of
adults20and to date there is no systematic review in relation to cancer-related fatigue of
children However as children are not a smaller version of adults it is inappropriate to
extrapolate the results of adults onto children Therefore there is a need to establish the
effectiveness of non-pharmacological intervention on the cancer-related fatigue of
children
Given the increase in childhood cancer survival rate the importance of decreasing
childrenrsquos cancer-related fatigue during treatments and so increase their quality of life has
become a focus of their medical teams The role of nurses during care intervention is to
confirm the major symptoms of children with illness and effectively treat each symptom to
increase the childrenrsquos quality of life21 Moreover the USA based NCCN also indicated in
the Care Standard for the Treatment of Cancer-related Fatigue of Children and
Adolescents that treatments for fatigue should be included in the health care teams and
the children and their family should be informed of relevant information The definition of
non-pharmacological interventions for childrenrsquos cancer ndashrelated fatigue include activity
enhancement (exercise physical activity) psychosocial interventions cognitive
behavioral therapy (CBT) stress management relaxation nutrition consultation
massage and educational interventions
643
11
The Cochrane Library of Systematic Reviews and The Joanna Briggs Institute Library of
Systematic Reviews were initially searched to ensure that systematic reviews on this
subject were not already published or being undertaken This initial search prior to the
commencement of the review did not yield any results
This systematic review has examined the effectiveness of non-pharmacologic
interventions on the cancer-related fatigue of children in hope of finding scientific
evidence that can support or refute such measures on children The results of this study
may serve as a reference for professional caregivers children with cancer and their
families or to be put into practice during the clinical care of children with cancer
Definition of terms
FatigueFatigue as a distressing persistent subjective sense of physical emotional
andor cognitive tiredness or exhaustion related to cancer or cancer treatments
that is not proportional to recent activity and interferes with daily function1 There
are various scales and measurements of the degree of fatiguewe have elected to
use the study authors own definitions of fatigue rather than applying a single
pre-set definition of the condition
Non-pharmacological interventionsReferring to reduce fatigue that does not involve
drugsNon-pharmacologic measures include activity enhancement psychosocial
interventions (eg cognitive behavioral therapy stress management relaxation
support groups) attention-restoring therapy and nutrition consultation1
ChemotherapyTreatment with drugs that kill cancer cells 1
644
12
Review QuestionsObjectives
Review Objective
The objective of this systematic review was to critically appraise synthesize and
present the best available evidence concerning the effects of non-pharmacological
interventions fatigue in children and adolescents with cancer
Review Question
The following specific question was addressed in this review
What is the effectiveness of non-pharmacological interventions on fatigue in
children and adolescents with cancer aged from one to 18 years
Criteria for Considering Studies for this Review
Types of studies
This review included randomised controlled trials (RCTs) and quasi-experimental
studies that examine the effectiveness of non-pharmacological intervention for fatigue in
children and adolescents with cancer
Types of participants
Children and adolescents aged from one to 18 years old experiencing fatigue
associated with cancer either during or after the chemotherapy or maintenance stage of
chemotherapy or survive stage The types of cancer to be included in this systematic
review will be ALL (Acute lymphoblastic leukemia) AML (Acute myeloid leukemia)
lymphoma and solid tumors
Exclusion criteria for Types of participants
645
13
newborn infants under 1 years of age
participants who do not have a specific diagnosis of cancer
participants who have received immunoglobulin or hydrocortisone
treatment
If participants have received immunoglobulin or hydrocortisone treatment may
inference the effectiveness of non-pharmacological interventions on fatigue
Types of intervention
This review considered studies that examine non-pharmacological interventions on
fatigue for children and adolescents with cancer including activity enhancement
(exercise physical activity) psychosocial interventions CBT stress management
relaxation nutrition consultation massage and educational interventions The
interventions descriptive included the length frequency setting and intervention
providers eg Nurse Psychologist Dietician
Exclusion criteria for types of interventions only pharmacological interventions were
tested
Types of outcome measures
The outcome measures considered were fatigue scores The literature demonstrates that
differences of opinion exist regarding the most valid and reliable method of measuring
cancer-related fatigue Therefore studies that used any validated scale for
cancer-related fatigue were considered for inclusion Currently commonly used scales to
measure fatigue include Checklist Individual Strength (CIS) Child Fatigue Scale (CFS)
The Fatigue Scale for 7-12 year Olds (FS-C) The Fatigue Scale for 13-18 year Olds
646
14
(FS-A)and Pediatric Quality of life Multidimensional Fatigue Scale (Peds QL-MFS)
Types of settings
Both hospital and community settings
Search Strategy
Before undertaking this systematic review the Cochrane Library Joanna Briggs Institute
Library of Systematic Reviews and CINAHL were searched and no systematic reviews on
this topic were found or identified as underway
The search strategy aimed to find both published and unpublished studies
A three-step search strategy was utilized in each component of this review An initial
limited search of CINAHL and MEDLINE was undertaken followed by an analysis of the
text words contained in the title and abstract and of the index terms used to describe the
article A second search using all identified keywords and index terms was undertaken
Lastly the reference lists of all identified reports and articles were searched for additional
studies
Types of languages
1 English
2 Chinese
The following databases were searched to identify keywords contained in the title and
abstract and relevant MeSH headings and descriptor terms
The Cochrane Library PsycINFO 1990 ndash 2010
647
15
Ovid MEDLINE 1966 ndash 2010 CINAHL Plus with Full Text 1960 ndash2010 EMBASE ProQuest Dissertations amp theses 1990-2010 Electronic theses and dissertations system 1956(abstract)1990(full text)-2010 MEDNAR Index to Taiwan periodical literature 1970-2010 Electronic thesis and dissertation system (Chinese) 1990-2010
Keyword search terms
1Types of studies experimental study random quasi-experimental study實驗性研究隨
機類實驗性研究
2 Types of participants childchildren adolescents pediatric cancer and oncology兒童
青少年兒科癌症腫瘤
3 Types of interventions non-pharmacological interventions massage exercise fitness
physical activity cognitive behavioral stress management energy conservation
sleep therapy relaxation distraction and psycho-education非藥物性處置按摩運動
身體活動認知行為壓力處置能量保存睡眠治療放鬆轉移注意力衛教
4 Types of outcome measures fatigue cancer-related fatigue loss of energy levels of
tiredness tired side effect symptoms疲憊癌性疲憊疲倦合併症症狀
Methods of the Review
Assessment of methodological quality Papers selected for retrieval were assessed by two independent reviewers for
methodological validity prior to inclusion in the review using the standardised critical
appraisal instruments (Appendix I) from the JBI-SUMARI (Joanna Briggs Institute
Systems for the Unified Management Assessment and Review of Information package)
Any disagreements that arise between the reviewers were resolved through discussion
648
16
with a third reviewer
Data extraction Data was extracted from papers included in the review using standardised data
extraction tool (Appendix II) from the JBI-SUMARI Details of eligible studies were
extracted and summarised independently by two reviewers
Data Synthesis
All data analysissynthesis were made using the JBI-SUMARI The studies were
assessed for clinical heterogeneity by considering the settings populations interventions
and outcomes Where possible these binary outcomes were analyzed by calculation of
the Odds Ratio with the 95 CI The weighted mean difference was calculated if the
pooled studies have used the same scale for continuous data The standardized mean
difference was calculated for continuous data measuring the same outcome on a
different scale In studies where statistical pooling of results was inappropriate the
findings were considered for inclusion as a narrative summary
Results The findings from the systematic review are presented first Followed by the results from
the meta-analysis component of this review
Description of studies From database search and hand search a total of 76 papers were identified Thirty
papers were then excluded because they did not meet the inclusion criteria Forty-six
full text were retrieved for further consideration for inclusion Of the 30 excluded reasons
for exclusion were follows 11articles were duplicated eight articles did not meet
649
17
participant inclusion criteria eight articles did not meet outcome criteria and nine articles
were correlation studies or discussion papers others articles were unclear reporting In
total after sorting six papers have been included in this article Figure 1 displays the
process used to identify relevant articles for inclusion in the systematic review
Figure 1 Stages of searching and inclusionexclusion of references for the review
Potentially relevant English-language and Chinese- language Studies Identified
Electronically and hand search (n=76)
Duplicate (n= 11) Papers excluded after evaluation of abstract (n=19)
Papers retrieved for detailed examination (N=46)
Papers excluded after review of full paper
(n=40)
Papers assessed for methodological
quality (n=6)
Papers included in systematic review
(n=6)
Methodological Quality
Of the six included articles 2722232425 two articles were RCT design224 with score 7 out
of 10 each paper from Critical Appraisal Checklist and four articles used
650
18
quasi-experimental design7222425 with socre 5 to 6 out of 10 because the quality of
the whole papers is still acceptable therefore these six articles were accepted after
primary reviewer and secondary reviewerrsquos decision
Randomisation
In two RCT articles224 one study24 used to a computer-generated program operated by
the St Jude Protocol and Data Management System to randomize the sample Another
study2 didnrsquot address how randomization was done
Allocation concealment
No studies reported allocation concealment
Intention-to-treat analysis
One quasi-experimental design7 stated Intention-to-treat analysis
Adequate follow up
The follow-up periods included 2or 3 days24 7 days2 4 week7 one month25 6 week25 12
week2216 week23 and 1 year23
Baseline comparability of groups
Three 22425 of six studies had baseline comparability in terms of age sex diagnosis
race institution duration of illness
Blinded outcome assessment
No studies used blinded outcome assessment The researchers including study team
patients staff and families were not blinded to the patientrsquos group assignment
Characteristics of included studies
651
19
There were six studies related to interventions designed to cancer-related fatigue for
pediatric patients than there are for adults There are a total of six including five
English-language papers 27222324 and one Chinese-language paper 25 ranging in year of
publication from 2007 to 2009
Patient characteristics
The research subjects of four papers included both school-aged children and
adolescents 7222324 one papers involved mainly adolescents25 and one paper sampled
only school-aged children 2 the range in ages was between six-18 years The number of
patients included in the samples ranged from nine to 60 The sources of case data were
from both outpatients and hospitalized children The types of cancer included acute
lymphoblastic leukemia (ALL) solid tumors acute myeloid leukemia (AML) and
lymphoma Overall ALL was the most commonly studied cancer type The stage of the
disease varied in these reports some patients were in the maintenance stage of
chemotherapy25 some had just received their first round of chemotherapy224 some had
completed two courses of treatments lasting 4-8 weeks each 7 and some had entered
the survivor stage 2223
Countries
Two RCTrsquos 2 24 were conducted in the USA There were four quasi-experimental design
studiesThree studies conducted in the USA7 22 23 and one in Taiwan25
Intervention types
652
20
The interventions included exercise training programs 2225 physical activity 2324
massage therapy 7 and health education 223 exercise training and physical activity as
an intervention method given in three different settings home 22 25 community 23 or
hospital 24 The studies used different types of exercise interventions including
home-based aerobic exercise use a Video Compact Disc 25 use of a bicycle-style
exerciser 24 aerobics2223 and various types of physical activities2 and strength-building
exercises 2223 The intensity of the exercise varied and often included gradual warm-up
exercises a period of main exercise and a cool down period For these studies2023 the
target exercise intensity was a heart rate of gt90 of the maximum heart rate (HR max) or
the increase in the percentage of heart rate reserve ( HRR) of 40-60
The number of weeks for the exercisephysical activity interventions duration including
2-4 days 24 6 weeks25 12 weeks22 and 16 weeks23 The frequency of exercise ranged
from 2-3 times per week to twice a day Typical duration of exercise ranged from 10 to 45
minutes There are three papers using exercise interventions based on ACSM (American
College of Sports Medicine) 2225 recommendations and one of these used an Activity
pyramid from the ACSM to determine intensity 24
One article did not clarify the type of exercise intervention or the reasons for their choices
23 In addition there was an article focusing on massage therapy 7 as an intervention in
this study the experimental group received four weeks of massage therapy either in the
clinic or in the patientrsquos room the therapy was applied by a professional masseur and
targeted the back legs arms chest stomach and face of the children However the
frequency of massage sessions per week and the duration of the massages were not
653
21
given There is another article about intervention measures combine health education
and physical activity 2 In this study patients were informed about the following (1) health
education patients received daily education about chemotherapy-related fatigue and
information from a health education manual written by the author (2) encouragement for
children to engage in activities such as listening to music drawing and reading and (3)
physical activity which involved walking along the corridors of the ward for 10-15 minutes
These health education measures were presented for 45-60 minutes a day for a total of
seven days The study design for non-pharmacological interventions used control groups
that included primarily people who had received standard treatment or people who did
not receive an exercise intervention
Outcome measures
Five measurement tools were used in this group of seven papers concerning childrenrsquos
fatigue (Appendix IV) Because those studies included both school-age children and
adolescents the following descriptions will be differentiated by age Fatigue
measurements for school-aged children with cancer include the following the Child
Fatigue Scale (CFS) 7 a scale that measures the frequency and intensity of fatigue and
the Fatigue Scale for 7-12 year Olds (FS-C) 224 a scale that can be used to evaluate the
intensity of fatigue On the other hand fatigue measurements for adolescent cancer
patients include the following the Fatigue Scale for 13-18-year-olds (FS-A) 24 a measure
that can help evaluate fatigue levels the Pediatric Quality of Life Multidimensional
Fatigue Scale (Peds QL-MFS) 2325 a tool that can be divided into three sub-scales to
understand the general cognitive and sleep rest components of fatigue and finally the
CIS-20 for school-age children and adolescents 22 a scale that measures four levels of
654
22
fatigue namely subjective experience attention motivation and physical activity Two
studies used the Peds QL-MFS scale to measure fatigue2325
Meta-analysis results Two studies of the included papers failed to provide sufficient raw data they could not be
included in the meta-analysis Hinds et al 24 did not include post-test data Genc et al 2
provided no pre-test data PostWhite et al7 reported that fatigue after the health
education intervention was not statistically different but they presented the results
without presenting fatigue-related data Therefore the meta-analysis included three
studies 222325
The heterogeneity of studies was analyzed with Chi square statistics and no statistical
significance was found Therefore the data was combined in meta-analysis according to
exercise intervention on fatigue In addition there were three articles using the Peds
QL-MFS as a research tool to examine childrenrsquos improvements in fatigue Among these
Keats 22 and Chiang 24 present the effectiveness of exercise interventions using three
subscales Therefore the meta-analysis also analysis of the effects of these exercise
intervention measures on three subscales of Peds QL-MFS general fatigue sleep rest
fatigue and cognitive fatigue
The effectiveness of exercise intervention for fatigue We analyzed the exercise intervention effect on fatigue A total of 2 studies 22 23 were
included Takken et al 22 used community-based exercise training program to reduce
fatigue of children 6 to 14 years (mean 93y) of age who survived ALL Fatigue
measurement by Checklist Individual Strength (CIS) after 12-week of training fatigue
655
23
show no significant differences between pre (meanplusmnSD 415plusmn147) and post training
(meanplusmnSD368plusmn217) but fatigue change from baseline mean reduction of 11
Keats et al23 although used community-based physical activity program to reduce fatigue
for adolescents 14 to 18 years of age (mean162 y) with cancer (Lymphoma leukemia CNS
tumor germ cell tumor) Studies used fatigue by PedsQLMFS Results show general fatigue
from baseline to 8 weeks and to 3 months follow up significantly improves General
fatigue sleeprest fatigue and total fatigue from baseline to 3 months follow up showed
significant improvements Sleeprest fatigue and total fatigue at 1 years followed up were
significant improvements
Figure 2 shows the overall effect of exercise intervention in children and adolescents with
cancers with a focus on improving fatigue Due to the lower heterogeneity (p>005) the
fixed effects model was used to pool the data for meta-analysis (Overall effect size=
-006 95 Confidence Interval (CI) -070 to 058) A result did not indicate a statistically
significant difference (p = 087)
656
24
Figure2 Meta-analysis results of exercise intervention on fatigue
In addition Keats23 and Chiang25 used the three sub-scales of Peds QL-MFS to
determine the general cognitive and sleep rest components of fatigue The following
present the effectiveness of exercise interventions using three subscales including
general fatigue sleep rest fatigue and cognitive fatigue 2325
Chiang et al 25 used a 6- week home-based aerobic exercise intervention to reduce
fatigue of children 7 to 18 years (mean age at experimental group was 1088 y in control
group was 1247 y) of age who with acute lymphoblastic leukemia Fatigue measurement
by Peds QL-MFS after training For intent-to ndash treat analysis the findings indicated that
there are no intervention effects and time differences by any items on the subscale of
fatigue For per-protocol analysis general fatigue( meanplusmnSD 422plusmn402) was the only
subscale that was significantly lower for children who received the exercise intervention
than those in control group at follow-up assessment (one month after the completion of
intervention)
Keats et al23 although used community-based physical activity program to reduce fatigue
for adolescents 14 to 18 years of age (mean162 y) with cancer (Lymphoma leukemia
CNS tumor germ cell tumor) Both studies used fatigue by PedsQLMFS Results show
general fatigue from baseline to 8 weeks and to 3 months follow up significantly improves
657
25
General fatigue sleeprest fatigue and total fatigue from baseline to 3 months follow up
showed significant improvements Sleeprest fatigue and total fatigue at 1 years followed
up were significant improvements
The effectiveness of exercise intervention for general fatigue
The impact of the exercise interventions upon levels of general fatigue was also analysed
The heterogeneity was low (p>005) Therefore the fixed effects model was used to
examine the effectiveness The effect size is -076 indicating a statistically significant
difference (p = 001 95 CI -135 to -017 Fig 3) The evidence suggests that exercise
intervention can reduce general fatigue in children with cancer
Fig 3 Meta-analysis results of exercise intervention for general fatigue
The effectiveness of exercise intervention for sleep rest fatigue
The following is the result of the meta-analysis of the effectiveness of exercise
interventions on sleep rest fatigue First the heterogeneity test was conducted with P gt
005 representing small heterogeneity and the fixed effects model was used Fig 4
shows the effect size is -035 indicating no statistically significant differences (p = 023
95 CI-092 to 022 Fig 4)
658
26
Fig 4 Meta-analysis results of exercise intervention for sleep rest fatigue
The effectiveness of exercise intervention for cognitive fatigue Lastly the following data reports the results of meta-analysis of the effectiveness of
exercise interventions for cognitive fatigue The heterogeneity was p>005 then the
fixed effects model was used The effect size is -035 indicating no statistically significant
differences (p = 024 95 CI-092 023 Fig 5)
Fig 5 Meta-analysis results of exercise intervention for cognitive fatigue
Narrative presentation of remaining included studies
Three studies were not included in meta-analysis Post-White et al7 one of the aims in
this study was to examine the effect of massage therapy on fatigue in children with
cancer The study was a quasi-experimental design Twenty-three childrenparent dyads
were enrolled 17completed all data points Children with cancer ages 7 to 18 years
received at least 2 identical cycles of chemotherapy and one parent participated in the
2-period crossover design in which 4 weekly massage sessions (MT) alternated with 4
659
27
weekly quiet-time (QT) control sessions There were no significant changes in fatigue in
children over the 4-week MT or QT conditions either independently (change over time) or
when we compared fatigue by condition
The lack of effect of massage on fatigue may be the difficulty some children had in
differentiating fatigue from being relaxed underscores the challenge of measuring fatigue
in children Some children interpreted being tired or relaxed as having greater fatigue
because they felt like lying around and sleeping or felt unmotivated to do their usual
activities all measures of fatigue in the instrument used in the study
Hinds et al24conducted a prospective two-site randomized controlled pilot study to
assess the feasibility of an enhanced physical activity (EPA) intervention in hospitalized
children and adolescents receiving treatment for a solid tumor or for acute myeloid
leukemia (AML) Twenty-nine patients (25 with a solid tumor and 4 with AML) participated
age range from 736 to 1816 (mean 1248 y) The EPA intervention selected was
pedaling a stationary bicycle-style exerciser (Chattanooga Peddler Deluxe Bio-Teck
Medical Memphis TN) for 30 minutes twice daily for 2 to 4 days of hospitalization The
mixed model analysis revealed no significant differences in patient reports of fatigue
between the two study arms or over time
Genc et al2 conducted a RCT involving children with cancer who are 7 to 12 years of age
and receiving chemotherapy treatment to determine the impact of educational
intervention by nurses on decreasing the fatigue syndrome The research sample was
composed of a total of 60 children with cancer with 30 children being included in the
660
28
experimental group (mean age 923)and 30 children included in the control group (mean
age 937) with their mothers In the experimental group after the 7th to 10th day of the
chemotherapy treatment throughout a week the researcher conducted the nursing
interventions every day for 45 to 60 minutes In the control group routine nursing
interventions were carried out The experimental group received education about the
fatigue with the chemotherapy and fatigue handbook was given which was developed by
the authors Children and mothers were consulted for including activities that could
decrease fatigue which were described as effective interventions A statistically
significant difference was found between the Fatigue Scale-Child mean scores of the
experimental (2723) and the control group (4213) The results suggest that fatigue of
children with cancer can be reduced by implementing appropriate nursing interventions
(t=567 Plt00)
Discussion The purpose of this systematic review was to determine the effectiveness of
non-pharmacological interventions specifically targeting fatigue for children and
adolescents with cancer undergoing chemotherapy or after receiving chemotherapy
Included articles about the effectiveness of non-pharmacological interventions for
children and adolescents with cancer were published between the years of 2007 and
2009 Although interventions for cancer fatigue for adults have been extensively studied
it can be seen from either the title of the paper or related content that an intervention
study on children was a pilot study or a feasibility study Representing a field in its early
stage these studies show that the fatigue issues with young cancer patients have only
recently been taken seriously
661
29
The results of our meta-analysis include measurement of the four performance indicators
fatigue and general fatigue sleep rest fatigue and cognitive fatigue The results show
that there is a statistically significant difference only in the domain of general fatigue
using an exercise intervention for children with cancer can improve the degree of fatigue
with the effect size reaching 0671 Other results do not indicate significant differences
The reasons may include the following
1 Characteristics of the cancer The exhaustion from cancer occurs not only during cancer treatment but also in during
long-term survival a time during which patients may continue to be affected by this
symptom 8 26 Therefore when using intervention measures to improve fatigue
circumstances should be considered such as the process of the treatment and the course
or stage of the disease Because cancer patients will experience different forms of
treatment or courses of treatment the disease itself or treatment differences should be
considered in the choice of intervention Even chemotherapy drugs should be taken into
consideration For example a period of general steroid treatment can increase patientsrsquo
fatigue In those studies of children with cancer few studies looked solely at one type of
cancer most studies included a variety of cancer patients Furthermore most studies do
not clearly explain the stage of the disease or course of treatment and most do not
include treatment variables in the control group Moreover children with cancer may
have different levels of physical function
2 Research design The sample size Currently there are few studies with large sample size and a rigorous
RCT design due to the small number of papers available for analysis The sample size
included in our studyrsquos data analysis is between 20 and 42 people this small sample size
will affect the power available to evaluate outcome variables
Although most of the non-pharmacological interventions still use exercise and physical
activity and these studies overall show better results for fatigue as compared with
controls more research is still needed to further confirm the efficacy of these findings
662
30
The dropout rate in the evaluated research varies a great deal ranging from 5 to 45
these dropout rates may result from the characteristics of the research subjects or the
lengthy time involved in participating in these studies The research data with a high
turnover rate might not reflect the actual outcomes of participation in exercise and the
quality of the research contained in articles with high subject turnover rates may be
lower
Exercise doses and time The exercise doses needed to reduce fatigue cannot be
determined additionally the amount of exercise completed by the patient is also
inconsistent interventions vary between 2-3 times per week and two times a day and
exercise duration varies between 10 and 45 minutes each time Furthermore the study
interventions vary in length between a couple of days and a long period of 16 weeks The
data collection times are different some were measured 12 weeks after the intervention
began some were measured during the 6 weeks of intervention some were measured
three months after the intervention was finished and some were measured after one
year
In addition disease-related symptoms decrease childrenrsquos willingness to participate in
exercise interventions inappropriate exercise intervention programs may actually
increase childrens fatigue In addition the children in the study are still developing
physically it is important to consider ways to design an interesting exercise intervention
to increase the compliance of patients in order to improve the effectiveness Although
intervention programs in the hospital or in a community sports center can improve the
effectiveness because they provide supervision the feasibility of these programs is
questionable However if the program is home-based the children need to be
supervised by parents in order to improve their compliance in doing the exercises
Furthermore regarding the nature of the intervention the results from this study indicate
that the researched non-pharmacological interventions include the following exercise
training programs physical activity massage therapy and health education interventions
However according to the National Comprehensive Cancer Network 1 clinical guidelines
663
31
for cancer non-drug measures for cancer fatigue can be separated into five categories
(1) activity enhancement (2) psychosocial interventions such as cognitive behavioral
therapy (CBT) stress management relaxation techniques and support groups (3)
attention-restoring therapy (4) nutritional consultation and (5) cognitive behavioral
therapy specifically targeting sleep disturbance Researchers have also suggested that
psychosocial interventions should be included in the future research for children with
cancer-related fatigue 22
(2) The measurement tools in the study The assessment of fatigue can be
one-dimensional or multidimensional One-dimensional assessment can help understand
the severity of fatigue symptoms however multidimensional scales are often more
credible Therefore when measuring cancer-related fatigue researchers should consider
whether there is a uniform definition of fatigue or a standardized tool for measuring
fatigue in order to facilitate further systematic meta-analyses and further develop the
clinical care guidelines
Limitations of the review The present review has some potential limitations First the low methodological quality
may influence the result Although exercise intervention seems promising quality of the
RCTs was generally quite low Future studies require better design and reporting if
methodological issues to establish evidence-based nonpharmcologic intervention
Second the identified studies covered only a limited types of nonpharmcological
intervention especially in exercise intervention The guidelines for cancer-related fatigue
in NCCN (2011)1 referred to more interventions than the ones included in this review
such as cognitive behavioral therapy and nutrition consultation Thirdly the small sample
size and effect size could be potentially having led to underpowered approach for
detecting the effects on fatigue Therefore we recommend that as research continues to
grow a re-analysis can be undertaken Fourthly Combining data in meta analysis from
664
32
studies where the ages were quite different is a potential source of heterogeneity and
may affect the interpretation of the results
Conclusion At present clinical treatment is widely used for cancer patients However child and
adolescent cancer patients often experience various side effects which cause short-term
or long-term discomfort both physically and psychologically In particular with the
increasing cure rate cancer related fatigue during or after treatment has become an
important issue This study result provided positive effect of exercise intervention on
general fatigue
Implications for practice The results of this systematic review and meta-analysis show that exercise interventions
can effectively improve the level of general fatigue In particular although the articles
were self-reported feasibility studies their results all indicate that exercise interventions
for fatigue are feasible and safe there was no conclusion to be made for the use of
massage therapy or health education measures because there was only one article for
each of these interventions
Recommendations for practice
Cancer-related fatigue is one of the most severe and frequent symptoms by pediatric
oncology children and adolescent suffered during treatment and the symptom existed
even after treatment has ended Until now no golden standard of treatment to fatigue is
established The findings call for more attention to how to reduce patientrsquos levels of
fatigue Based on the available information evaluated in this review the following
recommendations for practice are provided
665
33
bull For children aged 7 to 18 who has cancer (eg Lymphoma leukemia CNS tumor
germ cell tumor) an effective progressive aerobic exercise program is recommended to
be at least 2-3 times per week 20 to 45 minute for each session and last for 6-16 weeks
in order to reduce their general fatigue (tiredness physically weakness) In addition
adults should be involved in accompanying children while they are performing physical
exercise of which should be able to improve the adherence rate (level 2 ) ( Grade of
recommendation A)
bull For children aged 7 to 18 who has cancer (eg Lymphoma leukemia CNS tumor
germ cell tumor) an progressive aerobic exercise program will not be effective to reduce
their sleep andor rest (sleeping or resting a lot) or cognitive fatigue (problems with
thinking quickly or problems with remembering) (level 2 ) ( Grade of recommendation C)
bull Nursing interventions in educating treatment of fatigue include information about
activity nutrition energy preservation consulting and providing a useful fatigue
handbook will benefit those children who are 7 to 12 years have a new diagnosis of ALL
AML or lymphoma and receive for the first time after being diagnosed a 7- to 10-day
chemotherapy treatment (level 2) ( Grade of recommendation A)
bull A 4-week massage therapy program (the therapists massage childrenrsquos back legs
arms stomachchest and face) is not effective for children who are aged 7 to 18 and
have acute lymphoblastic leukemia brain tumors lymphoma rhabdomyosarcoma
Wilms tumor or Ewing sarcoma(level 2)( Grade of recommendation C)
bull Using a 12-week aerobic and strength exercise (45-min exercise sessions twice a
week) is not effective for children who are aged 6-14 and survived acute lymphoblaststic
leukemia age from 6 to 14(level 2) ( Grade of recommendation C)
bull Using a physical activity intervention (30minutestwice daily for 2-4days) is not
effective for children who are 7 to 18 years of age with soild tumor or AML(level 2)
( Grade of recommendation C)
666
34
Implications for research According to this systematic review and meta-analysis results there are suggestions to
improve the effectiveness of future research on non-pharmacological interventions for
children and young peoplersquos cancer-related fatigue
As the majority of included non-pharmacological interventions for the fatigue of cancer
patients consist of exercise programs future research should also consider various
non-pharmacological interventions in order to understand the effectiveness of different
methods
Regarding the exercise intervention methods and studies should consider multiple
factors including the age or personal condition of the subject the disease stage and the
amount of daily activities Studies should use design prescriptions (eg frequency
intensity duration and type of exercise) and consider the adherence to the measures in
order to enhance the study strength
In measuring the results of non-pharmacological interventions there should be standard
definitions or standard measurement tools to facilitate the following systematic review
and meta-analysis that can subsequently be developed into clinical care guidelines
Reviewing the effectiveness of the current non-pharmacological management of children
and adolescent cancer patients there is still a lack of rigorous RCT research Limited by
the characteristics of cancer there is still a lack of large sample sizes
Potential conflicts of interest There is no conflict of interest
Acknowledgements
Thank you to Dr Rie Konno Research Fellow Joanna Briggs Institute for her help in
assessing studies
667
35
References 1 National Comprehensive Cancer Network( NCCN) in USA NCCN clinical practice
guideline in oncology cancer-related fatigue 2011 2 Ekti Genc R amp Conk Z Impact of effective nursing interventions to the fatigue
syndrome in children who receive chemotherapy Cancer Nursing 200831(4)312-317
3 Childhood Cancer Foundation of ROC (2009March) The classification of diseases
and age sex statistical tables of case Childhood Cancer Foundation of ROC newsletter103105-106
4 Department of Health Executive Yuan ROC (TAIWAN)(2009 March 20)2009 cause of death statistic Health and National Health Insurance Annual Statistics Information Service 2010 June 28Available httpwwwdohgovtwstatisticdatavital statists9898health statistic--lifepdf
5 Chang TK (2007December 8) Common childhood cancer and its treatment Status
Childhood Cancer Foundation of ROC (TAIWAN) 2010 September 23 Available httpwwwccfrocorgtwchildchild_events_readphpe_id=45
6 Hockenberry MJ amp Wilson D Wongs nursing care of infants and children (8th ed) St
Louis MO Mosby 2007
7 Post-White J Fitzgerald M Savik K Hooke MC Hannahan AB amp Sencer SF
Massage therapy for children with cancer Journal of Pediatric Oncology Nursing 2009 26(1)16-28
8Chiang YC Yeh CH Wang WKamp Yang CP The experience of cancer-related fatigue
in Taiwanese children European Journal of Cancer Care 2009 18(1)43-49 9Langeveld NE Grootenhuis M A Voute P A de Haan RJ amp van den Bos C No excess
fatigue in young adult survivors of childhood cancer European Journal of Cancer 200339(2)204-214
10Piper BF Lindsey AM amp Dodd MJ Fatigue mechanisms in cancer patients
developing nursing theory Oncology Nursing Forum 1987 14(6)17-23 11Nail LM amp Winningham ML Fatigue In S L Groenwald M H Forgge M Goodman
amp C H Yarbro (Eds) Cancer Nursing Principles and practice (4 th ed) Boston Jones and Bartlett1997
12Irvine D Vincent L Graydon JE Bubela N amp Thompson L The prevalence and
correlates of fatigue in patients receiving treatment with chemotherapy and
668
36
radiotherapy A comparison with the fatigue experienced by healthy individuals Cancer Nursing 199417(5)367-378
13Hinds PS amp Hockenberry-Eaton M Developing a research program on fatigue in
children and adloescents diagnosed with cancer Journal of Pediatric Oncology Nursing 200118(2)3-12
14Aaronson LS Teel CS Cassmeyer V Neuberger GB Pallikkathayil L Pierce J Press
AN Williams DP amp Wingate A Defining and measuring fatigue Journal of Nursing scholarship 1999 31(1)45-50
15Yeh CH Wang CH Chiang YC Lin Lamp Chien LC Assessment of symptoms reported
by 10- to 18-year-old cancer patients in Taiwan 2009 38(5)738-746 16 Okuyama T Akechi T Kugaya A Okamura H Shima Yamp Maruguchi M
Development and validation of the cancer fatigue scale a brief three-dimensional self-rating scale for assessment of fatigue in cancer patients Journal of Pain amp Symptom Management 2000 19(1) 5-14
17Gibson F Mulhall AB Richardson A Edwards JL Ream E amp Sepion BJ A
phenomenologic study of fatigue in adolescents receiving treatment for cancer Oncology Nursing Forum200532(3)651-660
18Wolfe J Grier HE Klar N Levin SB Ellenbogen JMamp Salem-Schatz S et al
Symptoms and suffering at the end of life in children with cancer New England Journal of Medicine 2000342(5)326-333
19Whiting P Bagnall AM Sowden AJ Cornell JE Mulrow CD amp Ramirez G
Interventions for the treatment and management of chronic fatigue syndrome a systematic review JAMA the Journal of the American Medical Association 2001286(11)1360-1368
20 Kangas M Bovbjerg DHamp Montgomery G H Cancer-related fatigue a systematic
and meta-analytic review of non-pharmacological therapies for cancer patients Psychological Bulletin 2008134 (5)700-741
21Williams PD Schmideskamp J Ridder EL amp Williams AR Symptom monitoring and
dependent care during cancer treatment in children pilot study Cancer Nursing 200629(3)188-197
22Takken T van der Torre P Zwerink M Hulzebos EH Bierings M Helders PJMamp van
der Net J Development feasibility and efficacy of a community-based exercise training
669
37
program in pediatric cancer survivors Psycho-Oncology 200918(4)440-448
23Keats MR amp Culos-Reed SN A community-based physical activity program for
adolescents with cancer (project TREK) program feasibility and preliminary findings
Pediatric hematology and oncology 200830(4) 272-280
24Hinds PS Hockenberry M Rai SN Zhang L Razzouk B I Cremer L McCarthy K amp
Rodriguez-Galindo C Clinical field testing of an enhanced-activity intervention in
hospitalized children with cancer Journal of Pain amp Symptom Management 2007
33(6)686-697
25Chiang YC The effects of ldquo a home-based aerobic exercise interventionrdquo on fatigue
and cardiorespiratory fitness in children with acute lymphoblastic leukemia during the
maintenance stage of chemotherapy Unpublished thesis Taiwan Tao-Yuan 2007
26Langeveld N Ubbink M amp Smets E I dont have any energy The experience of
fatigue in young adult survivors of childhood cancer European journal of oncology
nursing 20004(1)20-28
27 Kisner C Colby L Therapeutic exercise Foundations and techniques 2nd ed Philadelphia PAFA Davies 2007
670
38
Appendix I JBI Critical Appraisal Checklist for Experimental studies
Author__________ Year_________ Record Number__________________
Questions 1 to 4 must be answered ldquoyesrdquo for study to be included in the metashyanalysis
1 Were the participants randomized to study groups
Yes No Not clear
2 Other than research intervention were participants in each groups treated the same
Yes No Not clear
3 Were the outcomes measured in the same manner for all participants
Yes No Not clear
4 Were groups comparable at entry
Yes No Not clear
5 Was randomization of participants blinded
Yes No Not clear
6 Were those assessing outcome blinded to treatment allocation (if outcome not objective such as survival or length of hospitalization)
Yes No Not clear
7 Was allocation to treatment groups concealed from the allocator
Yes No Not clear
8 Was an appropriate statistical analysis used
671
39
Yes No Not clear
9 Were outcomes measured in a reliable way
Yes No Not clear
10 Was there adequate followshyup of participants
Yes No Not clear
Summary
TOTAL
Yes No Not clear
DECISION
Use Reject
Narrative summary only Further information needed
COMMENTS
672
40
Appendix II JBI Data Extraction Tool for Quantitative Studies Authors and Year
Journal Title
Record NumberArticle Reference No
Reviewer
Method
Settings
Participants
Number of participants
Group A Group B Group C
Control Intervention 1 Intervention 2
Interventions
Group A
Control
Group B
Intervention 1
Group C
Intervention 2
Outcome measures
Definition
673
41
Other outcome measures
Outcome description ScaleMeasure
Results
Dichotomous Data
Outcome Control Group
Numbertotal number
Treatment Group
Numbertotal number
Continuous Data
Authorrsquos Conclusions
Comments
Outcome Control Group
Mean amp SD
Treatment Group
Mean amp SD
674
43
Appendix III Details of included studies (N=6)(2720212223) RefNo Author(s)
(years) Title Study question Research
method Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
22 Takken T van der Torre P Zwerink M Hulzebos E H Bierings M Helders P J Mamp van der Net J (2009)
Development feasibility and efficacy of a community-based exercise training program in pediatric cancer survivors
To develop a 12-week home-based exercise training program (comprising aerobic and strength exercises) for children who survived ALL and to study itrsquos feasibility and efficacy
Pre-post test design
No comparsion group
Survived ALL(N=9)ages 6-14 years
1anthropometry 2 muscle strength 3functional mobility 4cardio-pulmonary
exercise test 5Fatigue
1 Feasibility questionnaire 2 anthropometry electronic scale and a wallmounted stadiometerHarpenden skin fold calipers 3 muscle strength handheld dynamometer 4functional mobility Timed Up
and Go test (TUG) 5cardio-pulmonary exercise test electronically braked cycle ergometer 6Fatigue(mean)CSI-20 (subjective experience of fatigueconcentrationmotivationphysical activity)
112-week exercise training program
2 Patients were assessed before (T0) and after (T1) 12 weeks of training
1 muscle strength execapacity functional moand fatigue showed nosignificant differences between pre(meanplusmnSD415plusmn147) and post training(meanplusmnSD3687)
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
7 Post-White J Fitzgerald M Savik K Hooke M C Hannahan A B amp Sencer S F (2009)
Massage therapy for children with cancer
To determine whether 4 weekly sessions of massage compared with 4 quiet-time control conditions would reduce anxiety cortisol levels fatigue nausea and pain in children with cancer undergoing chemotherapy and would reduce anxiety fatigue and mood disturbance in a parent
2-period crossover design (Randomized)
quiet-time
control
sessions
Children with cancer 1 to 18 years of age Twenty-three childrenparent dyads were enrolled 17 completed all data points
children 1relaxation 2symptoms 3 fatigue
parents
1anxiety 2 fatigue
children 1relaxation (heart and respiratory rates blood pressure and salivary cortisol level)
2symptoms (pain nausea anxiety 3 fatigue 1-2y3-6yLansky Play Performance Scale (PPS) 7-13y
1 4 weekly massage (MT) sessions alternated with 4 weekly quiet-time(QT) control sessions
2 children included presession and postsession vital signs (heart rate respiratory rate blood pressure) and self-report (parent proxy report for age 1-2 years) of pain nausea and anxiety Fatigue was measured before sessions 1 and 4 and at each follow-up Parent measures
included anxiety fatigue and mood states
1Massage was moreeffective than quiet tireducing heart rate inchildren anxiety in cless than age 14 yeaparent anxiety 2There were no sign
changes in blood pcortisol pain naufatigue (no state d
3 Children reported tmassage helped thebetter lessened theirand worries and hadlasting effects than q
675
44
14-18yChild Fatigue Scale (CFS) (frequency
intensity) 2 parents anxiety and fatigue
676
45
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
24 Hinds P S Hockenberry M Rai S N Zhang L Razzouk B I Cremer L McCarthy K amp Rodriguez-Galindo C (2007)
Clinical field testing of an enhanced-activity intervention in hospitalized children with cancer
To determine the feasibility of an
enhanced physical activity EPA intervention in children and adolescents hospitalized to receive chemotherapy for a solid tumor or AML and to assess the sleep and fatigue outcomes of the intervention using two different statistical approaches to analyze the longitudinal symptom data
randomized prospective two-site and two-group pilot study
Standard care Twenty nine patients (25 with a solid tumor and 4 with AML)ages 7-18 years
1 sleep duration 2 sleep efficiency 3 fatigue
1sleep duration sleep efficiency The
Wrist Actigraph The Daily Sleep Diary-Parent 2 fatigue (mean) The Fatigue Scale(FS-C) for 7-12 (intensity) The Fatigue Scale(FS-A) for 13-18 The Fatigue Scale Parent Version (FS-P) The Fatigue Scale Staff Version (FS-S)
1enhanced physical activity (EPA) (hospital-based 30 minutes
twice daily for 2-4 days) 2 T0On the day of admission
(Day 0 or baseline)patient and parents completed the fatigue instruments and a team member applied the actigraph Patients wore the wrist actigraph T1 from Day 0 to 2 or 3 consecutive days (Days 0e3) In addition the patient same parent and staff nurses completed the daily sleep and fatigue reports in the late afternoons of Days 1-3
1 ANOVA model slesignificantly more the experimental athe control arm whdifferences from bsleep efficiency vaaveraged and com
2 The patient-reported mean fatigue scoresarms were higher amadolescents than for
3 The mixed model anarevealed no significandifferences in patientfatigue between
the two study arms otime( no final result iSD only give mixed result)
677
46
23 Keats M
R amp Culos-Reed S N (2008)
A community-based physical activity program for adolescents with cancer (project TREK) program feasibility and preliminary findings
To examine the
feasibility of a
theoretically-based
physical activity (PA)
intervention in
adolescents with
cancerand
examination of the
impact of the
program on
participant QOL
including social
emotional and
physical
well-being(including fatigue)
Repeat measures longitudinal design
No comparsion group
10 adolescents(Lymphoma(4)leukemia(4)CNS tumor(1)germ cell tumor(1)) ages 14-18 years
1physical fitness 2quality of life (QOL) 3PA behavior 4fatigue
1 Feasibility was assessed by participant recruitment attendance and adherence
2physical fitness Fitnessgram 3quality of life (QOL) Pediatric Quality of Life Inventory (PedsQL) 4PA behavior leisure score index (LSI) 5fatigue (mean) pediatric Quality of life
Multidimensional Fatigue Scale (Peds QL-MFS)
(Generalsleepcognitive fatigue)
116week physical activity (PA)
2 total PA physical fitness and overall QOL was assessed at 5 different intervals T0 preintervention (baseline) T1midintervention (after the
first 8 wk) T2 postintervention
(16 wk) T3 3-months
postintervention T4 1-year poststudy
initiation
1 from baseline -wkssig Improvementstotal PA physfitness and Qgeneral fatigue(meanplusmnSD 796plusmn135)
2 from baseline to 3FUsig Improvin general fatigue(meanplusmnSD824plusmn131)slefatigue(meanplusmnSD755plusmn191)totafatigue(meanplusmnSD778plusmn150)
3at 1 years FUsImprovements in sleeprest fatigue(meanplusmnSD725plusmn203)total (meanplusmnSD 763plusmn
678
47
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
2 Gene R E amp Conk Z (2008)
Impact of Effective Nursing Interventions to the Fatigue Syndrome in Children Who Receive Chemotherapy
1 to examine the effects of an effective nursing intervention to the fatigue syndrome of children 7 to 12 years of age who receive chemotherapy 2Tto examine the relationship between fatigue and demographic variables (age sex) diagnoses ([ALL AML] lymphoma) and therapy-related variables (eg level of hemoglobin
experimental randomized controlled study
Routine nursing care
A total of 60 children who are 7-12 years of age(a new diagnosis of ALL AML or lymphoma and receiving for the first time after being diagnosed a 7- to 10-day chemotherapy treatment )
fatigue The Fatigue Scale(FS-C) for 7-12 (intensity)
The Fatigue Scale Parent Version (FS-P)
1 effective nursing interventions(45- 60mdaya week)education about the fatigue with the chemotherapy and fatigue handbook 2 T1 After a 7-day period the children
and parent were evaluated with the Fatigue Scale
1The difference betwthe 2 mean values wafound to be statisticallsignificant 2 statistically significadifference was found between the Fatigue Scale-Child mean scothe experimental (272the control group (4213)children
679
48
25 Chiang et
al(2007)
The effects of ldquo a home ndashbased aerobic exercise interventionrdquo on fatigue and cardiorespiratory fitness in children with Acute Lymphoblastic Leukemia during the maintenance stage of chemotherapy
To examine the effect of ldquo a home ndashbased aerobic exercise interventionrdquo on fatigue and cardiorespiratory fitness in children with Acute Lymphoblastic Leukemia during the maintenance stage of chemotherapy
Quasi-experi -mental
Routine
nursing care
14 pediatric oncology patients in the experimental group and 10 in control group who were matched by age and sex ages7-18 years
1Cardiorespiratory fitness
2Fatigue
1Cardiorespiratory fitness Physical Activity Recall
VO2maxHR peak 6MWT
2 Fatigue PedsQL-MFS(Generalsleepcognitive fatigue)
1A six-week home-based aerobic exercise intervention 2 8 time points T0 baseline T1-T6 every week during the
intervention(6 weeks) T7 post intervention T8 follow-up (one month after
the end of the home-based exercise program)
1 For intent-to ndash treatthe findings indicated are no intervention efftime differences by anon the subscale of fat2 For per-protocol angeneral fatigue( mean422plusmn402) was the osubscale that was siglower for children whothe exercise interventthose in control groupfollow-up assessmentmonth after the compintervention) 3 The VO2peak are significantly improvingexperimental group atbaseline- and post-intassessment The VO2was significantly highechildren who were in experimental group thcontrol subjects at post-intervention assefor the per-protocol an
680
49
Appendix IV Instrument used to measure fatigue
Name Instrument
developers
Description Used in
age in
ref
Reliability
Consistency of
instrument
Checklist Individual Strength
(CIS)22
Vercoulen et
al1996
20 items using 7-point Likert scale of
fatigue To measure four aspects of
fatiguesubjective experience
contractionmotivation physical
Activity
6-14 Not reported
Child Fatigue Scale (CFS)7 Hockenberry
et al2003
14 items 2 part questionnaire frequency
(yes or no) 5-point Likert scale of the
intensity of any yes responses
7-13
14-18 α073-o84
The Fatigue Scale for 7-12
year Olds (FS-C)224
Hockenberry
et al
14 items provide a fatigue intensity score
5-point Likert scale
7-12 αo84
The Fatigue Scale for 13-18
year Olds (FS-A)24
Hockenberry
et al
14 items provide a fatigue intensity score
5-point Likert scale
13-18 α076-o96
Pediatric Quality of life
Multidimensional Fatigue
Scale (Peds QL-MFS)2325
Varni2002 18 items to measure three aspects of
fatigueGeneralsleepcognitive
14-18 Not reported
681
50
Appendix V Excluded studies and reasons for exclusion
Baggott C Dodd M Kennedy C Marina N Miaskowski C Multiple Symptoms in Pediatric Oncology
Patients A Systematic Review Journal of Pediatric Oncology Nursing 2009 Nov-Dec 27(6)
325-339
Reason for exclusion Not outcome of interest
Barlow JH Ellard DR Psycho-educational interventions for children with chronic disease parents and
siblings an overview of the research evidence base Care Health amp Development 2004 Nov
30(6)637-45
Reason for exclusion Not outcome of interest
Bedider S Moyer CA Randomized controlled trials of pediatric massage A review Evid Based
Complement Alternat Med 2007 Mar 4(1)23-34 Epub 2006 Nov 3
Reason for exclusion Not outcome of interest
de Nijs EJ Ros W Grijpdonck MH Nursing intervention for fatigue during the treatment for cancer Cancer
Nursing 2008 31(3)191-206
Reason for exclusion Not population of interest
Edwards JL Gibson F Richardson A Sepion B Ream E Fatigue in adolescents with and following a
cancer diagnosis developing an evidence base for practice European Journal of Cancer 2003
Dec 39(18)2671-80
Reason for exclusion Not experimental or quasi-experimental study
Hinds PS Hockenberry-Eatan M Developing a research program on fatigue in children and adolescents
diagnosed with cancer Journal of Pediatric Oncology Nursing 2001 Mar-Apr 18(2 Suppl
1)3-12
Reason for exclusion Not experimental or quasi-experimental study
Hockenberry-Eaton M Hinds PS Alcoser P ONeill JB Euell K Howard V Gattuso J Taylor J Fatigue in
Children and Adolescents With Cancer Journal of Pediatric Oncology Nursing 1998 July
15(3)172-182
Reason for exclusion Not experimental or quasi-experimental study
Jean-Pierre P Mustian K Kohli S Roscoe JA Hickok JT Morrow GR Community-based clinical oncology
research trials for cancer-related fatigue The Journal of Supportive Oncology 2006 Nov-Dec
4(10)511-6
682
51
Reason for exclusion Not population of interest
Kangas M Bovbjerg DH Montgomery GH Cancer-Related Fatigue A Systematic and Meta-Analytic
Review of Non-Pharmacological Therapies for Cancer Patients Psychological Bulletin 2008 Sep
134(5)700-41
Reason for exclusion Not population of interest
Lotfi-Jam K Carey M Jefford M Schofield P Charleson C Aranda S Nonpharmacologic strategies for
managing common chemotherapy adverse effects A systematic review Journal of Clinical
Oncology 2008 Dec 1 26(34)5618-29 Epub 2008 Nov 3
Reason for exclusion Not outcome of interest
Marchese VG Chiarello LA Lange BJ Effects of physical therapy intervention for children with acute
lymphoblastic leukemia Pediatr Blood Cancer 2004 Feb42(2)127-33
Reason for exclusion Not outcome of interest
Meeske KA Siegel SE Globe DR Mack WJ Bernstein L Prevalence and correlates of fatigue in
long-term survivors of childhood leukemia Journal of Clinical Oncology 2005 Aug 20
23(24)5501-10
Reason for exclusion Not intervention study
Minton O Richardson A Sharpe M Hotopf Stone P A systematic review and meta-analysis of the
pharmacological treatment of cancer-related fatigue J Natl Cancer Inst 2008 Aug 20
100(16)1155-66 Epub 2008 Aug 11
Reason for exclusion Not population and intervention of interest
Mustian KM Morrow GR Carroll JK Figueroa-Moseley CD Pascal JP Williams GC Integrative
nonpharmacologic behavioral interventions for the management of Cancer-Related fatigue The
Oncologist 2007 12(1)52-67
Reason for exclusion Not population of interest
Neill J Belan I Ried K Effectiveness of non-pharmacological interventions for fatigue in adults with
multiple sclerosis rheumatoid arthritis or systemic lupus erythematosus a systematic review
Journal of Advanced Nursing 2006 Dec 56(6)617-35
Reason for exclusion Not population of interest
Rheingans JI A systematic review of nonpharmacologic adjunctive therapies for symptom management
Journal of Pediatric Oncology Nursing 2007 24(2) 81-94
683
52
Reason for exclusion Not outcome of interest
Rheingans JI Pediatric oncology nursesrsquo management of patients symptoms Journal of Pediatric
Oncology Nursing 2008 Nov 25(6) 303-11
Reason for exclusion Not outcome of interest
San Juan AF Fleck SJ Chamorro-Vintildea C Mateacute-Muntildeoz JL Moral S Peacuterez M Cardona C Del Valle MF
Hernaacutendez M Ramiacuterez M Madero L Lucia A Effects of an intrahospital exercise program
intervention for children with leukemia Medicine amp Science in Sports amp Exercise 2007 Jan
39(1)13-21
Reason for exclusion Not outcome of interest
Sanford SD Okuma JO Pan J Srivastava DK West N Farr L Hinds PS Gender differences in sleep
fatigue and daytime activity in a pediatric oncology sample receiving dexamethasone Journal of
Pediatric Psychology 2008 Apr 33(3)298-306 Epub 2007 Nov 17
Reason for exclusion Not experimental or quasi-experimental study
Schmitz KH Holtzman J Courneya KS Macircsse LC Duval S Kane R Controlled physical activity trials in
cancer survivors a systematic review and meta-analysis Cancer Epidemiol Biomarkers Prev
2005 Jul 14(7)1588-95
Reason for exclusion Not population of interest
van Brussel M Takken T Lucia A van der Net J Helders PJ Is physical fitness decreased in survivors of
childhood leukemia A systematic review Leukemia 2005 Jan 19(1)13-7
Reason for exclusion Not population of interest
Whiting P Bagnall AM Snowden AJ Cornell JE Mulrow CD Ramirez G Interventions for the treatment
and management of chronic fatigue syndrome JAMA 2001 Sep 19 286(11)1360-8
Reason for exclusion Not intervention of interest
Whitsett SF Gudmundsdottir M Davies B McCarthy P Friedman D Chemotherapy-related fatigue in
childhood cancer correlates consequences and coping strategies Journal of Pediatric
Oncology Nursing 2008 Mar-Apr 25(2)86-96 Epub 2008 Feb 29
Reason for exclusion Not experimental or quasi-experimental study
Winner C Muumlller C Hoffmann C Boos J Rosenbaum D Physical activity and childhood cancer Pediatr
Blood Cancer 2010 Apr 54(4)501-10
Reason for exclusion Not research study
684
53
Wu M Hsu L Zhang B Shen N Lu H Li S The experiences of cancer-related fatigue among Chinese
children with leukaemia A phenomenological study Journal of Nursing Studies 2010 Jan
47(1)49-59 Epub 2009 Aug 25
Reason for exclusion Not experimental or quasi-experimental study
Yeh CH Chiang YC Lin L Yang CP Chien LC Weaver MA Chuang HL Clinical factors associated with
fatigue over time in paediatric oncology patients receiving chemotherapy British Journal of
Cancer 2008 Jul 8 99(1)23-9 Epub 2008 Jun 24
Reason for exclusion Not experimental or quasi-experimental study
685
11
The Cochrane Library of Systematic Reviews and The Joanna Briggs Institute Library of
Systematic Reviews were initially searched to ensure that systematic reviews on this
subject were not already published or being undertaken This initial search prior to the
commencement of the review did not yield any results
This systematic review has examined the effectiveness of non-pharmacologic
interventions on the cancer-related fatigue of children in hope of finding scientific
evidence that can support or refute such measures on children The results of this study
may serve as a reference for professional caregivers children with cancer and their
families or to be put into practice during the clinical care of children with cancer
Definition of terms
FatigueFatigue as a distressing persistent subjective sense of physical emotional
andor cognitive tiredness or exhaustion related to cancer or cancer treatments
that is not proportional to recent activity and interferes with daily function1 There
are various scales and measurements of the degree of fatiguewe have elected to
use the study authors own definitions of fatigue rather than applying a single
pre-set definition of the condition
Non-pharmacological interventionsReferring to reduce fatigue that does not involve
drugsNon-pharmacologic measures include activity enhancement psychosocial
interventions (eg cognitive behavioral therapy stress management relaxation
support groups) attention-restoring therapy and nutrition consultation1
ChemotherapyTreatment with drugs that kill cancer cells 1
644
12
Review QuestionsObjectives
Review Objective
The objective of this systematic review was to critically appraise synthesize and
present the best available evidence concerning the effects of non-pharmacological
interventions fatigue in children and adolescents with cancer
Review Question
The following specific question was addressed in this review
What is the effectiveness of non-pharmacological interventions on fatigue in
children and adolescents with cancer aged from one to 18 years
Criteria for Considering Studies for this Review
Types of studies
This review included randomised controlled trials (RCTs) and quasi-experimental
studies that examine the effectiveness of non-pharmacological intervention for fatigue in
children and adolescents with cancer
Types of participants
Children and adolescents aged from one to 18 years old experiencing fatigue
associated with cancer either during or after the chemotherapy or maintenance stage of
chemotherapy or survive stage The types of cancer to be included in this systematic
review will be ALL (Acute lymphoblastic leukemia) AML (Acute myeloid leukemia)
lymphoma and solid tumors
Exclusion criteria for Types of participants
645
13
newborn infants under 1 years of age
participants who do not have a specific diagnosis of cancer
participants who have received immunoglobulin or hydrocortisone
treatment
If participants have received immunoglobulin or hydrocortisone treatment may
inference the effectiveness of non-pharmacological interventions on fatigue
Types of intervention
This review considered studies that examine non-pharmacological interventions on
fatigue for children and adolescents with cancer including activity enhancement
(exercise physical activity) psychosocial interventions CBT stress management
relaxation nutrition consultation massage and educational interventions The
interventions descriptive included the length frequency setting and intervention
providers eg Nurse Psychologist Dietician
Exclusion criteria for types of interventions only pharmacological interventions were
tested
Types of outcome measures
The outcome measures considered were fatigue scores The literature demonstrates that
differences of opinion exist regarding the most valid and reliable method of measuring
cancer-related fatigue Therefore studies that used any validated scale for
cancer-related fatigue were considered for inclusion Currently commonly used scales to
measure fatigue include Checklist Individual Strength (CIS) Child Fatigue Scale (CFS)
The Fatigue Scale for 7-12 year Olds (FS-C) The Fatigue Scale for 13-18 year Olds
646
14
(FS-A)and Pediatric Quality of life Multidimensional Fatigue Scale (Peds QL-MFS)
Types of settings
Both hospital and community settings
Search Strategy
Before undertaking this systematic review the Cochrane Library Joanna Briggs Institute
Library of Systematic Reviews and CINAHL were searched and no systematic reviews on
this topic were found or identified as underway
The search strategy aimed to find both published and unpublished studies
A three-step search strategy was utilized in each component of this review An initial
limited search of CINAHL and MEDLINE was undertaken followed by an analysis of the
text words contained in the title and abstract and of the index terms used to describe the
article A second search using all identified keywords and index terms was undertaken
Lastly the reference lists of all identified reports and articles were searched for additional
studies
Types of languages
1 English
2 Chinese
The following databases were searched to identify keywords contained in the title and
abstract and relevant MeSH headings and descriptor terms
The Cochrane Library PsycINFO 1990 ndash 2010
647
15
Ovid MEDLINE 1966 ndash 2010 CINAHL Plus with Full Text 1960 ndash2010 EMBASE ProQuest Dissertations amp theses 1990-2010 Electronic theses and dissertations system 1956(abstract)1990(full text)-2010 MEDNAR Index to Taiwan periodical literature 1970-2010 Electronic thesis and dissertation system (Chinese) 1990-2010
Keyword search terms
1Types of studies experimental study random quasi-experimental study實驗性研究隨
機類實驗性研究
2 Types of participants childchildren adolescents pediatric cancer and oncology兒童
青少年兒科癌症腫瘤
3 Types of interventions non-pharmacological interventions massage exercise fitness
physical activity cognitive behavioral stress management energy conservation
sleep therapy relaxation distraction and psycho-education非藥物性處置按摩運動
身體活動認知行為壓力處置能量保存睡眠治療放鬆轉移注意力衛教
4 Types of outcome measures fatigue cancer-related fatigue loss of energy levels of
tiredness tired side effect symptoms疲憊癌性疲憊疲倦合併症症狀
Methods of the Review
Assessment of methodological quality Papers selected for retrieval were assessed by two independent reviewers for
methodological validity prior to inclusion in the review using the standardised critical
appraisal instruments (Appendix I) from the JBI-SUMARI (Joanna Briggs Institute
Systems for the Unified Management Assessment and Review of Information package)
Any disagreements that arise between the reviewers were resolved through discussion
648
16
with a third reviewer
Data extraction Data was extracted from papers included in the review using standardised data
extraction tool (Appendix II) from the JBI-SUMARI Details of eligible studies were
extracted and summarised independently by two reviewers
Data Synthesis
All data analysissynthesis were made using the JBI-SUMARI The studies were
assessed for clinical heterogeneity by considering the settings populations interventions
and outcomes Where possible these binary outcomes were analyzed by calculation of
the Odds Ratio with the 95 CI The weighted mean difference was calculated if the
pooled studies have used the same scale for continuous data The standardized mean
difference was calculated for continuous data measuring the same outcome on a
different scale In studies where statistical pooling of results was inappropriate the
findings were considered for inclusion as a narrative summary
Results The findings from the systematic review are presented first Followed by the results from
the meta-analysis component of this review
Description of studies From database search and hand search a total of 76 papers were identified Thirty
papers were then excluded because they did not meet the inclusion criteria Forty-six
full text were retrieved for further consideration for inclusion Of the 30 excluded reasons
for exclusion were follows 11articles were duplicated eight articles did not meet
649
17
participant inclusion criteria eight articles did not meet outcome criteria and nine articles
were correlation studies or discussion papers others articles were unclear reporting In
total after sorting six papers have been included in this article Figure 1 displays the
process used to identify relevant articles for inclusion in the systematic review
Figure 1 Stages of searching and inclusionexclusion of references for the review
Potentially relevant English-language and Chinese- language Studies Identified
Electronically and hand search (n=76)
Duplicate (n= 11) Papers excluded after evaluation of abstract (n=19)
Papers retrieved for detailed examination (N=46)
Papers excluded after review of full paper
(n=40)
Papers assessed for methodological
quality (n=6)
Papers included in systematic review
(n=6)
Methodological Quality
Of the six included articles 2722232425 two articles were RCT design224 with score 7 out
of 10 each paper from Critical Appraisal Checklist and four articles used
650
18
quasi-experimental design7222425 with socre 5 to 6 out of 10 because the quality of
the whole papers is still acceptable therefore these six articles were accepted after
primary reviewer and secondary reviewerrsquos decision
Randomisation
In two RCT articles224 one study24 used to a computer-generated program operated by
the St Jude Protocol and Data Management System to randomize the sample Another
study2 didnrsquot address how randomization was done
Allocation concealment
No studies reported allocation concealment
Intention-to-treat analysis
One quasi-experimental design7 stated Intention-to-treat analysis
Adequate follow up
The follow-up periods included 2or 3 days24 7 days2 4 week7 one month25 6 week25 12
week2216 week23 and 1 year23
Baseline comparability of groups
Three 22425 of six studies had baseline comparability in terms of age sex diagnosis
race institution duration of illness
Blinded outcome assessment
No studies used blinded outcome assessment The researchers including study team
patients staff and families were not blinded to the patientrsquos group assignment
Characteristics of included studies
651
19
There were six studies related to interventions designed to cancer-related fatigue for
pediatric patients than there are for adults There are a total of six including five
English-language papers 27222324 and one Chinese-language paper 25 ranging in year of
publication from 2007 to 2009
Patient characteristics
The research subjects of four papers included both school-aged children and
adolescents 7222324 one papers involved mainly adolescents25 and one paper sampled
only school-aged children 2 the range in ages was between six-18 years The number of
patients included in the samples ranged from nine to 60 The sources of case data were
from both outpatients and hospitalized children The types of cancer included acute
lymphoblastic leukemia (ALL) solid tumors acute myeloid leukemia (AML) and
lymphoma Overall ALL was the most commonly studied cancer type The stage of the
disease varied in these reports some patients were in the maintenance stage of
chemotherapy25 some had just received their first round of chemotherapy224 some had
completed two courses of treatments lasting 4-8 weeks each 7 and some had entered
the survivor stage 2223
Countries
Two RCTrsquos 2 24 were conducted in the USA There were four quasi-experimental design
studiesThree studies conducted in the USA7 22 23 and one in Taiwan25
Intervention types
652
20
The interventions included exercise training programs 2225 physical activity 2324
massage therapy 7 and health education 223 exercise training and physical activity as
an intervention method given in three different settings home 22 25 community 23 or
hospital 24 The studies used different types of exercise interventions including
home-based aerobic exercise use a Video Compact Disc 25 use of a bicycle-style
exerciser 24 aerobics2223 and various types of physical activities2 and strength-building
exercises 2223 The intensity of the exercise varied and often included gradual warm-up
exercises a period of main exercise and a cool down period For these studies2023 the
target exercise intensity was a heart rate of gt90 of the maximum heart rate (HR max) or
the increase in the percentage of heart rate reserve ( HRR) of 40-60
The number of weeks for the exercisephysical activity interventions duration including
2-4 days 24 6 weeks25 12 weeks22 and 16 weeks23 The frequency of exercise ranged
from 2-3 times per week to twice a day Typical duration of exercise ranged from 10 to 45
minutes There are three papers using exercise interventions based on ACSM (American
College of Sports Medicine) 2225 recommendations and one of these used an Activity
pyramid from the ACSM to determine intensity 24
One article did not clarify the type of exercise intervention or the reasons for their choices
23 In addition there was an article focusing on massage therapy 7 as an intervention in
this study the experimental group received four weeks of massage therapy either in the
clinic or in the patientrsquos room the therapy was applied by a professional masseur and
targeted the back legs arms chest stomach and face of the children However the
frequency of massage sessions per week and the duration of the massages were not
653
21
given There is another article about intervention measures combine health education
and physical activity 2 In this study patients were informed about the following (1) health
education patients received daily education about chemotherapy-related fatigue and
information from a health education manual written by the author (2) encouragement for
children to engage in activities such as listening to music drawing and reading and (3)
physical activity which involved walking along the corridors of the ward for 10-15 minutes
These health education measures were presented for 45-60 minutes a day for a total of
seven days The study design for non-pharmacological interventions used control groups
that included primarily people who had received standard treatment or people who did
not receive an exercise intervention
Outcome measures
Five measurement tools were used in this group of seven papers concerning childrenrsquos
fatigue (Appendix IV) Because those studies included both school-age children and
adolescents the following descriptions will be differentiated by age Fatigue
measurements for school-aged children with cancer include the following the Child
Fatigue Scale (CFS) 7 a scale that measures the frequency and intensity of fatigue and
the Fatigue Scale for 7-12 year Olds (FS-C) 224 a scale that can be used to evaluate the
intensity of fatigue On the other hand fatigue measurements for adolescent cancer
patients include the following the Fatigue Scale for 13-18-year-olds (FS-A) 24 a measure
that can help evaluate fatigue levels the Pediatric Quality of Life Multidimensional
Fatigue Scale (Peds QL-MFS) 2325 a tool that can be divided into three sub-scales to
understand the general cognitive and sleep rest components of fatigue and finally the
CIS-20 for school-age children and adolescents 22 a scale that measures four levels of
654
22
fatigue namely subjective experience attention motivation and physical activity Two
studies used the Peds QL-MFS scale to measure fatigue2325
Meta-analysis results Two studies of the included papers failed to provide sufficient raw data they could not be
included in the meta-analysis Hinds et al 24 did not include post-test data Genc et al 2
provided no pre-test data PostWhite et al7 reported that fatigue after the health
education intervention was not statistically different but they presented the results
without presenting fatigue-related data Therefore the meta-analysis included three
studies 222325
The heterogeneity of studies was analyzed with Chi square statistics and no statistical
significance was found Therefore the data was combined in meta-analysis according to
exercise intervention on fatigue In addition there were three articles using the Peds
QL-MFS as a research tool to examine childrenrsquos improvements in fatigue Among these
Keats 22 and Chiang 24 present the effectiveness of exercise interventions using three
subscales Therefore the meta-analysis also analysis of the effects of these exercise
intervention measures on three subscales of Peds QL-MFS general fatigue sleep rest
fatigue and cognitive fatigue
The effectiveness of exercise intervention for fatigue We analyzed the exercise intervention effect on fatigue A total of 2 studies 22 23 were
included Takken et al 22 used community-based exercise training program to reduce
fatigue of children 6 to 14 years (mean 93y) of age who survived ALL Fatigue
measurement by Checklist Individual Strength (CIS) after 12-week of training fatigue
655
23
show no significant differences between pre (meanplusmnSD 415plusmn147) and post training
(meanplusmnSD368plusmn217) but fatigue change from baseline mean reduction of 11
Keats et al23 although used community-based physical activity program to reduce fatigue
for adolescents 14 to 18 years of age (mean162 y) with cancer (Lymphoma leukemia CNS
tumor germ cell tumor) Studies used fatigue by PedsQLMFS Results show general fatigue
from baseline to 8 weeks and to 3 months follow up significantly improves General
fatigue sleeprest fatigue and total fatigue from baseline to 3 months follow up showed
significant improvements Sleeprest fatigue and total fatigue at 1 years followed up were
significant improvements
Figure 2 shows the overall effect of exercise intervention in children and adolescents with
cancers with a focus on improving fatigue Due to the lower heterogeneity (p>005) the
fixed effects model was used to pool the data for meta-analysis (Overall effect size=
-006 95 Confidence Interval (CI) -070 to 058) A result did not indicate a statistically
significant difference (p = 087)
656
24
Figure2 Meta-analysis results of exercise intervention on fatigue
In addition Keats23 and Chiang25 used the three sub-scales of Peds QL-MFS to
determine the general cognitive and sleep rest components of fatigue The following
present the effectiveness of exercise interventions using three subscales including
general fatigue sleep rest fatigue and cognitive fatigue 2325
Chiang et al 25 used a 6- week home-based aerobic exercise intervention to reduce
fatigue of children 7 to 18 years (mean age at experimental group was 1088 y in control
group was 1247 y) of age who with acute lymphoblastic leukemia Fatigue measurement
by Peds QL-MFS after training For intent-to ndash treat analysis the findings indicated that
there are no intervention effects and time differences by any items on the subscale of
fatigue For per-protocol analysis general fatigue( meanplusmnSD 422plusmn402) was the only
subscale that was significantly lower for children who received the exercise intervention
than those in control group at follow-up assessment (one month after the completion of
intervention)
Keats et al23 although used community-based physical activity program to reduce fatigue
for adolescents 14 to 18 years of age (mean162 y) with cancer (Lymphoma leukemia
CNS tumor germ cell tumor) Both studies used fatigue by PedsQLMFS Results show
general fatigue from baseline to 8 weeks and to 3 months follow up significantly improves
657
25
General fatigue sleeprest fatigue and total fatigue from baseline to 3 months follow up
showed significant improvements Sleeprest fatigue and total fatigue at 1 years followed
up were significant improvements
The effectiveness of exercise intervention for general fatigue
The impact of the exercise interventions upon levels of general fatigue was also analysed
The heterogeneity was low (p>005) Therefore the fixed effects model was used to
examine the effectiveness The effect size is -076 indicating a statistically significant
difference (p = 001 95 CI -135 to -017 Fig 3) The evidence suggests that exercise
intervention can reduce general fatigue in children with cancer
Fig 3 Meta-analysis results of exercise intervention for general fatigue
The effectiveness of exercise intervention for sleep rest fatigue
The following is the result of the meta-analysis of the effectiveness of exercise
interventions on sleep rest fatigue First the heterogeneity test was conducted with P gt
005 representing small heterogeneity and the fixed effects model was used Fig 4
shows the effect size is -035 indicating no statistically significant differences (p = 023
95 CI-092 to 022 Fig 4)
658
26
Fig 4 Meta-analysis results of exercise intervention for sleep rest fatigue
The effectiveness of exercise intervention for cognitive fatigue Lastly the following data reports the results of meta-analysis of the effectiveness of
exercise interventions for cognitive fatigue The heterogeneity was p>005 then the
fixed effects model was used The effect size is -035 indicating no statistically significant
differences (p = 024 95 CI-092 023 Fig 5)
Fig 5 Meta-analysis results of exercise intervention for cognitive fatigue
Narrative presentation of remaining included studies
Three studies were not included in meta-analysis Post-White et al7 one of the aims in
this study was to examine the effect of massage therapy on fatigue in children with
cancer The study was a quasi-experimental design Twenty-three childrenparent dyads
were enrolled 17completed all data points Children with cancer ages 7 to 18 years
received at least 2 identical cycles of chemotherapy and one parent participated in the
2-period crossover design in which 4 weekly massage sessions (MT) alternated with 4
659
27
weekly quiet-time (QT) control sessions There were no significant changes in fatigue in
children over the 4-week MT or QT conditions either independently (change over time) or
when we compared fatigue by condition
The lack of effect of massage on fatigue may be the difficulty some children had in
differentiating fatigue from being relaxed underscores the challenge of measuring fatigue
in children Some children interpreted being tired or relaxed as having greater fatigue
because they felt like lying around and sleeping or felt unmotivated to do their usual
activities all measures of fatigue in the instrument used in the study
Hinds et al24conducted a prospective two-site randomized controlled pilot study to
assess the feasibility of an enhanced physical activity (EPA) intervention in hospitalized
children and adolescents receiving treatment for a solid tumor or for acute myeloid
leukemia (AML) Twenty-nine patients (25 with a solid tumor and 4 with AML) participated
age range from 736 to 1816 (mean 1248 y) The EPA intervention selected was
pedaling a stationary bicycle-style exerciser (Chattanooga Peddler Deluxe Bio-Teck
Medical Memphis TN) for 30 minutes twice daily for 2 to 4 days of hospitalization The
mixed model analysis revealed no significant differences in patient reports of fatigue
between the two study arms or over time
Genc et al2 conducted a RCT involving children with cancer who are 7 to 12 years of age
and receiving chemotherapy treatment to determine the impact of educational
intervention by nurses on decreasing the fatigue syndrome The research sample was
composed of a total of 60 children with cancer with 30 children being included in the
660
28
experimental group (mean age 923)and 30 children included in the control group (mean
age 937) with their mothers In the experimental group after the 7th to 10th day of the
chemotherapy treatment throughout a week the researcher conducted the nursing
interventions every day for 45 to 60 minutes In the control group routine nursing
interventions were carried out The experimental group received education about the
fatigue with the chemotherapy and fatigue handbook was given which was developed by
the authors Children and mothers were consulted for including activities that could
decrease fatigue which were described as effective interventions A statistically
significant difference was found between the Fatigue Scale-Child mean scores of the
experimental (2723) and the control group (4213) The results suggest that fatigue of
children with cancer can be reduced by implementing appropriate nursing interventions
(t=567 Plt00)
Discussion The purpose of this systematic review was to determine the effectiveness of
non-pharmacological interventions specifically targeting fatigue for children and
adolescents with cancer undergoing chemotherapy or after receiving chemotherapy
Included articles about the effectiveness of non-pharmacological interventions for
children and adolescents with cancer were published between the years of 2007 and
2009 Although interventions for cancer fatigue for adults have been extensively studied
it can be seen from either the title of the paper or related content that an intervention
study on children was a pilot study or a feasibility study Representing a field in its early
stage these studies show that the fatigue issues with young cancer patients have only
recently been taken seriously
661
29
The results of our meta-analysis include measurement of the four performance indicators
fatigue and general fatigue sleep rest fatigue and cognitive fatigue The results show
that there is a statistically significant difference only in the domain of general fatigue
using an exercise intervention for children with cancer can improve the degree of fatigue
with the effect size reaching 0671 Other results do not indicate significant differences
The reasons may include the following
1 Characteristics of the cancer The exhaustion from cancer occurs not only during cancer treatment but also in during
long-term survival a time during which patients may continue to be affected by this
symptom 8 26 Therefore when using intervention measures to improve fatigue
circumstances should be considered such as the process of the treatment and the course
or stage of the disease Because cancer patients will experience different forms of
treatment or courses of treatment the disease itself or treatment differences should be
considered in the choice of intervention Even chemotherapy drugs should be taken into
consideration For example a period of general steroid treatment can increase patientsrsquo
fatigue In those studies of children with cancer few studies looked solely at one type of
cancer most studies included a variety of cancer patients Furthermore most studies do
not clearly explain the stage of the disease or course of treatment and most do not
include treatment variables in the control group Moreover children with cancer may
have different levels of physical function
2 Research design The sample size Currently there are few studies with large sample size and a rigorous
RCT design due to the small number of papers available for analysis The sample size
included in our studyrsquos data analysis is between 20 and 42 people this small sample size
will affect the power available to evaluate outcome variables
Although most of the non-pharmacological interventions still use exercise and physical
activity and these studies overall show better results for fatigue as compared with
controls more research is still needed to further confirm the efficacy of these findings
662
30
The dropout rate in the evaluated research varies a great deal ranging from 5 to 45
these dropout rates may result from the characteristics of the research subjects or the
lengthy time involved in participating in these studies The research data with a high
turnover rate might not reflect the actual outcomes of participation in exercise and the
quality of the research contained in articles with high subject turnover rates may be
lower
Exercise doses and time The exercise doses needed to reduce fatigue cannot be
determined additionally the amount of exercise completed by the patient is also
inconsistent interventions vary between 2-3 times per week and two times a day and
exercise duration varies between 10 and 45 minutes each time Furthermore the study
interventions vary in length between a couple of days and a long period of 16 weeks The
data collection times are different some were measured 12 weeks after the intervention
began some were measured during the 6 weeks of intervention some were measured
three months after the intervention was finished and some were measured after one
year
In addition disease-related symptoms decrease childrenrsquos willingness to participate in
exercise interventions inappropriate exercise intervention programs may actually
increase childrens fatigue In addition the children in the study are still developing
physically it is important to consider ways to design an interesting exercise intervention
to increase the compliance of patients in order to improve the effectiveness Although
intervention programs in the hospital or in a community sports center can improve the
effectiveness because they provide supervision the feasibility of these programs is
questionable However if the program is home-based the children need to be
supervised by parents in order to improve their compliance in doing the exercises
Furthermore regarding the nature of the intervention the results from this study indicate
that the researched non-pharmacological interventions include the following exercise
training programs physical activity massage therapy and health education interventions
However according to the National Comprehensive Cancer Network 1 clinical guidelines
663
31
for cancer non-drug measures for cancer fatigue can be separated into five categories
(1) activity enhancement (2) psychosocial interventions such as cognitive behavioral
therapy (CBT) stress management relaxation techniques and support groups (3)
attention-restoring therapy (4) nutritional consultation and (5) cognitive behavioral
therapy specifically targeting sleep disturbance Researchers have also suggested that
psychosocial interventions should be included in the future research for children with
cancer-related fatigue 22
(2) The measurement tools in the study The assessment of fatigue can be
one-dimensional or multidimensional One-dimensional assessment can help understand
the severity of fatigue symptoms however multidimensional scales are often more
credible Therefore when measuring cancer-related fatigue researchers should consider
whether there is a uniform definition of fatigue or a standardized tool for measuring
fatigue in order to facilitate further systematic meta-analyses and further develop the
clinical care guidelines
Limitations of the review The present review has some potential limitations First the low methodological quality
may influence the result Although exercise intervention seems promising quality of the
RCTs was generally quite low Future studies require better design and reporting if
methodological issues to establish evidence-based nonpharmcologic intervention
Second the identified studies covered only a limited types of nonpharmcological
intervention especially in exercise intervention The guidelines for cancer-related fatigue
in NCCN (2011)1 referred to more interventions than the ones included in this review
such as cognitive behavioral therapy and nutrition consultation Thirdly the small sample
size and effect size could be potentially having led to underpowered approach for
detecting the effects on fatigue Therefore we recommend that as research continues to
grow a re-analysis can be undertaken Fourthly Combining data in meta analysis from
664
32
studies where the ages were quite different is a potential source of heterogeneity and
may affect the interpretation of the results
Conclusion At present clinical treatment is widely used for cancer patients However child and
adolescent cancer patients often experience various side effects which cause short-term
or long-term discomfort both physically and psychologically In particular with the
increasing cure rate cancer related fatigue during or after treatment has become an
important issue This study result provided positive effect of exercise intervention on
general fatigue
Implications for practice The results of this systematic review and meta-analysis show that exercise interventions
can effectively improve the level of general fatigue In particular although the articles
were self-reported feasibility studies their results all indicate that exercise interventions
for fatigue are feasible and safe there was no conclusion to be made for the use of
massage therapy or health education measures because there was only one article for
each of these interventions
Recommendations for practice
Cancer-related fatigue is one of the most severe and frequent symptoms by pediatric
oncology children and adolescent suffered during treatment and the symptom existed
even after treatment has ended Until now no golden standard of treatment to fatigue is
established The findings call for more attention to how to reduce patientrsquos levels of
fatigue Based on the available information evaluated in this review the following
recommendations for practice are provided
665
33
bull For children aged 7 to 18 who has cancer (eg Lymphoma leukemia CNS tumor
germ cell tumor) an effective progressive aerobic exercise program is recommended to
be at least 2-3 times per week 20 to 45 minute for each session and last for 6-16 weeks
in order to reduce their general fatigue (tiredness physically weakness) In addition
adults should be involved in accompanying children while they are performing physical
exercise of which should be able to improve the adherence rate (level 2 ) ( Grade of
recommendation A)
bull For children aged 7 to 18 who has cancer (eg Lymphoma leukemia CNS tumor
germ cell tumor) an progressive aerobic exercise program will not be effective to reduce
their sleep andor rest (sleeping or resting a lot) or cognitive fatigue (problems with
thinking quickly or problems with remembering) (level 2 ) ( Grade of recommendation C)
bull Nursing interventions in educating treatment of fatigue include information about
activity nutrition energy preservation consulting and providing a useful fatigue
handbook will benefit those children who are 7 to 12 years have a new diagnosis of ALL
AML or lymphoma and receive for the first time after being diagnosed a 7- to 10-day
chemotherapy treatment (level 2) ( Grade of recommendation A)
bull A 4-week massage therapy program (the therapists massage childrenrsquos back legs
arms stomachchest and face) is not effective for children who are aged 7 to 18 and
have acute lymphoblastic leukemia brain tumors lymphoma rhabdomyosarcoma
Wilms tumor or Ewing sarcoma(level 2)( Grade of recommendation C)
bull Using a 12-week aerobic and strength exercise (45-min exercise sessions twice a
week) is not effective for children who are aged 6-14 and survived acute lymphoblaststic
leukemia age from 6 to 14(level 2) ( Grade of recommendation C)
bull Using a physical activity intervention (30minutestwice daily for 2-4days) is not
effective for children who are 7 to 18 years of age with soild tumor or AML(level 2)
( Grade of recommendation C)
666
34
Implications for research According to this systematic review and meta-analysis results there are suggestions to
improve the effectiveness of future research on non-pharmacological interventions for
children and young peoplersquos cancer-related fatigue
As the majority of included non-pharmacological interventions for the fatigue of cancer
patients consist of exercise programs future research should also consider various
non-pharmacological interventions in order to understand the effectiveness of different
methods
Regarding the exercise intervention methods and studies should consider multiple
factors including the age or personal condition of the subject the disease stage and the
amount of daily activities Studies should use design prescriptions (eg frequency
intensity duration and type of exercise) and consider the adherence to the measures in
order to enhance the study strength
In measuring the results of non-pharmacological interventions there should be standard
definitions or standard measurement tools to facilitate the following systematic review
and meta-analysis that can subsequently be developed into clinical care guidelines
Reviewing the effectiveness of the current non-pharmacological management of children
and adolescent cancer patients there is still a lack of rigorous RCT research Limited by
the characteristics of cancer there is still a lack of large sample sizes
Potential conflicts of interest There is no conflict of interest
Acknowledgements
Thank you to Dr Rie Konno Research Fellow Joanna Briggs Institute for her help in
assessing studies
667
35
References 1 National Comprehensive Cancer Network( NCCN) in USA NCCN clinical practice
guideline in oncology cancer-related fatigue 2011 2 Ekti Genc R amp Conk Z Impact of effective nursing interventions to the fatigue
syndrome in children who receive chemotherapy Cancer Nursing 200831(4)312-317
3 Childhood Cancer Foundation of ROC (2009March) The classification of diseases
and age sex statistical tables of case Childhood Cancer Foundation of ROC newsletter103105-106
4 Department of Health Executive Yuan ROC (TAIWAN)(2009 March 20)2009 cause of death statistic Health and National Health Insurance Annual Statistics Information Service 2010 June 28Available httpwwwdohgovtwstatisticdatavital statists9898health statistic--lifepdf
5 Chang TK (2007December 8) Common childhood cancer and its treatment Status
Childhood Cancer Foundation of ROC (TAIWAN) 2010 September 23 Available httpwwwccfrocorgtwchildchild_events_readphpe_id=45
6 Hockenberry MJ amp Wilson D Wongs nursing care of infants and children (8th ed) St
Louis MO Mosby 2007
7 Post-White J Fitzgerald M Savik K Hooke MC Hannahan AB amp Sencer SF
Massage therapy for children with cancer Journal of Pediatric Oncology Nursing 2009 26(1)16-28
8Chiang YC Yeh CH Wang WKamp Yang CP The experience of cancer-related fatigue
in Taiwanese children European Journal of Cancer Care 2009 18(1)43-49 9Langeveld NE Grootenhuis M A Voute P A de Haan RJ amp van den Bos C No excess
fatigue in young adult survivors of childhood cancer European Journal of Cancer 200339(2)204-214
10Piper BF Lindsey AM amp Dodd MJ Fatigue mechanisms in cancer patients
developing nursing theory Oncology Nursing Forum 1987 14(6)17-23 11Nail LM amp Winningham ML Fatigue In S L Groenwald M H Forgge M Goodman
amp C H Yarbro (Eds) Cancer Nursing Principles and practice (4 th ed) Boston Jones and Bartlett1997
12Irvine D Vincent L Graydon JE Bubela N amp Thompson L The prevalence and
correlates of fatigue in patients receiving treatment with chemotherapy and
668
36
radiotherapy A comparison with the fatigue experienced by healthy individuals Cancer Nursing 199417(5)367-378
13Hinds PS amp Hockenberry-Eaton M Developing a research program on fatigue in
children and adloescents diagnosed with cancer Journal of Pediatric Oncology Nursing 200118(2)3-12
14Aaronson LS Teel CS Cassmeyer V Neuberger GB Pallikkathayil L Pierce J Press
AN Williams DP amp Wingate A Defining and measuring fatigue Journal of Nursing scholarship 1999 31(1)45-50
15Yeh CH Wang CH Chiang YC Lin Lamp Chien LC Assessment of symptoms reported
by 10- to 18-year-old cancer patients in Taiwan 2009 38(5)738-746 16 Okuyama T Akechi T Kugaya A Okamura H Shima Yamp Maruguchi M
Development and validation of the cancer fatigue scale a brief three-dimensional self-rating scale for assessment of fatigue in cancer patients Journal of Pain amp Symptom Management 2000 19(1) 5-14
17Gibson F Mulhall AB Richardson A Edwards JL Ream E amp Sepion BJ A
phenomenologic study of fatigue in adolescents receiving treatment for cancer Oncology Nursing Forum200532(3)651-660
18Wolfe J Grier HE Klar N Levin SB Ellenbogen JMamp Salem-Schatz S et al
Symptoms and suffering at the end of life in children with cancer New England Journal of Medicine 2000342(5)326-333
19Whiting P Bagnall AM Sowden AJ Cornell JE Mulrow CD amp Ramirez G
Interventions for the treatment and management of chronic fatigue syndrome a systematic review JAMA the Journal of the American Medical Association 2001286(11)1360-1368
20 Kangas M Bovbjerg DHamp Montgomery G H Cancer-related fatigue a systematic
and meta-analytic review of non-pharmacological therapies for cancer patients Psychological Bulletin 2008134 (5)700-741
21Williams PD Schmideskamp J Ridder EL amp Williams AR Symptom monitoring and
dependent care during cancer treatment in children pilot study Cancer Nursing 200629(3)188-197
22Takken T van der Torre P Zwerink M Hulzebos EH Bierings M Helders PJMamp van
der Net J Development feasibility and efficacy of a community-based exercise training
669
37
program in pediatric cancer survivors Psycho-Oncology 200918(4)440-448
23Keats MR amp Culos-Reed SN A community-based physical activity program for
adolescents with cancer (project TREK) program feasibility and preliminary findings
Pediatric hematology and oncology 200830(4) 272-280
24Hinds PS Hockenberry M Rai SN Zhang L Razzouk B I Cremer L McCarthy K amp
Rodriguez-Galindo C Clinical field testing of an enhanced-activity intervention in
hospitalized children with cancer Journal of Pain amp Symptom Management 2007
33(6)686-697
25Chiang YC The effects of ldquo a home-based aerobic exercise interventionrdquo on fatigue
and cardiorespiratory fitness in children with acute lymphoblastic leukemia during the
maintenance stage of chemotherapy Unpublished thesis Taiwan Tao-Yuan 2007
26Langeveld N Ubbink M amp Smets E I dont have any energy The experience of
fatigue in young adult survivors of childhood cancer European journal of oncology
nursing 20004(1)20-28
27 Kisner C Colby L Therapeutic exercise Foundations and techniques 2nd ed Philadelphia PAFA Davies 2007
670
38
Appendix I JBI Critical Appraisal Checklist for Experimental studies
Author__________ Year_________ Record Number__________________
Questions 1 to 4 must be answered ldquoyesrdquo for study to be included in the metashyanalysis
1 Were the participants randomized to study groups
Yes No Not clear
2 Other than research intervention were participants in each groups treated the same
Yes No Not clear
3 Were the outcomes measured in the same manner for all participants
Yes No Not clear
4 Were groups comparable at entry
Yes No Not clear
5 Was randomization of participants blinded
Yes No Not clear
6 Were those assessing outcome blinded to treatment allocation (if outcome not objective such as survival or length of hospitalization)
Yes No Not clear
7 Was allocation to treatment groups concealed from the allocator
Yes No Not clear
8 Was an appropriate statistical analysis used
671
39
Yes No Not clear
9 Were outcomes measured in a reliable way
Yes No Not clear
10 Was there adequate followshyup of participants
Yes No Not clear
Summary
TOTAL
Yes No Not clear
DECISION
Use Reject
Narrative summary only Further information needed
COMMENTS
672
40
Appendix II JBI Data Extraction Tool for Quantitative Studies Authors and Year
Journal Title
Record NumberArticle Reference No
Reviewer
Method
Settings
Participants
Number of participants
Group A Group B Group C
Control Intervention 1 Intervention 2
Interventions
Group A
Control
Group B
Intervention 1
Group C
Intervention 2
Outcome measures
Definition
673
41
Other outcome measures
Outcome description ScaleMeasure
Results
Dichotomous Data
Outcome Control Group
Numbertotal number
Treatment Group
Numbertotal number
Continuous Data
Authorrsquos Conclusions
Comments
Outcome Control Group
Mean amp SD
Treatment Group
Mean amp SD
674
43
Appendix III Details of included studies (N=6)(2720212223) RefNo Author(s)
(years) Title Study question Research
method Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
22 Takken T van der Torre P Zwerink M Hulzebos E H Bierings M Helders P J Mamp van der Net J (2009)
Development feasibility and efficacy of a community-based exercise training program in pediatric cancer survivors
To develop a 12-week home-based exercise training program (comprising aerobic and strength exercises) for children who survived ALL and to study itrsquos feasibility and efficacy
Pre-post test design
No comparsion group
Survived ALL(N=9)ages 6-14 years
1anthropometry 2 muscle strength 3functional mobility 4cardio-pulmonary
exercise test 5Fatigue
1 Feasibility questionnaire 2 anthropometry electronic scale and a wallmounted stadiometerHarpenden skin fold calipers 3 muscle strength handheld dynamometer 4functional mobility Timed Up
and Go test (TUG) 5cardio-pulmonary exercise test electronically braked cycle ergometer 6Fatigue(mean)CSI-20 (subjective experience of fatigueconcentrationmotivationphysical activity)
112-week exercise training program
2 Patients were assessed before (T0) and after (T1) 12 weeks of training
1 muscle strength execapacity functional moand fatigue showed nosignificant differences between pre(meanplusmnSD415plusmn147) and post training(meanplusmnSD3687)
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
7 Post-White J Fitzgerald M Savik K Hooke M C Hannahan A B amp Sencer S F (2009)
Massage therapy for children with cancer
To determine whether 4 weekly sessions of massage compared with 4 quiet-time control conditions would reduce anxiety cortisol levels fatigue nausea and pain in children with cancer undergoing chemotherapy and would reduce anxiety fatigue and mood disturbance in a parent
2-period crossover design (Randomized)
quiet-time
control
sessions
Children with cancer 1 to 18 years of age Twenty-three childrenparent dyads were enrolled 17 completed all data points
children 1relaxation 2symptoms 3 fatigue
parents
1anxiety 2 fatigue
children 1relaxation (heart and respiratory rates blood pressure and salivary cortisol level)
2symptoms (pain nausea anxiety 3 fatigue 1-2y3-6yLansky Play Performance Scale (PPS) 7-13y
1 4 weekly massage (MT) sessions alternated with 4 weekly quiet-time(QT) control sessions
2 children included presession and postsession vital signs (heart rate respiratory rate blood pressure) and self-report (parent proxy report for age 1-2 years) of pain nausea and anxiety Fatigue was measured before sessions 1 and 4 and at each follow-up Parent measures
included anxiety fatigue and mood states
1Massage was moreeffective than quiet tireducing heart rate inchildren anxiety in cless than age 14 yeaparent anxiety 2There were no sign
changes in blood pcortisol pain naufatigue (no state d
3 Children reported tmassage helped thebetter lessened theirand worries and hadlasting effects than q
675
44
14-18yChild Fatigue Scale (CFS) (frequency
intensity) 2 parents anxiety and fatigue
676
45
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
24 Hinds P S Hockenberry M Rai S N Zhang L Razzouk B I Cremer L McCarthy K amp Rodriguez-Galindo C (2007)
Clinical field testing of an enhanced-activity intervention in hospitalized children with cancer
To determine the feasibility of an
enhanced physical activity EPA intervention in children and adolescents hospitalized to receive chemotherapy for a solid tumor or AML and to assess the sleep and fatigue outcomes of the intervention using two different statistical approaches to analyze the longitudinal symptom data
randomized prospective two-site and two-group pilot study
Standard care Twenty nine patients (25 with a solid tumor and 4 with AML)ages 7-18 years
1 sleep duration 2 sleep efficiency 3 fatigue
1sleep duration sleep efficiency The
Wrist Actigraph The Daily Sleep Diary-Parent 2 fatigue (mean) The Fatigue Scale(FS-C) for 7-12 (intensity) The Fatigue Scale(FS-A) for 13-18 The Fatigue Scale Parent Version (FS-P) The Fatigue Scale Staff Version (FS-S)
1enhanced physical activity (EPA) (hospital-based 30 minutes
twice daily for 2-4 days) 2 T0On the day of admission
(Day 0 or baseline)patient and parents completed the fatigue instruments and a team member applied the actigraph Patients wore the wrist actigraph T1 from Day 0 to 2 or 3 consecutive days (Days 0e3) In addition the patient same parent and staff nurses completed the daily sleep and fatigue reports in the late afternoons of Days 1-3
1 ANOVA model slesignificantly more the experimental athe control arm whdifferences from bsleep efficiency vaaveraged and com
2 The patient-reported mean fatigue scoresarms were higher amadolescents than for
3 The mixed model anarevealed no significandifferences in patientfatigue between
the two study arms otime( no final result iSD only give mixed result)
677
46
23 Keats M
R amp Culos-Reed S N (2008)
A community-based physical activity program for adolescents with cancer (project TREK) program feasibility and preliminary findings
To examine the
feasibility of a
theoretically-based
physical activity (PA)
intervention in
adolescents with
cancerand
examination of the
impact of the
program on
participant QOL
including social
emotional and
physical
well-being(including fatigue)
Repeat measures longitudinal design
No comparsion group
10 adolescents(Lymphoma(4)leukemia(4)CNS tumor(1)germ cell tumor(1)) ages 14-18 years
1physical fitness 2quality of life (QOL) 3PA behavior 4fatigue
1 Feasibility was assessed by participant recruitment attendance and adherence
2physical fitness Fitnessgram 3quality of life (QOL) Pediatric Quality of Life Inventory (PedsQL) 4PA behavior leisure score index (LSI) 5fatigue (mean) pediatric Quality of life
Multidimensional Fatigue Scale (Peds QL-MFS)
(Generalsleepcognitive fatigue)
116week physical activity (PA)
2 total PA physical fitness and overall QOL was assessed at 5 different intervals T0 preintervention (baseline) T1midintervention (after the
first 8 wk) T2 postintervention
(16 wk) T3 3-months
postintervention T4 1-year poststudy
initiation
1 from baseline -wkssig Improvementstotal PA physfitness and Qgeneral fatigue(meanplusmnSD 796plusmn135)
2 from baseline to 3FUsig Improvin general fatigue(meanplusmnSD824plusmn131)slefatigue(meanplusmnSD755plusmn191)totafatigue(meanplusmnSD778plusmn150)
3at 1 years FUsImprovements in sleeprest fatigue(meanplusmnSD725plusmn203)total (meanplusmnSD 763plusmn
678
47
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
2 Gene R E amp Conk Z (2008)
Impact of Effective Nursing Interventions to the Fatigue Syndrome in Children Who Receive Chemotherapy
1 to examine the effects of an effective nursing intervention to the fatigue syndrome of children 7 to 12 years of age who receive chemotherapy 2Tto examine the relationship between fatigue and demographic variables (age sex) diagnoses ([ALL AML] lymphoma) and therapy-related variables (eg level of hemoglobin
experimental randomized controlled study
Routine nursing care
A total of 60 children who are 7-12 years of age(a new diagnosis of ALL AML or lymphoma and receiving for the first time after being diagnosed a 7- to 10-day chemotherapy treatment )
fatigue The Fatigue Scale(FS-C) for 7-12 (intensity)
The Fatigue Scale Parent Version (FS-P)
1 effective nursing interventions(45- 60mdaya week)education about the fatigue with the chemotherapy and fatigue handbook 2 T1 After a 7-day period the children
and parent were evaluated with the Fatigue Scale
1The difference betwthe 2 mean values wafound to be statisticallsignificant 2 statistically significadifference was found between the Fatigue Scale-Child mean scothe experimental (272the control group (4213)children
679
48
25 Chiang et
al(2007)
The effects of ldquo a home ndashbased aerobic exercise interventionrdquo on fatigue and cardiorespiratory fitness in children with Acute Lymphoblastic Leukemia during the maintenance stage of chemotherapy
To examine the effect of ldquo a home ndashbased aerobic exercise interventionrdquo on fatigue and cardiorespiratory fitness in children with Acute Lymphoblastic Leukemia during the maintenance stage of chemotherapy
Quasi-experi -mental
Routine
nursing care
14 pediatric oncology patients in the experimental group and 10 in control group who were matched by age and sex ages7-18 years
1Cardiorespiratory fitness
2Fatigue
1Cardiorespiratory fitness Physical Activity Recall
VO2maxHR peak 6MWT
2 Fatigue PedsQL-MFS(Generalsleepcognitive fatigue)
1A six-week home-based aerobic exercise intervention 2 8 time points T0 baseline T1-T6 every week during the
intervention(6 weeks) T7 post intervention T8 follow-up (one month after
the end of the home-based exercise program)
1 For intent-to ndash treatthe findings indicated are no intervention efftime differences by anon the subscale of fat2 For per-protocol angeneral fatigue( mean422plusmn402) was the osubscale that was siglower for children whothe exercise interventthose in control groupfollow-up assessmentmonth after the compintervention) 3 The VO2peak are significantly improvingexperimental group atbaseline- and post-intassessment The VO2was significantly highechildren who were in experimental group thcontrol subjects at post-intervention assefor the per-protocol an
680
49
Appendix IV Instrument used to measure fatigue
Name Instrument
developers
Description Used in
age in
ref
Reliability
Consistency of
instrument
Checklist Individual Strength
(CIS)22
Vercoulen et
al1996
20 items using 7-point Likert scale of
fatigue To measure four aspects of
fatiguesubjective experience
contractionmotivation physical
Activity
6-14 Not reported
Child Fatigue Scale (CFS)7 Hockenberry
et al2003
14 items 2 part questionnaire frequency
(yes or no) 5-point Likert scale of the
intensity of any yes responses
7-13
14-18 α073-o84
The Fatigue Scale for 7-12
year Olds (FS-C)224
Hockenberry
et al
14 items provide a fatigue intensity score
5-point Likert scale
7-12 αo84
The Fatigue Scale for 13-18
year Olds (FS-A)24
Hockenberry
et al
14 items provide a fatigue intensity score
5-point Likert scale
13-18 α076-o96
Pediatric Quality of life
Multidimensional Fatigue
Scale (Peds QL-MFS)2325
Varni2002 18 items to measure three aspects of
fatigueGeneralsleepcognitive
14-18 Not reported
681
50
Appendix V Excluded studies and reasons for exclusion
Baggott C Dodd M Kennedy C Marina N Miaskowski C Multiple Symptoms in Pediatric Oncology
Patients A Systematic Review Journal of Pediatric Oncology Nursing 2009 Nov-Dec 27(6)
325-339
Reason for exclusion Not outcome of interest
Barlow JH Ellard DR Psycho-educational interventions for children with chronic disease parents and
siblings an overview of the research evidence base Care Health amp Development 2004 Nov
30(6)637-45
Reason for exclusion Not outcome of interest
Bedider S Moyer CA Randomized controlled trials of pediatric massage A review Evid Based
Complement Alternat Med 2007 Mar 4(1)23-34 Epub 2006 Nov 3
Reason for exclusion Not outcome of interest
de Nijs EJ Ros W Grijpdonck MH Nursing intervention for fatigue during the treatment for cancer Cancer
Nursing 2008 31(3)191-206
Reason for exclusion Not population of interest
Edwards JL Gibson F Richardson A Sepion B Ream E Fatigue in adolescents with and following a
cancer diagnosis developing an evidence base for practice European Journal of Cancer 2003
Dec 39(18)2671-80
Reason for exclusion Not experimental or quasi-experimental study
Hinds PS Hockenberry-Eatan M Developing a research program on fatigue in children and adolescents
diagnosed with cancer Journal of Pediatric Oncology Nursing 2001 Mar-Apr 18(2 Suppl
1)3-12
Reason for exclusion Not experimental or quasi-experimental study
Hockenberry-Eaton M Hinds PS Alcoser P ONeill JB Euell K Howard V Gattuso J Taylor J Fatigue in
Children and Adolescents With Cancer Journal of Pediatric Oncology Nursing 1998 July
15(3)172-182
Reason for exclusion Not experimental or quasi-experimental study
Jean-Pierre P Mustian K Kohli S Roscoe JA Hickok JT Morrow GR Community-based clinical oncology
research trials for cancer-related fatigue The Journal of Supportive Oncology 2006 Nov-Dec
4(10)511-6
682
51
Reason for exclusion Not population of interest
Kangas M Bovbjerg DH Montgomery GH Cancer-Related Fatigue A Systematic and Meta-Analytic
Review of Non-Pharmacological Therapies for Cancer Patients Psychological Bulletin 2008 Sep
134(5)700-41
Reason for exclusion Not population of interest
Lotfi-Jam K Carey M Jefford M Schofield P Charleson C Aranda S Nonpharmacologic strategies for
managing common chemotherapy adverse effects A systematic review Journal of Clinical
Oncology 2008 Dec 1 26(34)5618-29 Epub 2008 Nov 3
Reason for exclusion Not outcome of interest
Marchese VG Chiarello LA Lange BJ Effects of physical therapy intervention for children with acute
lymphoblastic leukemia Pediatr Blood Cancer 2004 Feb42(2)127-33
Reason for exclusion Not outcome of interest
Meeske KA Siegel SE Globe DR Mack WJ Bernstein L Prevalence and correlates of fatigue in
long-term survivors of childhood leukemia Journal of Clinical Oncology 2005 Aug 20
23(24)5501-10
Reason for exclusion Not intervention study
Minton O Richardson A Sharpe M Hotopf Stone P A systematic review and meta-analysis of the
pharmacological treatment of cancer-related fatigue J Natl Cancer Inst 2008 Aug 20
100(16)1155-66 Epub 2008 Aug 11
Reason for exclusion Not population and intervention of interest
Mustian KM Morrow GR Carroll JK Figueroa-Moseley CD Pascal JP Williams GC Integrative
nonpharmacologic behavioral interventions for the management of Cancer-Related fatigue The
Oncologist 2007 12(1)52-67
Reason for exclusion Not population of interest
Neill J Belan I Ried K Effectiveness of non-pharmacological interventions for fatigue in adults with
multiple sclerosis rheumatoid arthritis or systemic lupus erythematosus a systematic review
Journal of Advanced Nursing 2006 Dec 56(6)617-35
Reason for exclusion Not population of interest
Rheingans JI A systematic review of nonpharmacologic adjunctive therapies for symptom management
Journal of Pediatric Oncology Nursing 2007 24(2) 81-94
683
52
Reason for exclusion Not outcome of interest
Rheingans JI Pediatric oncology nursesrsquo management of patients symptoms Journal of Pediatric
Oncology Nursing 2008 Nov 25(6) 303-11
Reason for exclusion Not outcome of interest
San Juan AF Fleck SJ Chamorro-Vintildea C Mateacute-Muntildeoz JL Moral S Peacuterez M Cardona C Del Valle MF
Hernaacutendez M Ramiacuterez M Madero L Lucia A Effects of an intrahospital exercise program
intervention for children with leukemia Medicine amp Science in Sports amp Exercise 2007 Jan
39(1)13-21
Reason for exclusion Not outcome of interest
Sanford SD Okuma JO Pan J Srivastava DK West N Farr L Hinds PS Gender differences in sleep
fatigue and daytime activity in a pediatric oncology sample receiving dexamethasone Journal of
Pediatric Psychology 2008 Apr 33(3)298-306 Epub 2007 Nov 17
Reason for exclusion Not experimental or quasi-experimental study
Schmitz KH Holtzman J Courneya KS Macircsse LC Duval S Kane R Controlled physical activity trials in
cancer survivors a systematic review and meta-analysis Cancer Epidemiol Biomarkers Prev
2005 Jul 14(7)1588-95
Reason for exclusion Not population of interest
van Brussel M Takken T Lucia A van der Net J Helders PJ Is physical fitness decreased in survivors of
childhood leukemia A systematic review Leukemia 2005 Jan 19(1)13-7
Reason for exclusion Not population of interest
Whiting P Bagnall AM Snowden AJ Cornell JE Mulrow CD Ramirez G Interventions for the treatment
and management of chronic fatigue syndrome JAMA 2001 Sep 19 286(11)1360-8
Reason for exclusion Not intervention of interest
Whitsett SF Gudmundsdottir M Davies B McCarthy P Friedman D Chemotherapy-related fatigue in
childhood cancer correlates consequences and coping strategies Journal of Pediatric
Oncology Nursing 2008 Mar-Apr 25(2)86-96 Epub 2008 Feb 29
Reason for exclusion Not experimental or quasi-experimental study
Winner C Muumlller C Hoffmann C Boos J Rosenbaum D Physical activity and childhood cancer Pediatr
Blood Cancer 2010 Apr 54(4)501-10
Reason for exclusion Not research study
684
53
Wu M Hsu L Zhang B Shen N Lu H Li S The experiences of cancer-related fatigue among Chinese
children with leukaemia A phenomenological study Journal of Nursing Studies 2010 Jan
47(1)49-59 Epub 2009 Aug 25
Reason for exclusion Not experimental or quasi-experimental study
Yeh CH Chiang YC Lin L Yang CP Chien LC Weaver MA Chuang HL Clinical factors associated with
fatigue over time in paediatric oncology patients receiving chemotherapy British Journal of
Cancer 2008 Jul 8 99(1)23-9 Epub 2008 Jun 24
Reason for exclusion Not experimental or quasi-experimental study
685
12
Review QuestionsObjectives
Review Objective
The objective of this systematic review was to critically appraise synthesize and
present the best available evidence concerning the effects of non-pharmacological
interventions fatigue in children and adolescents with cancer
Review Question
The following specific question was addressed in this review
What is the effectiveness of non-pharmacological interventions on fatigue in
children and adolescents with cancer aged from one to 18 years
Criteria for Considering Studies for this Review
Types of studies
This review included randomised controlled trials (RCTs) and quasi-experimental
studies that examine the effectiveness of non-pharmacological intervention for fatigue in
children and adolescents with cancer
Types of participants
Children and adolescents aged from one to 18 years old experiencing fatigue
associated with cancer either during or after the chemotherapy or maintenance stage of
chemotherapy or survive stage The types of cancer to be included in this systematic
review will be ALL (Acute lymphoblastic leukemia) AML (Acute myeloid leukemia)
lymphoma and solid tumors
Exclusion criteria for Types of participants
645
13
newborn infants under 1 years of age
participants who do not have a specific diagnosis of cancer
participants who have received immunoglobulin or hydrocortisone
treatment
If participants have received immunoglobulin or hydrocortisone treatment may
inference the effectiveness of non-pharmacological interventions on fatigue
Types of intervention
This review considered studies that examine non-pharmacological interventions on
fatigue for children and adolescents with cancer including activity enhancement
(exercise physical activity) psychosocial interventions CBT stress management
relaxation nutrition consultation massage and educational interventions The
interventions descriptive included the length frequency setting and intervention
providers eg Nurse Psychologist Dietician
Exclusion criteria for types of interventions only pharmacological interventions were
tested
Types of outcome measures
The outcome measures considered were fatigue scores The literature demonstrates that
differences of opinion exist regarding the most valid and reliable method of measuring
cancer-related fatigue Therefore studies that used any validated scale for
cancer-related fatigue were considered for inclusion Currently commonly used scales to
measure fatigue include Checklist Individual Strength (CIS) Child Fatigue Scale (CFS)
The Fatigue Scale for 7-12 year Olds (FS-C) The Fatigue Scale for 13-18 year Olds
646
14
(FS-A)and Pediatric Quality of life Multidimensional Fatigue Scale (Peds QL-MFS)
Types of settings
Both hospital and community settings
Search Strategy
Before undertaking this systematic review the Cochrane Library Joanna Briggs Institute
Library of Systematic Reviews and CINAHL were searched and no systematic reviews on
this topic were found or identified as underway
The search strategy aimed to find both published and unpublished studies
A three-step search strategy was utilized in each component of this review An initial
limited search of CINAHL and MEDLINE was undertaken followed by an analysis of the
text words contained in the title and abstract and of the index terms used to describe the
article A second search using all identified keywords and index terms was undertaken
Lastly the reference lists of all identified reports and articles were searched for additional
studies
Types of languages
1 English
2 Chinese
The following databases were searched to identify keywords contained in the title and
abstract and relevant MeSH headings and descriptor terms
The Cochrane Library PsycINFO 1990 ndash 2010
647
15
Ovid MEDLINE 1966 ndash 2010 CINAHL Plus with Full Text 1960 ndash2010 EMBASE ProQuest Dissertations amp theses 1990-2010 Electronic theses and dissertations system 1956(abstract)1990(full text)-2010 MEDNAR Index to Taiwan periodical literature 1970-2010 Electronic thesis and dissertation system (Chinese) 1990-2010
Keyword search terms
1Types of studies experimental study random quasi-experimental study實驗性研究隨
機類實驗性研究
2 Types of participants childchildren adolescents pediatric cancer and oncology兒童
青少年兒科癌症腫瘤
3 Types of interventions non-pharmacological interventions massage exercise fitness
physical activity cognitive behavioral stress management energy conservation
sleep therapy relaxation distraction and psycho-education非藥物性處置按摩運動
身體活動認知行為壓力處置能量保存睡眠治療放鬆轉移注意力衛教
4 Types of outcome measures fatigue cancer-related fatigue loss of energy levels of
tiredness tired side effect symptoms疲憊癌性疲憊疲倦合併症症狀
Methods of the Review
Assessment of methodological quality Papers selected for retrieval were assessed by two independent reviewers for
methodological validity prior to inclusion in the review using the standardised critical
appraisal instruments (Appendix I) from the JBI-SUMARI (Joanna Briggs Institute
Systems for the Unified Management Assessment and Review of Information package)
Any disagreements that arise between the reviewers were resolved through discussion
648
16
with a third reviewer
Data extraction Data was extracted from papers included in the review using standardised data
extraction tool (Appendix II) from the JBI-SUMARI Details of eligible studies were
extracted and summarised independently by two reviewers
Data Synthesis
All data analysissynthesis were made using the JBI-SUMARI The studies were
assessed for clinical heterogeneity by considering the settings populations interventions
and outcomes Where possible these binary outcomes were analyzed by calculation of
the Odds Ratio with the 95 CI The weighted mean difference was calculated if the
pooled studies have used the same scale for continuous data The standardized mean
difference was calculated for continuous data measuring the same outcome on a
different scale In studies where statistical pooling of results was inappropriate the
findings were considered for inclusion as a narrative summary
Results The findings from the systematic review are presented first Followed by the results from
the meta-analysis component of this review
Description of studies From database search and hand search a total of 76 papers were identified Thirty
papers were then excluded because they did not meet the inclusion criteria Forty-six
full text were retrieved for further consideration for inclusion Of the 30 excluded reasons
for exclusion were follows 11articles were duplicated eight articles did not meet
649
17
participant inclusion criteria eight articles did not meet outcome criteria and nine articles
were correlation studies or discussion papers others articles were unclear reporting In
total after sorting six papers have been included in this article Figure 1 displays the
process used to identify relevant articles for inclusion in the systematic review
Figure 1 Stages of searching and inclusionexclusion of references for the review
Potentially relevant English-language and Chinese- language Studies Identified
Electronically and hand search (n=76)
Duplicate (n= 11) Papers excluded after evaluation of abstract (n=19)
Papers retrieved for detailed examination (N=46)
Papers excluded after review of full paper
(n=40)
Papers assessed for methodological
quality (n=6)
Papers included in systematic review
(n=6)
Methodological Quality
Of the six included articles 2722232425 two articles were RCT design224 with score 7 out
of 10 each paper from Critical Appraisal Checklist and four articles used
650
18
quasi-experimental design7222425 with socre 5 to 6 out of 10 because the quality of
the whole papers is still acceptable therefore these six articles were accepted after
primary reviewer and secondary reviewerrsquos decision
Randomisation
In two RCT articles224 one study24 used to a computer-generated program operated by
the St Jude Protocol and Data Management System to randomize the sample Another
study2 didnrsquot address how randomization was done
Allocation concealment
No studies reported allocation concealment
Intention-to-treat analysis
One quasi-experimental design7 stated Intention-to-treat analysis
Adequate follow up
The follow-up periods included 2or 3 days24 7 days2 4 week7 one month25 6 week25 12
week2216 week23 and 1 year23
Baseline comparability of groups
Three 22425 of six studies had baseline comparability in terms of age sex diagnosis
race institution duration of illness
Blinded outcome assessment
No studies used blinded outcome assessment The researchers including study team
patients staff and families were not blinded to the patientrsquos group assignment
Characteristics of included studies
651
19
There were six studies related to interventions designed to cancer-related fatigue for
pediatric patients than there are for adults There are a total of six including five
English-language papers 27222324 and one Chinese-language paper 25 ranging in year of
publication from 2007 to 2009
Patient characteristics
The research subjects of four papers included both school-aged children and
adolescents 7222324 one papers involved mainly adolescents25 and one paper sampled
only school-aged children 2 the range in ages was between six-18 years The number of
patients included in the samples ranged from nine to 60 The sources of case data were
from both outpatients and hospitalized children The types of cancer included acute
lymphoblastic leukemia (ALL) solid tumors acute myeloid leukemia (AML) and
lymphoma Overall ALL was the most commonly studied cancer type The stage of the
disease varied in these reports some patients were in the maintenance stage of
chemotherapy25 some had just received their first round of chemotherapy224 some had
completed two courses of treatments lasting 4-8 weeks each 7 and some had entered
the survivor stage 2223
Countries
Two RCTrsquos 2 24 were conducted in the USA There were four quasi-experimental design
studiesThree studies conducted in the USA7 22 23 and one in Taiwan25
Intervention types
652
20
The interventions included exercise training programs 2225 physical activity 2324
massage therapy 7 and health education 223 exercise training and physical activity as
an intervention method given in three different settings home 22 25 community 23 or
hospital 24 The studies used different types of exercise interventions including
home-based aerobic exercise use a Video Compact Disc 25 use of a bicycle-style
exerciser 24 aerobics2223 and various types of physical activities2 and strength-building
exercises 2223 The intensity of the exercise varied and often included gradual warm-up
exercises a period of main exercise and a cool down period For these studies2023 the
target exercise intensity was a heart rate of gt90 of the maximum heart rate (HR max) or
the increase in the percentage of heart rate reserve ( HRR) of 40-60
The number of weeks for the exercisephysical activity interventions duration including
2-4 days 24 6 weeks25 12 weeks22 and 16 weeks23 The frequency of exercise ranged
from 2-3 times per week to twice a day Typical duration of exercise ranged from 10 to 45
minutes There are three papers using exercise interventions based on ACSM (American
College of Sports Medicine) 2225 recommendations and one of these used an Activity
pyramid from the ACSM to determine intensity 24
One article did not clarify the type of exercise intervention or the reasons for their choices
23 In addition there was an article focusing on massage therapy 7 as an intervention in
this study the experimental group received four weeks of massage therapy either in the
clinic or in the patientrsquos room the therapy was applied by a professional masseur and
targeted the back legs arms chest stomach and face of the children However the
frequency of massage sessions per week and the duration of the massages were not
653
21
given There is another article about intervention measures combine health education
and physical activity 2 In this study patients were informed about the following (1) health
education patients received daily education about chemotherapy-related fatigue and
information from a health education manual written by the author (2) encouragement for
children to engage in activities such as listening to music drawing and reading and (3)
physical activity which involved walking along the corridors of the ward for 10-15 minutes
These health education measures were presented for 45-60 minutes a day for a total of
seven days The study design for non-pharmacological interventions used control groups
that included primarily people who had received standard treatment or people who did
not receive an exercise intervention
Outcome measures
Five measurement tools were used in this group of seven papers concerning childrenrsquos
fatigue (Appendix IV) Because those studies included both school-age children and
adolescents the following descriptions will be differentiated by age Fatigue
measurements for school-aged children with cancer include the following the Child
Fatigue Scale (CFS) 7 a scale that measures the frequency and intensity of fatigue and
the Fatigue Scale for 7-12 year Olds (FS-C) 224 a scale that can be used to evaluate the
intensity of fatigue On the other hand fatigue measurements for adolescent cancer
patients include the following the Fatigue Scale for 13-18-year-olds (FS-A) 24 a measure
that can help evaluate fatigue levels the Pediatric Quality of Life Multidimensional
Fatigue Scale (Peds QL-MFS) 2325 a tool that can be divided into three sub-scales to
understand the general cognitive and sleep rest components of fatigue and finally the
CIS-20 for school-age children and adolescents 22 a scale that measures four levels of
654
22
fatigue namely subjective experience attention motivation and physical activity Two
studies used the Peds QL-MFS scale to measure fatigue2325
Meta-analysis results Two studies of the included papers failed to provide sufficient raw data they could not be
included in the meta-analysis Hinds et al 24 did not include post-test data Genc et al 2
provided no pre-test data PostWhite et al7 reported that fatigue after the health
education intervention was not statistically different but they presented the results
without presenting fatigue-related data Therefore the meta-analysis included three
studies 222325
The heterogeneity of studies was analyzed with Chi square statistics and no statistical
significance was found Therefore the data was combined in meta-analysis according to
exercise intervention on fatigue In addition there were three articles using the Peds
QL-MFS as a research tool to examine childrenrsquos improvements in fatigue Among these
Keats 22 and Chiang 24 present the effectiveness of exercise interventions using three
subscales Therefore the meta-analysis also analysis of the effects of these exercise
intervention measures on three subscales of Peds QL-MFS general fatigue sleep rest
fatigue and cognitive fatigue
The effectiveness of exercise intervention for fatigue We analyzed the exercise intervention effect on fatigue A total of 2 studies 22 23 were
included Takken et al 22 used community-based exercise training program to reduce
fatigue of children 6 to 14 years (mean 93y) of age who survived ALL Fatigue
measurement by Checklist Individual Strength (CIS) after 12-week of training fatigue
655
23
show no significant differences between pre (meanplusmnSD 415plusmn147) and post training
(meanplusmnSD368plusmn217) but fatigue change from baseline mean reduction of 11
Keats et al23 although used community-based physical activity program to reduce fatigue
for adolescents 14 to 18 years of age (mean162 y) with cancer (Lymphoma leukemia CNS
tumor germ cell tumor) Studies used fatigue by PedsQLMFS Results show general fatigue
from baseline to 8 weeks and to 3 months follow up significantly improves General
fatigue sleeprest fatigue and total fatigue from baseline to 3 months follow up showed
significant improvements Sleeprest fatigue and total fatigue at 1 years followed up were
significant improvements
Figure 2 shows the overall effect of exercise intervention in children and adolescents with
cancers with a focus on improving fatigue Due to the lower heterogeneity (p>005) the
fixed effects model was used to pool the data for meta-analysis (Overall effect size=
-006 95 Confidence Interval (CI) -070 to 058) A result did not indicate a statistically
significant difference (p = 087)
656
24
Figure2 Meta-analysis results of exercise intervention on fatigue
In addition Keats23 and Chiang25 used the three sub-scales of Peds QL-MFS to
determine the general cognitive and sleep rest components of fatigue The following
present the effectiveness of exercise interventions using three subscales including
general fatigue sleep rest fatigue and cognitive fatigue 2325
Chiang et al 25 used a 6- week home-based aerobic exercise intervention to reduce
fatigue of children 7 to 18 years (mean age at experimental group was 1088 y in control
group was 1247 y) of age who with acute lymphoblastic leukemia Fatigue measurement
by Peds QL-MFS after training For intent-to ndash treat analysis the findings indicated that
there are no intervention effects and time differences by any items on the subscale of
fatigue For per-protocol analysis general fatigue( meanplusmnSD 422plusmn402) was the only
subscale that was significantly lower for children who received the exercise intervention
than those in control group at follow-up assessment (one month after the completion of
intervention)
Keats et al23 although used community-based physical activity program to reduce fatigue
for adolescents 14 to 18 years of age (mean162 y) with cancer (Lymphoma leukemia
CNS tumor germ cell tumor) Both studies used fatigue by PedsQLMFS Results show
general fatigue from baseline to 8 weeks and to 3 months follow up significantly improves
657
25
General fatigue sleeprest fatigue and total fatigue from baseline to 3 months follow up
showed significant improvements Sleeprest fatigue and total fatigue at 1 years followed
up were significant improvements
The effectiveness of exercise intervention for general fatigue
The impact of the exercise interventions upon levels of general fatigue was also analysed
The heterogeneity was low (p>005) Therefore the fixed effects model was used to
examine the effectiveness The effect size is -076 indicating a statistically significant
difference (p = 001 95 CI -135 to -017 Fig 3) The evidence suggests that exercise
intervention can reduce general fatigue in children with cancer
Fig 3 Meta-analysis results of exercise intervention for general fatigue
The effectiveness of exercise intervention for sleep rest fatigue
The following is the result of the meta-analysis of the effectiveness of exercise
interventions on sleep rest fatigue First the heterogeneity test was conducted with P gt
005 representing small heterogeneity and the fixed effects model was used Fig 4
shows the effect size is -035 indicating no statistically significant differences (p = 023
95 CI-092 to 022 Fig 4)
658
26
Fig 4 Meta-analysis results of exercise intervention for sleep rest fatigue
The effectiveness of exercise intervention for cognitive fatigue Lastly the following data reports the results of meta-analysis of the effectiveness of
exercise interventions for cognitive fatigue The heterogeneity was p>005 then the
fixed effects model was used The effect size is -035 indicating no statistically significant
differences (p = 024 95 CI-092 023 Fig 5)
Fig 5 Meta-analysis results of exercise intervention for cognitive fatigue
Narrative presentation of remaining included studies
Three studies were not included in meta-analysis Post-White et al7 one of the aims in
this study was to examine the effect of massage therapy on fatigue in children with
cancer The study was a quasi-experimental design Twenty-three childrenparent dyads
were enrolled 17completed all data points Children with cancer ages 7 to 18 years
received at least 2 identical cycles of chemotherapy and one parent participated in the
2-period crossover design in which 4 weekly massage sessions (MT) alternated with 4
659
27
weekly quiet-time (QT) control sessions There were no significant changes in fatigue in
children over the 4-week MT or QT conditions either independently (change over time) or
when we compared fatigue by condition
The lack of effect of massage on fatigue may be the difficulty some children had in
differentiating fatigue from being relaxed underscores the challenge of measuring fatigue
in children Some children interpreted being tired or relaxed as having greater fatigue
because they felt like lying around and sleeping or felt unmotivated to do their usual
activities all measures of fatigue in the instrument used in the study
Hinds et al24conducted a prospective two-site randomized controlled pilot study to
assess the feasibility of an enhanced physical activity (EPA) intervention in hospitalized
children and adolescents receiving treatment for a solid tumor or for acute myeloid
leukemia (AML) Twenty-nine patients (25 with a solid tumor and 4 with AML) participated
age range from 736 to 1816 (mean 1248 y) The EPA intervention selected was
pedaling a stationary bicycle-style exerciser (Chattanooga Peddler Deluxe Bio-Teck
Medical Memphis TN) for 30 minutes twice daily for 2 to 4 days of hospitalization The
mixed model analysis revealed no significant differences in patient reports of fatigue
between the two study arms or over time
Genc et al2 conducted a RCT involving children with cancer who are 7 to 12 years of age
and receiving chemotherapy treatment to determine the impact of educational
intervention by nurses on decreasing the fatigue syndrome The research sample was
composed of a total of 60 children with cancer with 30 children being included in the
660
28
experimental group (mean age 923)and 30 children included in the control group (mean
age 937) with their mothers In the experimental group after the 7th to 10th day of the
chemotherapy treatment throughout a week the researcher conducted the nursing
interventions every day for 45 to 60 minutes In the control group routine nursing
interventions were carried out The experimental group received education about the
fatigue with the chemotherapy and fatigue handbook was given which was developed by
the authors Children and mothers were consulted for including activities that could
decrease fatigue which were described as effective interventions A statistically
significant difference was found between the Fatigue Scale-Child mean scores of the
experimental (2723) and the control group (4213) The results suggest that fatigue of
children with cancer can be reduced by implementing appropriate nursing interventions
(t=567 Plt00)
Discussion The purpose of this systematic review was to determine the effectiveness of
non-pharmacological interventions specifically targeting fatigue for children and
adolescents with cancer undergoing chemotherapy or after receiving chemotherapy
Included articles about the effectiveness of non-pharmacological interventions for
children and adolescents with cancer were published between the years of 2007 and
2009 Although interventions for cancer fatigue for adults have been extensively studied
it can be seen from either the title of the paper or related content that an intervention
study on children was a pilot study or a feasibility study Representing a field in its early
stage these studies show that the fatigue issues with young cancer patients have only
recently been taken seriously
661
29
The results of our meta-analysis include measurement of the four performance indicators
fatigue and general fatigue sleep rest fatigue and cognitive fatigue The results show
that there is a statistically significant difference only in the domain of general fatigue
using an exercise intervention for children with cancer can improve the degree of fatigue
with the effect size reaching 0671 Other results do not indicate significant differences
The reasons may include the following
1 Characteristics of the cancer The exhaustion from cancer occurs not only during cancer treatment but also in during
long-term survival a time during which patients may continue to be affected by this
symptom 8 26 Therefore when using intervention measures to improve fatigue
circumstances should be considered such as the process of the treatment and the course
or stage of the disease Because cancer patients will experience different forms of
treatment or courses of treatment the disease itself or treatment differences should be
considered in the choice of intervention Even chemotherapy drugs should be taken into
consideration For example a period of general steroid treatment can increase patientsrsquo
fatigue In those studies of children with cancer few studies looked solely at one type of
cancer most studies included a variety of cancer patients Furthermore most studies do
not clearly explain the stage of the disease or course of treatment and most do not
include treatment variables in the control group Moreover children with cancer may
have different levels of physical function
2 Research design The sample size Currently there are few studies with large sample size and a rigorous
RCT design due to the small number of papers available for analysis The sample size
included in our studyrsquos data analysis is between 20 and 42 people this small sample size
will affect the power available to evaluate outcome variables
Although most of the non-pharmacological interventions still use exercise and physical
activity and these studies overall show better results for fatigue as compared with
controls more research is still needed to further confirm the efficacy of these findings
662
30
The dropout rate in the evaluated research varies a great deal ranging from 5 to 45
these dropout rates may result from the characteristics of the research subjects or the
lengthy time involved in participating in these studies The research data with a high
turnover rate might not reflect the actual outcomes of participation in exercise and the
quality of the research contained in articles with high subject turnover rates may be
lower
Exercise doses and time The exercise doses needed to reduce fatigue cannot be
determined additionally the amount of exercise completed by the patient is also
inconsistent interventions vary between 2-3 times per week and two times a day and
exercise duration varies between 10 and 45 minutes each time Furthermore the study
interventions vary in length between a couple of days and a long period of 16 weeks The
data collection times are different some were measured 12 weeks after the intervention
began some were measured during the 6 weeks of intervention some were measured
three months after the intervention was finished and some were measured after one
year
In addition disease-related symptoms decrease childrenrsquos willingness to participate in
exercise interventions inappropriate exercise intervention programs may actually
increase childrens fatigue In addition the children in the study are still developing
physically it is important to consider ways to design an interesting exercise intervention
to increase the compliance of patients in order to improve the effectiveness Although
intervention programs in the hospital or in a community sports center can improve the
effectiveness because they provide supervision the feasibility of these programs is
questionable However if the program is home-based the children need to be
supervised by parents in order to improve their compliance in doing the exercises
Furthermore regarding the nature of the intervention the results from this study indicate
that the researched non-pharmacological interventions include the following exercise
training programs physical activity massage therapy and health education interventions
However according to the National Comprehensive Cancer Network 1 clinical guidelines
663
31
for cancer non-drug measures for cancer fatigue can be separated into five categories
(1) activity enhancement (2) psychosocial interventions such as cognitive behavioral
therapy (CBT) stress management relaxation techniques and support groups (3)
attention-restoring therapy (4) nutritional consultation and (5) cognitive behavioral
therapy specifically targeting sleep disturbance Researchers have also suggested that
psychosocial interventions should be included in the future research for children with
cancer-related fatigue 22
(2) The measurement tools in the study The assessment of fatigue can be
one-dimensional or multidimensional One-dimensional assessment can help understand
the severity of fatigue symptoms however multidimensional scales are often more
credible Therefore when measuring cancer-related fatigue researchers should consider
whether there is a uniform definition of fatigue or a standardized tool for measuring
fatigue in order to facilitate further systematic meta-analyses and further develop the
clinical care guidelines
Limitations of the review The present review has some potential limitations First the low methodological quality
may influence the result Although exercise intervention seems promising quality of the
RCTs was generally quite low Future studies require better design and reporting if
methodological issues to establish evidence-based nonpharmcologic intervention
Second the identified studies covered only a limited types of nonpharmcological
intervention especially in exercise intervention The guidelines for cancer-related fatigue
in NCCN (2011)1 referred to more interventions than the ones included in this review
such as cognitive behavioral therapy and nutrition consultation Thirdly the small sample
size and effect size could be potentially having led to underpowered approach for
detecting the effects on fatigue Therefore we recommend that as research continues to
grow a re-analysis can be undertaken Fourthly Combining data in meta analysis from
664
32
studies where the ages were quite different is a potential source of heterogeneity and
may affect the interpretation of the results
Conclusion At present clinical treatment is widely used for cancer patients However child and
adolescent cancer patients often experience various side effects which cause short-term
or long-term discomfort both physically and psychologically In particular with the
increasing cure rate cancer related fatigue during or after treatment has become an
important issue This study result provided positive effect of exercise intervention on
general fatigue
Implications for practice The results of this systematic review and meta-analysis show that exercise interventions
can effectively improve the level of general fatigue In particular although the articles
were self-reported feasibility studies their results all indicate that exercise interventions
for fatigue are feasible and safe there was no conclusion to be made for the use of
massage therapy or health education measures because there was only one article for
each of these interventions
Recommendations for practice
Cancer-related fatigue is one of the most severe and frequent symptoms by pediatric
oncology children and adolescent suffered during treatment and the symptom existed
even after treatment has ended Until now no golden standard of treatment to fatigue is
established The findings call for more attention to how to reduce patientrsquos levels of
fatigue Based on the available information evaluated in this review the following
recommendations for practice are provided
665
33
bull For children aged 7 to 18 who has cancer (eg Lymphoma leukemia CNS tumor
germ cell tumor) an effective progressive aerobic exercise program is recommended to
be at least 2-3 times per week 20 to 45 minute for each session and last for 6-16 weeks
in order to reduce their general fatigue (tiredness physically weakness) In addition
adults should be involved in accompanying children while they are performing physical
exercise of which should be able to improve the adherence rate (level 2 ) ( Grade of
recommendation A)
bull For children aged 7 to 18 who has cancer (eg Lymphoma leukemia CNS tumor
germ cell tumor) an progressive aerobic exercise program will not be effective to reduce
their sleep andor rest (sleeping or resting a lot) or cognitive fatigue (problems with
thinking quickly or problems with remembering) (level 2 ) ( Grade of recommendation C)
bull Nursing interventions in educating treatment of fatigue include information about
activity nutrition energy preservation consulting and providing a useful fatigue
handbook will benefit those children who are 7 to 12 years have a new diagnosis of ALL
AML or lymphoma and receive for the first time after being diagnosed a 7- to 10-day
chemotherapy treatment (level 2) ( Grade of recommendation A)
bull A 4-week massage therapy program (the therapists massage childrenrsquos back legs
arms stomachchest and face) is not effective for children who are aged 7 to 18 and
have acute lymphoblastic leukemia brain tumors lymphoma rhabdomyosarcoma
Wilms tumor or Ewing sarcoma(level 2)( Grade of recommendation C)
bull Using a 12-week aerobic and strength exercise (45-min exercise sessions twice a
week) is not effective for children who are aged 6-14 and survived acute lymphoblaststic
leukemia age from 6 to 14(level 2) ( Grade of recommendation C)
bull Using a physical activity intervention (30minutestwice daily for 2-4days) is not
effective for children who are 7 to 18 years of age with soild tumor or AML(level 2)
( Grade of recommendation C)
666
34
Implications for research According to this systematic review and meta-analysis results there are suggestions to
improve the effectiveness of future research on non-pharmacological interventions for
children and young peoplersquos cancer-related fatigue
As the majority of included non-pharmacological interventions for the fatigue of cancer
patients consist of exercise programs future research should also consider various
non-pharmacological interventions in order to understand the effectiveness of different
methods
Regarding the exercise intervention methods and studies should consider multiple
factors including the age or personal condition of the subject the disease stage and the
amount of daily activities Studies should use design prescriptions (eg frequency
intensity duration and type of exercise) and consider the adherence to the measures in
order to enhance the study strength
In measuring the results of non-pharmacological interventions there should be standard
definitions or standard measurement tools to facilitate the following systematic review
and meta-analysis that can subsequently be developed into clinical care guidelines
Reviewing the effectiveness of the current non-pharmacological management of children
and adolescent cancer patients there is still a lack of rigorous RCT research Limited by
the characteristics of cancer there is still a lack of large sample sizes
Potential conflicts of interest There is no conflict of interest
Acknowledgements
Thank you to Dr Rie Konno Research Fellow Joanna Briggs Institute for her help in
assessing studies
667
35
References 1 National Comprehensive Cancer Network( NCCN) in USA NCCN clinical practice
guideline in oncology cancer-related fatigue 2011 2 Ekti Genc R amp Conk Z Impact of effective nursing interventions to the fatigue
syndrome in children who receive chemotherapy Cancer Nursing 200831(4)312-317
3 Childhood Cancer Foundation of ROC (2009March) The classification of diseases
and age sex statistical tables of case Childhood Cancer Foundation of ROC newsletter103105-106
4 Department of Health Executive Yuan ROC (TAIWAN)(2009 March 20)2009 cause of death statistic Health and National Health Insurance Annual Statistics Information Service 2010 June 28Available httpwwwdohgovtwstatisticdatavital statists9898health statistic--lifepdf
5 Chang TK (2007December 8) Common childhood cancer and its treatment Status
Childhood Cancer Foundation of ROC (TAIWAN) 2010 September 23 Available httpwwwccfrocorgtwchildchild_events_readphpe_id=45
6 Hockenberry MJ amp Wilson D Wongs nursing care of infants and children (8th ed) St
Louis MO Mosby 2007
7 Post-White J Fitzgerald M Savik K Hooke MC Hannahan AB amp Sencer SF
Massage therapy for children with cancer Journal of Pediatric Oncology Nursing 2009 26(1)16-28
8Chiang YC Yeh CH Wang WKamp Yang CP The experience of cancer-related fatigue
in Taiwanese children European Journal of Cancer Care 2009 18(1)43-49 9Langeveld NE Grootenhuis M A Voute P A de Haan RJ amp van den Bos C No excess
fatigue in young adult survivors of childhood cancer European Journal of Cancer 200339(2)204-214
10Piper BF Lindsey AM amp Dodd MJ Fatigue mechanisms in cancer patients
developing nursing theory Oncology Nursing Forum 1987 14(6)17-23 11Nail LM amp Winningham ML Fatigue In S L Groenwald M H Forgge M Goodman
amp C H Yarbro (Eds) Cancer Nursing Principles and practice (4 th ed) Boston Jones and Bartlett1997
12Irvine D Vincent L Graydon JE Bubela N amp Thompson L The prevalence and
correlates of fatigue in patients receiving treatment with chemotherapy and
668
36
radiotherapy A comparison with the fatigue experienced by healthy individuals Cancer Nursing 199417(5)367-378
13Hinds PS amp Hockenberry-Eaton M Developing a research program on fatigue in
children and adloescents diagnosed with cancer Journal of Pediatric Oncology Nursing 200118(2)3-12
14Aaronson LS Teel CS Cassmeyer V Neuberger GB Pallikkathayil L Pierce J Press
AN Williams DP amp Wingate A Defining and measuring fatigue Journal of Nursing scholarship 1999 31(1)45-50
15Yeh CH Wang CH Chiang YC Lin Lamp Chien LC Assessment of symptoms reported
by 10- to 18-year-old cancer patients in Taiwan 2009 38(5)738-746 16 Okuyama T Akechi T Kugaya A Okamura H Shima Yamp Maruguchi M
Development and validation of the cancer fatigue scale a brief three-dimensional self-rating scale for assessment of fatigue in cancer patients Journal of Pain amp Symptom Management 2000 19(1) 5-14
17Gibson F Mulhall AB Richardson A Edwards JL Ream E amp Sepion BJ A
phenomenologic study of fatigue in adolescents receiving treatment for cancer Oncology Nursing Forum200532(3)651-660
18Wolfe J Grier HE Klar N Levin SB Ellenbogen JMamp Salem-Schatz S et al
Symptoms and suffering at the end of life in children with cancer New England Journal of Medicine 2000342(5)326-333
19Whiting P Bagnall AM Sowden AJ Cornell JE Mulrow CD amp Ramirez G
Interventions for the treatment and management of chronic fatigue syndrome a systematic review JAMA the Journal of the American Medical Association 2001286(11)1360-1368
20 Kangas M Bovbjerg DHamp Montgomery G H Cancer-related fatigue a systematic
and meta-analytic review of non-pharmacological therapies for cancer patients Psychological Bulletin 2008134 (5)700-741
21Williams PD Schmideskamp J Ridder EL amp Williams AR Symptom monitoring and
dependent care during cancer treatment in children pilot study Cancer Nursing 200629(3)188-197
22Takken T van der Torre P Zwerink M Hulzebos EH Bierings M Helders PJMamp van
der Net J Development feasibility and efficacy of a community-based exercise training
669
37
program in pediatric cancer survivors Psycho-Oncology 200918(4)440-448
23Keats MR amp Culos-Reed SN A community-based physical activity program for
adolescents with cancer (project TREK) program feasibility and preliminary findings
Pediatric hematology and oncology 200830(4) 272-280
24Hinds PS Hockenberry M Rai SN Zhang L Razzouk B I Cremer L McCarthy K amp
Rodriguez-Galindo C Clinical field testing of an enhanced-activity intervention in
hospitalized children with cancer Journal of Pain amp Symptom Management 2007
33(6)686-697
25Chiang YC The effects of ldquo a home-based aerobic exercise interventionrdquo on fatigue
and cardiorespiratory fitness in children with acute lymphoblastic leukemia during the
maintenance stage of chemotherapy Unpublished thesis Taiwan Tao-Yuan 2007
26Langeveld N Ubbink M amp Smets E I dont have any energy The experience of
fatigue in young adult survivors of childhood cancer European journal of oncology
nursing 20004(1)20-28
27 Kisner C Colby L Therapeutic exercise Foundations and techniques 2nd ed Philadelphia PAFA Davies 2007
670
38
Appendix I JBI Critical Appraisal Checklist for Experimental studies
Author__________ Year_________ Record Number__________________
Questions 1 to 4 must be answered ldquoyesrdquo for study to be included in the metashyanalysis
1 Were the participants randomized to study groups
Yes No Not clear
2 Other than research intervention were participants in each groups treated the same
Yes No Not clear
3 Were the outcomes measured in the same manner for all participants
Yes No Not clear
4 Were groups comparable at entry
Yes No Not clear
5 Was randomization of participants blinded
Yes No Not clear
6 Were those assessing outcome blinded to treatment allocation (if outcome not objective such as survival or length of hospitalization)
Yes No Not clear
7 Was allocation to treatment groups concealed from the allocator
Yes No Not clear
8 Was an appropriate statistical analysis used
671
39
Yes No Not clear
9 Were outcomes measured in a reliable way
Yes No Not clear
10 Was there adequate followshyup of participants
Yes No Not clear
Summary
TOTAL
Yes No Not clear
DECISION
Use Reject
Narrative summary only Further information needed
COMMENTS
672
40
Appendix II JBI Data Extraction Tool for Quantitative Studies Authors and Year
Journal Title
Record NumberArticle Reference No
Reviewer
Method
Settings
Participants
Number of participants
Group A Group B Group C
Control Intervention 1 Intervention 2
Interventions
Group A
Control
Group B
Intervention 1
Group C
Intervention 2
Outcome measures
Definition
673
41
Other outcome measures
Outcome description ScaleMeasure
Results
Dichotomous Data
Outcome Control Group
Numbertotal number
Treatment Group
Numbertotal number
Continuous Data
Authorrsquos Conclusions
Comments
Outcome Control Group
Mean amp SD
Treatment Group
Mean amp SD
674
43
Appendix III Details of included studies (N=6)(2720212223) RefNo Author(s)
(years) Title Study question Research
method Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
22 Takken T van der Torre P Zwerink M Hulzebos E H Bierings M Helders P J Mamp van der Net J (2009)
Development feasibility and efficacy of a community-based exercise training program in pediatric cancer survivors
To develop a 12-week home-based exercise training program (comprising aerobic and strength exercises) for children who survived ALL and to study itrsquos feasibility and efficacy
Pre-post test design
No comparsion group
Survived ALL(N=9)ages 6-14 years
1anthropometry 2 muscle strength 3functional mobility 4cardio-pulmonary
exercise test 5Fatigue
1 Feasibility questionnaire 2 anthropometry electronic scale and a wallmounted stadiometerHarpenden skin fold calipers 3 muscle strength handheld dynamometer 4functional mobility Timed Up
and Go test (TUG) 5cardio-pulmonary exercise test electronically braked cycle ergometer 6Fatigue(mean)CSI-20 (subjective experience of fatigueconcentrationmotivationphysical activity)
112-week exercise training program
2 Patients were assessed before (T0) and after (T1) 12 weeks of training
1 muscle strength execapacity functional moand fatigue showed nosignificant differences between pre(meanplusmnSD415plusmn147) and post training(meanplusmnSD3687)
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
7 Post-White J Fitzgerald M Savik K Hooke M C Hannahan A B amp Sencer S F (2009)
Massage therapy for children with cancer
To determine whether 4 weekly sessions of massage compared with 4 quiet-time control conditions would reduce anxiety cortisol levels fatigue nausea and pain in children with cancer undergoing chemotherapy and would reduce anxiety fatigue and mood disturbance in a parent
2-period crossover design (Randomized)
quiet-time
control
sessions
Children with cancer 1 to 18 years of age Twenty-three childrenparent dyads were enrolled 17 completed all data points
children 1relaxation 2symptoms 3 fatigue
parents
1anxiety 2 fatigue
children 1relaxation (heart and respiratory rates blood pressure and salivary cortisol level)
2symptoms (pain nausea anxiety 3 fatigue 1-2y3-6yLansky Play Performance Scale (PPS) 7-13y
1 4 weekly massage (MT) sessions alternated with 4 weekly quiet-time(QT) control sessions
2 children included presession and postsession vital signs (heart rate respiratory rate blood pressure) and self-report (parent proxy report for age 1-2 years) of pain nausea and anxiety Fatigue was measured before sessions 1 and 4 and at each follow-up Parent measures
included anxiety fatigue and mood states
1Massage was moreeffective than quiet tireducing heart rate inchildren anxiety in cless than age 14 yeaparent anxiety 2There were no sign
changes in blood pcortisol pain naufatigue (no state d
3 Children reported tmassage helped thebetter lessened theirand worries and hadlasting effects than q
675
44
14-18yChild Fatigue Scale (CFS) (frequency
intensity) 2 parents anxiety and fatigue
676
45
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
24 Hinds P S Hockenberry M Rai S N Zhang L Razzouk B I Cremer L McCarthy K amp Rodriguez-Galindo C (2007)
Clinical field testing of an enhanced-activity intervention in hospitalized children with cancer
To determine the feasibility of an
enhanced physical activity EPA intervention in children and adolescents hospitalized to receive chemotherapy for a solid tumor or AML and to assess the sleep and fatigue outcomes of the intervention using two different statistical approaches to analyze the longitudinal symptom data
randomized prospective two-site and two-group pilot study
Standard care Twenty nine patients (25 with a solid tumor and 4 with AML)ages 7-18 years
1 sleep duration 2 sleep efficiency 3 fatigue
1sleep duration sleep efficiency The
Wrist Actigraph The Daily Sleep Diary-Parent 2 fatigue (mean) The Fatigue Scale(FS-C) for 7-12 (intensity) The Fatigue Scale(FS-A) for 13-18 The Fatigue Scale Parent Version (FS-P) The Fatigue Scale Staff Version (FS-S)
1enhanced physical activity (EPA) (hospital-based 30 minutes
twice daily for 2-4 days) 2 T0On the day of admission
(Day 0 or baseline)patient and parents completed the fatigue instruments and a team member applied the actigraph Patients wore the wrist actigraph T1 from Day 0 to 2 or 3 consecutive days (Days 0e3) In addition the patient same parent and staff nurses completed the daily sleep and fatigue reports in the late afternoons of Days 1-3
1 ANOVA model slesignificantly more the experimental athe control arm whdifferences from bsleep efficiency vaaveraged and com
2 The patient-reported mean fatigue scoresarms were higher amadolescents than for
3 The mixed model anarevealed no significandifferences in patientfatigue between
the two study arms otime( no final result iSD only give mixed result)
677
46
23 Keats M
R amp Culos-Reed S N (2008)
A community-based physical activity program for adolescents with cancer (project TREK) program feasibility and preliminary findings
To examine the
feasibility of a
theoretically-based
physical activity (PA)
intervention in
adolescents with
cancerand
examination of the
impact of the
program on
participant QOL
including social
emotional and
physical
well-being(including fatigue)
Repeat measures longitudinal design
No comparsion group
10 adolescents(Lymphoma(4)leukemia(4)CNS tumor(1)germ cell tumor(1)) ages 14-18 years
1physical fitness 2quality of life (QOL) 3PA behavior 4fatigue
1 Feasibility was assessed by participant recruitment attendance and adherence
2physical fitness Fitnessgram 3quality of life (QOL) Pediatric Quality of Life Inventory (PedsQL) 4PA behavior leisure score index (LSI) 5fatigue (mean) pediatric Quality of life
Multidimensional Fatigue Scale (Peds QL-MFS)
(Generalsleepcognitive fatigue)
116week physical activity (PA)
2 total PA physical fitness and overall QOL was assessed at 5 different intervals T0 preintervention (baseline) T1midintervention (after the
first 8 wk) T2 postintervention
(16 wk) T3 3-months
postintervention T4 1-year poststudy
initiation
1 from baseline -wkssig Improvementstotal PA physfitness and Qgeneral fatigue(meanplusmnSD 796plusmn135)
2 from baseline to 3FUsig Improvin general fatigue(meanplusmnSD824plusmn131)slefatigue(meanplusmnSD755plusmn191)totafatigue(meanplusmnSD778plusmn150)
3at 1 years FUsImprovements in sleeprest fatigue(meanplusmnSD725plusmn203)total (meanplusmnSD 763plusmn
678
47
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
2 Gene R E amp Conk Z (2008)
Impact of Effective Nursing Interventions to the Fatigue Syndrome in Children Who Receive Chemotherapy
1 to examine the effects of an effective nursing intervention to the fatigue syndrome of children 7 to 12 years of age who receive chemotherapy 2Tto examine the relationship between fatigue and demographic variables (age sex) diagnoses ([ALL AML] lymphoma) and therapy-related variables (eg level of hemoglobin
experimental randomized controlled study
Routine nursing care
A total of 60 children who are 7-12 years of age(a new diagnosis of ALL AML or lymphoma and receiving for the first time after being diagnosed a 7- to 10-day chemotherapy treatment )
fatigue The Fatigue Scale(FS-C) for 7-12 (intensity)
The Fatigue Scale Parent Version (FS-P)
1 effective nursing interventions(45- 60mdaya week)education about the fatigue with the chemotherapy and fatigue handbook 2 T1 After a 7-day period the children
and parent were evaluated with the Fatigue Scale
1The difference betwthe 2 mean values wafound to be statisticallsignificant 2 statistically significadifference was found between the Fatigue Scale-Child mean scothe experimental (272the control group (4213)children
679
48
25 Chiang et
al(2007)
The effects of ldquo a home ndashbased aerobic exercise interventionrdquo on fatigue and cardiorespiratory fitness in children with Acute Lymphoblastic Leukemia during the maintenance stage of chemotherapy
To examine the effect of ldquo a home ndashbased aerobic exercise interventionrdquo on fatigue and cardiorespiratory fitness in children with Acute Lymphoblastic Leukemia during the maintenance stage of chemotherapy
Quasi-experi -mental
Routine
nursing care
14 pediatric oncology patients in the experimental group and 10 in control group who were matched by age and sex ages7-18 years
1Cardiorespiratory fitness
2Fatigue
1Cardiorespiratory fitness Physical Activity Recall
VO2maxHR peak 6MWT
2 Fatigue PedsQL-MFS(Generalsleepcognitive fatigue)
1A six-week home-based aerobic exercise intervention 2 8 time points T0 baseline T1-T6 every week during the
intervention(6 weeks) T7 post intervention T8 follow-up (one month after
the end of the home-based exercise program)
1 For intent-to ndash treatthe findings indicated are no intervention efftime differences by anon the subscale of fat2 For per-protocol angeneral fatigue( mean422plusmn402) was the osubscale that was siglower for children whothe exercise interventthose in control groupfollow-up assessmentmonth after the compintervention) 3 The VO2peak are significantly improvingexperimental group atbaseline- and post-intassessment The VO2was significantly highechildren who were in experimental group thcontrol subjects at post-intervention assefor the per-protocol an
680
49
Appendix IV Instrument used to measure fatigue
Name Instrument
developers
Description Used in
age in
ref
Reliability
Consistency of
instrument
Checklist Individual Strength
(CIS)22
Vercoulen et
al1996
20 items using 7-point Likert scale of
fatigue To measure four aspects of
fatiguesubjective experience
contractionmotivation physical
Activity
6-14 Not reported
Child Fatigue Scale (CFS)7 Hockenberry
et al2003
14 items 2 part questionnaire frequency
(yes or no) 5-point Likert scale of the
intensity of any yes responses
7-13
14-18 α073-o84
The Fatigue Scale for 7-12
year Olds (FS-C)224
Hockenberry
et al
14 items provide a fatigue intensity score
5-point Likert scale
7-12 αo84
The Fatigue Scale for 13-18
year Olds (FS-A)24
Hockenberry
et al
14 items provide a fatigue intensity score
5-point Likert scale
13-18 α076-o96
Pediatric Quality of life
Multidimensional Fatigue
Scale (Peds QL-MFS)2325
Varni2002 18 items to measure three aspects of
fatigueGeneralsleepcognitive
14-18 Not reported
681
50
Appendix V Excluded studies and reasons for exclusion
Baggott C Dodd M Kennedy C Marina N Miaskowski C Multiple Symptoms in Pediatric Oncology
Patients A Systematic Review Journal of Pediatric Oncology Nursing 2009 Nov-Dec 27(6)
325-339
Reason for exclusion Not outcome of interest
Barlow JH Ellard DR Psycho-educational interventions for children with chronic disease parents and
siblings an overview of the research evidence base Care Health amp Development 2004 Nov
30(6)637-45
Reason for exclusion Not outcome of interest
Bedider S Moyer CA Randomized controlled trials of pediatric massage A review Evid Based
Complement Alternat Med 2007 Mar 4(1)23-34 Epub 2006 Nov 3
Reason for exclusion Not outcome of interest
de Nijs EJ Ros W Grijpdonck MH Nursing intervention for fatigue during the treatment for cancer Cancer
Nursing 2008 31(3)191-206
Reason for exclusion Not population of interest
Edwards JL Gibson F Richardson A Sepion B Ream E Fatigue in adolescents with and following a
cancer diagnosis developing an evidence base for practice European Journal of Cancer 2003
Dec 39(18)2671-80
Reason for exclusion Not experimental or quasi-experimental study
Hinds PS Hockenberry-Eatan M Developing a research program on fatigue in children and adolescents
diagnosed with cancer Journal of Pediatric Oncology Nursing 2001 Mar-Apr 18(2 Suppl
1)3-12
Reason for exclusion Not experimental or quasi-experimental study
Hockenberry-Eaton M Hinds PS Alcoser P ONeill JB Euell K Howard V Gattuso J Taylor J Fatigue in
Children and Adolescents With Cancer Journal of Pediatric Oncology Nursing 1998 July
15(3)172-182
Reason for exclusion Not experimental or quasi-experimental study
Jean-Pierre P Mustian K Kohli S Roscoe JA Hickok JT Morrow GR Community-based clinical oncology
research trials for cancer-related fatigue The Journal of Supportive Oncology 2006 Nov-Dec
4(10)511-6
682
51
Reason for exclusion Not population of interest
Kangas M Bovbjerg DH Montgomery GH Cancer-Related Fatigue A Systematic and Meta-Analytic
Review of Non-Pharmacological Therapies for Cancer Patients Psychological Bulletin 2008 Sep
134(5)700-41
Reason for exclusion Not population of interest
Lotfi-Jam K Carey M Jefford M Schofield P Charleson C Aranda S Nonpharmacologic strategies for
managing common chemotherapy adverse effects A systematic review Journal of Clinical
Oncology 2008 Dec 1 26(34)5618-29 Epub 2008 Nov 3
Reason for exclusion Not outcome of interest
Marchese VG Chiarello LA Lange BJ Effects of physical therapy intervention for children with acute
lymphoblastic leukemia Pediatr Blood Cancer 2004 Feb42(2)127-33
Reason for exclusion Not outcome of interest
Meeske KA Siegel SE Globe DR Mack WJ Bernstein L Prevalence and correlates of fatigue in
long-term survivors of childhood leukemia Journal of Clinical Oncology 2005 Aug 20
23(24)5501-10
Reason for exclusion Not intervention study
Minton O Richardson A Sharpe M Hotopf Stone P A systematic review and meta-analysis of the
pharmacological treatment of cancer-related fatigue J Natl Cancer Inst 2008 Aug 20
100(16)1155-66 Epub 2008 Aug 11
Reason for exclusion Not population and intervention of interest
Mustian KM Morrow GR Carroll JK Figueroa-Moseley CD Pascal JP Williams GC Integrative
nonpharmacologic behavioral interventions for the management of Cancer-Related fatigue The
Oncologist 2007 12(1)52-67
Reason for exclusion Not population of interest
Neill J Belan I Ried K Effectiveness of non-pharmacological interventions for fatigue in adults with
multiple sclerosis rheumatoid arthritis or systemic lupus erythematosus a systematic review
Journal of Advanced Nursing 2006 Dec 56(6)617-35
Reason for exclusion Not population of interest
Rheingans JI A systematic review of nonpharmacologic adjunctive therapies for symptom management
Journal of Pediatric Oncology Nursing 2007 24(2) 81-94
683
52
Reason for exclusion Not outcome of interest
Rheingans JI Pediatric oncology nursesrsquo management of patients symptoms Journal of Pediatric
Oncology Nursing 2008 Nov 25(6) 303-11
Reason for exclusion Not outcome of interest
San Juan AF Fleck SJ Chamorro-Vintildea C Mateacute-Muntildeoz JL Moral S Peacuterez M Cardona C Del Valle MF
Hernaacutendez M Ramiacuterez M Madero L Lucia A Effects of an intrahospital exercise program
intervention for children with leukemia Medicine amp Science in Sports amp Exercise 2007 Jan
39(1)13-21
Reason for exclusion Not outcome of interest
Sanford SD Okuma JO Pan J Srivastava DK West N Farr L Hinds PS Gender differences in sleep
fatigue and daytime activity in a pediatric oncology sample receiving dexamethasone Journal of
Pediatric Psychology 2008 Apr 33(3)298-306 Epub 2007 Nov 17
Reason for exclusion Not experimental or quasi-experimental study
Schmitz KH Holtzman J Courneya KS Macircsse LC Duval S Kane R Controlled physical activity trials in
cancer survivors a systematic review and meta-analysis Cancer Epidemiol Biomarkers Prev
2005 Jul 14(7)1588-95
Reason for exclusion Not population of interest
van Brussel M Takken T Lucia A van der Net J Helders PJ Is physical fitness decreased in survivors of
childhood leukemia A systematic review Leukemia 2005 Jan 19(1)13-7
Reason for exclusion Not population of interest
Whiting P Bagnall AM Snowden AJ Cornell JE Mulrow CD Ramirez G Interventions for the treatment
and management of chronic fatigue syndrome JAMA 2001 Sep 19 286(11)1360-8
Reason for exclusion Not intervention of interest
Whitsett SF Gudmundsdottir M Davies B McCarthy P Friedman D Chemotherapy-related fatigue in
childhood cancer correlates consequences and coping strategies Journal of Pediatric
Oncology Nursing 2008 Mar-Apr 25(2)86-96 Epub 2008 Feb 29
Reason for exclusion Not experimental or quasi-experimental study
Winner C Muumlller C Hoffmann C Boos J Rosenbaum D Physical activity and childhood cancer Pediatr
Blood Cancer 2010 Apr 54(4)501-10
Reason for exclusion Not research study
684
53
Wu M Hsu L Zhang B Shen N Lu H Li S The experiences of cancer-related fatigue among Chinese
children with leukaemia A phenomenological study Journal of Nursing Studies 2010 Jan
47(1)49-59 Epub 2009 Aug 25
Reason for exclusion Not experimental or quasi-experimental study
Yeh CH Chiang YC Lin L Yang CP Chien LC Weaver MA Chuang HL Clinical factors associated with
fatigue over time in paediatric oncology patients receiving chemotherapy British Journal of
Cancer 2008 Jul 8 99(1)23-9 Epub 2008 Jun 24
Reason for exclusion Not experimental or quasi-experimental study
685
13
newborn infants under 1 years of age
participants who do not have a specific diagnosis of cancer
participants who have received immunoglobulin or hydrocortisone
treatment
If participants have received immunoglobulin or hydrocortisone treatment may
inference the effectiveness of non-pharmacological interventions on fatigue
Types of intervention
This review considered studies that examine non-pharmacological interventions on
fatigue for children and adolescents with cancer including activity enhancement
(exercise physical activity) psychosocial interventions CBT stress management
relaxation nutrition consultation massage and educational interventions The
interventions descriptive included the length frequency setting and intervention
providers eg Nurse Psychologist Dietician
Exclusion criteria for types of interventions only pharmacological interventions were
tested
Types of outcome measures
The outcome measures considered were fatigue scores The literature demonstrates that
differences of opinion exist regarding the most valid and reliable method of measuring
cancer-related fatigue Therefore studies that used any validated scale for
cancer-related fatigue were considered for inclusion Currently commonly used scales to
measure fatigue include Checklist Individual Strength (CIS) Child Fatigue Scale (CFS)
The Fatigue Scale for 7-12 year Olds (FS-C) The Fatigue Scale for 13-18 year Olds
646
14
(FS-A)and Pediatric Quality of life Multidimensional Fatigue Scale (Peds QL-MFS)
Types of settings
Both hospital and community settings
Search Strategy
Before undertaking this systematic review the Cochrane Library Joanna Briggs Institute
Library of Systematic Reviews and CINAHL were searched and no systematic reviews on
this topic were found or identified as underway
The search strategy aimed to find both published and unpublished studies
A three-step search strategy was utilized in each component of this review An initial
limited search of CINAHL and MEDLINE was undertaken followed by an analysis of the
text words contained in the title and abstract and of the index terms used to describe the
article A second search using all identified keywords and index terms was undertaken
Lastly the reference lists of all identified reports and articles were searched for additional
studies
Types of languages
1 English
2 Chinese
The following databases were searched to identify keywords contained in the title and
abstract and relevant MeSH headings and descriptor terms
The Cochrane Library PsycINFO 1990 ndash 2010
647
15
Ovid MEDLINE 1966 ndash 2010 CINAHL Plus with Full Text 1960 ndash2010 EMBASE ProQuest Dissertations amp theses 1990-2010 Electronic theses and dissertations system 1956(abstract)1990(full text)-2010 MEDNAR Index to Taiwan periodical literature 1970-2010 Electronic thesis and dissertation system (Chinese) 1990-2010
Keyword search terms
1Types of studies experimental study random quasi-experimental study實驗性研究隨
機類實驗性研究
2 Types of participants childchildren adolescents pediatric cancer and oncology兒童
青少年兒科癌症腫瘤
3 Types of interventions non-pharmacological interventions massage exercise fitness
physical activity cognitive behavioral stress management energy conservation
sleep therapy relaxation distraction and psycho-education非藥物性處置按摩運動
身體活動認知行為壓力處置能量保存睡眠治療放鬆轉移注意力衛教
4 Types of outcome measures fatigue cancer-related fatigue loss of energy levels of
tiredness tired side effect symptoms疲憊癌性疲憊疲倦合併症症狀
Methods of the Review
Assessment of methodological quality Papers selected for retrieval were assessed by two independent reviewers for
methodological validity prior to inclusion in the review using the standardised critical
appraisal instruments (Appendix I) from the JBI-SUMARI (Joanna Briggs Institute
Systems for the Unified Management Assessment and Review of Information package)
Any disagreements that arise between the reviewers were resolved through discussion
648
16
with a third reviewer
Data extraction Data was extracted from papers included in the review using standardised data
extraction tool (Appendix II) from the JBI-SUMARI Details of eligible studies were
extracted and summarised independently by two reviewers
Data Synthesis
All data analysissynthesis were made using the JBI-SUMARI The studies were
assessed for clinical heterogeneity by considering the settings populations interventions
and outcomes Where possible these binary outcomes were analyzed by calculation of
the Odds Ratio with the 95 CI The weighted mean difference was calculated if the
pooled studies have used the same scale for continuous data The standardized mean
difference was calculated for continuous data measuring the same outcome on a
different scale In studies where statistical pooling of results was inappropriate the
findings were considered for inclusion as a narrative summary
Results The findings from the systematic review are presented first Followed by the results from
the meta-analysis component of this review
Description of studies From database search and hand search a total of 76 papers were identified Thirty
papers were then excluded because they did not meet the inclusion criteria Forty-six
full text were retrieved for further consideration for inclusion Of the 30 excluded reasons
for exclusion were follows 11articles were duplicated eight articles did not meet
649
17
participant inclusion criteria eight articles did not meet outcome criteria and nine articles
were correlation studies or discussion papers others articles were unclear reporting In
total after sorting six papers have been included in this article Figure 1 displays the
process used to identify relevant articles for inclusion in the systematic review
Figure 1 Stages of searching and inclusionexclusion of references for the review
Potentially relevant English-language and Chinese- language Studies Identified
Electronically and hand search (n=76)
Duplicate (n= 11) Papers excluded after evaluation of abstract (n=19)
Papers retrieved for detailed examination (N=46)
Papers excluded after review of full paper
(n=40)
Papers assessed for methodological
quality (n=6)
Papers included in systematic review
(n=6)
Methodological Quality
Of the six included articles 2722232425 two articles were RCT design224 with score 7 out
of 10 each paper from Critical Appraisal Checklist and four articles used
650
18
quasi-experimental design7222425 with socre 5 to 6 out of 10 because the quality of
the whole papers is still acceptable therefore these six articles were accepted after
primary reviewer and secondary reviewerrsquos decision
Randomisation
In two RCT articles224 one study24 used to a computer-generated program operated by
the St Jude Protocol and Data Management System to randomize the sample Another
study2 didnrsquot address how randomization was done
Allocation concealment
No studies reported allocation concealment
Intention-to-treat analysis
One quasi-experimental design7 stated Intention-to-treat analysis
Adequate follow up
The follow-up periods included 2or 3 days24 7 days2 4 week7 one month25 6 week25 12
week2216 week23 and 1 year23
Baseline comparability of groups
Three 22425 of six studies had baseline comparability in terms of age sex diagnosis
race institution duration of illness
Blinded outcome assessment
No studies used blinded outcome assessment The researchers including study team
patients staff and families were not blinded to the patientrsquos group assignment
Characteristics of included studies
651
19
There were six studies related to interventions designed to cancer-related fatigue for
pediatric patients than there are for adults There are a total of six including five
English-language papers 27222324 and one Chinese-language paper 25 ranging in year of
publication from 2007 to 2009
Patient characteristics
The research subjects of four papers included both school-aged children and
adolescents 7222324 one papers involved mainly adolescents25 and one paper sampled
only school-aged children 2 the range in ages was between six-18 years The number of
patients included in the samples ranged from nine to 60 The sources of case data were
from both outpatients and hospitalized children The types of cancer included acute
lymphoblastic leukemia (ALL) solid tumors acute myeloid leukemia (AML) and
lymphoma Overall ALL was the most commonly studied cancer type The stage of the
disease varied in these reports some patients were in the maintenance stage of
chemotherapy25 some had just received their first round of chemotherapy224 some had
completed two courses of treatments lasting 4-8 weeks each 7 and some had entered
the survivor stage 2223
Countries
Two RCTrsquos 2 24 were conducted in the USA There were four quasi-experimental design
studiesThree studies conducted in the USA7 22 23 and one in Taiwan25
Intervention types
652
20
The interventions included exercise training programs 2225 physical activity 2324
massage therapy 7 and health education 223 exercise training and physical activity as
an intervention method given in three different settings home 22 25 community 23 or
hospital 24 The studies used different types of exercise interventions including
home-based aerobic exercise use a Video Compact Disc 25 use of a bicycle-style
exerciser 24 aerobics2223 and various types of physical activities2 and strength-building
exercises 2223 The intensity of the exercise varied and often included gradual warm-up
exercises a period of main exercise and a cool down period For these studies2023 the
target exercise intensity was a heart rate of gt90 of the maximum heart rate (HR max) or
the increase in the percentage of heart rate reserve ( HRR) of 40-60
The number of weeks for the exercisephysical activity interventions duration including
2-4 days 24 6 weeks25 12 weeks22 and 16 weeks23 The frequency of exercise ranged
from 2-3 times per week to twice a day Typical duration of exercise ranged from 10 to 45
minutes There are three papers using exercise interventions based on ACSM (American
College of Sports Medicine) 2225 recommendations and one of these used an Activity
pyramid from the ACSM to determine intensity 24
One article did not clarify the type of exercise intervention or the reasons for their choices
23 In addition there was an article focusing on massage therapy 7 as an intervention in
this study the experimental group received four weeks of massage therapy either in the
clinic or in the patientrsquos room the therapy was applied by a professional masseur and
targeted the back legs arms chest stomach and face of the children However the
frequency of massage sessions per week and the duration of the massages were not
653
21
given There is another article about intervention measures combine health education
and physical activity 2 In this study patients were informed about the following (1) health
education patients received daily education about chemotherapy-related fatigue and
information from a health education manual written by the author (2) encouragement for
children to engage in activities such as listening to music drawing and reading and (3)
physical activity which involved walking along the corridors of the ward for 10-15 minutes
These health education measures were presented for 45-60 minutes a day for a total of
seven days The study design for non-pharmacological interventions used control groups
that included primarily people who had received standard treatment or people who did
not receive an exercise intervention
Outcome measures
Five measurement tools were used in this group of seven papers concerning childrenrsquos
fatigue (Appendix IV) Because those studies included both school-age children and
adolescents the following descriptions will be differentiated by age Fatigue
measurements for school-aged children with cancer include the following the Child
Fatigue Scale (CFS) 7 a scale that measures the frequency and intensity of fatigue and
the Fatigue Scale for 7-12 year Olds (FS-C) 224 a scale that can be used to evaluate the
intensity of fatigue On the other hand fatigue measurements for adolescent cancer
patients include the following the Fatigue Scale for 13-18-year-olds (FS-A) 24 a measure
that can help evaluate fatigue levels the Pediatric Quality of Life Multidimensional
Fatigue Scale (Peds QL-MFS) 2325 a tool that can be divided into three sub-scales to
understand the general cognitive and sleep rest components of fatigue and finally the
CIS-20 for school-age children and adolescents 22 a scale that measures four levels of
654
22
fatigue namely subjective experience attention motivation and physical activity Two
studies used the Peds QL-MFS scale to measure fatigue2325
Meta-analysis results Two studies of the included papers failed to provide sufficient raw data they could not be
included in the meta-analysis Hinds et al 24 did not include post-test data Genc et al 2
provided no pre-test data PostWhite et al7 reported that fatigue after the health
education intervention was not statistically different but they presented the results
without presenting fatigue-related data Therefore the meta-analysis included three
studies 222325
The heterogeneity of studies was analyzed with Chi square statistics and no statistical
significance was found Therefore the data was combined in meta-analysis according to
exercise intervention on fatigue In addition there were three articles using the Peds
QL-MFS as a research tool to examine childrenrsquos improvements in fatigue Among these
Keats 22 and Chiang 24 present the effectiveness of exercise interventions using three
subscales Therefore the meta-analysis also analysis of the effects of these exercise
intervention measures on three subscales of Peds QL-MFS general fatigue sleep rest
fatigue and cognitive fatigue
The effectiveness of exercise intervention for fatigue We analyzed the exercise intervention effect on fatigue A total of 2 studies 22 23 were
included Takken et al 22 used community-based exercise training program to reduce
fatigue of children 6 to 14 years (mean 93y) of age who survived ALL Fatigue
measurement by Checklist Individual Strength (CIS) after 12-week of training fatigue
655
23
show no significant differences between pre (meanplusmnSD 415plusmn147) and post training
(meanplusmnSD368plusmn217) but fatigue change from baseline mean reduction of 11
Keats et al23 although used community-based physical activity program to reduce fatigue
for adolescents 14 to 18 years of age (mean162 y) with cancer (Lymphoma leukemia CNS
tumor germ cell tumor) Studies used fatigue by PedsQLMFS Results show general fatigue
from baseline to 8 weeks and to 3 months follow up significantly improves General
fatigue sleeprest fatigue and total fatigue from baseline to 3 months follow up showed
significant improvements Sleeprest fatigue and total fatigue at 1 years followed up were
significant improvements
Figure 2 shows the overall effect of exercise intervention in children and adolescents with
cancers with a focus on improving fatigue Due to the lower heterogeneity (p>005) the
fixed effects model was used to pool the data for meta-analysis (Overall effect size=
-006 95 Confidence Interval (CI) -070 to 058) A result did not indicate a statistically
significant difference (p = 087)
656
24
Figure2 Meta-analysis results of exercise intervention on fatigue
In addition Keats23 and Chiang25 used the three sub-scales of Peds QL-MFS to
determine the general cognitive and sleep rest components of fatigue The following
present the effectiveness of exercise interventions using three subscales including
general fatigue sleep rest fatigue and cognitive fatigue 2325
Chiang et al 25 used a 6- week home-based aerobic exercise intervention to reduce
fatigue of children 7 to 18 years (mean age at experimental group was 1088 y in control
group was 1247 y) of age who with acute lymphoblastic leukemia Fatigue measurement
by Peds QL-MFS after training For intent-to ndash treat analysis the findings indicated that
there are no intervention effects and time differences by any items on the subscale of
fatigue For per-protocol analysis general fatigue( meanplusmnSD 422plusmn402) was the only
subscale that was significantly lower for children who received the exercise intervention
than those in control group at follow-up assessment (one month after the completion of
intervention)
Keats et al23 although used community-based physical activity program to reduce fatigue
for adolescents 14 to 18 years of age (mean162 y) with cancer (Lymphoma leukemia
CNS tumor germ cell tumor) Both studies used fatigue by PedsQLMFS Results show
general fatigue from baseline to 8 weeks and to 3 months follow up significantly improves
657
25
General fatigue sleeprest fatigue and total fatigue from baseline to 3 months follow up
showed significant improvements Sleeprest fatigue and total fatigue at 1 years followed
up were significant improvements
The effectiveness of exercise intervention for general fatigue
The impact of the exercise interventions upon levels of general fatigue was also analysed
The heterogeneity was low (p>005) Therefore the fixed effects model was used to
examine the effectiveness The effect size is -076 indicating a statistically significant
difference (p = 001 95 CI -135 to -017 Fig 3) The evidence suggests that exercise
intervention can reduce general fatigue in children with cancer
Fig 3 Meta-analysis results of exercise intervention for general fatigue
The effectiveness of exercise intervention for sleep rest fatigue
The following is the result of the meta-analysis of the effectiveness of exercise
interventions on sleep rest fatigue First the heterogeneity test was conducted with P gt
005 representing small heterogeneity and the fixed effects model was used Fig 4
shows the effect size is -035 indicating no statistically significant differences (p = 023
95 CI-092 to 022 Fig 4)
658
26
Fig 4 Meta-analysis results of exercise intervention for sleep rest fatigue
The effectiveness of exercise intervention for cognitive fatigue Lastly the following data reports the results of meta-analysis of the effectiveness of
exercise interventions for cognitive fatigue The heterogeneity was p>005 then the
fixed effects model was used The effect size is -035 indicating no statistically significant
differences (p = 024 95 CI-092 023 Fig 5)
Fig 5 Meta-analysis results of exercise intervention for cognitive fatigue
Narrative presentation of remaining included studies
Three studies were not included in meta-analysis Post-White et al7 one of the aims in
this study was to examine the effect of massage therapy on fatigue in children with
cancer The study was a quasi-experimental design Twenty-three childrenparent dyads
were enrolled 17completed all data points Children with cancer ages 7 to 18 years
received at least 2 identical cycles of chemotherapy and one parent participated in the
2-period crossover design in which 4 weekly massage sessions (MT) alternated with 4
659
27
weekly quiet-time (QT) control sessions There were no significant changes in fatigue in
children over the 4-week MT or QT conditions either independently (change over time) or
when we compared fatigue by condition
The lack of effect of massage on fatigue may be the difficulty some children had in
differentiating fatigue from being relaxed underscores the challenge of measuring fatigue
in children Some children interpreted being tired or relaxed as having greater fatigue
because they felt like lying around and sleeping or felt unmotivated to do their usual
activities all measures of fatigue in the instrument used in the study
Hinds et al24conducted a prospective two-site randomized controlled pilot study to
assess the feasibility of an enhanced physical activity (EPA) intervention in hospitalized
children and adolescents receiving treatment for a solid tumor or for acute myeloid
leukemia (AML) Twenty-nine patients (25 with a solid tumor and 4 with AML) participated
age range from 736 to 1816 (mean 1248 y) The EPA intervention selected was
pedaling a stationary bicycle-style exerciser (Chattanooga Peddler Deluxe Bio-Teck
Medical Memphis TN) for 30 minutes twice daily for 2 to 4 days of hospitalization The
mixed model analysis revealed no significant differences in patient reports of fatigue
between the two study arms or over time
Genc et al2 conducted a RCT involving children with cancer who are 7 to 12 years of age
and receiving chemotherapy treatment to determine the impact of educational
intervention by nurses on decreasing the fatigue syndrome The research sample was
composed of a total of 60 children with cancer with 30 children being included in the
660
28
experimental group (mean age 923)and 30 children included in the control group (mean
age 937) with their mothers In the experimental group after the 7th to 10th day of the
chemotherapy treatment throughout a week the researcher conducted the nursing
interventions every day for 45 to 60 minutes In the control group routine nursing
interventions were carried out The experimental group received education about the
fatigue with the chemotherapy and fatigue handbook was given which was developed by
the authors Children and mothers were consulted for including activities that could
decrease fatigue which were described as effective interventions A statistically
significant difference was found between the Fatigue Scale-Child mean scores of the
experimental (2723) and the control group (4213) The results suggest that fatigue of
children with cancer can be reduced by implementing appropriate nursing interventions
(t=567 Plt00)
Discussion The purpose of this systematic review was to determine the effectiveness of
non-pharmacological interventions specifically targeting fatigue for children and
adolescents with cancer undergoing chemotherapy or after receiving chemotherapy
Included articles about the effectiveness of non-pharmacological interventions for
children and adolescents with cancer were published between the years of 2007 and
2009 Although interventions for cancer fatigue for adults have been extensively studied
it can be seen from either the title of the paper or related content that an intervention
study on children was a pilot study or a feasibility study Representing a field in its early
stage these studies show that the fatigue issues with young cancer patients have only
recently been taken seriously
661
29
The results of our meta-analysis include measurement of the four performance indicators
fatigue and general fatigue sleep rest fatigue and cognitive fatigue The results show
that there is a statistically significant difference only in the domain of general fatigue
using an exercise intervention for children with cancer can improve the degree of fatigue
with the effect size reaching 0671 Other results do not indicate significant differences
The reasons may include the following
1 Characteristics of the cancer The exhaustion from cancer occurs not only during cancer treatment but also in during
long-term survival a time during which patients may continue to be affected by this
symptom 8 26 Therefore when using intervention measures to improve fatigue
circumstances should be considered such as the process of the treatment and the course
or stage of the disease Because cancer patients will experience different forms of
treatment or courses of treatment the disease itself or treatment differences should be
considered in the choice of intervention Even chemotherapy drugs should be taken into
consideration For example a period of general steroid treatment can increase patientsrsquo
fatigue In those studies of children with cancer few studies looked solely at one type of
cancer most studies included a variety of cancer patients Furthermore most studies do
not clearly explain the stage of the disease or course of treatment and most do not
include treatment variables in the control group Moreover children with cancer may
have different levels of physical function
2 Research design The sample size Currently there are few studies with large sample size and a rigorous
RCT design due to the small number of papers available for analysis The sample size
included in our studyrsquos data analysis is between 20 and 42 people this small sample size
will affect the power available to evaluate outcome variables
Although most of the non-pharmacological interventions still use exercise and physical
activity and these studies overall show better results for fatigue as compared with
controls more research is still needed to further confirm the efficacy of these findings
662
30
The dropout rate in the evaluated research varies a great deal ranging from 5 to 45
these dropout rates may result from the characteristics of the research subjects or the
lengthy time involved in participating in these studies The research data with a high
turnover rate might not reflect the actual outcomes of participation in exercise and the
quality of the research contained in articles with high subject turnover rates may be
lower
Exercise doses and time The exercise doses needed to reduce fatigue cannot be
determined additionally the amount of exercise completed by the patient is also
inconsistent interventions vary between 2-3 times per week and two times a day and
exercise duration varies between 10 and 45 minutes each time Furthermore the study
interventions vary in length between a couple of days and a long period of 16 weeks The
data collection times are different some were measured 12 weeks after the intervention
began some were measured during the 6 weeks of intervention some were measured
three months after the intervention was finished and some were measured after one
year
In addition disease-related symptoms decrease childrenrsquos willingness to participate in
exercise interventions inappropriate exercise intervention programs may actually
increase childrens fatigue In addition the children in the study are still developing
physically it is important to consider ways to design an interesting exercise intervention
to increase the compliance of patients in order to improve the effectiveness Although
intervention programs in the hospital or in a community sports center can improve the
effectiveness because they provide supervision the feasibility of these programs is
questionable However if the program is home-based the children need to be
supervised by parents in order to improve their compliance in doing the exercises
Furthermore regarding the nature of the intervention the results from this study indicate
that the researched non-pharmacological interventions include the following exercise
training programs physical activity massage therapy and health education interventions
However according to the National Comprehensive Cancer Network 1 clinical guidelines
663
31
for cancer non-drug measures for cancer fatigue can be separated into five categories
(1) activity enhancement (2) psychosocial interventions such as cognitive behavioral
therapy (CBT) stress management relaxation techniques and support groups (3)
attention-restoring therapy (4) nutritional consultation and (5) cognitive behavioral
therapy specifically targeting sleep disturbance Researchers have also suggested that
psychosocial interventions should be included in the future research for children with
cancer-related fatigue 22
(2) The measurement tools in the study The assessment of fatigue can be
one-dimensional or multidimensional One-dimensional assessment can help understand
the severity of fatigue symptoms however multidimensional scales are often more
credible Therefore when measuring cancer-related fatigue researchers should consider
whether there is a uniform definition of fatigue or a standardized tool for measuring
fatigue in order to facilitate further systematic meta-analyses and further develop the
clinical care guidelines
Limitations of the review The present review has some potential limitations First the low methodological quality
may influence the result Although exercise intervention seems promising quality of the
RCTs was generally quite low Future studies require better design and reporting if
methodological issues to establish evidence-based nonpharmcologic intervention
Second the identified studies covered only a limited types of nonpharmcological
intervention especially in exercise intervention The guidelines for cancer-related fatigue
in NCCN (2011)1 referred to more interventions than the ones included in this review
such as cognitive behavioral therapy and nutrition consultation Thirdly the small sample
size and effect size could be potentially having led to underpowered approach for
detecting the effects on fatigue Therefore we recommend that as research continues to
grow a re-analysis can be undertaken Fourthly Combining data in meta analysis from
664
32
studies where the ages were quite different is a potential source of heterogeneity and
may affect the interpretation of the results
Conclusion At present clinical treatment is widely used for cancer patients However child and
adolescent cancer patients often experience various side effects which cause short-term
or long-term discomfort both physically and psychologically In particular with the
increasing cure rate cancer related fatigue during or after treatment has become an
important issue This study result provided positive effect of exercise intervention on
general fatigue
Implications for practice The results of this systematic review and meta-analysis show that exercise interventions
can effectively improve the level of general fatigue In particular although the articles
were self-reported feasibility studies their results all indicate that exercise interventions
for fatigue are feasible and safe there was no conclusion to be made for the use of
massage therapy or health education measures because there was only one article for
each of these interventions
Recommendations for practice
Cancer-related fatigue is one of the most severe and frequent symptoms by pediatric
oncology children and adolescent suffered during treatment and the symptom existed
even after treatment has ended Until now no golden standard of treatment to fatigue is
established The findings call for more attention to how to reduce patientrsquos levels of
fatigue Based on the available information evaluated in this review the following
recommendations for practice are provided
665
33
bull For children aged 7 to 18 who has cancer (eg Lymphoma leukemia CNS tumor
germ cell tumor) an effective progressive aerobic exercise program is recommended to
be at least 2-3 times per week 20 to 45 minute for each session and last for 6-16 weeks
in order to reduce their general fatigue (tiredness physically weakness) In addition
adults should be involved in accompanying children while they are performing physical
exercise of which should be able to improve the adherence rate (level 2 ) ( Grade of
recommendation A)
bull For children aged 7 to 18 who has cancer (eg Lymphoma leukemia CNS tumor
germ cell tumor) an progressive aerobic exercise program will not be effective to reduce
their sleep andor rest (sleeping or resting a lot) or cognitive fatigue (problems with
thinking quickly or problems with remembering) (level 2 ) ( Grade of recommendation C)
bull Nursing interventions in educating treatment of fatigue include information about
activity nutrition energy preservation consulting and providing a useful fatigue
handbook will benefit those children who are 7 to 12 years have a new diagnosis of ALL
AML or lymphoma and receive for the first time after being diagnosed a 7- to 10-day
chemotherapy treatment (level 2) ( Grade of recommendation A)
bull A 4-week massage therapy program (the therapists massage childrenrsquos back legs
arms stomachchest and face) is not effective for children who are aged 7 to 18 and
have acute lymphoblastic leukemia brain tumors lymphoma rhabdomyosarcoma
Wilms tumor or Ewing sarcoma(level 2)( Grade of recommendation C)
bull Using a 12-week aerobic and strength exercise (45-min exercise sessions twice a
week) is not effective for children who are aged 6-14 and survived acute lymphoblaststic
leukemia age from 6 to 14(level 2) ( Grade of recommendation C)
bull Using a physical activity intervention (30minutestwice daily for 2-4days) is not
effective for children who are 7 to 18 years of age with soild tumor or AML(level 2)
( Grade of recommendation C)
666
34
Implications for research According to this systematic review and meta-analysis results there are suggestions to
improve the effectiveness of future research on non-pharmacological interventions for
children and young peoplersquos cancer-related fatigue
As the majority of included non-pharmacological interventions for the fatigue of cancer
patients consist of exercise programs future research should also consider various
non-pharmacological interventions in order to understand the effectiveness of different
methods
Regarding the exercise intervention methods and studies should consider multiple
factors including the age or personal condition of the subject the disease stage and the
amount of daily activities Studies should use design prescriptions (eg frequency
intensity duration and type of exercise) and consider the adherence to the measures in
order to enhance the study strength
In measuring the results of non-pharmacological interventions there should be standard
definitions or standard measurement tools to facilitate the following systematic review
and meta-analysis that can subsequently be developed into clinical care guidelines
Reviewing the effectiveness of the current non-pharmacological management of children
and adolescent cancer patients there is still a lack of rigorous RCT research Limited by
the characteristics of cancer there is still a lack of large sample sizes
Potential conflicts of interest There is no conflict of interest
Acknowledgements
Thank you to Dr Rie Konno Research Fellow Joanna Briggs Institute for her help in
assessing studies
667
35
References 1 National Comprehensive Cancer Network( NCCN) in USA NCCN clinical practice
guideline in oncology cancer-related fatigue 2011 2 Ekti Genc R amp Conk Z Impact of effective nursing interventions to the fatigue
syndrome in children who receive chemotherapy Cancer Nursing 200831(4)312-317
3 Childhood Cancer Foundation of ROC (2009March) The classification of diseases
and age sex statistical tables of case Childhood Cancer Foundation of ROC newsletter103105-106
4 Department of Health Executive Yuan ROC (TAIWAN)(2009 March 20)2009 cause of death statistic Health and National Health Insurance Annual Statistics Information Service 2010 June 28Available httpwwwdohgovtwstatisticdatavital statists9898health statistic--lifepdf
5 Chang TK (2007December 8) Common childhood cancer and its treatment Status
Childhood Cancer Foundation of ROC (TAIWAN) 2010 September 23 Available httpwwwccfrocorgtwchildchild_events_readphpe_id=45
6 Hockenberry MJ amp Wilson D Wongs nursing care of infants and children (8th ed) St
Louis MO Mosby 2007
7 Post-White J Fitzgerald M Savik K Hooke MC Hannahan AB amp Sencer SF
Massage therapy for children with cancer Journal of Pediatric Oncology Nursing 2009 26(1)16-28
8Chiang YC Yeh CH Wang WKamp Yang CP The experience of cancer-related fatigue
in Taiwanese children European Journal of Cancer Care 2009 18(1)43-49 9Langeveld NE Grootenhuis M A Voute P A de Haan RJ amp van den Bos C No excess
fatigue in young adult survivors of childhood cancer European Journal of Cancer 200339(2)204-214
10Piper BF Lindsey AM amp Dodd MJ Fatigue mechanisms in cancer patients
developing nursing theory Oncology Nursing Forum 1987 14(6)17-23 11Nail LM amp Winningham ML Fatigue In S L Groenwald M H Forgge M Goodman
amp C H Yarbro (Eds) Cancer Nursing Principles and practice (4 th ed) Boston Jones and Bartlett1997
12Irvine D Vincent L Graydon JE Bubela N amp Thompson L The prevalence and
correlates of fatigue in patients receiving treatment with chemotherapy and
668
36
radiotherapy A comparison with the fatigue experienced by healthy individuals Cancer Nursing 199417(5)367-378
13Hinds PS amp Hockenberry-Eaton M Developing a research program on fatigue in
children and adloescents diagnosed with cancer Journal of Pediatric Oncology Nursing 200118(2)3-12
14Aaronson LS Teel CS Cassmeyer V Neuberger GB Pallikkathayil L Pierce J Press
AN Williams DP amp Wingate A Defining and measuring fatigue Journal of Nursing scholarship 1999 31(1)45-50
15Yeh CH Wang CH Chiang YC Lin Lamp Chien LC Assessment of symptoms reported
by 10- to 18-year-old cancer patients in Taiwan 2009 38(5)738-746 16 Okuyama T Akechi T Kugaya A Okamura H Shima Yamp Maruguchi M
Development and validation of the cancer fatigue scale a brief three-dimensional self-rating scale for assessment of fatigue in cancer patients Journal of Pain amp Symptom Management 2000 19(1) 5-14
17Gibson F Mulhall AB Richardson A Edwards JL Ream E amp Sepion BJ A
phenomenologic study of fatigue in adolescents receiving treatment for cancer Oncology Nursing Forum200532(3)651-660
18Wolfe J Grier HE Klar N Levin SB Ellenbogen JMamp Salem-Schatz S et al
Symptoms and suffering at the end of life in children with cancer New England Journal of Medicine 2000342(5)326-333
19Whiting P Bagnall AM Sowden AJ Cornell JE Mulrow CD amp Ramirez G
Interventions for the treatment and management of chronic fatigue syndrome a systematic review JAMA the Journal of the American Medical Association 2001286(11)1360-1368
20 Kangas M Bovbjerg DHamp Montgomery G H Cancer-related fatigue a systematic
and meta-analytic review of non-pharmacological therapies for cancer patients Psychological Bulletin 2008134 (5)700-741
21Williams PD Schmideskamp J Ridder EL amp Williams AR Symptom monitoring and
dependent care during cancer treatment in children pilot study Cancer Nursing 200629(3)188-197
22Takken T van der Torre P Zwerink M Hulzebos EH Bierings M Helders PJMamp van
der Net J Development feasibility and efficacy of a community-based exercise training
669
37
program in pediatric cancer survivors Psycho-Oncology 200918(4)440-448
23Keats MR amp Culos-Reed SN A community-based physical activity program for
adolescents with cancer (project TREK) program feasibility and preliminary findings
Pediatric hematology and oncology 200830(4) 272-280
24Hinds PS Hockenberry M Rai SN Zhang L Razzouk B I Cremer L McCarthy K amp
Rodriguez-Galindo C Clinical field testing of an enhanced-activity intervention in
hospitalized children with cancer Journal of Pain amp Symptom Management 2007
33(6)686-697
25Chiang YC The effects of ldquo a home-based aerobic exercise interventionrdquo on fatigue
and cardiorespiratory fitness in children with acute lymphoblastic leukemia during the
maintenance stage of chemotherapy Unpublished thesis Taiwan Tao-Yuan 2007
26Langeveld N Ubbink M amp Smets E I dont have any energy The experience of
fatigue in young adult survivors of childhood cancer European journal of oncology
nursing 20004(1)20-28
27 Kisner C Colby L Therapeutic exercise Foundations and techniques 2nd ed Philadelphia PAFA Davies 2007
670
38
Appendix I JBI Critical Appraisal Checklist for Experimental studies
Author__________ Year_________ Record Number__________________
Questions 1 to 4 must be answered ldquoyesrdquo for study to be included in the metashyanalysis
1 Were the participants randomized to study groups
Yes No Not clear
2 Other than research intervention were participants in each groups treated the same
Yes No Not clear
3 Were the outcomes measured in the same manner for all participants
Yes No Not clear
4 Were groups comparable at entry
Yes No Not clear
5 Was randomization of participants blinded
Yes No Not clear
6 Were those assessing outcome blinded to treatment allocation (if outcome not objective such as survival or length of hospitalization)
Yes No Not clear
7 Was allocation to treatment groups concealed from the allocator
Yes No Not clear
8 Was an appropriate statistical analysis used
671
39
Yes No Not clear
9 Were outcomes measured in a reliable way
Yes No Not clear
10 Was there adequate followshyup of participants
Yes No Not clear
Summary
TOTAL
Yes No Not clear
DECISION
Use Reject
Narrative summary only Further information needed
COMMENTS
672
40
Appendix II JBI Data Extraction Tool for Quantitative Studies Authors and Year
Journal Title
Record NumberArticle Reference No
Reviewer
Method
Settings
Participants
Number of participants
Group A Group B Group C
Control Intervention 1 Intervention 2
Interventions
Group A
Control
Group B
Intervention 1
Group C
Intervention 2
Outcome measures
Definition
673
41
Other outcome measures
Outcome description ScaleMeasure
Results
Dichotomous Data
Outcome Control Group
Numbertotal number
Treatment Group
Numbertotal number
Continuous Data
Authorrsquos Conclusions
Comments
Outcome Control Group
Mean amp SD
Treatment Group
Mean amp SD
674
43
Appendix III Details of included studies (N=6)(2720212223) RefNo Author(s)
(years) Title Study question Research
method Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
22 Takken T van der Torre P Zwerink M Hulzebos E H Bierings M Helders P J Mamp van der Net J (2009)
Development feasibility and efficacy of a community-based exercise training program in pediatric cancer survivors
To develop a 12-week home-based exercise training program (comprising aerobic and strength exercises) for children who survived ALL and to study itrsquos feasibility and efficacy
Pre-post test design
No comparsion group
Survived ALL(N=9)ages 6-14 years
1anthropometry 2 muscle strength 3functional mobility 4cardio-pulmonary
exercise test 5Fatigue
1 Feasibility questionnaire 2 anthropometry electronic scale and a wallmounted stadiometerHarpenden skin fold calipers 3 muscle strength handheld dynamometer 4functional mobility Timed Up
and Go test (TUG) 5cardio-pulmonary exercise test electronically braked cycle ergometer 6Fatigue(mean)CSI-20 (subjective experience of fatigueconcentrationmotivationphysical activity)
112-week exercise training program
2 Patients were assessed before (T0) and after (T1) 12 weeks of training
1 muscle strength execapacity functional moand fatigue showed nosignificant differences between pre(meanplusmnSD415plusmn147) and post training(meanplusmnSD3687)
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
7 Post-White J Fitzgerald M Savik K Hooke M C Hannahan A B amp Sencer S F (2009)
Massage therapy for children with cancer
To determine whether 4 weekly sessions of massage compared with 4 quiet-time control conditions would reduce anxiety cortisol levels fatigue nausea and pain in children with cancer undergoing chemotherapy and would reduce anxiety fatigue and mood disturbance in a parent
2-period crossover design (Randomized)
quiet-time
control
sessions
Children with cancer 1 to 18 years of age Twenty-three childrenparent dyads were enrolled 17 completed all data points
children 1relaxation 2symptoms 3 fatigue
parents
1anxiety 2 fatigue
children 1relaxation (heart and respiratory rates blood pressure and salivary cortisol level)
2symptoms (pain nausea anxiety 3 fatigue 1-2y3-6yLansky Play Performance Scale (PPS) 7-13y
1 4 weekly massage (MT) sessions alternated with 4 weekly quiet-time(QT) control sessions
2 children included presession and postsession vital signs (heart rate respiratory rate blood pressure) and self-report (parent proxy report for age 1-2 years) of pain nausea and anxiety Fatigue was measured before sessions 1 and 4 and at each follow-up Parent measures
included anxiety fatigue and mood states
1Massage was moreeffective than quiet tireducing heart rate inchildren anxiety in cless than age 14 yeaparent anxiety 2There were no sign
changes in blood pcortisol pain naufatigue (no state d
3 Children reported tmassage helped thebetter lessened theirand worries and hadlasting effects than q
675
44
14-18yChild Fatigue Scale (CFS) (frequency
intensity) 2 parents anxiety and fatigue
676
45
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
24 Hinds P S Hockenberry M Rai S N Zhang L Razzouk B I Cremer L McCarthy K amp Rodriguez-Galindo C (2007)
Clinical field testing of an enhanced-activity intervention in hospitalized children with cancer
To determine the feasibility of an
enhanced physical activity EPA intervention in children and adolescents hospitalized to receive chemotherapy for a solid tumor or AML and to assess the sleep and fatigue outcomes of the intervention using two different statistical approaches to analyze the longitudinal symptom data
randomized prospective two-site and two-group pilot study
Standard care Twenty nine patients (25 with a solid tumor and 4 with AML)ages 7-18 years
1 sleep duration 2 sleep efficiency 3 fatigue
1sleep duration sleep efficiency The
Wrist Actigraph The Daily Sleep Diary-Parent 2 fatigue (mean) The Fatigue Scale(FS-C) for 7-12 (intensity) The Fatigue Scale(FS-A) for 13-18 The Fatigue Scale Parent Version (FS-P) The Fatigue Scale Staff Version (FS-S)
1enhanced physical activity (EPA) (hospital-based 30 minutes
twice daily for 2-4 days) 2 T0On the day of admission
(Day 0 or baseline)patient and parents completed the fatigue instruments and a team member applied the actigraph Patients wore the wrist actigraph T1 from Day 0 to 2 or 3 consecutive days (Days 0e3) In addition the patient same parent and staff nurses completed the daily sleep and fatigue reports in the late afternoons of Days 1-3
1 ANOVA model slesignificantly more the experimental athe control arm whdifferences from bsleep efficiency vaaveraged and com
2 The patient-reported mean fatigue scoresarms were higher amadolescents than for
3 The mixed model anarevealed no significandifferences in patientfatigue between
the two study arms otime( no final result iSD only give mixed result)
677
46
23 Keats M
R amp Culos-Reed S N (2008)
A community-based physical activity program for adolescents with cancer (project TREK) program feasibility and preliminary findings
To examine the
feasibility of a
theoretically-based
physical activity (PA)
intervention in
adolescents with
cancerand
examination of the
impact of the
program on
participant QOL
including social
emotional and
physical
well-being(including fatigue)
Repeat measures longitudinal design
No comparsion group
10 adolescents(Lymphoma(4)leukemia(4)CNS tumor(1)germ cell tumor(1)) ages 14-18 years
1physical fitness 2quality of life (QOL) 3PA behavior 4fatigue
1 Feasibility was assessed by participant recruitment attendance and adherence
2physical fitness Fitnessgram 3quality of life (QOL) Pediatric Quality of Life Inventory (PedsQL) 4PA behavior leisure score index (LSI) 5fatigue (mean) pediatric Quality of life
Multidimensional Fatigue Scale (Peds QL-MFS)
(Generalsleepcognitive fatigue)
116week physical activity (PA)
2 total PA physical fitness and overall QOL was assessed at 5 different intervals T0 preintervention (baseline) T1midintervention (after the
first 8 wk) T2 postintervention
(16 wk) T3 3-months
postintervention T4 1-year poststudy
initiation
1 from baseline -wkssig Improvementstotal PA physfitness and Qgeneral fatigue(meanplusmnSD 796plusmn135)
2 from baseline to 3FUsig Improvin general fatigue(meanplusmnSD824plusmn131)slefatigue(meanplusmnSD755plusmn191)totafatigue(meanplusmnSD778plusmn150)
3at 1 years FUsImprovements in sleeprest fatigue(meanplusmnSD725plusmn203)total (meanplusmnSD 763plusmn
678
47
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
2 Gene R E amp Conk Z (2008)
Impact of Effective Nursing Interventions to the Fatigue Syndrome in Children Who Receive Chemotherapy
1 to examine the effects of an effective nursing intervention to the fatigue syndrome of children 7 to 12 years of age who receive chemotherapy 2Tto examine the relationship between fatigue and demographic variables (age sex) diagnoses ([ALL AML] lymphoma) and therapy-related variables (eg level of hemoglobin
experimental randomized controlled study
Routine nursing care
A total of 60 children who are 7-12 years of age(a new diagnosis of ALL AML or lymphoma and receiving for the first time after being diagnosed a 7- to 10-day chemotherapy treatment )
fatigue The Fatigue Scale(FS-C) for 7-12 (intensity)
The Fatigue Scale Parent Version (FS-P)
1 effective nursing interventions(45- 60mdaya week)education about the fatigue with the chemotherapy and fatigue handbook 2 T1 After a 7-day period the children
and parent were evaluated with the Fatigue Scale
1The difference betwthe 2 mean values wafound to be statisticallsignificant 2 statistically significadifference was found between the Fatigue Scale-Child mean scothe experimental (272the control group (4213)children
679
48
25 Chiang et
al(2007)
The effects of ldquo a home ndashbased aerobic exercise interventionrdquo on fatigue and cardiorespiratory fitness in children with Acute Lymphoblastic Leukemia during the maintenance stage of chemotherapy
To examine the effect of ldquo a home ndashbased aerobic exercise interventionrdquo on fatigue and cardiorespiratory fitness in children with Acute Lymphoblastic Leukemia during the maintenance stage of chemotherapy
Quasi-experi -mental
Routine
nursing care
14 pediatric oncology patients in the experimental group and 10 in control group who were matched by age and sex ages7-18 years
1Cardiorespiratory fitness
2Fatigue
1Cardiorespiratory fitness Physical Activity Recall
VO2maxHR peak 6MWT
2 Fatigue PedsQL-MFS(Generalsleepcognitive fatigue)
1A six-week home-based aerobic exercise intervention 2 8 time points T0 baseline T1-T6 every week during the
intervention(6 weeks) T7 post intervention T8 follow-up (one month after
the end of the home-based exercise program)
1 For intent-to ndash treatthe findings indicated are no intervention efftime differences by anon the subscale of fat2 For per-protocol angeneral fatigue( mean422plusmn402) was the osubscale that was siglower for children whothe exercise interventthose in control groupfollow-up assessmentmonth after the compintervention) 3 The VO2peak are significantly improvingexperimental group atbaseline- and post-intassessment The VO2was significantly highechildren who were in experimental group thcontrol subjects at post-intervention assefor the per-protocol an
680
49
Appendix IV Instrument used to measure fatigue
Name Instrument
developers
Description Used in
age in
ref
Reliability
Consistency of
instrument
Checklist Individual Strength
(CIS)22
Vercoulen et
al1996
20 items using 7-point Likert scale of
fatigue To measure four aspects of
fatiguesubjective experience
contractionmotivation physical
Activity
6-14 Not reported
Child Fatigue Scale (CFS)7 Hockenberry
et al2003
14 items 2 part questionnaire frequency
(yes or no) 5-point Likert scale of the
intensity of any yes responses
7-13
14-18 α073-o84
The Fatigue Scale for 7-12
year Olds (FS-C)224
Hockenberry
et al
14 items provide a fatigue intensity score
5-point Likert scale
7-12 αo84
The Fatigue Scale for 13-18
year Olds (FS-A)24
Hockenberry
et al
14 items provide a fatigue intensity score
5-point Likert scale
13-18 α076-o96
Pediatric Quality of life
Multidimensional Fatigue
Scale (Peds QL-MFS)2325
Varni2002 18 items to measure three aspects of
fatigueGeneralsleepcognitive
14-18 Not reported
681
50
Appendix V Excluded studies and reasons for exclusion
Baggott C Dodd M Kennedy C Marina N Miaskowski C Multiple Symptoms in Pediatric Oncology
Patients A Systematic Review Journal of Pediatric Oncology Nursing 2009 Nov-Dec 27(6)
325-339
Reason for exclusion Not outcome of interest
Barlow JH Ellard DR Psycho-educational interventions for children with chronic disease parents and
siblings an overview of the research evidence base Care Health amp Development 2004 Nov
30(6)637-45
Reason for exclusion Not outcome of interest
Bedider S Moyer CA Randomized controlled trials of pediatric massage A review Evid Based
Complement Alternat Med 2007 Mar 4(1)23-34 Epub 2006 Nov 3
Reason for exclusion Not outcome of interest
de Nijs EJ Ros W Grijpdonck MH Nursing intervention for fatigue during the treatment for cancer Cancer
Nursing 2008 31(3)191-206
Reason for exclusion Not population of interest
Edwards JL Gibson F Richardson A Sepion B Ream E Fatigue in adolescents with and following a
cancer diagnosis developing an evidence base for practice European Journal of Cancer 2003
Dec 39(18)2671-80
Reason for exclusion Not experimental or quasi-experimental study
Hinds PS Hockenberry-Eatan M Developing a research program on fatigue in children and adolescents
diagnosed with cancer Journal of Pediatric Oncology Nursing 2001 Mar-Apr 18(2 Suppl
1)3-12
Reason for exclusion Not experimental or quasi-experimental study
Hockenberry-Eaton M Hinds PS Alcoser P ONeill JB Euell K Howard V Gattuso J Taylor J Fatigue in
Children and Adolescents With Cancer Journal of Pediatric Oncology Nursing 1998 July
15(3)172-182
Reason for exclusion Not experimental or quasi-experimental study
Jean-Pierre P Mustian K Kohli S Roscoe JA Hickok JT Morrow GR Community-based clinical oncology
research trials for cancer-related fatigue The Journal of Supportive Oncology 2006 Nov-Dec
4(10)511-6
682
51
Reason for exclusion Not population of interest
Kangas M Bovbjerg DH Montgomery GH Cancer-Related Fatigue A Systematic and Meta-Analytic
Review of Non-Pharmacological Therapies for Cancer Patients Psychological Bulletin 2008 Sep
134(5)700-41
Reason for exclusion Not population of interest
Lotfi-Jam K Carey M Jefford M Schofield P Charleson C Aranda S Nonpharmacologic strategies for
managing common chemotherapy adverse effects A systematic review Journal of Clinical
Oncology 2008 Dec 1 26(34)5618-29 Epub 2008 Nov 3
Reason for exclusion Not outcome of interest
Marchese VG Chiarello LA Lange BJ Effects of physical therapy intervention for children with acute
lymphoblastic leukemia Pediatr Blood Cancer 2004 Feb42(2)127-33
Reason for exclusion Not outcome of interest
Meeske KA Siegel SE Globe DR Mack WJ Bernstein L Prevalence and correlates of fatigue in
long-term survivors of childhood leukemia Journal of Clinical Oncology 2005 Aug 20
23(24)5501-10
Reason for exclusion Not intervention study
Minton O Richardson A Sharpe M Hotopf Stone P A systematic review and meta-analysis of the
pharmacological treatment of cancer-related fatigue J Natl Cancer Inst 2008 Aug 20
100(16)1155-66 Epub 2008 Aug 11
Reason for exclusion Not population and intervention of interest
Mustian KM Morrow GR Carroll JK Figueroa-Moseley CD Pascal JP Williams GC Integrative
nonpharmacologic behavioral interventions for the management of Cancer-Related fatigue The
Oncologist 2007 12(1)52-67
Reason for exclusion Not population of interest
Neill J Belan I Ried K Effectiveness of non-pharmacological interventions for fatigue in adults with
multiple sclerosis rheumatoid arthritis or systemic lupus erythematosus a systematic review
Journal of Advanced Nursing 2006 Dec 56(6)617-35
Reason for exclusion Not population of interest
Rheingans JI A systematic review of nonpharmacologic adjunctive therapies for symptom management
Journal of Pediatric Oncology Nursing 2007 24(2) 81-94
683
52
Reason for exclusion Not outcome of interest
Rheingans JI Pediatric oncology nursesrsquo management of patients symptoms Journal of Pediatric
Oncology Nursing 2008 Nov 25(6) 303-11
Reason for exclusion Not outcome of interest
San Juan AF Fleck SJ Chamorro-Vintildea C Mateacute-Muntildeoz JL Moral S Peacuterez M Cardona C Del Valle MF
Hernaacutendez M Ramiacuterez M Madero L Lucia A Effects of an intrahospital exercise program
intervention for children with leukemia Medicine amp Science in Sports amp Exercise 2007 Jan
39(1)13-21
Reason for exclusion Not outcome of interest
Sanford SD Okuma JO Pan J Srivastava DK West N Farr L Hinds PS Gender differences in sleep
fatigue and daytime activity in a pediatric oncology sample receiving dexamethasone Journal of
Pediatric Psychology 2008 Apr 33(3)298-306 Epub 2007 Nov 17
Reason for exclusion Not experimental or quasi-experimental study
Schmitz KH Holtzman J Courneya KS Macircsse LC Duval S Kane R Controlled physical activity trials in
cancer survivors a systematic review and meta-analysis Cancer Epidemiol Biomarkers Prev
2005 Jul 14(7)1588-95
Reason for exclusion Not population of interest
van Brussel M Takken T Lucia A van der Net J Helders PJ Is physical fitness decreased in survivors of
childhood leukemia A systematic review Leukemia 2005 Jan 19(1)13-7
Reason for exclusion Not population of interest
Whiting P Bagnall AM Snowden AJ Cornell JE Mulrow CD Ramirez G Interventions for the treatment
and management of chronic fatigue syndrome JAMA 2001 Sep 19 286(11)1360-8
Reason for exclusion Not intervention of interest
Whitsett SF Gudmundsdottir M Davies B McCarthy P Friedman D Chemotherapy-related fatigue in
childhood cancer correlates consequences and coping strategies Journal of Pediatric
Oncology Nursing 2008 Mar-Apr 25(2)86-96 Epub 2008 Feb 29
Reason for exclusion Not experimental or quasi-experimental study
Winner C Muumlller C Hoffmann C Boos J Rosenbaum D Physical activity and childhood cancer Pediatr
Blood Cancer 2010 Apr 54(4)501-10
Reason for exclusion Not research study
684
53
Wu M Hsu L Zhang B Shen N Lu H Li S The experiences of cancer-related fatigue among Chinese
children with leukaemia A phenomenological study Journal of Nursing Studies 2010 Jan
47(1)49-59 Epub 2009 Aug 25
Reason for exclusion Not experimental or quasi-experimental study
Yeh CH Chiang YC Lin L Yang CP Chien LC Weaver MA Chuang HL Clinical factors associated with
fatigue over time in paediatric oncology patients receiving chemotherapy British Journal of
Cancer 2008 Jul 8 99(1)23-9 Epub 2008 Jun 24
Reason for exclusion Not experimental or quasi-experimental study
685
14
(FS-A)and Pediatric Quality of life Multidimensional Fatigue Scale (Peds QL-MFS)
Types of settings
Both hospital and community settings
Search Strategy
Before undertaking this systematic review the Cochrane Library Joanna Briggs Institute
Library of Systematic Reviews and CINAHL were searched and no systematic reviews on
this topic were found or identified as underway
The search strategy aimed to find both published and unpublished studies
A three-step search strategy was utilized in each component of this review An initial
limited search of CINAHL and MEDLINE was undertaken followed by an analysis of the
text words contained in the title and abstract and of the index terms used to describe the
article A second search using all identified keywords and index terms was undertaken
Lastly the reference lists of all identified reports and articles were searched for additional
studies
Types of languages
1 English
2 Chinese
The following databases were searched to identify keywords contained in the title and
abstract and relevant MeSH headings and descriptor terms
The Cochrane Library PsycINFO 1990 ndash 2010
647
15
Ovid MEDLINE 1966 ndash 2010 CINAHL Plus with Full Text 1960 ndash2010 EMBASE ProQuest Dissertations amp theses 1990-2010 Electronic theses and dissertations system 1956(abstract)1990(full text)-2010 MEDNAR Index to Taiwan periodical literature 1970-2010 Electronic thesis and dissertation system (Chinese) 1990-2010
Keyword search terms
1Types of studies experimental study random quasi-experimental study實驗性研究隨
機類實驗性研究
2 Types of participants childchildren adolescents pediatric cancer and oncology兒童
青少年兒科癌症腫瘤
3 Types of interventions non-pharmacological interventions massage exercise fitness
physical activity cognitive behavioral stress management energy conservation
sleep therapy relaxation distraction and psycho-education非藥物性處置按摩運動
身體活動認知行為壓力處置能量保存睡眠治療放鬆轉移注意力衛教
4 Types of outcome measures fatigue cancer-related fatigue loss of energy levels of
tiredness tired side effect symptoms疲憊癌性疲憊疲倦合併症症狀
Methods of the Review
Assessment of methodological quality Papers selected for retrieval were assessed by two independent reviewers for
methodological validity prior to inclusion in the review using the standardised critical
appraisal instruments (Appendix I) from the JBI-SUMARI (Joanna Briggs Institute
Systems for the Unified Management Assessment and Review of Information package)
Any disagreements that arise between the reviewers were resolved through discussion
648
16
with a third reviewer
Data extraction Data was extracted from papers included in the review using standardised data
extraction tool (Appendix II) from the JBI-SUMARI Details of eligible studies were
extracted and summarised independently by two reviewers
Data Synthesis
All data analysissynthesis were made using the JBI-SUMARI The studies were
assessed for clinical heterogeneity by considering the settings populations interventions
and outcomes Where possible these binary outcomes were analyzed by calculation of
the Odds Ratio with the 95 CI The weighted mean difference was calculated if the
pooled studies have used the same scale for continuous data The standardized mean
difference was calculated for continuous data measuring the same outcome on a
different scale In studies where statistical pooling of results was inappropriate the
findings were considered for inclusion as a narrative summary
Results The findings from the systematic review are presented first Followed by the results from
the meta-analysis component of this review
Description of studies From database search and hand search a total of 76 papers were identified Thirty
papers were then excluded because they did not meet the inclusion criteria Forty-six
full text were retrieved for further consideration for inclusion Of the 30 excluded reasons
for exclusion were follows 11articles were duplicated eight articles did not meet
649
17
participant inclusion criteria eight articles did not meet outcome criteria and nine articles
were correlation studies or discussion papers others articles were unclear reporting In
total after sorting six papers have been included in this article Figure 1 displays the
process used to identify relevant articles for inclusion in the systematic review
Figure 1 Stages of searching and inclusionexclusion of references for the review
Potentially relevant English-language and Chinese- language Studies Identified
Electronically and hand search (n=76)
Duplicate (n= 11) Papers excluded after evaluation of abstract (n=19)
Papers retrieved for detailed examination (N=46)
Papers excluded after review of full paper
(n=40)
Papers assessed for methodological
quality (n=6)
Papers included in systematic review
(n=6)
Methodological Quality
Of the six included articles 2722232425 two articles were RCT design224 with score 7 out
of 10 each paper from Critical Appraisal Checklist and four articles used
650
18
quasi-experimental design7222425 with socre 5 to 6 out of 10 because the quality of
the whole papers is still acceptable therefore these six articles were accepted after
primary reviewer and secondary reviewerrsquos decision
Randomisation
In two RCT articles224 one study24 used to a computer-generated program operated by
the St Jude Protocol and Data Management System to randomize the sample Another
study2 didnrsquot address how randomization was done
Allocation concealment
No studies reported allocation concealment
Intention-to-treat analysis
One quasi-experimental design7 stated Intention-to-treat analysis
Adequate follow up
The follow-up periods included 2or 3 days24 7 days2 4 week7 one month25 6 week25 12
week2216 week23 and 1 year23
Baseline comparability of groups
Three 22425 of six studies had baseline comparability in terms of age sex diagnosis
race institution duration of illness
Blinded outcome assessment
No studies used blinded outcome assessment The researchers including study team
patients staff and families were not blinded to the patientrsquos group assignment
Characteristics of included studies
651
19
There were six studies related to interventions designed to cancer-related fatigue for
pediatric patients than there are for adults There are a total of six including five
English-language papers 27222324 and one Chinese-language paper 25 ranging in year of
publication from 2007 to 2009
Patient characteristics
The research subjects of four papers included both school-aged children and
adolescents 7222324 one papers involved mainly adolescents25 and one paper sampled
only school-aged children 2 the range in ages was between six-18 years The number of
patients included in the samples ranged from nine to 60 The sources of case data were
from both outpatients and hospitalized children The types of cancer included acute
lymphoblastic leukemia (ALL) solid tumors acute myeloid leukemia (AML) and
lymphoma Overall ALL was the most commonly studied cancer type The stage of the
disease varied in these reports some patients were in the maintenance stage of
chemotherapy25 some had just received their first round of chemotherapy224 some had
completed two courses of treatments lasting 4-8 weeks each 7 and some had entered
the survivor stage 2223
Countries
Two RCTrsquos 2 24 were conducted in the USA There were four quasi-experimental design
studiesThree studies conducted in the USA7 22 23 and one in Taiwan25
Intervention types
652
20
The interventions included exercise training programs 2225 physical activity 2324
massage therapy 7 and health education 223 exercise training and physical activity as
an intervention method given in three different settings home 22 25 community 23 or
hospital 24 The studies used different types of exercise interventions including
home-based aerobic exercise use a Video Compact Disc 25 use of a bicycle-style
exerciser 24 aerobics2223 and various types of physical activities2 and strength-building
exercises 2223 The intensity of the exercise varied and often included gradual warm-up
exercises a period of main exercise and a cool down period For these studies2023 the
target exercise intensity was a heart rate of gt90 of the maximum heart rate (HR max) or
the increase in the percentage of heart rate reserve ( HRR) of 40-60
The number of weeks for the exercisephysical activity interventions duration including
2-4 days 24 6 weeks25 12 weeks22 and 16 weeks23 The frequency of exercise ranged
from 2-3 times per week to twice a day Typical duration of exercise ranged from 10 to 45
minutes There are three papers using exercise interventions based on ACSM (American
College of Sports Medicine) 2225 recommendations and one of these used an Activity
pyramid from the ACSM to determine intensity 24
One article did not clarify the type of exercise intervention or the reasons for their choices
23 In addition there was an article focusing on massage therapy 7 as an intervention in
this study the experimental group received four weeks of massage therapy either in the
clinic or in the patientrsquos room the therapy was applied by a professional masseur and
targeted the back legs arms chest stomach and face of the children However the
frequency of massage sessions per week and the duration of the massages were not
653
21
given There is another article about intervention measures combine health education
and physical activity 2 In this study patients were informed about the following (1) health
education patients received daily education about chemotherapy-related fatigue and
information from a health education manual written by the author (2) encouragement for
children to engage in activities such as listening to music drawing and reading and (3)
physical activity which involved walking along the corridors of the ward for 10-15 minutes
These health education measures were presented for 45-60 minutes a day for a total of
seven days The study design for non-pharmacological interventions used control groups
that included primarily people who had received standard treatment or people who did
not receive an exercise intervention
Outcome measures
Five measurement tools were used in this group of seven papers concerning childrenrsquos
fatigue (Appendix IV) Because those studies included both school-age children and
adolescents the following descriptions will be differentiated by age Fatigue
measurements for school-aged children with cancer include the following the Child
Fatigue Scale (CFS) 7 a scale that measures the frequency and intensity of fatigue and
the Fatigue Scale for 7-12 year Olds (FS-C) 224 a scale that can be used to evaluate the
intensity of fatigue On the other hand fatigue measurements for adolescent cancer
patients include the following the Fatigue Scale for 13-18-year-olds (FS-A) 24 a measure
that can help evaluate fatigue levels the Pediatric Quality of Life Multidimensional
Fatigue Scale (Peds QL-MFS) 2325 a tool that can be divided into three sub-scales to
understand the general cognitive and sleep rest components of fatigue and finally the
CIS-20 for school-age children and adolescents 22 a scale that measures four levels of
654
22
fatigue namely subjective experience attention motivation and physical activity Two
studies used the Peds QL-MFS scale to measure fatigue2325
Meta-analysis results Two studies of the included papers failed to provide sufficient raw data they could not be
included in the meta-analysis Hinds et al 24 did not include post-test data Genc et al 2
provided no pre-test data PostWhite et al7 reported that fatigue after the health
education intervention was not statistically different but they presented the results
without presenting fatigue-related data Therefore the meta-analysis included three
studies 222325
The heterogeneity of studies was analyzed with Chi square statistics and no statistical
significance was found Therefore the data was combined in meta-analysis according to
exercise intervention on fatigue In addition there were three articles using the Peds
QL-MFS as a research tool to examine childrenrsquos improvements in fatigue Among these
Keats 22 and Chiang 24 present the effectiveness of exercise interventions using three
subscales Therefore the meta-analysis also analysis of the effects of these exercise
intervention measures on three subscales of Peds QL-MFS general fatigue sleep rest
fatigue and cognitive fatigue
The effectiveness of exercise intervention for fatigue We analyzed the exercise intervention effect on fatigue A total of 2 studies 22 23 were
included Takken et al 22 used community-based exercise training program to reduce
fatigue of children 6 to 14 years (mean 93y) of age who survived ALL Fatigue
measurement by Checklist Individual Strength (CIS) after 12-week of training fatigue
655
23
show no significant differences between pre (meanplusmnSD 415plusmn147) and post training
(meanplusmnSD368plusmn217) but fatigue change from baseline mean reduction of 11
Keats et al23 although used community-based physical activity program to reduce fatigue
for adolescents 14 to 18 years of age (mean162 y) with cancer (Lymphoma leukemia CNS
tumor germ cell tumor) Studies used fatigue by PedsQLMFS Results show general fatigue
from baseline to 8 weeks and to 3 months follow up significantly improves General
fatigue sleeprest fatigue and total fatigue from baseline to 3 months follow up showed
significant improvements Sleeprest fatigue and total fatigue at 1 years followed up were
significant improvements
Figure 2 shows the overall effect of exercise intervention in children and adolescents with
cancers with a focus on improving fatigue Due to the lower heterogeneity (p>005) the
fixed effects model was used to pool the data for meta-analysis (Overall effect size=
-006 95 Confidence Interval (CI) -070 to 058) A result did not indicate a statistically
significant difference (p = 087)
656
24
Figure2 Meta-analysis results of exercise intervention on fatigue
In addition Keats23 and Chiang25 used the three sub-scales of Peds QL-MFS to
determine the general cognitive and sleep rest components of fatigue The following
present the effectiveness of exercise interventions using three subscales including
general fatigue sleep rest fatigue and cognitive fatigue 2325
Chiang et al 25 used a 6- week home-based aerobic exercise intervention to reduce
fatigue of children 7 to 18 years (mean age at experimental group was 1088 y in control
group was 1247 y) of age who with acute lymphoblastic leukemia Fatigue measurement
by Peds QL-MFS after training For intent-to ndash treat analysis the findings indicated that
there are no intervention effects and time differences by any items on the subscale of
fatigue For per-protocol analysis general fatigue( meanplusmnSD 422plusmn402) was the only
subscale that was significantly lower for children who received the exercise intervention
than those in control group at follow-up assessment (one month after the completion of
intervention)
Keats et al23 although used community-based physical activity program to reduce fatigue
for adolescents 14 to 18 years of age (mean162 y) with cancer (Lymphoma leukemia
CNS tumor germ cell tumor) Both studies used fatigue by PedsQLMFS Results show
general fatigue from baseline to 8 weeks and to 3 months follow up significantly improves
657
25
General fatigue sleeprest fatigue and total fatigue from baseline to 3 months follow up
showed significant improvements Sleeprest fatigue and total fatigue at 1 years followed
up were significant improvements
The effectiveness of exercise intervention for general fatigue
The impact of the exercise interventions upon levels of general fatigue was also analysed
The heterogeneity was low (p>005) Therefore the fixed effects model was used to
examine the effectiveness The effect size is -076 indicating a statistically significant
difference (p = 001 95 CI -135 to -017 Fig 3) The evidence suggests that exercise
intervention can reduce general fatigue in children with cancer
Fig 3 Meta-analysis results of exercise intervention for general fatigue
The effectiveness of exercise intervention for sleep rest fatigue
The following is the result of the meta-analysis of the effectiveness of exercise
interventions on sleep rest fatigue First the heterogeneity test was conducted with P gt
005 representing small heterogeneity and the fixed effects model was used Fig 4
shows the effect size is -035 indicating no statistically significant differences (p = 023
95 CI-092 to 022 Fig 4)
658
26
Fig 4 Meta-analysis results of exercise intervention for sleep rest fatigue
The effectiveness of exercise intervention for cognitive fatigue Lastly the following data reports the results of meta-analysis of the effectiveness of
exercise interventions for cognitive fatigue The heterogeneity was p>005 then the
fixed effects model was used The effect size is -035 indicating no statistically significant
differences (p = 024 95 CI-092 023 Fig 5)
Fig 5 Meta-analysis results of exercise intervention for cognitive fatigue
Narrative presentation of remaining included studies
Three studies were not included in meta-analysis Post-White et al7 one of the aims in
this study was to examine the effect of massage therapy on fatigue in children with
cancer The study was a quasi-experimental design Twenty-three childrenparent dyads
were enrolled 17completed all data points Children with cancer ages 7 to 18 years
received at least 2 identical cycles of chemotherapy and one parent participated in the
2-period crossover design in which 4 weekly massage sessions (MT) alternated with 4
659
27
weekly quiet-time (QT) control sessions There were no significant changes in fatigue in
children over the 4-week MT or QT conditions either independently (change over time) or
when we compared fatigue by condition
The lack of effect of massage on fatigue may be the difficulty some children had in
differentiating fatigue from being relaxed underscores the challenge of measuring fatigue
in children Some children interpreted being tired or relaxed as having greater fatigue
because they felt like lying around and sleeping or felt unmotivated to do their usual
activities all measures of fatigue in the instrument used in the study
Hinds et al24conducted a prospective two-site randomized controlled pilot study to
assess the feasibility of an enhanced physical activity (EPA) intervention in hospitalized
children and adolescents receiving treatment for a solid tumor or for acute myeloid
leukemia (AML) Twenty-nine patients (25 with a solid tumor and 4 with AML) participated
age range from 736 to 1816 (mean 1248 y) The EPA intervention selected was
pedaling a stationary bicycle-style exerciser (Chattanooga Peddler Deluxe Bio-Teck
Medical Memphis TN) for 30 minutes twice daily for 2 to 4 days of hospitalization The
mixed model analysis revealed no significant differences in patient reports of fatigue
between the two study arms or over time
Genc et al2 conducted a RCT involving children with cancer who are 7 to 12 years of age
and receiving chemotherapy treatment to determine the impact of educational
intervention by nurses on decreasing the fatigue syndrome The research sample was
composed of a total of 60 children with cancer with 30 children being included in the
660
28
experimental group (mean age 923)and 30 children included in the control group (mean
age 937) with their mothers In the experimental group after the 7th to 10th day of the
chemotherapy treatment throughout a week the researcher conducted the nursing
interventions every day for 45 to 60 minutes In the control group routine nursing
interventions were carried out The experimental group received education about the
fatigue with the chemotherapy and fatigue handbook was given which was developed by
the authors Children and mothers were consulted for including activities that could
decrease fatigue which were described as effective interventions A statistically
significant difference was found between the Fatigue Scale-Child mean scores of the
experimental (2723) and the control group (4213) The results suggest that fatigue of
children with cancer can be reduced by implementing appropriate nursing interventions
(t=567 Plt00)
Discussion The purpose of this systematic review was to determine the effectiveness of
non-pharmacological interventions specifically targeting fatigue for children and
adolescents with cancer undergoing chemotherapy or after receiving chemotherapy
Included articles about the effectiveness of non-pharmacological interventions for
children and adolescents with cancer were published between the years of 2007 and
2009 Although interventions for cancer fatigue for adults have been extensively studied
it can be seen from either the title of the paper or related content that an intervention
study on children was a pilot study or a feasibility study Representing a field in its early
stage these studies show that the fatigue issues with young cancer patients have only
recently been taken seriously
661
29
The results of our meta-analysis include measurement of the four performance indicators
fatigue and general fatigue sleep rest fatigue and cognitive fatigue The results show
that there is a statistically significant difference only in the domain of general fatigue
using an exercise intervention for children with cancer can improve the degree of fatigue
with the effect size reaching 0671 Other results do not indicate significant differences
The reasons may include the following
1 Characteristics of the cancer The exhaustion from cancer occurs not only during cancer treatment but also in during
long-term survival a time during which patients may continue to be affected by this
symptom 8 26 Therefore when using intervention measures to improve fatigue
circumstances should be considered such as the process of the treatment and the course
or stage of the disease Because cancer patients will experience different forms of
treatment or courses of treatment the disease itself or treatment differences should be
considered in the choice of intervention Even chemotherapy drugs should be taken into
consideration For example a period of general steroid treatment can increase patientsrsquo
fatigue In those studies of children with cancer few studies looked solely at one type of
cancer most studies included a variety of cancer patients Furthermore most studies do
not clearly explain the stage of the disease or course of treatment and most do not
include treatment variables in the control group Moreover children with cancer may
have different levels of physical function
2 Research design The sample size Currently there are few studies with large sample size and a rigorous
RCT design due to the small number of papers available for analysis The sample size
included in our studyrsquos data analysis is between 20 and 42 people this small sample size
will affect the power available to evaluate outcome variables
Although most of the non-pharmacological interventions still use exercise and physical
activity and these studies overall show better results for fatigue as compared with
controls more research is still needed to further confirm the efficacy of these findings
662
30
The dropout rate in the evaluated research varies a great deal ranging from 5 to 45
these dropout rates may result from the characteristics of the research subjects or the
lengthy time involved in participating in these studies The research data with a high
turnover rate might not reflect the actual outcomes of participation in exercise and the
quality of the research contained in articles with high subject turnover rates may be
lower
Exercise doses and time The exercise doses needed to reduce fatigue cannot be
determined additionally the amount of exercise completed by the patient is also
inconsistent interventions vary between 2-3 times per week and two times a day and
exercise duration varies between 10 and 45 minutes each time Furthermore the study
interventions vary in length between a couple of days and a long period of 16 weeks The
data collection times are different some were measured 12 weeks after the intervention
began some were measured during the 6 weeks of intervention some were measured
three months after the intervention was finished and some were measured after one
year
In addition disease-related symptoms decrease childrenrsquos willingness to participate in
exercise interventions inappropriate exercise intervention programs may actually
increase childrens fatigue In addition the children in the study are still developing
physically it is important to consider ways to design an interesting exercise intervention
to increase the compliance of patients in order to improve the effectiveness Although
intervention programs in the hospital or in a community sports center can improve the
effectiveness because they provide supervision the feasibility of these programs is
questionable However if the program is home-based the children need to be
supervised by parents in order to improve their compliance in doing the exercises
Furthermore regarding the nature of the intervention the results from this study indicate
that the researched non-pharmacological interventions include the following exercise
training programs physical activity massage therapy and health education interventions
However according to the National Comprehensive Cancer Network 1 clinical guidelines
663
31
for cancer non-drug measures for cancer fatigue can be separated into five categories
(1) activity enhancement (2) psychosocial interventions such as cognitive behavioral
therapy (CBT) stress management relaxation techniques and support groups (3)
attention-restoring therapy (4) nutritional consultation and (5) cognitive behavioral
therapy specifically targeting sleep disturbance Researchers have also suggested that
psychosocial interventions should be included in the future research for children with
cancer-related fatigue 22
(2) The measurement tools in the study The assessment of fatigue can be
one-dimensional or multidimensional One-dimensional assessment can help understand
the severity of fatigue symptoms however multidimensional scales are often more
credible Therefore when measuring cancer-related fatigue researchers should consider
whether there is a uniform definition of fatigue or a standardized tool for measuring
fatigue in order to facilitate further systematic meta-analyses and further develop the
clinical care guidelines
Limitations of the review The present review has some potential limitations First the low methodological quality
may influence the result Although exercise intervention seems promising quality of the
RCTs was generally quite low Future studies require better design and reporting if
methodological issues to establish evidence-based nonpharmcologic intervention
Second the identified studies covered only a limited types of nonpharmcological
intervention especially in exercise intervention The guidelines for cancer-related fatigue
in NCCN (2011)1 referred to more interventions than the ones included in this review
such as cognitive behavioral therapy and nutrition consultation Thirdly the small sample
size and effect size could be potentially having led to underpowered approach for
detecting the effects on fatigue Therefore we recommend that as research continues to
grow a re-analysis can be undertaken Fourthly Combining data in meta analysis from
664
32
studies where the ages were quite different is a potential source of heterogeneity and
may affect the interpretation of the results
Conclusion At present clinical treatment is widely used for cancer patients However child and
adolescent cancer patients often experience various side effects which cause short-term
or long-term discomfort both physically and psychologically In particular with the
increasing cure rate cancer related fatigue during or after treatment has become an
important issue This study result provided positive effect of exercise intervention on
general fatigue
Implications for practice The results of this systematic review and meta-analysis show that exercise interventions
can effectively improve the level of general fatigue In particular although the articles
were self-reported feasibility studies their results all indicate that exercise interventions
for fatigue are feasible and safe there was no conclusion to be made for the use of
massage therapy or health education measures because there was only one article for
each of these interventions
Recommendations for practice
Cancer-related fatigue is one of the most severe and frequent symptoms by pediatric
oncology children and adolescent suffered during treatment and the symptom existed
even after treatment has ended Until now no golden standard of treatment to fatigue is
established The findings call for more attention to how to reduce patientrsquos levels of
fatigue Based on the available information evaluated in this review the following
recommendations for practice are provided
665
33
bull For children aged 7 to 18 who has cancer (eg Lymphoma leukemia CNS tumor
germ cell tumor) an effective progressive aerobic exercise program is recommended to
be at least 2-3 times per week 20 to 45 minute for each session and last for 6-16 weeks
in order to reduce their general fatigue (tiredness physically weakness) In addition
adults should be involved in accompanying children while they are performing physical
exercise of which should be able to improve the adherence rate (level 2 ) ( Grade of
recommendation A)
bull For children aged 7 to 18 who has cancer (eg Lymphoma leukemia CNS tumor
germ cell tumor) an progressive aerobic exercise program will not be effective to reduce
their sleep andor rest (sleeping or resting a lot) or cognitive fatigue (problems with
thinking quickly or problems with remembering) (level 2 ) ( Grade of recommendation C)
bull Nursing interventions in educating treatment of fatigue include information about
activity nutrition energy preservation consulting and providing a useful fatigue
handbook will benefit those children who are 7 to 12 years have a new diagnosis of ALL
AML or lymphoma and receive for the first time after being diagnosed a 7- to 10-day
chemotherapy treatment (level 2) ( Grade of recommendation A)
bull A 4-week massage therapy program (the therapists massage childrenrsquos back legs
arms stomachchest and face) is not effective for children who are aged 7 to 18 and
have acute lymphoblastic leukemia brain tumors lymphoma rhabdomyosarcoma
Wilms tumor or Ewing sarcoma(level 2)( Grade of recommendation C)
bull Using a 12-week aerobic and strength exercise (45-min exercise sessions twice a
week) is not effective for children who are aged 6-14 and survived acute lymphoblaststic
leukemia age from 6 to 14(level 2) ( Grade of recommendation C)
bull Using a physical activity intervention (30minutestwice daily for 2-4days) is not
effective for children who are 7 to 18 years of age with soild tumor or AML(level 2)
( Grade of recommendation C)
666
34
Implications for research According to this systematic review and meta-analysis results there are suggestions to
improve the effectiveness of future research on non-pharmacological interventions for
children and young peoplersquos cancer-related fatigue
As the majority of included non-pharmacological interventions for the fatigue of cancer
patients consist of exercise programs future research should also consider various
non-pharmacological interventions in order to understand the effectiveness of different
methods
Regarding the exercise intervention methods and studies should consider multiple
factors including the age or personal condition of the subject the disease stage and the
amount of daily activities Studies should use design prescriptions (eg frequency
intensity duration and type of exercise) and consider the adherence to the measures in
order to enhance the study strength
In measuring the results of non-pharmacological interventions there should be standard
definitions or standard measurement tools to facilitate the following systematic review
and meta-analysis that can subsequently be developed into clinical care guidelines
Reviewing the effectiveness of the current non-pharmacological management of children
and adolescent cancer patients there is still a lack of rigorous RCT research Limited by
the characteristics of cancer there is still a lack of large sample sizes
Potential conflicts of interest There is no conflict of interest
Acknowledgements
Thank you to Dr Rie Konno Research Fellow Joanna Briggs Institute for her help in
assessing studies
667
35
References 1 National Comprehensive Cancer Network( NCCN) in USA NCCN clinical practice
guideline in oncology cancer-related fatigue 2011 2 Ekti Genc R amp Conk Z Impact of effective nursing interventions to the fatigue
syndrome in children who receive chemotherapy Cancer Nursing 200831(4)312-317
3 Childhood Cancer Foundation of ROC (2009March) The classification of diseases
and age sex statistical tables of case Childhood Cancer Foundation of ROC newsletter103105-106
4 Department of Health Executive Yuan ROC (TAIWAN)(2009 March 20)2009 cause of death statistic Health and National Health Insurance Annual Statistics Information Service 2010 June 28Available httpwwwdohgovtwstatisticdatavital statists9898health statistic--lifepdf
5 Chang TK (2007December 8) Common childhood cancer and its treatment Status
Childhood Cancer Foundation of ROC (TAIWAN) 2010 September 23 Available httpwwwccfrocorgtwchildchild_events_readphpe_id=45
6 Hockenberry MJ amp Wilson D Wongs nursing care of infants and children (8th ed) St
Louis MO Mosby 2007
7 Post-White J Fitzgerald M Savik K Hooke MC Hannahan AB amp Sencer SF
Massage therapy for children with cancer Journal of Pediatric Oncology Nursing 2009 26(1)16-28
8Chiang YC Yeh CH Wang WKamp Yang CP The experience of cancer-related fatigue
in Taiwanese children European Journal of Cancer Care 2009 18(1)43-49 9Langeveld NE Grootenhuis M A Voute P A de Haan RJ amp van den Bos C No excess
fatigue in young adult survivors of childhood cancer European Journal of Cancer 200339(2)204-214
10Piper BF Lindsey AM amp Dodd MJ Fatigue mechanisms in cancer patients
developing nursing theory Oncology Nursing Forum 1987 14(6)17-23 11Nail LM amp Winningham ML Fatigue In S L Groenwald M H Forgge M Goodman
amp C H Yarbro (Eds) Cancer Nursing Principles and practice (4 th ed) Boston Jones and Bartlett1997
12Irvine D Vincent L Graydon JE Bubela N amp Thompson L The prevalence and
correlates of fatigue in patients receiving treatment with chemotherapy and
668
36
radiotherapy A comparison with the fatigue experienced by healthy individuals Cancer Nursing 199417(5)367-378
13Hinds PS amp Hockenberry-Eaton M Developing a research program on fatigue in
children and adloescents diagnosed with cancer Journal of Pediatric Oncology Nursing 200118(2)3-12
14Aaronson LS Teel CS Cassmeyer V Neuberger GB Pallikkathayil L Pierce J Press
AN Williams DP amp Wingate A Defining and measuring fatigue Journal of Nursing scholarship 1999 31(1)45-50
15Yeh CH Wang CH Chiang YC Lin Lamp Chien LC Assessment of symptoms reported
by 10- to 18-year-old cancer patients in Taiwan 2009 38(5)738-746 16 Okuyama T Akechi T Kugaya A Okamura H Shima Yamp Maruguchi M
Development and validation of the cancer fatigue scale a brief three-dimensional self-rating scale for assessment of fatigue in cancer patients Journal of Pain amp Symptom Management 2000 19(1) 5-14
17Gibson F Mulhall AB Richardson A Edwards JL Ream E amp Sepion BJ A
phenomenologic study of fatigue in adolescents receiving treatment for cancer Oncology Nursing Forum200532(3)651-660
18Wolfe J Grier HE Klar N Levin SB Ellenbogen JMamp Salem-Schatz S et al
Symptoms and suffering at the end of life in children with cancer New England Journal of Medicine 2000342(5)326-333
19Whiting P Bagnall AM Sowden AJ Cornell JE Mulrow CD amp Ramirez G
Interventions for the treatment and management of chronic fatigue syndrome a systematic review JAMA the Journal of the American Medical Association 2001286(11)1360-1368
20 Kangas M Bovbjerg DHamp Montgomery G H Cancer-related fatigue a systematic
and meta-analytic review of non-pharmacological therapies for cancer patients Psychological Bulletin 2008134 (5)700-741
21Williams PD Schmideskamp J Ridder EL amp Williams AR Symptom monitoring and
dependent care during cancer treatment in children pilot study Cancer Nursing 200629(3)188-197
22Takken T van der Torre P Zwerink M Hulzebos EH Bierings M Helders PJMamp van
der Net J Development feasibility and efficacy of a community-based exercise training
669
37
program in pediatric cancer survivors Psycho-Oncology 200918(4)440-448
23Keats MR amp Culos-Reed SN A community-based physical activity program for
adolescents with cancer (project TREK) program feasibility and preliminary findings
Pediatric hematology and oncology 200830(4) 272-280
24Hinds PS Hockenberry M Rai SN Zhang L Razzouk B I Cremer L McCarthy K amp
Rodriguez-Galindo C Clinical field testing of an enhanced-activity intervention in
hospitalized children with cancer Journal of Pain amp Symptom Management 2007
33(6)686-697
25Chiang YC The effects of ldquo a home-based aerobic exercise interventionrdquo on fatigue
and cardiorespiratory fitness in children with acute lymphoblastic leukemia during the
maintenance stage of chemotherapy Unpublished thesis Taiwan Tao-Yuan 2007
26Langeveld N Ubbink M amp Smets E I dont have any energy The experience of
fatigue in young adult survivors of childhood cancer European journal of oncology
nursing 20004(1)20-28
27 Kisner C Colby L Therapeutic exercise Foundations and techniques 2nd ed Philadelphia PAFA Davies 2007
670
38
Appendix I JBI Critical Appraisal Checklist for Experimental studies
Author__________ Year_________ Record Number__________________
Questions 1 to 4 must be answered ldquoyesrdquo for study to be included in the metashyanalysis
1 Were the participants randomized to study groups
Yes No Not clear
2 Other than research intervention were participants in each groups treated the same
Yes No Not clear
3 Were the outcomes measured in the same manner for all participants
Yes No Not clear
4 Were groups comparable at entry
Yes No Not clear
5 Was randomization of participants blinded
Yes No Not clear
6 Were those assessing outcome blinded to treatment allocation (if outcome not objective such as survival or length of hospitalization)
Yes No Not clear
7 Was allocation to treatment groups concealed from the allocator
Yes No Not clear
8 Was an appropriate statistical analysis used
671
39
Yes No Not clear
9 Were outcomes measured in a reliable way
Yes No Not clear
10 Was there adequate followshyup of participants
Yes No Not clear
Summary
TOTAL
Yes No Not clear
DECISION
Use Reject
Narrative summary only Further information needed
COMMENTS
672
40
Appendix II JBI Data Extraction Tool for Quantitative Studies Authors and Year
Journal Title
Record NumberArticle Reference No
Reviewer
Method
Settings
Participants
Number of participants
Group A Group B Group C
Control Intervention 1 Intervention 2
Interventions
Group A
Control
Group B
Intervention 1
Group C
Intervention 2
Outcome measures
Definition
673
41
Other outcome measures
Outcome description ScaleMeasure
Results
Dichotomous Data
Outcome Control Group
Numbertotal number
Treatment Group
Numbertotal number
Continuous Data
Authorrsquos Conclusions
Comments
Outcome Control Group
Mean amp SD
Treatment Group
Mean amp SD
674
43
Appendix III Details of included studies (N=6)(2720212223) RefNo Author(s)
(years) Title Study question Research
method Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
22 Takken T van der Torre P Zwerink M Hulzebos E H Bierings M Helders P J Mamp van der Net J (2009)
Development feasibility and efficacy of a community-based exercise training program in pediatric cancer survivors
To develop a 12-week home-based exercise training program (comprising aerobic and strength exercises) for children who survived ALL and to study itrsquos feasibility and efficacy
Pre-post test design
No comparsion group
Survived ALL(N=9)ages 6-14 years
1anthropometry 2 muscle strength 3functional mobility 4cardio-pulmonary
exercise test 5Fatigue
1 Feasibility questionnaire 2 anthropometry electronic scale and a wallmounted stadiometerHarpenden skin fold calipers 3 muscle strength handheld dynamometer 4functional mobility Timed Up
and Go test (TUG) 5cardio-pulmonary exercise test electronically braked cycle ergometer 6Fatigue(mean)CSI-20 (subjective experience of fatigueconcentrationmotivationphysical activity)
112-week exercise training program
2 Patients were assessed before (T0) and after (T1) 12 weeks of training
1 muscle strength execapacity functional moand fatigue showed nosignificant differences between pre(meanplusmnSD415plusmn147) and post training(meanplusmnSD3687)
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
7 Post-White J Fitzgerald M Savik K Hooke M C Hannahan A B amp Sencer S F (2009)
Massage therapy for children with cancer
To determine whether 4 weekly sessions of massage compared with 4 quiet-time control conditions would reduce anxiety cortisol levels fatigue nausea and pain in children with cancer undergoing chemotherapy and would reduce anxiety fatigue and mood disturbance in a parent
2-period crossover design (Randomized)
quiet-time
control
sessions
Children with cancer 1 to 18 years of age Twenty-three childrenparent dyads were enrolled 17 completed all data points
children 1relaxation 2symptoms 3 fatigue
parents
1anxiety 2 fatigue
children 1relaxation (heart and respiratory rates blood pressure and salivary cortisol level)
2symptoms (pain nausea anxiety 3 fatigue 1-2y3-6yLansky Play Performance Scale (PPS) 7-13y
1 4 weekly massage (MT) sessions alternated with 4 weekly quiet-time(QT) control sessions
2 children included presession and postsession vital signs (heart rate respiratory rate blood pressure) and self-report (parent proxy report for age 1-2 years) of pain nausea and anxiety Fatigue was measured before sessions 1 and 4 and at each follow-up Parent measures
included anxiety fatigue and mood states
1Massage was moreeffective than quiet tireducing heart rate inchildren anxiety in cless than age 14 yeaparent anxiety 2There were no sign
changes in blood pcortisol pain naufatigue (no state d
3 Children reported tmassage helped thebetter lessened theirand worries and hadlasting effects than q
675
44
14-18yChild Fatigue Scale (CFS) (frequency
intensity) 2 parents anxiety and fatigue
676
45
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
24 Hinds P S Hockenberry M Rai S N Zhang L Razzouk B I Cremer L McCarthy K amp Rodriguez-Galindo C (2007)
Clinical field testing of an enhanced-activity intervention in hospitalized children with cancer
To determine the feasibility of an
enhanced physical activity EPA intervention in children and adolescents hospitalized to receive chemotherapy for a solid tumor or AML and to assess the sleep and fatigue outcomes of the intervention using two different statistical approaches to analyze the longitudinal symptom data
randomized prospective two-site and two-group pilot study
Standard care Twenty nine patients (25 with a solid tumor and 4 with AML)ages 7-18 years
1 sleep duration 2 sleep efficiency 3 fatigue
1sleep duration sleep efficiency The
Wrist Actigraph The Daily Sleep Diary-Parent 2 fatigue (mean) The Fatigue Scale(FS-C) for 7-12 (intensity) The Fatigue Scale(FS-A) for 13-18 The Fatigue Scale Parent Version (FS-P) The Fatigue Scale Staff Version (FS-S)
1enhanced physical activity (EPA) (hospital-based 30 minutes
twice daily for 2-4 days) 2 T0On the day of admission
(Day 0 or baseline)patient and parents completed the fatigue instruments and a team member applied the actigraph Patients wore the wrist actigraph T1 from Day 0 to 2 or 3 consecutive days (Days 0e3) In addition the patient same parent and staff nurses completed the daily sleep and fatigue reports in the late afternoons of Days 1-3
1 ANOVA model slesignificantly more the experimental athe control arm whdifferences from bsleep efficiency vaaveraged and com
2 The patient-reported mean fatigue scoresarms were higher amadolescents than for
3 The mixed model anarevealed no significandifferences in patientfatigue between
the two study arms otime( no final result iSD only give mixed result)
677
46
23 Keats M
R amp Culos-Reed S N (2008)
A community-based physical activity program for adolescents with cancer (project TREK) program feasibility and preliminary findings
To examine the
feasibility of a
theoretically-based
physical activity (PA)
intervention in
adolescents with
cancerand
examination of the
impact of the
program on
participant QOL
including social
emotional and
physical
well-being(including fatigue)
Repeat measures longitudinal design
No comparsion group
10 adolescents(Lymphoma(4)leukemia(4)CNS tumor(1)germ cell tumor(1)) ages 14-18 years
1physical fitness 2quality of life (QOL) 3PA behavior 4fatigue
1 Feasibility was assessed by participant recruitment attendance and adherence
2physical fitness Fitnessgram 3quality of life (QOL) Pediatric Quality of Life Inventory (PedsQL) 4PA behavior leisure score index (LSI) 5fatigue (mean) pediatric Quality of life
Multidimensional Fatigue Scale (Peds QL-MFS)
(Generalsleepcognitive fatigue)
116week physical activity (PA)
2 total PA physical fitness and overall QOL was assessed at 5 different intervals T0 preintervention (baseline) T1midintervention (after the
first 8 wk) T2 postintervention
(16 wk) T3 3-months
postintervention T4 1-year poststudy
initiation
1 from baseline -wkssig Improvementstotal PA physfitness and Qgeneral fatigue(meanplusmnSD 796plusmn135)
2 from baseline to 3FUsig Improvin general fatigue(meanplusmnSD824plusmn131)slefatigue(meanplusmnSD755plusmn191)totafatigue(meanplusmnSD778plusmn150)
3at 1 years FUsImprovements in sleeprest fatigue(meanplusmnSD725plusmn203)total (meanplusmnSD 763plusmn
678
47
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
2 Gene R E amp Conk Z (2008)
Impact of Effective Nursing Interventions to the Fatigue Syndrome in Children Who Receive Chemotherapy
1 to examine the effects of an effective nursing intervention to the fatigue syndrome of children 7 to 12 years of age who receive chemotherapy 2Tto examine the relationship between fatigue and demographic variables (age sex) diagnoses ([ALL AML] lymphoma) and therapy-related variables (eg level of hemoglobin
experimental randomized controlled study
Routine nursing care
A total of 60 children who are 7-12 years of age(a new diagnosis of ALL AML or lymphoma and receiving for the first time after being diagnosed a 7- to 10-day chemotherapy treatment )
fatigue The Fatigue Scale(FS-C) for 7-12 (intensity)
The Fatigue Scale Parent Version (FS-P)
1 effective nursing interventions(45- 60mdaya week)education about the fatigue with the chemotherapy and fatigue handbook 2 T1 After a 7-day period the children
and parent were evaluated with the Fatigue Scale
1The difference betwthe 2 mean values wafound to be statisticallsignificant 2 statistically significadifference was found between the Fatigue Scale-Child mean scothe experimental (272the control group (4213)children
679
48
25 Chiang et
al(2007)
The effects of ldquo a home ndashbased aerobic exercise interventionrdquo on fatigue and cardiorespiratory fitness in children with Acute Lymphoblastic Leukemia during the maintenance stage of chemotherapy
To examine the effect of ldquo a home ndashbased aerobic exercise interventionrdquo on fatigue and cardiorespiratory fitness in children with Acute Lymphoblastic Leukemia during the maintenance stage of chemotherapy
Quasi-experi -mental
Routine
nursing care
14 pediatric oncology patients in the experimental group and 10 in control group who were matched by age and sex ages7-18 years
1Cardiorespiratory fitness
2Fatigue
1Cardiorespiratory fitness Physical Activity Recall
VO2maxHR peak 6MWT
2 Fatigue PedsQL-MFS(Generalsleepcognitive fatigue)
1A six-week home-based aerobic exercise intervention 2 8 time points T0 baseline T1-T6 every week during the
intervention(6 weeks) T7 post intervention T8 follow-up (one month after
the end of the home-based exercise program)
1 For intent-to ndash treatthe findings indicated are no intervention efftime differences by anon the subscale of fat2 For per-protocol angeneral fatigue( mean422plusmn402) was the osubscale that was siglower for children whothe exercise interventthose in control groupfollow-up assessmentmonth after the compintervention) 3 The VO2peak are significantly improvingexperimental group atbaseline- and post-intassessment The VO2was significantly highechildren who were in experimental group thcontrol subjects at post-intervention assefor the per-protocol an
680
49
Appendix IV Instrument used to measure fatigue
Name Instrument
developers
Description Used in
age in
ref
Reliability
Consistency of
instrument
Checklist Individual Strength
(CIS)22
Vercoulen et
al1996
20 items using 7-point Likert scale of
fatigue To measure four aspects of
fatiguesubjective experience
contractionmotivation physical
Activity
6-14 Not reported
Child Fatigue Scale (CFS)7 Hockenberry
et al2003
14 items 2 part questionnaire frequency
(yes or no) 5-point Likert scale of the
intensity of any yes responses
7-13
14-18 α073-o84
The Fatigue Scale for 7-12
year Olds (FS-C)224
Hockenberry
et al
14 items provide a fatigue intensity score
5-point Likert scale
7-12 αo84
The Fatigue Scale for 13-18
year Olds (FS-A)24
Hockenberry
et al
14 items provide a fatigue intensity score
5-point Likert scale
13-18 α076-o96
Pediatric Quality of life
Multidimensional Fatigue
Scale (Peds QL-MFS)2325
Varni2002 18 items to measure three aspects of
fatigueGeneralsleepcognitive
14-18 Not reported
681
50
Appendix V Excluded studies and reasons for exclusion
Baggott C Dodd M Kennedy C Marina N Miaskowski C Multiple Symptoms in Pediatric Oncology
Patients A Systematic Review Journal of Pediatric Oncology Nursing 2009 Nov-Dec 27(6)
325-339
Reason for exclusion Not outcome of interest
Barlow JH Ellard DR Psycho-educational interventions for children with chronic disease parents and
siblings an overview of the research evidence base Care Health amp Development 2004 Nov
30(6)637-45
Reason for exclusion Not outcome of interest
Bedider S Moyer CA Randomized controlled trials of pediatric massage A review Evid Based
Complement Alternat Med 2007 Mar 4(1)23-34 Epub 2006 Nov 3
Reason for exclusion Not outcome of interest
de Nijs EJ Ros W Grijpdonck MH Nursing intervention for fatigue during the treatment for cancer Cancer
Nursing 2008 31(3)191-206
Reason for exclusion Not population of interest
Edwards JL Gibson F Richardson A Sepion B Ream E Fatigue in adolescents with and following a
cancer diagnosis developing an evidence base for practice European Journal of Cancer 2003
Dec 39(18)2671-80
Reason for exclusion Not experimental or quasi-experimental study
Hinds PS Hockenberry-Eatan M Developing a research program on fatigue in children and adolescents
diagnosed with cancer Journal of Pediatric Oncology Nursing 2001 Mar-Apr 18(2 Suppl
1)3-12
Reason for exclusion Not experimental or quasi-experimental study
Hockenberry-Eaton M Hinds PS Alcoser P ONeill JB Euell K Howard V Gattuso J Taylor J Fatigue in
Children and Adolescents With Cancer Journal of Pediatric Oncology Nursing 1998 July
15(3)172-182
Reason for exclusion Not experimental or quasi-experimental study
Jean-Pierre P Mustian K Kohli S Roscoe JA Hickok JT Morrow GR Community-based clinical oncology
research trials for cancer-related fatigue The Journal of Supportive Oncology 2006 Nov-Dec
4(10)511-6
682
51
Reason for exclusion Not population of interest
Kangas M Bovbjerg DH Montgomery GH Cancer-Related Fatigue A Systematic and Meta-Analytic
Review of Non-Pharmacological Therapies for Cancer Patients Psychological Bulletin 2008 Sep
134(5)700-41
Reason for exclusion Not population of interest
Lotfi-Jam K Carey M Jefford M Schofield P Charleson C Aranda S Nonpharmacologic strategies for
managing common chemotherapy adverse effects A systematic review Journal of Clinical
Oncology 2008 Dec 1 26(34)5618-29 Epub 2008 Nov 3
Reason for exclusion Not outcome of interest
Marchese VG Chiarello LA Lange BJ Effects of physical therapy intervention for children with acute
lymphoblastic leukemia Pediatr Blood Cancer 2004 Feb42(2)127-33
Reason for exclusion Not outcome of interest
Meeske KA Siegel SE Globe DR Mack WJ Bernstein L Prevalence and correlates of fatigue in
long-term survivors of childhood leukemia Journal of Clinical Oncology 2005 Aug 20
23(24)5501-10
Reason for exclusion Not intervention study
Minton O Richardson A Sharpe M Hotopf Stone P A systematic review and meta-analysis of the
pharmacological treatment of cancer-related fatigue J Natl Cancer Inst 2008 Aug 20
100(16)1155-66 Epub 2008 Aug 11
Reason for exclusion Not population and intervention of interest
Mustian KM Morrow GR Carroll JK Figueroa-Moseley CD Pascal JP Williams GC Integrative
nonpharmacologic behavioral interventions for the management of Cancer-Related fatigue The
Oncologist 2007 12(1)52-67
Reason for exclusion Not population of interest
Neill J Belan I Ried K Effectiveness of non-pharmacological interventions for fatigue in adults with
multiple sclerosis rheumatoid arthritis or systemic lupus erythematosus a systematic review
Journal of Advanced Nursing 2006 Dec 56(6)617-35
Reason for exclusion Not population of interest
Rheingans JI A systematic review of nonpharmacologic adjunctive therapies for symptom management
Journal of Pediatric Oncology Nursing 2007 24(2) 81-94
683
52
Reason for exclusion Not outcome of interest
Rheingans JI Pediatric oncology nursesrsquo management of patients symptoms Journal of Pediatric
Oncology Nursing 2008 Nov 25(6) 303-11
Reason for exclusion Not outcome of interest
San Juan AF Fleck SJ Chamorro-Vintildea C Mateacute-Muntildeoz JL Moral S Peacuterez M Cardona C Del Valle MF
Hernaacutendez M Ramiacuterez M Madero L Lucia A Effects of an intrahospital exercise program
intervention for children with leukemia Medicine amp Science in Sports amp Exercise 2007 Jan
39(1)13-21
Reason for exclusion Not outcome of interest
Sanford SD Okuma JO Pan J Srivastava DK West N Farr L Hinds PS Gender differences in sleep
fatigue and daytime activity in a pediatric oncology sample receiving dexamethasone Journal of
Pediatric Psychology 2008 Apr 33(3)298-306 Epub 2007 Nov 17
Reason for exclusion Not experimental or quasi-experimental study
Schmitz KH Holtzman J Courneya KS Macircsse LC Duval S Kane R Controlled physical activity trials in
cancer survivors a systematic review and meta-analysis Cancer Epidemiol Biomarkers Prev
2005 Jul 14(7)1588-95
Reason for exclusion Not population of interest
van Brussel M Takken T Lucia A van der Net J Helders PJ Is physical fitness decreased in survivors of
childhood leukemia A systematic review Leukemia 2005 Jan 19(1)13-7
Reason for exclusion Not population of interest
Whiting P Bagnall AM Snowden AJ Cornell JE Mulrow CD Ramirez G Interventions for the treatment
and management of chronic fatigue syndrome JAMA 2001 Sep 19 286(11)1360-8
Reason for exclusion Not intervention of interest
Whitsett SF Gudmundsdottir M Davies B McCarthy P Friedman D Chemotherapy-related fatigue in
childhood cancer correlates consequences and coping strategies Journal of Pediatric
Oncology Nursing 2008 Mar-Apr 25(2)86-96 Epub 2008 Feb 29
Reason for exclusion Not experimental or quasi-experimental study
Winner C Muumlller C Hoffmann C Boos J Rosenbaum D Physical activity and childhood cancer Pediatr
Blood Cancer 2010 Apr 54(4)501-10
Reason for exclusion Not research study
684
53
Wu M Hsu L Zhang B Shen N Lu H Li S The experiences of cancer-related fatigue among Chinese
children with leukaemia A phenomenological study Journal of Nursing Studies 2010 Jan
47(1)49-59 Epub 2009 Aug 25
Reason for exclusion Not experimental or quasi-experimental study
Yeh CH Chiang YC Lin L Yang CP Chien LC Weaver MA Chuang HL Clinical factors associated with
fatigue over time in paediatric oncology patients receiving chemotherapy British Journal of
Cancer 2008 Jul 8 99(1)23-9 Epub 2008 Jun 24
Reason for exclusion Not experimental or quasi-experimental study
685
15
Ovid MEDLINE 1966 ndash 2010 CINAHL Plus with Full Text 1960 ndash2010 EMBASE ProQuest Dissertations amp theses 1990-2010 Electronic theses and dissertations system 1956(abstract)1990(full text)-2010 MEDNAR Index to Taiwan periodical literature 1970-2010 Electronic thesis and dissertation system (Chinese) 1990-2010
Keyword search terms
1Types of studies experimental study random quasi-experimental study實驗性研究隨
機類實驗性研究
2 Types of participants childchildren adolescents pediatric cancer and oncology兒童
青少年兒科癌症腫瘤
3 Types of interventions non-pharmacological interventions massage exercise fitness
physical activity cognitive behavioral stress management energy conservation
sleep therapy relaxation distraction and psycho-education非藥物性處置按摩運動
身體活動認知行為壓力處置能量保存睡眠治療放鬆轉移注意力衛教
4 Types of outcome measures fatigue cancer-related fatigue loss of energy levels of
tiredness tired side effect symptoms疲憊癌性疲憊疲倦合併症症狀
Methods of the Review
Assessment of methodological quality Papers selected for retrieval were assessed by two independent reviewers for
methodological validity prior to inclusion in the review using the standardised critical
appraisal instruments (Appendix I) from the JBI-SUMARI (Joanna Briggs Institute
Systems for the Unified Management Assessment and Review of Information package)
Any disagreements that arise between the reviewers were resolved through discussion
648
16
with a third reviewer
Data extraction Data was extracted from papers included in the review using standardised data
extraction tool (Appendix II) from the JBI-SUMARI Details of eligible studies were
extracted and summarised independently by two reviewers
Data Synthesis
All data analysissynthesis were made using the JBI-SUMARI The studies were
assessed for clinical heterogeneity by considering the settings populations interventions
and outcomes Where possible these binary outcomes were analyzed by calculation of
the Odds Ratio with the 95 CI The weighted mean difference was calculated if the
pooled studies have used the same scale for continuous data The standardized mean
difference was calculated for continuous data measuring the same outcome on a
different scale In studies where statistical pooling of results was inappropriate the
findings were considered for inclusion as a narrative summary
Results The findings from the systematic review are presented first Followed by the results from
the meta-analysis component of this review
Description of studies From database search and hand search a total of 76 papers were identified Thirty
papers were then excluded because they did not meet the inclusion criteria Forty-six
full text were retrieved for further consideration for inclusion Of the 30 excluded reasons
for exclusion were follows 11articles were duplicated eight articles did not meet
649
17
participant inclusion criteria eight articles did not meet outcome criteria and nine articles
were correlation studies or discussion papers others articles were unclear reporting In
total after sorting six papers have been included in this article Figure 1 displays the
process used to identify relevant articles for inclusion in the systematic review
Figure 1 Stages of searching and inclusionexclusion of references for the review
Potentially relevant English-language and Chinese- language Studies Identified
Electronically and hand search (n=76)
Duplicate (n= 11) Papers excluded after evaluation of abstract (n=19)
Papers retrieved for detailed examination (N=46)
Papers excluded after review of full paper
(n=40)
Papers assessed for methodological
quality (n=6)
Papers included in systematic review
(n=6)
Methodological Quality
Of the six included articles 2722232425 two articles were RCT design224 with score 7 out
of 10 each paper from Critical Appraisal Checklist and four articles used
650
18
quasi-experimental design7222425 with socre 5 to 6 out of 10 because the quality of
the whole papers is still acceptable therefore these six articles were accepted after
primary reviewer and secondary reviewerrsquos decision
Randomisation
In two RCT articles224 one study24 used to a computer-generated program operated by
the St Jude Protocol and Data Management System to randomize the sample Another
study2 didnrsquot address how randomization was done
Allocation concealment
No studies reported allocation concealment
Intention-to-treat analysis
One quasi-experimental design7 stated Intention-to-treat analysis
Adequate follow up
The follow-up periods included 2or 3 days24 7 days2 4 week7 one month25 6 week25 12
week2216 week23 and 1 year23
Baseline comparability of groups
Three 22425 of six studies had baseline comparability in terms of age sex diagnosis
race institution duration of illness
Blinded outcome assessment
No studies used blinded outcome assessment The researchers including study team
patients staff and families were not blinded to the patientrsquos group assignment
Characteristics of included studies
651
19
There were six studies related to interventions designed to cancer-related fatigue for
pediatric patients than there are for adults There are a total of six including five
English-language papers 27222324 and one Chinese-language paper 25 ranging in year of
publication from 2007 to 2009
Patient characteristics
The research subjects of four papers included both school-aged children and
adolescents 7222324 one papers involved mainly adolescents25 and one paper sampled
only school-aged children 2 the range in ages was between six-18 years The number of
patients included in the samples ranged from nine to 60 The sources of case data were
from both outpatients and hospitalized children The types of cancer included acute
lymphoblastic leukemia (ALL) solid tumors acute myeloid leukemia (AML) and
lymphoma Overall ALL was the most commonly studied cancer type The stage of the
disease varied in these reports some patients were in the maintenance stage of
chemotherapy25 some had just received their first round of chemotherapy224 some had
completed two courses of treatments lasting 4-8 weeks each 7 and some had entered
the survivor stage 2223
Countries
Two RCTrsquos 2 24 were conducted in the USA There were four quasi-experimental design
studiesThree studies conducted in the USA7 22 23 and one in Taiwan25
Intervention types
652
20
The interventions included exercise training programs 2225 physical activity 2324
massage therapy 7 and health education 223 exercise training and physical activity as
an intervention method given in three different settings home 22 25 community 23 or
hospital 24 The studies used different types of exercise interventions including
home-based aerobic exercise use a Video Compact Disc 25 use of a bicycle-style
exerciser 24 aerobics2223 and various types of physical activities2 and strength-building
exercises 2223 The intensity of the exercise varied and often included gradual warm-up
exercises a period of main exercise and a cool down period For these studies2023 the
target exercise intensity was a heart rate of gt90 of the maximum heart rate (HR max) or
the increase in the percentage of heart rate reserve ( HRR) of 40-60
The number of weeks for the exercisephysical activity interventions duration including
2-4 days 24 6 weeks25 12 weeks22 and 16 weeks23 The frequency of exercise ranged
from 2-3 times per week to twice a day Typical duration of exercise ranged from 10 to 45
minutes There are three papers using exercise interventions based on ACSM (American
College of Sports Medicine) 2225 recommendations and one of these used an Activity
pyramid from the ACSM to determine intensity 24
One article did not clarify the type of exercise intervention or the reasons for their choices
23 In addition there was an article focusing on massage therapy 7 as an intervention in
this study the experimental group received four weeks of massage therapy either in the
clinic or in the patientrsquos room the therapy was applied by a professional masseur and
targeted the back legs arms chest stomach and face of the children However the
frequency of massage sessions per week and the duration of the massages were not
653
21
given There is another article about intervention measures combine health education
and physical activity 2 In this study patients were informed about the following (1) health
education patients received daily education about chemotherapy-related fatigue and
information from a health education manual written by the author (2) encouragement for
children to engage in activities such as listening to music drawing and reading and (3)
physical activity which involved walking along the corridors of the ward for 10-15 minutes
These health education measures were presented for 45-60 minutes a day for a total of
seven days The study design for non-pharmacological interventions used control groups
that included primarily people who had received standard treatment or people who did
not receive an exercise intervention
Outcome measures
Five measurement tools were used in this group of seven papers concerning childrenrsquos
fatigue (Appendix IV) Because those studies included both school-age children and
adolescents the following descriptions will be differentiated by age Fatigue
measurements for school-aged children with cancer include the following the Child
Fatigue Scale (CFS) 7 a scale that measures the frequency and intensity of fatigue and
the Fatigue Scale for 7-12 year Olds (FS-C) 224 a scale that can be used to evaluate the
intensity of fatigue On the other hand fatigue measurements for adolescent cancer
patients include the following the Fatigue Scale for 13-18-year-olds (FS-A) 24 a measure
that can help evaluate fatigue levels the Pediatric Quality of Life Multidimensional
Fatigue Scale (Peds QL-MFS) 2325 a tool that can be divided into three sub-scales to
understand the general cognitive and sleep rest components of fatigue and finally the
CIS-20 for school-age children and adolescents 22 a scale that measures four levels of
654
22
fatigue namely subjective experience attention motivation and physical activity Two
studies used the Peds QL-MFS scale to measure fatigue2325
Meta-analysis results Two studies of the included papers failed to provide sufficient raw data they could not be
included in the meta-analysis Hinds et al 24 did not include post-test data Genc et al 2
provided no pre-test data PostWhite et al7 reported that fatigue after the health
education intervention was not statistically different but they presented the results
without presenting fatigue-related data Therefore the meta-analysis included three
studies 222325
The heterogeneity of studies was analyzed with Chi square statistics and no statistical
significance was found Therefore the data was combined in meta-analysis according to
exercise intervention on fatigue In addition there were three articles using the Peds
QL-MFS as a research tool to examine childrenrsquos improvements in fatigue Among these
Keats 22 and Chiang 24 present the effectiveness of exercise interventions using three
subscales Therefore the meta-analysis also analysis of the effects of these exercise
intervention measures on three subscales of Peds QL-MFS general fatigue sleep rest
fatigue and cognitive fatigue
The effectiveness of exercise intervention for fatigue We analyzed the exercise intervention effect on fatigue A total of 2 studies 22 23 were
included Takken et al 22 used community-based exercise training program to reduce
fatigue of children 6 to 14 years (mean 93y) of age who survived ALL Fatigue
measurement by Checklist Individual Strength (CIS) after 12-week of training fatigue
655
23
show no significant differences between pre (meanplusmnSD 415plusmn147) and post training
(meanplusmnSD368plusmn217) but fatigue change from baseline mean reduction of 11
Keats et al23 although used community-based physical activity program to reduce fatigue
for adolescents 14 to 18 years of age (mean162 y) with cancer (Lymphoma leukemia CNS
tumor germ cell tumor) Studies used fatigue by PedsQLMFS Results show general fatigue
from baseline to 8 weeks and to 3 months follow up significantly improves General
fatigue sleeprest fatigue and total fatigue from baseline to 3 months follow up showed
significant improvements Sleeprest fatigue and total fatigue at 1 years followed up were
significant improvements
Figure 2 shows the overall effect of exercise intervention in children and adolescents with
cancers with a focus on improving fatigue Due to the lower heterogeneity (p>005) the
fixed effects model was used to pool the data for meta-analysis (Overall effect size=
-006 95 Confidence Interval (CI) -070 to 058) A result did not indicate a statistically
significant difference (p = 087)
656
24
Figure2 Meta-analysis results of exercise intervention on fatigue
In addition Keats23 and Chiang25 used the three sub-scales of Peds QL-MFS to
determine the general cognitive and sleep rest components of fatigue The following
present the effectiveness of exercise interventions using three subscales including
general fatigue sleep rest fatigue and cognitive fatigue 2325
Chiang et al 25 used a 6- week home-based aerobic exercise intervention to reduce
fatigue of children 7 to 18 years (mean age at experimental group was 1088 y in control
group was 1247 y) of age who with acute lymphoblastic leukemia Fatigue measurement
by Peds QL-MFS after training For intent-to ndash treat analysis the findings indicated that
there are no intervention effects and time differences by any items on the subscale of
fatigue For per-protocol analysis general fatigue( meanplusmnSD 422plusmn402) was the only
subscale that was significantly lower for children who received the exercise intervention
than those in control group at follow-up assessment (one month after the completion of
intervention)
Keats et al23 although used community-based physical activity program to reduce fatigue
for adolescents 14 to 18 years of age (mean162 y) with cancer (Lymphoma leukemia
CNS tumor germ cell tumor) Both studies used fatigue by PedsQLMFS Results show
general fatigue from baseline to 8 weeks and to 3 months follow up significantly improves
657
25
General fatigue sleeprest fatigue and total fatigue from baseline to 3 months follow up
showed significant improvements Sleeprest fatigue and total fatigue at 1 years followed
up were significant improvements
The effectiveness of exercise intervention for general fatigue
The impact of the exercise interventions upon levels of general fatigue was also analysed
The heterogeneity was low (p>005) Therefore the fixed effects model was used to
examine the effectiveness The effect size is -076 indicating a statistically significant
difference (p = 001 95 CI -135 to -017 Fig 3) The evidence suggests that exercise
intervention can reduce general fatigue in children with cancer
Fig 3 Meta-analysis results of exercise intervention for general fatigue
The effectiveness of exercise intervention for sleep rest fatigue
The following is the result of the meta-analysis of the effectiveness of exercise
interventions on sleep rest fatigue First the heterogeneity test was conducted with P gt
005 representing small heterogeneity and the fixed effects model was used Fig 4
shows the effect size is -035 indicating no statistically significant differences (p = 023
95 CI-092 to 022 Fig 4)
658
26
Fig 4 Meta-analysis results of exercise intervention for sleep rest fatigue
The effectiveness of exercise intervention for cognitive fatigue Lastly the following data reports the results of meta-analysis of the effectiveness of
exercise interventions for cognitive fatigue The heterogeneity was p>005 then the
fixed effects model was used The effect size is -035 indicating no statistically significant
differences (p = 024 95 CI-092 023 Fig 5)
Fig 5 Meta-analysis results of exercise intervention for cognitive fatigue
Narrative presentation of remaining included studies
Three studies were not included in meta-analysis Post-White et al7 one of the aims in
this study was to examine the effect of massage therapy on fatigue in children with
cancer The study was a quasi-experimental design Twenty-three childrenparent dyads
were enrolled 17completed all data points Children with cancer ages 7 to 18 years
received at least 2 identical cycles of chemotherapy and one parent participated in the
2-period crossover design in which 4 weekly massage sessions (MT) alternated with 4
659
27
weekly quiet-time (QT) control sessions There were no significant changes in fatigue in
children over the 4-week MT or QT conditions either independently (change over time) or
when we compared fatigue by condition
The lack of effect of massage on fatigue may be the difficulty some children had in
differentiating fatigue from being relaxed underscores the challenge of measuring fatigue
in children Some children interpreted being tired or relaxed as having greater fatigue
because they felt like lying around and sleeping or felt unmotivated to do their usual
activities all measures of fatigue in the instrument used in the study
Hinds et al24conducted a prospective two-site randomized controlled pilot study to
assess the feasibility of an enhanced physical activity (EPA) intervention in hospitalized
children and adolescents receiving treatment for a solid tumor or for acute myeloid
leukemia (AML) Twenty-nine patients (25 with a solid tumor and 4 with AML) participated
age range from 736 to 1816 (mean 1248 y) The EPA intervention selected was
pedaling a stationary bicycle-style exerciser (Chattanooga Peddler Deluxe Bio-Teck
Medical Memphis TN) for 30 minutes twice daily for 2 to 4 days of hospitalization The
mixed model analysis revealed no significant differences in patient reports of fatigue
between the two study arms or over time
Genc et al2 conducted a RCT involving children with cancer who are 7 to 12 years of age
and receiving chemotherapy treatment to determine the impact of educational
intervention by nurses on decreasing the fatigue syndrome The research sample was
composed of a total of 60 children with cancer with 30 children being included in the
660
28
experimental group (mean age 923)and 30 children included in the control group (mean
age 937) with their mothers In the experimental group after the 7th to 10th day of the
chemotherapy treatment throughout a week the researcher conducted the nursing
interventions every day for 45 to 60 minutes In the control group routine nursing
interventions were carried out The experimental group received education about the
fatigue with the chemotherapy and fatigue handbook was given which was developed by
the authors Children and mothers were consulted for including activities that could
decrease fatigue which were described as effective interventions A statistically
significant difference was found between the Fatigue Scale-Child mean scores of the
experimental (2723) and the control group (4213) The results suggest that fatigue of
children with cancer can be reduced by implementing appropriate nursing interventions
(t=567 Plt00)
Discussion The purpose of this systematic review was to determine the effectiveness of
non-pharmacological interventions specifically targeting fatigue for children and
adolescents with cancer undergoing chemotherapy or after receiving chemotherapy
Included articles about the effectiveness of non-pharmacological interventions for
children and adolescents with cancer were published between the years of 2007 and
2009 Although interventions for cancer fatigue for adults have been extensively studied
it can be seen from either the title of the paper or related content that an intervention
study on children was a pilot study or a feasibility study Representing a field in its early
stage these studies show that the fatigue issues with young cancer patients have only
recently been taken seriously
661
29
The results of our meta-analysis include measurement of the four performance indicators
fatigue and general fatigue sleep rest fatigue and cognitive fatigue The results show
that there is a statistically significant difference only in the domain of general fatigue
using an exercise intervention for children with cancer can improve the degree of fatigue
with the effect size reaching 0671 Other results do not indicate significant differences
The reasons may include the following
1 Characteristics of the cancer The exhaustion from cancer occurs not only during cancer treatment but also in during
long-term survival a time during which patients may continue to be affected by this
symptom 8 26 Therefore when using intervention measures to improve fatigue
circumstances should be considered such as the process of the treatment and the course
or stage of the disease Because cancer patients will experience different forms of
treatment or courses of treatment the disease itself or treatment differences should be
considered in the choice of intervention Even chemotherapy drugs should be taken into
consideration For example a period of general steroid treatment can increase patientsrsquo
fatigue In those studies of children with cancer few studies looked solely at one type of
cancer most studies included a variety of cancer patients Furthermore most studies do
not clearly explain the stage of the disease or course of treatment and most do not
include treatment variables in the control group Moreover children with cancer may
have different levels of physical function
2 Research design The sample size Currently there are few studies with large sample size and a rigorous
RCT design due to the small number of papers available for analysis The sample size
included in our studyrsquos data analysis is between 20 and 42 people this small sample size
will affect the power available to evaluate outcome variables
Although most of the non-pharmacological interventions still use exercise and physical
activity and these studies overall show better results for fatigue as compared with
controls more research is still needed to further confirm the efficacy of these findings
662
30
The dropout rate in the evaluated research varies a great deal ranging from 5 to 45
these dropout rates may result from the characteristics of the research subjects or the
lengthy time involved in participating in these studies The research data with a high
turnover rate might not reflect the actual outcomes of participation in exercise and the
quality of the research contained in articles with high subject turnover rates may be
lower
Exercise doses and time The exercise doses needed to reduce fatigue cannot be
determined additionally the amount of exercise completed by the patient is also
inconsistent interventions vary between 2-3 times per week and two times a day and
exercise duration varies between 10 and 45 minutes each time Furthermore the study
interventions vary in length between a couple of days and a long period of 16 weeks The
data collection times are different some were measured 12 weeks after the intervention
began some were measured during the 6 weeks of intervention some were measured
three months after the intervention was finished and some were measured after one
year
In addition disease-related symptoms decrease childrenrsquos willingness to participate in
exercise interventions inappropriate exercise intervention programs may actually
increase childrens fatigue In addition the children in the study are still developing
physically it is important to consider ways to design an interesting exercise intervention
to increase the compliance of patients in order to improve the effectiveness Although
intervention programs in the hospital or in a community sports center can improve the
effectiveness because they provide supervision the feasibility of these programs is
questionable However if the program is home-based the children need to be
supervised by parents in order to improve their compliance in doing the exercises
Furthermore regarding the nature of the intervention the results from this study indicate
that the researched non-pharmacological interventions include the following exercise
training programs physical activity massage therapy and health education interventions
However according to the National Comprehensive Cancer Network 1 clinical guidelines
663
31
for cancer non-drug measures for cancer fatigue can be separated into five categories
(1) activity enhancement (2) psychosocial interventions such as cognitive behavioral
therapy (CBT) stress management relaxation techniques and support groups (3)
attention-restoring therapy (4) nutritional consultation and (5) cognitive behavioral
therapy specifically targeting sleep disturbance Researchers have also suggested that
psychosocial interventions should be included in the future research for children with
cancer-related fatigue 22
(2) The measurement tools in the study The assessment of fatigue can be
one-dimensional or multidimensional One-dimensional assessment can help understand
the severity of fatigue symptoms however multidimensional scales are often more
credible Therefore when measuring cancer-related fatigue researchers should consider
whether there is a uniform definition of fatigue or a standardized tool for measuring
fatigue in order to facilitate further systematic meta-analyses and further develop the
clinical care guidelines
Limitations of the review The present review has some potential limitations First the low methodological quality
may influence the result Although exercise intervention seems promising quality of the
RCTs was generally quite low Future studies require better design and reporting if
methodological issues to establish evidence-based nonpharmcologic intervention
Second the identified studies covered only a limited types of nonpharmcological
intervention especially in exercise intervention The guidelines for cancer-related fatigue
in NCCN (2011)1 referred to more interventions than the ones included in this review
such as cognitive behavioral therapy and nutrition consultation Thirdly the small sample
size and effect size could be potentially having led to underpowered approach for
detecting the effects on fatigue Therefore we recommend that as research continues to
grow a re-analysis can be undertaken Fourthly Combining data in meta analysis from
664
32
studies where the ages were quite different is a potential source of heterogeneity and
may affect the interpretation of the results
Conclusion At present clinical treatment is widely used for cancer patients However child and
adolescent cancer patients often experience various side effects which cause short-term
or long-term discomfort both physically and psychologically In particular with the
increasing cure rate cancer related fatigue during or after treatment has become an
important issue This study result provided positive effect of exercise intervention on
general fatigue
Implications for practice The results of this systematic review and meta-analysis show that exercise interventions
can effectively improve the level of general fatigue In particular although the articles
were self-reported feasibility studies their results all indicate that exercise interventions
for fatigue are feasible and safe there was no conclusion to be made for the use of
massage therapy or health education measures because there was only one article for
each of these interventions
Recommendations for practice
Cancer-related fatigue is one of the most severe and frequent symptoms by pediatric
oncology children and adolescent suffered during treatment and the symptom existed
even after treatment has ended Until now no golden standard of treatment to fatigue is
established The findings call for more attention to how to reduce patientrsquos levels of
fatigue Based on the available information evaluated in this review the following
recommendations for practice are provided
665
33
bull For children aged 7 to 18 who has cancer (eg Lymphoma leukemia CNS tumor
germ cell tumor) an effective progressive aerobic exercise program is recommended to
be at least 2-3 times per week 20 to 45 minute for each session and last for 6-16 weeks
in order to reduce their general fatigue (tiredness physically weakness) In addition
adults should be involved in accompanying children while they are performing physical
exercise of which should be able to improve the adherence rate (level 2 ) ( Grade of
recommendation A)
bull For children aged 7 to 18 who has cancer (eg Lymphoma leukemia CNS tumor
germ cell tumor) an progressive aerobic exercise program will not be effective to reduce
their sleep andor rest (sleeping or resting a lot) or cognitive fatigue (problems with
thinking quickly or problems with remembering) (level 2 ) ( Grade of recommendation C)
bull Nursing interventions in educating treatment of fatigue include information about
activity nutrition energy preservation consulting and providing a useful fatigue
handbook will benefit those children who are 7 to 12 years have a new diagnosis of ALL
AML or lymphoma and receive for the first time after being diagnosed a 7- to 10-day
chemotherapy treatment (level 2) ( Grade of recommendation A)
bull A 4-week massage therapy program (the therapists massage childrenrsquos back legs
arms stomachchest and face) is not effective for children who are aged 7 to 18 and
have acute lymphoblastic leukemia brain tumors lymphoma rhabdomyosarcoma
Wilms tumor or Ewing sarcoma(level 2)( Grade of recommendation C)
bull Using a 12-week aerobic and strength exercise (45-min exercise sessions twice a
week) is not effective for children who are aged 6-14 and survived acute lymphoblaststic
leukemia age from 6 to 14(level 2) ( Grade of recommendation C)
bull Using a physical activity intervention (30minutestwice daily for 2-4days) is not
effective for children who are 7 to 18 years of age with soild tumor or AML(level 2)
( Grade of recommendation C)
666
34
Implications for research According to this systematic review and meta-analysis results there are suggestions to
improve the effectiveness of future research on non-pharmacological interventions for
children and young peoplersquos cancer-related fatigue
As the majority of included non-pharmacological interventions for the fatigue of cancer
patients consist of exercise programs future research should also consider various
non-pharmacological interventions in order to understand the effectiveness of different
methods
Regarding the exercise intervention methods and studies should consider multiple
factors including the age or personal condition of the subject the disease stage and the
amount of daily activities Studies should use design prescriptions (eg frequency
intensity duration and type of exercise) and consider the adherence to the measures in
order to enhance the study strength
In measuring the results of non-pharmacological interventions there should be standard
definitions or standard measurement tools to facilitate the following systematic review
and meta-analysis that can subsequently be developed into clinical care guidelines
Reviewing the effectiveness of the current non-pharmacological management of children
and adolescent cancer patients there is still a lack of rigorous RCT research Limited by
the characteristics of cancer there is still a lack of large sample sizes
Potential conflicts of interest There is no conflict of interest
Acknowledgements
Thank you to Dr Rie Konno Research Fellow Joanna Briggs Institute for her help in
assessing studies
667
35
References 1 National Comprehensive Cancer Network( NCCN) in USA NCCN clinical practice
guideline in oncology cancer-related fatigue 2011 2 Ekti Genc R amp Conk Z Impact of effective nursing interventions to the fatigue
syndrome in children who receive chemotherapy Cancer Nursing 200831(4)312-317
3 Childhood Cancer Foundation of ROC (2009March) The classification of diseases
and age sex statistical tables of case Childhood Cancer Foundation of ROC newsletter103105-106
4 Department of Health Executive Yuan ROC (TAIWAN)(2009 March 20)2009 cause of death statistic Health and National Health Insurance Annual Statistics Information Service 2010 June 28Available httpwwwdohgovtwstatisticdatavital statists9898health statistic--lifepdf
5 Chang TK (2007December 8) Common childhood cancer and its treatment Status
Childhood Cancer Foundation of ROC (TAIWAN) 2010 September 23 Available httpwwwccfrocorgtwchildchild_events_readphpe_id=45
6 Hockenberry MJ amp Wilson D Wongs nursing care of infants and children (8th ed) St
Louis MO Mosby 2007
7 Post-White J Fitzgerald M Savik K Hooke MC Hannahan AB amp Sencer SF
Massage therapy for children with cancer Journal of Pediatric Oncology Nursing 2009 26(1)16-28
8Chiang YC Yeh CH Wang WKamp Yang CP The experience of cancer-related fatigue
in Taiwanese children European Journal of Cancer Care 2009 18(1)43-49 9Langeveld NE Grootenhuis M A Voute P A de Haan RJ amp van den Bos C No excess
fatigue in young adult survivors of childhood cancer European Journal of Cancer 200339(2)204-214
10Piper BF Lindsey AM amp Dodd MJ Fatigue mechanisms in cancer patients
developing nursing theory Oncology Nursing Forum 1987 14(6)17-23 11Nail LM amp Winningham ML Fatigue In S L Groenwald M H Forgge M Goodman
amp C H Yarbro (Eds) Cancer Nursing Principles and practice (4 th ed) Boston Jones and Bartlett1997
12Irvine D Vincent L Graydon JE Bubela N amp Thompson L The prevalence and
correlates of fatigue in patients receiving treatment with chemotherapy and
668
36
radiotherapy A comparison with the fatigue experienced by healthy individuals Cancer Nursing 199417(5)367-378
13Hinds PS amp Hockenberry-Eaton M Developing a research program on fatigue in
children and adloescents diagnosed with cancer Journal of Pediatric Oncology Nursing 200118(2)3-12
14Aaronson LS Teel CS Cassmeyer V Neuberger GB Pallikkathayil L Pierce J Press
AN Williams DP amp Wingate A Defining and measuring fatigue Journal of Nursing scholarship 1999 31(1)45-50
15Yeh CH Wang CH Chiang YC Lin Lamp Chien LC Assessment of symptoms reported
by 10- to 18-year-old cancer patients in Taiwan 2009 38(5)738-746 16 Okuyama T Akechi T Kugaya A Okamura H Shima Yamp Maruguchi M
Development and validation of the cancer fatigue scale a brief three-dimensional self-rating scale for assessment of fatigue in cancer patients Journal of Pain amp Symptom Management 2000 19(1) 5-14
17Gibson F Mulhall AB Richardson A Edwards JL Ream E amp Sepion BJ A
phenomenologic study of fatigue in adolescents receiving treatment for cancer Oncology Nursing Forum200532(3)651-660
18Wolfe J Grier HE Klar N Levin SB Ellenbogen JMamp Salem-Schatz S et al
Symptoms and suffering at the end of life in children with cancer New England Journal of Medicine 2000342(5)326-333
19Whiting P Bagnall AM Sowden AJ Cornell JE Mulrow CD amp Ramirez G
Interventions for the treatment and management of chronic fatigue syndrome a systematic review JAMA the Journal of the American Medical Association 2001286(11)1360-1368
20 Kangas M Bovbjerg DHamp Montgomery G H Cancer-related fatigue a systematic
and meta-analytic review of non-pharmacological therapies for cancer patients Psychological Bulletin 2008134 (5)700-741
21Williams PD Schmideskamp J Ridder EL amp Williams AR Symptom monitoring and
dependent care during cancer treatment in children pilot study Cancer Nursing 200629(3)188-197
22Takken T van der Torre P Zwerink M Hulzebos EH Bierings M Helders PJMamp van
der Net J Development feasibility and efficacy of a community-based exercise training
669
37
program in pediatric cancer survivors Psycho-Oncology 200918(4)440-448
23Keats MR amp Culos-Reed SN A community-based physical activity program for
adolescents with cancer (project TREK) program feasibility and preliminary findings
Pediatric hematology and oncology 200830(4) 272-280
24Hinds PS Hockenberry M Rai SN Zhang L Razzouk B I Cremer L McCarthy K amp
Rodriguez-Galindo C Clinical field testing of an enhanced-activity intervention in
hospitalized children with cancer Journal of Pain amp Symptom Management 2007
33(6)686-697
25Chiang YC The effects of ldquo a home-based aerobic exercise interventionrdquo on fatigue
and cardiorespiratory fitness in children with acute lymphoblastic leukemia during the
maintenance stage of chemotherapy Unpublished thesis Taiwan Tao-Yuan 2007
26Langeveld N Ubbink M amp Smets E I dont have any energy The experience of
fatigue in young adult survivors of childhood cancer European journal of oncology
nursing 20004(1)20-28
27 Kisner C Colby L Therapeutic exercise Foundations and techniques 2nd ed Philadelphia PAFA Davies 2007
670
38
Appendix I JBI Critical Appraisal Checklist for Experimental studies
Author__________ Year_________ Record Number__________________
Questions 1 to 4 must be answered ldquoyesrdquo for study to be included in the metashyanalysis
1 Were the participants randomized to study groups
Yes No Not clear
2 Other than research intervention were participants in each groups treated the same
Yes No Not clear
3 Were the outcomes measured in the same manner for all participants
Yes No Not clear
4 Were groups comparable at entry
Yes No Not clear
5 Was randomization of participants blinded
Yes No Not clear
6 Were those assessing outcome blinded to treatment allocation (if outcome not objective such as survival or length of hospitalization)
Yes No Not clear
7 Was allocation to treatment groups concealed from the allocator
Yes No Not clear
8 Was an appropriate statistical analysis used
671
39
Yes No Not clear
9 Were outcomes measured in a reliable way
Yes No Not clear
10 Was there adequate followshyup of participants
Yes No Not clear
Summary
TOTAL
Yes No Not clear
DECISION
Use Reject
Narrative summary only Further information needed
COMMENTS
672
40
Appendix II JBI Data Extraction Tool for Quantitative Studies Authors and Year
Journal Title
Record NumberArticle Reference No
Reviewer
Method
Settings
Participants
Number of participants
Group A Group B Group C
Control Intervention 1 Intervention 2
Interventions
Group A
Control
Group B
Intervention 1
Group C
Intervention 2
Outcome measures
Definition
673
41
Other outcome measures
Outcome description ScaleMeasure
Results
Dichotomous Data
Outcome Control Group
Numbertotal number
Treatment Group
Numbertotal number
Continuous Data
Authorrsquos Conclusions
Comments
Outcome Control Group
Mean amp SD
Treatment Group
Mean amp SD
674
43
Appendix III Details of included studies (N=6)(2720212223) RefNo Author(s)
(years) Title Study question Research
method Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
22 Takken T van der Torre P Zwerink M Hulzebos E H Bierings M Helders P J Mamp van der Net J (2009)
Development feasibility and efficacy of a community-based exercise training program in pediatric cancer survivors
To develop a 12-week home-based exercise training program (comprising aerobic and strength exercises) for children who survived ALL and to study itrsquos feasibility and efficacy
Pre-post test design
No comparsion group
Survived ALL(N=9)ages 6-14 years
1anthropometry 2 muscle strength 3functional mobility 4cardio-pulmonary
exercise test 5Fatigue
1 Feasibility questionnaire 2 anthropometry electronic scale and a wallmounted stadiometerHarpenden skin fold calipers 3 muscle strength handheld dynamometer 4functional mobility Timed Up
and Go test (TUG) 5cardio-pulmonary exercise test electronically braked cycle ergometer 6Fatigue(mean)CSI-20 (subjective experience of fatigueconcentrationmotivationphysical activity)
112-week exercise training program
2 Patients were assessed before (T0) and after (T1) 12 weeks of training
1 muscle strength execapacity functional moand fatigue showed nosignificant differences between pre(meanplusmnSD415plusmn147) and post training(meanplusmnSD3687)
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
7 Post-White J Fitzgerald M Savik K Hooke M C Hannahan A B amp Sencer S F (2009)
Massage therapy for children with cancer
To determine whether 4 weekly sessions of massage compared with 4 quiet-time control conditions would reduce anxiety cortisol levels fatigue nausea and pain in children with cancer undergoing chemotherapy and would reduce anxiety fatigue and mood disturbance in a parent
2-period crossover design (Randomized)
quiet-time
control
sessions
Children with cancer 1 to 18 years of age Twenty-three childrenparent dyads were enrolled 17 completed all data points
children 1relaxation 2symptoms 3 fatigue
parents
1anxiety 2 fatigue
children 1relaxation (heart and respiratory rates blood pressure and salivary cortisol level)
2symptoms (pain nausea anxiety 3 fatigue 1-2y3-6yLansky Play Performance Scale (PPS) 7-13y
1 4 weekly massage (MT) sessions alternated with 4 weekly quiet-time(QT) control sessions
2 children included presession and postsession vital signs (heart rate respiratory rate blood pressure) and self-report (parent proxy report for age 1-2 years) of pain nausea and anxiety Fatigue was measured before sessions 1 and 4 and at each follow-up Parent measures
included anxiety fatigue and mood states
1Massage was moreeffective than quiet tireducing heart rate inchildren anxiety in cless than age 14 yeaparent anxiety 2There were no sign
changes in blood pcortisol pain naufatigue (no state d
3 Children reported tmassage helped thebetter lessened theirand worries and hadlasting effects than q
675
44
14-18yChild Fatigue Scale (CFS) (frequency
intensity) 2 parents anxiety and fatigue
676
45
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
24 Hinds P S Hockenberry M Rai S N Zhang L Razzouk B I Cremer L McCarthy K amp Rodriguez-Galindo C (2007)
Clinical field testing of an enhanced-activity intervention in hospitalized children with cancer
To determine the feasibility of an
enhanced physical activity EPA intervention in children and adolescents hospitalized to receive chemotherapy for a solid tumor or AML and to assess the sleep and fatigue outcomes of the intervention using two different statistical approaches to analyze the longitudinal symptom data
randomized prospective two-site and two-group pilot study
Standard care Twenty nine patients (25 with a solid tumor and 4 with AML)ages 7-18 years
1 sleep duration 2 sleep efficiency 3 fatigue
1sleep duration sleep efficiency The
Wrist Actigraph The Daily Sleep Diary-Parent 2 fatigue (mean) The Fatigue Scale(FS-C) for 7-12 (intensity) The Fatigue Scale(FS-A) for 13-18 The Fatigue Scale Parent Version (FS-P) The Fatigue Scale Staff Version (FS-S)
1enhanced physical activity (EPA) (hospital-based 30 minutes
twice daily for 2-4 days) 2 T0On the day of admission
(Day 0 or baseline)patient and parents completed the fatigue instruments and a team member applied the actigraph Patients wore the wrist actigraph T1 from Day 0 to 2 or 3 consecutive days (Days 0e3) In addition the patient same parent and staff nurses completed the daily sleep and fatigue reports in the late afternoons of Days 1-3
1 ANOVA model slesignificantly more the experimental athe control arm whdifferences from bsleep efficiency vaaveraged and com
2 The patient-reported mean fatigue scoresarms were higher amadolescents than for
3 The mixed model anarevealed no significandifferences in patientfatigue between
the two study arms otime( no final result iSD only give mixed result)
677
46
23 Keats M
R amp Culos-Reed S N (2008)
A community-based physical activity program for adolescents with cancer (project TREK) program feasibility and preliminary findings
To examine the
feasibility of a
theoretically-based
physical activity (PA)
intervention in
adolescents with
cancerand
examination of the
impact of the
program on
participant QOL
including social
emotional and
physical
well-being(including fatigue)
Repeat measures longitudinal design
No comparsion group
10 adolescents(Lymphoma(4)leukemia(4)CNS tumor(1)germ cell tumor(1)) ages 14-18 years
1physical fitness 2quality of life (QOL) 3PA behavior 4fatigue
1 Feasibility was assessed by participant recruitment attendance and adherence
2physical fitness Fitnessgram 3quality of life (QOL) Pediatric Quality of Life Inventory (PedsQL) 4PA behavior leisure score index (LSI) 5fatigue (mean) pediatric Quality of life
Multidimensional Fatigue Scale (Peds QL-MFS)
(Generalsleepcognitive fatigue)
116week physical activity (PA)
2 total PA physical fitness and overall QOL was assessed at 5 different intervals T0 preintervention (baseline) T1midintervention (after the
first 8 wk) T2 postintervention
(16 wk) T3 3-months
postintervention T4 1-year poststudy
initiation
1 from baseline -wkssig Improvementstotal PA physfitness and Qgeneral fatigue(meanplusmnSD 796plusmn135)
2 from baseline to 3FUsig Improvin general fatigue(meanplusmnSD824plusmn131)slefatigue(meanplusmnSD755plusmn191)totafatigue(meanplusmnSD778plusmn150)
3at 1 years FUsImprovements in sleeprest fatigue(meanplusmnSD725plusmn203)total (meanplusmnSD 763plusmn
678
47
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
2 Gene R E amp Conk Z (2008)
Impact of Effective Nursing Interventions to the Fatigue Syndrome in Children Who Receive Chemotherapy
1 to examine the effects of an effective nursing intervention to the fatigue syndrome of children 7 to 12 years of age who receive chemotherapy 2Tto examine the relationship between fatigue and demographic variables (age sex) diagnoses ([ALL AML] lymphoma) and therapy-related variables (eg level of hemoglobin
experimental randomized controlled study
Routine nursing care
A total of 60 children who are 7-12 years of age(a new diagnosis of ALL AML or lymphoma and receiving for the first time after being diagnosed a 7- to 10-day chemotherapy treatment )
fatigue The Fatigue Scale(FS-C) for 7-12 (intensity)
The Fatigue Scale Parent Version (FS-P)
1 effective nursing interventions(45- 60mdaya week)education about the fatigue with the chemotherapy and fatigue handbook 2 T1 After a 7-day period the children
and parent were evaluated with the Fatigue Scale
1The difference betwthe 2 mean values wafound to be statisticallsignificant 2 statistically significadifference was found between the Fatigue Scale-Child mean scothe experimental (272the control group (4213)children
679
48
25 Chiang et
al(2007)
The effects of ldquo a home ndashbased aerobic exercise interventionrdquo on fatigue and cardiorespiratory fitness in children with Acute Lymphoblastic Leukemia during the maintenance stage of chemotherapy
To examine the effect of ldquo a home ndashbased aerobic exercise interventionrdquo on fatigue and cardiorespiratory fitness in children with Acute Lymphoblastic Leukemia during the maintenance stage of chemotherapy
Quasi-experi -mental
Routine
nursing care
14 pediatric oncology patients in the experimental group and 10 in control group who were matched by age and sex ages7-18 years
1Cardiorespiratory fitness
2Fatigue
1Cardiorespiratory fitness Physical Activity Recall
VO2maxHR peak 6MWT
2 Fatigue PedsQL-MFS(Generalsleepcognitive fatigue)
1A six-week home-based aerobic exercise intervention 2 8 time points T0 baseline T1-T6 every week during the
intervention(6 weeks) T7 post intervention T8 follow-up (one month after
the end of the home-based exercise program)
1 For intent-to ndash treatthe findings indicated are no intervention efftime differences by anon the subscale of fat2 For per-protocol angeneral fatigue( mean422plusmn402) was the osubscale that was siglower for children whothe exercise interventthose in control groupfollow-up assessmentmonth after the compintervention) 3 The VO2peak are significantly improvingexperimental group atbaseline- and post-intassessment The VO2was significantly highechildren who were in experimental group thcontrol subjects at post-intervention assefor the per-protocol an
680
49
Appendix IV Instrument used to measure fatigue
Name Instrument
developers
Description Used in
age in
ref
Reliability
Consistency of
instrument
Checklist Individual Strength
(CIS)22
Vercoulen et
al1996
20 items using 7-point Likert scale of
fatigue To measure four aspects of
fatiguesubjective experience
contractionmotivation physical
Activity
6-14 Not reported
Child Fatigue Scale (CFS)7 Hockenberry
et al2003
14 items 2 part questionnaire frequency
(yes or no) 5-point Likert scale of the
intensity of any yes responses
7-13
14-18 α073-o84
The Fatigue Scale for 7-12
year Olds (FS-C)224
Hockenberry
et al
14 items provide a fatigue intensity score
5-point Likert scale
7-12 αo84
The Fatigue Scale for 13-18
year Olds (FS-A)24
Hockenberry
et al
14 items provide a fatigue intensity score
5-point Likert scale
13-18 α076-o96
Pediatric Quality of life
Multidimensional Fatigue
Scale (Peds QL-MFS)2325
Varni2002 18 items to measure three aspects of
fatigueGeneralsleepcognitive
14-18 Not reported
681
50
Appendix V Excluded studies and reasons for exclusion
Baggott C Dodd M Kennedy C Marina N Miaskowski C Multiple Symptoms in Pediatric Oncology
Patients A Systematic Review Journal of Pediatric Oncology Nursing 2009 Nov-Dec 27(6)
325-339
Reason for exclusion Not outcome of interest
Barlow JH Ellard DR Psycho-educational interventions for children with chronic disease parents and
siblings an overview of the research evidence base Care Health amp Development 2004 Nov
30(6)637-45
Reason for exclusion Not outcome of interest
Bedider S Moyer CA Randomized controlled trials of pediatric massage A review Evid Based
Complement Alternat Med 2007 Mar 4(1)23-34 Epub 2006 Nov 3
Reason for exclusion Not outcome of interest
de Nijs EJ Ros W Grijpdonck MH Nursing intervention for fatigue during the treatment for cancer Cancer
Nursing 2008 31(3)191-206
Reason for exclusion Not population of interest
Edwards JL Gibson F Richardson A Sepion B Ream E Fatigue in adolescents with and following a
cancer diagnosis developing an evidence base for practice European Journal of Cancer 2003
Dec 39(18)2671-80
Reason for exclusion Not experimental or quasi-experimental study
Hinds PS Hockenberry-Eatan M Developing a research program on fatigue in children and adolescents
diagnosed with cancer Journal of Pediatric Oncology Nursing 2001 Mar-Apr 18(2 Suppl
1)3-12
Reason for exclusion Not experimental or quasi-experimental study
Hockenberry-Eaton M Hinds PS Alcoser P ONeill JB Euell K Howard V Gattuso J Taylor J Fatigue in
Children and Adolescents With Cancer Journal of Pediatric Oncology Nursing 1998 July
15(3)172-182
Reason for exclusion Not experimental or quasi-experimental study
Jean-Pierre P Mustian K Kohli S Roscoe JA Hickok JT Morrow GR Community-based clinical oncology
research trials for cancer-related fatigue The Journal of Supportive Oncology 2006 Nov-Dec
4(10)511-6
682
51
Reason for exclusion Not population of interest
Kangas M Bovbjerg DH Montgomery GH Cancer-Related Fatigue A Systematic and Meta-Analytic
Review of Non-Pharmacological Therapies for Cancer Patients Psychological Bulletin 2008 Sep
134(5)700-41
Reason for exclusion Not population of interest
Lotfi-Jam K Carey M Jefford M Schofield P Charleson C Aranda S Nonpharmacologic strategies for
managing common chemotherapy adverse effects A systematic review Journal of Clinical
Oncology 2008 Dec 1 26(34)5618-29 Epub 2008 Nov 3
Reason for exclusion Not outcome of interest
Marchese VG Chiarello LA Lange BJ Effects of physical therapy intervention for children with acute
lymphoblastic leukemia Pediatr Blood Cancer 2004 Feb42(2)127-33
Reason for exclusion Not outcome of interest
Meeske KA Siegel SE Globe DR Mack WJ Bernstein L Prevalence and correlates of fatigue in
long-term survivors of childhood leukemia Journal of Clinical Oncology 2005 Aug 20
23(24)5501-10
Reason for exclusion Not intervention study
Minton O Richardson A Sharpe M Hotopf Stone P A systematic review and meta-analysis of the
pharmacological treatment of cancer-related fatigue J Natl Cancer Inst 2008 Aug 20
100(16)1155-66 Epub 2008 Aug 11
Reason for exclusion Not population and intervention of interest
Mustian KM Morrow GR Carroll JK Figueroa-Moseley CD Pascal JP Williams GC Integrative
nonpharmacologic behavioral interventions for the management of Cancer-Related fatigue The
Oncologist 2007 12(1)52-67
Reason for exclusion Not population of interest
Neill J Belan I Ried K Effectiveness of non-pharmacological interventions for fatigue in adults with
multiple sclerosis rheumatoid arthritis or systemic lupus erythematosus a systematic review
Journal of Advanced Nursing 2006 Dec 56(6)617-35
Reason for exclusion Not population of interest
Rheingans JI A systematic review of nonpharmacologic adjunctive therapies for symptom management
Journal of Pediatric Oncology Nursing 2007 24(2) 81-94
683
52
Reason for exclusion Not outcome of interest
Rheingans JI Pediatric oncology nursesrsquo management of patients symptoms Journal of Pediatric
Oncology Nursing 2008 Nov 25(6) 303-11
Reason for exclusion Not outcome of interest
San Juan AF Fleck SJ Chamorro-Vintildea C Mateacute-Muntildeoz JL Moral S Peacuterez M Cardona C Del Valle MF
Hernaacutendez M Ramiacuterez M Madero L Lucia A Effects of an intrahospital exercise program
intervention for children with leukemia Medicine amp Science in Sports amp Exercise 2007 Jan
39(1)13-21
Reason for exclusion Not outcome of interest
Sanford SD Okuma JO Pan J Srivastava DK West N Farr L Hinds PS Gender differences in sleep
fatigue and daytime activity in a pediatric oncology sample receiving dexamethasone Journal of
Pediatric Psychology 2008 Apr 33(3)298-306 Epub 2007 Nov 17
Reason for exclusion Not experimental or quasi-experimental study
Schmitz KH Holtzman J Courneya KS Macircsse LC Duval S Kane R Controlled physical activity trials in
cancer survivors a systematic review and meta-analysis Cancer Epidemiol Biomarkers Prev
2005 Jul 14(7)1588-95
Reason for exclusion Not population of interest
van Brussel M Takken T Lucia A van der Net J Helders PJ Is physical fitness decreased in survivors of
childhood leukemia A systematic review Leukemia 2005 Jan 19(1)13-7
Reason for exclusion Not population of interest
Whiting P Bagnall AM Snowden AJ Cornell JE Mulrow CD Ramirez G Interventions for the treatment
and management of chronic fatigue syndrome JAMA 2001 Sep 19 286(11)1360-8
Reason for exclusion Not intervention of interest
Whitsett SF Gudmundsdottir M Davies B McCarthy P Friedman D Chemotherapy-related fatigue in
childhood cancer correlates consequences and coping strategies Journal of Pediatric
Oncology Nursing 2008 Mar-Apr 25(2)86-96 Epub 2008 Feb 29
Reason for exclusion Not experimental or quasi-experimental study
Winner C Muumlller C Hoffmann C Boos J Rosenbaum D Physical activity and childhood cancer Pediatr
Blood Cancer 2010 Apr 54(4)501-10
Reason for exclusion Not research study
684
53
Wu M Hsu L Zhang B Shen N Lu H Li S The experiences of cancer-related fatigue among Chinese
children with leukaemia A phenomenological study Journal of Nursing Studies 2010 Jan
47(1)49-59 Epub 2009 Aug 25
Reason for exclusion Not experimental or quasi-experimental study
Yeh CH Chiang YC Lin L Yang CP Chien LC Weaver MA Chuang HL Clinical factors associated with
fatigue over time in paediatric oncology patients receiving chemotherapy British Journal of
Cancer 2008 Jul 8 99(1)23-9 Epub 2008 Jun 24
Reason for exclusion Not experimental or quasi-experimental study
685
16
with a third reviewer
Data extraction Data was extracted from papers included in the review using standardised data
extraction tool (Appendix II) from the JBI-SUMARI Details of eligible studies were
extracted and summarised independently by two reviewers
Data Synthesis
All data analysissynthesis were made using the JBI-SUMARI The studies were
assessed for clinical heterogeneity by considering the settings populations interventions
and outcomes Where possible these binary outcomes were analyzed by calculation of
the Odds Ratio with the 95 CI The weighted mean difference was calculated if the
pooled studies have used the same scale for continuous data The standardized mean
difference was calculated for continuous data measuring the same outcome on a
different scale In studies where statistical pooling of results was inappropriate the
findings were considered for inclusion as a narrative summary
Results The findings from the systematic review are presented first Followed by the results from
the meta-analysis component of this review
Description of studies From database search and hand search a total of 76 papers were identified Thirty
papers were then excluded because they did not meet the inclusion criteria Forty-six
full text were retrieved for further consideration for inclusion Of the 30 excluded reasons
for exclusion were follows 11articles were duplicated eight articles did not meet
649
17
participant inclusion criteria eight articles did not meet outcome criteria and nine articles
were correlation studies or discussion papers others articles were unclear reporting In
total after sorting six papers have been included in this article Figure 1 displays the
process used to identify relevant articles for inclusion in the systematic review
Figure 1 Stages of searching and inclusionexclusion of references for the review
Potentially relevant English-language and Chinese- language Studies Identified
Electronically and hand search (n=76)
Duplicate (n= 11) Papers excluded after evaluation of abstract (n=19)
Papers retrieved for detailed examination (N=46)
Papers excluded after review of full paper
(n=40)
Papers assessed for methodological
quality (n=6)
Papers included in systematic review
(n=6)
Methodological Quality
Of the six included articles 2722232425 two articles were RCT design224 with score 7 out
of 10 each paper from Critical Appraisal Checklist and four articles used
650
18
quasi-experimental design7222425 with socre 5 to 6 out of 10 because the quality of
the whole papers is still acceptable therefore these six articles were accepted after
primary reviewer and secondary reviewerrsquos decision
Randomisation
In two RCT articles224 one study24 used to a computer-generated program operated by
the St Jude Protocol and Data Management System to randomize the sample Another
study2 didnrsquot address how randomization was done
Allocation concealment
No studies reported allocation concealment
Intention-to-treat analysis
One quasi-experimental design7 stated Intention-to-treat analysis
Adequate follow up
The follow-up periods included 2or 3 days24 7 days2 4 week7 one month25 6 week25 12
week2216 week23 and 1 year23
Baseline comparability of groups
Three 22425 of six studies had baseline comparability in terms of age sex diagnosis
race institution duration of illness
Blinded outcome assessment
No studies used blinded outcome assessment The researchers including study team
patients staff and families were not blinded to the patientrsquos group assignment
Characteristics of included studies
651
19
There were six studies related to interventions designed to cancer-related fatigue for
pediatric patients than there are for adults There are a total of six including five
English-language papers 27222324 and one Chinese-language paper 25 ranging in year of
publication from 2007 to 2009
Patient characteristics
The research subjects of four papers included both school-aged children and
adolescents 7222324 one papers involved mainly adolescents25 and one paper sampled
only school-aged children 2 the range in ages was between six-18 years The number of
patients included in the samples ranged from nine to 60 The sources of case data were
from both outpatients and hospitalized children The types of cancer included acute
lymphoblastic leukemia (ALL) solid tumors acute myeloid leukemia (AML) and
lymphoma Overall ALL was the most commonly studied cancer type The stage of the
disease varied in these reports some patients were in the maintenance stage of
chemotherapy25 some had just received their first round of chemotherapy224 some had
completed two courses of treatments lasting 4-8 weeks each 7 and some had entered
the survivor stage 2223
Countries
Two RCTrsquos 2 24 were conducted in the USA There were four quasi-experimental design
studiesThree studies conducted in the USA7 22 23 and one in Taiwan25
Intervention types
652
20
The interventions included exercise training programs 2225 physical activity 2324
massage therapy 7 and health education 223 exercise training and physical activity as
an intervention method given in three different settings home 22 25 community 23 or
hospital 24 The studies used different types of exercise interventions including
home-based aerobic exercise use a Video Compact Disc 25 use of a bicycle-style
exerciser 24 aerobics2223 and various types of physical activities2 and strength-building
exercises 2223 The intensity of the exercise varied and often included gradual warm-up
exercises a period of main exercise and a cool down period For these studies2023 the
target exercise intensity was a heart rate of gt90 of the maximum heart rate (HR max) or
the increase in the percentage of heart rate reserve ( HRR) of 40-60
The number of weeks for the exercisephysical activity interventions duration including
2-4 days 24 6 weeks25 12 weeks22 and 16 weeks23 The frequency of exercise ranged
from 2-3 times per week to twice a day Typical duration of exercise ranged from 10 to 45
minutes There are three papers using exercise interventions based on ACSM (American
College of Sports Medicine) 2225 recommendations and one of these used an Activity
pyramid from the ACSM to determine intensity 24
One article did not clarify the type of exercise intervention or the reasons for their choices
23 In addition there was an article focusing on massage therapy 7 as an intervention in
this study the experimental group received four weeks of massage therapy either in the
clinic or in the patientrsquos room the therapy was applied by a professional masseur and
targeted the back legs arms chest stomach and face of the children However the
frequency of massage sessions per week and the duration of the massages were not
653
21
given There is another article about intervention measures combine health education
and physical activity 2 In this study patients were informed about the following (1) health
education patients received daily education about chemotherapy-related fatigue and
information from a health education manual written by the author (2) encouragement for
children to engage in activities such as listening to music drawing and reading and (3)
physical activity which involved walking along the corridors of the ward for 10-15 minutes
These health education measures were presented for 45-60 minutes a day for a total of
seven days The study design for non-pharmacological interventions used control groups
that included primarily people who had received standard treatment or people who did
not receive an exercise intervention
Outcome measures
Five measurement tools were used in this group of seven papers concerning childrenrsquos
fatigue (Appendix IV) Because those studies included both school-age children and
adolescents the following descriptions will be differentiated by age Fatigue
measurements for school-aged children with cancer include the following the Child
Fatigue Scale (CFS) 7 a scale that measures the frequency and intensity of fatigue and
the Fatigue Scale for 7-12 year Olds (FS-C) 224 a scale that can be used to evaluate the
intensity of fatigue On the other hand fatigue measurements for adolescent cancer
patients include the following the Fatigue Scale for 13-18-year-olds (FS-A) 24 a measure
that can help evaluate fatigue levels the Pediatric Quality of Life Multidimensional
Fatigue Scale (Peds QL-MFS) 2325 a tool that can be divided into three sub-scales to
understand the general cognitive and sleep rest components of fatigue and finally the
CIS-20 for school-age children and adolescents 22 a scale that measures four levels of
654
22
fatigue namely subjective experience attention motivation and physical activity Two
studies used the Peds QL-MFS scale to measure fatigue2325
Meta-analysis results Two studies of the included papers failed to provide sufficient raw data they could not be
included in the meta-analysis Hinds et al 24 did not include post-test data Genc et al 2
provided no pre-test data PostWhite et al7 reported that fatigue after the health
education intervention was not statistically different but they presented the results
without presenting fatigue-related data Therefore the meta-analysis included three
studies 222325
The heterogeneity of studies was analyzed with Chi square statistics and no statistical
significance was found Therefore the data was combined in meta-analysis according to
exercise intervention on fatigue In addition there were three articles using the Peds
QL-MFS as a research tool to examine childrenrsquos improvements in fatigue Among these
Keats 22 and Chiang 24 present the effectiveness of exercise interventions using three
subscales Therefore the meta-analysis also analysis of the effects of these exercise
intervention measures on three subscales of Peds QL-MFS general fatigue sleep rest
fatigue and cognitive fatigue
The effectiveness of exercise intervention for fatigue We analyzed the exercise intervention effect on fatigue A total of 2 studies 22 23 were
included Takken et al 22 used community-based exercise training program to reduce
fatigue of children 6 to 14 years (mean 93y) of age who survived ALL Fatigue
measurement by Checklist Individual Strength (CIS) after 12-week of training fatigue
655
23
show no significant differences between pre (meanplusmnSD 415plusmn147) and post training
(meanplusmnSD368plusmn217) but fatigue change from baseline mean reduction of 11
Keats et al23 although used community-based physical activity program to reduce fatigue
for adolescents 14 to 18 years of age (mean162 y) with cancer (Lymphoma leukemia CNS
tumor germ cell tumor) Studies used fatigue by PedsQLMFS Results show general fatigue
from baseline to 8 weeks and to 3 months follow up significantly improves General
fatigue sleeprest fatigue and total fatigue from baseline to 3 months follow up showed
significant improvements Sleeprest fatigue and total fatigue at 1 years followed up were
significant improvements
Figure 2 shows the overall effect of exercise intervention in children and adolescents with
cancers with a focus on improving fatigue Due to the lower heterogeneity (p>005) the
fixed effects model was used to pool the data for meta-analysis (Overall effect size=
-006 95 Confidence Interval (CI) -070 to 058) A result did not indicate a statistically
significant difference (p = 087)
656
24
Figure2 Meta-analysis results of exercise intervention on fatigue
In addition Keats23 and Chiang25 used the three sub-scales of Peds QL-MFS to
determine the general cognitive and sleep rest components of fatigue The following
present the effectiveness of exercise interventions using three subscales including
general fatigue sleep rest fatigue and cognitive fatigue 2325
Chiang et al 25 used a 6- week home-based aerobic exercise intervention to reduce
fatigue of children 7 to 18 years (mean age at experimental group was 1088 y in control
group was 1247 y) of age who with acute lymphoblastic leukemia Fatigue measurement
by Peds QL-MFS after training For intent-to ndash treat analysis the findings indicated that
there are no intervention effects and time differences by any items on the subscale of
fatigue For per-protocol analysis general fatigue( meanplusmnSD 422plusmn402) was the only
subscale that was significantly lower for children who received the exercise intervention
than those in control group at follow-up assessment (one month after the completion of
intervention)
Keats et al23 although used community-based physical activity program to reduce fatigue
for adolescents 14 to 18 years of age (mean162 y) with cancer (Lymphoma leukemia
CNS tumor germ cell tumor) Both studies used fatigue by PedsQLMFS Results show
general fatigue from baseline to 8 weeks and to 3 months follow up significantly improves
657
25
General fatigue sleeprest fatigue and total fatigue from baseline to 3 months follow up
showed significant improvements Sleeprest fatigue and total fatigue at 1 years followed
up were significant improvements
The effectiveness of exercise intervention for general fatigue
The impact of the exercise interventions upon levels of general fatigue was also analysed
The heterogeneity was low (p>005) Therefore the fixed effects model was used to
examine the effectiveness The effect size is -076 indicating a statistically significant
difference (p = 001 95 CI -135 to -017 Fig 3) The evidence suggests that exercise
intervention can reduce general fatigue in children with cancer
Fig 3 Meta-analysis results of exercise intervention for general fatigue
The effectiveness of exercise intervention for sleep rest fatigue
The following is the result of the meta-analysis of the effectiveness of exercise
interventions on sleep rest fatigue First the heterogeneity test was conducted with P gt
005 representing small heterogeneity and the fixed effects model was used Fig 4
shows the effect size is -035 indicating no statistically significant differences (p = 023
95 CI-092 to 022 Fig 4)
658
26
Fig 4 Meta-analysis results of exercise intervention for sleep rest fatigue
The effectiveness of exercise intervention for cognitive fatigue Lastly the following data reports the results of meta-analysis of the effectiveness of
exercise interventions for cognitive fatigue The heterogeneity was p>005 then the
fixed effects model was used The effect size is -035 indicating no statistically significant
differences (p = 024 95 CI-092 023 Fig 5)
Fig 5 Meta-analysis results of exercise intervention for cognitive fatigue
Narrative presentation of remaining included studies
Three studies were not included in meta-analysis Post-White et al7 one of the aims in
this study was to examine the effect of massage therapy on fatigue in children with
cancer The study was a quasi-experimental design Twenty-three childrenparent dyads
were enrolled 17completed all data points Children with cancer ages 7 to 18 years
received at least 2 identical cycles of chemotherapy and one parent participated in the
2-period crossover design in which 4 weekly massage sessions (MT) alternated with 4
659
27
weekly quiet-time (QT) control sessions There were no significant changes in fatigue in
children over the 4-week MT or QT conditions either independently (change over time) or
when we compared fatigue by condition
The lack of effect of massage on fatigue may be the difficulty some children had in
differentiating fatigue from being relaxed underscores the challenge of measuring fatigue
in children Some children interpreted being tired or relaxed as having greater fatigue
because they felt like lying around and sleeping or felt unmotivated to do their usual
activities all measures of fatigue in the instrument used in the study
Hinds et al24conducted a prospective two-site randomized controlled pilot study to
assess the feasibility of an enhanced physical activity (EPA) intervention in hospitalized
children and adolescents receiving treatment for a solid tumor or for acute myeloid
leukemia (AML) Twenty-nine patients (25 with a solid tumor and 4 with AML) participated
age range from 736 to 1816 (mean 1248 y) The EPA intervention selected was
pedaling a stationary bicycle-style exerciser (Chattanooga Peddler Deluxe Bio-Teck
Medical Memphis TN) for 30 minutes twice daily for 2 to 4 days of hospitalization The
mixed model analysis revealed no significant differences in patient reports of fatigue
between the two study arms or over time
Genc et al2 conducted a RCT involving children with cancer who are 7 to 12 years of age
and receiving chemotherapy treatment to determine the impact of educational
intervention by nurses on decreasing the fatigue syndrome The research sample was
composed of a total of 60 children with cancer with 30 children being included in the
660
28
experimental group (mean age 923)and 30 children included in the control group (mean
age 937) with their mothers In the experimental group after the 7th to 10th day of the
chemotherapy treatment throughout a week the researcher conducted the nursing
interventions every day for 45 to 60 minutes In the control group routine nursing
interventions were carried out The experimental group received education about the
fatigue with the chemotherapy and fatigue handbook was given which was developed by
the authors Children and mothers were consulted for including activities that could
decrease fatigue which were described as effective interventions A statistically
significant difference was found between the Fatigue Scale-Child mean scores of the
experimental (2723) and the control group (4213) The results suggest that fatigue of
children with cancer can be reduced by implementing appropriate nursing interventions
(t=567 Plt00)
Discussion The purpose of this systematic review was to determine the effectiveness of
non-pharmacological interventions specifically targeting fatigue for children and
adolescents with cancer undergoing chemotherapy or after receiving chemotherapy
Included articles about the effectiveness of non-pharmacological interventions for
children and adolescents with cancer were published between the years of 2007 and
2009 Although interventions for cancer fatigue for adults have been extensively studied
it can be seen from either the title of the paper or related content that an intervention
study on children was a pilot study or a feasibility study Representing a field in its early
stage these studies show that the fatigue issues with young cancer patients have only
recently been taken seriously
661
29
The results of our meta-analysis include measurement of the four performance indicators
fatigue and general fatigue sleep rest fatigue and cognitive fatigue The results show
that there is a statistically significant difference only in the domain of general fatigue
using an exercise intervention for children with cancer can improve the degree of fatigue
with the effect size reaching 0671 Other results do not indicate significant differences
The reasons may include the following
1 Characteristics of the cancer The exhaustion from cancer occurs not only during cancer treatment but also in during
long-term survival a time during which patients may continue to be affected by this
symptom 8 26 Therefore when using intervention measures to improve fatigue
circumstances should be considered such as the process of the treatment and the course
or stage of the disease Because cancer patients will experience different forms of
treatment or courses of treatment the disease itself or treatment differences should be
considered in the choice of intervention Even chemotherapy drugs should be taken into
consideration For example a period of general steroid treatment can increase patientsrsquo
fatigue In those studies of children with cancer few studies looked solely at one type of
cancer most studies included a variety of cancer patients Furthermore most studies do
not clearly explain the stage of the disease or course of treatment and most do not
include treatment variables in the control group Moreover children with cancer may
have different levels of physical function
2 Research design The sample size Currently there are few studies with large sample size and a rigorous
RCT design due to the small number of papers available for analysis The sample size
included in our studyrsquos data analysis is between 20 and 42 people this small sample size
will affect the power available to evaluate outcome variables
Although most of the non-pharmacological interventions still use exercise and physical
activity and these studies overall show better results for fatigue as compared with
controls more research is still needed to further confirm the efficacy of these findings
662
30
The dropout rate in the evaluated research varies a great deal ranging from 5 to 45
these dropout rates may result from the characteristics of the research subjects or the
lengthy time involved in participating in these studies The research data with a high
turnover rate might not reflect the actual outcomes of participation in exercise and the
quality of the research contained in articles with high subject turnover rates may be
lower
Exercise doses and time The exercise doses needed to reduce fatigue cannot be
determined additionally the amount of exercise completed by the patient is also
inconsistent interventions vary between 2-3 times per week and two times a day and
exercise duration varies between 10 and 45 minutes each time Furthermore the study
interventions vary in length between a couple of days and a long period of 16 weeks The
data collection times are different some were measured 12 weeks after the intervention
began some were measured during the 6 weeks of intervention some were measured
three months after the intervention was finished and some were measured after one
year
In addition disease-related symptoms decrease childrenrsquos willingness to participate in
exercise interventions inappropriate exercise intervention programs may actually
increase childrens fatigue In addition the children in the study are still developing
physically it is important to consider ways to design an interesting exercise intervention
to increase the compliance of patients in order to improve the effectiveness Although
intervention programs in the hospital or in a community sports center can improve the
effectiveness because they provide supervision the feasibility of these programs is
questionable However if the program is home-based the children need to be
supervised by parents in order to improve their compliance in doing the exercises
Furthermore regarding the nature of the intervention the results from this study indicate
that the researched non-pharmacological interventions include the following exercise
training programs physical activity massage therapy and health education interventions
However according to the National Comprehensive Cancer Network 1 clinical guidelines
663
31
for cancer non-drug measures for cancer fatigue can be separated into five categories
(1) activity enhancement (2) psychosocial interventions such as cognitive behavioral
therapy (CBT) stress management relaxation techniques and support groups (3)
attention-restoring therapy (4) nutritional consultation and (5) cognitive behavioral
therapy specifically targeting sleep disturbance Researchers have also suggested that
psychosocial interventions should be included in the future research for children with
cancer-related fatigue 22
(2) The measurement tools in the study The assessment of fatigue can be
one-dimensional or multidimensional One-dimensional assessment can help understand
the severity of fatigue symptoms however multidimensional scales are often more
credible Therefore when measuring cancer-related fatigue researchers should consider
whether there is a uniform definition of fatigue or a standardized tool for measuring
fatigue in order to facilitate further systematic meta-analyses and further develop the
clinical care guidelines
Limitations of the review The present review has some potential limitations First the low methodological quality
may influence the result Although exercise intervention seems promising quality of the
RCTs was generally quite low Future studies require better design and reporting if
methodological issues to establish evidence-based nonpharmcologic intervention
Second the identified studies covered only a limited types of nonpharmcological
intervention especially in exercise intervention The guidelines for cancer-related fatigue
in NCCN (2011)1 referred to more interventions than the ones included in this review
such as cognitive behavioral therapy and nutrition consultation Thirdly the small sample
size and effect size could be potentially having led to underpowered approach for
detecting the effects on fatigue Therefore we recommend that as research continues to
grow a re-analysis can be undertaken Fourthly Combining data in meta analysis from
664
32
studies where the ages were quite different is a potential source of heterogeneity and
may affect the interpretation of the results
Conclusion At present clinical treatment is widely used for cancer patients However child and
adolescent cancer patients often experience various side effects which cause short-term
or long-term discomfort both physically and psychologically In particular with the
increasing cure rate cancer related fatigue during or after treatment has become an
important issue This study result provided positive effect of exercise intervention on
general fatigue
Implications for practice The results of this systematic review and meta-analysis show that exercise interventions
can effectively improve the level of general fatigue In particular although the articles
were self-reported feasibility studies their results all indicate that exercise interventions
for fatigue are feasible and safe there was no conclusion to be made for the use of
massage therapy or health education measures because there was only one article for
each of these interventions
Recommendations for practice
Cancer-related fatigue is one of the most severe and frequent symptoms by pediatric
oncology children and adolescent suffered during treatment and the symptom existed
even after treatment has ended Until now no golden standard of treatment to fatigue is
established The findings call for more attention to how to reduce patientrsquos levels of
fatigue Based on the available information evaluated in this review the following
recommendations for practice are provided
665
33
bull For children aged 7 to 18 who has cancer (eg Lymphoma leukemia CNS tumor
germ cell tumor) an effective progressive aerobic exercise program is recommended to
be at least 2-3 times per week 20 to 45 minute for each session and last for 6-16 weeks
in order to reduce their general fatigue (tiredness physically weakness) In addition
adults should be involved in accompanying children while they are performing physical
exercise of which should be able to improve the adherence rate (level 2 ) ( Grade of
recommendation A)
bull For children aged 7 to 18 who has cancer (eg Lymphoma leukemia CNS tumor
germ cell tumor) an progressive aerobic exercise program will not be effective to reduce
their sleep andor rest (sleeping or resting a lot) or cognitive fatigue (problems with
thinking quickly or problems with remembering) (level 2 ) ( Grade of recommendation C)
bull Nursing interventions in educating treatment of fatigue include information about
activity nutrition energy preservation consulting and providing a useful fatigue
handbook will benefit those children who are 7 to 12 years have a new diagnosis of ALL
AML or lymphoma and receive for the first time after being diagnosed a 7- to 10-day
chemotherapy treatment (level 2) ( Grade of recommendation A)
bull A 4-week massage therapy program (the therapists massage childrenrsquos back legs
arms stomachchest and face) is not effective for children who are aged 7 to 18 and
have acute lymphoblastic leukemia brain tumors lymphoma rhabdomyosarcoma
Wilms tumor or Ewing sarcoma(level 2)( Grade of recommendation C)
bull Using a 12-week aerobic and strength exercise (45-min exercise sessions twice a
week) is not effective for children who are aged 6-14 and survived acute lymphoblaststic
leukemia age from 6 to 14(level 2) ( Grade of recommendation C)
bull Using a physical activity intervention (30minutestwice daily for 2-4days) is not
effective for children who are 7 to 18 years of age with soild tumor or AML(level 2)
( Grade of recommendation C)
666
34
Implications for research According to this systematic review and meta-analysis results there are suggestions to
improve the effectiveness of future research on non-pharmacological interventions for
children and young peoplersquos cancer-related fatigue
As the majority of included non-pharmacological interventions for the fatigue of cancer
patients consist of exercise programs future research should also consider various
non-pharmacological interventions in order to understand the effectiveness of different
methods
Regarding the exercise intervention methods and studies should consider multiple
factors including the age or personal condition of the subject the disease stage and the
amount of daily activities Studies should use design prescriptions (eg frequency
intensity duration and type of exercise) and consider the adherence to the measures in
order to enhance the study strength
In measuring the results of non-pharmacological interventions there should be standard
definitions or standard measurement tools to facilitate the following systematic review
and meta-analysis that can subsequently be developed into clinical care guidelines
Reviewing the effectiveness of the current non-pharmacological management of children
and adolescent cancer patients there is still a lack of rigorous RCT research Limited by
the characteristics of cancer there is still a lack of large sample sizes
Potential conflicts of interest There is no conflict of interest
Acknowledgements
Thank you to Dr Rie Konno Research Fellow Joanna Briggs Institute for her help in
assessing studies
667
35
References 1 National Comprehensive Cancer Network( NCCN) in USA NCCN clinical practice
guideline in oncology cancer-related fatigue 2011 2 Ekti Genc R amp Conk Z Impact of effective nursing interventions to the fatigue
syndrome in children who receive chemotherapy Cancer Nursing 200831(4)312-317
3 Childhood Cancer Foundation of ROC (2009March) The classification of diseases
and age sex statistical tables of case Childhood Cancer Foundation of ROC newsletter103105-106
4 Department of Health Executive Yuan ROC (TAIWAN)(2009 March 20)2009 cause of death statistic Health and National Health Insurance Annual Statistics Information Service 2010 June 28Available httpwwwdohgovtwstatisticdatavital statists9898health statistic--lifepdf
5 Chang TK (2007December 8) Common childhood cancer and its treatment Status
Childhood Cancer Foundation of ROC (TAIWAN) 2010 September 23 Available httpwwwccfrocorgtwchildchild_events_readphpe_id=45
6 Hockenberry MJ amp Wilson D Wongs nursing care of infants and children (8th ed) St
Louis MO Mosby 2007
7 Post-White J Fitzgerald M Savik K Hooke MC Hannahan AB amp Sencer SF
Massage therapy for children with cancer Journal of Pediatric Oncology Nursing 2009 26(1)16-28
8Chiang YC Yeh CH Wang WKamp Yang CP The experience of cancer-related fatigue
in Taiwanese children European Journal of Cancer Care 2009 18(1)43-49 9Langeveld NE Grootenhuis M A Voute P A de Haan RJ amp van den Bos C No excess
fatigue in young adult survivors of childhood cancer European Journal of Cancer 200339(2)204-214
10Piper BF Lindsey AM amp Dodd MJ Fatigue mechanisms in cancer patients
developing nursing theory Oncology Nursing Forum 1987 14(6)17-23 11Nail LM amp Winningham ML Fatigue In S L Groenwald M H Forgge M Goodman
amp C H Yarbro (Eds) Cancer Nursing Principles and practice (4 th ed) Boston Jones and Bartlett1997
12Irvine D Vincent L Graydon JE Bubela N amp Thompson L The prevalence and
correlates of fatigue in patients receiving treatment with chemotherapy and
668
36
radiotherapy A comparison with the fatigue experienced by healthy individuals Cancer Nursing 199417(5)367-378
13Hinds PS amp Hockenberry-Eaton M Developing a research program on fatigue in
children and adloescents diagnosed with cancer Journal of Pediatric Oncology Nursing 200118(2)3-12
14Aaronson LS Teel CS Cassmeyer V Neuberger GB Pallikkathayil L Pierce J Press
AN Williams DP amp Wingate A Defining and measuring fatigue Journal of Nursing scholarship 1999 31(1)45-50
15Yeh CH Wang CH Chiang YC Lin Lamp Chien LC Assessment of symptoms reported
by 10- to 18-year-old cancer patients in Taiwan 2009 38(5)738-746 16 Okuyama T Akechi T Kugaya A Okamura H Shima Yamp Maruguchi M
Development and validation of the cancer fatigue scale a brief three-dimensional self-rating scale for assessment of fatigue in cancer patients Journal of Pain amp Symptom Management 2000 19(1) 5-14
17Gibson F Mulhall AB Richardson A Edwards JL Ream E amp Sepion BJ A
phenomenologic study of fatigue in adolescents receiving treatment for cancer Oncology Nursing Forum200532(3)651-660
18Wolfe J Grier HE Klar N Levin SB Ellenbogen JMamp Salem-Schatz S et al
Symptoms and suffering at the end of life in children with cancer New England Journal of Medicine 2000342(5)326-333
19Whiting P Bagnall AM Sowden AJ Cornell JE Mulrow CD amp Ramirez G
Interventions for the treatment and management of chronic fatigue syndrome a systematic review JAMA the Journal of the American Medical Association 2001286(11)1360-1368
20 Kangas M Bovbjerg DHamp Montgomery G H Cancer-related fatigue a systematic
and meta-analytic review of non-pharmacological therapies for cancer patients Psychological Bulletin 2008134 (5)700-741
21Williams PD Schmideskamp J Ridder EL amp Williams AR Symptom monitoring and
dependent care during cancer treatment in children pilot study Cancer Nursing 200629(3)188-197
22Takken T van der Torre P Zwerink M Hulzebos EH Bierings M Helders PJMamp van
der Net J Development feasibility and efficacy of a community-based exercise training
669
37
program in pediatric cancer survivors Psycho-Oncology 200918(4)440-448
23Keats MR amp Culos-Reed SN A community-based physical activity program for
adolescents with cancer (project TREK) program feasibility and preliminary findings
Pediatric hematology and oncology 200830(4) 272-280
24Hinds PS Hockenberry M Rai SN Zhang L Razzouk B I Cremer L McCarthy K amp
Rodriguez-Galindo C Clinical field testing of an enhanced-activity intervention in
hospitalized children with cancer Journal of Pain amp Symptom Management 2007
33(6)686-697
25Chiang YC The effects of ldquo a home-based aerobic exercise interventionrdquo on fatigue
and cardiorespiratory fitness in children with acute lymphoblastic leukemia during the
maintenance stage of chemotherapy Unpublished thesis Taiwan Tao-Yuan 2007
26Langeveld N Ubbink M amp Smets E I dont have any energy The experience of
fatigue in young adult survivors of childhood cancer European journal of oncology
nursing 20004(1)20-28
27 Kisner C Colby L Therapeutic exercise Foundations and techniques 2nd ed Philadelphia PAFA Davies 2007
670
38
Appendix I JBI Critical Appraisal Checklist for Experimental studies
Author__________ Year_________ Record Number__________________
Questions 1 to 4 must be answered ldquoyesrdquo for study to be included in the metashyanalysis
1 Were the participants randomized to study groups
Yes No Not clear
2 Other than research intervention were participants in each groups treated the same
Yes No Not clear
3 Were the outcomes measured in the same manner for all participants
Yes No Not clear
4 Were groups comparable at entry
Yes No Not clear
5 Was randomization of participants blinded
Yes No Not clear
6 Were those assessing outcome blinded to treatment allocation (if outcome not objective such as survival or length of hospitalization)
Yes No Not clear
7 Was allocation to treatment groups concealed from the allocator
Yes No Not clear
8 Was an appropriate statistical analysis used
671
39
Yes No Not clear
9 Were outcomes measured in a reliable way
Yes No Not clear
10 Was there adequate followshyup of participants
Yes No Not clear
Summary
TOTAL
Yes No Not clear
DECISION
Use Reject
Narrative summary only Further information needed
COMMENTS
672
40
Appendix II JBI Data Extraction Tool for Quantitative Studies Authors and Year
Journal Title
Record NumberArticle Reference No
Reviewer
Method
Settings
Participants
Number of participants
Group A Group B Group C
Control Intervention 1 Intervention 2
Interventions
Group A
Control
Group B
Intervention 1
Group C
Intervention 2
Outcome measures
Definition
673
41
Other outcome measures
Outcome description ScaleMeasure
Results
Dichotomous Data
Outcome Control Group
Numbertotal number
Treatment Group
Numbertotal number
Continuous Data
Authorrsquos Conclusions
Comments
Outcome Control Group
Mean amp SD
Treatment Group
Mean amp SD
674
43
Appendix III Details of included studies (N=6)(2720212223) RefNo Author(s)
(years) Title Study question Research
method Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
22 Takken T van der Torre P Zwerink M Hulzebos E H Bierings M Helders P J Mamp van der Net J (2009)
Development feasibility and efficacy of a community-based exercise training program in pediatric cancer survivors
To develop a 12-week home-based exercise training program (comprising aerobic and strength exercises) for children who survived ALL and to study itrsquos feasibility and efficacy
Pre-post test design
No comparsion group
Survived ALL(N=9)ages 6-14 years
1anthropometry 2 muscle strength 3functional mobility 4cardio-pulmonary
exercise test 5Fatigue
1 Feasibility questionnaire 2 anthropometry electronic scale and a wallmounted stadiometerHarpenden skin fold calipers 3 muscle strength handheld dynamometer 4functional mobility Timed Up
and Go test (TUG) 5cardio-pulmonary exercise test electronically braked cycle ergometer 6Fatigue(mean)CSI-20 (subjective experience of fatigueconcentrationmotivationphysical activity)
112-week exercise training program
2 Patients were assessed before (T0) and after (T1) 12 weeks of training
1 muscle strength execapacity functional moand fatigue showed nosignificant differences between pre(meanplusmnSD415plusmn147) and post training(meanplusmnSD3687)
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
7 Post-White J Fitzgerald M Savik K Hooke M C Hannahan A B amp Sencer S F (2009)
Massage therapy for children with cancer
To determine whether 4 weekly sessions of massage compared with 4 quiet-time control conditions would reduce anxiety cortisol levels fatigue nausea and pain in children with cancer undergoing chemotherapy and would reduce anxiety fatigue and mood disturbance in a parent
2-period crossover design (Randomized)
quiet-time
control
sessions
Children with cancer 1 to 18 years of age Twenty-three childrenparent dyads were enrolled 17 completed all data points
children 1relaxation 2symptoms 3 fatigue
parents
1anxiety 2 fatigue
children 1relaxation (heart and respiratory rates blood pressure and salivary cortisol level)
2symptoms (pain nausea anxiety 3 fatigue 1-2y3-6yLansky Play Performance Scale (PPS) 7-13y
1 4 weekly massage (MT) sessions alternated with 4 weekly quiet-time(QT) control sessions
2 children included presession and postsession vital signs (heart rate respiratory rate blood pressure) and self-report (parent proxy report for age 1-2 years) of pain nausea and anxiety Fatigue was measured before sessions 1 and 4 and at each follow-up Parent measures
included anxiety fatigue and mood states
1Massage was moreeffective than quiet tireducing heart rate inchildren anxiety in cless than age 14 yeaparent anxiety 2There were no sign
changes in blood pcortisol pain naufatigue (no state d
3 Children reported tmassage helped thebetter lessened theirand worries and hadlasting effects than q
675
44
14-18yChild Fatigue Scale (CFS) (frequency
intensity) 2 parents anxiety and fatigue
676
45
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
24 Hinds P S Hockenberry M Rai S N Zhang L Razzouk B I Cremer L McCarthy K amp Rodriguez-Galindo C (2007)
Clinical field testing of an enhanced-activity intervention in hospitalized children with cancer
To determine the feasibility of an
enhanced physical activity EPA intervention in children and adolescents hospitalized to receive chemotherapy for a solid tumor or AML and to assess the sleep and fatigue outcomes of the intervention using two different statistical approaches to analyze the longitudinal symptom data
randomized prospective two-site and two-group pilot study
Standard care Twenty nine patients (25 with a solid tumor and 4 with AML)ages 7-18 years
1 sleep duration 2 sleep efficiency 3 fatigue
1sleep duration sleep efficiency The
Wrist Actigraph The Daily Sleep Diary-Parent 2 fatigue (mean) The Fatigue Scale(FS-C) for 7-12 (intensity) The Fatigue Scale(FS-A) for 13-18 The Fatigue Scale Parent Version (FS-P) The Fatigue Scale Staff Version (FS-S)
1enhanced physical activity (EPA) (hospital-based 30 minutes
twice daily for 2-4 days) 2 T0On the day of admission
(Day 0 or baseline)patient and parents completed the fatigue instruments and a team member applied the actigraph Patients wore the wrist actigraph T1 from Day 0 to 2 or 3 consecutive days (Days 0e3) In addition the patient same parent and staff nurses completed the daily sleep and fatigue reports in the late afternoons of Days 1-3
1 ANOVA model slesignificantly more the experimental athe control arm whdifferences from bsleep efficiency vaaveraged and com
2 The patient-reported mean fatigue scoresarms were higher amadolescents than for
3 The mixed model anarevealed no significandifferences in patientfatigue between
the two study arms otime( no final result iSD only give mixed result)
677
46
23 Keats M
R amp Culos-Reed S N (2008)
A community-based physical activity program for adolescents with cancer (project TREK) program feasibility and preliminary findings
To examine the
feasibility of a
theoretically-based
physical activity (PA)
intervention in
adolescents with
cancerand
examination of the
impact of the
program on
participant QOL
including social
emotional and
physical
well-being(including fatigue)
Repeat measures longitudinal design
No comparsion group
10 adolescents(Lymphoma(4)leukemia(4)CNS tumor(1)germ cell tumor(1)) ages 14-18 years
1physical fitness 2quality of life (QOL) 3PA behavior 4fatigue
1 Feasibility was assessed by participant recruitment attendance and adherence
2physical fitness Fitnessgram 3quality of life (QOL) Pediatric Quality of Life Inventory (PedsQL) 4PA behavior leisure score index (LSI) 5fatigue (mean) pediatric Quality of life
Multidimensional Fatigue Scale (Peds QL-MFS)
(Generalsleepcognitive fatigue)
116week physical activity (PA)
2 total PA physical fitness and overall QOL was assessed at 5 different intervals T0 preintervention (baseline) T1midintervention (after the
first 8 wk) T2 postintervention
(16 wk) T3 3-months
postintervention T4 1-year poststudy
initiation
1 from baseline -wkssig Improvementstotal PA physfitness and Qgeneral fatigue(meanplusmnSD 796plusmn135)
2 from baseline to 3FUsig Improvin general fatigue(meanplusmnSD824plusmn131)slefatigue(meanplusmnSD755plusmn191)totafatigue(meanplusmnSD778plusmn150)
3at 1 years FUsImprovements in sleeprest fatigue(meanplusmnSD725plusmn203)total (meanplusmnSD 763plusmn
678
47
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
2 Gene R E amp Conk Z (2008)
Impact of Effective Nursing Interventions to the Fatigue Syndrome in Children Who Receive Chemotherapy
1 to examine the effects of an effective nursing intervention to the fatigue syndrome of children 7 to 12 years of age who receive chemotherapy 2Tto examine the relationship between fatigue and demographic variables (age sex) diagnoses ([ALL AML] lymphoma) and therapy-related variables (eg level of hemoglobin
experimental randomized controlled study
Routine nursing care
A total of 60 children who are 7-12 years of age(a new diagnosis of ALL AML or lymphoma and receiving for the first time after being diagnosed a 7- to 10-day chemotherapy treatment )
fatigue The Fatigue Scale(FS-C) for 7-12 (intensity)
The Fatigue Scale Parent Version (FS-P)
1 effective nursing interventions(45- 60mdaya week)education about the fatigue with the chemotherapy and fatigue handbook 2 T1 After a 7-day period the children
and parent were evaluated with the Fatigue Scale
1The difference betwthe 2 mean values wafound to be statisticallsignificant 2 statistically significadifference was found between the Fatigue Scale-Child mean scothe experimental (272the control group (4213)children
679
48
25 Chiang et
al(2007)
The effects of ldquo a home ndashbased aerobic exercise interventionrdquo on fatigue and cardiorespiratory fitness in children with Acute Lymphoblastic Leukemia during the maintenance stage of chemotherapy
To examine the effect of ldquo a home ndashbased aerobic exercise interventionrdquo on fatigue and cardiorespiratory fitness in children with Acute Lymphoblastic Leukemia during the maintenance stage of chemotherapy
Quasi-experi -mental
Routine
nursing care
14 pediatric oncology patients in the experimental group and 10 in control group who were matched by age and sex ages7-18 years
1Cardiorespiratory fitness
2Fatigue
1Cardiorespiratory fitness Physical Activity Recall
VO2maxHR peak 6MWT
2 Fatigue PedsQL-MFS(Generalsleepcognitive fatigue)
1A six-week home-based aerobic exercise intervention 2 8 time points T0 baseline T1-T6 every week during the
intervention(6 weeks) T7 post intervention T8 follow-up (one month after
the end of the home-based exercise program)
1 For intent-to ndash treatthe findings indicated are no intervention efftime differences by anon the subscale of fat2 For per-protocol angeneral fatigue( mean422plusmn402) was the osubscale that was siglower for children whothe exercise interventthose in control groupfollow-up assessmentmonth after the compintervention) 3 The VO2peak are significantly improvingexperimental group atbaseline- and post-intassessment The VO2was significantly highechildren who were in experimental group thcontrol subjects at post-intervention assefor the per-protocol an
680
49
Appendix IV Instrument used to measure fatigue
Name Instrument
developers
Description Used in
age in
ref
Reliability
Consistency of
instrument
Checklist Individual Strength
(CIS)22
Vercoulen et
al1996
20 items using 7-point Likert scale of
fatigue To measure four aspects of
fatiguesubjective experience
contractionmotivation physical
Activity
6-14 Not reported
Child Fatigue Scale (CFS)7 Hockenberry
et al2003
14 items 2 part questionnaire frequency
(yes or no) 5-point Likert scale of the
intensity of any yes responses
7-13
14-18 α073-o84
The Fatigue Scale for 7-12
year Olds (FS-C)224
Hockenberry
et al
14 items provide a fatigue intensity score
5-point Likert scale
7-12 αo84
The Fatigue Scale for 13-18
year Olds (FS-A)24
Hockenberry
et al
14 items provide a fatigue intensity score
5-point Likert scale
13-18 α076-o96
Pediatric Quality of life
Multidimensional Fatigue
Scale (Peds QL-MFS)2325
Varni2002 18 items to measure three aspects of
fatigueGeneralsleepcognitive
14-18 Not reported
681
50
Appendix V Excluded studies and reasons for exclusion
Baggott C Dodd M Kennedy C Marina N Miaskowski C Multiple Symptoms in Pediatric Oncology
Patients A Systematic Review Journal of Pediatric Oncology Nursing 2009 Nov-Dec 27(6)
325-339
Reason for exclusion Not outcome of interest
Barlow JH Ellard DR Psycho-educational interventions for children with chronic disease parents and
siblings an overview of the research evidence base Care Health amp Development 2004 Nov
30(6)637-45
Reason for exclusion Not outcome of interest
Bedider S Moyer CA Randomized controlled trials of pediatric massage A review Evid Based
Complement Alternat Med 2007 Mar 4(1)23-34 Epub 2006 Nov 3
Reason for exclusion Not outcome of interest
de Nijs EJ Ros W Grijpdonck MH Nursing intervention for fatigue during the treatment for cancer Cancer
Nursing 2008 31(3)191-206
Reason for exclusion Not population of interest
Edwards JL Gibson F Richardson A Sepion B Ream E Fatigue in adolescents with and following a
cancer diagnosis developing an evidence base for practice European Journal of Cancer 2003
Dec 39(18)2671-80
Reason for exclusion Not experimental or quasi-experimental study
Hinds PS Hockenberry-Eatan M Developing a research program on fatigue in children and adolescents
diagnosed with cancer Journal of Pediatric Oncology Nursing 2001 Mar-Apr 18(2 Suppl
1)3-12
Reason for exclusion Not experimental or quasi-experimental study
Hockenberry-Eaton M Hinds PS Alcoser P ONeill JB Euell K Howard V Gattuso J Taylor J Fatigue in
Children and Adolescents With Cancer Journal of Pediatric Oncology Nursing 1998 July
15(3)172-182
Reason for exclusion Not experimental or quasi-experimental study
Jean-Pierre P Mustian K Kohli S Roscoe JA Hickok JT Morrow GR Community-based clinical oncology
research trials for cancer-related fatigue The Journal of Supportive Oncology 2006 Nov-Dec
4(10)511-6
682
51
Reason for exclusion Not population of interest
Kangas M Bovbjerg DH Montgomery GH Cancer-Related Fatigue A Systematic and Meta-Analytic
Review of Non-Pharmacological Therapies for Cancer Patients Psychological Bulletin 2008 Sep
134(5)700-41
Reason for exclusion Not population of interest
Lotfi-Jam K Carey M Jefford M Schofield P Charleson C Aranda S Nonpharmacologic strategies for
managing common chemotherapy adverse effects A systematic review Journal of Clinical
Oncology 2008 Dec 1 26(34)5618-29 Epub 2008 Nov 3
Reason for exclusion Not outcome of interest
Marchese VG Chiarello LA Lange BJ Effects of physical therapy intervention for children with acute
lymphoblastic leukemia Pediatr Blood Cancer 2004 Feb42(2)127-33
Reason for exclusion Not outcome of interest
Meeske KA Siegel SE Globe DR Mack WJ Bernstein L Prevalence and correlates of fatigue in
long-term survivors of childhood leukemia Journal of Clinical Oncology 2005 Aug 20
23(24)5501-10
Reason for exclusion Not intervention study
Minton O Richardson A Sharpe M Hotopf Stone P A systematic review and meta-analysis of the
pharmacological treatment of cancer-related fatigue J Natl Cancer Inst 2008 Aug 20
100(16)1155-66 Epub 2008 Aug 11
Reason for exclusion Not population and intervention of interest
Mustian KM Morrow GR Carroll JK Figueroa-Moseley CD Pascal JP Williams GC Integrative
nonpharmacologic behavioral interventions for the management of Cancer-Related fatigue The
Oncologist 2007 12(1)52-67
Reason for exclusion Not population of interest
Neill J Belan I Ried K Effectiveness of non-pharmacological interventions for fatigue in adults with
multiple sclerosis rheumatoid arthritis or systemic lupus erythematosus a systematic review
Journal of Advanced Nursing 2006 Dec 56(6)617-35
Reason for exclusion Not population of interest
Rheingans JI A systematic review of nonpharmacologic adjunctive therapies for symptom management
Journal of Pediatric Oncology Nursing 2007 24(2) 81-94
683
52
Reason for exclusion Not outcome of interest
Rheingans JI Pediatric oncology nursesrsquo management of patients symptoms Journal of Pediatric
Oncology Nursing 2008 Nov 25(6) 303-11
Reason for exclusion Not outcome of interest
San Juan AF Fleck SJ Chamorro-Vintildea C Mateacute-Muntildeoz JL Moral S Peacuterez M Cardona C Del Valle MF
Hernaacutendez M Ramiacuterez M Madero L Lucia A Effects of an intrahospital exercise program
intervention for children with leukemia Medicine amp Science in Sports amp Exercise 2007 Jan
39(1)13-21
Reason for exclusion Not outcome of interest
Sanford SD Okuma JO Pan J Srivastava DK West N Farr L Hinds PS Gender differences in sleep
fatigue and daytime activity in a pediatric oncology sample receiving dexamethasone Journal of
Pediatric Psychology 2008 Apr 33(3)298-306 Epub 2007 Nov 17
Reason for exclusion Not experimental or quasi-experimental study
Schmitz KH Holtzman J Courneya KS Macircsse LC Duval S Kane R Controlled physical activity trials in
cancer survivors a systematic review and meta-analysis Cancer Epidemiol Biomarkers Prev
2005 Jul 14(7)1588-95
Reason for exclusion Not population of interest
van Brussel M Takken T Lucia A van der Net J Helders PJ Is physical fitness decreased in survivors of
childhood leukemia A systematic review Leukemia 2005 Jan 19(1)13-7
Reason for exclusion Not population of interest
Whiting P Bagnall AM Snowden AJ Cornell JE Mulrow CD Ramirez G Interventions for the treatment
and management of chronic fatigue syndrome JAMA 2001 Sep 19 286(11)1360-8
Reason for exclusion Not intervention of interest
Whitsett SF Gudmundsdottir M Davies B McCarthy P Friedman D Chemotherapy-related fatigue in
childhood cancer correlates consequences and coping strategies Journal of Pediatric
Oncology Nursing 2008 Mar-Apr 25(2)86-96 Epub 2008 Feb 29
Reason for exclusion Not experimental or quasi-experimental study
Winner C Muumlller C Hoffmann C Boos J Rosenbaum D Physical activity and childhood cancer Pediatr
Blood Cancer 2010 Apr 54(4)501-10
Reason for exclusion Not research study
684
53
Wu M Hsu L Zhang B Shen N Lu H Li S The experiences of cancer-related fatigue among Chinese
children with leukaemia A phenomenological study Journal of Nursing Studies 2010 Jan
47(1)49-59 Epub 2009 Aug 25
Reason for exclusion Not experimental or quasi-experimental study
Yeh CH Chiang YC Lin L Yang CP Chien LC Weaver MA Chuang HL Clinical factors associated with
fatigue over time in paediatric oncology patients receiving chemotherapy British Journal of
Cancer 2008 Jul 8 99(1)23-9 Epub 2008 Jun 24
Reason for exclusion Not experimental or quasi-experimental study
685
17
participant inclusion criteria eight articles did not meet outcome criteria and nine articles
were correlation studies or discussion papers others articles were unclear reporting In
total after sorting six papers have been included in this article Figure 1 displays the
process used to identify relevant articles for inclusion in the systematic review
Figure 1 Stages of searching and inclusionexclusion of references for the review
Potentially relevant English-language and Chinese- language Studies Identified
Electronically and hand search (n=76)
Duplicate (n= 11) Papers excluded after evaluation of abstract (n=19)
Papers retrieved for detailed examination (N=46)
Papers excluded after review of full paper
(n=40)
Papers assessed for methodological
quality (n=6)
Papers included in systematic review
(n=6)
Methodological Quality
Of the six included articles 2722232425 two articles were RCT design224 with score 7 out
of 10 each paper from Critical Appraisal Checklist and four articles used
650
18
quasi-experimental design7222425 with socre 5 to 6 out of 10 because the quality of
the whole papers is still acceptable therefore these six articles were accepted after
primary reviewer and secondary reviewerrsquos decision
Randomisation
In two RCT articles224 one study24 used to a computer-generated program operated by
the St Jude Protocol and Data Management System to randomize the sample Another
study2 didnrsquot address how randomization was done
Allocation concealment
No studies reported allocation concealment
Intention-to-treat analysis
One quasi-experimental design7 stated Intention-to-treat analysis
Adequate follow up
The follow-up periods included 2or 3 days24 7 days2 4 week7 one month25 6 week25 12
week2216 week23 and 1 year23
Baseline comparability of groups
Three 22425 of six studies had baseline comparability in terms of age sex diagnosis
race institution duration of illness
Blinded outcome assessment
No studies used blinded outcome assessment The researchers including study team
patients staff and families were not blinded to the patientrsquos group assignment
Characteristics of included studies
651
19
There were six studies related to interventions designed to cancer-related fatigue for
pediatric patients than there are for adults There are a total of six including five
English-language papers 27222324 and one Chinese-language paper 25 ranging in year of
publication from 2007 to 2009
Patient characteristics
The research subjects of four papers included both school-aged children and
adolescents 7222324 one papers involved mainly adolescents25 and one paper sampled
only school-aged children 2 the range in ages was between six-18 years The number of
patients included in the samples ranged from nine to 60 The sources of case data were
from both outpatients and hospitalized children The types of cancer included acute
lymphoblastic leukemia (ALL) solid tumors acute myeloid leukemia (AML) and
lymphoma Overall ALL was the most commonly studied cancer type The stage of the
disease varied in these reports some patients were in the maintenance stage of
chemotherapy25 some had just received their first round of chemotherapy224 some had
completed two courses of treatments lasting 4-8 weeks each 7 and some had entered
the survivor stage 2223
Countries
Two RCTrsquos 2 24 were conducted in the USA There were four quasi-experimental design
studiesThree studies conducted in the USA7 22 23 and one in Taiwan25
Intervention types
652
20
The interventions included exercise training programs 2225 physical activity 2324
massage therapy 7 and health education 223 exercise training and physical activity as
an intervention method given in three different settings home 22 25 community 23 or
hospital 24 The studies used different types of exercise interventions including
home-based aerobic exercise use a Video Compact Disc 25 use of a bicycle-style
exerciser 24 aerobics2223 and various types of physical activities2 and strength-building
exercises 2223 The intensity of the exercise varied and often included gradual warm-up
exercises a period of main exercise and a cool down period For these studies2023 the
target exercise intensity was a heart rate of gt90 of the maximum heart rate (HR max) or
the increase in the percentage of heart rate reserve ( HRR) of 40-60
The number of weeks for the exercisephysical activity interventions duration including
2-4 days 24 6 weeks25 12 weeks22 and 16 weeks23 The frequency of exercise ranged
from 2-3 times per week to twice a day Typical duration of exercise ranged from 10 to 45
minutes There are three papers using exercise interventions based on ACSM (American
College of Sports Medicine) 2225 recommendations and one of these used an Activity
pyramid from the ACSM to determine intensity 24
One article did not clarify the type of exercise intervention or the reasons for their choices
23 In addition there was an article focusing on massage therapy 7 as an intervention in
this study the experimental group received four weeks of massage therapy either in the
clinic or in the patientrsquos room the therapy was applied by a professional masseur and
targeted the back legs arms chest stomach and face of the children However the
frequency of massage sessions per week and the duration of the massages were not
653
21
given There is another article about intervention measures combine health education
and physical activity 2 In this study patients were informed about the following (1) health
education patients received daily education about chemotherapy-related fatigue and
information from a health education manual written by the author (2) encouragement for
children to engage in activities such as listening to music drawing and reading and (3)
physical activity which involved walking along the corridors of the ward for 10-15 minutes
These health education measures were presented for 45-60 minutes a day for a total of
seven days The study design for non-pharmacological interventions used control groups
that included primarily people who had received standard treatment or people who did
not receive an exercise intervention
Outcome measures
Five measurement tools were used in this group of seven papers concerning childrenrsquos
fatigue (Appendix IV) Because those studies included both school-age children and
adolescents the following descriptions will be differentiated by age Fatigue
measurements for school-aged children with cancer include the following the Child
Fatigue Scale (CFS) 7 a scale that measures the frequency and intensity of fatigue and
the Fatigue Scale for 7-12 year Olds (FS-C) 224 a scale that can be used to evaluate the
intensity of fatigue On the other hand fatigue measurements for adolescent cancer
patients include the following the Fatigue Scale for 13-18-year-olds (FS-A) 24 a measure
that can help evaluate fatigue levels the Pediatric Quality of Life Multidimensional
Fatigue Scale (Peds QL-MFS) 2325 a tool that can be divided into three sub-scales to
understand the general cognitive and sleep rest components of fatigue and finally the
CIS-20 for school-age children and adolescents 22 a scale that measures four levels of
654
22
fatigue namely subjective experience attention motivation and physical activity Two
studies used the Peds QL-MFS scale to measure fatigue2325
Meta-analysis results Two studies of the included papers failed to provide sufficient raw data they could not be
included in the meta-analysis Hinds et al 24 did not include post-test data Genc et al 2
provided no pre-test data PostWhite et al7 reported that fatigue after the health
education intervention was not statistically different but they presented the results
without presenting fatigue-related data Therefore the meta-analysis included three
studies 222325
The heterogeneity of studies was analyzed with Chi square statistics and no statistical
significance was found Therefore the data was combined in meta-analysis according to
exercise intervention on fatigue In addition there were three articles using the Peds
QL-MFS as a research tool to examine childrenrsquos improvements in fatigue Among these
Keats 22 and Chiang 24 present the effectiveness of exercise interventions using three
subscales Therefore the meta-analysis also analysis of the effects of these exercise
intervention measures on three subscales of Peds QL-MFS general fatigue sleep rest
fatigue and cognitive fatigue
The effectiveness of exercise intervention for fatigue We analyzed the exercise intervention effect on fatigue A total of 2 studies 22 23 were
included Takken et al 22 used community-based exercise training program to reduce
fatigue of children 6 to 14 years (mean 93y) of age who survived ALL Fatigue
measurement by Checklist Individual Strength (CIS) after 12-week of training fatigue
655
23
show no significant differences between pre (meanplusmnSD 415plusmn147) and post training
(meanplusmnSD368plusmn217) but fatigue change from baseline mean reduction of 11
Keats et al23 although used community-based physical activity program to reduce fatigue
for adolescents 14 to 18 years of age (mean162 y) with cancer (Lymphoma leukemia CNS
tumor germ cell tumor) Studies used fatigue by PedsQLMFS Results show general fatigue
from baseline to 8 weeks and to 3 months follow up significantly improves General
fatigue sleeprest fatigue and total fatigue from baseline to 3 months follow up showed
significant improvements Sleeprest fatigue and total fatigue at 1 years followed up were
significant improvements
Figure 2 shows the overall effect of exercise intervention in children and adolescents with
cancers with a focus on improving fatigue Due to the lower heterogeneity (p>005) the
fixed effects model was used to pool the data for meta-analysis (Overall effect size=
-006 95 Confidence Interval (CI) -070 to 058) A result did not indicate a statistically
significant difference (p = 087)
656
24
Figure2 Meta-analysis results of exercise intervention on fatigue
In addition Keats23 and Chiang25 used the three sub-scales of Peds QL-MFS to
determine the general cognitive and sleep rest components of fatigue The following
present the effectiveness of exercise interventions using three subscales including
general fatigue sleep rest fatigue and cognitive fatigue 2325
Chiang et al 25 used a 6- week home-based aerobic exercise intervention to reduce
fatigue of children 7 to 18 years (mean age at experimental group was 1088 y in control
group was 1247 y) of age who with acute lymphoblastic leukemia Fatigue measurement
by Peds QL-MFS after training For intent-to ndash treat analysis the findings indicated that
there are no intervention effects and time differences by any items on the subscale of
fatigue For per-protocol analysis general fatigue( meanplusmnSD 422plusmn402) was the only
subscale that was significantly lower for children who received the exercise intervention
than those in control group at follow-up assessment (one month after the completion of
intervention)
Keats et al23 although used community-based physical activity program to reduce fatigue
for adolescents 14 to 18 years of age (mean162 y) with cancer (Lymphoma leukemia
CNS tumor germ cell tumor) Both studies used fatigue by PedsQLMFS Results show
general fatigue from baseline to 8 weeks and to 3 months follow up significantly improves
657
25
General fatigue sleeprest fatigue and total fatigue from baseline to 3 months follow up
showed significant improvements Sleeprest fatigue and total fatigue at 1 years followed
up were significant improvements
The effectiveness of exercise intervention for general fatigue
The impact of the exercise interventions upon levels of general fatigue was also analysed
The heterogeneity was low (p>005) Therefore the fixed effects model was used to
examine the effectiveness The effect size is -076 indicating a statistically significant
difference (p = 001 95 CI -135 to -017 Fig 3) The evidence suggests that exercise
intervention can reduce general fatigue in children with cancer
Fig 3 Meta-analysis results of exercise intervention for general fatigue
The effectiveness of exercise intervention for sleep rest fatigue
The following is the result of the meta-analysis of the effectiveness of exercise
interventions on sleep rest fatigue First the heterogeneity test was conducted with P gt
005 representing small heterogeneity and the fixed effects model was used Fig 4
shows the effect size is -035 indicating no statistically significant differences (p = 023
95 CI-092 to 022 Fig 4)
658
26
Fig 4 Meta-analysis results of exercise intervention for sleep rest fatigue
The effectiveness of exercise intervention for cognitive fatigue Lastly the following data reports the results of meta-analysis of the effectiveness of
exercise interventions for cognitive fatigue The heterogeneity was p>005 then the
fixed effects model was used The effect size is -035 indicating no statistically significant
differences (p = 024 95 CI-092 023 Fig 5)
Fig 5 Meta-analysis results of exercise intervention for cognitive fatigue
Narrative presentation of remaining included studies
Three studies were not included in meta-analysis Post-White et al7 one of the aims in
this study was to examine the effect of massage therapy on fatigue in children with
cancer The study was a quasi-experimental design Twenty-three childrenparent dyads
were enrolled 17completed all data points Children with cancer ages 7 to 18 years
received at least 2 identical cycles of chemotherapy and one parent participated in the
2-period crossover design in which 4 weekly massage sessions (MT) alternated with 4
659
27
weekly quiet-time (QT) control sessions There were no significant changes in fatigue in
children over the 4-week MT or QT conditions either independently (change over time) or
when we compared fatigue by condition
The lack of effect of massage on fatigue may be the difficulty some children had in
differentiating fatigue from being relaxed underscores the challenge of measuring fatigue
in children Some children interpreted being tired or relaxed as having greater fatigue
because they felt like lying around and sleeping or felt unmotivated to do their usual
activities all measures of fatigue in the instrument used in the study
Hinds et al24conducted a prospective two-site randomized controlled pilot study to
assess the feasibility of an enhanced physical activity (EPA) intervention in hospitalized
children and adolescents receiving treatment for a solid tumor or for acute myeloid
leukemia (AML) Twenty-nine patients (25 with a solid tumor and 4 with AML) participated
age range from 736 to 1816 (mean 1248 y) The EPA intervention selected was
pedaling a stationary bicycle-style exerciser (Chattanooga Peddler Deluxe Bio-Teck
Medical Memphis TN) for 30 minutes twice daily for 2 to 4 days of hospitalization The
mixed model analysis revealed no significant differences in patient reports of fatigue
between the two study arms or over time
Genc et al2 conducted a RCT involving children with cancer who are 7 to 12 years of age
and receiving chemotherapy treatment to determine the impact of educational
intervention by nurses on decreasing the fatigue syndrome The research sample was
composed of a total of 60 children with cancer with 30 children being included in the
660
28
experimental group (mean age 923)and 30 children included in the control group (mean
age 937) with their mothers In the experimental group after the 7th to 10th day of the
chemotherapy treatment throughout a week the researcher conducted the nursing
interventions every day for 45 to 60 minutes In the control group routine nursing
interventions were carried out The experimental group received education about the
fatigue with the chemotherapy and fatigue handbook was given which was developed by
the authors Children and mothers were consulted for including activities that could
decrease fatigue which were described as effective interventions A statistically
significant difference was found between the Fatigue Scale-Child mean scores of the
experimental (2723) and the control group (4213) The results suggest that fatigue of
children with cancer can be reduced by implementing appropriate nursing interventions
(t=567 Plt00)
Discussion The purpose of this systematic review was to determine the effectiveness of
non-pharmacological interventions specifically targeting fatigue for children and
adolescents with cancer undergoing chemotherapy or after receiving chemotherapy
Included articles about the effectiveness of non-pharmacological interventions for
children and adolescents with cancer were published between the years of 2007 and
2009 Although interventions for cancer fatigue for adults have been extensively studied
it can be seen from either the title of the paper or related content that an intervention
study on children was a pilot study or a feasibility study Representing a field in its early
stage these studies show that the fatigue issues with young cancer patients have only
recently been taken seriously
661
29
The results of our meta-analysis include measurement of the four performance indicators
fatigue and general fatigue sleep rest fatigue and cognitive fatigue The results show
that there is a statistically significant difference only in the domain of general fatigue
using an exercise intervention for children with cancer can improve the degree of fatigue
with the effect size reaching 0671 Other results do not indicate significant differences
The reasons may include the following
1 Characteristics of the cancer The exhaustion from cancer occurs not only during cancer treatment but also in during
long-term survival a time during which patients may continue to be affected by this
symptom 8 26 Therefore when using intervention measures to improve fatigue
circumstances should be considered such as the process of the treatment and the course
or stage of the disease Because cancer patients will experience different forms of
treatment or courses of treatment the disease itself or treatment differences should be
considered in the choice of intervention Even chemotherapy drugs should be taken into
consideration For example a period of general steroid treatment can increase patientsrsquo
fatigue In those studies of children with cancer few studies looked solely at one type of
cancer most studies included a variety of cancer patients Furthermore most studies do
not clearly explain the stage of the disease or course of treatment and most do not
include treatment variables in the control group Moreover children with cancer may
have different levels of physical function
2 Research design The sample size Currently there are few studies with large sample size and a rigorous
RCT design due to the small number of papers available for analysis The sample size
included in our studyrsquos data analysis is between 20 and 42 people this small sample size
will affect the power available to evaluate outcome variables
Although most of the non-pharmacological interventions still use exercise and physical
activity and these studies overall show better results for fatigue as compared with
controls more research is still needed to further confirm the efficacy of these findings
662
30
The dropout rate in the evaluated research varies a great deal ranging from 5 to 45
these dropout rates may result from the characteristics of the research subjects or the
lengthy time involved in participating in these studies The research data with a high
turnover rate might not reflect the actual outcomes of participation in exercise and the
quality of the research contained in articles with high subject turnover rates may be
lower
Exercise doses and time The exercise doses needed to reduce fatigue cannot be
determined additionally the amount of exercise completed by the patient is also
inconsistent interventions vary between 2-3 times per week and two times a day and
exercise duration varies between 10 and 45 minutes each time Furthermore the study
interventions vary in length between a couple of days and a long period of 16 weeks The
data collection times are different some were measured 12 weeks after the intervention
began some were measured during the 6 weeks of intervention some were measured
three months after the intervention was finished and some were measured after one
year
In addition disease-related symptoms decrease childrenrsquos willingness to participate in
exercise interventions inappropriate exercise intervention programs may actually
increase childrens fatigue In addition the children in the study are still developing
physically it is important to consider ways to design an interesting exercise intervention
to increase the compliance of patients in order to improve the effectiveness Although
intervention programs in the hospital or in a community sports center can improve the
effectiveness because they provide supervision the feasibility of these programs is
questionable However if the program is home-based the children need to be
supervised by parents in order to improve their compliance in doing the exercises
Furthermore regarding the nature of the intervention the results from this study indicate
that the researched non-pharmacological interventions include the following exercise
training programs physical activity massage therapy and health education interventions
However according to the National Comprehensive Cancer Network 1 clinical guidelines
663
31
for cancer non-drug measures for cancer fatigue can be separated into five categories
(1) activity enhancement (2) psychosocial interventions such as cognitive behavioral
therapy (CBT) stress management relaxation techniques and support groups (3)
attention-restoring therapy (4) nutritional consultation and (5) cognitive behavioral
therapy specifically targeting sleep disturbance Researchers have also suggested that
psychosocial interventions should be included in the future research for children with
cancer-related fatigue 22
(2) The measurement tools in the study The assessment of fatigue can be
one-dimensional or multidimensional One-dimensional assessment can help understand
the severity of fatigue symptoms however multidimensional scales are often more
credible Therefore when measuring cancer-related fatigue researchers should consider
whether there is a uniform definition of fatigue or a standardized tool for measuring
fatigue in order to facilitate further systematic meta-analyses and further develop the
clinical care guidelines
Limitations of the review The present review has some potential limitations First the low methodological quality
may influence the result Although exercise intervention seems promising quality of the
RCTs was generally quite low Future studies require better design and reporting if
methodological issues to establish evidence-based nonpharmcologic intervention
Second the identified studies covered only a limited types of nonpharmcological
intervention especially in exercise intervention The guidelines for cancer-related fatigue
in NCCN (2011)1 referred to more interventions than the ones included in this review
such as cognitive behavioral therapy and nutrition consultation Thirdly the small sample
size and effect size could be potentially having led to underpowered approach for
detecting the effects on fatigue Therefore we recommend that as research continues to
grow a re-analysis can be undertaken Fourthly Combining data in meta analysis from
664
32
studies where the ages were quite different is a potential source of heterogeneity and
may affect the interpretation of the results
Conclusion At present clinical treatment is widely used for cancer patients However child and
adolescent cancer patients often experience various side effects which cause short-term
or long-term discomfort both physically and psychologically In particular with the
increasing cure rate cancer related fatigue during or after treatment has become an
important issue This study result provided positive effect of exercise intervention on
general fatigue
Implications for practice The results of this systematic review and meta-analysis show that exercise interventions
can effectively improve the level of general fatigue In particular although the articles
were self-reported feasibility studies their results all indicate that exercise interventions
for fatigue are feasible and safe there was no conclusion to be made for the use of
massage therapy or health education measures because there was only one article for
each of these interventions
Recommendations for practice
Cancer-related fatigue is one of the most severe and frequent symptoms by pediatric
oncology children and adolescent suffered during treatment and the symptom existed
even after treatment has ended Until now no golden standard of treatment to fatigue is
established The findings call for more attention to how to reduce patientrsquos levels of
fatigue Based on the available information evaluated in this review the following
recommendations for practice are provided
665
33
bull For children aged 7 to 18 who has cancer (eg Lymphoma leukemia CNS tumor
germ cell tumor) an effective progressive aerobic exercise program is recommended to
be at least 2-3 times per week 20 to 45 minute for each session and last for 6-16 weeks
in order to reduce their general fatigue (tiredness physically weakness) In addition
adults should be involved in accompanying children while they are performing physical
exercise of which should be able to improve the adherence rate (level 2 ) ( Grade of
recommendation A)
bull For children aged 7 to 18 who has cancer (eg Lymphoma leukemia CNS tumor
germ cell tumor) an progressive aerobic exercise program will not be effective to reduce
their sleep andor rest (sleeping or resting a lot) or cognitive fatigue (problems with
thinking quickly or problems with remembering) (level 2 ) ( Grade of recommendation C)
bull Nursing interventions in educating treatment of fatigue include information about
activity nutrition energy preservation consulting and providing a useful fatigue
handbook will benefit those children who are 7 to 12 years have a new diagnosis of ALL
AML or lymphoma and receive for the first time after being diagnosed a 7- to 10-day
chemotherapy treatment (level 2) ( Grade of recommendation A)
bull A 4-week massage therapy program (the therapists massage childrenrsquos back legs
arms stomachchest and face) is not effective for children who are aged 7 to 18 and
have acute lymphoblastic leukemia brain tumors lymphoma rhabdomyosarcoma
Wilms tumor or Ewing sarcoma(level 2)( Grade of recommendation C)
bull Using a 12-week aerobic and strength exercise (45-min exercise sessions twice a
week) is not effective for children who are aged 6-14 and survived acute lymphoblaststic
leukemia age from 6 to 14(level 2) ( Grade of recommendation C)
bull Using a physical activity intervention (30minutestwice daily for 2-4days) is not
effective for children who are 7 to 18 years of age with soild tumor or AML(level 2)
( Grade of recommendation C)
666
34
Implications for research According to this systematic review and meta-analysis results there are suggestions to
improve the effectiveness of future research on non-pharmacological interventions for
children and young peoplersquos cancer-related fatigue
As the majority of included non-pharmacological interventions for the fatigue of cancer
patients consist of exercise programs future research should also consider various
non-pharmacological interventions in order to understand the effectiveness of different
methods
Regarding the exercise intervention methods and studies should consider multiple
factors including the age or personal condition of the subject the disease stage and the
amount of daily activities Studies should use design prescriptions (eg frequency
intensity duration and type of exercise) and consider the adherence to the measures in
order to enhance the study strength
In measuring the results of non-pharmacological interventions there should be standard
definitions or standard measurement tools to facilitate the following systematic review
and meta-analysis that can subsequently be developed into clinical care guidelines
Reviewing the effectiveness of the current non-pharmacological management of children
and adolescent cancer patients there is still a lack of rigorous RCT research Limited by
the characteristics of cancer there is still a lack of large sample sizes
Potential conflicts of interest There is no conflict of interest
Acknowledgements
Thank you to Dr Rie Konno Research Fellow Joanna Briggs Institute for her help in
assessing studies
667
35
References 1 National Comprehensive Cancer Network( NCCN) in USA NCCN clinical practice
guideline in oncology cancer-related fatigue 2011 2 Ekti Genc R amp Conk Z Impact of effective nursing interventions to the fatigue
syndrome in children who receive chemotherapy Cancer Nursing 200831(4)312-317
3 Childhood Cancer Foundation of ROC (2009March) The classification of diseases
and age sex statistical tables of case Childhood Cancer Foundation of ROC newsletter103105-106
4 Department of Health Executive Yuan ROC (TAIWAN)(2009 March 20)2009 cause of death statistic Health and National Health Insurance Annual Statistics Information Service 2010 June 28Available httpwwwdohgovtwstatisticdatavital statists9898health statistic--lifepdf
5 Chang TK (2007December 8) Common childhood cancer and its treatment Status
Childhood Cancer Foundation of ROC (TAIWAN) 2010 September 23 Available httpwwwccfrocorgtwchildchild_events_readphpe_id=45
6 Hockenberry MJ amp Wilson D Wongs nursing care of infants and children (8th ed) St
Louis MO Mosby 2007
7 Post-White J Fitzgerald M Savik K Hooke MC Hannahan AB amp Sencer SF
Massage therapy for children with cancer Journal of Pediatric Oncology Nursing 2009 26(1)16-28
8Chiang YC Yeh CH Wang WKamp Yang CP The experience of cancer-related fatigue
in Taiwanese children European Journal of Cancer Care 2009 18(1)43-49 9Langeveld NE Grootenhuis M A Voute P A de Haan RJ amp van den Bos C No excess
fatigue in young adult survivors of childhood cancer European Journal of Cancer 200339(2)204-214
10Piper BF Lindsey AM amp Dodd MJ Fatigue mechanisms in cancer patients
developing nursing theory Oncology Nursing Forum 1987 14(6)17-23 11Nail LM amp Winningham ML Fatigue In S L Groenwald M H Forgge M Goodman
amp C H Yarbro (Eds) Cancer Nursing Principles and practice (4 th ed) Boston Jones and Bartlett1997
12Irvine D Vincent L Graydon JE Bubela N amp Thompson L The prevalence and
correlates of fatigue in patients receiving treatment with chemotherapy and
668
36
radiotherapy A comparison with the fatigue experienced by healthy individuals Cancer Nursing 199417(5)367-378
13Hinds PS amp Hockenberry-Eaton M Developing a research program on fatigue in
children and adloescents diagnosed with cancer Journal of Pediatric Oncology Nursing 200118(2)3-12
14Aaronson LS Teel CS Cassmeyer V Neuberger GB Pallikkathayil L Pierce J Press
AN Williams DP amp Wingate A Defining and measuring fatigue Journal of Nursing scholarship 1999 31(1)45-50
15Yeh CH Wang CH Chiang YC Lin Lamp Chien LC Assessment of symptoms reported
by 10- to 18-year-old cancer patients in Taiwan 2009 38(5)738-746 16 Okuyama T Akechi T Kugaya A Okamura H Shima Yamp Maruguchi M
Development and validation of the cancer fatigue scale a brief three-dimensional self-rating scale for assessment of fatigue in cancer patients Journal of Pain amp Symptom Management 2000 19(1) 5-14
17Gibson F Mulhall AB Richardson A Edwards JL Ream E amp Sepion BJ A
phenomenologic study of fatigue in adolescents receiving treatment for cancer Oncology Nursing Forum200532(3)651-660
18Wolfe J Grier HE Klar N Levin SB Ellenbogen JMamp Salem-Schatz S et al
Symptoms and suffering at the end of life in children with cancer New England Journal of Medicine 2000342(5)326-333
19Whiting P Bagnall AM Sowden AJ Cornell JE Mulrow CD amp Ramirez G
Interventions for the treatment and management of chronic fatigue syndrome a systematic review JAMA the Journal of the American Medical Association 2001286(11)1360-1368
20 Kangas M Bovbjerg DHamp Montgomery G H Cancer-related fatigue a systematic
and meta-analytic review of non-pharmacological therapies for cancer patients Psychological Bulletin 2008134 (5)700-741
21Williams PD Schmideskamp J Ridder EL amp Williams AR Symptom monitoring and
dependent care during cancer treatment in children pilot study Cancer Nursing 200629(3)188-197
22Takken T van der Torre P Zwerink M Hulzebos EH Bierings M Helders PJMamp van
der Net J Development feasibility and efficacy of a community-based exercise training
669
37
program in pediatric cancer survivors Psycho-Oncology 200918(4)440-448
23Keats MR amp Culos-Reed SN A community-based physical activity program for
adolescents with cancer (project TREK) program feasibility and preliminary findings
Pediatric hematology and oncology 200830(4) 272-280
24Hinds PS Hockenberry M Rai SN Zhang L Razzouk B I Cremer L McCarthy K amp
Rodriguez-Galindo C Clinical field testing of an enhanced-activity intervention in
hospitalized children with cancer Journal of Pain amp Symptom Management 2007
33(6)686-697
25Chiang YC The effects of ldquo a home-based aerobic exercise interventionrdquo on fatigue
and cardiorespiratory fitness in children with acute lymphoblastic leukemia during the
maintenance stage of chemotherapy Unpublished thesis Taiwan Tao-Yuan 2007
26Langeveld N Ubbink M amp Smets E I dont have any energy The experience of
fatigue in young adult survivors of childhood cancer European journal of oncology
nursing 20004(1)20-28
27 Kisner C Colby L Therapeutic exercise Foundations and techniques 2nd ed Philadelphia PAFA Davies 2007
670
38
Appendix I JBI Critical Appraisal Checklist for Experimental studies
Author__________ Year_________ Record Number__________________
Questions 1 to 4 must be answered ldquoyesrdquo for study to be included in the metashyanalysis
1 Were the participants randomized to study groups
Yes No Not clear
2 Other than research intervention were participants in each groups treated the same
Yes No Not clear
3 Were the outcomes measured in the same manner for all participants
Yes No Not clear
4 Were groups comparable at entry
Yes No Not clear
5 Was randomization of participants blinded
Yes No Not clear
6 Were those assessing outcome blinded to treatment allocation (if outcome not objective such as survival or length of hospitalization)
Yes No Not clear
7 Was allocation to treatment groups concealed from the allocator
Yes No Not clear
8 Was an appropriate statistical analysis used
671
39
Yes No Not clear
9 Were outcomes measured in a reliable way
Yes No Not clear
10 Was there adequate followshyup of participants
Yes No Not clear
Summary
TOTAL
Yes No Not clear
DECISION
Use Reject
Narrative summary only Further information needed
COMMENTS
672
40
Appendix II JBI Data Extraction Tool for Quantitative Studies Authors and Year
Journal Title
Record NumberArticle Reference No
Reviewer
Method
Settings
Participants
Number of participants
Group A Group B Group C
Control Intervention 1 Intervention 2
Interventions
Group A
Control
Group B
Intervention 1
Group C
Intervention 2
Outcome measures
Definition
673
41
Other outcome measures
Outcome description ScaleMeasure
Results
Dichotomous Data
Outcome Control Group
Numbertotal number
Treatment Group
Numbertotal number
Continuous Data
Authorrsquos Conclusions
Comments
Outcome Control Group
Mean amp SD
Treatment Group
Mean amp SD
674
43
Appendix III Details of included studies (N=6)(2720212223) RefNo Author(s)
(years) Title Study question Research
method Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
22 Takken T van der Torre P Zwerink M Hulzebos E H Bierings M Helders P J Mamp van der Net J (2009)
Development feasibility and efficacy of a community-based exercise training program in pediatric cancer survivors
To develop a 12-week home-based exercise training program (comprising aerobic and strength exercises) for children who survived ALL and to study itrsquos feasibility and efficacy
Pre-post test design
No comparsion group
Survived ALL(N=9)ages 6-14 years
1anthropometry 2 muscle strength 3functional mobility 4cardio-pulmonary
exercise test 5Fatigue
1 Feasibility questionnaire 2 anthropometry electronic scale and a wallmounted stadiometerHarpenden skin fold calipers 3 muscle strength handheld dynamometer 4functional mobility Timed Up
and Go test (TUG) 5cardio-pulmonary exercise test electronically braked cycle ergometer 6Fatigue(mean)CSI-20 (subjective experience of fatigueconcentrationmotivationphysical activity)
112-week exercise training program
2 Patients were assessed before (T0) and after (T1) 12 weeks of training
1 muscle strength execapacity functional moand fatigue showed nosignificant differences between pre(meanplusmnSD415plusmn147) and post training(meanplusmnSD3687)
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
7 Post-White J Fitzgerald M Savik K Hooke M C Hannahan A B amp Sencer S F (2009)
Massage therapy for children with cancer
To determine whether 4 weekly sessions of massage compared with 4 quiet-time control conditions would reduce anxiety cortisol levels fatigue nausea and pain in children with cancer undergoing chemotherapy and would reduce anxiety fatigue and mood disturbance in a parent
2-period crossover design (Randomized)
quiet-time
control
sessions
Children with cancer 1 to 18 years of age Twenty-three childrenparent dyads were enrolled 17 completed all data points
children 1relaxation 2symptoms 3 fatigue
parents
1anxiety 2 fatigue
children 1relaxation (heart and respiratory rates blood pressure and salivary cortisol level)
2symptoms (pain nausea anxiety 3 fatigue 1-2y3-6yLansky Play Performance Scale (PPS) 7-13y
1 4 weekly massage (MT) sessions alternated with 4 weekly quiet-time(QT) control sessions
2 children included presession and postsession vital signs (heart rate respiratory rate blood pressure) and self-report (parent proxy report for age 1-2 years) of pain nausea and anxiety Fatigue was measured before sessions 1 and 4 and at each follow-up Parent measures
included anxiety fatigue and mood states
1Massage was moreeffective than quiet tireducing heart rate inchildren anxiety in cless than age 14 yeaparent anxiety 2There were no sign
changes in blood pcortisol pain naufatigue (no state d
3 Children reported tmassage helped thebetter lessened theirand worries and hadlasting effects than q
675
44
14-18yChild Fatigue Scale (CFS) (frequency
intensity) 2 parents anxiety and fatigue
676
45
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
24 Hinds P S Hockenberry M Rai S N Zhang L Razzouk B I Cremer L McCarthy K amp Rodriguez-Galindo C (2007)
Clinical field testing of an enhanced-activity intervention in hospitalized children with cancer
To determine the feasibility of an
enhanced physical activity EPA intervention in children and adolescents hospitalized to receive chemotherapy for a solid tumor or AML and to assess the sleep and fatigue outcomes of the intervention using two different statistical approaches to analyze the longitudinal symptom data
randomized prospective two-site and two-group pilot study
Standard care Twenty nine patients (25 with a solid tumor and 4 with AML)ages 7-18 years
1 sleep duration 2 sleep efficiency 3 fatigue
1sleep duration sleep efficiency The
Wrist Actigraph The Daily Sleep Diary-Parent 2 fatigue (mean) The Fatigue Scale(FS-C) for 7-12 (intensity) The Fatigue Scale(FS-A) for 13-18 The Fatigue Scale Parent Version (FS-P) The Fatigue Scale Staff Version (FS-S)
1enhanced physical activity (EPA) (hospital-based 30 minutes
twice daily for 2-4 days) 2 T0On the day of admission
(Day 0 or baseline)patient and parents completed the fatigue instruments and a team member applied the actigraph Patients wore the wrist actigraph T1 from Day 0 to 2 or 3 consecutive days (Days 0e3) In addition the patient same parent and staff nurses completed the daily sleep and fatigue reports in the late afternoons of Days 1-3
1 ANOVA model slesignificantly more the experimental athe control arm whdifferences from bsleep efficiency vaaveraged and com
2 The patient-reported mean fatigue scoresarms were higher amadolescents than for
3 The mixed model anarevealed no significandifferences in patientfatigue between
the two study arms otime( no final result iSD only give mixed result)
677
46
23 Keats M
R amp Culos-Reed S N (2008)
A community-based physical activity program for adolescents with cancer (project TREK) program feasibility and preliminary findings
To examine the
feasibility of a
theoretically-based
physical activity (PA)
intervention in
adolescents with
cancerand
examination of the
impact of the
program on
participant QOL
including social
emotional and
physical
well-being(including fatigue)
Repeat measures longitudinal design
No comparsion group
10 adolescents(Lymphoma(4)leukemia(4)CNS tumor(1)germ cell tumor(1)) ages 14-18 years
1physical fitness 2quality of life (QOL) 3PA behavior 4fatigue
1 Feasibility was assessed by participant recruitment attendance and adherence
2physical fitness Fitnessgram 3quality of life (QOL) Pediatric Quality of Life Inventory (PedsQL) 4PA behavior leisure score index (LSI) 5fatigue (mean) pediatric Quality of life
Multidimensional Fatigue Scale (Peds QL-MFS)
(Generalsleepcognitive fatigue)
116week physical activity (PA)
2 total PA physical fitness and overall QOL was assessed at 5 different intervals T0 preintervention (baseline) T1midintervention (after the
first 8 wk) T2 postintervention
(16 wk) T3 3-months
postintervention T4 1-year poststudy
initiation
1 from baseline -wkssig Improvementstotal PA physfitness and Qgeneral fatigue(meanplusmnSD 796plusmn135)
2 from baseline to 3FUsig Improvin general fatigue(meanplusmnSD824plusmn131)slefatigue(meanplusmnSD755plusmn191)totafatigue(meanplusmnSD778plusmn150)
3at 1 years FUsImprovements in sleeprest fatigue(meanplusmnSD725plusmn203)total (meanplusmnSD 763plusmn
678
47
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
2 Gene R E amp Conk Z (2008)
Impact of Effective Nursing Interventions to the Fatigue Syndrome in Children Who Receive Chemotherapy
1 to examine the effects of an effective nursing intervention to the fatigue syndrome of children 7 to 12 years of age who receive chemotherapy 2Tto examine the relationship between fatigue and demographic variables (age sex) diagnoses ([ALL AML] lymphoma) and therapy-related variables (eg level of hemoglobin
experimental randomized controlled study
Routine nursing care
A total of 60 children who are 7-12 years of age(a new diagnosis of ALL AML or lymphoma and receiving for the first time after being diagnosed a 7- to 10-day chemotherapy treatment )
fatigue The Fatigue Scale(FS-C) for 7-12 (intensity)
The Fatigue Scale Parent Version (FS-P)
1 effective nursing interventions(45- 60mdaya week)education about the fatigue with the chemotherapy and fatigue handbook 2 T1 After a 7-day period the children
and parent were evaluated with the Fatigue Scale
1The difference betwthe 2 mean values wafound to be statisticallsignificant 2 statistically significadifference was found between the Fatigue Scale-Child mean scothe experimental (272the control group (4213)children
679
48
25 Chiang et
al(2007)
The effects of ldquo a home ndashbased aerobic exercise interventionrdquo on fatigue and cardiorespiratory fitness in children with Acute Lymphoblastic Leukemia during the maintenance stage of chemotherapy
To examine the effect of ldquo a home ndashbased aerobic exercise interventionrdquo on fatigue and cardiorespiratory fitness in children with Acute Lymphoblastic Leukemia during the maintenance stage of chemotherapy
Quasi-experi -mental
Routine
nursing care
14 pediatric oncology patients in the experimental group and 10 in control group who were matched by age and sex ages7-18 years
1Cardiorespiratory fitness
2Fatigue
1Cardiorespiratory fitness Physical Activity Recall
VO2maxHR peak 6MWT
2 Fatigue PedsQL-MFS(Generalsleepcognitive fatigue)
1A six-week home-based aerobic exercise intervention 2 8 time points T0 baseline T1-T6 every week during the
intervention(6 weeks) T7 post intervention T8 follow-up (one month after
the end of the home-based exercise program)
1 For intent-to ndash treatthe findings indicated are no intervention efftime differences by anon the subscale of fat2 For per-protocol angeneral fatigue( mean422plusmn402) was the osubscale that was siglower for children whothe exercise interventthose in control groupfollow-up assessmentmonth after the compintervention) 3 The VO2peak are significantly improvingexperimental group atbaseline- and post-intassessment The VO2was significantly highechildren who were in experimental group thcontrol subjects at post-intervention assefor the per-protocol an
680
49
Appendix IV Instrument used to measure fatigue
Name Instrument
developers
Description Used in
age in
ref
Reliability
Consistency of
instrument
Checklist Individual Strength
(CIS)22
Vercoulen et
al1996
20 items using 7-point Likert scale of
fatigue To measure four aspects of
fatiguesubjective experience
contractionmotivation physical
Activity
6-14 Not reported
Child Fatigue Scale (CFS)7 Hockenberry
et al2003
14 items 2 part questionnaire frequency
(yes or no) 5-point Likert scale of the
intensity of any yes responses
7-13
14-18 α073-o84
The Fatigue Scale for 7-12
year Olds (FS-C)224
Hockenberry
et al
14 items provide a fatigue intensity score
5-point Likert scale
7-12 αo84
The Fatigue Scale for 13-18
year Olds (FS-A)24
Hockenberry
et al
14 items provide a fatigue intensity score
5-point Likert scale
13-18 α076-o96
Pediatric Quality of life
Multidimensional Fatigue
Scale (Peds QL-MFS)2325
Varni2002 18 items to measure three aspects of
fatigueGeneralsleepcognitive
14-18 Not reported
681
50
Appendix V Excluded studies and reasons for exclusion
Baggott C Dodd M Kennedy C Marina N Miaskowski C Multiple Symptoms in Pediatric Oncology
Patients A Systematic Review Journal of Pediatric Oncology Nursing 2009 Nov-Dec 27(6)
325-339
Reason for exclusion Not outcome of interest
Barlow JH Ellard DR Psycho-educational interventions for children with chronic disease parents and
siblings an overview of the research evidence base Care Health amp Development 2004 Nov
30(6)637-45
Reason for exclusion Not outcome of interest
Bedider S Moyer CA Randomized controlled trials of pediatric massage A review Evid Based
Complement Alternat Med 2007 Mar 4(1)23-34 Epub 2006 Nov 3
Reason for exclusion Not outcome of interest
de Nijs EJ Ros W Grijpdonck MH Nursing intervention for fatigue during the treatment for cancer Cancer
Nursing 2008 31(3)191-206
Reason for exclusion Not population of interest
Edwards JL Gibson F Richardson A Sepion B Ream E Fatigue in adolescents with and following a
cancer diagnosis developing an evidence base for practice European Journal of Cancer 2003
Dec 39(18)2671-80
Reason for exclusion Not experimental or quasi-experimental study
Hinds PS Hockenberry-Eatan M Developing a research program on fatigue in children and adolescents
diagnosed with cancer Journal of Pediatric Oncology Nursing 2001 Mar-Apr 18(2 Suppl
1)3-12
Reason for exclusion Not experimental or quasi-experimental study
Hockenberry-Eaton M Hinds PS Alcoser P ONeill JB Euell K Howard V Gattuso J Taylor J Fatigue in
Children and Adolescents With Cancer Journal of Pediatric Oncology Nursing 1998 July
15(3)172-182
Reason for exclusion Not experimental or quasi-experimental study
Jean-Pierre P Mustian K Kohli S Roscoe JA Hickok JT Morrow GR Community-based clinical oncology
research trials for cancer-related fatigue The Journal of Supportive Oncology 2006 Nov-Dec
4(10)511-6
682
51
Reason for exclusion Not population of interest
Kangas M Bovbjerg DH Montgomery GH Cancer-Related Fatigue A Systematic and Meta-Analytic
Review of Non-Pharmacological Therapies for Cancer Patients Psychological Bulletin 2008 Sep
134(5)700-41
Reason for exclusion Not population of interest
Lotfi-Jam K Carey M Jefford M Schofield P Charleson C Aranda S Nonpharmacologic strategies for
managing common chemotherapy adverse effects A systematic review Journal of Clinical
Oncology 2008 Dec 1 26(34)5618-29 Epub 2008 Nov 3
Reason for exclusion Not outcome of interest
Marchese VG Chiarello LA Lange BJ Effects of physical therapy intervention for children with acute
lymphoblastic leukemia Pediatr Blood Cancer 2004 Feb42(2)127-33
Reason for exclusion Not outcome of interest
Meeske KA Siegel SE Globe DR Mack WJ Bernstein L Prevalence and correlates of fatigue in
long-term survivors of childhood leukemia Journal of Clinical Oncology 2005 Aug 20
23(24)5501-10
Reason for exclusion Not intervention study
Minton O Richardson A Sharpe M Hotopf Stone P A systematic review and meta-analysis of the
pharmacological treatment of cancer-related fatigue J Natl Cancer Inst 2008 Aug 20
100(16)1155-66 Epub 2008 Aug 11
Reason for exclusion Not population and intervention of interest
Mustian KM Morrow GR Carroll JK Figueroa-Moseley CD Pascal JP Williams GC Integrative
nonpharmacologic behavioral interventions for the management of Cancer-Related fatigue The
Oncologist 2007 12(1)52-67
Reason for exclusion Not population of interest
Neill J Belan I Ried K Effectiveness of non-pharmacological interventions for fatigue in adults with
multiple sclerosis rheumatoid arthritis or systemic lupus erythematosus a systematic review
Journal of Advanced Nursing 2006 Dec 56(6)617-35
Reason for exclusion Not population of interest
Rheingans JI A systematic review of nonpharmacologic adjunctive therapies for symptom management
Journal of Pediatric Oncology Nursing 2007 24(2) 81-94
683
52
Reason for exclusion Not outcome of interest
Rheingans JI Pediatric oncology nursesrsquo management of patients symptoms Journal of Pediatric
Oncology Nursing 2008 Nov 25(6) 303-11
Reason for exclusion Not outcome of interest
San Juan AF Fleck SJ Chamorro-Vintildea C Mateacute-Muntildeoz JL Moral S Peacuterez M Cardona C Del Valle MF
Hernaacutendez M Ramiacuterez M Madero L Lucia A Effects of an intrahospital exercise program
intervention for children with leukemia Medicine amp Science in Sports amp Exercise 2007 Jan
39(1)13-21
Reason for exclusion Not outcome of interest
Sanford SD Okuma JO Pan J Srivastava DK West N Farr L Hinds PS Gender differences in sleep
fatigue and daytime activity in a pediatric oncology sample receiving dexamethasone Journal of
Pediatric Psychology 2008 Apr 33(3)298-306 Epub 2007 Nov 17
Reason for exclusion Not experimental or quasi-experimental study
Schmitz KH Holtzman J Courneya KS Macircsse LC Duval S Kane R Controlled physical activity trials in
cancer survivors a systematic review and meta-analysis Cancer Epidemiol Biomarkers Prev
2005 Jul 14(7)1588-95
Reason for exclusion Not population of interest
van Brussel M Takken T Lucia A van der Net J Helders PJ Is physical fitness decreased in survivors of
childhood leukemia A systematic review Leukemia 2005 Jan 19(1)13-7
Reason for exclusion Not population of interest
Whiting P Bagnall AM Snowden AJ Cornell JE Mulrow CD Ramirez G Interventions for the treatment
and management of chronic fatigue syndrome JAMA 2001 Sep 19 286(11)1360-8
Reason for exclusion Not intervention of interest
Whitsett SF Gudmundsdottir M Davies B McCarthy P Friedman D Chemotherapy-related fatigue in
childhood cancer correlates consequences and coping strategies Journal of Pediatric
Oncology Nursing 2008 Mar-Apr 25(2)86-96 Epub 2008 Feb 29
Reason for exclusion Not experimental or quasi-experimental study
Winner C Muumlller C Hoffmann C Boos J Rosenbaum D Physical activity and childhood cancer Pediatr
Blood Cancer 2010 Apr 54(4)501-10
Reason for exclusion Not research study
684
53
Wu M Hsu L Zhang B Shen N Lu H Li S The experiences of cancer-related fatigue among Chinese
children with leukaemia A phenomenological study Journal of Nursing Studies 2010 Jan
47(1)49-59 Epub 2009 Aug 25
Reason for exclusion Not experimental or quasi-experimental study
Yeh CH Chiang YC Lin L Yang CP Chien LC Weaver MA Chuang HL Clinical factors associated with
fatigue over time in paediatric oncology patients receiving chemotherapy British Journal of
Cancer 2008 Jul 8 99(1)23-9 Epub 2008 Jun 24
Reason for exclusion Not experimental or quasi-experimental study
685
18
quasi-experimental design7222425 with socre 5 to 6 out of 10 because the quality of
the whole papers is still acceptable therefore these six articles were accepted after
primary reviewer and secondary reviewerrsquos decision
Randomisation
In two RCT articles224 one study24 used to a computer-generated program operated by
the St Jude Protocol and Data Management System to randomize the sample Another
study2 didnrsquot address how randomization was done
Allocation concealment
No studies reported allocation concealment
Intention-to-treat analysis
One quasi-experimental design7 stated Intention-to-treat analysis
Adequate follow up
The follow-up periods included 2or 3 days24 7 days2 4 week7 one month25 6 week25 12
week2216 week23 and 1 year23
Baseline comparability of groups
Three 22425 of six studies had baseline comparability in terms of age sex diagnosis
race institution duration of illness
Blinded outcome assessment
No studies used blinded outcome assessment The researchers including study team
patients staff and families were not blinded to the patientrsquos group assignment
Characteristics of included studies
651
19
There were six studies related to interventions designed to cancer-related fatigue for
pediatric patients than there are for adults There are a total of six including five
English-language papers 27222324 and one Chinese-language paper 25 ranging in year of
publication from 2007 to 2009
Patient characteristics
The research subjects of four papers included both school-aged children and
adolescents 7222324 one papers involved mainly adolescents25 and one paper sampled
only school-aged children 2 the range in ages was between six-18 years The number of
patients included in the samples ranged from nine to 60 The sources of case data were
from both outpatients and hospitalized children The types of cancer included acute
lymphoblastic leukemia (ALL) solid tumors acute myeloid leukemia (AML) and
lymphoma Overall ALL was the most commonly studied cancer type The stage of the
disease varied in these reports some patients were in the maintenance stage of
chemotherapy25 some had just received their first round of chemotherapy224 some had
completed two courses of treatments lasting 4-8 weeks each 7 and some had entered
the survivor stage 2223
Countries
Two RCTrsquos 2 24 were conducted in the USA There were four quasi-experimental design
studiesThree studies conducted in the USA7 22 23 and one in Taiwan25
Intervention types
652
20
The interventions included exercise training programs 2225 physical activity 2324
massage therapy 7 and health education 223 exercise training and physical activity as
an intervention method given in three different settings home 22 25 community 23 or
hospital 24 The studies used different types of exercise interventions including
home-based aerobic exercise use a Video Compact Disc 25 use of a bicycle-style
exerciser 24 aerobics2223 and various types of physical activities2 and strength-building
exercises 2223 The intensity of the exercise varied and often included gradual warm-up
exercises a period of main exercise and a cool down period For these studies2023 the
target exercise intensity was a heart rate of gt90 of the maximum heart rate (HR max) or
the increase in the percentage of heart rate reserve ( HRR) of 40-60
The number of weeks for the exercisephysical activity interventions duration including
2-4 days 24 6 weeks25 12 weeks22 and 16 weeks23 The frequency of exercise ranged
from 2-3 times per week to twice a day Typical duration of exercise ranged from 10 to 45
minutes There are three papers using exercise interventions based on ACSM (American
College of Sports Medicine) 2225 recommendations and one of these used an Activity
pyramid from the ACSM to determine intensity 24
One article did not clarify the type of exercise intervention or the reasons for their choices
23 In addition there was an article focusing on massage therapy 7 as an intervention in
this study the experimental group received four weeks of massage therapy either in the
clinic or in the patientrsquos room the therapy was applied by a professional masseur and
targeted the back legs arms chest stomach and face of the children However the
frequency of massage sessions per week and the duration of the massages were not
653
21
given There is another article about intervention measures combine health education
and physical activity 2 In this study patients were informed about the following (1) health
education patients received daily education about chemotherapy-related fatigue and
information from a health education manual written by the author (2) encouragement for
children to engage in activities such as listening to music drawing and reading and (3)
physical activity which involved walking along the corridors of the ward for 10-15 minutes
These health education measures were presented for 45-60 minutes a day for a total of
seven days The study design for non-pharmacological interventions used control groups
that included primarily people who had received standard treatment or people who did
not receive an exercise intervention
Outcome measures
Five measurement tools were used in this group of seven papers concerning childrenrsquos
fatigue (Appendix IV) Because those studies included both school-age children and
adolescents the following descriptions will be differentiated by age Fatigue
measurements for school-aged children with cancer include the following the Child
Fatigue Scale (CFS) 7 a scale that measures the frequency and intensity of fatigue and
the Fatigue Scale for 7-12 year Olds (FS-C) 224 a scale that can be used to evaluate the
intensity of fatigue On the other hand fatigue measurements for adolescent cancer
patients include the following the Fatigue Scale for 13-18-year-olds (FS-A) 24 a measure
that can help evaluate fatigue levels the Pediatric Quality of Life Multidimensional
Fatigue Scale (Peds QL-MFS) 2325 a tool that can be divided into three sub-scales to
understand the general cognitive and sleep rest components of fatigue and finally the
CIS-20 for school-age children and adolescents 22 a scale that measures four levels of
654
22
fatigue namely subjective experience attention motivation and physical activity Two
studies used the Peds QL-MFS scale to measure fatigue2325
Meta-analysis results Two studies of the included papers failed to provide sufficient raw data they could not be
included in the meta-analysis Hinds et al 24 did not include post-test data Genc et al 2
provided no pre-test data PostWhite et al7 reported that fatigue after the health
education intervention was not statistically different but they presented the results
without presenting fatigue-related data Therefore the meta-analysis included three
studies 222325
The heterogeneity of studies was analyzed with Chi square statistics and no statistical
significance was found Therefore the data was combined in meta-analysis according to
exercise intervention on fatigue In addition there were three articles using the Peds
QL-MFS as a research tool to examine childrenrsquos improvements in fatigue Among these
Keats 22 and Chiang 24 present the effectiveness of exercise interventions using three
subscales Therefore the meta-analysis also analysis of the effects of these exercise
intervention measures on three subscales of Peds QL-MFS general fatigue sleep rest
fatigue and cognitive fatigue
The effectiveness of exercise intervention for fatigue We analyzed the exercise intervention effect on fatigue A total of 2 studies 22 23 were
included Takken et al 22 used community-based exercise training program to reduce
fatigue of children 6 to 14 years (mean 93y) of age who survived ALL Fatigue
measurement by Checklist Individual Strength (CIS) after 12-week of training fatigue
655
23
show no significant differences between pre (meanplusmnSD 415plusmn147) and post training
(meanplusmnSD368plusmn217) but fatigue change from baseline mean reduction of 11
Keats et al23 although used community-based physical activity program to reduce fatigue
for adolescents 14 to 18 years of age (mean162 y) with cancer (Lymphoma leukemia CNS
tumor germ cell tumor) Studies used fatigue by PedsQLMFS Results show general fatigue
from baseline to 8 weeks and to 3 months follow up significantly improves General
fatigue sleeprest fatigue and total fatigue from baseline to 3 months follow up showed
significant improvements Sleeprest fatigue and total fatigue at 1 years followed up were
significant improvements
Figure 2 shows the overall effect of exercise intervention in children and adolescents with
cancers with a focus on improving fatigue Due to the lower heterogeneity (p>005) the
fixed effects model was used to pool the data for meta-analysis (Overall effect size=
-006 95 Confidence Interval (CI) -070 to 058) A result did not indicate a statistically
significant difference (p = 087)
656
24
Figure2 Meta-analysis results of exercise intervention on fatigue
In addition Keats23 and Chiang25 used the three sub-scales of Peds QL-MFS to
determine the general cognitive and sleep rest components of fatigue The following
present the effectiveness of exercise interventions using three subscales including
general fatigue sleep rest fatigue and cognitive fatigue 2325
Chiang et al 25 used a 6- week home-based aerobic exercise intervention to reduce
fatigue of children 7 to 18 years (mean age at experimental group was 1088 y in control
group was 1247 y) of age who with acute lymphoblastic leukemia Fatigue measurement
by Peds QL-MFS after training For intent-to ndash treat analysis the findings indicated that
there are no intervention effects and time differences by any items on the subscale of
fatigue For per-protocol analysis general fatigue( meanplusmnSD 422plusmn402) was the only
subscale that was significantly lower for children who received the exercise intervention
than those in control group at follow-up assessment (one month after the completion of
intervention)
Keats et al23 although used community-based physical activity program to reduce fatigue
for adolescents 14 to 18 years of age (mean162 y) with cancer (Lymphoma leukemia
CNS tumor germ cell tumor) Both studies used fatigue by PedsQLMFS Results show
general fatigue from baseline to 8 weeks and to 3 months follow up significantly improves
657
25
General fatigue sleeprest fatigue and total fatigue from baseline to 3 months follow up
showed significant improvements Sleeprest fatigue and total fatigue at 1 years followed
up were significant improvements
The effectiveness of exercise intervention for general fatigue
The impact of the exercise interventions upon levels of general fatigue was also analysed
The heterogeneity was low (p>005) Therefore the fixed effects model was used to
examine the effectiveness The effect size is -076 indicating a statistically significant
difference (p = 001 95 CI -135 to -017 Fig 3) The evidence suggests that exercise
intervention can reduce general fatigue in children with cancer
Fig 3 Meta-analysis results of exercise intervention for general fatigue
The effectiveness of exercise intervention for sleep rest fatigue
The following is the result of the meta-analysis of the effectiveness of exercise
interventions on sleep rest fatigue First the heterogeneity test was conducted with P gt
005 representing small heterogeneity and the fixed effects model was used Fig 4
shows the effect size is -035 indicating no statistically significant differences (p = 023
95 CI-092 to 022 Fig 4)
658
26
Fig 4 Meta-analysis results of exercise intervention for sleep rest fatigue
The effectiveness of exercise intervention for cognitive fatigue Lastly the following data reports the results of meta-analysis of the effectiveness of
exercise interventions for cognitive fatigue The heterogeneity was p>005 then the
fixed effects model was used The effect size is -035 indicating no statistically significant
differences (p = 024 95 CI-092 023 Fig 5)
Fig 5 Meta-analysis results of exercise intervention for cognitive fatigue
Narrative presentation of remaining included studies
Three studies were not included in meta-analysis Post-White et al7 one of the aims in
this study was to examine the effect of massage therapy on fatigue in children with
cancer The study was a quasi-experimental design Twenty-three childrenparent dyads
were enrolled 17completed all data points Children with cancer ages 7 to 18 years
received at least 2 identical cycles of chemotherapy and one parent participated in the
2-period crossover design in which 4 weekly massage sessions (MT) alternated with 4
659
27
weekly quiet-time (QT) control sessions There were no significant changes in fatigue in
children over the 4-week MT or QT conditions either independently (change over time) or
when we compared fatigue by condition
The lack of effect of massage on fatigue may be the difficulty some children had in
differentiating fatigue from being relaxed underscores the challenge of measuring fatigue
in children Some children interpreted being tired or relaxed as having greater fatigue
because they felt like lying around and sleeping or felt unmotivated to do their usual
activities all measures of fatigue in the instrument used in the study
Hinds et al24conducted a prospective two-site randomized controlled pilot study to
assess the feasibility of an enhanced physical activity (EPA) intervention in hospitalized
children and adolescents receiving treatment for a solid tumor or for acute myeloid
leukemia (AML) Twenty-nine patients (25 with a solid tumor and 4 with AML) participated
age range from 736 to 1816 (mean 1248 y) The EPA intervention selected was
pedaling a stationary bicycle-style exerciser (Chattanooga Peddler Deluxe Bio-Teck
Medical Memphis TN) for 30 minutes twice daily for 2 to 4 days of hospitalization The
mixed model analysis revealed no significant differences in patient reports of fatigue
between the two study arms or over time
Genc et al2 conducted a RCT involving children with cancer who are 7 to 12 years of age
and receiving chemotherapy treatment to determine the impact of educational
intervention by nurses on decreasing the fatigue syndrome The research sample was
composed of a total of 60 children with cancer with 30 children being included in the
660
28
experimental group (mean age 923)and 30 children included in the control group (mean
age 937) with their mothers In the experimental group after the 7th to 10th day of the
chemotherapy treatment throughout a week the researcher conducted the nursing
interventions every day for 45 to 60 minutes In the control group routine nursing
interventions were carried out The experimental group received education about the
fatigue with the chemotherapy and fatigue handbook was given which was developed by
the authors Children and mothers were consulted for including activities that could
decrease fatigue which were described as effective interventions A statistically
significant difference was found between the Fatigue Scale-Child mean scores of the
experimental (2723) and the control group (4213) The results suggest that fatigue of
children with cancer can be reduced by implementing appropriate nursing interventions
(t=567 Plt00)
Discussion The purpose of this systematic review was to determine the effectiveness of
non-pharmacological interventions specifically targeting fatigue for children and
adolescents with cancer undergoing chemotherapy or after receiving chemotherapy
Included articles about the effectiveness of non-pharmacological interventions for
children and adolescents with cancer were published between the years of 2007 and
2009 Although interventions for cancer fatigue for adults have been extensively studied
it can be seen from either the title of the paper or related content that an intervention
study on children was a pilot study or a feasibility study Representing a field in its early
stage these studies show that the fatigue issues with young cancer patients have only
recently been taken seriously
661
29
The results of our meta-analysis include measurement of the four performance indicators
fatigue and general fatigue sleep rest fatigue and cognitive fatigue The results show
that there is a statistically significant difference only in the domain of general fatigue
using an exercise intervention for children with cancer can improve the degree of fatigue
with the effect size reaching 0671 Other results do not indicate significant differences
The reasons may include the following
1 Characteristics of the cancer The exhaustion from cancer occurs not only during cancer treatment but also in during
long-term survival a time during which patients may continue to be affected by this
symptom 8 26 Therefore when using intervention measures to improve fatigue
circumstances should be considered such as the process of the treatment and the course
or stage of the disease Because cancer patients will experience different forms of
treatment or courses of treatment the disease itself or treatment differences should be
considered in the choice of intervention Even chemotherapy drugs should be taken into
consideration For example a period of general steroid treatment can increase patientsrsquo
fatigue In those studies of children with cancer few studies looked solely at one type of
cancer most studies included a variety of cancer patients Furthermore most studies do
not clearly explain the stage of the disease or course of treatment and most do not
include treatment variables in the control group Moreover children with cancer may
have different levels of physical function
2 Research design The sample size Currently there are few studies with large sample size and a rigorous
RCT design due to the small number of papers available for analysis The sample size
included in our studyrsquos data analysis is between 20 and 42 people this small sample size
will affect the power available to evaluate outcome variables
Although most of the non-pharmacological interventions still use exercise and physical
activity and these studies overall show better results for fatigue as compared with
controls more research is still needed to further confirm the efficacy of these findings
662
30
The dropout rate in the evaluated research varies a great deal ranging from 5 to 45
these dropout rates may result from the characteristics of the research subjects or the
lengthy time involved in participating in these studies The research data with a high
turnover rate might not reflect the actual outcomes of participation in exercise and the
quality of the research contained in articles with high subject turnover rates may be
lower
Exercise doses and time The exercise doses needed to reduce fatigue cannot be
determined additionally the amount of exercise completed by the patient is also
inconsistent interventions vary between 2-3 times per week and two times a day and
exercise duration varies between 10 and 45 minutes each time Furthermore the study
interventions vary in length between a couple of days and a long period of 16 weeks The
data collection times are different some were measured 12 weeks after the intervention
began some were measured during the 6 weeks of intervention some were measured
three months after the intervention was finished and some were measured after one
year
In addition disease-related symptoms decrease childrenrsquos willingness to participate in
exercise interventions inappropriate exercise intervention programs may actually
increase childrens fatigue In addition the children in the study are still developing
physically it is important to consider ways to design an interesting exercise intervention
to increase the compliance of patients in order to improve the effectiveness Although
intervention programs in the hospital or in a community sports center can improve the
effectiveness because they provide supervision the feasibility of these programs is
questionable However if the program is home-based the children need to be
supervised by parents in order to improve their compliance in doing the exercises
Furthermore regarding the nature of the intervention the results from this study indicate
that the researched non-pharmacological interventions include the following exercise
training programs physical activity massage therapy and health education interventions
However according to the National Comprehensive Cancer Network 1 clinical guidelines
663
31
for cancer non-drug measures for cancer fatigue can be separated into five categories
(1) activity enhancement (2) psychosocial interventions such as cognitive behavioral
therapy (CBT) stress management relaxation techniques and support groups (3)
attention-restoring therapy (4) nutritional consultation and (5) cognitive behavioral
therapy specifically targeting sleep disturbance Researchers have also suggested that
psychosocial interventions should be included in the future research for children with
cancer-related fatigue 22
(2) The measurement tools in the study The assessment of fatigue can be
one-dimensional or multidimensional One-dimensional assessment can help understand
the severity of fatigue symptoms however multidimensional scales are often more
credible Therefore when measuring cancer-related fatigue researchers should consider
whether there is a uniform definition of fatigue or a standardized tool for measuring
fatigue in order to facilitate further systematic meta-analyses and further develop the
clinical care guidelines
Limitations of the review The present review has some potential limitations First the low methodological quality
may influence the result Although exercise intervention seems promising quality of the
RCTs was generally quite low Future studies require better design and reporting if
methodological issues to establish evidence-based nonpharmcologic intervention
Second the identified studies covered only a limited types of nonpharmcological
intervention especially in exercise intervention The guidelines for cancer-related fatigue
in NCCN (2011)1 referred to more interventions than the ones included in this review
such as cognitive behavioral therapy and nutrition consultation Thirdly the small sample
size and effect size could be potentially having led to underpowered approach for
detecting the effects on fatigue Therefore we recommend that as research continues to
grow a re-analysis can be undertaken Fourthly Combining data in meta analysis from
664
32
studies where the ages were quite different is a potential source of heterogeneity and
may affect the interpretation of the results
Conclusion At present clinical treatment is widely used for cancer patients However child and
adolescent cancer patients often experience various side effects which cause short-term
or long-term discomfort both physically and psychologically In particular with the
increasing cure rate cancer related fatigue during or after treatment has become an
important issue This study result provided positive effect of exercise intervention on
general fatigue
Implications for practice The results of this systematic review and meta-analysis show that exercise interventions
can effectively improve the level of general fatigue In particular although the articles
were self-reported feasibility studies their results all indicate that exercise interventions
for fatigue are feasible and safe there was no conclusion to be made for the use of
massage therapy or health education measures because there was only one article for
each of these interventions
Recommendations for practice
Cancer-related fatigue is one of the most severe and frequent symptoms by pediatric
oncology children and adolescent suffered during treatment and the symptom existed
even after treatment has ended Until now no golden standard of treatment to fatigue is
established The findings call for more attention to how to reduce patientrsquos levels of
fatigue Based on the available information evaluated in this review the following
recommendations for practice are provided
665
33
bull For children aged 7 to 18 who has cancer (eg Lymphoma leukemia CNS tumor
germ cell tumor) an effective progressive aerobic exercise program is recommended to
be at least 2-3 times per week 20 to 45 minute for each session and last for 6-16 weeks
in order to reduce their general fatigue (tiredness physically weakness) In addition
adults should be involved in accompanying children while they are performing physical
exercise of which should be able to improve the adherence rate (level 2 ) ( Grade of
recommendation A)
bull For children aged 7 to 18 who has cancer (eg Lymphoma leukemia CNS tumor
germ cell tumor) an progressive aerobic exercise program will not be effective to reduce
their sleep andor rest (sleeping or resting a lot) or cognitive fatigue (problems with
thinking quickly or problems with remembering) (level 2 ) ( Grade of recommendation C)
bull Nursing interventions in educating treatment of fatigue include information about
activity nutrition energy preservation consulting and providing a useful fatigue
handbook will benefit those children who are 7 to 12 years have a new diagnosis of ALL
AML or lymphoma and receive for the first time after being diagnosed a 7- to 10-day
chemotherapy treatment (level 2) ( Grade of recommendation A)
bull A 4-week massage therapy program (the therapists massage childrenrsquos back legs
arms stomachchest and face) is not effective for children who are aged 7 to 18 and
have acute lymphoblastic leukemia brain tumors lymphoma rhabdomyosarcoma
Wilms tumor or Ewing sarcoma(level 2)( Grade of recommendation C)
bull Using a 12-week aerobic and strength exercise (45-min exercise sessions twice a
week) is not effective for children who are aged 6-14 and survived acute lymphoblaststic
leukemia age from 6 to 14(level 2) ( Grade of recommendation C)
bull Using a physical activity intervention (30minutestwice daily for 2-4days) is not
effective for children who are 7 to 18 years of age with soild tumor or AML(level 2)
( Grade of recommendation C)
666
34
Implications for research According to this systematic review and meta-analysis results there are suggestions to
improve the effectiveness of future research on non-pharmacological interventions for
children and young peoplersquos cancer-related fatigue
As the majority of included non-pharmacological interventions for the fatigue of cancer
patients consist of exercise programs future research should also consider various
non-pharmacological interventions in order to understand the effectiveness of different
methods
Regarding the exercise intervention methods and studies should consider multiple
factors including the age or personal condition of the subject the disease stage and the
amount of daily activities Studies should use design prescriptions (eg frequency
intensity duration and type of exercise) and consider the adherence to the measures in
order to enhance the study strength
In measuring the results of non-pharmacological interventions there should be standard
definitions or standard measurement tools to facilitate the following systematic review
and meta-analysis that can subsequently be developed into clinical care guidelines
Reviewing the effectiveness of the current non-pharmacological management of children
and adolescent cancer patients there is still a lack of rigorous RCT research Limited by
the characteristics of cancer there is still a lack of large sample sizes
Potential conflicts of interest There is no conflict of interest
Acknowledgements
Thank you to Dr Rie Konno Research Fellow Joanna Briggs Institute for her help in
assessing studies
667
35
References 1 National Comprehensive Cancer Network( NCCN) in USA NCCN clinical practice
guideline in oncology cancer-related fatigue 2011 2 Ekti Genc R amp Conk Z Impact of effective nursing interventions to the fatigue
syndrome in children who receive chemotherapy Cancer Nursing 200831(4)312-317
3 Childhood Cancer Foundation of ROC (2009March) The classification of diseases
and age sex statistical tables of case Childhood Cancer Foundation of ROC newsletter103105-106
4 Department of Health Executive Yuan ROC (TAIWAN)(2009 March 20)2009 cause of death statistic Health and National Health Insurance Annual Statistics Information Service 2010 June 28Available httpwwwdohgovtwstatisticdatavital statists9898health statistic--lifepdf
5 Chang TK (2007December 8) Common childhood cancer and its treatment Status
Childhood Cancer Foundation of ROC (TAIWAN) 2010 September 23 Available httpwwwccfrocorgtwchildchild_events_readphpe_id=45
6 Hockenberry MJ amp Wilson D Wongs nursing care of infants and children (8th ed) St
Louis MO Mosby 2007
7 Post-White J Fitzgerald M Savik K Hooke MC Hannahan AB amp Sencer SF
Massage therapy for children with cancer Journal of Pediatric Oncology Nursing 2009 26(1)16-28
8Chiang YC Yeh CH Wang WKamp Yang CP The experience of cancer-related fatigue
in Taiwanese children European Journal of Cancer Care 2009 18(1)43-49 9Langeveld NE Grootenhuis M A Voute P A de Haan RJ amp van den Bos C No excess
fatigue in young adult survivors of childhood cancer European Journal of Cancer 200339(2)204-214
10Piper BF Lindsey AM amp Dodd MJ Fatigue mechanisms in cancer patients
developing nursing theory Oncology Nursing Forum 1987 14(6)17-23 11Nail LM amp Winningham ML Fatigue In S L Groenwald M H Forgge M Goodman
amp C H Yarbro (Eds) Cancer Nursing Principles and practice (4 th ed) Boston Jones and Bartlett1997
12Irvine D Vincent L Graydon JE Bubela N amp Thompson L The prevalence and
correlates of fatigue in patients receiving treatment with chemotherapy and
668
36
radiotherapy A comparison with the fatigue experienced by healthy individuals Cancer Nursing 199417(5)367-378
13Hinds PS amp Hockenberry-Eaton M Developing a research program on fatigue in
children and adloescents diagnosed with cancer Journal of Pediatric Oncology Nursing 200118(2)3-12
14Aaronson LS Teel CS Cassmeyer V Neuberger GB Pallikkathayil L Pierce J Press
AN Williams DP amp Wingate A Defining and measuring fatigue Journal of Nursing scholarship 1999 31(1)45-50
15Yeh CH Wang CH Chiang YC Lin Lamp Chien LC Assessment of symptoms reported
by 10- to 18-year-old cancer patients in Taiwan 2009 38(5)738-746 16 Okuyama T Akechi T Kugaya A Okamura H Shima Yamp Maruguchi M
Development and validation of the cancer fatigue scale a brief three-dimensional self-rating scale for assessment of fatigue in cancer patients Journal of Pain amp Symptom Management 2000 19(1) 5-14
17Gibson F Mulhall AB Richardson A Edwards JL Ream E amp Sepion BJ A
phenomenologic study of fatigue in adolescents receiving treatment for cancer Oncology Nursing Forum200532(3)651-660
18Wolfe J Grier HE Klar N Levin SB Ellenbogen JMamp Salem-Schatz S et al
Symptoms and suffering at the end of life in children with cancer New England Journal of Medicine 2000342(5)326-333
19Whiting P Bagnall AM Sowden AJ Cornell JE Mulrow CD amp Ramirez G
Interventions for the treatment and management of chronic fatigue syndrome a systematic review JAMA the Journal of the American Medical Association 2001286(11)1360-1368
20 Kangas M Bovbjerg DHamp Montgomery G H Cancer-related fatigue a systematic
and meta-analytic review of non-pharmacological therapies for cancer patients Psychological Bulletin 2008134 (5)700-741
21Williams PD Schmideskamp J Ridder EL amp Williams AR Symptom monitoring and
dependent care during cancer treatment in children pilot study Cancer Nursing 200629(3)188-197
22Takken T van der Torre P Zwerink M Hulzebos EH Bierings M Helders PJMamp van
der Net J Development feasibility and efficacy of a community-based exercise training
669
37
program in pediatric cancer survivors Psycho-Oncology 200918(4)440-448
23Keats MR amp Culos-Reed SN A community-based physical activity program for
adolescents with cancer (project TREK) program feasibility and preliminary findings
Pediatric hematology and oncology 200830(4) 272-280
24Hinds PS Hockenberry M Rai SN Zhang L Razzouk B I Cremer L McCarthy K amp
Rodriguez-Galindo C Clinical field testing of an enhanced-activity intervention in
hospitalized children with cancer Journal of Pain amp Symptom Management 2007
33(6)686-697
25Chiang YC The effects of ldquo a home-based aerobic exercise interventionrdquo on fatigue
and cardiorespiratory fitness in children with acute lymphoblastic leukemia during the
maintenance stage of chemotherapy Unpublished thesis Taiwan Tao-Yuan 2007
26Langeveld N Ubbink M amp Smets E I dont have any energy The experience of
fatigue in young adult survivors of childhood cancer European journal of oncology
nursing 20004(1)20-28
27 Kisner C Colby L Therapeutic exercise Foundations and techniques 2nd ed Philadelphia PAFA Davies 2007
670
38
Appendix I JBI Critical Appraisal Checklist for Experimental studies
Author__________ Year_________ Record Number__________________
Questions 1 to 4 must be answered ldquoyesrdquo for study to be included in the metashyanalysis
1 Were the participants randomized to study groups
Yes No Not clear
2 Other than research intervention were participants in each groups treated the same
Yes No Not clear
3 Were the outcomes measured in the same manner for all participants
Yes No Not clear
4 Were groups comparable at entry
Yes No Not clear
5 Was randomization of participants blinded
Yes No Not clear
6 Were those assessing outcome blinded to treatment allocation (if outcome not objective such as survival or length of hospitalization)
Yes No Not clear
7 Was allocation to treatment groups concealed from the allocator
Yes No Not clear
8 Was an appropriate statistical analysis used
671
39
Yes No Not clear
9 Were outcomes measured in a reliable way
Yes No Not clear
10 Was there adequate followshyup of participants
Yes No Not clear
Summary
TOTAL
Yes No Not clear
DECISION
Use Reject
Narrative summary only Further information needed
COMMENTS
672
40
Appendix II JBI Data Extraction Tool for Quantitative Studies Authors and Year
Journal Title
Record NumberArticle Reference No
Reviewer
Method
Settings
Participants
Number of participants
Group A Group B Group C
Control Intervention 1 Intervention 2
Interventions
Group A
Control
Group B
Intervention 1
Group C
Intervention 2
Outcome measures
Definition
673
41
Other outcome measures
Outcome description ScaleMeasure
Results
Dichotomous Data
Outcome Control Group
Numbertotal number
Treatment Group
Numbertotal number
Continuous Data
Authorrsquos Conclusions
Comments
Outcome Control Group
Mean amp SD
Treatment Group
Mean amp SD
674
43
Appendix III Details of included studies (N=6)(2720212223) RefNo Author(s)
(years) Title Study question Research
method Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
22 Takken T van der Torre P Zwerink M Hulzebos E H Bierings M Helders P J Mamp van der Net J (2009)
Development feasibility and efficacy of a community-based exercise training program in pediatric cancer survivors
To develop a 12-week home-based exercise training program (comprising aerobic and strength exercises) for children who survived ALL and to study itrsquos feasibility and efficacy
Pre-post test design
No comparsion group
Survived ALL(N=9)ages 6-14 years
1anthropometry 2 muscle strength 3functional mobility 4cardio-pulmonary
exercise test 5Fatigue
1 Feasibility questionnaire 2 anthropometry electronic scale and a wallmounted stadiometerHarpenden skin fold calipers 3 muscle strength handheld dynamometer 4functional mobility Timed Up
and Go test (TUG) 5cardio-pulmonary exercise test electronically braked cycle ergometer 6Fatigue(mean)CSI-20 (subjective experience of fatigueconcentrationmotivationphysical activity)
112-week exercise training program
2 Patients were assessed before (T0) and after (T1) 12 weeks of training
1 muscle strength execapacity functional moand fatigue showed nosignificant differences between pre(meanplusmnSD415plusmn147) and post training(meanplusmnSD3687)
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
7 Post-White J Fitzgerald M Savik K Hooke M C Hannahan A B amp Sencer S F (2009)
Massage therapy for children with cancer
To determine whether 4 weekly sessions of massage compared with 4 quiet-time control conditions would reduce anxiety cortisol levels fatigue nausea and pain in children with cancer undergoing chemotherapy and would reduce anxiety fatigue and mood disturbance in a parent
2-period crossover design (Randomized)
quiet-time
control
sessions
Children with cancer 1 to 18 years of age Twenty-three childrenparent dyads were enrolled 17 completed all data points
children 1relaxation 2symptoms 3 fatigue
parents
1anxiety 2 fatigue
children 1relaxation (heart and respiratory rates blood pressure and salivary cortisol level)
2symptoms (pain nausea anxiety 3 fatigue 1-2y3-6yLansky Play Performance Scale (PPS) 7-13y
1 4 weekly massage (MT) sessions alternated with 4 weekly quiet-time(QT) control sessions
2 children included presession and postsession vital signs (heart rate respiratory rate blood pressure) and self-report (parent proxy report for age 1-2 years) of pain nausea and anxiety Fatigue was measured before sessions 1 and 4 and at each follow-up Parent measures
included anxiety fatigue and mood states
1Massage was moreeffective than quiet tireducing heart rate inchildren anxiety in cless than age 14 yeaparent anxiety 2There were no sign
changes in blood pcortisol pain naufatigue (no state d
3 Children reported tmassage helped thebetter lessened theirand worries and hadlasting effects than q
675
44
14-18yChild Fatigue Scale (CFS) (frequency
intensity) 2 parents anxiety and fatigue
676
45
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
24 Hinds P S Hockenberry M Rai S N Zhang L Razzouk B I Cremer L McCarthy K amp Rodriguez-Galindo C (2007)
Clinical field testing of an enhanced-activity intervention in hospitalized children with cancer
To determine the feasibility of an
enhanced physical activity EPA intervention in children and adolescents hospitalized to receive chemotherapy for a solid tumor or AML and to assess the sleep and fatigue outcomes of the intervention using two different statistical approaches to analyze the longitudinal symptom data
randomized prospective two-site and two-group pilot study
Standard care Twenty nine patients (25 with a solid tumor and 4 with AML)ages 7-18 years
1 sleep duration 2 sleep efficiency 3 fatigue
1sleep duration sleep efficiency The
Wrist Actigraph The Daily Sleep Diary-Parent 2 fatigue (mean) The Fatigue Scale(FS-C) for 7-12 (intensity) The Fatigue Scale(FS-A) for 13-18 The Fatigue Scale Parent Version (FS-P) The Fatigue Scale Staff Version (FS-S)
1enhanced physical activity (EPA) (hospital-based 30 minutes
twice daily for 2-4 days) 2 T0On the day of admission
(Day 0 or baseline)patient and parents completed the fatigue instruments and a team member applied the actigraph Patients wore the wrist actigraph T1 from Day 0 to 2 or 3 consecutive days (Days 0e3) In addition the patient same parent and staff nurses completed the daily sleep and fatigue reports in the late afternoons of Days 1-3
1 ANOVA model slesignificantly more the experimental athe control arm whdifferences from bsleep efficiency vaaveraged and com
2 The patient-reported mean fatigue scoresarms were higher amadolescents than for
3 The mixed model anarevealed no significandifferences in patientfatigue between
the two study arms otime( no final result iSD only give mixed result)
677
46
23 Keats M
R amp Culos-Reed S N (2008)
A community-based physical activity program for adolescents with cancer (project TREK) program feasibility and preliminary findings
To examine the
feasibility of a
theoretically-based
physical activity (PA)
intervention in
adolescents with
cancerand
examination of the
impact of the
program on
participant QOL
including social
emotional and
physical
well-being(including fatigue)
Repeat measures longitudinal design
No comparsion group
10 adolescents(Lymphoma(4)leukemia(4)CNS tumor(1)germ cell tumor(1)) ages 14-18 years
1physical fitness 2quality of life (QOL) 3PA behavior 4fatigue
1 Feasibility was assessed by participant recruitment attendance and adherence
2physical fitness Fitnessgram 3quality of life (QOL) Pediatric Quality of Life Inventory (PedsQL) 4PA behavior leisure score index (LSI) 5fatigue (mean) pediatric Quality of life
Multidimensional Fatigue Scale (Peds QL-MFS)
(Generalsleepcognitive fatigue)
116week physical activity (PA)
2 total PA physical fitness and overall QOL was assessed at 5 different intervals T0 preintervention (baseline) T1midintervention (after the
first 8 wk) T2 postintervention
(16 wk) T3 3-months
postintervention T4 1-year poststudy
initiation
1 from baseline -wkssig Improvementstotal PA physfitness and Qgeneral fatigue(meanplusmnSD 796plusmn135)
2 from baseline to 3FUsig Improvin general fatigue(meanplusmnSD824plusmn131)slefatigue(meanplusmnSD755plusmn191)totafatigue(meanplusmnSD778plusmn150)
3at 1 years FUsImprovements in sleeprest fatigue(meanplusmnSD725plusmn203)total (meanplusmnSD 763plusmn
678
47
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
2 Gene R E amp Conk Z (2008)
Impact of Effective Nursing Interventions to the Fatigue Syndrome in Children Who Receive Chemotherapy
1 to examine the effects of an effective nursing intervention to the fatigue syndrome of children 7 to 12 years of age who receive chemotherapy 2Tto examine the relationship between fatigue and demographic variables (age sex) diagnoses ([ALL AML] lymphoma) and therapy-related variables (eg level of hemoglobin
experimental randomized controlled study
Routine nursing care
A total of 60 children who are 7-12 years of age(a new diagnosis of ALL AML or lymphoma and receiving for the first time after being diagnosed a 7- to 10-day chemotherapy treatment )
fatigue The Fatigue Scale(FS-C) for 7-12 (intensity)
The Fatigue Scale Parent Version (FS-P)
1 effective nursing interventions(45- 60mdaya week)education about the fatigue with the chemotherapy and fatigue handbook 2 T1 After a 7-day period the children
and parent were evaluated with the Fatigue Scale
1The difference betwthe 2 mean values wafound to be statisticallsignificant 2 statistically significadifference was found between the Fatigue Scale-Child mean scothe experimental (272the control group (4213)children
679
48
25 Chiang et
al(2007)
The effects of ldquo a home ndashbased aerobic exercise interventionrdquo on fatigue and cardiorespiratory fitness in children with Acute Lymphoblastic Leukemia during the maintenance stage of chemotherapy
To examine the effect of ldquo a home ndashbased aerobic exercise interventionrdquo on fatigue and cardiorespiratory fitness in children with Acute Lymphoblastic Leukemia during the maintenance stage of chemotherapy
Quasi-experi -mental
Routine
nursing care
14 pediatric oncology patients in the experimental group and 10 in control group who were matched by age and sex ages7-18 years
1Cardiorespiratory fitness
2Fatigue
1Cardiorespiratory fitness Physical Activity Recall
VO2maxHR peak 6MWT
2 Fatigue PedsQL-MFS(Generalsleepcognitive fatigue)
1A six-week home-based aerobic exercise intervention 2 8 time points T0 baseline T1-T6 every week during the
intervention(6 weeks) T7 post intervention T8 follow-up (one month after
the end of the home-based exercise program)
1 For intent-to ndash treatthe findings indicated are no intervention efftime differences by anon the subscale of fat2 For per-protocol angeneral fatigue( mean422plusmn402) was the osubscale that was siglower for children whothe exercise interventthose in control groupfollow-up assessmentmonth after the compintervention) 3 The VO2peak are significantly improvingexperimental group atbaseline- and post-intassessment The VO2was significantly highechildren who were in experimental group thcontrol subjects at post-intervention assefor the per-protocol an
680
49
Appendix IV Instrument used to measure fatigue
Name Instrument
developers
Description Used in
age in
ref
Reliability
Consistency of
instrument
Checklist Individual Strength
(CIS)22
Vercoulen et
al1996
20 items using 7-point Likert scale of
fatigue To measure four aspects of
fatiguesubjective experience
contractionmotivation physical
Activity
6-14 Not reported
Child Fatigue Scale (CFS)7 Hockenberry
et al2003
14 items 2 part questionnaire frequency
(yes or no) 5-point Likert scale of the
intensity of any yes responses
7-13
14-18 α073-o84
The Fatigue Scale for 7-12
year Olds (FS-C)224
Hockenberry
et al
14 items provide a fatigue intensity score
5-point Likert scale
7-12 αo84
The Fatigue Scale for 13-18
year Olds (FS-A)24
Hockenberry
et al
14 items provide a fatigue intensity score
5-point Likert scale
13-18 α076-o96
Pediatric Quality of life
Multidimensional Fatigue
Scale (Peds QL-MFS)2325
Varni2002 18 items to measure three aspects of
fatigueGeneralsleepcognitive
14-18 Not reported
681
50
Appendix V Excluded studies and reasons for exclusion
Baggott C Dodd M Kennedy C Marina N Miaskowski C Multiple Symptoms in Pediatric Oncology
Patients A Systematic Review Journal of Pediatric Oncology Nursing 2009 Nov-Dec 27(6)
325-339
Reason for exclusion Not outcome of interest
Barlow JH Ellard DR Psycho-educational interventions for children with chronic disease parents and
siblings an overview of the research evidence base Care Health amp Development 2004 Nov
30(6)637-45
Reason for exclusion Not outcome of interest
Bedider S Moyer CA Randomized controlled trials of pediatric massage A review Evid Based
Complement Alternat Med 2007 Mar 4(1)23-34 Epub 2006 Nov 3
Reason for exclusion Not outcome of interest
de Nijs EJ Ros W Grijpdonck MH Nursing intervention for fatigue during the treatment for cancer Cancer
Nursing 2008 31(3)191-206
Reason for exclusion Not population of interest
Edwards JL Gibson F Richardson A Sepion B Ream E Fatigue in adolescents with and following a
cancer diagnosis developing an evidence base for practice European Journal of Cancer 2003
Dec 39(18)2671-80
Reason for exclusion Not experimental or quasi-experimental study
Hinds PS Hockenberry-Eatan M Developing a research program on fatigue in children and adolescents
diagnosed with cancer Journal of Pediatric Oncology Nursing 2001 Mar-Apr 18(2 Suppl
1)3-12
Reason for exclusion Not experimental or quasi-experimental study
Hockenberry-Eaton M Hinds PS Alcoser P ONeill JB Euell K Howard V Gattuso J Taylor J Fatigue in
Children and Adolescents With Cancer Journal of Pediatric Oncology Nursing 1998 July
15(3)172-182
Reason for exclusion Not experimental or quasi-experimental study
Jean-Pierre P Mustian K Kohli S Roscoe JA Hickok JT Morrow GR Community-based clinical oncology
research trials for cancer-related fatigue The Journal of Supportive Oncology 2006 Nov-Dec
4(10)511-6
682
51
Reason for exclusion Not population of interest
Kangas M Bovbjerg DH Montgomery GH Cancer-Related Fatigue A Systematic and Meta-Analytic
Review of Non-Pharmacological Therapies for Cancer Patients Psychological Bulletin 2008 Sep
134(5)700-41
Reason for exclusion Not population of interest
Lotfi-Jam K Carey M Jefford M Schofield P Charleson C Aranda S Nonpharmacologic strategies for
managing common chemotherapy adverse effects A systematic review Journal of Clinical
Oncology 2008 Dec 1 26(34)5618-29 Epub 2008 Nov 3
Reason for exclusion Not outcome of interest
Marchese VG Chiarello LA Lange BJ Effects of physical therapy intervention for children with acute
lymphoblastic leukemia Pediatr Blood Cancer 2004 Feb42(2)127-33
Reason for exclusion Not outcome of interest
Meeske KA Siegel SE Globe DR Mack WJ Bernstein L Prevalence and correlates of fatigue in
long-term survivors of childhood leukemia Journal of Clinical Oncology 2005 Aug 20
23(24)5501-10
Reason for exclusion Not intervention study
Minton O Richardson A Sharpe M Hotopf Stone P A systematic review and meta-analysis of the
pharmacological treatment of cancer-related fatigue J Natl Cancer Inst 2008 Aug 20
100(16)1155-66 Epub 2008 Aug 11
Reason for exclusion Not population and intervention of interest
Mustian KM Morrow GR Carroll JK Figueroa-Moseley CD Pascal JP Williams GC Integrative
nonpharmacologic behavioral interventions for the management of Cancer-Related fatigue The
Oncologist 2007 12(1)52-67
Reason for exclusion Not population of interest
Neill J Belan I Ried K Effectiveness of non-pharmacological interventions for fatigue in adults with
multiple sclerosis rheumatoid arthritis or systemic lupus erythematosus a systematic review
Journal of Advanced Nursing 2006 Dec 56(6)617-35
Reason for exclusion Not population of interest
Rheingans JI A systematic review of nonpharmacologic adjunctive therapies for symptom management
Journal of Pediatric Oncology Nursing 2007 24(2) 81-94
683
52
Reason for exclusion Not outcome of interest
Rheingans JI Pediatric oncology nursesrsquo management of patients symptoms Journal of Pediatric
Oncology Nursing 2008 Nov 25(6) 303-11
Reason for exclusion Not outcome of interest
San Juan AF Fleck SJ Chamorro-Vintildea C Mateacute-Muntildeoz JL Moral S Peacuterez M Cardona C Del Valle MF
Hernaacutendez M Ramiacuterez M Madero L Lucia A Effects of an intrahospital exercise program
intervention for children with leukemia Medicine amp Science in Sports amp Exercise 2007 Jan
39(1)13-21
Reason for exclusion Not outcome of interest
Sanford SD Okuma JO Pan J Srivastava DK West N Farr L Hinds PS Gender differences in sleep
fatigue and daytime activity in a pediatric oncology sample receiving dexamethasone Journal of
Pediatric Psychology 2008 Apr 33(3)298-306 Epub 2007 Nov 17
Reason for exclusion Not experimental or quasi-experimental study
Schmitz KH Holtzman J Courneya KS Macircsse LC Duval S Kane R Controlled physical activity trials in
cancer survivors a systematic review and meta-analysis Cancer Epidemiol Biomarkers Prev
2005 Jul 14(7)1588-95
Reason for exclusion Not population of interest
van Brussel M Takken T Lucia A van der Net J Helders PJ Is physical fitness decreased in survivors of
childhood leukemia A systematic review Leukemia 2005 Jan 19(1)13-7
Reason for exclusion Not population of interest
Whiting P Bagnall AM Snowden AJ Cornell JE Mulrow CD Ramirez G Interventions for the treatment
and management of chronic fatigue syndrome JAMA 2001 Sep 19 286(11)1360-8
Reason for exclusion Not intervention of interest
Whitsett SF Gudmundsdottir M Davies B McCarthy P Friedman D Chemotherapy-related fatigue in
childhood cancer correlates consequences and coping strategies Journal of Pediatric
Oncology Nursing 2008 Mar-Apr 25(2)86-96 Epub 2008 Feb 29
Reason for exclusion Not experimental or quasi-experimental study
Winner C Muumlller C Hoffmann C Boos J Rosenbaum D Physical activity and childhood cancer Pediatr
Blood Cancer 2010 Apr 54(4)501-10
Reason for exclusion Not research study
684
53
Wu M Hsu L Zhang B Shen N Lu H Li S The experiences of cancer-related fatigue among Chinese
children with leukaemia A phenomenological study Journal of Nursing Studies 2010 Jan
47(1)49-59 Epub 2009 Aug 25
Reason for exclusion Not experimental or quasi-experimental study
Yeh CH Chiang YC Lin L Yang CP Chien LC Weaver MA Chuang HL Clinical factors associated with
fatigue over time in paediatric oncology patients receiving chemotherapy British Journal of
Cancer 2008 Jul 8 99(1)23-9 Epub 2008 Jun 24
Reason for exclusion Not experimental or quasi-experimental study
685
19
There were six studies related to interventions designed to cancer-related fatigue for
pediatric patients than there are for adults There are a total of six including five
English-language papers 27222324 and one Chinese-language paper 25 ranging in year of
publication from 2007 to 2009
Patient characteristics
The research subjects of four papers included both school-aged children and
adolescents 7222324 one papers involved mainly adolescents25 and one paper sampled
only school-aged children 2 the range in ages was between six-18 years The number of
patients included in the samples ranged from nine to 60 The sources of case data were
from both outpatients and hospitalized children The types of cancer included acute
lymphoblastic leukemia (ALL) solid tumors acute myeloid leukemia (AML) and
lymphoma Overall ALL was the most commonly studied cancer type The stage of the
disease varied in these reports some patients were in the maintenance stage of
chemotherapy25 some had just received their first round of chemotherapy224 some had
completed two courses of treatments lasting 4-8 weeks each 7 and some had entered
the survivor stage 2223
Countries
Two RCTrsquos 2 24 were conducted in the USA There were four quasi-experimental design
studiesThree studies conducted in the USA7 22 23 and one in Taiwan25
Intervention types
652
20
The interventions included exercise training programs 2225 physical activity 2324
massage therapy 7 and health education 223 exercise training and physical activity as
an intervention method given in three different settings home 22 25 community 23 or
hospital 24 The studies used different types of exercise interventions including
home-based aerobic exercise use a Video Compact Disc 25 use of a bicycle-style
exerciser 24 aerobics2223 and various types of physical activities2 and strength-building
exercises 2223 The intensity of the exercise varied and often included gradual warm-up
exercises a period of main exercise and a cool down period For these studies2023 the
target exercise intensity was a heart rate of gt90 of the maximum heart rate (HR max) or
the increase in the percentage of heart rate reserve ( HRR) of 40-60
The number of weeks for the exercisephysical activity interventions duration including
2-4 days 24 6 weeks25 12 weeks22 and 16 weeks23 The frequency of exercise ranged
from 2-3 times per week to twice a day Typical duration of exercise ranged from 10 to 45
minutes There are three papers using exercise interventions based on ACSM (American
College of Sports Medicine) 2225 recommendations and one of these used an Activity
pyramid from the ACSM to determine intensity 24
One article did not clarify the type of exercise intervention or the reasons for their choices
23 In addition there was an article focusing on massage therapy 7 as an intervention in
this study the experimental group received four weeks of massage therapy either in the
clinic or in the patientrsquos room the therapy was applied by a professional masseur and
targeted the back legs arms chest stomach and face of the children However the
frequency of massage sessions per week and the duration of the massages were not
653
21
given There is another article about intervention measures combine health education
and physical activity 2 In this study patients were informed about the following (1) health
education patients received daily education about chemotherapy-related fatigue and
information from a health education manual written by the author (2) encouragement for
children to engage in activities such as listening to music drawing and reading and (3)
physical activity which involved walking along the corridors of the ward for 10-15 minutes
These health education measures were presented for 45-60 minutes a day for a total of
seven days The study design for non-pharmacological interventions used control groups
that included primarily people who had received standard treatment or people who did
not receive an exercise intervention
Outcome measures
Five measurement tools were used in this group of seven papers concerning childrenrsquos
fatigue (Appendix IV) Because those studies included both school-age children and
adolescents the following descriptions will be differentiated by age Fatigue
measurements for school-aged children with cancer include the following the Child
Fatigue Scale (CFS) 7 a scale that measures the frequency and intensity of fatigue and
the Fatigue Scale for 7-12 year Olds (FS-C) 224 a scale that can be used to evaluate the
intensity of fatigue On the other hand fatigue measurements for adolescent cancer
patients include the following the Fatigue Scale for 13-18-year-olds (FS-A) 24 a measure
that can help evaluate fatigue levels the Pediatric Quality of Life Multidimensional
Fatigue Scale (Peds QL-MFS) 2325 a tool that can be divided into three sub-scales to
understand the general cognitive and sleep rest components of fatigue and finally the
CIS-20 for school-age children and adolescents 22 a scale that measures four levels of
654
22
fatigue namely subjective experience attention motivation and physical activity Two
studies used the Peds QL-MFS scale to measure fatigue2325
Meta-analysis results Two studies of the included papers failed to provide sufficient raw data they could not be
included in the meta-analysis Hinds et al 24 did not include post-test data Genc et al 2
provided no pre-test data PostWhite et al7 reported that fatigue after the health
education intervention was not statistically different but they presented the results
without presenting fatigue-related data Therefore the meta-analysis included three
studies 222325
The heterogeneity of studies was analyzed with Chi square statistics and no statistical
significance was found Therefore the data was combined in meta-analysis according to
exercise intervention on fatigue In addition there were three articles using the Peds
QL-MFS as a research tool to examine childrenrsquos improvements in fatigue Among these
Keats 22 and Chiang 24 present the effectiveness of exercise interventions using three
subscales Therefore the meta-analysis also analysis of the effects of these exercise
intervention measures on three subscales of Peds QL-MFS general fatigue sleep rest
fatigue and cognitive fatigue
The effectiveness of exercise intervention for fatigue We analyzed the exercise intervention effect on fatigue A total of 2 studies 22 23 were
included Takken et al 22 used community-based exercise training program to reduce
fatigue of children 6 to 14 years (mean 93y) of age who survived ALL Fatigue
measurement by Checklist Individual Strength (CIS) after 12-week of training fatigue
655
23
show no significant differences between pre (meanplusmnSD 415plusmn147) and post training
(meanplusmnSD368plusmn217) but fatigue change from baseline mean reduction of 11
Keats et al23 although used community-based physical activity program to reduce fatigue
for adolescents 14 to 18 years of age (mean162 y) with cancer (Lymphoma leukemia CNS
tumor germ cell tumor) Studies used fatigue by PedsQLMFS Results show general fatigue
from baseline to 8 weeks and to 3 months follow up significantly improves General
fatigue sleeprest fatigue and total fatigue from baseline to 3 months follow up showed
significant improvements Sleeprest fatigue and total fatigue at 1 years followed up were
significant improvements
Figure 2 shows the overall effect of exercise intervention in children and adolescents with
cancers with a focus on improving fatigue Due to the lower heterogeneity (p>005) the
fixed effects model was used to pool the data for meta-analysis (Overall effect size=
-006 95 Confidence Interval (CI) -070 to 058) A result did not indicate a statistically
significant difference (p = 087)
656
24
Figure2 Meta-analysis results of exercise intervention on fatigue
In addition Keats23 and Chiang25 used the three sub-scales of Peds QL-MFS to
determine the general cognitive and sleep rest components of fatigue The following
present the effectiveness of exercise interventions using three subscales including
general fatigue sleep rest fatigue and cognitive fatigue 2325
Chiang et al 25 used a 6- week home-based aerobic exercise intervention to reduce
fatigue of children 7 to 18 years (mean age at experimental group was 1088 y in control
group was 1247 y) of age who with acute lymphoblastic leukemia Fatigue measurement
by Peds QL-MFS after training For intent-to ndash treat analysis the findings indicated that
there are no intervention effects and time differences by any items on the subscale of
fatigue For per-protocol analysis general fatigue( meanplusmnSD 422plusmn402) was the only
subscale that was significantly lower for children who received the exercise intervention
than those in control group at follow-up assessment (one month after the completion of
intervention)
Keats et al23 although used community-based physical activity program to reduce fatigue
for adolescents 14 to 18 years of age (mean162 y) with cancer (Lymphoma leukemia
CNS tumor germ cell tumor) Both studies used fatigue by PedsQLMFS Results show
general fatigue from baseline to 8 weeks and to 3 months follow up significantly improves
657
25
General fatigue sleeprest fatigue and total fatigue from baseline to 3 months follow up
showed significant improvements Sleeprest fatigue and total fatigue at 1 years followed
up were significant improvements
The effectiveness of exercise intervention for general fatigue
The impact of the exercise interventions upon levels of general fatigue was also analysed
The heterogeneity was low (p>005) Therefore the fixed effects model was used to
examine the effectiveness The effect size is -076 indicating a statistically significant
difference (p = 001 95 CI -135 to -017 Fig 3) The evidence suggests that exercise
intervention can reduce general fatigue in children with cancer
Fig 3 Meta-analysis results of exercise intervention for general fatigue
The effectiveness of exercise intervention for sleep rest fatigue
The following is the result of the meta-analysis of the effectiveness of exercise
interventions on sleep rest fatigue First the heterogeneity test was conducted with P gt
005 representing small heterogeneity and the fixed effects model was used Fig 4
shows the effect size is -035 indicating no statistically significant differences (p = 023
95 CI-092 to 022 Fig 4)
658
26
Fig 4 Meta-analysis results of exercise intervention for sleep rest fatigue
The effectiveness of exercise intervention for cognitive fatigue Lastly the following data reports the results of meta-analysis of the effectiveness of
exercise interventions for cognitive fatigue The heterogeneity was p>005 then the
fixed effects model was used The effect size is -035 indicating no statistically significant
differences (p = 024 95 CI-092 023 Fig 5)
Fig 5 Meta-analysis results of exercise intervention for cognitive fatigue
Narrative presentation of remaining included studies
Three studies were not included in meta-analysis Post-White et al7 one of the aims in
this study was to examine the effect of massage therapy on fatigue in children with
cancer The study was a quasi-experimental design Twenty-three childrenparent dyads
were enrolled 17completed all data points Children with cancer ages 7 to 18 years
received at least 2 identical cycles of chemotherapy and one parent participated in the
2-period crossover design in which 4 weekly massage sessions (MT) alternated with 4
659
27
weekly quiet-time (QT) control sessions There were no significant changes in fatigue in
children over the 4-week MT or QT conditions either independently (change over time) or
when we compared fatigue by condition
The lack of effect of massage on fatigue may be the difficulty some children had in
differentiating fatigue from being relaxed underscores the challenge of measuring fatigue
in children Some children interpreted being tired or relaxed as having greater fatigue
because they felt like lying around and sleeping or felt unmotivated to do their usual
activities all measures of fatigue in the instrument used in the study
Hinds et al24conducted a prospective two-site randomized controlled pilot study to
assess the feasibility of an enhanced physical activity (EPA) intervention in hospitalized
children and adolescents receiving treatment for a solid tumor or for acute myeloid
leukemia (AML) Twenty-nine patients (25 with a solid tumor and 4 with AML) participated
age range from 736 to 1816 (mean 1248 y) The EPA intervention selected was
pedaling a stationary bicycle-style exerciser (Chattanooga Peddler Deluxe Bio-Teck
Medical Memphis TN) for 30 minutes twice daily for 2 to 4 days of hospitalization The
mixed model analysis revealed no significant differences in patient reports of fatigue
between the two study arms or over time
Genc et al2 conducted a RCT involving children with cancer who are 7 to 12 years of age
and receiving chemotherapy treatment to determine the impact of educational
intervention by nurses on decreasing the fatigue syndrome The research sample was
composed of a total of 60 children with cancer with 30 children being included in the
660
28
experimental group (mean age 923)and 30 children included in the control group (mean
age 937) with their mothers In the experimental group after the 7th to 10th day of the
chemotherapy treatment throughout a week the researcher conducted the nursing
interventions every day for 45 to 60 minutes In the control group routine nursing
interventions were carried out The experimental group received education about the
fatigue with the chemotherapy and fatigue handbook was given which was developed by
the authors Children and mothers were consulted for including activities that could
decrease fatigue which were described as effective interventions A statistically
significant difference was found between the Fatigue Scale-Child mean scores of the
experimental (2723) and the control group (4213) The results suggest that fatigue of
children with cancer can be reduced by implementing appropriate nursing interventions
(t=567 Plt00)
Discussion The purpose of this systematic review was to determine the effectiveness of
non-pharmacological interventions specifically targeting fatigue for children and
adolescents with cancer undergoing chemotherapy or after receiving chemotherapy
Included articles about the effectiveness of non-pharmacological interventions for
children and adolescents with cancer were published between the years of 2007 and
2009 Although interventions for cancer fatigue for adults have been extensively studied
it can be seen from either the title of the paper or related content that an intervention
study on children was a pilot study or a feasibility study Representing a field in its early
stage these studies show that the fatigue issues with young cancer patients have only
recently been taken seriously
661
29
The results of our meta-analysis include measurement of the four performance indicators
fatigue and general fatigue sleep rest fatigue and cognitive fatigue The results show
that there is a statistically significant difference only in the domain of general fatigue
using an exercise intervention for children with cancer can improve the degree of fatigue
with the effect size reaching 0671 Other results do not indicate significant differences
The reasons may include the following
1 Characteristics of the cancer The exhaustion from cancer occurs not only during cancer treatment but also in during
long-term survival a time during which patients may continue to be affected by this
symptom 8 26 Therefore when using intervention measures to improve fatigue
circumstances should be considered such as the process of the treatment and the course
or stage of the disease Because cancer patients will experience different forms of
treatment or courses of treatment the disease itself or treatment differences should be
considered in the choice of intervention Even chemotherapy drugs should be taken into
consideration For example a period of general steroid treatment can increase patientsrsquo
fatigue In those studies of children with cancer few studies looked solely at one type of
cancer most studies included a variety of cancer patients Furthermore most studies do
not clearly explain the stage of the disease or course of treatment and most do not
include treatment variables in the control group Moreover children with cancer may
have different levels of physical function
2 Research design The sample size Currently there are few studies with large sample size and a rigorous
RCT design due to the small number of papers available for analysis The sample size
included in our studyrsquos data analysis is between 20 and 42 people this small sample size
will affect the power available to evaluate outcome variables
Although most of the non-pharmacological interventions still use exercise and physical
activity and these studies overall show better results for fatigue as compared with
controls more research is still needed to further confirm the efficacy of these findings
662
30
The dropout rate in the evaluated research varies a great deal ranging from 5 to 45
these dropout rates may result from the characteristics of the research subjects or the
lengthy time involved in participating in these studies The research data with a high
turnover rate might not reflect the actual outcomes of participation in exercise and the
quality of the research contained in articles with high subject turnover rates may be
lower
Exercise doses and time The exercise doses needed to reduce fatigue cannot be
determined additionally the amount of exercise completed by the patient is also
inconsistent interventions vary between 2-3 times per week and two times a day and
exercise duration varies between 10 and 45 minutes each time Furthermore the study
interventions vary in length between a couple of days and a long period of 16 weeks The
data collection times are different some were measured 12 weeks after the intervention
began some were measured during the 6 weeks of intervention some were measured
three months after the intervention was finished and some were measured after one
year
In addition disease-related symptoms decrease childrenrsquos willingness to participate in
exercise interventions inappropriate exercise intervention programs may actually
increase childrens fatigue In addition the children in the study are still developing
physically it is important to consider ways to design an interesting exercise intervention
to increase the compliance of patients in order to improve the effectiveness Although
intervention programs in the hospital or in a community sports center can improve the
effectiveness because they provide supervision the feasibility of these programs is
questionable However if the program is home-based the children need to be
supervised by parents in order to improve their compliance in doing the exercises
Furthermore regarding the nature of the intervention the results from this study indicate
that the researched non-pharmacological interventions include the following exercise
training programs physical activity massage therapy and health education interventions
However according to the National Comprehensive Cancer Network 1 clinical guidelines
663
31
for cancer non-drug measures for cancer fatigue can be separated into five categories
(1) activity enhancement (2) psychosocial interventions such as cognitive behavioral
therapy (CBT) stress management relaxation techniques and support groups (3)
attention-restoring therapy (4) nutritional consultation and (5) cognitive behavioral
therapy specifically targeting sleep disturbance Researchers have also suggested that
psychosocial interventions should be included in the future research for children with
cancer-related fatigue 22
(2) The measurement tools in the study The assessment of fatigue can be
one-dimensional or multidimensional One-dimensional assessment can help understand
the severity of fatigue symptoms however multidimensional scales are often more
credible Therefore when measuring cancer-related fatigue researchers should consider
whether there is a uniform definition of fatigue or a standardized tool for measuring
fatigue in order to facilitate further systematic meta-analyses and further develop the
clinical care guidelines
Limitations of the review The present review has some potential limitations First the low methodological quality
may influence the result Although exercise intervention seems promising quality of the
RCTs was generally quite low Future studies require better design and reporting if
methodological issues to establish evidence-based nonpharmcologic intervention
Second the identified studies covered only a limited types of nonpharmcological
intervention especially in exercise intervention The guidelines for cancer-related fatigue
in NCCN (2011)1 referred to more interventions than the ones included in this review
such as cognitive behavioral therapy and nutrition consultation Thirdly the small sample
size and effect size could be potentially having led to underpowered approach for
detecting the effects on fatigue Therefore we recommend that as research continues to
grow a re-analysis can be undertaken Fourthly Combining data in meta analysis from
664
32
studies where the ages were quite different is a potential source of heterogeneity and
may affect the interpretation of the results
Conclusion At present clinical treatment is widely used for cancer patients However child and
adolescent cancer patients often experience various side effects which cause short-term
or long-term discomfort both physically and psychologically In particular with the
increasing cure rate cancer related fatigue during or after treatment has become an
important issue This study result provided positive effect of exercise intervention on
general fatigue
Implications for practice The results of this systematic review and meta-analysis show that exercise interventions
can effectively improve the level of general fatigue In particular although the articles
were self-reported feasibility studies their results all indicate that exercise interventions
for fatigue are feasible and safe there was no conclusion to be made for the use of
massage therapy or health education measures because there was only one article for
each of these interventions
Recommendations for practice
Cancer-related fatigue is one of the most severe and frequent symptoms by pediatric
oncology children and adolescent suffered during treatment and the symptom existed
even after treatment has ended Until now no golden standard of treatment to fatigue is
established The findings call for more attention to how to reduce patientrsquos levels of
fatigue Based on the available information evaluated in this review the following
recommendations for practice are provided
665
33
bull For children aged 7 to 18 who has cancer (eg Lymphoma leukemia CNS tumor
germ cell tumor) an effective progressive aerobic exercise program is recommended to
be at least 2-3 times per week 20 to 45 minute for each session and last for 6-16 weeks
in order to reduce their general fatigue (tiredness physically weakness) In addition
adults should be involved in accompanying children while they are performing physical
exercise of which should be able to improve the adherence rate (level 2 ) ( Grade of
recommendation A)
bull For children aged 7 to 18 who has cancer (eg Lymphoma leukemia CNS tumor
germ cell tumor) an progressive aerobic exercise program will not be effective to reduce
their sleep andor rest (sleeping or resting a lot) or cognitive fatigue (problems with
thinking quickly or problems with remembering) (level 2 ) ( Grade of recommendation C)
bull Nursing interventions in educating treatment of fatigue include information about
activity nutrition energy preservation consulting and providing a useful fatigue
handbook will benefit those children who are 7 to 12 years have a new diagnosis of ALL
AML or lymphoma and receive for the first time after being diagnosed a 7- to 10-day
chemotherapy treatment (level 2) ( Grade of recommendation A)
bull A 4-week massage therapy program (the therapists massage childrenrsquos back legs
arms stomachchest and face) is not effective for children who are aged 7 to 18 and
have acute lymphoblastic leukemia brain tumors lymphoma rhabdomyosarcoma
Wilms tumor or Ewing sarcoma(level 2)( Grade of recommendation C)
bull Using a 12-week aerobic and strength exercise (45-min exercise sessions twice a
week) is not effective for children who are aged 6-14 and survived acute lymphoblaststic
leukemia age from 6 to 14(level 2) ( Grade of recommendation C)
bull Using a physical activity intervention (30minutestwice daily for 2-4days) is not
effective for children who are 7 to 18 years of age with soild tumor or AML(level 2)
( Grade of recommendation C)
666
34
Implications for research According to this systematic review and meta-analysis results there are suggestions to
improve the effectiveness of future research on non-pharmacological interventions for
children and young peoplersquos cancer-related fatigue
As the majority of included non-pharmacological interventions for the fatigue of cancer
patients consist of exercise programs future research should also consider various
non-pharmacological interventions in order to understand the effectiveness of different
methods
Regarding the exercise intervention methods and studies should consider multiple
factors including the age or personal condition of the subject the disease stage and the
amount of daily activities Studies should use design prescriptions (eg frequency
intensity duration and type of exercise) and consider the adherence to the measures in
order to enhance the study strength
In measuring the results of non-pharmacological interventions there should be standard
definitions or standard measurement tools to facilitate the following systematic review
and meta-analysis that can subsequently be developed into clinical care guidelines
Reviewing the effectiveness of the current non-pharmacological management of children
and adolescent cancer patients there is still a lack of rigorous RCT research Limited by
the characteristics of cancer there is still a lack of large sample sizes
Potential conflicts of interest There is no conflict of interest
Acknowledgements
Thank you to Dr Rie Konno Research Fellow Joanna Briggs Institute for her help in
assessing studies
667
35
References 1 National Comprehensive Cancer Network( NCCN) in USA NCCN clinical practice
guideline in oncology cancer-related fatigue 2011 2 Ekti Genc R amp Conk Z Impact of effective nursing interventions to the fatigue
syndrome in children who receive chemotherapy Cancer Nursing 200831(4)312-317
3 Childhood Cancer Foundation of ROC (2009March) The classification of diseases
and age sex statistical tables of case Childhood Cancer Foundation of ROC newsletter103105-106
4 Department of Health Executive Yuan ROC (TAIWAN)(2009 March 20)2009 cause of death statistic Health and National Health Insurance Annual Statistics Information Service 2010 June 28Available httpwwwdohgovtwstatisticdatavital statists9898health statistic--lifepdf
5 Chang TK (2007December 8) Common childhood cancer and its treatment Status
Childhood Cancer Foundation of ROC (TAIWAN) 2010 September 23 Available httpwwwccfrocorgtwchildchild_events_readphpe_id=45
6 Hockenberry MJ amp Wilson D Wongs nursing care of infants and children (8th ed) St
Louis MO Mosby 2007
7 Post-White J Fitzgerald M Savik K Hooke MC Hannahan AB amp Sencer SF
Massage therapy for children with cancer Journal of Pediatric Oncology Nursing 2009 26(1)16-28
8Chiang YC Yeh CH Wang WKamp Yang CP The experience of cancer-related fatigue
in Taiwanese children European Journal of Cancer Care 2009 18(1)43-49 9Langeveld NE Grootenhuis M A Voute P A de Haan RJ amp van den Bos C No excess
fatigue in young adult survivors of childhood cancer European Journal of Cancer 200339(2)204-214
10Piper BF Lindsey AM amp Dodd MJ Fatigue mechanisms in cancer patients
developing nursing theory Oncology Nursing Forum 1987 14(6)17-23 11Nail LM amp Winningham ML Fatigue In S L Groenwald M H Forgge M Goodman
amp C H Yarbro (Eds) Cancer Nursing Principles and practice (4 th ed) Boston Jones and Bartlett1997
12Irvine D Vincent L Graydon JE Bubela N amp Thompson L The prevalence and
correlates of fatigue in patients receiving treatment with chemotherapy and
668
36
radiotherapy A comparison with the fatigue experienced by healthy individuals Cancer Nursing 199417(5)367-378
13Hinds PS amp Hockenberry-Eaton M Developing a research program on fatigue in
children and adloescents diagnosed with cancer Journal of Pediatric Oncology Nursing 200118(2)3-12
14Aaronson LS Teel CS Cassmeyer V Neuberger GB Pallikkathayil L Pierce J Press
AN Williams DP amp Wingate A Defining and measuring fatigue Journal of Nursing scholarship 1999 31(1)45-50
15Yeh CH Wang CH Chiang YC Lin Lamp Chien LC Assessment of symptoms reported
by 10- to 18-year-old cancer patients in Taiwan 2009 38(5)738-746 16 Okuyama T Akechi T Kugaya A Okamura H Shima Yamp Maruguchi M
Development and validation of the cancer fatigue scale a brief three-dimensional self-rating scale for assessment of fatigue in cancer patients Journal of Pain amp Symptom Management 2000 19(1) 5-14
17Gibson F Mulhall AB Richardson A Edwards JL Ream E amp Sepion BJ A
phenomenologic study of fatigue in adolescents receiving treatment for cancer Oncology Nursing Forum200532(3)651-660
18Wolfe J Grier HE Klar N Levin SB Ellenbogen JMamp Salem-Schatz S et al
Symptoms and suffering at the end of life in children with cancer New England Journal of Medicine 2000342(5)326-333
19Whiting P Bagnall AM Sowden AJ Cornell JE Mulrow CD amp Ramirez G
Interventions for the treatment and management of chronic fatigue syndrome a systematic review JAMA the Journal of the American Medical Association 2001286(11)1360-1368
20 Kangas M Bovbjerg DHamp Montgomery G H Cancer-related fatigue a systematic
and meta-analytic review of non-pharmacological therapies for cancer patients Psychological Bulletin 2008134 (5)700-741
21Williams PD Schmideskamp J Ridder EL amp Williams AR Symptom monitoring and
dependent care during cancer treatment in children pilot study Cancer Nursing 200629(3)188-197
22Takken T van der Torre P Zwerink M Hulzebos EH Bierings M Helders PJMamp van
der Net J Development feasibility and efficacy of a community-based exercise training
669
37
program in pediatric cancer survivors Psycho-Oncology 200918(4)440-448
23Keats MR amp Culos-Reed SN A community-based physical activity program for
adolescents with cancer (project TREK) program feasibility and preliminary findings
Pediatric hematology and oncology 200830(4) 272-280
24Hinds PS Hockenberry M Rai SN Zhang L Razzouk B I Cremer L McCarthy K amp
Rodriguez-Galindo C Clinical field testing of an enhanced-activity intervention in
hospitalized children with cancer Journal of Pain amp Symptom Management 2007
33(6)686-697
25Chiang YC The effects of ldquo a home-based aerobic exercise interventionrdquo on fatigue
and cardiorespiratory fitness in children with acute lymphoblastic leukemia during the
maintenance stage of chemotherapy Unpublished thesis Taiwan Tao-Yuan 2007
26Langeveld N Ubbink M amp Smets E I dont have any energy The experience of
fatigue in young adult survivors of childhood cancer European journal of oncology
nursing 20004(1)20-28
27 Kisner C Colby L Therapeutic exercise Foundations and techniques 2nd ed Philadelphia PAFA Davies 2007
670
38
Appendix I JBI Critical Appraisal Checklist for Experimental studies
Author__________ Year_________ Record Number__________________
Questions 1 to 4 must be answered ldquoyesrdquo for study to be included in the metashyanalysis
1 Were the participants randomized to study groups
Yes No Not clear
2 Other than research intervention were participants in each groups treated the same
Yes No Not clear
3 Were the outcomes measured in the same manner for all participants
Yes No Not clear
4 Were groups comparable at entry
Yes No Not clear
5 Was randomization of participants blinded
Yes No Not clear
6 Were those assessing outcome blinded to treatment allocation (if outcome not objective such as survival or length of hospitalization)
Yes No Not clear
7 Was allocation to treatment groups concealed from the allocator
Yes No Not clear
8 Was an appropriate statistical analysis used
671
39
Yes No Not clear
9 Were outcomes measured in a reliable way
Yes No Not clear
10 Was there adequate followshyup of participants
Yes No Not clear
Summary
TOTAL
Yes No Not clear
DECISION
Use Reject
Narrative summary only Further information needed
COMMENTS
672
40
Appendix II JBI Data Extraction Tool for Quantitative Studies Authors and Year
Journal Title
Record NumberArticle Reference No
Reviewer
Method
Settings
Participants
Number of participants
Group A Group B Group C
Control Intervention 1 Intervention 2
Interventions
Group A
Control
Group B
Intervention 1
Group C
Intervention 2
Outcome measures
Definition
673
41
Other outcome measures
Outcome description ScaleMeasure
Results
Dichotomous Data
Outcome Control Group
Numbertotal number
Treatment Group
Numbertotal number
Continuous Data
Authorrsquos Conclusions
Comments
Outcome Control Group
Mean amp SD
Treatment Group
Mean amp SD
674
43
Appendix III Details of included studies (N=6)(2720212223) RefNo Author(s)
(years) Title Study question Research
method Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
22 Takken T van der Torre P Zwerink M Hulzebos E H Bierings M Helders P J Mamp van der Net J (2009)
Development feasibility and efficacy of a community-based exercise training program in pediatric cancer survivors
To develop a 12-week home-based exercise training program (comprising aerobic and strength exercises) for children who survived ALL and to study itrsquos feasibility and efficacy
Pre-post test design
No comparsion group
Survived ALL(N=9)ages 6-14 years
1anthropometry 2 muscle strength 3functional mobility 4cardio-pulmonary
exercise test 5Fatigue
1 Feasibility questionnaire 2 anthropometry electronic scale and a wallmounted stadiometerHarpenden skin fold calipers 3 muscle strength handheld dynamometer 4functional mobility Timed Up
and Go test (TUG) 5cardio-pulmonary exercise test electronically braked cycle ergometer 6Fatigue(mean)CSI-20 (subjective experience of fatigueconcentrationmotivationphysical activity)
112-week exercise training program
2 Patients were assessed before (T0) and after (T1) 12 weeks of training
1 muscle strength execapacity functional moand fatigue showed nosignificant differences between pre(meanplusmnSD415plusmn147) and post training(meanplusmnSD3687)
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
7 Post-White J Fitzgerald M Savik K Hooke M C Hannahan A B amp Sencer S F (2009)
Massage therapy for children with cancer
To determine whether 4 weekly sessions of massage compared with 4 quiet-time control conditions would reduce anxiety cortisol levels fatigue nausea and pain in children with cancer undergoing chemotherapy and would reduce anxiety fatigue and mood disturbance in a parent
2-period crossover design (Randomized)
quiet-time
control
sessions
Children with cancer 1 to 18 years of age Twenty-three childrenparent dyads were enrolled 17 completed all data points
children 1relaxation 2symptoms 3 fatigue
parents
1anxiety 2 fatigue
children 1relaxation (heart and respiratory rates blood pressure and salivary cortisol level)
2symptoms (pain nausea anxiety 3 fatigue 1-2y3-6yLansky Play Performance Scale (PPS) 7-13y
1 4 weekly massage (MT) sessions alternated with 4 weekly quiet-time(QT) control sessions
2 children included presession and postsession vital signs (heart rate respiratory rate blood pressure) and self-report (parent proxy report for age 1-2 years) of pain nausea and anxiety Fatigue was measured before sessions 1 and 4 and at each follow-up Parent measures
included anxiety fatigue and mood states
1Massage was moreeffective than quiet tireducing heart rate inchildren anxiety in cless than age 14 yeaparent anxiety 2There were no sign
changes in blood pcortisol pain naufatigue (no state d
3 Children reported tmassage helped thebetter lessened theirand worries and hadlasting effects than q
675
44
14-18yChild Fatigue Scale (CFS) (frequency
intensity) 2 parents anxiety and fatigue
676
45
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
24 Hinds P S Hockenberry M Rai S N Zhang L Razzouk B I Cremer L McCarthy K amp Rodriguez-Galindo C (2007)
Clinical field testing of an enhanced-activity intervention in hospitalized children with cancer
To determine the feasibility of an
enhanced physical activity EPA intervention in children and adolescents hospitalized to receive chemotherapy for a solid tumor or AML and to assess the sleep and fatigue outcomes of the intervention using two different statistical approaches to analyze the longitudinal symptom data
randomized prospective two-site and two-group pilot study
Standard care Twenty nine patients (25 with a solid tumor and 4 with AML)ages 7-18 years
1 sleep duration 2 sleep efficiency 3 fatigue
1sleep duration sleep efficiency The
Wrist Actigraph The Daily Sleep Diary-Parent 2 fatigue (mean) The Fatigue Scale(FS-C) for 7-12 (intensity) The Fatigue Scale(FS-A) for 13-18 The Fatigue Scale Parent Version (FS-P) The Fatigue Scale Staff Version (FS-S)
1enhanced physical activity (EPA) (hospital-based 30 minutes
twice daily for 2-4 days) 2 T0On the day of admission
(Day 0 or baseline)patient and parents completed the fatigue instruments and a team member applied the actigraph Patients wore the wrist actigraph T1 from Day 0 to 2 or 3 consecutive days (Days 0e3) In addition the patient same parent and staff nurses completed the daily sleep and fatigue reports in the late afternoons of Days 1-3
1 ANOVA model slesignificantly more the experimental athe control arm whdifferences from bsleep efficiency vaaveraged and com
2 The patient-reported mean fatigue scoresarms were higher amadolescents than for
3 The mixed model anarevealed no significandifferences in patientfatigue between
the two study arms otime( no final result iSD only give mixed result)
677
46
23 Keats M
R amp Culos-Reed S N (2008)
A community-based physical activity program for adolescents with cancer (project TREK) program feasibility and preliminary findings
To examine the
feasibility of a
theoretically-based
physical activity (PA)
intervention in
adolescents with
cancerand
examination of the
impact of the
program on
participant QOL
including social
emotional and
physical
well-being(including fatigue)
Repeat measures longitudinal design
No comparsion group
10 adolescents(Lymphoma(4)leukemia(4)CNS tumor(1)germ cell tumor(1)) ages 14-18 years
1physical fitness 2quality of life (QOL) 3PA behavior 4fatigue
1 Feasibility was assessed by participant recruitment attendance and adherence
2physical fitness Fitnessgram 3quality of life (QOL) Pediatric Quality of Life Inventory (PedsQL) 4PA behavior leisure score index (LSI) 5fatigue (mean) pediatric Quality of life
Multidimensional Fatigue Scale (Peds QL-MFS)
(Generalsleepcognitive fatigue)
116week physical activity (PA)
2 total PA physical fitness and overall QOL was assessed at 5 different intervals T0 preintervention (baseline) T1midintervention (after the
first 8 wk) T2 postintervention
(16 wk) T3 3-months
postintervention T4 1-year poststudy
initiation
1 from baseline -wkssig Improvementstotal PA physfitness and Qgeneral fatigue(meanplusmnSD 796plusmn135)
2 from baseline to 3FUsig Improvin general fatigue(meanplusmnSD824plusmn131)slefatigue(meanplusmnSD755plusmn191)totafatigue(meanplusmnSD778plusmn150)
3at 1 years FUsImprovements in sleeprest fatigue(meanplusmnSD725plusmn203)total (meanplusmnSD 763plusmn
678
47
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
2 Gene R E amp Conk Z (2008)
Impact of Effective Nursing Interventions to the Fatigue Syndrome in Children Who Receive Chemotherapy
1 to examine the effects of an effective nursing intervention to the fatigue syndrome of children 7 to 12 years of age who receive chemotherapy 2Tto examine the relationship between fatigue and demographic variables (age sex) diagnoses ([ALL AML] lymphoma) and therapy-related variables (eg level of hemoglobin
experimental randomized controlled study
Routine nursing care
A total of 60 children who are 7-12 years of age(a new diagnosis of ALL AML or lymphoma and receiving for the first time after being diagnosed a 7- to 10-day chemotherapy treatment )
fatigue The Fatigue Scale(FS-C) for 7-12 (intensity)
The Fatigue Scale Parent Version (FS-P)
1 effective nursing interventions(45- 60mdaya week)education about the fatigue with the chemotherapy and fatigue handbook 2 T1 After a 7-day period the children
and parent were evaluated with the Fatigue Scale
1The difference betwthe 2 mean values wafound to be statisticallsignificant 2 statistically significadifference was found between the Fatigue Scale-Child mean scothe experimental (272the control group (4213)children
679
48
25 Chiang et
al(2007)
The effects of ldquo a home ndashbased aerobic exercise interventionrdquo on fatigue and cardiorespiratory fitness in children with Acute Lymphoblastic Leukemia during the maintenance stage of chemotherapy
To examine the effect of ldquo a home ndashbased aerobic exercise interventionrdquo on fatigue and cardiorespiratory fitness in children with Acute Lymphoblastic Leukemia during the maintenance stage of chemotherapy
Quasi-experi -mental
Routine
nursing care
14 pediatric oncology patients in the experimental group and 10 in control group who were matched by age and sex ages7-18 years
1Cardiorespiratory fitness
2Fatigue
1Cardiorespiratory fitness Physical Activity Recall
VO2maxHR peak 6MWT
2 Fatigue PedsQL-MFS(Generalsleepcognitive fatigue)
1A six-week home-based aerobic exercise intervention 2 8 time points T0 baseline T1-T6 every week during the
intervention(6 weeks) T7 post intervention T8 follow-up (one month after
the end of the home-based exercise program)
1 For intent-to ndash treatthe findings indicated are no intervention efftime differences by anon the subscale of fat2 For per-protocol angeneral fatigue( mean422plusmn402) was the osubscale that was siglower for children whothe exercise interventthose in control groupfollow-up assessmentmonth after the compintervention) 3 The VO2peak are significantly improvingexperimental group atbaseline- and post-intassessment The VO2was significantly highechildren who were in experimental group thcontrol subjects at post-intervention assefor the per-protocol an
680
49
Appendix IV Instrument used to measure fatigue
Name Instrument
developers
Description Used in
age in
ref
Reliability
Consistency of
instrument
Checklist Individual Strength
(CIS)22
Vercoulen et
al1996
20 items using 7-point Likert scale of
fatigue To measure four aspects of
fatiguesubjective experience
contractionmotivation physical
Activity
6-14 Not reported
Child Fatigue Scale (CFS)7 Hockenberry
et al2003
14 items 2 part questionnaire frequency
(yes or no) 5-point Likert scale of the
intensity of any yes responses
7-13
14-18 α073-o84
The Fatigue Scale for 7-12
year Olds (FS-C)224
Hockenberry
et al
14 items provide a fatigue intensity score
5-point Likert scale
7-12 αo84
The Fatigue Scale for 13-18
year Olds (FS-A)24
Hockenberry
et al
14 items provide a fatigue intensity score
5-point Likert scale
13-18 α076-o96
Pediatric Quality of life
Multidimensional Fatigue
Scale (Peds QL-MFS)2325
Varni2002 18 items to measure three aspects of
fatigueGeneralsleepcognitive
14-18 Not reported
681
50
Appendix V Excluded studies and reasons for exclusion
Baggott C Dodd M Kennedy C Marina N Miaskowski C Multiple Symptoms in Pediatric Oncology
Patients A Systematic Review Journal of Pediatric Oncology Nursing 2009 Nov-Dec 27(6)
325-339
Reason for exclusion Not outcome of interest
Barlow JH Ellard DR Psycho-educational interventions for children with chronic disease parents and
siblings an overview of the research evidence base Care Health amp Development 2004 Nov
30(6)637-45
Reason for exclusion Not outcome of interest
Bedider S Moyer CA Randomized controlled trials of pediatric massage A review Evid Based
Complement Alternat Med 2007 Mar 4(1)23-34 Epub 2006 Nov 3
Reason for exclusion Not outcome of interest
de Nijs EJ Ros W Grijpdonck MH Nursing intervention for fatigue during the treatment for cancer Cancer
Nursing 2008 31(3)191-206
Reason for exclusion Not population of interest
Edwards JL Gibson F Richardson A Sepion B Ream E Fatigue in adolescents with and following a
cancer diagnosis developing an evidence base for practice European Journal of Cancer 2003
Dec 39(18)2671-80
Reason for exclusion Not experimental or quasi-experimental study
Hinds PS Hockenberry-Eatan M Developing a research program on fatigue in children and adolescents
diagnosed with cancer Journal of Pediatric Oncology Nursing 2001 Mar-Apr 18(2 Suppl
1)3-12
Reason for exclusion Not experimental or quasi-experimental study
Hockenberry-Eaton M Hinds PS Alcoser P ONeill JB Euell K Howard V Gattuso J Taylor J Fatigue in
Children and Adolescents With Cancer Journal of Pediatric Oncology Nursing 1998 July
15(3)172-182
Reason for exclusion Not experimental or quasi-experimental study
Jean-Pierre P Mustian K Kohli S Roscoe JA Hickok JT Morrow GR Community-based clinical oncology
research trials for cancer-related fatigue The Journal of Supportive Oncology 2006 Nov-Dec
4(10)511-6
682
51
Reason for exclusion Not population of interest
Kangas M Bovbjerg DH Montgomery GH Cancer-Related Fatigue A Systematic and Meta-Analytic
Review of Non-Pharmacological Therapies for Cancer Patients Psychological Bulletin 2008 Sep
134(5)700-41
Reason for exclusion Not population of interest
Lotfi-Jam K Carey M Jefford M Schofield P Charleson C Aranda S Nonpharmacologic strategies for
managing common chemotherapy adverse effects A systematic review Journal of Clinical
Oncology 2008 Dec 1 26(34)5618-29 Epub 2008 Nov 3
Reason for exclusion Not outcome of interest
Marchese VG Chiarello LA Lange BJ Effects of physical therapy intervention for children with acute
lymphoblastic leukemia Pediatr Blood Cancer 2004 Feb42(2)127-33
Reason for exclusion Not outcome of interest
Meeske KA Siegel SE Globe DR Mack WJ Bernstein L Prevalence and correlates of fatigue in
long-term survivors of childhood leukemia Journal of Clinical Oncology 2005 Aug 20
23(24)5501-10
Reason for exclusion Not intervention study
Minton O Richardson A Sharpe M Hotopf Stone P A systematic review and meta-analysis of the
pharmacological treatment of cancer-related fatigue J Natl Cancer Inst 2008 Aug 20
100(16)1155-66 Epub 2008 Aug 11
Reason for exclusion Not population and intervention of interest
Mustian KM Morrow GR Carroll JK Figueroa-Moseley CD Pascal JP Williams GC Integrative
nonpharmacologic behavioral interventions for the management of Cancer-Related fatigue The
Oncologist 2007 12(1)52-67
Reason for exclusion Not population of interest
Neill J Belan I Ried K Effectiveness of non-pharmacological interventions for fatigue in adults with
multiple sclerosis rheumatoid arthritis or systemic lupus erythematosus a systematic review
Journal of Advanced Nursing 2006 Dec 56(6)617-35
Reason for exclusion Not population of interest
Rheingans JI A systematic review of nonpharmacologic adjunctive therapies for symptom management
Journal of Pediatric Oncology Nursing 2007 24(2) 81-94
683
52
Reason for exclusion Not outcome of interest
Rheingans JI Pediatric oncology nursesrsquo management of patients symptoms Journal of Pediatric
Oncology Nursing 2008 Nov 25(6) 303-11
Reason for exclusion Not outcome of interest
San Juan AF Fleck SJ Chamorro-Vintildea C Mateacute-Muntildeoz JL Moral S Peacuterez M Cardona C Del Valle MF
Hernaacutendez M Ramiacuterez M Madero L Lucia A Effects of an intrahospital exercise program
intervention for children with leukemia Medicine amp Science in Sports amp Exercise 2007 Jan
39(1)13-21
Reason for exclusion Not outcome of interest
Sanford SD Okuma JO Pan J Srivastava DK West N Farr L Hinds PS Gender differences in sleep
fatigue and daytime activity in a pediatric oncology sample receiving dexamethasone Journal of
Pediatric Psychology 2008 Apr 33(3)298-306 Epub 2007 Nov 17
Reason for exclusion Not experimental or quasi-experimental study
Schmitz KH Holtzman J Courneya KS Macircsse LC Duval S Kane R Controlled physical activity trials in
cancer survivors a systematic review and meta-analysis Cancer Epidemiol Biomarkers Prev
2005 Jul 14(7)1588-95
Reason for exclusion Not population of interest
van Brussel M Takken T Lucia A van der Net J Helders PJ Is physical fitness decreased in survivors of
childhood leukemia A systematic review Leukemia 2005 Jan 19(1)13-7
Reason for exclusion Not population of interest
Whiting P Bagnall AM Snowden AJ Cornell JE Mulrow CD Ramirez G Interventions for the treatment
and management of chronic fatigue syndrome JAMA 2001 Sep 19 286(11)1360-8
Reason for exclusion Not intervention of interest
Whitsett SF Gudmundsdottir M Davies B McCarthy P Friedman D Chemotherapy-related fatigue in
childhood cancer correlates consequences and coping strategies Journal of Pediatric
Oncology Nursing 2008 Mar-Apr 25(2)86-96 Epub 2008 Feb 29
Reason for exclusion Not experimental or quasi-experimental study
Winner C Muumlller C Hoffmann C Boos J Rosenbaum D Physical activity and childhood cancer Pediatr
Blood Cancer 2010 Apr 54(4)501-10
Reason for exclusion Not research study
684
53
Wu M Hsu L Zhang B Shen N Lu H Li S The experiences of cancer-related fatigue among Chinese
children with leukaemia A phenomenological study Journal of Nursing Studies 2010 Jan
47(1)49-59 Epub 2009 Aug 25
Reason for exclusion Not experimental or quasi-experimental study
Yeh CH Chiang YC Lin L Yang CP Chien LC Weaver MA Chuang HL Clinical factors associated with
fatigue over time in paediatric oncology patients receiving chemotherapy British Journal of
Cancer 2008 Jul 8 99(1)23-9 Epub 2008 Jun 24
Reason for exclusion Not experimental or quasi-experimental study
685
20
The interventions included exercise training programs 2225 physical activity 2324
massage therapy 7 and health education 223 exercise training and physical activity as
an intervention method given in three different settings home 22 25 community 23 or
hospital 24 The studies used different types of exercise interventions including
home-based aerobic exercise use a Video Compact Disc 25 use of a bicycle-style
exerciser 24 aerobics2223 and various types of physical activities2 and strength-building
exercises 2223 The intensity of the exercise varied and often included gradual warm-up
exercises a period of main exercise and a cool down period For these studies2023 the
target exercise intensity was a heart rate of gt90 of the maximum heart rate (HR max) or
the increase in the percentage of heart rate reserve ( HRR) of 40-60
The number of weeks for the exercisephysical activity interventions duration including
2-4 days 24 6 weeks25 12 weeks22 and 16 weeks23 The frequency of exercise ranged
from 2-3 times per week to twice a day Typical duration of exercise ranged from 10 to 45
minutes There are three papers using exercise interventions based on ACSM (American
College of Sports Medicine) 2225 recommendations and one of these used an Activity
pyramid from the ACSM to determine intensity 24
One article did not clarify the type of exercise intervention or the reasons for their choices
23 In addition there was an article focusing on massage therapy 7 as an intervention in
this study the experimental group received four weeks of massage therapy either in the
clinic or in the patientrsquos room the therapy was applied by a professional masseur and
targeted the back legs arms chest stomach and face of the children However the
frequency of massage sessions per week and the duration of the massages were not
653
21
given There is another article about intervention measures combine health education
and physical activity 2 In this study patients were informed about the following (1) health
education patients received daily education about chemotherapy-related fatigue and
information from a health education manual written by the author (2) encouragement for
children to engage in activities such as listening to music drawing and reading and (3)
physical activity which involved walking along the corridors of the ward for 10-15 minutes
These health education measures were presented for 45-60 minutes a day for a total of
seven days The study design for non-pharmacological interventions used control groups
that included primarily people who had received standard treatment or people who did
not receive an exercise intervention
Outcome measures
Five measurement tools were used in this group of seven papers concerning childrenrsquos
fatigue (Appendix IV) Because those studies included both school-age children and
adolescents the following descriptions will be differentiated by age Fatigue
measurements for school-aged children with cancer include the following the Child
Fatigue Scale (CFS) 7 a scale that measures the frequency and intensity of fatigue and
the Fatigue Scale for 7-12 year Olds (FS-C) 224 a scale that can be used to evaluate the
intensity of fatigue On the other hand fatigue measurements for adolescent cancer
patients include the following the Fatigue Scale for 13-18-year-olds (FS-A) 24 a measure
that can help evaluate fatigue levels the Pediatric Quality of Life Multidimensional
Fatigue Scale (Peds QL-MFS) 2325 a tool that can be divided into three sub-scales to
understand the general cognitive and sleep rest components of fatigue and finally the
CIS-20 for school-age children and adolescents 22 a scale that measures four levels of
654
22
fatigue namely subjective experience attention motivation and physical activity Two
studies used the Peds QL-MFS scale to measure fatigue2325
Meta-analysis results Two studies of the included papers failed to provide sufficient raw data they could not be
included in the meta-analysis Hinds et al 24 did not include post-test data Genc et al 2
provided no pre-test data PostWhite et al7 reported that fatigue after the health
education intervention was not statistically different but they presented the results
without presenting fatigue-related data Therefore the meta-analysis included three
studies 222325
The heterogeneity of studies was analyzed with Chi square statistics and no statistical
significance was found Therefore the data was combined in meta-analysis according to
exercise intervention on fatigue In addition there were three articles using the Peds
QL-MFS as a research tool to examine childrenrsquos improvements in fatigue Among these
Keats 22 and Chiang 24 present the effectiveness of exercise interventions using three
subscales Therefore the meta-analysis also analysis of the effects of these exercise
intervention measures on three subscales of Peds QL-MFS general fatigue sleep rest
fatigue and cognitive fatigue
The effectiveness of exercise intervention for fatigue We analyzed the exercise intervention effect on fatigue A total of 2 studies 22 23 were
included Takken et al 22 used community-based exercise training program to reduce
fatigue of children 6 to 14 years (mean 93y) of age who survived ALL Fatigue
measurement by Checklist Individual Strength (CIS) after 12-week of training fatigue
655
23
show no significant differences between pre (meanplusmnSD 415plusmn147) and post training
(meanplusmnSD368plusmn217) but fatigue change from baseline mean reduction of 11
Keats et al23 although used community-based physical activity program to reduce fatigue
for adolescents 14 to 18 years of age (mean162 y) with cancer (Lymphoma leukemia CNS
tumor germ cell tumor) Studies used fatigue by PedsQLMFS Results show general fatigue
from baseline to 8 weeks and to 3 months follow up significantly improves General
fatigue sleeprest fatigue and total fatigue from baseline to 3 months follow up showed
significant improvements Sleeprest fatigue and total fatigue at 1 years followed up were
significant improvements
Figure 2 shows the overall effect of exercise intervention in children and adolescents with
cancers with a focus on improving fatigue Due to the lower heterogeneity (p>005) the
fixed effects model was used to pool the data for meta-analysis (Overall effect size=
-006 95 Confidence Interval (CI) -070 to 058) A result did not indicate a statistically
significant difference (p = 087)
656
24
Figure2 Meta-analysis results of exercise intervention on fatigue
In addition Keats23 and Chiang25 used the three sub-scales of Peds QL-MFS to
determine the general cognitive and sleep rest components of fatigue The following
present the effectiveness of exercise interventions using three subscales including
general fatigue sleep rest fatigue and cognitive fatigue 2325
Chiang et al 25 used a 6- week home-based aerobic exercise intervention to reduce
fatigue of children 7 to 18 years (mean age at experimental group was 1088 y in control
group was 1247 y) of age who with acute lymphoblastic leukemia Fatigue measurement
by Peds QL-MFS after training For intent-to ndash treat analysis the findings indicated that
there are no intervention effects and time differences by any items on the subscale of
fatigue For per-protocol analysis general fatigue( meanplusmnSD 422plusmn402) was the only
subscale that was significantly lower for children who received the exercise intervention
than those in control group at follow-up assessment (one month after the completion of
intervention)
Keats et al23 although used community-based physical activity program to reduce fatigue
for adolescents 14 to 18 years of age (mean162 y) with cancer (Lymphoma leukemia
CNS tumor germ cell tumor) Both studies used fatigue by PedsQLMFS Results show
general fatigue from baseline to 8 weeks and to 3 months follow up significantly improves
657
25
General fatigue sleeprest fatigue and total fatigue from baseline to 3 months follow up
showed significant improvements Sleeprest fatigue and total fatigue at 1 years followed
up were significant improvements
The effectiveness of exercise intervention for general fatigue
The impact of the exercise interventions upon levels of general fatigue was also analysed
The heterogeneity was low (p>005) Therefore the fixed effects model was used to
examine the effectiveness The effect size is -076 indicating a statistically significant
difference (p = 001 95 CI -135 to -017 Fig 3) The evidence suggests that exercise
intervention can reduce general fatigue in children with cancer
Fig 3 Meta-analysis results of exercise intervention for general fatigue
The effectiveness of exercise intervention for sleep rest fatigue
The following is the result of the meta-analysis of the effectiveness of exercise
interventions on sleep rest fatigue First the heterogeneity test was conducted with P gt
005 representing small heterogeneity and the fixed effects model was used Fig 4
shows the effect size is -035 indicating no statistically significant differences (p = 023
95 CI-092 to 022 Fig 4)
658
26
Fig 4 Meta-analysis results of exercise intervention for sleep rest fatigue
The effectiveness of exercise intervention for cognitive fatigue Lastly the following data reports the results of meta-analysis of the effectiveness of
exercise interventions for cognitive fatigue The heterogeneity was p>005 then the
fixed effects model was used The effect size is -035 indicating no statistically significant
differences (p = 024 95 CI-092 023 Fig 5)
Fig 5 Meta-analysis results of exercise intervention for cognitive fatigue
Narrative presentation of remaining included studies
Three studies were not included in meta-analysis Post-White et al7 one of the aims in
this study was to examine the effect of massage therapy on fatigue in children with
cancer The study was a quasi-experimental design Twenty-three childrenparent dyads
were enrolled 17completed all data points Children with cancer ages 7 to 18 years
received at least 2 identical cycles of chemotherapy and one parent participated in the
2-period crossover design in which 4 weekly massage sessions (MT) alternated with 4
659
27
weekly quiet-time (QT) control sessions There were no significant changes in fatigue in
children over the 4-week MT or QT conditions either independently (change over time) or
when we compared fatigue by condition
The lack of effect of massage on fatigue may be the difficulty some children had in
differentiating fatigue from being relaxed underscores the challenge of measuring fatigue
in children Some children interpreted being tired or relaxed as having greater fatigue
because they felt like lying around and sleeping or felt unmotivated to do their usual
activities all measures of fatigue in the instrument used in the study
Hinds et al24conducted a prospective two-site randomized controlled pilot study to
assess the feasibility of an enhanced physical activity (EPA) intervention in hospitalized
children and adolescents receiving treatment for a solid tumor or for acute myeloid
leukemia (AML) Twenty-nine patients (25 with a solid tumor and 4 with AML) participated
age range from 736 to 1816 (mean 1248 y) The EPA intervention selected was
pedaling a stationary bicycle-style exerciser (Chattanooga Peddler Deluxe Bio-Teck
Medical Memphis TN) for 30 minutes twice daily for 2 to 4 days of hospitalization The
mixed model analysis revealed no significant differences in patient reports of fatigue
between the two study arms or over time
Genc et al2 conducted a RCT involving children with cancer who are 7 to 12 years of age
and receiving chemotherapy treatment to determine the impact of educational
intervention by nurses on decreasing the fatigue syndrome The research sample was
composed of a total of 60 children with cancer with 30 children being included in the
660
28
experimental group (mean age 923)and 30 children included in the control group (mean
age 937) with their mothers In the experimental group after the 7th to 10th day of the
chemotherapy treatment throughout a week the researcher conducted the nursing
interventions every day for 45 to 60 minutes In the control group routine nursing
interventions were carried out The experimental group received education about the
fatigue with the chemotherapy and fatigue handbook was given which was developed by
the authors Children and mothers were consulted for including activities that could
decrease fatigue which were described as effective interventions A statistically
significant difference was found between the Fatigue Scale-Child mean scores of the
experimental (2723) and the control group (4213) The results suggest that fatigue of
children with cancer can be reduced by implementing appropriate nursing interventions
(t=567 Plt00)
Discussion The purpose of this systematic review was to determine the effectiveness of
non-pharmacological interventions specifically targeting fatigue for children and
adolescents with cancer undergoing chemotherapy or after receiving chemotherapy
Included articles about the effectiveness of non-pharmacological interventions for
children and adolescents with cancer were published between the years of 2007 and
2009 Although interventions for cancer fatigue for adults have been extensively studied
it can be seen from either the title of the paper or related content that an intervention
study on children was a pilot study or a feasibility study Representing a field in its early
stage these studies show that the fatigue issues with young cancer patients have only
recently been taken seriously
661
29
The results of our meta-analysis include measurement of the four performance indicators
fatigue and general fatigue sleep rest fatigue and cognitive fatigue The results show
that there is a statistically significant difference only in the domain of general fatigue
using an exercise intervention for children with cancer can improve the degree of fatigue
with the effect size reaching 0671 Other results do not indicate significant differences
The reasons may include the following
1 Characteristics of the cancer The exhaustion from cancer occurs not only during cancer treatment but also in during
long-term survival a time during which patients may continue to be affected by this
symptom 8 26 Therefore when using intervention measures to improve fatigue
circumstances should be considered such as the process of the treatment and the course
or stage of the disease Because cancer patients will experience different forms of
treatment or courses of treatment the disease itself or treatment differences should be
considered in the choice of intervention Even chemotherapy drugs should be taken into
consideration For example a period of general steroid treatment can increase patientsrsquo
fatigue In those studies of children with cancer few studies looked solely at one type of
cancer most studies included a variety of cancer patients Furthermore most studies do
not clearly explain the stage of the disease or course of treatment and most do not
include treatment variables in the control group Moreover children with cancer may
have different levels of physical function
2 Research design The sample size Currently there are few studies with large sample size and a rigorous
RCT design due to the small number of papers available for analysis The sample size
included in our studyrsquos data analysis is between 20 and 42 people this small sample size
will affect the power available to evaluate outcome variables
Although most of the non-pharmacological interventions still use exercise and physical
activity and these studies overall show better results for fatigue as compared with
controls more research is still needed to further confirm the efficacy of these findings
662
30
The dropout rate in the evaluated research varies a great deal ranging from 5 to 45
these dropout rates may result from the characteristics of the research subjects or the
lengthy time involved in participating in these studies The research data with a high
turnover rate might not reflect the actual outcomes of participation in exercise and the
quality of the research contained in articles with high subject turnover rates may be
lower
Exercise doses and time The exercise doses needed to reduce fatigue cannot be
determined additionally the amount of exercise completed by the patient is also
inconsistent interventions vary between 2-3 times per week and two times a day and
exercise duration varies between 10 and 45 minutes each time Furthermore the study
interventions vary in length between a couple of days and a long period of 16 weeks The
data collection times are different some were measured 12 weeks after the intervention
began some were measured during the 6 weeks of intervention some were measured
three months after the intervention was finished and some were measured after one
year
In addition disease-related symptoms decrease childrenrsquos willingness to participate in
exercise interventions inappropriate exercise intervention programs may actually
increase childrens fatigue In addition the children in the study are still developing
physically it is important to consider ways to design an interesting exercise intervention
to increase the compliance of patients in order to improve the effectiveness Although
intervention programs in the hospital or in a community sports center can improve the
effectiveness because they provide supervision the feasibility of these programs is
questionable However if the program is home-based the children need to be
supervised by parents in order to improve their compliance in doing the exercises
Furthermore regarding the nature of the intervention the results from this study indicate
that the researched non-pharmacological interventions include the following exercise
training programs physical activity massage therapy and health education interventions
However according to the National Comprehensive Cancer Network 1 clinical guidelines
663
31
for cancer non-drug measures for cancer fatigue can be separated into five categories
(1) activity enhancement (2) psychosocial interventions such as cognitive behavioral
therapy (CBT) stress management relaxation techniques and support groups (3)
attention-restoring therapy (4) nutritional consultation and (5) cognitive behavioral
therapy specifically targeting sleep disturbance Researchers have also suggested that
psychosocial interventions should be included in the future research for children with
cancer-related fatigue 22
(2) The measurement tools in the study The assessment of fatigue can be
one-dimensional or multidimensional One-dimensional assessment can help understand
the severity of fatigue symptoms however multidimensional scales are often more
credible Therefore when measuring cancer-related fatigue researchers should consider
whether there is a uniform definition of fatigue or a standardized tool for measuring
fatigue in order to facilitate further systematic meta-analyses and further develop the
clinical care guidelines
Limitations of the review The present review has some potential limitations First the low methodological quality
may influence the result Although exercise intervention seems promising quality of the
RCTs was generally quite low Future studies require better design and reporting if
methodological issues to establish evidence-based nonpharmcologic intervention
Second the identified studies covered only a limited types of nonpharmcological
intervention especially in exercise intervention The guidelines for cancer-related fatigue
in NCCN (2011)1 referred to more interventions than the ones included in this review
such as cognitive behavioral therapy and nutrition consultation Thirdly the small sample
size and effect size could be potentially having led to underpowered approach for
detecting the effects on fatigue Therefore we recommend that as research continues to
grow a re-analysis can be undertaken Fourthly Combining data in meta analysis from
664
32
studies where the ages were quite different is a potential source of heterogeneity and
may affect the interpretation of the results
Conclusion At present clinical treatment is widely used for cancer patients However child and
adolescent cancer patients often experience various side effects which cause short-term
or long-term discomfort both physically and psychologically In particular with the
increasing cure rate cancer related fatigue during or after treatment has become an
important issue This study result provided positive effect of exercise intervention on
general fatigue
Implications for practice The results of this systematic review and meta-analysis show that exercise interventions
can effectively improve the level of general fatigue In particular although the articles
were self-reported feasibility studies their results all indicate that exercise interventions
for fatigue are feasible and safe there was no conclusion to be made for the use of
massage therapy or health education measures because there was only one article for
each of these interventions
Recommendations for practice
Cancer-related fatigue is one of the most severe and frequent symptoms by pediatric
oncology children and adolescent suffered during treatment and the symptom existed
even after treatment has ended Until now no golden standard of treatment to fatigue is
established The findings call for more attention to how to reduce patientrsquos levels of
fatigue Based on the available information evaluated in this review the following
recommendations for practice are provided
665
33
bull For children aged 7 to 18 who has cancer (eg Lymphoma leukemia CNS tumor
germ cell tumor) an effective progressive aerobic exercise program is recommended to
be at least 2-3 times per week 20 to 45 minute for each session and last for 6-16 weeks
in order to reduce their general fatigue (tiredness physically weakness) In addition
adults should be involved in accompanying children while they are performing physical
exercise of which should be able to improve the adherence rate (level 2 ) ( Grade of
recommendation A)
bull For children aged 7 to 18 who has cancer (eg Lymphoma leukemia CNS tumor
germ cell tumor) an progressive aerobic exercise program will not be effective to reduce
their sleep andor rest (sleeping or resting a lot) or cognitive fatigue (problems with
thinking quickly or problems with remembering) (level 2 ) ( Grade of recommendation C)
bull Nursing interventions in educating treatment of fatigue include information about
activity nutrition energy preservation consulting and providing a useful fatigue
handbook will benefit those children who are 7 to 12 years have a new diagnosis of ALL
AML or lymphoma and receive for the first time after being diagnosed a 7- to 10-day
chemotherapy treatment (level 2) ( Grade of recommendation A)
bull A 4-week massage therapy program (the therapists massage childrenrsquos back legs
arms stomachchest and face) is not effective for children who are aged 7 to 18 and
have acute lymphoblastic leukemia brain tumors lymphoma rhabdomyosarcoma
Wilms tumor or Ewing sarcoma(level 2)( Grade of recommendation C)
bull Using a 12-week aerobic and strength exercise (45-min exercise sessions twice a
week) is not effective for children who are aged 6-14 and survived acute lymphoblaststic
leukemia age from 6 to 14(level 2) ( Grade of recommendation C)
bull Using a physical activity intervention (30minutestwice daily for 2-4days) is not
effective for children who are 7 to 18 years of age with soild tumor or AML(level 2)
( Grade of recommendation C)
666
34
Implications for research According to this systematic review and meta-analysis results there are suggestions to
improve the effectiveness of future research on non-pharmacological interventions for
children and young peoplersquos cancer-related fatigue
As the majority of included non-pharmacological interventions for the fatigue of cancer
patients consist of exercise programs future research should also consider various
non-pharmacological interventions in order to understand the effectiveness of different
methods
Regarding the exercise intervention methods and studies should consider multiple
factors including the age or personal condition of the subject the disease stage and the
amount of daily activities Studies should use design prescriptions (eg frequency
intensity duration and type of exercise) and consider the adherence to the measures in
order to enhance the study strength
In measuring the results of non-pharmacological interventions there should be standard
definitions or standard measurement tools to facilitate the following systematic review
and meta-analysis that can subsequently be developed into clinical care guidelines
Reviewing the effectiveness of the current non-pharmacological management of children
and adolescent cancer patients there is still a lack of rigorous RCT research Limited by
the characteristics of cancer there is still a lack of large sample sizes
Potential conflicts of interest There is no conflict of interest
Acknowledgements
Thank you to Dr Rie Konno Research Fellow Joanna Briggs Institute for her help in
assessing studies
667
35
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guideline in oncology cancer-related fatigue 2011 2 Ekti Genc R amp Conk Z Impact of effective nursing interventions to the fatigue
syndrome in children who receive chemotherapy Cancer Nursing 200831(4)312-317
3 Childhood Cancer Foundation of ROC (2009March) The classification of diseases
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5 Chang TK (2007December 8) Common childhood cancer and its treatment Status
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6 Hockenberry MJ amp Wilson D Wongs nursing care of infants and children (8th ed) St
Louis MO Mosby 2007
7 Post-White J Fitzgerald M Savik K Hooke MC Hannahan AB amp Sencer SF
Massage therapy for children with cancer Journal of Pediatric Oncology Nursing 2009 26(1)16-28
8Chiang YC Yeh CH Wang WKamp Yang CP The experience of cancer-related fatigue
in Taiwanese children European Journal of Cancer Care 2009 18(1)43-49 9Langeveld NE Grootenhuis M A Voute P A de Haan RJ amp van den Bos C No excess
fatigue in young adult survivors of childhood cancer European Journal of Cancer 200339(2)204-214
10Piper BF Lindsey AM amp Dodd MJ Fatigue mechanisms in cancer patients
developing nursing theory Oncology Nursing Forum 1987 14(6)17-23 11Nail LM amp Winningham ML Fatigue In S L Groenwald M H Forgge M Goodman
amp C H Yarbro (Eds) Cancer Nursing Principles and practice (4 th ed) Boston Jones and Bartlett1997
12Irvine D Vincent L Graydon JE Bubela N amp Thompson L The prevalence and
correlates of fatigue in patients receiving treatment with chemotherapy and
668
36
radiotherapy A comparison with the fatigue experienced by healthy individuals Cancer Nursing 199417(5)367-378
13Hinds PS amp Hockenberry-Eaton M Developing a research program on fatigue in
children and adloescents diagnosed with cancer Journal of Pediatric Oncology Nursing 200118(2)3-12
14Aaronson LS Teel CS Cassmeyer V Neuberger GB Pallikkathayil L Pierce J Press
AN Williams DP amp Wingate A Defining and measuring fatigue Journal of Nursing scholarship 1999 31(1)45-50
15Yeh CH Wang CH Chiang YC Lin Lamp Chien LC Assessment of symptoms reported
by 10- to 18-year-old cancer patients in Taiwan 2009 38(5)738-746 16 Okuyama T Akechi T Kugaya A Okamura H Shima Yamp Maruguchi M
Development and validation of the cancer fatigue scale a brief three-dimensional self-rating scale for assessment of fatigue in cancer patients Journal of Pain amp Symptom Management 2000 19(1) 5-14
17Gibson F Mulhall AB Richardson A Edwards JL Ream E amp Sepion BJ A
phenomenologic study of fatigue in adolescents receiving treatment for cancer Oncology Nursing Forum200532(3)651-660
18Wolfe J Grier HE Klar N Levin SB Ellenbogen JMamp Salem-Schatz S et al
Symptoms and suffering at the end of life in children with cancer New England Journal of Medicine 2000342(5)326-333
19Whiting P Bagnall AM Sowden AJ Cornell JE Mulrow CD amp Ramirez G
Interventions for the treatment and management of chronic fatigue syndrome a systematic review JAMA the Journal of the American Medical Association 2001286(11)1360-1368
20 Kangas M Bovbjerg DHamp Montgomery G H Cancer-related fatigue a systematic
and meta-analytic review of non-pharmacological therapies for cancer patients Psychological Bulletin 2008134 (5)700-741
21Williams PD Schmideskamp J Ridder EL amp Williams AR Symptom monitoring and
dependent care during cancer treatment in children pilot study Cancer Nursing 200629(3)188-197
22Takken T van der Torre P Zwerink M Hulzebos EH Bierings M Helders PJMamp van
der Net J Development feasibility and efficacy of a community-based exercise training
669
37
program in pediatric cancer survivors Psycho-Oncology 200918(4)440-448
23Keats MR amp Culos-Reed SN A community-based physical activity program for
adolescents with cancer (project TREK) program feasibility and preliminary findings
Pediatric hematology and oncology 200830(4) 272-280
24Hinds PS Hockenberry M Rai SN Zhang L Razzouk B I Cremer L McCarthy K amp
Rodriguez-Galindo C Clinical field testing of an enhanced-activity intervention in
hospitalized children with cancer Journal of Pain amp Symptom Management 2007
33(6)686-697
25Chiang YC The effects of ldquo a home-based aerobic exercise interventionrdquo on fatigue
and cardiorespiratory fitness in children with acute lymphoblastic leukemia during the
maintenance stage of chemotherapy Unpublished thesis Taiwan Tao-Yuan 2007
26Langeveld N Ubbink M amp Smets E I dont have any energy The experience of
fatigue in young adult survivors of childhood cancer European journal of oncology
nursing 20004(1)20-28
27 Kisner C Colby L Therapeutic exercise Foundations and techniques 2nd ed Philadelphia PAFA Davies 2007
670
38
Appendix I JBI Critical Appraisal Checklist for Experimental studies
Author__________ Year_________ Record Number__________________
Questions 1 to 4 must be answered ldquoyesrdquo for study to be included in the metashyanalysis
1 Were the participants randomized to study groups
Yes No Not clear
2 Other than research intervention were participants in each groups treated the same
Yes No Not clear
3 Were the outcomes measured in the same manner for all participants
Yes No Not clear
4 Were groups comparable at entry
Yes No Not clear
5 Was randomization of participants blinded
Yes No Not clear
6 Were those assessing outcome blinded to treatment allocation (if outcome not objective such as survival or length of hospitalization)
Yes No Not clear
7 Was allocation to treatment groups concealed from the allocator
Yes No Not clear
8 Was an appropriate statistical analysis used
671
39
Yes No Not clear
9 Were outcomes measured in a reliable way
Yes No Not clear
10 Was there adequate followshyup of participants
Yes No Not clear
Summary
TOTAL
Yes No Not clear
DECISION
Use Reject
Narrative summary only Further information needed
COMMENTS
672
40
Appendix II JBI Data Extraction Tool for Quantitative Studies Authors and Year
Journal Title
Record NumberArticle Reference No
Reviewer
Method
Settings
Participants
Number of participants
Group A Group B Group C
Control Intervention 1 Intervention 2
Interventions
Group A
Control
Group B
Intervention 1
Group C
Intervention 2
Outcome measures
Definition
673
41
Other outcome measures
Outcome description ScaleMeasure
Results
Dichotomous Data
Outcome Control Group
Numbertotal number
Treatment Group
Numbertotal number
Continuous Data
Authorrsquos Conclusions
Comments
Outcome Control Group
Mean amp SD
Treatment Group
Mean amp SD
674
43
Appendix III Details of included studies (N=6)(2720212223) RefNo Author(s)
(years) Title Study question Research
method Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
22 Takken T van der Torre P Zwerink M Hulzebos E H Bierings M Helders P J Mamp van der Net J (2009)
Development feasibility and efficacy of a community-based exercise training program in pediatric cancer survivors
To develop a 12-week home-based exercise training program (comprising aerobic and strength exercises) for children who survived ALL and to study itrsquos feasibility and efficacy
Pre-post test design
No comparsion group
Survived ALL(N=9)ages 6-14 years
1anthropometry 2 muscle strength 3functional mobility 4cardio-pulmonary
exercise test 5Fatigue
1 Feasibility questionnaire 2 anthropometry electronic scale and a wallmounted stadiometerHarpenden skin fold calipers 3 muscle strength handheld dynamometer 4functional mobility Timed Up
and Go test (TUG) 5cardio-pulmonary exercise test electronically braked cycle ergometer 6Fatigue(mean)CSI-20 (subjective experience of fatigueconcentrationmotivationphysical activity)
112-week exercise training program
2 Patients were assessed before (T0) and after (T1) 12 weeks of training
1 muscle strength execapacity functional moand fatigue showed nosignificant differences between pre(meanplusmnSD415plusmn147) and post training(meanplusmnSD3687)
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
7 Post-White J Fitzgerald M Savik K Hooke M C Hannahan A B amp Sencer S F (2009)
Massage therapy for children with cancer
To determine whether 4 weekly sessions of massage compared with 4 quiet-time control conditions would reduce anxiety cortisol levels fatigue nausea and pain in children with cancer undergoing chemotherapy and would reduce anxiety fatigue and mood disturbance in a parent
2-period crossover design (Randomized)
quiet-time
control
sessions
Children with cancer 1 to 18 years of age Twenty-three childrenparent dyads were enrolled 17 completed all data points
children 1relaxation 2symptoms 3 fatigue
parents
1anxiety 2 fatigue
children 1relaxation (heart and respiratory rates blood pressure and salivary cortisol level)
2symptoms (pain nausea anxiety 3 fatigue 1-2y3-6yLansky Play Performance Scale (PPS) 7-13y
1 4 weekly massage (MT) sessions alternated with 4 weekly quiet-time(QT) control sessions
2 children included presession and postsession vital signs (heart rate respiratory rate blood pressure) and self-report (parent proxy report for age 1-2 years) of pain nausea and anxiety Fatigue was measured before sessions 1 and 4 and at each follow-up Parent measures
included anxiety fatigue and mood states
1Massage was moreeffective than quiet tireducing heart rate inchildren anxiety in cless than age 14 yeaparent anxiety 2There were no sign
changes in blood pcortisol pain naufatigue (no state d
3 Children reported tmassage helped thebetter lessened theirand worries and hadlasting effects than q
675
44
14-18yChild Fatigue Scale (CFS) (frequency
intensity) 2 parents anxiety and fatigue
676
45
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
24 Hinds P S Hockenberry M Rai S N Zhang L Razzouk B I Cremer L McCarthy K amp Rodriguez-Galindo C (2007)
Clinical field testing of an enhanced-activity intervention in hospitalized children with cancer
To determine the feasibility of an
enhanced physical activity EPA intervention in children and adolescents hospitalized to receive chemotherapy for a solid tumor or AML and to assess the sleep and fatigue outcomes of the intervention using two different statistical approaches to analyze the longitudinal symptom data
randomized prospective two-site and two-group pilot study
Standard care Twenty nine patients (25 with a solid tumor and 4 with AML)ages 7-18 years
1 sleep duration 2 sleep efficiency 3 fatigue
1sleep duration sleep efficiency The
Wrist Actigraph The Daily Sleep Diary-Parent 2 fatigue (mean) The Fatigue Scale(FS-C) for 7-12 (intensity) The Fatigue Scale(FS-A) for 13-18 The Fatigue Scale Parent Version (FS-P) The Fatigue Scale Staff Version (FS-S)
1enhanced physical activity (EPA) (hospital-based 30 minutes
twice daily for 2-4 days) 2 T0On the day of admission
(Day 0 or baseline)patient and parents completed the fatigue instruments and a team member applied the actigraph Patients wore the wrist actigraph T1 from Day 0 to 2 or 3 consecutive days (Days 0e3) In addition the patient same parent and staff nurses completed the daily sleep and fatigue reports in the late afternoons of Days 1-3
1 ANOVA model slesignificantly more the experimental athe control arm whdifferences from bsleep efficiency vaaveraged and com
2 The patient-reported mean fatigue scoresarms were higher amadolescents than for
3 The mixed model anarevealed no significandifferences in patientfatigue between
the two study arms otime( no final result iSD only give mixed result)
677
46
23 Keats M
R amp Culos-Reed S N (2008)
A community-based physical activity program for adolescents with cancer (project TREK) program feasibility and preliminary findings
To examine the
feasibility of a
theoretically-based
physical activity (PA)
intervention in
adolescents with
cancerand
examination of the
impact of the
program on
participant QOL
including social
emotional and
physical
well-being(including fatigue)
Repeat measures longitudinal design
No comparsion group
10 adolescents(Lymphoma(4)leukemia(4)CNS tumor(1)germ cell tumor(1)) ages 14-18 years
1physical fitness 2quality of life (QOL) 3PA behavior 4fatigue
1 Feasibility was assessed by participant recruitment attendance and adherence
2physical fitness Fitnessgram 3quality of life (QOL) Pediatric Quality of Life Inventory (PedsQL) 4PA behavior leisure score index (LSI) 5fatigue (mean) pediatric Quality of life
Multidimensional Fatigue Scale (Peds QL-MFS)
(Generalsleepcognitive fatigue)
116week physical activity (PA)
2 total PA physical fitness and overall QOL was assessed at 5 different intervals T0 preintervention (baseline) T1midintervention (after the
first 8 wk) T2 postintervention
(16 wk) T3 3-months
postintervention T4 1-year poststudy
initiation
1 from baseline -wkssig Improvementstotal PA physfitness and Qgeneral fatigue(meanplusmnSD 796plusmn135)
2 from baseline to 3FUsig Improvin general fatigue(meanplusmnSD824plusmn131)slefatigue(meanplusmnSD755plusmn191)totafatigue(meanplusmnSD778plusmn150)
3at 1 years FUsImprovements in sleeprest fatigue(meanplusmnSD725plusmn203)total (meanplusmnSD 763plusmn
678
47
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
2 Gene R E amp Conk Z (2008)
Impact of Effective Nursing Interventions to the Fatigue Syndrome in Children Who Receive Chemotherapy
1 to examine the effects of an effective nursing intervention to the fatigue syndrome of children 7 to 12 years of age who receive chemotherapy 2Tto examine the relationship between fatigue and demographic variables (age sex) diagnoses ([ALL AML] lymphoma) and therapy-related variables (eg level of hemoglobin
experimental randomized controlled study
Routine nursing care
A total of 60 children who are 7-12 years of age(a new diagnosis of ALL AML or lymphoma and receiving for the first time after being diagnosed a 7- to 10-day chemotherapy treatment )
fatigue The Fatigue Scale(FS-C) for 7-12 (intensity)
The Fatigue Scale Parent Version (FS-P)
1 effective nursing interventions(45- 60mdaya week)education about the fatigue with the chemotherapy and fatigue handbook 2 T1 After a 7-day period the children
and parent were evaluated with the Fatigue Scale
1The difference betwthe 2 mean values wafound to be statisticallsignificant 2 statistically significadifference was found between the Fatigue Scale-Child mean scothe experimental (272the control group (4213)children
679
48
25 Chiang et
al(2007)
The effects of ldquo a home ndashbased aerobic exercise interventionrdquo on fatigue and cardiorespiratory fitness in children with Acute Lymphoblastic Leukemia during the maintenance stage of chemotherapy
To examine the effect of ldquo a home ndashbased aerobic exercise interventionrdquo on fatigue and cardiorespiratory fitness in children with Acute Lymphoblastic Leukemia during the maintenance stage of chemotherapy
Quasi-experi -mental
Routine
nursing care
14 pediatric oncology patients in the experimental group and 10 in control group who were matched by age and sex ages7-18 years
1Cardiorespiratory fitness
2Fatigue
1Cardiorespiratory fitness Physical Activity Recall
VO2maxHR peak 6MWT
2 Fatigue PedsQL-MFS(Generalsleepcognitive fatigue)
1A six-week home-based aerobic exercise intervention 2 8 time points T0 baseline T1-T6 every week during the
intervention(6 weeks) T7 post intervention T8 follow-up (one month after
the end of the home-based exercise program)
1 For intent-to ndash treatthe findings indicated are no intervention efftime differences by anon the subscale of fat2 For per-protocol angeneral fatigue( mean422plusmn402) was the osubscale that was siglower for children whothe exercise interventthose in control groupfollow-up assessmentmonth after the compintervention) 3 The VO2peak are significantly improvingexperimental group atbaseline- and post-intassessment The VO2was significantly highechildren who were in experimental group thcontrol subjects at post-intervention assefor the per-protocol an
680
49
Appendix IV Instrument used to measure fatigue
Name Instrument
developers
Description Used in
age in
ref
Reliability
Consistency of
instrument
Checklist Individual Strength
(CIS)22
Vercoulen et
al1996
20 items using 7-point Likert scale of
fatigue To measure four aspects of
fatiguesubjective experience
contractionmotivation physical
Activity
6-14 Not reported
Child Fatigue Scale (CFS)7 Hockenberry
et al2003
14 items 2 part questionnaire frequency
(yes or no) 5-point Likert scale of the
intensity of any yes responses
7-13
14-18 α073-o84
The Fatigue Scale for 7-12
year Olds (FS-C)224
Hockenberry
et al
14 items provide a fatigue intensity score
5-point Likert scale
7-12 αo84
The Fatigue Scale for 13-18
year Olds (FS-A)24
Hockenberry
et al
14 items provide a fatigue intensity score
5-point Likert scale
13-18 α076-o96
Pediatric Quality of life
Multidimensional Fatigue
Scale (Peds QL-MFS)2325
Varni2002 18 items to measure three aspects of
fatigueGeneralsleepcognitive
14-18 Not reported
681
50
Appendix V Excluded studies and reasons for exclusion
Baggott C Dodd M Kennedy C Marina N Miaskowski C Multiple Symptoms in Pediatric Oncology
Patients A Systematic Review Journal of Pediatric Oncology Nursing 2009 Nov-Dec 27(6)
325-339
Reason for exclusion Not outcome of interest
Barlow JH Ellard DR Psycho-educational interventions for children with chronic disease parents and
siblings an overview of the research evidence base Care Health amp Development 2004 Nov
30(6)637-45
Reason for exclusion Not outcome of interest
Bedider S Moyer CA Randomized controlled trials of pediatric massage A review Evid Based
Complement Alternat Med 2007 Mar 4(1)23-34 Epub 2006 Nov 3
Reason for exclusion Not outcome of interest
de Nijs EJ Ros W Grijpdonck MH Nursing intervention for fatigue during the treatment for cancer Cancer
Nursing 2008 31(3)191-206
Reason for exclusion Not population of interest
Edwards JL Gibson F Richardson A Sepion B Ream E Fatigue in adolescents with and following a
cancer diagnosis developing an evidence base for practice European Journal of Cancer 2003
Dec 39(18)2671-80
Reason for exclusion Not experimental or quasi-experimental study
Hinds PS Hockenberry-Eatan M Developing a research program on fatigue in children and adolescents
diagnosed with cancer Journal of Pediatric Oncology Nursing 2001 Mar-Apr 18(2 Suppl
1)3-12
Reason for exclusion Not experimental or quasi-experimental study
Hockenberry-Eaton M Hinds PS Alcoser P ONeill JB Euell K Howard V Gattuso J Taylor J Fatigue in
Children and Adolescents With Cancer Journal of Pediatric Oncology Nursing 1998 July
15(3)172-182
Reason for exclusion Not experimental or quasi-experimental study
Jean-Pierre P Mustian K Kohli S Roscoe JA Hickok JT Morrow GR Community-based clinical oncology
research trials for cancer-related fatigue The Journal of Supportive Oncology 2006 Nov-Dec
4(10)511-6
682
51
Reason for exclusion Not population of interest
Kangas M Bovbjerg DH Montgomery GH Cancer-Related Fatigue A Systematic and Meta-Analytic
Review of Non-Pharmacological Therapies for Cancer Patients Psychological Bulletin 2008 Sep
134(5)700-41
Reason for exclusion Not population of interest
Lotfi-Jam K Carey M Jefford M Schofield P Charleson C Aranda S Nonpharmacologic strategies for
managing common chemotherapy adverse effects A systematic review Journal of Clinical
Oncology 2008 Dec 1 26(34)5618-29 Epub 2008 Nov 3
Reason for exclusion Not outcome of interest
Marchese VG Chiarello LA Lange BJ Effects of physical therapy intervention for children with acute
lymphoblastic leukemia Pediatr Blood Cancer 2004 Feb42(2)127-33
Reason for exclusion Not outcome of interest
Meeske KA Siegel SE Globe DR Mack WJ Bernstein L Prevalence and correlates of fatigue in
long-term survivors of childhood leukemia Journal of Clinical Oncology 2005 Aug 20
23(24)5501-10
Reason for exclusion Not intervention study
Minton O Richardson A Sharpe M Hotopf Stone P A systematic review and meta-analysis of the
pharmacological treatment of cancer-related fatigue J Natl Cancer Inst 2008 Aug 20
100(16)1155-66 Epub 2008 Aug 11
Reason for exclusion Not population and intervention of interest
Mustian KM Morrow GR Carroll JK Figueroa-Moseley CD Pascal JP Williams GC Integrative
nonpharmacologic behavioral interventions for the management of Cancer-Related fatigue The
Oncologist 2007 12(1)52-67
Reason for exclusion Not population of interest
Neill J Belan I Ried K Effectiveness of non-pharmacological interventions for fatigue in adults with
multiple sclerosis rheumatoid arthritis or systemic lupus erythematosus a systematic review
Journal of Advanced Nursing 2006 Dec 56(6)617-35
Reason for exclusion Not population of interest
Rheingans JI A systematic review of nonpharmacologic adjunctive therapies for symptom management
Journal of Pediatric Oncology Nursing 2007 24(2) 81-94
683
52
Reason for exclusion Not outcome of interest
Rheingans JI Pediatric oncology nursesrsquo management of patients symptoms Journal of Pediatric
Oncology Nursing 2008 Nov 25(6) 303-11
Reason for exclusion Not outcome of interest
San Juan AF Fleck SJ Chamorro-Vintildea C Mateacute-Muntildeoz JL Moral S Peacuterez M Cardona C Del Valle MF
Hernaacutendez M Ramiacuterez M Madero L Lucia A Effects of an intrahospital exercise program
intervention for children with leukemia Medicine amp Science in Sports amp Exercise 2007 Jan
39(1)13-21
Reason for exclusion Not outcome of interest
Sanford SD Okuma JO Pan J Srivastava DK West N Farr L Hinds PS Gender differences in sleep
fatigue and daytime activity in a pediatric oncology sample receiving dexamethasone Journal of
Pediatric Psychology 2008 Apr 33(3)298-306 Epub 2007 Nov 17
Reason for exclusion Not experimental or quasi-experimental study
Schmitz KH Holtzman J Courneya KS Macircsse LC Duval S Kane R Controlled physical activity trials in
cancer survivors a systematic review and meta-analysis Cancer Epidemiol Biomarkers Prev
2005 Jul 14(7)1588-95
Reason for exclusion Not population of interest
van Brussel M Takken T Lucia A van der Net J Helders PJ Is physical fitness decreased in survivors of
childhood leukemia A systematic review Leukemia 2005 Jan 19(1)13-7
Reason for exclusion Not population of interest
Whiting P Bagnall AM Snowden AJ Cornell JE Mulrow CD Ramirez G Interventions for the treatment
and management of chronic fatigue syndrome JAMA 2001 Sep 19 286(11)1360-8
Reason for exclusion Not intervention of interest
Whitsett SF Gudmundsdottir M Davies B McCarthy P Friedman D Chemotherapy-related fatigue in
childhood cancer correlates consequences and coping strategies Journal of Pediatric
Oncology Nursing 2008 Mar-Apr 25(2)86-96 Epub 2008 Feb 29
Reason for exclusion Not experimental or quasi-experimental study
Winner C Muumlller C Hoffmann C Boos J Rosenbaum D Physical activity and childhood cancer Pediatr
Blood Cancer 2010 Apr 54(4)501-10
Reason for exclusion Not research study
684
53
Wu M Hsu L Zhang B Shen N Lu H Li S The experiences of cancer-related fatigue among Chinese
children with leukaemia A phenomenological study Journal of Nursing Studies 2010 Jan
47(1)49-59 Epub 2009 Aug 25
Reason for exclusion Not experimental or quasi-experimental study
Yeh CH Chiang YC Lin L Yang CP Chien LC Weaver MA Chuang HL Clinical factors associated with
fatigue over time in paediatric oncology patients receiving chemotherapy British Journal of
Cancer 2008 Jul 8 99(1)23-9 Epub 2008 Jun 24
Reason for exclusion Not experimental or quasi-experimental study
685
21
given There is another article about intervention measures combine health education
and physical activity 2 In this study patients were informed about the following (1) health
education patients received daily education about chemotherapy-related fatigue and
information from a health education manual written by the author (2) encouragement for
children to engage in activities such as listening to music drawing and reading and (3)
physical activity which involved walking along the corridors of the ward for 10-15 minutes
These health education measures were presented for 45-60 minutes a day for a total of
seven days The study design for non-pharmacological interventions used control groups
that included primarily people who had received standard treatment or people who did
not receive an exercise intervention
Outcome measures
Five measurement tools were used in this group of seven papers concerning childrenrsquos
fatigue (Appendix IV) Because those studies included both school-age children and
adolescents the following descriptions will be differentiated by age Fatigue
measurements for school-aged children with cancer include the following the Child
Fatigue Scale (CFS) 7 a scale that measures the frequency and intensity of fatigue and
the Fatigue Scale for 7-12 year Olds (FS-C) 224 a scale that can be used to evaluate the
intensity of fatigue On the other hand fatigue measurements for adolescent cancer
patients include the following the Fatigue Scale for 13-18-year-olds (FS-A) 24 a measure
that can help evaluate fatigue levels the Pediatric Quality of Life Multidimensional
Fatigue Scale (Peds QL-MFS) 2325 a tool that can be divided into three sub-scales to
understand the general cognitive and sleep rest components of fatigue and finally the
CIS-20 for school-age children and adolescents 22 a scale that measures four levels of
654
22
fatigue namely subjective experience attention motivation and physical activity Two
studies used the Peds QL-MFS scale to measure fatigue2325
Meta-analysis results Two studies of the included papers failed to provide sufficient raw data they could not be
included in the meta-analysis Hinds et al 24 did not include post-test data Genc et al 2
provided no pre-test data PostWhite et al7 reported that fatigue after the health
education intervention was not statistically different but they presented the results
without presenting fatigue-related data Therefore the meta-analysis included three
studies 222325
The heterogeneity of studies was analyzed with Chi square statistics and no statistical
significance was found Therefore the data was combined in meta-analysis according to
exercise intervention on fatigue In addition there were three articles using the Peds
QL-MFS as a research tool to examine childrenrsquos improvements in fatigue Among these
Keats 22 and Chiang 24 present the effectiveness of exercise interventions using three
subscales Therefore the meta-analysis also analysis of the effects of these exercise
intervention measures on three subscales of Peds QL-MFS general fatigue sleep rest
fatigue and cognitive fatigue
The effectiveness of exercise intervention for fatigue We analyzed the exercise intervention effect on fatigue A total of 2 studies 22 23 were
included Takken et al 22 used community-based exercise training program to reduce
fatigue of children 6 to 14 years (mean 93y) of age who survived ALL Fatigue
measurement by Checklist Individual Strength (CIS) after 12-week of training fatigue
655
23
show no significant differences between pre (meanplusmnSD 415plusmn147) and post training
(meanplusmnSD368plusmn217) but fatigue change from baseline mean reduction of 11
Keats et al23 although used community-based physical activity program to reduce fatigue
for adolescents 14 to 18 years of age (mean162 y) with cancer (Lymphoma leukemia CNS
tumor germ cell tumor) Studies used fatigue by PedsQLMFS Results show general fatigue
from baseline to 8 weeks and to 3 months follow up significantly improves General
fatigue sleeprest fatigue and total fatigue from baseline to 3 months follow up showed
significant improvements Sleeprest fatigue and total fatigue at 1 years followed up were
significant improvements
Figure 2 shows the overall effect of exercise intervention in children and adolescents with
cancers with a focus on improving fatigue Due to the lower heterogeneity (p>005) the
fixed effects model was used to pool the data for meta-analysis (Overall effect size=
-006 95 Confidence Interval (CI) -070 to 058) A result did not indicate a statistically
significant difference (p = 087)
656
24
Figure2 Meta-analysis results of exercise intervention on fatigue
In addition Keats23 and Chiang25 used the three sub-scales of Peds QL-MFS to
determine the general cognitive and sleep rest components of fatigue The following
present the effectiveness of exercise interventions using three subscales including
general fatigue sleep rest fatigue and cognitive fatigue 2325
Chiang et al 25 used a 6- week home-based aerobic exercise intervention to reduce
fatigue of children 7 to 18 years (mean age at experimental group was 1088 y in control
group was 1247 y) of age who with acute lymphoblastic leukemia Fatigue measurement
by Peds QL-MFS after training For intent-to ndash treat analysis the findings indicated that
there are no intervention effects and time differences by any items on the subscale of
fatigue For per-protocol analysis general fatigue( meanplusmnSD 422plusmn402) was the only
subscale that was significantly lower for children who received the exercise intervention
than those in control group at follow-up assessment (one month after the completion of
intervention)
Keats et al23 although used community-based physical activity program to reduce fatigue
for adolescents 14 to 18 years of age (mean162 y) with cancer (Lymphoma leukemia
CNS tumor germ cell tumor) Both studies used fatigue by PedsQLMFS Results show
general fatigue from baseline to 8 weeks and to 3 months follow up significantly improves
657
25
General fatigue sleeprest fatigue and total fatigue from baseline to 3 months follow up
showed significant improvements Sleeprest fatigue and total fatigue at 1 years followed
up were significant improvements
The effectiveness of exercise intervention for general fatigue
The impact of the exercise interventions upon levels of general fatigue was also analysed
The heterogeneity was low (p>005) Therefore the fixed effects model was used to
examine the effectiveness The effect size is -076 indicating a statistically significant
difference (p = 001 95 CI -135 to -017 Fig 3) The evidence suggests that exercise
intervention can reduce general fatigue in children with cancer
Fig 3 Meta-analysis results of exercise intervention for general fatigue
The effectiveness of exercise intervention for sleep rest fatigue
The following is the result of the meta-analysis of the effectiveness of exercise
interventions on sleep rest fatigue First the heterogeneity test was conducted with P gt
005 representing small heterogeneity and the fixed effects model was used Fig 4
shows the effect size is -035 indicating no statistically significant differences (p = 023
95 CI-092 to 022 Fig 4)
658
26
Fig 4 Meta-analysis results of exercise intervention for sleep rest fatigue
The effectiveness of exercise intervention for cognitive fatigue Lastly the following data reports the results of meta-analysis of the effectiveness of
exercise interventions for cognitive fatigue The heterogeneity was p>005 then the
fixed effects model was used The effect size is -035 indicating no statistically significant
differences (p = 024 95 CI-092 023 Fig 5)
Fig 5 Meta-analysis results of exercise intervention for cognitive fatigue
Narrative presentation of remaining included studies
Three studies were not included in meta-analysis Post-White et al7 one of the aims in
this study was to examine the effect of massage therapy on fatigue in children with
cancer The study was a quasi-experimental design Twenty-three childrenparent dyads
were enrolled 17completed all data points Children with cancer ages 7 to 18 years
received at least 2 identical cycles of chemotherapy and one parent participated in the
2-period crossover design in which 4 weekly massage sessions (MT) alternated with 4
659
27
weekly quiet-time (QT) control sessions There were no significant changes in fatigue in
children over the 4-week MT or QT conditions either independently (change over time) or
when we compared fatigue by condition
The lack of effect of massage on fatigue may be the difficulty some children had in
differentiating fatigue from being relaxed underscores the challenge of measuring fatigue
in children Some children interpreted being tired or relaxed as having greater fatigue
because they felt like lying around and sleeping or felt unmotivated to do their usual
activities all measures of fatigue in the instrument used in the study
Hinds et al24conducted a prospective two-site randomized controlled pilot study to
assess the feasibility of an enhanced physical activity (EPA) intervention in hospitalized
children and adolescents receiving treatment for a solid tumor or for acute myeloid
leukemia (AML) Twenty-nine patients (25 with a solid tumor and 4 with AML) participated
age range from 736 to 1816 (mean 1248 y) The EPA intervention selected was
pedaling a stationary bicycle-style exerciser (Chattanooga Peddler Deluxe Bio-Teck
Medical Memphis TN) for 30 minutes twice daily for 2 to 4 days of hospitalization The
mixed model analysis revealed no significant differences in patient reports of fatigue
between the two study arms or over time
Genc et al2 conducted a RCT involving children with cancer who are 7 to 12 years of age
and receiving chemotherapy treatment to determine the impact of educational
intervention by nurses on decreasing the fatigue syndrome The research sample was
composed of a total of 60 children with cancer with 30 children being included in the
660
28
experimental group (mean age 923)and 30 children included in the control group (mean
age 937) with their mothers In the experimental group after the 7th to 10th day of the
chemotherapy treatment throughout a week the researcher conducted the nursing
interventions every day for 45 to 60 minutes In the control group routine nursing
interventions were carried out The experimental group received education about the
fatigue with the chemotherapy and fatigue handbook was given which was developed by
the authors Children and mothers were consulted for including activities that could
decrease fatigue which were described as effective interventions A statistically
significant difference was found between the Fatigue Scale-Child mean scores of the
experimental (2723) and the control group (4213) The results suggest that fatigue of
children with cancer can be reduced by implementing appropriate nursing interventions
(t=567 Plt00)
Discussion The purpose of this systematic review was to determine the effectiveness of
non-pharmacological interventions specifically targeting fatigue for children and
adolescents with cancer undergoing chemotherapy or after receiving chemotherapy
Included articles about the effectiveness of non-pharmacological interventions for
children and adolescents with cancer were published between the years of 2007 and
2009 Although interventions for cancer fatigue for adults have been extensively studied
it can be seen from either the title of the paper or related content that an intervention
study on children was a pilot study or a feasibility study Representing a field in its early
stage these studies show that the fatigue issues with young cancer patients have only
recently been taken seriously
661
29
The results of our meta-analysis include measurement of the four performance indicators
fatigue and general fatigue sleep rest fatigue and cognitive fatigue The results show
that there is a statistically significant difference only in the domain of general fatigue
using an exercise intervention for children with cancer can improve the degree of fatigue
with the effect size reaching 0671 Other results do not indicate significant differences
The reasons may include the following
1 Characteristics of the cancer The exhaustion from cancer occurs not only during cancer treatment but also in during
long-term survival a time during which patients may continue to be affected by this
symptom 8 26 Therefore when using intervention measures to improve fatigue
circumstances should be considered such as the process of the treatment and the course
or stage of the disease Because cancer patients will experience different forms of
treatment or courses of treatment the disease itself or treatment differences should be
considered in the choice of intervention Even chemotherapy drugs should be taken into
consideration For example a period of general steroid treatment can increase patientsrsquo
fatigue In those studies of children with cancer few studies looked solely at one type of
cancer most studies included a variety of cancer patients Furthermore most studies do
not clearly explain the stage of the disease or course of treatment and most do not
include treatment variables in the control group Moreover children with cancer may
have different levels of physical function
2 Research design The sample size Currently there are few studies with large sample size and a rigorous
RCT design due to the small number of papers available for analysis The sample size
included in our studyrsquos data analysis is between 20 and 42 people this small sample size
will affect the power available to evaluate outcome variables
Although most of the non-pharmacological interventions still use exercise and physical
activity and these studies overall show better results for fatigue as compared with
controls more research is still needed to further confirm the efficacy of these findings
662
30
The dropout rate in the evaluated research varies a great deal ranging from 5 to 45
these dropout rates may result from the characteristics of the research subjects or the
lengthy time involved in participating in these studies The research data with a high
turnover rate might not reflect the actual outcomes of participation in exercise and the
quality of the research contained in articles with high subject turnover rates may be
lower
Exercise doses and time The exercise doses needed to reduce fatigue cannot be
determined additionally the amount of exercise completed by the patient is also
inconsistent interventions vary between 2-3 times per week and two times a day and
exercise duration varies between 10 and 45 minutes each time Furthermore the study
interventions vary in length between a couple of days and a long period of 16 weeks The
data collection times are different some were measured 12 weeks after the intervention
began some were measured during the 6 weeks of intervention some were measured
three months after the intervention was finished and some were measured after one
year
In addition disease-related symptoms decrease childrenrsquos willingness to participate in
exercise interventions inappropriate exercise intervention programs may actually
increase childrens fatigue In addition the children in the study are still developing
physically it is important to consider ways to design an interesting exercise intervention
to increase the compliance of patients in order to improve the effectiveness Although
intervention programs in the hospital or in a community sports center can improve the
effectiveness because they provide supervision the feasibility of these programs is
questionable However if the program is home-based the children need to be
supervised by parents in order to improve their compliance in doing the exercises
Furthermore regarding the nature of the intervention the results from this study indicate
that the researched non-pharmacological interventions include the following exercise
training programs physical activity massage therapy and health education interventions
However according to the National Comprehensive Cancer Network 1 clinical guidelines
663
31
for cancer non-drug measures for cancer fatigue can be separated into five categories
(1) activity enhancement (2) psychosocial interventions such as cognitive behavioral
therapy (CBT) stress management relaxation techniques and support groups (3)
attention-restoring therapy (4) nutritional consultation and (5) cognitive behavioral
therapy specifically targeting sleep disturbance Researchers have also suggested that
psychosocial interventions should be included in the future research for children with
cancer-related fatigue 22
(2) The measurement tools in the study The assessment of fatigue can be
one-dimensional or multidimensional One-dimensional assessment can help understand
the severity of fatigue symptoms however multidimensional scales are often more
credible Therefore when measuring cancer-related fatigue researchers should consider
whether there is a uniform definition of fatigue or a standardized tool for measuring
fatigue in order to facilitate further systematic meta-analyses and further develop the
clinical care guidelines
Limitations of the review The present review has some potential limitations First the low methodological quality
may influence the result Although exercise intervention seems promising quality of the
RCTs was generally quite low Future studies require better design and reporting if
methodological issues to establish evidence-based nonpharmcologic intervention
Second the identified studies covered only a limited types of nonpharmcological
intervention especially in exercise intervention The guidelines for cancer-related fatigue
in NCCN (2011)1 referred to more interventions than the ones included in this review
such as cognitive behavioral therapy and nutrition consultation Thirdly the small sample
size and effect size could be potentially having led to underpowered approach for
detecting the effects on fatigue Therefore we recommend that as research continues to
grow a re-analysis can be undertaken Fourthly Combining data in meta analysis from
664
32
studies where the ages were quite different is a potential source of heterogeneity and
may affect the interpretation of the results
Conclusion At present clinical treatment is widely used for cancer patients However child and
adolescent cancer patients often experience various side effects which cause short-term
or long-term discomfort both physically and psychologically In particular with the
increasing cure rate cancer related fatigue during or after treatment has become an
important issue This study result provided positive effect of exercise intervention on
general fatigue
Implications for practice The results of this systematic review and meta-analysis show that exercise interventions
can effectively improve the level of general fatigue In particular although the articles
were self-reported feasibility studies their results all indicate that exercise interventions
for fatigue are feasible and safe there was no conclusion to be made for the use of
massage therapy or health education measures because there was only one article for
each of these interventions
Recommendations for practice
Cancer-related fatigue is one of the most severe and frequent symptoms by pediatric
oncology children and adolescent suffered during treatment and the symptom existed
even after treatment has ended Until now no golden standard of treatment to fatigue is
established The findings call for more attention to how to reduce patientrsquos levels of
fatigue Based on the available information evaluated in this review the following
recommendations for practice are provided
665
33
bull For children aged 7 to 18 who has cancer (eg Lymphoma leukemia CNS tumor
germ cell tumor) an effective progressive aerobic exercise program is recommended to
be at least 2-3 times per week 20 to 45 minute for each session and last for 6-16 weeks
in order to reduce their general fatigue (tiredness physically weakness) In addition
adults should be involved in accompanying children while they are performing physical
exercise of which should be able to improve the adherence rate (level 2 ) ( Grade of
recommendation A)
bull For children aged 7 to 18 who has cancer (eg Lymphoma leukemia CNS tumor
germ cell tumor) an progressive aerobic exercise program will not be effective to reduce
their sleep andor rest (sleeping or resting a lot) or cognitive fatigue (problems with
thinking quickly or problems with remembering) (level 2 ) ( Grade of recommendation C)
bull Nursing interventions in educating treatment of fatigue include information about
activity nutrition energy preservation consulting and providing a useful fatigue
handbook will benefit those children who are 7 to 12 years have a new diagnosis of ALL
AML or lymphoma and receive for the first time after being diagnosed a 7- to 10-day
chemotherapy treatment (level 2) ( Grade of recommendation A)
bull A 4-week massage therapy program (the therapists massage childrenrsquos back legs
arms stomachchest and face) is not effective for children who are aged 7 to 18 and
have acute lymphoblastic leukemia brain tumors lymphoma rhabdomyosarcoma
Wilms tumor or Ewing sarcoma(level 2)( Grade of recommendation C)
bull Using a 12-week aerobic and strength exercise (45-min exercise sessions twice a
week) is not effective for children who are aged 6-14 and survived acute lymphoblaststic
leukemia age from 6 to 14(level 2) ( Grade of recommendation C)
bull Using a physical activity intervention (30minutestwice daily for 2-4days) is not
effective for children who are 7 to 18 years of age with soild tumor or AML(level 2)
( Grade of recommendation C)
666
34
Implications for research According to this systematic review and meta-analysis results there are suggestions to
improve the effectiveness of future research on non-pharmacological interventions for
children and young peoplersquos cancer-related fatigue
As the majority of included non-pharmacological interventions for the fatigue of cancer
patients consist of exercise programs future research should also consider various
non-pharmacological interventions in order to understand the effectiveness of different
methods
Regarding the exercise intervention methods and studies should consider multiple
factors including the age or personal condition of the subject the disease stage and the
amount of daily activities Studies should use design prescriptions (eg frequency
intensity duration and type of exercise) and consider the adherence to the measures in
order to enhance the study strength
In measuring the results of non-pharmacological interventions there should be standard
definitions or standard measurement tools to facilitate the following systematic review
and meta-analysis that can subsequently be developed into clinical care guidelines
Reviewing the effectiveness of the current non-pharmacological management of children
and adolescent cancer patients there is still a lack of rigorous RCT research Limited by
the characteristics of cancer there is still a lack of large sample sizes
Potential conflicts of interest There is no conflict of interest
Acknowledgements
Thank you to Dr Rie Konno Research Fellow Joanna Briggs Institute for her help in
assessing studies
667
35
References 1 National Comprehensive Cancer Network( NCCN) in USA NCCN clinical practice
guideline in oncology cancer-related fatigue 2011 2 Ekti Genc R amp Conk Z Impact of effective nursing interventions to the fatigue
syndrome in children who receive chemotherapy Cancer Nursing 200831(4)312-317
3 Childhood Cancer Foundation of ROC (2009March) The classification of diseases
and age sex statistical tables of case Childhood Cancer Foundation of ROC newsletter103105-106
4 Department of Health Executive Yuan ROC (TAIWAN)(2009 March 20)2009 cause of death statistic Health and National Health Insurance Annual Statistics Information Service 2010 June 28Available httpwwwdohgovtwstatisticdatavital statists9898health statistic--lifepdf
5 Chang TK (2007December 8) Common childhood cancer and its treatment Status
Childhood Cancer Foundation of ROC (TAIWAN) 2010 September 23 Available httpwwwccfrocorgtwchildchild_events_readphpe_id=45
6 Hockenberry MJ amp Wilson D Wongs nursing care of infants and children (8th ed) St
Louis MO Mosby 2007
7 Post-White J Fitzgerald M Savik K Hooke MC Hannahan AB amp Sencer SF
Massage therapy for children with cancer Journal of Pediatric Oncology Nursing 2009 26(1)16-28
8Chiang YC Yeh CH Wang WKamp Yang CP The experience of cancer-related fatigue
in Taiwanese children European Journal of Cancer Care 2009 18(1)43-49 9Langeveld NE Grootenhuis M A Voute P A de Haan RJ amp van den Bos C No excess
fatigue in young adult survivors of childhood cancer European Journal of Cancer 200339(2)204-214
10Piper BF Lindsey AM amp Dodd MJ Fatigue mechanisms in cancer patients
developing nursing theory Oncology Nursing Forum 1987 14(6)17-23 11Nail LM amp Winningham ML Fatigue In S L Groenwald M H Forgge M Goodman
amp C H Yarbro (Eds) Cancer Nursing Principles and practice (4 th ed) Boston Jones and Bartlett1997
12Irvine D Vincent L Graydon JE Bubela N amp Thompson L The prevalence and
correlates of fatigue in patients receiving treatment with chemotherapy and
668
36
radiotherapy A comparison with the fatigue experienced by healthy individuals Cancer Nursing 199417(5)367-378
13Hinds PS amp Hockenberry-Eaton M Developing a research program on fatigue in
children and adloescents diagnosed with cancer Journal of Pediatric Oncology Nursing 200118(2)3-12
14Aaronson LS Teel CS Cassmeyer V Neuberger GB Pallikkathayil L Pierce J Press
AN Williams DP amp Wingate A Defining and measuring fatigue Journal of Nursing scholarship 1999 31(1)45-50
15Yeh CH Wang CH Chiang YC Lin Lamp Chien LC Assessment of symptoms reported
by 10- to 18-year-old cancer patients in Taiwan 2009 38(5)738-746 16 Okuyama T Akechi T Kugaya A Okamura H Shima Yamp Maruguchi M
Development and validation of the cancer fatigue scale a brief three-dimensional self-rating scale for assessment of fatigue in cancer patients Journal of Pain amp Symptom Management 2000 19(1) 5-14
17Gibson F Mulhall AB Richardson A Edwards JL Ream E amp Sepion BJ A
phenomenologic study of fatigue in adolescents receiving treatment for cancer Oncology Nursing Forum200532(3)651-660
18Wolfe J Grier HE Klar N Levin SB Ellenbogen JMamp Salem-Schatz S et al
Symptoms and suffering at the end of life in children with cancer New England Journal of Medicine 2000342(5)326-333
19Whiting P Bagnall AM Sowden AJ Cornell JE Mulrow CD amp Ramirez G
Interventions for the treatment and management of chronic fatigue syndrome a systematic review JAMA the Journal of the American Medical Association 2001286(11)1360-1368
20 Kangas M Bovbjerg DHamp Montgomery G H Cancer-related fatigue a systematic
and meta-analytic review of non-pharmacological therapies for cancer patients Psychological Bulletin 2008134 (5)700-741
21Williams PD Schmideskamp J Ridder EL amp Williams AR Symptom monitoring and
dependent care during cancer treatment in children pilot study Cancer Nursing 200629(3)188-197
22Takken T van der Torre P Zwerink M Hulzebos EH Bierings M Helders PJMamp van
der Net J Development feasibility and efficacy of a community-based exercise training
669
37
program in pediatric cancer survivors Psycho-Oncology 200918(4)440-448
23Keats MR amp Culos-Reed SN A community-based physical activity program for
adolescents with cancer (project TREK) program feasibility and preliminary findings
Pediatric hematology and oncology 200830(4) 272-280
24Hinds PS Hockenberry M Rai SN Zhang L Razzouk B I Cremer L McCarthy K amp
Rodriguez-Galindo C Clinical field testing of an enhanced-activity intervention in
hospitalized children with cancer Journal of Pain amp Symptom Management 2007
33(6)686-697
25Chiang YC The effects of ldquo a home-based aerobic exercise interventionrdquo on fatigue
and cardiorespiratory fitness in children with acute lymphoblastic leukemia during the
maintenance stage of chemotherapy Unpublished thesis Taiwan Tao-Yuan 2007
26Langeveld N Ubbink M amp Smets E I dont have any energy The experience of
fatigue in young adult survivors of childhood cancer European journal of oncology
nursing 20004(1)20-28
27 Kisner C Colby L Therapeutic exercise Foundations and techniques 2nd ed Philadelphia PAFA Davies 2007
670
38
Appendix I JBI Critical Appraisal Checklist for Experimental studies
Author__________ Year_________ Record Number__________________
Questions 1 to 4 must be answered ldquoyesrdquo for study to be included in the metashyanalysis
1 Were the participants randomized to study groups
Yes No Not clear
2 Other than research intervention were participants in each groups treated the same
Yes No Not clear
3 Were the outcomes measured in the same manner for all participants
Yes No Not clear
4 Were groups comparable at entry
Yes No Not clear
5 Was randomization of participants blinded
Yes No Not clear
6 Were those assessing outcome blinded to treatment allocation (if outcome not objective such as survival or length of hospitalization)
Yes No Not clear
7 Was allocation to treatment groups concealed from the allocator
Yes No Not clear
8 Was an appropriate statistical analysis used
671
39
Yes No Not clear
9 Were outcomes measured in a reliable way
Yes No Not clear
10 Was there adequate followshyup of participants
Yes No Not clear
Summary
TOTAL
Yes No Not clear
DECISION
Use Reject
Narrative summary only Further information needed
COMMENTS
672
40
Appendix II JBI Data Extraction Tool for Quantitative Studies Authors and Year
Journal Title
Record NumberArticle Reference No
Reviewer
Method
Settings
Participants
Number of participants
Group A Group B Group C
Control Intervention 1 Intervention 2
Interventions
Group A
Control
Group B
Intervention 1
Group C
Intervention 2
Outcome measures
Definition
673
41
Other outcome measures
Outcome description ScaleMeasure
Results
Dichotomous Data
Outcome Control Group
Numbertotal number
Treatment Group
Numbertotal number
Continuous Data
Authorrsquos Conclusions
Comments
Outcome Control Group
Mean amp SD
Treatment Group
Mean amp SD
674
43
Appendix III Details of included studies (N=6)(2720212223) RefNo Author(s)
(years) Title Study question Research
method Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
22 Takken T van der Torre P Zwerink M Hulzebos E H Bierings M Helders P J Mamp van der Net J (2009)
Development feasibility and efficacy of a community-based exercise training program in pediatric cancer survivors
To develop a 12-week home-based exercise training program (comprising aerobic and strength exercises) for children who survived ALL and to study itrsquos feasibility and efficacy
Pre-post test design
No comparsion group
Survived ALL(N=9)ages 6-14 years
1anthropometry 2 muscle strength 3functional mobility 4cardio-pulmonary
exercise test 5Fatigue
1 Feasibility questionnaire 2 anthropometry electronic scale and a wallmounted stadiometerHarpenden skin fold calipers 3 muscle strength handheld dynamometer 4functional mobility Timed Up
and Go test (TUG) 5cardio-pulmonary exercise test electronically braked cycle ergometer 6Fatigue(mean)CSI-20 (subjective experience of fatigueconcentrationmotivationphysical activity)
112-week exercise training program
2 Patients were assessed before (T0) and after (T1) 12 weeks of training
1 muscle strength execapacity functional moand fatigue showed nosignificant differences between pre(meanplusmnSD415plusmn147) and post training(meanplusmnSD3687)
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
7 Post-White J Fitzgerald M Savik K Hooke M C Hannahan A B amp Sencer S F (2009)
Massage therapy for children with cancer
To determine whether 4 weekly sessions of massage compared with 4 quiet-time control conditions would reduce anxiety cortisol levels fatigue nausea and pain in children with cancer undergoing chemotherapy and would reduce anxiety fatigue and mood disturbance in a parent
2-period crossover design (Randomized)
quiet-time
control
sessions
Children with cancer 1 to 18 years of age Twenty-three childrenparent dyads were enrolled 17 completed all data points
children 1relaxation 2symptoms 3 fatigue
parents
1anxiety 2 fatigue
children 1relaxation (heart and respiratory rates blood pressure and salivary cortisol level)
2symptoms (pain nausea anxiety 3 fatigue 1-2y3-6yLansky Play Performance Scale (PPS) 7-13y
1 4 weekly massage (MT) sessions alternated with 4 weekly quiet-time(QT) control sessions
2 children included presession and postsession vital signs (heart rate respiratory rate blood pressure) and self-report (parent proxy report for age 1-2 years) of pain nausea and anxiety Fatigue was measured before sessions 1 and 4 and at each follow-up Parent measures
included anxiety fatigue and mood states
1Massage was moreeffective than quiet tireducing heart rate inchildren anxiety in cless than age 14 yeaparent anxiety 2There were no sign
changes in blood pcortisol pain naufatigue (no state d
3 Children reported tmassage helped thebetter lessened theirand worries and hadlasting effects than q
675
44
14-18yChild Fatigue Scale (CFS) (frequency
intensity) 2 parents anxiety and fatigue
676
45
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
24 Hinds P S Hockenberry M Rai S N Zhang L Razzouk B I Cremer L McCarthy K amp Rodriguez-Galindo C (2007)
Clinical field testing of an enhanced-activity intervention in hospitalized children with cancer
To determine the feasibility of an
enhanced physical activity EPA intervention in children and adolescents hospitalized to receive chemotherapy for a solid tumor or AML and to assess the sleep and fatigue outcomes of the intervention using two different statistical approaches to analyze the longitudinal symptom data
randomized prospective two-site and two-group pilot study
Standard care Twenty nine patients (25 with a solid tumor and 4 with AML)ages 7-18 years
1 sleep duration 2 sleep efficiency 3 fatigue
1sleep duration sleep efficiency The
Wrist Actigraph The Daily Sleep Diary-Parent 2 fatigue (mean) The Fatigue Scale(FS-C) for 7-12 (intensity) The Fatigue Scale(FS-A) for 13-18 The Fatigue Scale Parent Version (FS-P) The Fatigue Scale Staff Version (FS-S)
1enhanced physical activity (EPA) (hospital-based 30 minutes
twice daily for 2-4 days) 2 T0On the day of admission
(Day 0 or baseline)patient and parents completed the fatigue instruments and a team member applied the actigraph Patients wore the wrist actigraph T1 from Day 0 to 2 or 3 consecutive days (Days 0e3) In addition the patient same parent and staff nurses completed the daily sleep and fatigue reports in the late afternoons of Days 1-3
1 ANOVA model slesignificantly more the experimental athe control arm whdifferences from bsleep efficiency vaaveraged and com
2 The patient-reported mean fatigue scoresarms were higher amadolescents than for
3 The mixed model anarevealed no significandifferences in patientfatigue between
the two study arms otime( no final result iSD only give mixed result)
677
46
23 Keats M
R amp Culos-Reed S N (2008)
A community-based physical activity program for adolescents with cancer (project TREK) program feasibility and preliminary findings
To examine the
feasibility of a
theoretically-based
physical activity (PA)
intervention in
adolescents with
cancerand
examination of the
impact of the
program on
participant QOL
including social
emotional and
physical
well-being(including fatigue)
Repeat measures longitudinal design
No comparsion group
10 adolescents(Lymphoma(4)leukemia(4)CNS tumor(1)germ cell tumor(1)) ages 14-18 years
1physical fitness 2quality of life (QOL) 3PA behavior 4fatigue
1 Feasibility was assessed by participant recruitment attendance and adherence
2physical fitness Fitnessgram 3quality of life (QOL) Pediatric Quality of Life Inventory (PedsQL) 4PA behavior leisure score index (LSI) 5fatigue (mean) pediatric Quality of life
Multidimensional Fatigue Scale (Peds QL-MFS)
(Generalsleepcognitive fatigue)
116week physical activity (PA)
2 total PA physical fitness and overall QOL was assessed at 5 different intervals T0 preintervention (baseline) T1midintervention (after the
first 8 wk) T2 postintervention
(16 wk) T3 3-months
postintervention T4 1-year poststudy
initiation
1 from baseline -wkssig Improvementstotal PA physfitness and Qgeneral fatigue(meanplusmnSD 796plusmn135)
2 from baseline to 3FUsig Improvin general fatigue(meanplusmnSD824plusmn131)slefatigue(meanplusmnSD755plusmn191)totafatigue(meanplusmnSD778plusmn150)
3at 1 years FUsImprovements in sleeprest fatigue(meanplusmnSD725plusmn203)total (meanplusmnSD 763plusmn
678
47
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
2 Gene R E amp Conk Z (2008)
Impact of Effective Nursing Interventions to the Fatigue Syndrome in Children Who Receive Chemotherapy
1 to examine the effects of an effective nursing intervention to the fatigue syndrome of children 7 to 12 years of age who receive chemotherapy 2Tto examine the relationship between fatigue and demographic variables (age sex) diagnoses ([ALL AML] lymphoma) and therapy-related variables (eg level of hemoglobin
experimental randomized controlled study
Routine nursing care
A total of 60 children who are 7-12 years of age(a new diagnosis of ALL AML or lymphoma and receiving for the first time after being diagnosed a 7- to 10-day chemotherapy treatment )
fatigue The Fatigue Scale(FS-C) for 7-12 (intensity)
The Fatigue Scale Parent Version (FS-P)
1 effective nursing interventions(45- 60mdaya week)education about the fatigue with the chemotherapy and fatigue handbook 2 T1 After a 7-day period the children
and parent were evaluated with the Fatigue Scale
1The difference betwthe 2 mean values wafound to be statisticallsignificant 2 statistically significadifference was found between the Fatigue Scale-Child mean scothe experimental (272the control group (4213)children
679
48
25 Chiang et
al(2007)
The effects of ldquo a home ndashbased aerobic exercise interventionrdquo on fatigue and cardiorespiratory fitness in children with Acute Lymphoblastic Leukemia during the maintenance stage of chemotherapy
To examine the effect of ldquo a home ndashbased aerobic exercise interventionrdquo on fatigue and cardiorespiratory fitness in children with Acute Lymphoblastic Leukemia during the maintenance stage of chemotherapy
Quasi-experi -mental
Routine
nursing care
14 pediatric oncology patients in the experimental group and 10 in control group who were matched by age and sex ages7-18 years
1Cardiorespiratory fitness
2Fatigue
1Cardiorespiratory fitness Physical Activity Recall
VO2maxHR peak 6MWT
2 Fatigue PedsQL-MFS(Generalsleepcognitive fatigue)
1A six-week home-based aerobic exercise intervention 2 8 time points T0 baseline T1-T6 every week during the
intervention(6 weeks) T7 post intervention T8 follow-up (one month after
the end of the home-based exercise program)
1 For intent-to ndash treatthe findings indicated are no intervention efftime differences by anon the subscale of fat2 For per-protocol angeneral fatigue( mean422plusmn402) was the osubscale that was siglower for children whothe exercise interventthose in control groupfollow-up assessmentmonth after the compintervention) 3 The VO2peak are significantly improvingexperimental group atbaseline- and post-intassessment The VO2was significantly highechildren who were in experimental group thcontrol subjects at post-intervention assefor the per-protocol an
680
49
Appendix IV Instrument used to measure fatigue
Name Instrument
developers
Description Used in
age in
ref
Reliability
Consistency of
instrument
Checklist Individual Strength
(CIS)22
Vercoulen et
al1996
20 items using 7-point Likert scale of
fatigue To measure four aspects of
fatiguesubjective experience
contractionmotivation physical
Activity
6-14 Not reported
Child Fatigue Scale (CFS)7 Hockenberry
et al2003
14 items 2 part questionnaire frequency
(yes or no) 5-point Likert scale of the
intensity of any yes responses
7-13
14-18 α073-o84
The Fatigue Scale for 7-12
year Olds (FS-C)224
Hockenberry
et al
14 items provide a fatigue intensity score
5-point Likert scale
7-12 αo84
The Fatigue Scale for 13-18
year Olds (FS-A)24
Hockenberry
et al
14 items provide a fatigue intensity score
5-point Likert scale
13-18 α076-o96
Pediatric Quality of life
Multidimensional Fatigue
Scale (Peds QL-MFS)2325
Varni2002 18 items to measure three aspects of
fatigueGeneralsleepcognitive
14-18 Not reported
681
50
Appendix V Excluded studies and reasons for exclusion
Baggott C Dodd M Kennedy C Marina N Miaskowski C Multiple Symptoms in Pediatric Oncology
Patients A Systematic Review Journal of Pediatric Oncology Nursing 2009 Nov-Dec 27(6)
325-339
Reason for exclusion Not outcome of interest
Barlow JH Ellard DR Psycho-educational interventions for children with chronic disease parents and
siblings an overview of the research evidence base Care Health amp Development 2004 Nov
30(6)637-45
Reason for exclusion Not outcome of interest
Bedider S Moyer CA Randomized controlled trials of pediatric massage A review Evid Based
Complement Alternat Med 2007 Mar 4(1)23-34 Epub 2006 Nov 3
Reason for exclusion Not outcome of interest
de Nijs EJ Ros W Grijpdonck MH Nursing intervention for fatigue during the treatment for cancer Cancer
Nursing 2008 31(3)191-206
Reason for exclusion Not population of interest
Edwards JL Gibson F Richardson A Sepion B Ream E Fatigue in adolescents with and following a
cancer diagnosis developing an evidence base for practice European Journal of Cancer 2003
Dec 39(18)2671-80
Reason for exclusion Not experimental or quasi-experimental study
Hinds PS Hockenberry-Eatan M Developing a research program on fatigue in children and adolescents
diagnosed with cancer Journal of Pediatric Oncology Nursing 2001 Mar-Apr 18(2 Suppl
1)3-12
Reason for exclusion Not experimental or quasi-experimental study
Hockenberry-Eaton M Hinds PS Alcoser P ONeill JB Euell K Howard V Gattuso J Taylor J Fatigue in
Children and Adolescents With Cancer Journal of Pediatric Oncology Nursing 1998 July
15(3)172-182
Reason for exclusion Not experimental or quasi-experimental study
Jean-Pierre P Mustian K Kohli S Roscoe JA Hickok JT Morrow GR Community-based clinical oncology
research trials for cancer-related fatigue The Journal of Supportive Oncology 2006 Nov-Dec
4(10)511-6
682
51
Reason for exclusion Not population of interest
Kangas M Bovbjerg DH Montgomery GH Cancer-Related Fatigue A Systematic and Meta-Analytic
Review of Non-Pharmacological Therapies for Cancer Patients Psychological Bulletin 2008 Sep
134(5)700-41
Reason for exclusion Not population of interest
Lotfi-Jam K Carey M Jefford M Schofield P Charleson C Aranda S Nonpharmacologic strategies for
managing common chemotherapy adverse effects A systematic review Journal of Clinical
Oncology 2008 Dec 1 26(34)5618-29 Epub 2008 Nov 3
Reason for exclusion Not outcome of interest
Marchese VG Chiarello LA Lange BJ Effects of physical therapy intervention for children with acute
lymphoblastic leukemia Pediatr Blood Cancer 2004 Feb42(2)127-33
Reason for exclusion Not outcome of interest
Meeske KA Siegel SE Globe DR Mack WJ Bernstein L Prevalence and correlates of fatigue in
long-term survivors of childhood leukemia Journal of Clinical Oncology 2005 Aug 20
23(24)5501-10
Reason for exclusion Not intervention study
Minton O Richardson A Sharpe M Hotopf Stone P A systematic review and meta-analysis of the
pharmacological treatment of cancer-related fatigue J Natl Cancer Inst 2008 Aug 20
100(16)1155-66 Epub 2008 Aug 11
Reason for exclusion Not population and intervention of interest
Mustian KM Morrow GR Carroll JK Figueroa-Moseley CD Pascal JP Williams GC Integrative
nonpharmacologic behavioral interventions for the management of Cancer-Related fatigue The
Oncologist 2007 12(1)52-67
Reason for exclusion Not population of interest
Neill J Belan I Ried K Effectiveness of non-pharmacological interventions for fatigue in adults with
multiple sclerosis rheumatoid arthritis or systemic lupus erythematosus a systematic review
Journal of Advanced Nursing 2006 Dec 56(6)617-35
Reason for exclusion Not population of interest
Rheingans JI A systematic review of nonpharmacologic adjunctive therapies for symptom management
Journal of Pediatric Oncology Nursing 2007 24(2) 81-94
683
52
Reason for exclusion Not outcome of interest
Rheingans JI Pediatric oncology nursesrsquo management of patients symptoms Journal of Pediatric
Oncology Nursing 2008 Nov 25(6) 303-11
Reason for exclusion Not outcome of interest
San Juan AF Fleck SJ Chamorro-Vintildea C Mateacute-Muntildeoz JL Moral S Peacuterez M Cardona C Del Valle MF
Hernaacutendez M Ramiacuterez M Madero L Lucia A Effects of an intrahospital exercise program
intervention for children with leukemia Medicine amp Science in Sports amp Exercise 2007 Jan
39(1)13-21
Reason for exclusion Not outcome of interest
Sanford SD Okuma JO Pan J Srivastava DK West N Farr L Hinds PS Gender differences in sleep
fatigue and daytime activity in a pediatric oncology sample receiving dexamethasone Journal of
Pediatric Psychology 2008 Apr 33(3)298-306 Epub 2007 Nov 17
Reason for exclusion Not experimental or quasi-experimental study
Schmitz KH Holtzman J Courneya KS Macircsse LC Duval S Kane R Controlled physical activity trials in
cancer survivors a systematic review and meta-analysis Cancer Epidemiol Biomarkers Prev
2005 Jul 14(7)1588-95
Reason for exclusion Not population of interest
van Brussel M Takken T Lucia A van der Net J Helders PJ Is physical fitness decreased in survivors of
childhood leukemia A systematic review Leukemia 2005 Jan 19(1)13-7
Reason for exclusion Not population of interest
Whiting P Bagnall AM Snowden AJ Cornell JE Mulrow CD Ramirez G Interventions for the treatment
and management of chronic fatigue syndrome JAMA 2001 Sep 19 286(11)1360-8
Reason for exclusion Not intervention of interest
Whitsett SF Gudmundsdottir M Davies B McCarthy P Friedman D Chemotherapy-related fatigue in
childhood cancer correlates consequences and coping strategies Journal of Pediatric
Oncology Nursing 2008 Mar-Apr 25(2)86-96 Epub 2008 Feb 29
Reason for exclusion Not experimental or quasi-experimental study
Winner C Muumlller C Hoffmann C Boos J Rosenbaum D Physical activity and childhood cancer Pediatr
Blood Cancer 2010 Apr 54(4)501-10
Reason for exclusion Not research study
684
53
Wu M Hsu L Zhang B Shen N Lu H Li S The experiences of cancer-related fatigue among Chinese
children with leukaemia A phenomenological study Journal of Nursing Studies 2010 Jan
47(1)49-59 Epub 2009 Aug 25
Reason for exclusion Not experimental or quasi-experimental study
Yeh CH Chiang YC Lin L Yang CP Chien LC Weaver MA Chuang HL Clinical factors associated with
fatigue over time in paediatric oncology patients receiving chemotherapy British Journal of
Cancer 2008 Jul 8 99(1)23-9 Epub 2008 Jun 24
Reason for exclusion Not experimental or quasi-experimental study
685
22
fatigue namely subjective experience attention motivation and physical activity Two
studies used the Peds QL-MFS scale to measure fatigue2325
Meta-analysis results Two studies of the included papers failed to provide sufficient raw data they could not be
included in the meta-analysis Hinds et al 24 did not include post-test data Genc et al 2
provided no pre-test data PostWhite et al7 reported that fatigue after the health
education intervention was not statistically different but they presented the results
without presenting fatigue-related data Therefore the meta-analysis included three
studies 222325
The heterogeneity of studies was analyzed with Chi square statistics and no statistical
significance was found Therefore the data was combined in meta-analysis according to
exercise intervention on fatigue In addition there were three articles using the Peds
QL-MFS as a research tool to examine childrenrsquos improvements in fatigue Among these
Keats 22 and Chiang 24 present the effectiveness of exercise interventions using three
subscales Therefore the meta-analysis also analysis of the effects of these exercise
intervention measures on three subscales of Peds QL-MFS general fatigue sleep rest
fatigue and cognitive fatigue
The effectiveness of exercise intervention for fatigue We analyzed the exercise intervention effect on fatigue A total of 2 studies 22 23 were
included Takken et al 22 used community-based exercise training program to reduce
fatigue of children 6 to 14 years (mean 93y) of age who survived ALL Fatigue
measurement by Checklist Individual Strength (CIS) after 12-week of training fatigue
655
23
show no significant differences between pre (meanplusmnSD 415plusmn147) and post training
(meanplusmnSD368plusmn217) but fatigue change from baseline mean reduction of 11
Keats et al23 although used community-based physical activity program to reduce fatigue
for adolescents 14 to 18 years of age (mean162 y) with cancer (Lymphoma leukemia CNS
tumor germ cell tumor) Studies used fatigue by PedsQLMFS Results show general fatigue
from baseline to 8 weeks and to 3 months follow up significantly improves General
fatigue sleeprest fatigue and total fatigue from baseline to 3 months follow up showed
significant improvements Sleeprest fatigue and total fatigue at 1 years followed up were
significant improvements
Figure 2 shows the overall effect of exercise intervention in children and adolescents with
cancers with a focus on improving fatigue Due to the lower heterogeneity (p>005) the
fixed effects model was used to pool the data for meta-analysis (Overall effect size=
-006 95 Confidence Interval (CI) -070 to 058) A result did not indicate a statistically
significant difference (p = 087)
656
24
Figure2 Meta-analysis results of exercise intervention on fatigue
In addition Keats23 and Chiang25 used the three sub-scales of Peds QL-MFS to
determine the general cognitive and sleep rest components of fatigue The following
present the effectiveness of exercise interventions using three subscales including
general fatigue sleep rest fatigue and cognitive fatigue 2325
Chiang et al 25 used a 6- week home-based aerobic exercise intervention to reduce
fatigue of children 7 to 18 years (mean age at experimental group was 1088 y in control
group was 1247 y) of age who with acute lymphoblastic leukemia Fatigue measurement
by Peds QL-MFS after training For intent-to ndash treat analysis the findings indicated that
there are no intervention effects and time differences by any items on the subscale of
fatigue For per-protocol analysis general fatigue( meanplusmnSD 422plusmn402) was the only
subscale that was significantly lower for children who received the exercise intervention
than those in control group at follow-up assessment (one month after the completion of
intervention)
Keats et al23 although used community-based physical activity program to reduce fatigue
for adolescents 14 to 18 years of age (mean162 y) with cancer (Lymphoma leukemia
CNS tumor germ cell tumor) Both studies used fatigue by PedsQLMFS Results show
general fatigue from baseline to 8 weeks and to 3 months follow up significantly improves
657
25
General fatigue sleeprest fatigue and total fatigue from baseline to 3 months follow up
showed significant improvements Sleeprest fatigue and total fatigue at 1 years followed
up were significant improvements
The effectiveness of exercise intervention for general fatigue
The impact of the exercise interventions upon levels of general fatigue was also analysed
The heterogeneity was low (p>005) Therefore the fixed effects model was used to
examine the effectiveness The effect size is -076 indicating a statistically significant
difference (p = 001 95 CI -135 to -017 Fig 3) The evidence suggests that exercise
intervention can reduce general fatigue in children with cancer
Fig 3 Meta-analysis results of exercise intervention for general fatigue
The effectiveness of exercise intervention for sleep rest fatigue
The following is the result of the meta-analysis of the effectiveness of exercise
interventions on sleep rest fatigue First the heterogeneity test was conducted with P gt
005 representing small heterogeneity and the fixed effects model was used Fig 4
shows the effect size is -035 indicating no statistically significant differences (p = 023
95 CI-092 to 022 Fig 4)
658
26
Fig 4 Meta-analysis results of exercise intervention for sleep rest fatigue
The effectiveness of exercise intervention for cognitive fatigue Lastly the following data reports the results of meta-analysis of the effectiveness of
exercise interventions for cognitive fatigue The heterogeneity was p>005 then the
fixed effects model was used The effect size is -035 indicating no statistically significant
differences (p = 024 95 CI-092 023 Fig 5)
Fig 5 Meta-analysis results of exercise intervention for cognitive fatigue
Narrative presentation of remaining included studies
Three studies were not included in meta-analysis Post-White et al7 one of the aims in
this study was to examine the effect of massage therapy on fatigue in children with
cancer The study was a quasi-experimental design Twenty-three childrenparent dyads
were enrolled 17completed all data points Children with cancer ages 7 to 18 years
received at least 2 identical cycles of chemotherapy and one parent participated in the
2-period crossover design in which 4 weekly massage sessions (MT) alternated with 4
659
27
weekly quiet-time (QT) control sessions There were no significant changes in fatigue in
children over the 4-week MT or QT conditions either independently (change over time) or
when we compared fatigue by condition
The lack of effect of massage on fatigue may be the difficulty some children had in
differentiating fatigue from being relaxed underscores the challenge of measuring fatigue
in children Some children interpreted being tired or relaxed as having greater fatigue
because they felt like lying around and sleeping or felt unmotivated to do their usual
activities all measures of fatigue in the instrument used in the study
Hinds et al24conducted a prospective two-site randomized controlled pilot study to
assess the feasibility of an enhanced physical activity (EPA) intervention in hospitalized
children and adolescents receiving treatment for a solid tumor or for acute myeloid
leukemia (AML) Twenty-nine patients (25 with a solid tumor and 4 with AML) participated
age range from 736 to 1816 (mean 1248 y) The EPA intervention selected was
pedaling a stationary bicycle-style exerciser (Chattanooga Peddler Deluxe Bio-Teck
Medical Memphis TN) for 30 minutes twice daily for 2 to 4 days of hospitalization The
mixed model analysis revealed no significant differences in patient reports of fatigue
between the two study arms or over time
Genc et al2 conducted a RCT involving children with cancer who are 7 to 12 years of age
and receiving chemotherapy treatment to determine the impact of educational
intervention by nurses on decreasing the fatigue syndrome The research sample was
composed of a total of 60 children with cancer with 30 children being included in the
660
28
experimental group (mean age 923)and 30 children included in the control group (mean
age 937) with their mothers In the experimental group after the 7th to 10th day of the
chemotherapy treatment throughout a week the researcher conducted the nursing
interventions every day for 45 to 60 minutes In the control group routine nursing
interventions were carried out The experimental group received education about the
fatigue with the chemotherapy and fatigue handbook was given which was developed by
the authors Children and mothers were consulted for including activities that could
decrease fatigue which were described as effective interventions A statistically
significant difference was found between the Fatigue Scale-Child mean scores of the
experimental (2723) and the control group (4213) The results suggest that fatigue of
children with cancer can be reduced by implementing appropriate nursing interventions
(t=567 Plt00)
Discussion The purpose of this systematic review was to determine the effectiveness of
non-pharmacological interventions specifically targeting fatigue for children and
adolescents with cancer undergoing chemotherapy or after receiving chemotherapy
Included articles about the effectiveness of non-pharmacological interventions for
children and adolescents with cancer were published between the years of 2007 and
2009 Although interventions for cancer fatigue for adults have been extensively studied
it can be seen from either the title of the paper or related content that an intervention
study on children was a pilot study or a feasibility study Representing a field in its early
stage these studies show that the fatigue issues with young cancer patients have only
recently been taken seriously
661
29
The results of our meta-analysis include measurement of the four performance indicators
fatigue and general fatigue sleep rest fatigue and cognitive fatigue The results show
that there is a statistically significant difference only in the domain of general fatigue
using an exercise intervention for children with cancer can improve the degree of fatigue
with the effect size reaching 0671 Other results do not indicate significant differences
The reasons may include the following
1 Characteristics of the cancer The exhaustion from cancer occurs not only during cancer treatment but also in during
long-term survival a time during which patients may continue to be affected by this
symptom 8 26 Therefore when using intervention measures to improve fatigue
circumstances should be considered such as the process of the treatment and the course
or stage of the disease Because cancer patients will experience different forms of
treatment or courses of treatment the disease itself or treatment differences should be
considered in the choice of intervention Even chemotherapy drugs should be taken into
consideration For example a period of general steroid treatment can increase patientsrsquo
fatigue In those studies of children with cancer few studies looked solely at one type of
cancer most studies included a variety of cancer patients Furthermore most studies do
not clearly explain the stage of the disease or course of treatment and most do not
include treatment variables in the control group Moreover children with cancer may
have different levels of physical function
2 Research design The sample size Currently there are few studies with large sample size and a rigorous
RCT design due to the small number of papers available for analysis The sample size
included in our studyrsquos data analysis is between 20 and 42 people this small sample size
will affect the power available to evaluate outcome variables
Although most of the non-pharmacological interventions still use exercise and physical
activity and these studies overall show better results for fatigue as compared with
controls more research is still needed to further confirm the efficacy of these findings
662
30
The dropout rate in the evaluated research varies a great deal ranging from 5 to 45
these dropout rates may result from the characteristics of the research subjects or the
lengthy time involved in participating in these studies The research data with a high
turnover rate might not reflect the actual outcomes of participation in exercise and the
quality of the research contained in articles with high subject turnover rates may be
lower
Exercise doses and time The exercise doses needed to reduce fatigue cannot be
determined additionally the amount of exercise completed by the patient is also
inconsistent interventions vary between 2-3 times per week and two times a day and
exercise duration varies between 10 and 45 minutes each time Furthermore the study
interventions vary in length between a couple of days and a long period of 16 weeks The
data collection times are different some were measured 12 weeks after the intervention
began some were measured during the 6 weeks of intervention some were measured
three months after the intervention was finished and some were measured after one
year
In addition disease-related symptoms decrease childrenrsquos willingness to participate in
exercise interventions inappropriate exercise intervention programs may actually
increase childrens fatigue In addition the children in the study are still developing
physically it is important to consider ways to design an interesting exercise intervention
to increase the compliance of patients in order to improve the effectiveness Although
intervention programs in the hospital or in a community sports center can improve the
effectiveness because they provide supervision the feasibility of these programs is
questionable However if the program is home-based the children need to be
supervised by parents in order to improve their compliance in doing the exercises
Furthermore regarding the nature of the intervention the results from this study indicate
that the researched non-pharmacological interventions include the following exercise
training programs physical activity massage therapy and health education interventions
However according to the National Comprehensive Cancer Network 1 clinical guidelines
663
31
for cancer non-drug measures for cancer fatigue can be separated into five categories
(1) activity enhancement (2) psychosocial interventions such as cognitive behavioral
therapy (CBT) stress management relaxation techniques and support groups (3)
attention-restoring therapy (4) nutritional consultation and (5) cognitive behavioral
therapy specifically targeting sleep disturbance Researchers have also suggested that
psychosocial interventions should be included in the future research for children with
cancer-related fatigue 22
(2) The measurement tools in the study The assessment of fatigue can be
one-dimensional or multidimensional One-dimensional assessment can help understand
the severity of fatigue symptoms however multidimensional scales are often more
credible Therefore when measuring cancer-related fatigue researchers should consider
whether there is a uniform definition of fatigue or a standardized tool for measuring
fatigue in order to facilitate further systematic meta-analyses and further develop the
clinical care guidelines
Limitations of the review The present review has some potential limitations First the low methodological quality
may influence the result Although exercise intervention seems promising quality of the
RCTs was generally quite low Future studies require better design and reporting if
methodological issues to establish evidence-based nonpharmcologic intervention
Second the identified studies covered only a limited types of nonpharmcological
intervention especially in exercise intervention The guidelines for cancer-related fatigue
in NCCN (2011)1 referred to more interventions than the ones included in this review
such as cognitive behavioral therapy and nutrition consultation Thirdly the small sample
size and effect size could be potentially having led to underpowered approach for
detecting the effects on fatigue Therefore we recommend that as research continues to
grow a re-analysis can be undertaken Fourthly Combining data in meta analysis from
664
32
studies where the ages were quite different is a potential source of heterogeneity and
may affect the interpretation of the results
Conclusion At present clinical treatment is widely used for cancer patients However child and
adolescent cancer patients often experience various side effects which cause short-term
or long-term discomfort both physically and psychologically In particular with the
increasing cure rate cancer related fatigue during or after treatment has become an
important issue This study result provided positive effect of exercise intervention on
general fatigue
Implications for practice The results of this systematic review and meta-analysis show that exercise interventions
can effectively improve the level of general fatigue In particular although the articles
were self-reported feasibility studies their results all indicate that exercise interventions
for fatigue are feasible and safe there was no conclusion to be made for the use of
massage therapy or health education measures because there was only one article for
each of these interventions
Recommendations for practice
Cancer-related fatigue is one of the most severe and frequent symptoms by pediatric
oncology children and adolescent suffered during treatment and the symptom existed
even after treatment has ended Until now no golden standard of treatment to fatigue is
established The findings call for more attention to how to reduce patientrsquos levels of
fatigue Based on the available information evaluated in this review the following
recommendations for practice are provided
665
33
bull For children aged 7 to 18 who has cancer (eg Lymphoma leukemia CNS tumor
germ cell tumor) an effective progressive aerobic exercise program is recommended to
be at least 2-3 times per week 20 to 45 minute for each session and last for 6-16 weeks
in order to reduce their general fatigue (tiredness physically weakness) In addition
adults should be involved in accompanying children while they are performing physical
exercise of which should be able to improve the adherence rate (level 2 ) ( Grade of
recommendation A)
bull For children aged 7 to 18 who has cancer (eg Lymphoma leukemia CNS tumor
germ cell tumor) an progressive aerobic exercise program will not be effective to reduce
their sleep andor rest (sleeping or resting a lot) or cognitive fatigue (problems with
thinking quickly or problems with remembering) (level 2 ) ( Grade of recommendation C)
bull Nursing interventions in educating treatment of fatigue include information about
activity nutrition energy preservation consulting and providing a useful fatigue
handbook will benefit those children who are 7 to 12 years have a new diagnosis of ALL
AML or lymphoma and receive for the first time after being diagnosed a 7- to 10-day
chemotherapy treatment (level 2) ( Grade of recommendation A)
bull A 4-week massage therapy program (the therapists massage childrenrsquos back legs
arms stomachchest and face) is not effective for children who are aged 7 to 18 and
have acute lymphoblastic leukemia brain tumors lymphoma rhabdomyosarcoma
Wilms tumor or Ewing sarcoma(level 2)( Grade of recommendation C)
bull Using a 12-week aerobic and strength exercise (45-min exercise sessions twice a
week) is not effective for children who are aged 6-14 and survived acute lymphoblaststic
leukemia age from 6 to 14(level 2) ( Grade of recommendation C)
bull Using a physical activity intervention (30minutestwice daily for 2-4days) is not
effective for children who are 7 to 18 years of age with soild tumor or AML(level 2)
( Grade of recommendation C)
666
34
Implications for research According to this systematic review and meta-analysis results there are suggestions to
improve the effectiveness of future research on non-pharmacological interventions for
children and young peoplersquos cancer-related fatigue
As the majority of included non-pharmacological interventions for the fatigue of cancer
patients consist of exercise programs future research should also consider various
non-pharmacological interventions in order to understand the effectiveness of different
methods
Regarding the exercise intervention methods and studies should consider multiple
factors including the age or personal condition of the subject the disease stage and the
amount of daily activities Studies should use design prescriptions (eg frequency
intensity duration and type of exercise) and consider the adherence to the measures in
order to enhance the study strength
In measuring the results of non-pharmacological interventions there should be standard
definitions or standard measurement tools to facilitate the following systematic review
and meta-analysis that can subsequently be developed into clinical care guidelines
Reviewing the effectiveness of the current non-pharmacological management of children
and adolescent cancer patients there is still a lack of rigorous RCT research Limited by
the characteristics of cancer there is still a lack of large sample sizes
Potential conflicts of interest There is no conflict of interest
Acknowledgements
Thank you to Dr Rie Konno Research Fellow Joanna Briggs Institute for her help in
assessing studies
667
35
References 1 National Comprehensive Cancer Network( NCCN) in USA NCCN clinical practice
guideline in oncology cancer-related fatigue 2011 2 Ekti Genc R amp Conk Z Impact of effective nursing interventions to the fatigue
syndrome in children who receive chemotherapy Cancer Nursing 200831(4)312-317
3 Childhood Cancer Foundation of ROC (2009March) The classification of diseases
and age sex statistical tables of case Childhood Cancer Foundation of ROC newsletter103105-106
4 Department of Health Executive Yuan ROC (TAIWAN)(2009 March 20)2009 cause of death statistic Health and National Health Insurance Annual Statistics Information Service 2010 June 28Available httpwwwdohgovtwstatisticdatavital statists9898health statistic--lifepdf
5 Chang TK (2007December 8) Common childhood cancer and its treatment Status
Childhood Cancer Foundation of ROC (TAIWAN) 2010 September 23 Available httpwwwccfrocorgtwchildchild_events_readphpe_id=45
6 Hockenberry MJ amp Wilson D Wongs nursing care of infants and children (8th ed) St
Louis MO Mosby 2007
7 Post-White J Fitzgerald M Savik K Hooke MC Hannahan AB amp Sencer SF
Massage therapy for children with cancer Journal of Pediatric Oncology Nursing 2009 26(1)16-28
8Chiang YC Yeh CH Wang WKamp Yang CP The experience of cancer-related fatigue
in Taiwanese children European Journal of Cancer Care 2009 18(1)43-49 9Langeveld NE Grootenhuis M A Voute P A de Haan RJ amp van den Bos C No excess
fatigue in young adult survivors of childhood cancer European Journal of Cancer 200339(2)204-214
10Piper BF Lindsey AM amp Dodd MJ Fatigue mechanisms in cancer patients
developing nursing theory Oncology Nursing Forum 1987 14(6)17-23 11Nail LM amp Winningham ML Fatigue In S L Groenwald M H Forgge M Goodman
amp C H Yarbro (Eds) Cancer Nursing Principles and practice (4 th ed) Boston Jones and Bartlett1997
12Irvine D Vincent L Graydon JE Bubela N amp Thompson L The prevalence and
correlates of fatigue in patients receiving treatment with chemotherapy and
668
36
radiotherapy A comparison with the fatigue experienced by healthy individuals Cancer Nursing 199417(5)367-378
13Hinds PS amp Hockenberry-Eaton M Developing a research program on fatigue in
children and adloescents diagnosed with cancer Journal of Pediatric Oncology Nursing 200118(2)3-12
14Aaronson LS Teel CS Cassmeyer V Neuberger GB Pallikkathayil L Pierce J Press
AN Williams DP amp Wingate A Defining and measuring fatigue Journal of Nursing scholarship 1999 31(1)45-50
15Yeh CH Wang CH Chiang YC Lin Lamp Chien LC Assessment of symptoms reported
by 10- to 18-year-old cancer patients in Taiwan 2009 38(5)738-746 16 Okuyama T Akechi T Kugaya A Okamura H Shima Yamp Maruguchi M
Development and validation of the cancer fatigue scale a brief three-dimensional self-rating scale for assessment of fatigue in cancer patients Journal of Pain amp Symptom Management 2000 19(1) 5-14
17Gibson F Mulhall AB Richardson A Edwards JL Ream E amp Sepion BJ A
phenomenologic study of fatigue in adolescents receiving treatment for cancer Oncology Nursing Forum200532(3)651-660
18Wolfe J Grier HE Klar N Levin SB Ellenbogen JMamp Salem-Schatz S et al
Symptoms and suffering at the end of life in children with cancer New England Journal of Medicine 2000342(5)326-333
19Whiting P Bagnall AM Sowden AJ Cornell JE Mulrow CD amp Ramirez G
Interventions for the treatment and management of chronic fatigue syndrome a systematic review JAMA the Journal of the American Medical Association 2001286(11)1360-1368
20 Kangas M Bovbjerg DHamp Montgomery G H Cancer-related fatigue a systematic
and meta-analytic review of non-pharmacological therapies for cancer patients Psychological Bulletin 2008134 (5)700-741
21Williams PD Schmideskamp J Ridder EL amp Williams AR Symptom monitoring and
dependent care during cancer treatment in children pilot study Cancer Nursing 200629(3)188-197
22Takken T van der Torre P Zwerink M Hulzebos EH Bierings M Helders PJMamp van
der Net J Development feasibility and efficacy of a community-based exercise training
669
37
program in pediatric cancer survivors Psycho-Oncology 200918(4)440-448
23Keats MR amp Culos-Reed SN A community-based physical activity program for
adolescents with cancer (project TREK) program feasibility and preliminary findings
Pediatric hematology and oncology 200830(4) 272-280
24Hinds PS Hockenberry M Rai SN Zhang L Razzouk B I Cremer L McCarthy K amp
Rodriguez-Galindo C Clinical field testing of an enhanced-activity intervention in
hospitalized children with cancer Journal of Pain amp Symptom Management 2007
33(6)686-697
25Chiang YC The effects of ldquo a home-based aerobic exercise interventionrdquo on fatigue
and cardiorespiratory fitness in children with acute lymphoblastic leukemia during the
maintenance stage of chemotherapy Unpublished thesis Taiwan Tao-Yuan 2007
26Langeveld N Ubbink M amp Smets E I dont have any energy The experience of
fatigue in young adult survivors of childhood cancer European journal of oncology
nursing 20004(1)20-28
27 Kisner C Colby L Therapeutic exercise Foundations and techniques 2nd ed Philadelphia PAFA Davies 2007
670
38
Appendix I JBI Critical Appraisal Checklist for Experimental studies
Author__________ Year_________ Record Number__________________
Questions 1 to 4 must be answered ldquoyesrdquo for study to be included in the metashyanalysis
1 Were the participants randomized to study groups
Yes No Not clear
2 Other than research intervention were participants in each groups treated the same
Yes No Not clear
3 Were the outcomes measured in the same manner for all participants
Yes No Not clear
4 Were groups comparable at entry
Yes No Not clear
5 Was randomization of participants blinded
Yes No Not clear
6 Were those assessing outcome blinded to treatment allocation (if outcome not objective such as survival or length of hospitalization)
Yes No Not clear
7 Was allocation to treatment groups concealed from the allocator
Yes No Not clear
8 Was an appropriate statistical analysis used
671
39
Yes No Not clear
9 Were outcomes measured in a reliable way
Yes No Not clear
10 Was there adequate followshyup of participants
Yes No Not clear
Summary
TOTAL
Yes No Not clear
DECISION
Use Reject
Narrative summary only Further information needed
COMMENTS
672
40
Appendix II JBI Data Extraction Tool for Quantitative Studies Authors and Year
Journal Title
Record NumberArticle Reference No
Reviewer
Method
Settings
Participants
Number of participants
Group A Group B Group C
Control Intervention 1 Intervention 2
Interventions
Group A
Control
Group B
Intervention 1
Group C
Intervention 2
Outcome measures
Definition
673
41
Other outcome measures
Outcome description ScaleMeasure
Results
Dichotomous Data
Outcome Control Group
Numbertotal number
Treatment Group
Numbertotal number
Continuous Data
Authorrsquos Conclusions
Comments
Outcome Control Group
Mean amp SD
Treatment Group
Mean amp SD
674
43
Appendix III Details of included studies (N=6)(2720212223) RefNo Author(s)
(years) Title Study question Research
method Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
22 Takken T van der Torre P Zwerink M Hulzebos E H Bierings M Helders P J Mamp van der Net J (2009)
Development feasibility and efficacy of a community-based exercise training program in pediatric cancer survivors
To develop a 12-week home-based exercise training program (comprising aerobic and strength exercises) for children who survived ALL and to study itrsquos feasibility and efficacy
Pre-post test design
No comparsion group
Survived ALL(N=9)ages 6-14 years
1anthropometry 2 muscle strength 3functional mobility 4cardio-pulmonary
exercise test 5Fatigue
1 Feasibility questionnaire 2 anthropometry electronic scale and a wallmounted stadiometerHarpenden skin fold calipers 3 muscle strength handheld dynamometer 4functional mobility Timed Up
and Go test (TUG) 5cardio-pulmonary exercise test electronically braked cycle ergometer 6Fatigue(mean)CSI-20 (subjective experience of fatigueconcentrationmotivationphysical activity)
112-week exercise training program
2 Patients were assessed before (T0) and after (T1) 12 weeks of training
1 muscle strength execapacity functional moand fatigue showed nosignificant differences between pre(meanplusmnSD415plusmn147) and post training(meanplusmnSD3687)
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
7 Post-White J Fitzgerald M Savik K Hooke M C Hannahan A B amp Sencer S F (2009)
Massage therapy for children with cancer
To determine whether 4 weekly sessions of massage compared with 4 quiet-time control conditions would reduce anxiety cortisol levels fatigue nausea and pain in children with cancer undergoing chemotherapy and would reduce anxiety fatigue and mood disturbance in a parent
2-period crossover design (Randomized)
quiet-time
control
sessions
Children with cancer 1 to 18 years of age Twenty-three childrenparent dyads were enrolled 17 completed all data points
children 1relaxation 2symptoms 3 fatigue
parents
1anxiety 2 fatigue
children 1relaxation (heart and respiratory rates blood pressure and salivary cortisol level)
2symptoms (pain nausea anxiety 3 fatigue 1-2y3-6yLansky Play Performance Scale (PPS) 7-13y
1 4 weekly massage (MT) sessions alternated with 4 weekly quiet-time(QT) control sessions
2 children included presession and postsession vital signs (heart rate respiratory rate blood pressure) and self-report (parent proxy report for age 1-2 years) of pain nausea and anxiety Fatigue was measured before sessions 1 and 4 and at each follow-up Parent measures
included anxiety fatigue and mood states
1Massage was moreeffective than quiet tireducing heart rate inchildren anxiety in cless than age 14 yeaparent anxiety 2There were no sign
changes in blood pcortisol pain naufatigue (no state d
3 Children reported tmassage helped thebetter lessened theirand worries and hadlasting effects than q
675
44
14-18yChild Fatigue Scale (CFS) (frequency
intensity) 2 parents anxiety and fatigue
676
45
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
24 Hinds P S Hockenberry M Rai S N Zhang L Razzouk B I Cremer L McCarthy K amp Rodriguez-Galindo C (2007)
Clinical field testing of an enhanced-activity intervention in hospitalized children with cancer
To determine the feasibility of an
enhanced physical activity EPA intervention in children and adolescents hospitalized to receive chemotherapy for a solid tumor or AML and to assess the sleep and fatigue outcomes of the intervention using two different statistical approaches to analyze the longitudinal symptom data
randomized prospective two-site and two-group pilot study
Standard care Twenty nine patients (25 with a solid tumor and 4 with AML)ages 7-18 years
1 sleep duration 2 sleep efficiency 3 fatigue
1sleep duration sleep efficiency The
Wrist Actigraph The Daily Sleep Diary-Parent 2 fatigue (mean) The Fatigue Scale(FS-C) for 7-12 (intensity) The Fatigue Scale(FS-A) for 13-18 The Fatigue Scale Parent Version (FS-P) The Fatigue Scale Staff Version (FS-S)
1enhanced physical activity (EPA) (hospital-based 30 minutes
twice daily for 2-4 days) 2 T0On the day of admission
(Day 0 or baseline)patient and parents completed the fatigue instruments and a team member applied the actigraph Patients wore the wrist actigraph T1 from Day 0 to 2 or 3 consecutive days (Days 0e3) In addition the patient same parent and staff nurses completed the daily sleep and fatigue reports in the late afternoons of Days 1-3
1 ANOVA model slesignificantly more the experimental athe control arm whdifferences from bsleep efficiency vaaveraged and com
2 The patient-reported mean fatigue scoresarms were higher amadolescents than for
3 The mixed model anarevealed no significandifferences in patientfatigue between
the two study arms otime( no final result iSD only give mixed result)
677
46
23 Keats M
R amp Culos-Reed S N (2008)
A community-based physical activity program for adolescents with cancer (project TREK) program feasibility and preliminary findings
To examine the
feasibility of a
theoretically-based
physical activity (PA)
intervention in
adolescents with
cancerand
examination of the
impact of the
program on
participant QOL
including social
emotional and
physical
well-being(including fatigue)
Repeat measures longitudinal design
No comparsion group
10 adolescents(Lymphoma(4)leukemia(4)CNS tumor(1)germ cell tumor(1)) ages 14-18 years
1physical fitness 2quality of life (QOL) 3PA behavior 4fatigue
1 Feasibility was assessed by participant recruitment attendance and adherence
2physical fitness Fitnessgram 3quality of life (QOL) Pediatric Quality of Life Inventory (PedsQL) 4PA behavior leisure score index (LSI) 5fatigue (mean) pediatric Quality of life
Multidimensional Fatigue Scale (Peds QL-MFS)
(Generalsleepcognitive fatigue)
116week physical activity (PA)
2 total PA physical fitness and overall QOL was assessed at 5 different intervals T0 preintervention (baseline) T1midintervention (after the
first 8 wk) T2 postintervention
(16 wk) T3 3-months
postintervention T4 1-year poststudy
initiation
1 from baseline -wkssig Improvementstotal PA physfitness and Qgeneral fatigue(meanplusmnSD 796plusmn135)
2 from baseline to 3FUsig Improvin general fatigue(meanplusmnSD824plusmn131)slefatigue(meanplusmnSD755plusmn191)totafatigue(meanplusmnSD778plusmn150)
3at 1 years FUsImprovements in sleeprest fatigue(meanplusmnSD725plusmn203)total (meanplusmnSD 763plusmn
678
47
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
2 Gene R E amp Conk Z (2008)
Impact of Effective Nursing Interventions to the Fatigue Syndrome in Children Who Receive Chemotherapy
1 to examine the effects of an effective nursing intervention to the fatigue syndrome of children 7 to 12 years of age who receive chemotherapy 2Tto examine the relationship between fatigue and demographic variables (age sex) diagnoses ([ALL AML] lymphoma) and therapy-related variables (eg level of hemoglobin
experimental randomized controlled study
Routine nursing care
A total of 60 children who are 7-12 years of age(a new diagnosis of ALL AML or lymphoma and receiving for the first time after being diagnosed a 7- to 10-day chemotherapy treatment )
fatigue The Fatigue Scale(FS-C) for 7-12 (intensity)
The Fatigue Scale Parent Version (FS-P)
1 effective nursing interventions(45- 60mdaya week)education about the fatigue with the chemotherapy and fatigue handbook 2 T1 After a 7-day period the children
and parent were evaluated with the Fatigue Scale
1The difference betwthe 2 mean values wafound to be statisticallsignificant 2 statistically significadifference was found between the Fatigue Scale-Child mean scothe experimental (272the control group (4213)children
679
48
25 Chiang et
al(2007)
The effects of ldquo a home ndashbased aerobic exercise interventionrdquo on fatigue and cardiorespiratory fitness in children with Acute Lymphoblastic Leukemia during the maintenance stage of chemotherapy
To examine the effect of ldquo a home ndashbased aerobic exercise interventionrdquo on fatigue and cardiorespiratory fitness in children with Acute Lymphoblastic Leukemia during the maintenance stage of chemotherapy
Quasi-experi -mental
Routine
nursing care
14 pediatric oncology patients in the experimental group and 10 in control group who were matched by age and sex ages7-18 years
1Cardiorespiratory fitness
2Fatigue
1Cardiorespiratory fitness Physical Activity Recall
VO2maxHR peak 6MWT
2 Fatigue PedsQL-MFS(Generalsleepcognitive fatigue)
1A six-week home-based aerobic exercise intervention 2 8 time points T0 baseline T1-T6 every week during the
intervention(6 weeks) T7 post intervention T8 follow-up (one month after
the end of the home-based exercise program)
1 For intent-to ndash treatthe findings indicated are no intervention efftime differences by anon the subscale of fat2 For per-protocol angeneral fatigue( mean422plusmn402) was the osubscale that was siglower for children whothe exercise interventthose in control groupfollow-up assessmentmonth after the compintervention) 3 The VO2peak are significantly improvingexperimental group atbaseline- and post-intassessment The VO2was significantly highechildren who were in experimental group thcontrol subjects at post-intervention assefor the per-protocol an
680
49
Appendix IV Instrument used to measure fatigue
Name Instrument
developers
Description Used in
age in
ref
Reliability
Consistency of
instrument
Checklist Individual Strength
(CIS)22
Vercoulen et
al1996
20 items using 7-point Likert scale of
fatigue To measure four aspects of
fatiguesubjective experience
contractionmotivation physical
Activity
6-14 Not reported
Child Fatigue Scale (CFS)7 Hockenberry
et al2003
14 items 2 part questionnaire frequency
(yes or no) 5-point Likert scale of the
intensity of any yes responses
7-13
14-18 α073-o84
The Fatigue Scale for 7-12
year Olds (FS-C)224
Hockenberry
et al
14 items provide a fatigue intensity score
5-point Likert scale
7-12 αo84
The Fatigue Scale for 13-18
year Olds (FS-A)24
Hockenberry
et al
14 items provide a fatigue intensity score
5-point Likert scale
13-18 α076-o96
Pediatric Quality of life
Multidimensional Fatigue
Scale (Peds QL-MFS)2325
Varni2002 18 items to measure three aspects of
fatigueGeneralsleepcognitive
14-18 Not reported
681
50
Appendix V Excluded studies and reasons for exclusion
Baggott C Dodd M Kennedy C Marina N Miaskowski C Multiple Symptoms in Pediatric Oncology
Patients A Systematic Review Journal of Pediatric Oncology Nursing 2009 Nov-Dec 27(6)
325-339
Reason for exclusion Not outcome of interest
Barlow JH Ellard DR Psycho-educational interventions for children with chronic disease parents and
siblings an overview of the research evidence base Care Health amp Development 2004 Nov
30(6)637-45
Reason for exclusion Not outcome of interest
Bedider S Moyer CA Randomized controlled trials of pediatric massage A review Evid Based
Complement Alternat Med 2007 Mar 4(1)23-34 Epub 2006 Nov 3
Reason for exclusion Not outcome of interest
de Nijs EJ Ros W Grijpdonck MH Nursing intervention for fatigue during the treatment for cancer Cancer
Nursing 2008 31(3)191-206
Reason for exclusion Not population of interest
Edwards JL Gibson F Richardson A Sepion B Ream E Fatigue in adolescents with and following a
cancer diagnosis developing an evidence base for practice European Journal of Cancer 2003
Dec 39(18)2671-80
Reason for exclusion Not experimental or quasi-experimental study
Hinds PS Hockenberry-Eatan M Developing a research program on fatigue in children and adolescents
diagnosed with cancer Journal of Pediatric Oncology Nursing 2001 Mar-Apr 18(2 Suppl
1)3-12
Reason for exclusion Not experimental or quasi-experimental study
Hockenberry-Eaton M Hinds PS Alcoser P ONeill JB Euell K Howard V Gattuso J Taylor J Fatigue in
Children and Adolescents With Cancer Journal of Pediatric Oncology Nursing 1998 July
15(3)172-182
Reason for exclusion Not experimental or quasi-experimental study
Jean-Pierre P Mustian K Kohli S Roscoe JA Hickok JT Morrow GR Community-based clinical oncology
research trials for cancer-related fatigue The Journal of Supportive Oncology 2006 Nov-Dec
4(10)511-6
682
51
Reason for exclusion Not population of interest
Kangas M Bovbjerg DH Montgomery GH Cancer-Related Fatigue A Systematic and Meta-Analytic
Review of Non-Pharmacological Therapies for Cancer Patients Psychological Bulletin 2008 Sep
134(5)700-41
Reason for exclusion Not population of interest
Lotfi-Jam K Carey M Jefford M Schofield P Charleson C Aranda S Nonpharmacologic strategies for
managing common chemotherapy adverse effects A systematic review Journal of Clinical
Oncology 2008 Dec 1 26(34)5618-29 Epub 2008 Nov 3
Reason for exclusion Not outcome of interest
Marchese VG Chiarello LA Lange BJ Effects of physical therapy intervention for children with acute
lymphoblastic leukemia Pediatr Blood Cancer 2004 Feb42(2)127-33
Reason for exclusion Not outcome of interest
Meeske KA Siegel SE Globe DR Mack WJ Bernstein L Prevalence and correlates of fatigue in
long-term survivors of childhood leukemia Journal of Clinical Oncology 2005 Aug 20
23(24)5501-10
Reason for exclusion Not intervention study
Minton O Richardson A Sharpe M Hotopf Stone P A systematic review and meta-analysis of the
pharmacological treatment of cancer-related fatigue J Natl Cancer Inst 2008 Aug 20
100(16)1155-66 Epub 2008 Aug 11
Reason for exclusion Not population and intervention of interest
Mustian KM Morrow GR Carroll JK Figueroa-Moseley CD Pascal JP Williams GC Integrative
nonpharmacologic behavioral interventions for the management of Cancer-Related fatigue The
Oncologist 2007 12(1)52-67
Reason for exclusion Not population of interest
Neill J Belan I Ried K Effectiveness of non-pharmacological interventions for fatigue in adults with
multiple sclerosis rheumatoid arthritis or systemic lupus erythematosus a systematic review
Journal of Advanced Nursing 2006 Dec 56(6)617-35
Reason for exclusion Not population of interest
Rheingans JI A systematic review of nonpharmacologic adjunctive therapies for symptom management
Journal of Pediatric Oncology Nursing 2007 24(2) 81-94
683
52
Reason for exclusion Not outcome of interest
Rheingans JI Pediatric oncology nursesrsquo management of patients symptoms Journal of Pediatric
Oncology Nursing 2008 Nov 25(6) 303-11
Reason for exclusion Not outcome of interest
San Juan AF Fleck SJ Chamorro-Vintildea C Mateacute-Muntildeoz JL Moral S Peacuterez M Cardona C Del Valle MF
Hernaacutendez M Ramiacuterez M Madero L Lucia A Effects of an intrahospital exercise program
intervention for children with leukemia Medicine amp Science in Sports amp Exercise 2007 Jan
39(1)13-21
Reason for exclusion Not outcome of interest
Sanford SD Okuma JO Pan J Srivastava DK West N Farr L Hinds PS Gender differences in sleep
fatigue and daytime activity in a pediatric oncology sample receiving dexamethasone Journal of
Pediatric Psychology 2008 Apr 33(3)298-306 Epub 2007 Nov 17
Reason for exclusion Not experimental or quasi-experimental study
Schmitz KH Holtzman J Courneya KS Macircsse LC Duval S Kane R Controlled physical activity trials in
cancer survivors a systematic review and meta-analysis Cancer Epidemiol Biomarkers Prev
2005 Jul 14(7)1588-95
Reason for exclusion Not population of interest
van Brussel M Takken T Lucia A van der Net J Helders PJ Is physical fitness decreased in survivors of
childhood leukemia A systematic review Leukemia 2005 Jan 19(1)13-7
Reason for exclusion Not population of interest
Whiting P Bagnall AM Snowden AJ Cornell JE Mulrow CD Ramirez G Interventions for the treatment
and management of chronic fatigue syndrome JAMA 2001 Sep 19 286(11)1360-8
Reason for exclusion Not intervention of interest
Whitsett SF Gudmundsdottir M Davies B McCarthy P Friedman D Chemotherapy-related fatigue in
childhood cancer correlates consequences and coping strategies Journal of Pediatric
Oncology Nursing 2008 Mar-Apr 25(2)86-96 Epub 2008 Feb 29
Reason for exclusion Not experimental or quasi-experimental study
Winner C Muumlller C Hoffmann C Boos J Rosenbaum D Physical activity and childhood cancer Pediatr
Blood Cancer 2010 Apr 54(4)501-10
Reason for exclusion Not research study
684
53
Wu M Hsu L Zhang B Shen N Lu H Li S The experiences of cancer-related fatigue among Chinese
children with leukaemia A phenomenological study Journal of Nursing Studies 2010 Jan
47(1)49-59 Epub 2009 Aug 25
Reason for exclusion Not experimental or quasi-experimental study
Yeh CH Chiang YC Lin L Yang CP Chien LC Weaver MA Chuang HL Clinical factors associated with
fatigue over time in paediatric oncology patients receiving chemotherapy British Journal of
Cancer 2008 Jul 8 99(1)23-9 Epub 2008 Jun 24
Reason for exclusion Not experimental or quasi-experimental study
685
23
show no significant differences between pre (meanplusmnSD 415plusmn147) and post training
(meanplusmnSD368plusmn217) but fatigue change from baseline mean reduction of 11
Keats et al23 although used community-based physical activity program to reduce fatigue
for adolescents 14 to 18 years of age (mean162 y) with cancer (Lymphoma leukemia CNS
tumor germ cell tumor) Studies used fatigue by PedsQLMFS Results show general fatigue
from baseline to 8 weeks and to 3 months follow up significantly improves General
fatigue sleeprest fatigue and total fatigue from baseline to 3 months follow up showed
significant improvements Sleeprest fatigue and total fatigue at 1 years followed up were
significant improvements
Figure 2 shows the overall effect of exercise intervention in children and adolescents with
cancers with a focus on improving fatigue Due to the lower heterogeneity (p>005) the
fixed effects model was used to pool the data for meta-analysis (Overall effect size=
-006 95 Confidence Interval (CI) -070 to 058) A result did not indicate a statistically
significant difference (p = 087)
656
24
Figure2 Meta-analysis results of exercise intervention on fatigue
In addition Keats23 and Chiang25 used the three sub-scales of Peds QL-MFS to
determine the general cognitive and sleep rest components of fatigue The following
present the effectiveness of exercise interventions using three subscales including
general fatigue sleep rest fatigue and cognitive fatigue 2325
Chiang et al 25 used a 6- week home-based aerobic exercise intervention to reduce
fatigue of children 7 to 18 years (mean age at experimental group was 1088 y in control
group was 1247 y) of age who with acute lymphoblastic leukemia Fatigue measurement
by Peds QL-MFS after training For intent-to ndash treat analysis the findings indicated that
there are no intervention effects and time differences by any items on the subscale of
fatigue For per-protocol analysis general fatigue( meanplusmnSD 422plusmn402) was the only
subscale that was significantly lower for children who received the exercise intervention
than those in control group at follow-up assessment (one month after the completion of
intervention)
Keats et al23 although used community-based physical activity program to reduce fatigue
for adolescents 14 to 18 years of age (mean162 y) with cancer (Lymphoma leukemia
CNS tumor germ cell tumor) Both studies used fatigue by PedsQLMFS Results show
general fatigue from baseline to 8 weeks and to 3 months follow up significantly improves
657
25
General fatigue sleeprest fatigue and total fatigue from baseline to 3 months follow up
showed significant improvements Sleeprest fatigue and total fatigue at 1 years followed
up were significant improvements
The effectiveness of exercise intervention for general fatigue
The impact of the exercise interventions upon levels of general fatigue was also analysed
The heterogeneity was low (p>005) Therefore the fixed effects model was used to
examine the effectiveness The effect size is -076 indicating a statistically significant
difference (p = 001 95 CI -135 to -017 Fig 3) The evidence suggests that exercise
intervention can reduce general fatigue in children with cancer
Fig 3 Meta-analysis results of exercise intervention for general fatigue
The effectiveness of exercise intervention for sleep rest fatigue
The following is the result of the meta-analysis of the effectiveness of exercise
interventions on sleep rest fatigue First the heterogeneity test was conducted with P gt
005 representing small heterogeneity and the fixed effects model was used Fig 4
shows the effect size is -035 indicating no statistically significant differences (p = 023
95 CI-092 to 022 Fig 4)
658
26
Fig 4 Meta-analysis results of exercise intervention for sleep rest fatigue
The effectiveness of exercise intervention for cognitive fatigue Lastly the following data reports the results of meta-analysis of the effectiveness of
exercise interventions for cognitive fatigue The heterogeneity was p>005 then the
fixed effects model was used The effect size is -035 indicating no statistically significant
differences (p = 024 95 CI-092 023 Fig 5)
Fig 5 Meta-analysis results of exercise intervention for cognitive fatigue
Narrative presentation of remaining included studies
Three studies were not included in meta-analysis Post-White et al7 one of the aims in
this study was to examine the effect of massage therapy on fatigue in children with
cancer The study was a quasi-experimental design Twenty-three childrenparent dyads
were enrolled 17completed all data points Children with cancer ages 7 to 18 years
received at least 2 identical cycles of chemotherapy and one parent participated in the
2-period crossover design in which 4 weekly massage sessions (MT) alternated with 4
659
27
weekly quiet-time (QT) control sessions There were no significant changes in fatigue in
children over the 4-week MT or QT conditions either independently (change over time) or
when we compared fatigue by condition
The lack of effect of massage on fatigue may be the difficulty some children had in
differentiating fatigue from being relaxed underscores the challenge of measuring fatigue
in children Some children interpreted being tired or relaxed as having greater fatigue
because they felt like lying around and sleeping or felt unmotivated to do their usual
activities all measures of fatigue in the instrument used in the study
Hinds et al24conducted a prospective two-site randomized controlled pilot study to
assess the feasibility of an enhanced physical activity (EPA) intervention in hospitalized
children and adolescents receiving treatment for a solid tumor or for acute myeloid
leukemia (AML) Twenty-nine patients (25 with a solid tumor and 4 with AML) participated
age range from 736 to 1816 (mean 1248 y) The EPA intervention selected was
pedaling a stationary bicycle-style exerciser (Chattanooga Peddler Deluxe Bio-Teck
Medical Memphis TN) for 30 minutes twice daily for 2 to 4 days of hospitalization The
mixed model analysis revealed no significant differences in patient reports of fatigue
between the two study arms or over time
Genc et al2 conducted a RCT involving children with cancer who are 7 to 12 years of age
and receiving chemotherapy treatment to determine the impact of educational
intervention by nurses on decreasing the fatigue syndrome The research sample was
composed of a total of 60 children with cancer with 30 children being included in the
660
28
experimental group (mean age 923)and 30 children included in the control group (mean
age 937) with their mothers In the experimental group after the 7th to 10th day of the
chemotherapy treatment throughout a week the researcher conducted the nursing
interventions every day for 45 to 60 minutes In the control group routine nursing
interventions were carried out The experimental group received education about the
fatigue with the chemotherapy and fatigue handbook was given which was developed by
the authors Children and mothers were consulted for including activities that could
decrease fatigue which were described as effective interventions A statistically
significant difference was found between the Fatigue Scale-Child mean scores of the
experimental (2723) and the control group (4213) The results suggest that fatigue of
children with cancer can be reduced by implementing appropriate nursing interventions
(t=567 Plt00)
Discussion The purpose of this systematic review was to determine the effectiveness of
non-pharmacological interventions specifically targeting fatigue for children and
adolescents with cancer undergoing chemotherapy or after receiving chemotherapy
Included articles about the effectiveness of non-pharmacological interventions for
children and adolescents with cancer were published between the years of 2007 and
2009 Although interventions for cancer fatigue for adults have been extensively studied
it can be seen from either the title of the paper or related content that an intervention
study on children was a pilot study or a feasibility study Representing a field in its early
stage these studies show that the fatigue issues with young cancer patients have only
recently been taken seriously
661
29
The results of our meta-analysis include measurement of the four performance indicators
fatigue and general fatigue sleep rest fatigue and cognitive fatigue The results show
that there is a statistically significant difference only in the domain of general fatigue
using an exercise intervention for children with cancer can improve the degree of fatigue
with the effect size reaching 0671 Other results do not indicate significant differences
The reasons may include the following
1 Characteristics of the cancer The exhaustion from cancer occurs not only during cancer treatment but also in during
long-term survival a time during which patients may continue to be affected by this
symptom 8 26 Therefore when using intervention measures to improve fatigue
circumstances should be considered such as the process of the treatment and the course
or stage of the disease Because cancer patients will experience different forms of
treatment or courses of treatment the disease itself or treatment differences should be
considered in the choice of intervention Even chemotherapy drugs should be taken into
consideration For example a period of general steroid treatment can increase patientsrsquo
fatigue In those studies of children with cancer few studies looked solely at one type of
cancer most studies included a variety of cancer patients Furthermore most studies do
not clearly explain the stage of the disease or course of treatment and most do not
include treatment variables in the control group Moreover children with cancer may
have different levels of physical function
2 Research design The sample size Currently there are few studies with large sample size and a rigorous
RCT design due to the small number of papers available for analysis The sample size
included in our studyrsquos data analysis is between 20 and 42 people this small sample size
will affect the power available to evaluate outcome variables
Although most of the non-pharmacological interventions still use exercise and physical
activity and these studies overall show better results for fatigue as compared with
controls more research is still needed to further confirm the efficacy of these findings
662
30
The dropout rate in the evaluated research varies a great deal ranging from 5 to 45
these dropout rates may result from the characteristics of the research subjects or the
lengthy time involved in participating in these studies The research data with a high
turnover rate might not reflect the actual outcomes of participation in exercise and the
quality of the research contained in articles with high subject turnover rates may be
lower
Exercise doses and time The exercise doses needed to reduce fatigue cannot be
determined additionally the amount of exercise completed by the patient is also
inconsistent interventions vary between 2-3 times per week and two times a day and
exercise duration varies between 10 and 45 minutes each time Furthermore the study
interventions vary in length between a couple of days and a long period of 16 weeks The
data collection times are different some were measured 12 weeks after the intervention
began some were measured during the 6 weeks of intervention some were measured
three months after the intervention was finished and some were measured after one
year
In addition disease-related symptoms decrease childrenrsquos willingness to participate in
exercise interventions inappropriate exercise intervention programs may actually
increase childrens fatigue In addition the children in the study are still developing
physically it is important to consider ways to design an interesting exercise intervention
to increase the compliance of patients in order to improve the effectiveness Although
intervention programs in the hospital or in a community sports center can improve the
effectiveness because they provide supervision the feasibility of these programs is
questionable However if the program is home-based the children need to be
supervised by parents in order to improve their compliance in doing the exercises
Furthermore regarding the nature of the intervention the results from this study indicate
that the researched non-pharmacological interventions include the following exercise
training programs physical activity massage therapy and health education interventions
However according to the National Comprehensive Cancer Network 1 clinical guidelines
663
31
for cancer non-drug measures for cancer fatigue can be separated into five categories
(1) activity enhancement (2) psychosocial interventions such as cognitive behavioral
therapy (CBT) stress management relaxation techniques and support groups (3)
attention-restoring therapy (4) nutritional consultation and (5) cognitive behavioral
therapy specifically targeting sleep disturbance Researchers have also suggested that
psychosocial interventions should be included in the future research for children with
cancer-related fatigue 22
(2) The measurement tools in the study The assessment of fatigue can be
one-dimensional or multidimensional One-dimensional assessment can help understand
the severity of fatigue symptoms however multidimensional scales are often more
credible Therefore when measuring cancer-related fatigue researchers should consider
whether there is a uniform definition of fatigue or a standardized tool for measuring
fatigue in order to facilitate further systematic meta-analyses and further develop the
clinical care guidelines
Limitations of the review The present review has some potential limitations First the low methodological quality
may influence the result Although exercise intervention seems promising quality of the
RCTs was generally quite low Future studies require better design and reporting if
methodological issues to establish evidence-based nonpharmcologic intervention
Second the identified studies covered only a limited types of nonpharmcological
intervention especially in exercise intervention The guidelines for cancer-related fatigue
in NCCN (2011)1 referred to more interventions than the ones included in this review
such as cognitive behavioral therapy and nutrition consultation Thirdly the small sample
size and effect size could be potentially having led to underpowered approach for
detecting the effects on fatigue Therefore we recommend that as research continues to
grow a re-analysis can be undertaken Fourthly Combining data in meta analysis from
664
32
studies where the ages were quite different is a potential source of heterogeneity and
may affect the interpretation of the results
Conclusion At present clinical treatment is widely used for cancer patients However child and
adolescent cancer patients often experience various side effects which cause short-term
or long-term discomfort both physically and psychologically In particular with the
increasing cure rate cancer related fatigue during or after treatment has become an
important issue This study result provided positive effect of exercise intervention on
general fatigue
Implications for practice The results of this systematic review and meta-analysis show that exercise interventions
can effectively improve the level of general fatigue In particular although the articles
were self-reported feasibility studies their results all indicate that exercise interventions
for fatigue are feasible and safe there was no conclusion to be made for the use of
massage therapy or health education measures because there was only one article for
each of these interventions
Recommendations for practice
Cancer-related fatigue is one of the most severe and frequent symptoms by pediatric
oncology children and adolescent suffered during treatment and the symptom existed
even after treatment has ended Until now no golden standard of treatment to fatigue is
established The findings call for more attention to how to reduce patientrsquos levels of
fatigue Based on the available information evaluated in this review the following
recommendations for practice are provided
665
33
bull For children aged 7 to 18 who has cancer (eg Lymphoma leukemia CNS tumor
germ cell tumor) an effective progressive aerobic exercise program is recommended to
be at least 2-3 times per week 20 to 45 minute for each session and last for 6-16 weeks
in order to reduce their general fatigue (tiredness physically weakness) In addition
adults should be involved in accompanying children while they are performing physical
exercise of which should be able to improve the adherence rate (level 2 ) ( Grade of
recommendation A)
bull For children aged 7 to 18 who has cancer (eg Lymphoma leukemia CNS tumor
germ cell tumor) an progressive aerobic exercise program will not be effective to reduce
their sleep andor rest (sleeping or resting a lot) or cognitive fatigue (problems with
thinking quickly or problems with remembering) (level 2 ) ( Grade of recommendation C)
bull Nursing interventions in educating treatment of fatigue include information about
activity nutrition energy preservation consulting and providing a useful fatigue
handbook will benefit those children who are 7 to 12 years have a new diagnosis of ALL
AML or lymphoma and receive for the first time after being diagnosed a 7- to 10-day
chemotherapy treatment (level 2) ( Grade of recommendation A)
bull A 4-week massage therapy program (the therapists massage childrenrsquos back legs
arms stomachchest and face) is not effective for children who are aged 7 to 18 and
have acute lymphoblastic leukemia brain tumors lymphoma rhabdomyosarcoma
Wilms tumor or Ewing sarcoma(level 2)( Grade of recommendation C)
bull Using a 12-week aerobic and strength exercise (45-min exercise sessions twice a
week) is not effective for children who are aged 6-14 and survived acute lymphoblaststic
leukemia age from 6 to 14(level 2) ( Grade of recommendation C)
bull Using a physical activity intervention (30minutestwice daily for 2-4days) is not
effective for children who are 7 to 18 years of age with soild tumor or AML(level 2)
( Grade of recommendation C)
666
34
Implications for research According to this systematic review and meta-analysis results there are suggestions to
improve the effectiveness of future research on non-pharmacological interventions for
children and young peoplersquos cancer-related fatigue
As the majority of included non-pharmacological interventions for the fatigue of cancer
patients consist of exercise programs future research should also consider various
non-pharmacological interventions in order to understand the effectiveness of different
methods
Regarding the exercise intervention methods and studies should consider multiple
factors including the age or personal condition of the subject the disease stage and the
amount of daily activities Studies should use design prescriptions (eg frequency
intensity duration and type of exercise) and consider the adherence to the measures in
order to enhance the study strength
In measuring the results of non-pharmacological interventions there should be standard
definitions or standard measurement tools to facilitate the following systematic review
and meta-analysis that can subsequently be developed into clinical care guidelines
Reviewing the effectiveness of the current non-pharmacological management of children
and adolescent cancer patients there is still a lack of rigorous RCT research Limited by
the characteristics of cancer there is still a lack of large sample sizes
Potential conflicts of interest There is no conflict of interest
Acknowledgements
Thank you to Dr Rie Konno Research Fellow Joanna Briggs Institute for her help in
assessing studies
667
35
References 1 National Comprehensive Cancer Network( NCCN) in USA NCCN clinical practice
guideline in oncology cancer-related fatigue 2011 2 Ekti Genc R amp Conk Z Impact of effective nursing interventions to the fatigue
syndrome in children who receive chemotherapy Cancer Nursing 200831(4)312-317
3 Childhood Cancer Foundation of ROC (2009March) The classification of diseases
and age sex statistical tables of case Childhood Cancer Foundation of ROC newsletter103105-106
4 Department of Health Executive Yuan ROC (TAIWAN)(2009 March 20)2009 cause of death statistic Health and National Health Insurance Annual Statistics Information Service 2010 June 28Available httpwwwdohgovtwstatisticdatavital statists9898health statistic--lifepdf
5 Chang TK (2007December 8) Common childhood cancer and its treatment Status
Childhood Cancer Foundation of ROC (TAIWAN) 2010 September 23 Available httpwwwccfrocorgtwchildchild_events_readphpe_id=45
6 Hockenberry MJ amp Wilson D Wongs nursing care of infants and children (8th ed) St
Louis MO Mosby 2007
7 Post-White J Fitzgerald M Savik K Hooke MC Hannahan AB amp Sencer SF
Massage therapy for children with cancer Journal of Pediatric Oncology Nursing 2009 26(1)16-28
8Chiang YC Yeh CH Wang WKamp Yang CP The experience of cancer-related fatigue
in Taiwanese children European Journal of Cancer Care 2009 18(1)43-49 9Langeveld NE Grootenhuis M A Voute P A de Haan RJ amp van den Bos C No excess
fatigue in young adult survivors of childhood cancer European Journal of Cancer 200339(2)204-214
10Piper BF Lindsey AM amp Dodd MJ Fatigue mechanisms in cancer patients
developing nursing theory Oncology Nursing Forum 1987 14(6)17-23 11Nail LM amp Winningham ML Fatigue In S L Groenwald M H Forgge M Goodman
amp C H Yarbro (Eds) Cancer Nursing Principles and practice (4 th ed) Boston Jones and Bartlett1997
12Irvine D Vincent L Graydon JE Bubela N amp Thompson L The prevalence and
correlates of fatigue in patients receiving treatment with chemotherapy and
668
36
radiotherapy A comparison with the fatigue experienced by healthy individuals Cancer Nursing 199417(5)367-378
13Hinds PS amp Hockenberry-Eaton M Developing a research program on fatigue in
children and adloescents diagnosed with cancer Journal of Pediatric Oncology Nursing 200118(2)3-12
14Aaronson LS Teel CS Cassmeyer V Neuberger GB Pallikkathayil L Pierce J Press
AN Williams DP amp Wingate A Defining and measuring fatigue Journal of Nursing scholarship 1999 31(1)45-50
15Yeh CH Wang CH Chiang YC Lin Lamp Chien LC Assessment of symptoms reported
by 10- to 18-year-old cancer patients in Taiwan 2009 38(5)738-746 16 Okuyama T Akechi T Kugaya A Okamura H Shima Yamp Maruguchi M
Development and validation of the cancer fatigue scale a brief three-dimensional self-rating scale for assessment of fatigue in cancer patients Journal of Pain amp Symptom Management 2000 19(1) 5-14
17Gibson F Mulhall AB Richardson A Edwards JL Ream E amp Sepion BJ A
phenomenologic study of fatigue in adolescents receiving treatment for cancer Oncology Nursing Forum200532(3)651-660
18Wolfe J Grier HE Klar N Levin SB Ellenbogen JMamp Salem-Schatz S et al
Symptoms and suffering at the end of life in children with cancer New England Journal of Medicine 2000342(5)326-333
19Whiting P Bagnall AM Sowden AJ Cornell JE Mulrow CD amp Ramirez G
Interventions for the treatment and management of chronic fatigue syndrome a systematic review JAMA the Journal of the American Medical Association 2001286(11)1360-1368
20 Kangas M Bovbjerg DHamp Montgomery G H Cancer-related fatigue a systematic
and meta-analytic review of non-pharmacological therapies for cancer patients Psychological Bulletin 2008134 (5)700-741
21Williams PD Schmideskamp J Ridder EL amp Williams AR Symptom monitoring and
dependent care during cancer treatment in children pilot study Cancer Nursing 200629(3)188-197
22Takken T van der Torre P Zwerink M Hulzebos EH Bierings M Helders PJMamp van
der Net J Development feasibility and efficacy of a community-based exercise training
669
37
program in pediatric cancer survivors Psycho-Oncology 200918(4)440-448
23Keats MR amp Culos-Reed SN A community-based physical activity program for
adolescents with cancer (project TREK) program feasibility and preliminary findings
Pediatric hematology and oncology 200830(4) 272-280
24Hinds PS Hockenberry M Rai SN Zhang L Razzouk B I Cremer L McCarthy K amp
Rodriguez-Galindo C Clinical field testing of an enhanced-activity intervention in
hospitalized children with cancer Journal of Pain amp Symptom Management 2007
33(6)686-697
25Chiang YC The effects of ldquo a home-based aerobic exercise interventionrdquo on fatigue
and cardiorespiratory fitness in children with acute lymphoblastic leukemia during the
maintenance stage of chemotherapy Unpublished thesis Taiwan Tao-Yuan 2007
26Langeveld N Ubbink M amp Smets E I dont have any energy The experience of
fatigue in young adult survivors of childhood cancer European journal of oncology
nursing 20004(1)20-28
27 Kisner C Colby L Therapeutic exercise Foundations and techniques 2nd ed Philadelphia PAFA Davies 2007
670
38
Appendix I JBI Critical Appraisal Checklist for Experimental studies
Author__________ Year_________ Record Number__________________
Questions 1 to 4 must be answered ldquoyesrdquo for study to be included in the metashyanalysis
1 Were the participants randomized to study groups
Yes No Not clear
2 Other than research intervention were participants in each groups treated the same
Yes No Not clear
3 Were the outcomes measured in the same manner for all participants
Yes No Not clear
4 Were groups comparable at entry
Yes No Not clear
5 Was randomization of participants blinded
Yes No Not clear
6 Were those assessing outcome blinded to treatment allocation (if outcome not objective such as survival or length of hospitalization)
Yes No Not clear
7 Was allocation to treatment groups concealed from the allocator
Yes No Not clear
8 Was an appropriate statistical analysis used
671
39
Yes No Not clear
9 Were outcomes measured in a reliable way
Yes No Not clear
10 Was there adequate followshyup of participants
Yes No Not clear
Summary
TOTAL
Yes No Not clear
DECISION
Use Reject
Narrative summary only Further information needed
COMMENTS
672
40
Appendix II JBI Data Extraction Tool for Quantitative Studies Authors and Year
Journal Title
Record NumberArticle Reference No
Reviewer
Method
Settings
Participants
Number of participants
Group A Group B Group C
Control Intervention 1 Intervention 2
Interventions
Group A
Control
Group B
Intervention 1
Group C
Intervention 2
Outcome measures
Definition
673
41
Other outcome measures
Outcome description ScaleMeasure
Results
Dichotomous Data
Outcome Control Group
Numbertotal number
Treatment Group
Numbertotal number
Continuous Data
Authorrsquos Conclusions
Comments
Outcome Control Group
Mean amp SD
Treatment Group
Mean amp SD
674
43
Appendix III Details of included studies (N=6)(2720212223) RefNo Author(s)
(years) Title Study question Research
method Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
22 Takken T van der Torre P Zwerink M Hulzebos E H Bierings M Helders P J Mamp van der Net J (2009)
Development feasibility and efficacy of a community-based exercise training program in pediatric cancer survivors
To develop a 12-week home-based exercise training program (comprising aerobic and strength exercises) for children who survived ALL and to study itrsquos feasibility and efficacy
Pre-post test design
No comparsion group
Survived ALL(N=9)ages 6-14 years
1anthropometry 2 muscle strength 3functional mobility 4cardio-pulmonary
exercise test 5Fatigue
1 Feasibility questionnaire 2 anthropometry electronic scale and a wallmounted stadiometerHarpenden skin fold calipers 3 muscle strength handheld dynamometer 4functional mobility Timed Up
and Go test (TUG) 5cardio-pulmonary exercise test electronically braked cycle ergometer 6Fatigue(mean)CSI-20 (subjective experience of fatigueconcentrationmotivationphysical activity)
112-week exercise training program
2 Patients were assessed before (T0) and after (T1) 12 weeks of training
1 muscle strength execapacity functional moand fatigue showed nosignificant differences between pre(meanplusmnSD415plusmn147) and post training(meanplusmnSD3687)
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
7 Post-White J Fitzgerald M Savik K Hooke M C Hannahan A B amp Sencer S F (2009)
Massage therapy for children with cancer
To determine whether 4 weekly sessions of massage compared with 4 quiet-time control conditions would reduce anxiety cortisol levels fatigue nausea and pain in children with cancer undergoing chemotherapy and would reduce anxiety fatigue and mood disturbance in a parent
2-period crossover design (Randomized)
quiet-time
control
sessions
Children with cancer 1 to 18 years of age Twenty-three childrenparent dyads were enrolled 17 completed all data points
children 1relaxation 2symptoms 3 fatigue
parents
1anxiety 2 fatigue
children 1relaxation (heart and respiratory rates blood pressure and salivary cortisol level)
2symptoms (pain nausea anxiety 3 fatigue 1-2y3-6yLansky Play Performance Scale (PPS) 7-13y
1 4 weekly massage (MT) sessions alternated with 4 weekly quiet-time(QT) control sessions
2 children included presession and postsession vital signs (heart rate respiratory rate blood pressure) and self-report (parent proxy report for age 1-2 years) of pain nausea and anxiety Fatigue was measured before sessions 1 and 4 and at each follow-up Parent measures
included anxiety fatigue and mood states
1Massage was moreeffective than quiet tireducing heart rate inchildren anxiety in cless than age 14 yeaparent anxiety 2There were no sign
changes in blood pcortisol pain naufatigue (no state d
3 Children reported tmassage helped thebetter lessened theirand worries and hadlasting effects than q
675
44
14-18yChild Fatigue Scale (CFS) (frequency
intensity) 2 parents anxiety and fatigue
676
45
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
24 Hinds P S Hockenberry M Rai S N Zhang L Razzouk B I Cremer L McCarthy K amp Rodriguez-Galindo C (2007)
Clinical field testing of an enhanced-activity intervention in hospitalized children with cancer
To determine the feasibility of an
enhanced physical activity EPA intervention in children and adolescents hospitalized to receive chemotherapy for a solid tumor or AML and to assess the sleep and fatigue outcomes of the intervention using two different statistical approaches to analyze the longitudinal symptom data
randomized prospective two-site and two-group pilot study
Standard care Twenty nine patients (25 with a solid tumor and 4 with AML)ages 7-18 years
1 sleep duration 2 sleep efficiency 3 fatigue
1sleep duration sleep efficiency The
Wrist Actigraph The Daily Sleep Diary-Parent 2 fatigue (mean) The Fatigue Scale(FS-C) for 7-12 (intensity) The Fatigue Scale(FS-A) for 13-18 The Fatigue Scale Parent Version (FS-P) The Fatigue Scale Staff Version (FS-S)
1enhanced physical activity (EPA) (hospital-based 30 minutes
twice daily for 2-4 days) 2 T0On the day of admission
(Day 0 or baseline)patient and parents completed the fatigue instruments and a team member applied the actigraph Patients wore the wrist actigraph T1 from Day 0 to 2 or 3 consecutive days (Days 0e3) In addition the patient same parent and staff nurses completed the daily sleep and fatigue reports in the late afternoons of Days 1-3
1 ANOVA model slesignificantly more the experimental athe control arm whdifferences from bsleep efficiency vaaveraged and com
2 The patient-reported mean fatigue scoresarms were higher amadolescents than for
3 The mixed model anarevealed no significandifferences in patientfatigue between
the two study arms otime( no final result iSD only give mixed result)
677
46
23 Keats M
R amp Culos-Reed S N (2008)
A community-based physical activity program for adolescents with cancer (project TREK) program feasibility and preliminary findings
To examine the
feasibility of a
theoretically-based
physical activity (PA)
intervention in
adolescents with
cancerand
examination of the
impact of the
program on
participant QOL
including social
emotional and
physical
well-being(including fatigue)
Repeat measures longitudinal design
No comparsion group
10 adolescents(Lymphoma(4)leukemia(4)CNS tumor(1)germ cell tumor(1)) ages 14-18 years
1physical fitness 2quality of life (QOL) 3PA behavior 4fatigue
1 Feasibility was assessed by participant recruitment attendance and adherence
2physical fitness Fitnessgram 3quality of life (QOL) Pediatric Quality of Life Inventory (PedsQL) 4PA behavior leisure score index (LSI) 5fatigue (mean) pediatric Quality of life
Multidimensional Fatigue Scale (Peds QL-MFS)
(Generalsleepcognitive fatigue)
116week physical activity (PA)
2 total PA physical fitness and overall QOL was assessed at 5 different intervals T0 preintervention (baseline) T1midintervention (after the
first 8 wk) T2 postintervention
(16 wk) T3 3-months
postintervention T4 1-year poststudy
initiation
1 from baseline -wkssig Improvementstotal PA physfitness and Qgeneral fatigue(meanplusmnSD 796plusmn135)
2 from baseline to 3FUsig Improvin general fatigue(meanplusmnSD824plusmn131)slefatigue(meanplusmnSD755plusmn191)totafatigue(meanplusmnSD778plusmn150)
3at 1 years FUsImprovements in sleeprest fatigue(meanplusmnSD725plusmn203)total (meanplusmnSD 763plusmn
678
47
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
2 Gene R E amp Conk Z (2008)
Impact of Effective Nursing Interventions to the Fatigue Syndrome in Children Who Receive Chemotherapy
1 to examine the effects of an effective nursing intervention to the fatigue syndrome of children 7 to 12 years of age who receive chemotherapy 2Tto examine the relationship between fatigue and demographic variables (age sex) diagnoses ([ALL AML] lymphoma) and therapy-related variables (eg level of hemoglobin
experimental randomized controlled study
Routine nursing care
A total of 60 children who are 7-12 years of age(a new diagnosis of ALL AML or lymphoma and receiving for the first time after being diagnosed a 7- to 10-day chemotherapy treatment )
fatigue The Fatigue Scale(FS-C) for 7-12 (intensity)
The Fatigue Scale Parent Version (FS-P)
1 effective nursing interventions(45- 60mdaya week)education about the fatigue with the chemotherapy and fatigue handbook 2 T1 After a 7-day period the children
and parent were evaluated with the Fatigue Scale
1The difference betwthe 2 mean values wafound to be statisticallsignificant 2 statistically significadifference was found between the Fatigue Scale-Child mean scothe experimental (272the control group (4213)children
679
48
25 Chiang et
al(2007)
The effects of ldquo a home ndashbased aerobic exercise interventionrdquo on fatigue and cardiorespiratory fitness in children with Acute Lymphoblastic Leukemia during the maintenance stage of chemotherapy
To examine the effect of ldquo a home ndashbased aerobic exercise interventionrdquo on fatigue and cardiorespiratory fitness in children with Acute Lymphoblastic Leukemia during the maintenance stage of chemotherapy
Quasi-experi -mental
Routine
nursing care
14 pediatric oncology patients in the experimental group and 10 in control group who were matched by age and sex ages7-18 years
1Cardiorespiratory fitness
2Fatigue
1Cardiorespiratory fitness Physical Activity Recall
VO2maxHR peak 6MWT
2 Fatigue PedsQL-MFS(Generalsleepcognitive fatigue)
1A six-week home-based aerobic exercise intervention 2 8 time points T0 baseline T1-T6 every week during the
intervention(6 weeks) T7 post intervention T8 follow-up (one month after
the end of the home-based exercise program)
1 For intent-to ndash treatthe findings indicated are no intervention efftime differences by anon the subscale of fat2 For per-protocol angeneral fatigue( mean422plusmn402) was the osubscale that was siglower for children whothe exercise interventthose in control groupfollow-up assessmentmonth after the compintervention) 3 The VO2peak are significantly improvingexperimental group atbaseline- and post-intassessment The VO2was significantly highechildren who were in experimental group thcontrol subjects at post-intervention assefor the per-protocol an
680
49
Appendix IV Instrument used to measure fatigue
Name Instrument
developers
Description Used in
age in
ref
Reliability
Consistency of
instrument
Checklist Individual Strength
(CIS)22
Vercoulen et
al1996
20 items using 7-point Likert scale of
fatigue To measure four aspects of
fatiguesubjective experience
contractionmotivation physical
Activity
6-14 Not reported
Child Fatigue Scale (CFS)7 Hockenberry
et al2003
14 items 2 part questionnaire frequency
(yes or no) 5-point Likert scale of the
intensity of any yes responses
7-13
14-18 α073-o84
The Fatigue Scale for 7-12
year Olds (FS-C)224
Hockenberry
et al
14 items provide a fatigue intensity score
5-point Likert scale
7-12 αo84
The Fatigue Scale for 13-18
year Olds (FS-A)24
Hockenberry
et al
14 items provide a fatigue intensity score
5-point Likert scale
13-18 α076-o96
Pediatric Quality of life
Multidimensional Fatigue
Scale (Peds QL-MFS)2325
Varni2002 18 items to measure three aspects of
fatigueGeneralsleepcognitive
14-18 Not reported
681
50
Appendix V Excluded studies and reasons for exclusion
Baggott C Dodd M Kennedy C Marina N Miaskowski C Multiple Symptoms in Pediatric Oncology
Patients A Systematic Review Journal of Pediatric Oncology Nursing 2009 Nov-Dec 27(6)
325-339
Reason for exclusion Not outcome of interest
Barlow JH Ellard DR Psycho-educational interventions for children with chronic disease parents and
siblings an overview of the research evidence base Care Health amp Development 2004 Nov
30(6)637-45
Reason for exclusion Not outcome of interest
Bedider S Moyer CA Randomized controlled trials of pediatric massage A review Evid Based
Complement Alternat Med 2007 Mar 4(1)23-34 Epub 2006 Nov 3
Reason for exclusion Not outcome of interest
de Nijs EJ Ros W Grijpdonck MH Nursing intervention for fatigue during the treatment for cancer Cancer
Nursing 2008 31(3)191-206
Reason for exclusion Not population of interest
Edwards JL Gibson F Richardson A Sepion B Ream E Fatigue in adolescents with and following a
cancer diagnosis developing an evidence base for practice European Journal of Cancer 2003
Dec 39(18)2671-80
Reason for exclusion Not experimental or quasi-experimental study
Hinds PS Hockenberry-Eatan M Developing a research program on fatigue in children and adolescents
diagnosed with cancer Journal of Pediatric Oncology Nursing 2001 Mar-Apr 18(2 Suppl
1)3-12
Reason for exclusion Not experimental or quasi-experimental study
Hockenberry-Eaton M Hinds PS Alcoser P ONeill JB Euell K Howard V Gattuso J Taylor J Fatigue in
Children and Adolescents With Cancer Journal of Pediatric Oncology Nursing 1998 July
15(3)172-182
Reason for exclusion Not experimental or quasi-experimental study
Jean-Pierre P Mustian K Kohli S Roscoe JA Hickok JT Morrow GR Community-based clinical oncology
research trials for cancer-related fatigue The Journal of Supportive Oncology 2006 Nov-Dec
4(10)511-6
682
51
Reason for exclusion Not population of interest
Kangas M Bovbjerg DH Montgomery GH Cancer-Related Fatigue A Systematic and Meta-Analytic
Review of Non-Pharmacological Therapies for Cancer Patients Psychological Bulletin 2008 Sep
134(5)700-41
Reason for exclusion Not population of interest
Lotfi-Jam K Carey M Jefford M Schofield P Charleson C Aranda S Nonpharmacologic strategies for
managing common chemotherapy adverse effects A systematic review Journal of Clinical
Oncology 2008 Dec 1 26(34)5618-29 Epub 2008 Nov 3
Reason for exclusion Not outcome of interest
Marchese VG Chiarello LA Lange BJ Effects of physical therapy intervention for children with acute
lymphoblastic leukemia Pediatr Blood Cancer 2004 Feb42(2)127-33
Reason for exclusion Not outcome of interest
Meeske KA Siegel SE Globe DR Mack WJ Bernstein L Prevalence and correlates of fatigue in
long-term survivors of childhood leukemia Journal of Clinical Oncology 2005 Aug 20
23(24)5501-10
Reason for exclusion Not intervention study
Minton O Richardson A Sharpe M Hotopf Stone P A systematic review and meta-analysis of the
pharmacological treatment of cancer-related fatigue J Natl Cancer Inst 2008 Aug 20
100(16)1155-66 Epub 2008 Aug 11
Reason for exclusion Not population and intervention of interest
Mustian KM Morrow GR Carroll JK Figueroa-Moseley CD Pascal JP Williams GC Integrative
nonpharmacologic behavioral interventions for the management of Cancer-Related fatigue The
Oncologist 2007 12(1)52-67
Reason for exclusion Not population of interest
Neill J Belan I Ried K Effectiveness of non-pharmacological interventions for fatigue in adults with
multiple sclerosis rheumatoid arthritis or systemic lupus erythematosus a systematic review
Journal of Advanced Nursing 2006 Dec 56(6)617-35
Reason for exclusion Not population of interest
Rheingans JI A systematic review of nonpharmacologic adjunctive therapies for symptom management
Journal of Pediatric Oncology Nursing 2007 24(2) 81-94
683
52
Reason for exclusion Not outcome of interest
Rheingans JI Pediatric oncology nursesrsquo management of patients symptoms Journal of Pediatric
Oncology Nursing 2008 Nov 25(6) 303-11
Reason for exclusion Not outcome of interest
San Juan AF Fleck SJ Chamorro-Vintildea C Mateacute-Muntildeoz JL Moral S Peacuterez M Cardona C Del Valle MF
Hernaacutendez M Ramiacuterez M Madero L Lucia A Effects of an intrahospital exercise program
intervention for children with leukemia Medicine amp Science in Sports amp Exercise 2007 Jan
39(1)13-21
Reason for exclusion Not outcome of interest
Sanford SD Okuma JO Pan J Srivastava DK West N Farr L Hinds PS Gender differences in sleep
fatigue and daytime activity in a pediatric oncology sample receiving dexamethasone Journal of
Pediatric Psychology 2008 Apr 33(3)298-306 Epub 2007 Nov 17
Reason for exclusion Not experimental or quasi-experimental study
Schmitz KH Holtzman J Courneya KS Macircsse LC Duval S Kane R Controlled physical activity trials in
cancer survivors a systematic review and meta-analysis Cancer Epidemiol Biomarkers Prev
2005 Jul 14(7)1588-95
Reason for exclusion Not population of interest
van Brussel M Takken T Lucia A van der Net J Helders PJ Is physical fitness decreased in survivors of
childhood leukemia A systematic review Leukemia 2005 Jan 19(1)13-7
Reason for exclusion Not population of interest
Whiting P Bagnall AM Snowden AJ Cornell JE Mulrow CD Ramirez G Interventions for the treatment
and management of chronic fatigue syndrome JAMA 2001 Sep 19 286(11)1360-8
Reason for exclusion Not intervention of interest
Whitsett SF Gudmundsdottir M Davies B McCarthy P Friedman D Chemotherapy-related fatigue in
childhood cancer correlates consequences and coping strategies Journal of Pediatric
Oncology Nursing 2008 Mar-Apr 25(2)86-96 Epub 2008 Feb 29
Reason for exclusion Not experimental or quasi-experimental study
Winner C Muumlller C Hoffmann C Boos J Rosenbaum D Physical activity and childhood cancer Pediatr
Blood Cancer 2010 Apr 54(4)501-10
Reason for exclusion Not research study
684
53
Wu M Hsu L Zhang B Shen N Lu H Li S The experiences of cancer-related fatigue among Chinese
children with leukaemia A phenomenological study Journal of Nursing Studies 2010 Jan
47(1)49-59 Epub 2009 Aug 25
Reason for exclusion Not experimental or quasi-experimental study
Yeh CH Chiang YC Lin L Yang CP Chien LC Weaver MA Chuang HL Clinical factors associated with
fatigue over time in paediatric oncology patients receiving chemotherapy British Journal of
Cancer 2008 Jul 8 99(1)23-9 Epub 2008 Jun 24
Reason for exclusion Not experimental or quasi-experimental study
685
24
Figure2 Meta-analysis results of exercise intervention on fatigue
In addition Keats23 and Chiang25 used the three sub-scales of Peds QL-MFS to
determine the general cognitive and sleep rest components of fatigue The following
present the effectiveness of exercise interventions using three subscales including
general fatigue sleep rest fatigue and cognitive fatigue 2325
Chiang et al 25 used a 6- week home-based aerobic exercise intervention to reduce
fatigue of children 7 to 18 years (mean age at experimental group was 1088 y in control
group was 1247 y) of age who with acute lymphoblastic leukemia Fatigue measurement
by Peds QL-MFS after training For intent-to ndash treat analysis the findings indicated that
there are no intervention effects and time differences by any items on the subscale of
fatigue For per-protocol analysis general fatigue( meanplusmnSD 422plusmn402) was the only
subscale that was significantly lower for children who received the exercise intervention
than those in control group at follow-up assessment (one month after the completion of
intervention)
Keats et al23 although used community-based physical activity program to reduce fatigue
for adolescents 14 to 18 years of age (mean162 y) with cancer (Lymphoma leukemia
CNS tumor germ cell tumor) Both studies used fatigue by PedsQLMFS Results show
general fatigue from baseline to 8 weeks and to 3 months follow up significantly improves
657
25
General fatigue sleeprest fatigue and total fatigue from baseline to 3 months follow up
showed significant improvements Sleeprest fatigue and total fatigue at 1 years followed
up were significant improvements
The effectiveness of exercise intervention for general fatigue
The impact of the exercise interventions upon levels of general fatigue was also analysed
The heterogeneity was low (p>005) Therefore the fixed effects model was used to
examine the effectiveness The effect size is -076 indicating a statistically significant
difference (p = 001 95 CI -135 to -017 Fig 3) The evidence suggests that exercise
intervention can reduce general fatigue in children with cancer
Fig 3 Meta-analysis results of exercise intervention for general fatigue
The effectiveness of exercise intervention for sleep rest fatigue
The following is the result of the meta-analysis of the effectiveness of exercise
interventions on sleep rest fatigue First the heterogeneity test was conducted with P gt
005 representing small heterogeneity and the fixed effects model was used Fig 4
shows the effect size is -035 indicating no statistically significant differences (p = 023
95 CI-092 to 022 Fig 4)
658
26
Fig 4 Meta-analysis results of exercise intervention for sleep rest fatigue
The effectiveness of exercise intervention for cognitive fatigue Lastly the following data reports the results of meta-analysis of the effectiveness of
exercise interventions for cognitive fatigue The heterogeneity was p>005 then the
fixed effects model was used The effect size is -035 indicating no statistically significant
differences (p = 024 95 CI-092 023 Fig 5)
Fig 5 Meta-analysis results of exercise intervention for cognitive fatigue
Narrative presentation of remaining included studies
Three studies were not included in meta-analysis Post-White et al7 one of the aims in
this study was to examine the effect of massage therapy on fatigue in children with
cancer The study was a quasi-experimental design Twenty-three childrenparent dyads
were enrolled 17completed all data points Children with cancer ages 7 to 18 years
received at least 2 identical cycles of chemotherapy and one parent participated in the
2-period crossover design in which 4 weekly massage sessions (MT) alternated with 4
659
27
weekly quiet-time (QT) control sessions There were no significant changes in fatigue in
children over the 4-week MT or QT conditions either independently (change over time) or
when we compared fatigue by condition
The lack of effect of massage on fatigue may be the difficulty some children had in
differentiating fatigue from being relaxed underscores the challenge of measuring fatigue
in children Some children interpreted being tired or relaxed as having greater fatigue
because they felt like lying around and sleeping or felt unmotivated to do their usual
activities all measures of fatigue in the instrument used in the study
Hinds et al24conducted a prospective two-site randomized controlled pilot study to
assess the feasibility of an enhanced physical activity (EPA) intervention in hospitalized
children and adolescents receiving treatment for a solid tumor or for acute myeloid
leukemia (AML) Twenty-nine patients (25 with a solid tumor and 4 with AML) participated
age range from 736 to 1816 (mean 1248 y) The EPA intervention selected was
pedaling a stationary bicycle-style exerciser (Chattanooga Peddler Deluxe Bio-Teck
Medical Memphis TN) for 30 minutes twice daily for 2 to 4 days of hospitalization The
mixed model analysis revealed no significant differences in patient reports of fatigue
between the two study arms or over time
Genc et al2 conducted a RCT involving children with cancer who are 7 to 12 years of age
and receiving chemotherapy treatment to determine the impact of educational
intervention by nurses on decreasing the fatigue syndrome The research sample was
composed of a total of 60 children with cancer with 30 children being included in the
660
28
experimental group (mean age 923)and 30 children included in the control group (mean
age 937) with their mothers In the experimental group after the 7th to 10th day of the
chemotherapy treatment throughout a week the researcher conducted the nursing
interventions every day for 45 to 60 minutes In the control group routine nursing
interventions were carried out The experimental group received education about the
fatigue with the chemotherapy and fatigue handbook was given which was developed by
the authors Children and mothers were consulted for including activities that could
decrease fatigue which were described as effective interventions A statistically
significant difference was found between the Fatigue Scale-Child mean scores of the
experimental (2723) and the control group (4213) The results suggest that fatigue of
children with cancer can be reduced by implementing appropriate nursing interventions
(t=567 Plt00)
Discussion The purpose of this systematic review was to determine the effectiveness of
non-pharmacological interventions specifically targeting fatigue for children and
adolescents with cancer undergoing chemotherapy or after receiving chemotherapy
Included articles about the effectiveness of non-pharmacological interventions for
children and adolescents with cancer were published between the years of 2007 and
2009 Although interventions for cancer fatigue for adults have been extensively studied
it can be seen from either the title of the paper or related content that an intervention
study on children was a pilot study or a feasibility study Representing a field in its early
stage these studies show that the fatigue issues with young cancer patients have only
recently been taken seriously
661
29
The results of our meta-analysis include measurement of the four performance indicators
fatigue and general fatigue sleep rest fatigue and cognitive fatigue The results show
that there is a statistically significant difference only in the domain of general fatigue
using an exercise intervention for children with cancer can improve the degree of fatigue
with the effect size reaching 0671 Other results do not indicate significant differences
The reasons may include the following
1 Characteristics of the cancer The exhaustion from cancer occurs not only during cancer treatment but also in during
long-term survival a time during which patients may continue to be affected by this
symptom 8 26 Therefore when using intervention measures to improve fatigue
circumstances should be considered such as the process of the treatment and the course
or stage of the disease Because cancer patients will experience different forms of
treatment or courses of treatment the disease itself or treatment differences should be
considered in the choice of intervention Even chemotherapy drugs should be taken into
consideration For example a period of general steroid treatment can increase patientsrsquo
fatigue In those studies of children with cancer few studies looked solely at one type of
cancer most studies included a variety of cancer patients Furthermore most studies do
not clearly explain the stage of the disease or course of treatment and most do not
include treatment variables in the control group Moreover children with cancer may
have different levels of physical function
2 Research design The sample size Currently there are few studies with large sample size and a rigorous
RCT design due to the small number of papers available for analysis The sample size
included in our studyrsquos data analysis is between 20 and 42 people this small sample size
will affect the power available to evaluate outcome variables
Although most of the non-pharmacological interventions still use exercise and physical
activity and these studies overall show better results for fatigue as compared with
controls more research is still needed to further confirm the efficacy of these findings
662
30
The dropout rate in the evaluated research varies a great deal ranging from 5 to 45
these dropout rates may result from the characteristics of the research subjects or the
lengthy time involved in participating in these studies The research data with a high
turnover rate might not reflect the actual outcomes of participation in exercise and the
quality of the research contained in articles with high subject turnover rates may be
lower
Exercise doses and time The exercise doses needed to reduce fatigue cannot be
determined additionally the amount of exercise completed by the patient is also
inconsistent interventions vary between 2-3 times per week and two times a day and
exercise duration varies between 10 and 45 minutes each time Furthermore the study
interventions vary in length between a couple of days and a long period of 16 weeks The
data collection times are different some were measured 12 weeks after the intervention
began some were measured during the 6 weeks of intervention some were measured
three months after the intervention was finished and some were measured after one
year
In addition disease-related symptoms decrease childrenrsquos willingness to participate in
exercise interventions inappropriate exercise intervention programs may actually
increase childrens fatigue In addition the children in the study are still developing
physically it is important to consider ways to design an interesting exercise intervention
to increase the compliance of patients in order to improve the effectiveness Although
intervention programs in the hospital or in a community sports center can improve the
effectiveness because they provide supervision the feasibility of these programs is
questionable However if the program is home-based the children need to be
supervised by parents in order to improve their compliance in doing the exercises
Furthermore regarding the nature of the intervention the results from this study indicate
that the researched non-pharmacological interventions include the following exercise
training programs physical activity massage therapy and health education interventions
However according to the National Comprehensive Cancer Network 1 clinical guidelines
663
31
for cancer non-drug measures for cancer fatigue can be separated into five categories
(1) activity enhancement (2) psychosocial interventions such as cognitive behavioral
therapy (CBT) stress management relaxation techniques and support groups (3)
attention-restoring therapy (4) nutritional consultation and (5) cognitive behavioral
therapy specifically targeting sleep disturbance Researchers have also suggested that
psychosocial interventions should be included in the future research for children with
cancer-related fatigue 22
(2) The measurement tools in the study The assessment of fatigue can be
one-dimensional or multidimensional One-dimensional assessment can help understand
the severity of fatigue symptoms however multidimensional scales are often more
credible Therefore when measuring cancer-related fatigue researchers should consider
whether there is a uniform definition of fatigue or a standardized tool for measuring
fatigue in order to facilitate further systematic meta-analyses and further develop the
clinical care guidelines
Limitations of the review The present review has some potential limitations First the low methodological quality
may influence the result Although exercise intervention seems promising quality of the
RCTs was generally quite low Future studies require better design and reporting if
methodological issues to establish evidence-based nonpharmcologic intervention
Second the identified studies covered only a limited types of nonpharmcological
intervention especially in exercise intervention The guidelines for cancer-related fatigue
in NCCN (2011)1 referred to more interventions than the ones included in this review
such as cognitive behavioral therapy and nutrition consultation Thirdly the small sample
size and effect size could be potentially having led to underpowered approach for
detecting the effects on fatigue Therefore we recommend that as research continues to
grow a re-analysis can be undertaken Fourthly Combining data in meta analysis from
664
32
studies where the ages were quite different is a potential source of heterogeneity and
may affect the interpretation of the results
Conclusion At present clinical treatment is widely used for cancer patients However child and
adolescent cancer patients often experience various side effects which cause short-term
or long-term discomfort both physically and psychologically In particular with the
increasing cure rate cancer related fatigue during or after treatment has become an
important issue This study result provided positive effect of exercise intervention on
general fatigue
Implications for practice The results of this systematic review and meta-analysis show that exercise interventions
can effectively improve the level of general fatigue In particular although the articles
were self-reported feasibility studies their results all indicate that exercise interventions
for fatigue are feasible and safe there was no conclusion to be made for the use of
massage therapy or health education measures because there was only one article for
each of these interventions
Recommendations for practice
Cancer-related fatigue is one of the most severe and frequent symptoms by pediatric
oncology children and adolescent suffered during treatment and the symptom existed
even after treatment has ended Until now no golden standard of treatment to fatigue is
established The findings call for more attention to how to reduce patientrsquos levels of
fatigue Based on the available information evaluated in this review the following
recommendations for practice are provided
665
33
bull For children aged 7 to 18 who has cancer (eg Lymphoma leukemia CNS tumor
germ cell tumor) an effective progressive aerobic exercise program is recommended to
be at least 2-3 times per week 20 to 45 minute for each session and last for 6-16 weeks
in order to reduce their general fatigue (tiredness physically weakness) In addition
adults should be involved in accompanying children while they are performing physical
exercise of which should be able to improve the adherence rate (level 2 ) ( Grade of
recommendation A)
bull For children aged 7 to 18 who has cancer (eg Lymphoma leukemia CNS tumor
germ cell tumor) an progressive aerobic exercise program will not be effective to reduce
their sleep andor rest (sleeping or resting a lot) or cognitive fatigue (problems with
thinking quickly or problems with remembering) (level 2 ) ( Grade of recommendation C)
bull Nursing interventions in educating treatment of fatigue include information about
activity nutrition energy preservation consulting and providing a useful fatigue
handbook will benefit those children who are 7 to 12 years have a new diagnosis of ALL
AML or lymphoma and receive for the first time after being diagnosed a 7- to 10-day
chemotherapy treatment (level 2) ( Grade of recommendation A)
bull A 4-week massage therapy program (the therapists massage childrenrsquos back legs
arms stomachchest and face) is not effective for children who are aged 7 to 18 and
have acute lymphoblastic leukemia brain tumors lymphoma rhabdomyosarcoma
Wilms tumor or Ewing sarcoma(level 2)( Grade of recommendation C)
bull Using a 12-week aerobic and strength exercise (45-min exercise sessions twice a
week) is not effective for children who are aged 6-14 and survived acute lymphoblaststic
leukemia age from 6 to 14(level 2) ( Grade of recommendation C)
bull Using a physical activity intervention (30minutestwice daily for 2-4days) is not
effective for children who are 7 to 18 years of age with soild tumor or AML(level 2)
( Grade of recommendation C)
666
34
Implications for research According to this systematic review and meta-analysis results there are suggestions to
improve the effectiveness of future research on non-pharmacological interventions for
children and young peoplersquos cancer-related fatigue
As the majority of included non-pharmacological interventions for the fatigue of cancer
patients consist of exercise programs future research should also consider various
non-pharmacological interventions in order to understand the effectiveness of different
methods
Regarding the exercise intervention methods and studies should consider multiple
factors including the age or personal condition of the subject the disease stage and the
amount of daily activities Studies should use design prescriptions (eg frequency
intensity duration and type of exercise) and consider the adherence to the measures in
order to enhance the study strength
In measuring the results of non-pharmacological interventions there should be standard
definitions or standard measurement tools to facilitate the following systematic review
and meta-analysis that can subsequently be developed into clinical care guidelines
Reviewing the effectiveness of the current non-pharmacological management of children
and adolescent cancer patients there is still a lack of rigorous RCT research Limited by
the characteristics of cancer there is still a lack of large sample sizes
Potential conflicts of interest There is no conflict of interest
Acknowledgements
Thank you to Dr Rie Konno Research Fellow Joanna Briggs Institute for her help in
assessing studies
667
35
References 1 National Comprehensive Cancer Network( NCCN) in USA NCCN clinical practice
guideline in oncology cancer-related fatigue 2011 2 Ekti Genc R amp Conk Z Impact of effective nursing interventions to the fatigue
syndrome in children who receive chemotherapy Cancer Nursing 200831(4)312-317
3 Childhood Cancer Foundation of ROC (2009March) The classification of diseases
and age sex statistical tables of case Childhood Cancer Foundation of ROC newsletter103105-106
4 Department of Health Executive Yuan ROC (TAIWAN)(2009 March 20)2009 cause of death statistic Health and National Health Insurance Annual Statistics Information Service 2010 June 28Available httpwwwdohgovtwstatisticdatavital statists9898health statistic--lifepdf
5 Chang TK (2007December 8) Common childhood cancer and its treatment Status
Childhood Cancer Foundation of ROC (TAIWAN) 2010 September 23 Available httpwwwccfrocorgtwchildchild_events_readphpe_id=45
6 Hockenberry MJ amp Wilson D Wongs nursing care of infants and children (8th ed) St
Louis MO Mosby 2007
7 Post-White J Fitzgerald M Savik K Hooke MC Hannahan AB amp Sencer SF
Massage therapy for children with cancer Journal of Pediatric Oncology Nursing 2009 26(1)16-28
8Chiang YC Yeh CH Wang WKamp Yang CP The experience of cancer-related fatigue
in Taiwanese children European Journal of Cancer Care 2009 18(1)43-49 9Langeveld NE Grootenhuis M A Voute P A de Haan RJ amp van den Bos C No excess
fatigue in young adult survivors of childhood cancer European Journal of Cancer 200339(2)204-214
10Piper BF Lindsey AM amp Dodd MJ Fatigue mechanisms in cancer patients
developing nursing theory Oncology Nursing Forum 1987 14(6)17-23 11Nail LM amp Winningham ML Fatigue In S L Groenwald M H Forgge M Goodman
amp C H Yarbro (Eds) Cancer Nursing Principles and practice (4 th ed) Boston Jones and Bartlett1997
12Irvine D Vincent L Graydon JE Bubela N amp Thompson L The prevalence and
correlates of fatigue in patients receiving treatment with chemotherapy and
668
36
radiotherapy A comparison with the fatigue experienced by healthy individuals Cancer Nursing 199417(5)367-378
13Hinds PS amp Hockenberry-Eaton M Developing a research program on fatigue in
children and adloescents diagnosed with cancer Journal of Pediatric Oncology Nursing 200118(2)3-12
14Aaronson LS Teel CS Cassmeyer V Neuberger GB Pallikkathayil L Pierce J Press
AN Williams DP amp Wingate A Defining and measuring fatigue Journal of Nursing scholarship 1999 31(1)45-50
15Yeh CH Wang CH Chiang YC Lin Lamp Chien LC Assessment of symptoms reported
by 10- to 18-year-old cancer patients in Taiwan 2009 38(5)738-746 16 Okuyama T Akechi T Kugaya A Okamura H Shima Yamp Maruguchi M
Development and validation of the cancer fatigue scale a brief three-dimensional self-rating scale for assessment of fatigue in cancer patients Journal of Pain amp Symptom Management 2000 19(1) 5-14
17Gibson F Mulhall AB Richardson A Edwards JL Ream E amp Sepion BJ A
phenomenologic study of fatigue in adolescents receiving treatment for cancer Oncology Nursing Forum200532(3)651-660
18Wolfe J Grier HE Klar N Levin SB Ellenbogen JMamp Salem-Schatz S et al
Symptoms and suffering at the end of life in children with cancer New England Journal of Medicine 2000342(5)326-333
19Whiting P Bagnall AM Sowden AJ Cornell JE Mulrow CD amp Ramirez G
Interventions for the treatment and management of chronic fatigue syndrome a systematic review JAMA the Journal of the American Medical Association 2001286(11)1360-1368
20 Kangas M Bovbjerg DHamp Montgomery G H Cancer-related fatigue a systematic
and meta-analytic review of non-pharmacological therapies for cancer patients Psychological Bulletin 2008134 (5)700-741
21Williams PD Schmideskamp J Ridder EL amp Williams AR Symptom monitoring and
dependent care during cancer treatment in children pilot study Cancer Nursing 200629(3)188-197
22Takken T van der Torre P Zwerink M Hulzebos EH Bierings M Helders PJMamp van
der Net J Development feasibility and efficacy of a community-based exercise training
669
37
program in pediatric cancer survivors Psycho-Oncology 200918(4)440-448
23Keats MR amp Culos-Reed SN A community-based physical activity program for
adolescents with cancer (project TREK) program feasibility and preliminary findings
Pediatric hematology and oncology 200830(4) 272-280
24Hinds PS Hockenberry M Rai SN Zhang L Razzouk B I Cremer L McCarthy K amp
Rodriguez-Galindo C Clinical field testing of an enhanced-activity intervention in
hospitalized children with cancer Journal of Pain amp Symptom Management 2007
33(6)686-697
25Chiang YC The effects of ldquo a home-based aerobic exercise interventionrdquo on fatigue
and cardiorespiratory fitness in children with acute lymphoblastic leukemia during the
maintenance stage of chemotherapy Unpublished thesis Taiwan Tao-Yuan 2007
26Langeveld N Ubbink M amp Smets E I dont have any energy The experience of
fatigue in young adult survivors of childhood cancer European journal of oncology
nursing 20004(1)20-28
27 Kisner C Colby L Therapeutic exercise Foundations and techniques 2nd ed Philadelphia PAFA Davies 2007
670
38
Appendix I JBI Critical Appraisal Checklist for Experimental studies
Author__________ Year_________ Record Number__________________
Questions 1 to 4 must be answered ldquoyesrdquo for study to be included in the metashyanalysis
1 Were the participants randomized to study groups
Yes No Not clear
2 Other than research intervention were participants in each groups treated the same
Yes No Not clear
3 Were the outcomes measured in the same manner for all participants
Yes No Not clear
4 Were groups comparable at entry
Yes No Not clear
5 Was randomization of participants blinded
Yes No Not clear
6 Were those assessing outcome blinded to treatment allocation (if outcome not objective such as survival or length of hospitalization)
Yes No Not clear
7 Was allocation to treatment groups concealed from the allocator
Yes No Not clear
8 Was an appropriate statistical analysis used
671
39
Yes No Not clear
9 Were outcomes measured in a reliable way
Yes No Not clear
10 Was there adequate followshyup of participants
Yes No Not clear
Summary
TOTAL
Yes No Not clear
DECISION
Use Reject
Narrative summary only Further information needed
COMMENTS
672
40
Appendix II JBI Data Extraction Tool for Quantitative Studies Authors and Year
Journal Title
Record NumberArticle Reference No
Reviewer
Method
Settings
Participants
Number of participants
Group A Group B Group C
Control Intervention 1 Intervention 2
Interventions
Group A
Control
Group B
Intervention 1
Group C
Intervention 2
Outcome measures
Definition
673
41
Other outcome measures
Outcome description ScaleMeasure
Results
Dichotomous Data
Outcome Control Group
Numbertotal number
Treatment Group
Numbertotal number
Continuous Data
Authorrsquos Conclusions
Comments
Outcome Control Group
Mean amp SD
Treatment Group
Mean amp SD
674
43
Appendix III Details of included studies (N=6)(2720212223) RefNo Author(s)
(years) Title Study question Research
method Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
22 Takken T van der Torre P Zwerink M Hulzebos E H Bierings M Helders P J Mamp van der Net J (2009)
Development feasibility and efficacy of a community-based exercise training program in pediatric cancer survivors
To develop a 12-week home-based exercise training program (comprising aerobic and strength exercises) for children who survived ALL and to study itrsquos feasibility and efficacy
Pre-post test design
No comparsion group
Survived ALL(N=9)ages 6-14 years
1anthropometry 2 muscle strength 3functional mobility 4cardio-pulmonary
exercise test 5Fatigue
1 Feasibility questionnaire 2 anthropometry electronic scale and a wallmounted stadiometerHarpenden skin fold calipers 3 muscle strength handheld dynamometer 4functional mobility Timed Up
and Go test (TUG) 5cardio-pulmonary exercise test electronically braked cycle ergometer 6Fatigue(mean)CSI-20 (subjective experience of fatigueconcentrationmotivationphysical activity)
112-week exercise training program
2 Patients were assessed before (T0) and after (T1) 12 weeks of training
1 muscle strength execapacity functional moand fatigue showed nosignificant differences between pre(meanplusmnSD415plusmn147) and post training(meanplusmnSD3687)
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
7 Post-White J Fitzgerald M Savik K Hooke M C Hannahan A B amp Sencer S F (2009)
Massage therapy for children with cancer
To determine whether 4 weekly sessions of massage compared with 4 quiet-time control conditions would reduce anxiety cortisol levels fatigue nausea and pain in children with cancer undergoing chemotherapy and would reduce anxiety fatigue and mood disturbance in a parent
2-period crossover design (Randomized)
quiet-time
control
sessions
Children with cancer 1 to 18 years of age Twenty-three childrenparent dyads were enrolled 17 completed all data points
children 1relaxation 2symptoms 3 fatigue
parents
1anxiety 2 fatigue
children 1relaxation (heart and respiratory rates blood pressure and salivary cortisol level)
2symptoms (pain nausea anxiety 3 fatigue 1-2y3-6yLansky Play Performance Scale (PPS) 7-13y
1 4 weekly massage (MT) sessions alternated with 4 weekly quiet-time(QT) control sessions
2 children included presession and postsession vital signs (heart rate respiratory rate blood pressure) and self-report (parent proxy report for age 1-2 years) of pain nausea and anxiety Fatigue was measured before sessions 1 and 4 and at each follow-up Parent measures
included anxiety fatigue and mood states
1Massage was moreeffective than quiet tireducing heart rate inchildren anxiety in cless than age 14 yeaparent anxiety 2There were no sign
changes in blood pcortisol pain naufatigue (no state d
3 Children reported tmassage helped thebetter lessened theirand worries and hadlasting effects than q
675
44
14-18yChild Fatigue Scale (CFS) (frequency
intensity) 2 parents anxiety and fatigue
676
45
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
24 Hinds P S Hockenberry M Rai S N Zhang L Razzouk B I Cremer L McCarthy K amp Rodriguez-Galindo C (2007)
Clinical field testing of an enhanced-activity intervention in hospitalized children with cancer
To determine the feasibility of an
enhanced physical activity EPA intervention in children and adolescents hospitalized to receive chemotherapy for a solid tumor or AML and to assess the sleep and fatigue outcomes of the intervention using two different statistical approaches to analyze the longitudinal symptom data
randomized prospective two-site and two-group pilot study
Standard care Twenty nine patients (25 with a solid tumor and 4 with AML)ages 7-18 years
1 sleep duration 2 sleep efficiency 3 fatigue
1sleep duration sleep efficiency The
Wrist Actigraph The Daily Sleep Diary-Parent 2 fatigue (mean) The Fatigue Scale(FS-C) for 7-12 (intensity) The Fatigue Scale(FS-A) for 13-18 The Fatigue Scale Parent Version (FS-P) The Fatigue Scale Staff Version (FS-S)
1enhanced physical activity (EPA) (hospital-based 30 minutes
twice daily for 2-4 days) 2 T0On the day of admission
(Day 0 or baseline)patient and parents completed the fatigue instruments and a team member applied the actigraph Patients wore the wrist actigraph T1 from Day 0 to 2 or 3 consecutive days (Days 0e3) In addition the patient same parent and staff nurses completed the daily sleep and fatigue reports in the late afternoons of Days 1-3
1 ANOVA model slesignificantly more the experimental athe control arm whdifferences from bsleep efficiency vaaveraged and com
2 The patient-reported mean fatigue scoresarms were higher amadolescents than for
3 The mixed model anarevealed no significandifferences in patientfatigue between
the two study arms otime( no final result iSD only give mixed result)
677
46
23 Keats M
R amp Culos-Reed S N (2008)
A community-based physical activity program for adolescents with cancer (project TREK) program feasibility and preliminary findings
To examine the
feasibility of a
theoretically-based
physical activity (PA)
intervention in
adolescents with
cancerand
examination of the
impact of the
program on
participant QOL
including social
emotional and
physical
well-being(including fatigue)
Repeat measures longitudinal design
No comparsion group
10 adolescents(Lymphoma(4)leukemia(4)CNS tumor(1)germ cell tumor(1)) ages 14-18 years
1physical fitness 2quality of life (QOL) 3PA behavior 4fatigue
1 Feasibility was assessed by participant recruitment attendance and adherence
2physical fitness Fitnessgram 3quality of life (QOL) Pediatric Quality of Life Inventory (PedsQL) 4PA behavior leisure score index (LSI) 5fatigue (mean) pediatric Quality of life
Multidimensional Fatigue Scale (Peds QL-MFS)
(Generalsleepcognitive fatigue)
116week physical activity (PA)
2 total PA physical fitness and overall QOL was assessed at 5 different intervals T0 preintervention (baseline) T1midintervention (after the
first 8 wk) T2 postintervention
(16 wk) T3 3-months
postintervention T4 1-year poststudy
initiation
1 from baseline -wkssig Improvementstotal PA physfitness and Qgeneral fatigue(meanplusmnSD 796plusmn135)
2 from baseline to 3FUsig Improvin general fatigue(meanplusmnSD824plusmn131)slefatigue(meanplusmnSD755plusmn191)totafatigue(meanplusmnSD778plusmn150)
3at 1 years FUsImprovements in sleeprest fatigue(meanplusmnSD725plusmn203)total (meanplusmnSD 763plusmn
678
47
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
2 Gene R E amp Conk Z (2008)
Impact of Effective Nursing Interventions to the Fatigue Syndrome in Children Who Receive Chemotherapy
1 to examine the effects of an effective nursing intervention to the fatigue syndrome of children 7 to 12 years of age who receive chemotherapy 2Tto examine the relationship between fatigue and demographic variables (age sex) diagnoses ([ALL AML] lymphoma) and therapy-related variables (eg level of hemoglobin
experimental randomized controlled study
Routine nursing care
A total of 60 children who are 7-12 years of age(a new diagnosis of ALL AML or lymphoma and receiving for the first time after being diagnosed a 7- to 10-day chemotherapy treatment )
fatigue The Fatigue Scale(FS-C) for 7-12 (intensity)
The Fatigue Scale Parent Version (FS-P)
1 effective nursing interventions(45- 60mdaya week)education about the fatigue with the chemotherapy and fatigue handbook 2 T1 After a 7-day period the children
and parent were evaluated with the Fatigue Scale
1The difference betwthe 2 mean values wafound to be statisticallsignificant 2 statistically significadifference was found between the Fatigue Scale-Child mean scothe experimental (272the control group (4213)children
679
48
25 Chiang et
al(2007)
The effects of ldquo a home ndashbased aerobic exercise interventionrdquo on fatigue and cardiorespiratory fitness in children with Acute Lymphoblastic Leukemia during the maintenance stage of chemotherapy
To examine the effect of ldquo a home ndashbased aerobic exercise interventionrdquo on fatigue and cardiorespiratory fitness in children with Acute Lymphoblastic Leukemia during the maintenance stage of chemotherapy
Quasi-experi -mental
Routine
nursing care
14 pediatric oncology patients in the experimental group and 10 in control group who were matched by age and sex ages7-18 years
1Cardiorespiratory fitness
2Fatigue
1Cardiorespiratory fitness Physical Activity Recall
VO2maxHR peak 6MWT
2 Fatigue PedsQL-MFS(Generalsleepcognitive fatigue)
1A six-week home-based aerobic exercise intervention 2 8 time points T0 baseline T1-T6 every week during the
intervention(6 weeks) T7 post intervention T8 follow-up (one month after
the end of the home-based exercise program)
1 For intent-to ndash treatthe findings indicated are no intervention efftime differences by anon the subscale of fat2 For per-protocol angeneral fatigue( mean422plusmn402) was the osubscale that was siglower for children whothe exercise interventthose in control groupfollow-up assessmentmonth after the compintervention) 3 The VO2peak are significantly improvingexperimental group atbaseline- and post-intassessment The VO2was significantly highechildren who were in experimental group thcontrol subjects at post-intervention assefor the per-protocol an
680
49
Appendix IV Instrument used to measure fatigue
Name Instrument
developers
Description Used in
age in
ref
Reliability
Consistency of
instrument
Checklist Individual Strength
(CIS)22
Vercoulen et
al1996
20 items using 7-point Likert scale of
fatigue To measure four aspects of
fatiguesubjective experience
contractionmotivation physical
Activity
6-14 Not reported
Child Fatigue Scale (CFS)7 Hockenberry
et al2003
14 items 2 part questionnaire frequency
(yes or no) 5-point Likert scale of the
intensity of any yes responses
7-13
14-18 α073-o84
The Fatigue Scale for 7-12
year Olds (FS-C)224
Hockenberry
et al
14 items provide a fatigue intensity score
5-point Likert scale
7-12 αo84
The Fatigue Scale for 13-18
year Olds (FS-A)24
Hockenberry
et al
14 items provide a fatigue intensity score
5-point Likert scale
13-18 α076-o96
Pediatric Quality of life
Multidimensional Fatigue
Scale (Peds QL-MFS)2325
Varni2002 18 items to measure three aspects of
fatigueGeneralsleepcognitive
14-18 Not reported
681
50
Appendix V Excluded studies and reasons for exclusion
Baggott C Dodd M Kennedy C Marina N Miaskowski C Multiple Symptoms in Pediatric Oncology
Patients A Systematic Review Journal of Pediatric Oncology Nursing 2009 Nov-Dec 27(6)
325-339
Reason for exclusion Not outcome of interest
Barlow JH Ellard DR Psycho-educational interventions for children with chronic disease parents and
siblings an overview of the research evidence base Care Health amp Development 2004 Nov
30(6)637-45
Reason for exclusion Not outcome of interest
Bedider S Moyer CA Randomized controlled trials of pediatric massage A review Evid Based
Complement Alternat Med 2007 Mar 4(1)23-34 Epub 2006 Nov 3
Reason for exclusion Not outcome of interest
de Nijs EJ Ros W Grijpdonck MH Nursing intervention for fatigue during the treatment for cancer Cancer
Nursing 2008 31(3)191-206
Reason for exclusion Not population of interest
Edwards JL Gibson F Richardson A Sepion B Ream E Fatigue in adolescents with and following a
cancer diagnosis developing an evidence base for practice European Journal of Cancer 2003
Dec 39(18)2671-80
Reason for exclusion Not experimental or quasi-experimental study
Hinds PS Hockenberry-Eatan M Developing a research program on fatigue in children and adolescents
diagnosed with cancer Journal of Pediatric Oncology Nursing 2001 Mar-Apr 18(2 Suppl
1)3-12
Reason for exclusion Not experimental or quasi-experimental study
Hockenberry-Eaton M Hinds PS Alcoser P ONeill JB Euell K Howard V Gattuso J Taylor J Fatigue in
Children and Adolescents With Cancer Journal of Pediatric Oncology Nursing 1998 July
15(3)172-182
Reason for exclusion Not experimental or quasi-experimental study
Jean-Pierre P Mustian K Kohli S Roscoe JA Hickok JT Morrow GR Community-based clinical oncology
research trials for cancer-related fatigue The Journal of Supportive Oncology 2006 Nov-Dec
4(10)511-6
682
51
Reason for exclusion Not population of interest
Kangas M Bovbjerg DH Montgomery GH Cancer-Related Fatigue A Systematic and Meta-Analytic
Review of Non-Pharmacological Therapies for Cancer Patients Psychological Bulletin 2008 Sep
134(5)700-41
Reason for exclusion Not population of interest
Lotfi-Jam K Carey M Jefford M Schofield P Charleson C Aranda S Nonpharmacologic strategies for
managing common chemotherapy adverse effects A systematic review Journal of Clinical
Oncology 2008 Dec 1 26(34)5618-29 Epub 2008 Nov 3
Reason for exclusion Not outcome of interest
Marchese VG Chiarello LA Lange BJ Effects of physical therapy intervention for children with acute
lymphoblastic leukemia Pediatr Blood Cancer 2004 Feb42(2)127-33
Reason for exclusion Not outcome of interest
Meeske KA Siegel SE Globe DR Mack WJ Bernstein L Prevalence and correlates of fatigue in
long-term survivors of childhood leukemia Journal of Clinical Oncology 2005 Aug 20
23(24)5501-10
Reason for exclusion Not intervention study
Minton O Richardson A Sharpe M Hotopf Stone P A systematic review and meta-analysis of the
pharmacological treatment of cancer-related fatigue J Natl Cancer Inst 2008 Aug 20
100(16)1155-66 Epub 2008 Aug 11
Reason for exclusion Not population and intervention of interest
Mustian KM Morrow GR Carroll JK Figueroa-Moseley CD Pascal JP Williams GC Integrative
nonpharmacologic behavioral interventions for the management of Cancer-Related fatigue The
Oncologist 2007 12(1)52-67
Reason for exclusion Not population of interest
Neill J Belan I Ried K Effectiveness of non-pharmacological interventions for fatigue in adults with
multiple sclerosis rheumatoid arthritis or systemic lupus erythematosus a systematic review
Journal of Advanced Nursing 2006 Dec 56(6)617-35
Reason for exclusion Not population of interest
Rheingans JI A systematic review of nonpharmacologic adjunctive therapies for symptom management
Journal of Pediatric Oncology Nursing 2007 24(2) 81-94
683
52
Reason for exclusion Not outcome of interest
Rheingans JI Pediatric oncology nursesrsquo management of patients symptoms Journal of Pediatric
Oncology Nursing 2008 Nov 25(6) 303-11
Reason for exclusion Not outcome of interest
San Juan AF Fleck SJ Chamorro-Vintildea C Mateacute-Muntildeoz JL Moral S Peacuterez M Cardona C Del Valle MF
Hernaacutendez M Ramiacuterez M Madero L Lucia A Effects of an intrahospital exercise program
intervention for children with leukemia Medicine amp Science in Sports amp Exercise 2007 Jan
39(1)13-21
Reason for exclusion Not outcome of interest
Sanford SD Okuma JO Pan J Srivastava DK West N Farr L Hinds PS Gender differences in sleep
fatigue and daytime activity in a pediatric oncology sample receiving dexamethasone Journal of
Pediatric Psychology 2008 Apr 33(3)298-306 Epub 2007 Nov 17
Reason for exclusion Not experimental or quasi-experimental study
Schmitz KH Holtzman J Courneya KS Macircsse LC Duval S Kane R Controlled physical activity trials in
cancer survivors a systematic review and meta-analysis Cancer Epidemiol Biomarkers Prev
2005 Jul 14(7)1588-95
Reason for exclusion Not population of interest
van Brussel M Takken T Lucia A van der Net J Helders PJ Is physical fitness decreased in survivors of
childhood leukemia A systematic review Leukemia 2005 Jan 19(1)13-7
Reason for exclusion Not population of interest
Whiting P Bagnall AM Snowden AJ Cornell JE Mulrow CD Ramirez G Interventions for the treatment
and management of chronic fatigue syndrome JAMA 2001 Sep 19 286(11)1360-8
Reason for exclusion Not intervention of interest
Whitsett SF Gudmundsdottir M Davies B McCarthy P Friedman D Chemotherapy-related fatigue in
childhood cancer correlates consequences and coping strategies Journal of Pediatric
Oncology Nursing 2008 Mar-Apr 25(2)86-96 Epub 2008 Feb 29
Reason for exclusion Not experimental or quasi-experimental study
Winner C Muumlller C Hoffmann C Boos J Rosenbaum D Physical activity and childhood cancer Pediatr
Blood Cancer 2010 Apr 54(4)501-10
Reason for exclusion Not research study
684
53
Wu M Hsu L Zhang B Shen N Lu H Li S The experiences of cancer-related fatigue among Chinese
children with leukaemia A phenomenological study Journal of Nursing Studies 2010 Jan
47(1)49-59 Epub 2009 Aug 25
Reason for exclusion Not experimental or quasi-experimental study
Yeh CH Chiang YC Lin L Yang CP Chien LC Weaver MA Chuang HL Clinical factors associated with
fatigue over time in paediatric oncology patients receiving chemotherapy British Journal of
Cancer 2008 Jul 8 99(1)23-9 Epub 2008 Jun 24
Reason for exclusion Not experimental or quasi-experimental study
685
25
General fatigue sleeprest fatigue and total fatigue from baseline to 3 months follow up
showed significant improvements Sleeprest fatigue and total fatigue at 1 years followed
up were significant improvements
The effectiveness of exercise intervention for general fatigue
The impact of the exercise interventions upon levels of general fatigue was also analysed
The heterogeneity was low (p>005) Therefore the fixed effects model was used to
examine the effectiveness The effect size is -076 indicating a statistically significant
difference (p = 001 95 CI -135 to -017 Fig 3) The evidence suggests that exercise
intervention can reduce general fatigue in children with cancer
Fig 3 Meta-analysis results of exercise intervention for general fatigue
The effectiveness of exercise intervention for sleep rest fatigue
The following is the result of the meta-analysis of the effectiveness of exercise
interventions on sleep rest fatigue First the heterogeneity test was conducted with P gt
005 representing small heterogeneity and the fixed effects model was used Fig 4
shows the effect size is -035 indicating no statistically significant differences (p = 023
95 CI-092 to 022 Fig 4)
658
26
Fig 4 Meta-analysis results of exercise intervention for sleep rest fatigue
The effectiveness of exercise intervention for cognitive fatigue Lastly the following data reports the results of meta-analysis of the effectiveness of
exercise interventions for cognitive fatigue The heterogeneity was p>005 then the
fixed effects model was used The effect size is -035 indicating no statistically significant
differences (p = 024 95 CI-092 023 Fig 5)
Fig 5 Meta-analysis results of exercise intervention for cognitive fatigue
Narrative presentation of remaining included studies
Three studies were not included in meta-analysis Post-White et al7 one of the aims in
this study was to examine the effect of massage therapy on fatigue in children with
cancer The study was a quasi-experimental design Twenty-three childrenparent dyads
were enrolled 17completed all data points Children with cancer ages 7 to 18 years
received at least 2 identical cycles of chemotherapy and one parent participated in the
2-period crossover design in which 4 weekly massage sessions (MT) alternated with 4
659
27
weekly quiet-time (QT) control sessions There were no significant changes in fatigue in
children over the 4-week MT or QT conditions either independently (change over time) or
when we compared fatigue by condition
The lack of effect of massage on fatigue may be the difficulty some children had in
differentiating fatigue from being relaxed underscores the challenge of measuring fatigue
in children Some children interpreted being tired or relaxed as having greater fatigue
because they felt like lying around and sleeping or felt unmotivated to do their usual
activities all measures of fatigue in the instrument used in the study
Hinds et al24conducted a prospective two-site randomized controlled pilot study to
assess the feasibility of an enhanced physical activity (EPA) intervention in hospitalized
children and adolescents receiving treatment for a solid tumor or for acute myeloid
leukemia (AML) Twenty-nine patients (25 with a solid tumor and 4 with AML) participated
age range from 736 to 1816 (mean 1248 y) The EPA intervention selected was
pedaling a stationary bicycle-style exerciser (Chattanooga Peddler Deluxe Bio-Teck
Medical Memphis TN) for 30 minutes twice daily for 2 to 4 days of hospitalization The
mixed model analysis revealed no significant differences in patient reports of fatigue
between the two study arms or over time
Genc et al2 conducted a RCT involving children with cancer who are 7 to 12 years of age
and receiving chemotherapy treatment to determine the impact of educational
intervention by nurses on decreasing the fatigue syndrome The research sample was
composed of a total of 60 children with cancer with 30 children being included in the
660
28
experimental group (mean age 923)and 30 children included in the control group (mean
age 937) with their mothers In the experimental group after the 7th to 10th day of the
chemotherapy treatment throughout a week the researcher conducted the nursing
interventions every day for 45 to 60 minutes In the control group routine nursing
interventions were carried out The experimental group received education about the
fatigue with the chemotherapy and fatigue handbook was given which was developed by
the authors Children and mothers were consulted for including activities that could
decrease fatigue which were described as effective interventions A statistically
significant difference was found between the Fatigue Scale-Child mean scores of the
experimental (2723) and the control group (4213) The results suggest that fatigue of
children with cancer can be reduced by implementing appropriate nursing interventions
(t=567 Plt00)
Discussion The purpose of this systematic review was to determine the effectiveness of
non-pharmacological interventions specifically targeting fatigue for children and
adolescents with cancer undergoing chemotherapy or after receiving chemotherapy
Included articles about the effectiveness of non-pharmacological interventions for
children and adolescents with cancer were published between the years of 2007 and
2009 Although interventions for cancer fatigue for adults have been extensively studied
it can be seen from either the title of the paper or related content that an intervention
study on children was a pilot study or a feasibility study Representing a field in its early
stage these studies show that the fatigue issues with young cancer patients have only
recently been taken seriously
661
29
The results of our meta-analysis include measurement of the four performance indicators
fatigue and general fatigue sleep rest fatigue and cognitive fatigue The results show
that there is a statistically significant difference only in the domain of general fatigue
using an exercise intervention for children with cancer can improve the degree of fatigue
with the effect size reaching 0671 Other results do not indicate significant differences
The reasons may include the following
1 Characteristics of the cancer The exhaustion from cancer occurs not only during cancer treatment but also in during
long-term survival a time during which patients may continue to be affected by this
symptom 8 26 Therefore when using intervention measures to improve fatigue
circumstances should be considered such as the process of the treatment and the course
or stage of the disease Because cancer patients will experience different forms of
treatment or courses of treatment the disease itself or treatment differences should be
considered in the choice of intervention Even chemotherapy drugs should be taken into
consideration For example a period of general steroid treatment can increase patientsrsquo
fatigue In those studies of children with cancer few studies looked solely at one type of
cancer most studies included a variety of cancer patients Furthermore most studies do
not clearly explain the stage of the disease or course of treatment and most do not
include treatment variables in the control group Moreover children with cancer may
have different levels of physical function
2 Research design The sample size Currently there are few studies with large sample size and a rigorous
RCT design due to the small number of papers available for analysis The sample size
included in our studyrsquos data analysis is between 20 and 42 people this small sample size
will affect the power available to evaluate outcome variables
Although most of the non-pharmacological interventions still use exercise and physical
activity and these studies overall show better results for fatigue as compared with
controls more research is still needed to further confirm the efficacy of these findings
662
30
The dropout rate in the evaluated research varies a great deal ranging from 5 to 45
these dropout rates may result from the characteristics of the research subjects or the
lengthy time involved in participating in these studies The research data with a high
turnover rate might not reflect the actual outcomes of participation in exercise and the
quality of the research contained in articles with high subject turnover rates may be
lower
Exercise doses and time The exercise doses needed to reduce fatigue cannot be
determined additionally the amount of exercise completed by the patient is also
inconsistent interventions vary between 2-3 times per week and two times a day and
exercise duration varies between 10 and 45 minutes each time Furthermore the study
interventions vary in length between a couple of days and a long period of 16 weeks The
data collection times are different some were measured 12 weeks after the intervention
began some were measured during the 6 weeks of intervention some were measured
three months after the intervention was finished and some were measured after one
year
In addition disease-related symptoms decrease childrenrsquos willingness to participate in
exercise interventions inappropriate exercise intervention programs may actually
increase childrens fatigue In addition the children in the study are still developing
physically it is important to consider ways to design an interesting exercise intervention
to increase the compliance of patients in order to improve the effectiveness Although
intervention programs in the hospital or in a community sports center can improve the
effectiveness because they provide supervision the feasibility of these programs is
questionable However if the program is home-based the children need to be
supervised by parents in order to improve their compliance in doing the exercises
Furthermore regarding the nature of the intervention the results from this study indicate
that the researched non-pharmacological interventions include the following exercise
training programs physical activity massage therapy and health education interventions
However according to the National Comprehensive Cancer Network 1 clinical guidelines
663
31
for cancer non-drug measures for cancer fatigue can be separated into five categories
(1) activity enhancement (2) psychosocial interventions such as cognitive behavioral
therapy (CBT) stress management relaxation techniques and support groups (3)
attention-restoring therapy (4) nutritional consultation and (5) cognitive behavioral
therapy specifically targeting sleep disturbance Researchers have also suggested that
psychosocial interventions should be included in the future research for children with
cancer-related fatigue 22
(2) The measurement tools in the study The assessment of fatigue can be
one-dimensional or multidimensional One-dimensional assessment can help understand
the severity of fatigue symptoms however multidimensional scales are often more
credible Therefore when measuring cancer-related fatigue researchers should consider
whether there is a uniform definition of fatigue or a standardized tool for measuring
fatigue in order to facilitate further systematic meta-analyses and further develop the
clinical care guidelines
Limitations of the review The present review has some potential limitations First the low methodological quality
may influence the result Although exercise intervention seems promising quality of the
RCTs was generally quite low Future studies require better design and reporting if
methodological issues to establish evidence-based nonpharmcologic intervention
Second the identified studies covered only a limited types of nonpharmcological
intervention especially in exercise intervention The guidelines for cancer-related fatigue
in NCCN (2011)1 referred to more interventions than the ones included in this review
such as cognitive behavioral therapy and nutrition consultation Thirdly the small sample
size and effect size could be potentially having led to underpowered approach for
detecting the effects on fatigue Therefore we recommend that as research continues to
grow a re-analysis can be undertaken Fourthly Combining data in meta analysis from
664
32
studies where the ages were quite different is a potential source of heterogeneity and
may affect the interpretation of the results
Conclusion At present clinical treatment is widely used for cancer patients However child and
adolescent cancer patients often experience various side effects which cause short-term
or long-term discomfort both physically and psychologically In particular with the
increasing cure rate cancer related fatigue during or after treatment has become an
important issue This study result provided positive effect of exercise intervention on
general fatigue
Implications for practice The results of this systematic review and meta-analysis show that exercise interventions
can effectively improve the level of general fatigue In particular although the articles
were self-reported feasibility studies their results all indicate that exercise interventions
for fatigue are feasible and safe there was no conclusion to be made for the use of
massage therapy or health education measures because there was only one article for
each of these interventions
Recommendations for practice
Cancer-related fatigue is one of the most severe and frequent symptoms by pediatric
oncology children and adolescent suffered during treatment and the symptom existed
even after treatment has ended Until now no golden standard of treatment to fatigue is
established The findings call for more attention to how to reduce patientrsquos levels of
fatigue Based on the available information evaluated in this review the following
recommendations for practice are provided
665
33
bull For children aged 7 to 18 who has cancer (eg Lymphoma leukemia CNS tumor
germ cell tumor) an effective progressive aerobic exercise program is recommended to
be at least 2-3 times per week 20 to 45 minute for each session and last for 6-16 weeks
in order to reduce their general fatigue (tiredness physically weakness) In addition
adults should be involved in accompanying children while they are performing physical
exercise of which should be able to improve the adherence rate (level 2 ) ( Grade of
recommendation A)
bull For children aged 7 to 18 who has cancer (eg Lymphoma leukemia CNS tumor
germ cell tumor) an progressive aerobic exercise program will not be effective to reduce
their sleep andor rest (sleeping or resting a lot) or cognitive fatigue (problems with
thinking quickly or problems with remembering) (level 2 ) ( Grade of recommendation C)
bull Nursing interventions in educating treatment of fatigue include information about
activity nutrition energy preservation consulting and providing a useful fatigue
handbook will benefit those children who are 7 to 12 years have a new diagnosis of ALL
AML or lymphoma and receive for the first time after being diagnosed a 7- to 10-day
chemotherapy treatment (level 2) ( Grade of recommendation A)
bull A 4-week massage therapy program (the therapists massage childrenrsquos back legs
arms stomachchest and face) is not effective for children who are aged 7 to 18 and
have acute lymphoblastic leukemia brain tumors lymphoma rhabdomyosarcoma
Wilms tumor or Ewing sarcoma(level 2)( Grade of recommendation C)
bull Using a 12-week aerobic and strength exercise (45-min exercise sessions twice a
week) is not effective for children who are aged 6-14 and survived acute lymphoblaststic
leukemia age from 6 to 14(level 2) ( Grade of recommendation C)
bull Using a physical activity intervention (30minutestwice daily for 2-4days) is not
effective for children who are 7 to 18 years of age with soild tumor or AML(level 2)
( Grade of recommendation C)
666
34
Implications for research According to this systematic review and meta-analysis results there are suggestions to
improve the effectiveness of future research on non-pharmacological interventions for
children and young peoplersquos cancer-related fatigue
As the majority of included non-pharmacological interventions for the fatigue of cancer
patients consist of exercise programs future research should also consider various
non-pharmacological interventions in order to understand the effectiveness of different
methods
Regarding the exercise intervention methods and studies should consider multiple
factors including the age or personal condition of the subject the disease stage and the
amount of daily activities Studies should use design prescriptions (eg frequency
intensity duration and type of exercise) and consider the adherence to the measures in
order to enhance the study strength
In measuring the results of non-pharmacological interventions there should be standard
definitions or standard measurement tools to facilitate the following systematic review
and meta-analysis that can subsequently be developed into clinical care guidelines
Reviewing the effectiveness of the current non-pharmacological management of children
and adolescent cancer patients there is still a lack of rigorous RCT research Limited by
the characteristics of cancer there is still a lack of large sample sizes
Potential conflicts of interest There is no conflict of interest
Acknowledgements
Thank you to Dr Rie Konno Research Fellow Joanna Briggs Institute for her help in
assessing studies
667
35
References 1 National Comprehensive Cancer Network( NCCN) in USA NCCN clinical practice
guideline in oncology cancer-related fatigue 2011 2 Ekti Genc R amp Conk Z Impact of effective nursing interventions to the fatigue
syndrome in children who receive chemotherapy Cancer Nursing 200831(4)312-317
3 Childhood Cancer Foundation of ROC (2009March) The classification of diseases
and age sex statistical tables of case Childhood Cancer Foundation of ROC newsletter103105-106
4 Department of Health Executive Yuan ROC (TAIWAN)(2009 March 20)2009 cause of death statistic Health and National Health Insurance Annual Statistics Information Service 2010 June 28Available httpwwwdohgovtwstatisticdatavital statists9898health statistic--lifepdf
5 Chang TK (2007December 8) Common childhood cancer and its treatment Status
Childhood Cancer Foundation of ROC (TAIWAN) 2010 September 23 Available httpwwwccfrocorgtwchildchild_events_readphpe_id=45
6 Hockenberry MJ amp Wilson D Wongs nursing care of infants and children (8th ed) St
Louis MO Mosby 2007
7 Post-White J Fitzgerald M Savik K Hooke MC Hannahan AB amp Sencer SF
Massage therapy for children with cancer Journal of Pediatric Oncology Nursing 2009 26(1)16-28
8Chiang YC Yeh CH Wang WKamp Yang CP The experience of cancer-related fatigue
in Taiwanese children European Journal of Cancer Care 2009 18(1)43-49 9Langeveld NE Grootenhuis M A Voute P A de Haan RJ amp van den Bos C No excess
fatigue in young adult survivors of childhood cancer European Journal of Cancer 200339(2)204-214
10Piper BF Lindsey AM amp Dodd MJ Fatigue mechanisms in cancer patients
developing nursing theory Oncology Nursing Forum 1987 14(6)17-23 11Nail LM amp Winningham ML Fatigue In S L Groenwald M H Forgge M Goodman
amp C H Yarbro (Eds) Cancer Nursing Principles and practice (4 th ed) Boston Jones and Bartlett1997
12Irvine D Vincent L Graydon JE Bubela N amp Thompson L The prevalence and
correlates of fatigue in patients receiving treatment with chemotherapy and
668
36
radiotherapy A comparison with the fatigue experienced by healthy individuals Cancer Nursing 199417(5)367-378
13Hinds PS amp Hockenberry-Eaton M Developing a research program on fatigue in
children and adloescents diagnosed with cancer Journal of Pediatric Oncology Nursing 200118(2)3-12
14Aaronson LS Teel CS Cassmeyer V Neuberger GB Pallikkathayil L Pierce J Press
AN Williams DP amp Wingate A Defining and measuring fatigue Journal of Nursing scholarship 1999 31(1)45-50
15Yeh CH Wang CH Chiang YC Lin Lamp Chien LC Assessment of symptoms reported
by 10- to 18-year-old cancer patients in Taiwan 2009 38(5)738-746 16 Okuyama T Akechi T Kugaya A Okamura H Shima Yamp Maruguchi M
Development and validation of the cancer fatigue scale a brief three-dimensional self-rating scale for assessment of fatigue in cancer patients Journal of Pain amp Symptom Management 2000 19(1) 5-14
17Gibson F Mulhall AB Richardson A Edwards JL Ream E amp Sepion BJ A
phenomenologic study of fatigue in adolescents receiving treatment for cancer Oncology Nursing Forum200532(3)651-660
18Wolfe J Grier HE Klar N Levin SB Ellenbogen JMamp Salem-Schatz S et al
Symptoms and suffering at the end of life in children with cancer New England Journal of Medicine 2000342(5)326-333
19Whiting P Bagnall AM Sowden AJ Cornell JE Mulrow CD amp Ramirez G
Interventions for the treatment and management of chronic fatigue syndrome a systematic review JAMA the Journal of the American Medical Association 2001286(11)1360-1368
20 Kangas M Bovbjerg DHamp Montgomery G H Cancer-related fatigue a systematic
and meta-analytic review of non-pharmacological therapies for cancer patients Psychological Bulletin 2008134 (5)700-741
21Williams PD Schmideskamp J Ridder EL amp Williams AR Symptom monitoring and
dependent care during cancer treatment in children pilot study Cancer Nursing 200629(3)188-197
22Takken T van der Torre P Zwerink M Hulzebos EH Bierings M Helders PJMamp van
der Net J Development feasibility and efficacy of a community-based exercise training
669
37
program in pediatric cancer survivors Psycho-Oncology 200918(4)440-448
23Keats MR amp Culos-Reed SN A community-based physical activity program for
adolescents with cancer (project TREK) program feasibility and preliminary findings
Pediatric hematology and oncology 200830(4) 272-280
24Hinds PS Hockenberry M Rai SN Zhang L Razzouk B I Cremer L McCarthy K amp
Rodriguez-Galindo C Clinical field testing of an enhanced-activity intervention in
hospitalized children with cancer Journal of Pain amp Symptom Management 2007
33(6)686-697
25Chiang YC The effects of ldquo a home-based aerobic exercise interventionrdquo on fatigue
and cardiorespiratory fitness in children with acute lymphoblastic leukemia during the
maintenance stage of chemotherapy Unpublished thesis Taiwan Tao-Yuan 2007
26Langeveld N Ubbink M amp Smets E I dont have any energy The experience of
fatigue in young adult survivors of childhood cancer European journal of oncology
nursing 20004(1)20-28
27 Kisner C Colby L Therapeutic exercise Foundations and techniques 2nd ed Philadelphia PAFA Davies 2007
670
38
Appendix I JBI Critical Appraisal Checklist for Experimental studies
Author__________ Year_________ Record Number__________________
Questions 1 to 4 must be answered ldquoyesrdquo for study to be included in the metashyanalysis
1 Were the participants randomized to study groups
Yes No Not clear
2 Other than research intervention were participants in each groups treated the same
Yes No Not clear
3 Were the outcomes measured in the same manner for all participants
Yes No Not clear
4 Were groups comparable at entry
Yes No Not clear
5 Was randomization of participants blinded
Yes No Not clear
6 Were those assessing outcome blinded to treatment allocation (if outcome not objective such as survival or length of hospitalization)
Yes No Not clear
7 Was allocation to treatment groups concealed from the allocator
Yes No Not clear
8 Was an appropriate statistical analysis used
671
39
Yes No Not clear
9 Were outcomes measured in a reliable way
Yes No Not clear
10 Was there adequate followshyup of participants
Yes No Not clear
Summary
TOTAL
Yes No Not clear
DECISION
Use Reject
Narrative summary only Further information needed
COMMENTS
672
40
Appendix II JBI Data Extraction Tool for Quantitative Studies Authors and Year
Journal Title
Record NumberArticle Reference No
Reviewer
Method
Settings
Participants
Number of participants
Group A Group B Group C
Control Intervention 1 Intervention 2
Interventions
Group A
Control
Group B
Intervention 1
Group C
Intervention 2
Outcome measures
Definition
673
41
Other outcome measures
Outcome description ScaleMeasure
Results
Dichotomous Data
Outcome Control Group
Numbertotal number
Treatment Group
Numbertotal number
Continuous Data
Authorrsquos Conclusions
Comments
Outcome Control Group
Mean amp SD
Treatment Group
Mean amp SD
674
43
Appendix III Details of included studies (N=6)(2720212223) RefNo Author(s)
(years) Title Study question Research
method Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
22 Takken T van der Torre P Zwerink M Hulzebos E H Bierings M Helders P J Mamp van der Net J (2009)
Development feasibility and efficacy of a community-based exercise training program in pediatric cancer survivors
To develop a 12-week home-based exercise training program (comprising aerobic and strength exercises) for children who survived ALL and to study itrsquos feasibility and efficacy
Pre-post test design
No comparsion group
Survived ALL(N=9)ages 6-14 years
1anthropometry 2 muscle strength 3functional mobility 4cardio-pulmonary
exercise test 5Fatigue
1 Feasibility questionnaire 2 anthropometry electronic scale and a wallmounted stadiometerHarpenden skin fold calipers 3 muscle strength handheld dynamometer 4functional mobility Timed Up
and Go test (TUG) 5cardio-pulmonary exercise test electronically braked cycle ergometer 6Fatigue(mean)CSI-20 (subjective experience of fatigueconcentrationmotivationphysical activity)
112-week exercise training program
2 Patients were assessed before (T0) and after (T1) 12 weeks of training
1 muscle strength execapacity functional moand fatigue showed nosignificant differences between pre(meanplusmnSD415plusmn147) and post training(meanplusmnSD3687)
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
7 Post-White J Fitzgerald M Savik K Hooke M C Hannahan A B amp Sencer S F (2009)
Massage therapy for children with cancer
To determine whether 4 weekly sessions of massage compared with 4 quiet-time control conditions would reduce anxiety cortisol levels fatigue nausea and pain in children with cancer undergoing chemotherapy and would reduce anxiety fatigue and mood disturbance in a parent
2-period crossover design (Randomized)
quiet-time
control
sessions
Children with cancer 1 to 18 years of age Twenty-three childrenparent dyads were enrolled 17 completed all data points
children 1relaxation 2symptoms 3 fatigue
parents
1anxiety 2 fatigue
children 1relaxation (heart and respiratory rates blood pressure and salivary cortisol level)
2symptoms (pain nausea anxiety 3 fatigue 1-2y3-6yLansky Play Performance Scale (PPS) 7-13y
1 4 weekly massage (MT) sessions alternated with 4 weekly quiet-time(QT) control sessions
2 children included presession and postsession vital signs (heart rate respiratory rate blood pressure) and self-report (parent proxy report for age 1-2 years) of pain nausea and anxiety Fatigue was measured before sessions 1 and 4 and at each follow-up Parent measures
included anxiety fatigue and mood states
1Massage was moreeffective than quiet tireducing heart rate inchildren anxiety in cless than age 14 yeaparent anxiety 2There were no sign
changes in blood pcortisol pain naufatigue (no state d
3 Children reported tmassage helped thebetter lessened theirand worries and hadlasting effects than q
675
44
14-18yChild Fatigue Scale (CFS) (frequency
intensity) 2 parents anxiety and fatigue
676
45
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
24 Hinds P S Hockenberry M Rai S N Zhang L Razzouk B I Cremer L McCarthy K amp Rodriguez-Galindo C (2007)
Clinical field testing of an enhanced-activity intervention in hospitalized children with cancer
To determine the feasibility of an
enhanced physical activity EPA intervention in children and adolescents hospitalized to receive chemotherapy for a solid tumor or AML and to assess the sleep and fatigue outcomes of the intervention using two different statistical approaches to analyze the longitudinal symptom data
randomized prospective two-site and two-group pilot study
Standard care Twenty nine patients (25 with a solid tumor and 4 with AML)ages 7-18 years
1 sleep duration 2 sleep efficiency 3 fatigue
1sleep duration sleep efficiency The
Wrist Actigraph The Daily Sleep Diary-Parent 2 fatigue (mean) The Fatigue Scale(FS-C) for 7-12 (intensity) The Fatigue Scale(FS-A) for 13-18 The Fatigue Scale Parent Version (FS-P) The Fatigue Scale Staff Version (FS-S)
1enhanced physical activity (EPA) (hospital-based 30 minutes
twice daily for 2-4 days) 2 T0On the day of admission
(Day 0 or baseline)patient and parents completed the fatigue instruments and a team member applied the actigraph Patients wore the wrist actigraph T1 from Day 0 to 2 or 3 consecutive days (Days 0e3) In addition the patient same parent and staff nurses completed the daily sleep and fatigue reports in the late afternoons of Days 1-3
1 ANOVA model slesignificantly more the experimental athe control arm whdifferences from bsleep efficiency vaaveraged and com
2 The patient-reported mean fatigue scoresarms were higher amadolescents than for
3 The mixed model anarevealed no significandifferences in patientfatigue between
the two study arms otime( no final result iSD only give mixed result)
677
46
23 Keats M
R amp Culos-Reed S N (2008)
A community-based physical activity program for adolescents with cancer (project TREK) program feasibility and preliminary findings
To examine the
feasibility of a
theoretically-based
physical activity (PA)
intervention in
adolescents with
cancerand
examination of the
impact of the
program on
participant QOL
including social
emotional and
physical
well-being(including fatigue)
Repeat measures longitudinal design
No comparsion group
10 adolescents(Lymphoma(4)leukemia(4)CNS tumor(1)germ cell tumor(1)) ages 14-18 years
1physical fitness 2quality of life (QOL) 3PA behavior 4fatigue
1 Feasibility was assessed by participant recruitment attendance and adherence
2physical fitness Fitnessgram 3quality of life (QOL) Pediatric Quality of Life Inventory (PedsQL) 4PA behavior leisure score index (LSI) 5fatigue (mean) pediatric Quality of life
Multidimensional Fatigue Scale (Peds QL-MFS)
(Generalsleepcognitive fatigue)
116week physical activity (PA)
2 total PA physical fitness and overall QOL was assessed at 5 different intervals T0 preintervention (baseline) T1midintervention (after the
first 8 wk) T2 postintervention
(16 wk) T3 3-months
postintervention T4 1-year poststudy
initiation
1 from baseline -wkssig Improvementstotal PA physfitness and Qgeneral fatigue(meanplusmnSD 796plusmn135)
2 from baseline to 3FUsig Improvin general fatigue(meanplusmnSD824plusmn131)slefatigue(meanplusmnSD755plusmn191)totafatigue(meanplusmnSD778plusmn150)
3at 1 years FUsImprovements in sleeprest fatigue(meanplusmnSD725plusmn203)total (meanplusmnSD 763plusmn
678
47
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
2 Gene R E amp Conk Z (2008)
Impact of Effective Nursing Interventions to the Fatigue Syndrome in Children Who Receive Chemotherapy
1 to examine the effects of an effective nursing intervention to the fatigue syndrome of children 7 to 12 years of age who receive chemotherapy 2Tto examine the relationship between fatigue and demographic variables (age sex) diagnoses ([ALL AML] lymphoma) and therapy-related variables (eg level of hemoglobin
experimental randomized controlled study
Routine nursing care
A total of 60 children who are 7-12 years of age(a new diagnosis of ALL AML or lymphoma and receiving for the first time after being diagnosed a 7- to 10-day chemotherapy treatment )
fatigue The Fatigue Scale(FS-C) for 7-12 (intensity)
The Fatigue Scale Parent Version (FS-P)
1 effective nursing interventions(45- 60mdaya week)education about the fatigue with the chemotherapy and fatigue handbook 2 T1 After a 7-day period the children
and parent were evaluated with the Fatigue Scale
1The difference betwthe 2 mean values wafound to be statisticallsignificant 2 statistically significadifference was found between the Fatigue Scale-Child mean scothe experimental (272the control group (4213)children
679
48
25 Chiang et
al(2007)
The effects of ldquo a home ndashbased aerobic exercise interventionrdquo on fatigue and cardiorespiratory fitness in children with Acute Lymphoblastic Leukemia during the maintenance stage of chemotherapy
To examine the effect of ldquo a home ndashbased aerobic exercise interventionrdquo on fatigue and cardiorespiratory fitness in children with Acute Lymphoblastic Leukemia during the maintenance stage of chemotherapy
Quasi-experi -mental
Routine
nursing care
14 pediatric oncology patients in the experimental group and 10 in control group who were matched by age and sex ages7-18 years
1Cardiorespiratory fitness
2Fatigue
1Cardiorespiratory fitness Physical Activity Recall
VO2maxHR peak 6MWT
2 Fatigue PedsQL-MFS(Generalsleepcognitive fatigue)
1A six-week home-based aerobic exercise intervention 2 8 time points T0 baseline T1-T6 every week during the
intervention(6 weeks) T7 post intervention T8 follow-up (one month after
the end of the home-based exercise program)
1 For intent-to ndash treatthe findings indicated are no intervention efftime differences by anon the subscale of fat2 For per-protocol angeneral fatigue( mean422plusmn402) was the osubscale that was siglower for children whothe exercise interventthose in control groupfollow-up assessmentmonth after the compintervention) 3 The VO2peak are significantly improvingexperimental group atbaseline- and post-intassessment The VO2was significantly highechildren who were in experimental group thcontrol subjects at post-intervention assefor the per-protocol an
680
49
Appendix IV Instrument used to measure fatigue
Name Instrument
developers
Description Used in
age in
ref
Reliability
Consistency of
instrument
Checklist Individual Strength
(CIS)22
Vercoulen et
al1996
20 items using 7-point Likert scale of
fatigue To measure four aspects of
fatiguesubjective experience
contractionmotivation physical
Activity
6-14 Not reported
Child Fatigue Scale (CFS)7 Hockenberry
et al2003
14 items 2 part questionnaire frequency
(yes or no) 5-point Likert scale of the
intensity of any yes responses
7-13
14-18 α073-o84
The Fatigue Scale for 7-12
year Olds (FS-C)224
Hockenberry
et al
14 items provide a fatigue intensity score
5-point Likert scale
7-12 αo84
The Fatigue Scale for 13-18
year Olds (FS-A)24
Hockenberry
et al
14 items provide a fatigue intensity score
5-point Likert scale
13-18 α076-o96
Pediatric Quality of life
Multidimensional Fatigue
Scale (Peds QL-MFS)2325
Varni2002 18 items to measure three aspects of
fatigueGeneralsleepcognitive
14-18 Not reported
681
50
Appendix V Excluded studies and reasons for exclusion
Baggott C Dodd M Kennedy C Marina N Miaskowski C Multiple Symptoms in Pediatric Oncology
Patients A Systematic Review Journal of Pediatric Oncology Nursing 2009 Nov-Dec 27(6)
325-339
Reason for exclusion Not outcome of interest
Barlow JH Ellard DR Psycho-educational interventions for children with chronic disease parents and
siblings an overview of the research evidence base Care Health amp Development 2004 Nov
30(6)637-45
Reason for exclusion Not outcome of interest
Bedider S Moyer CA Randomized controlled trials of pediatric massage A review Evid Based
Complement Alternat Med 2007 Mar 4(1)23-34 Epub 2006 Nov 3
Reason for exclusion Not outcome of interest
de Nijs EJ Ros W Grijpdonck MH Nursing intervention for fatigue during the treatment for cancer Cancer
Nursing 2008 31(3)191-206
Reason for exclusion Not population of interest
Edwards JL Gibson F Richardson A Sepion B Ream E Fatigue in adolescents with and following a
cancer diagnosis developing an evidence base for practice European Journal of Cancer 2003
Dec 39(18)2671-80
Reason for exclusion Not experimental or quasi-experimental study
Hinds PS Hockenberry-Eatan M Developing a research program on fatigue in children and adolescents
diagnosed with cancer Journal of Pediatric Oncology Nursing 2001 Mar-Apr 18(2 Suppl
1)3-12
Reason for exclusion Not experimental or quasi-experimental study
Hockenberry-Eaton M Hinds PS Alcoser P ONeill JB Euell K Howard V Gattuso J Taylor J Fatigue in
Children and Adolescents With Cancer Journal of Pediatric Oncology Nursing 1998 July
15(3)172-182
Reason for exclusion Not experimental or quasi-experimental study
Jean-Pierre P Mustian K Kohli S Roscoe JA Hickok JT Morrow GR Community-based clinical oncology
research trials for cancer-related fatigue The Journal of Supportive Oncology 2006 Nov-Dec
4(10)511-6
682
51
Reason for exclusion Not population of interest
Kangas M Bovbjerg DH Montgomery GH Cancer-Related Fatigue A Systematic and Meta-Analytic
Review of Non-Pharmacological Therapies for Cancer Patients Psychological Bulletin 2008 Sep
134(5)700-41
Reason for exclusion Not population of interest
Lotfi-Jam K Carey M Jefford M Schofield P Charleson C Aranda S Nonpharmacologic strategies for
managing common chemotherapy adverse effects A systematic review Journal of Clinical
Oncology 2008 Dec 1 26(34)5618-29 Epub 2008 Nov 3
Reason for exclusion Not outcome of interest
Marchese VG Chiarello LA Lange BJ Effects of physical therapy intervention for children with acute
lymphoblastic leukemia Pediatr Blood Cancer 2004 Feb42(2)127-33
Reason for exclusion Not outcome of interest
Meeske KA Siegel SE Globe DR Mack WJ Bernstein L Prevalence and correlates of fatigue in
long-term survivors of childhood leukemia Journal of Clinical Oncology 2005 Aug 20
23(24)5501-10
Reason for exclusion Not intervention study
Minton O Richardson A Sharpe M Hotopf Stone P A systematic review and meta-analysis of the
pharmacological treatment of cancer-related fatigue J Natl Cancer Inst 2008 Aug 20
100(16)1155-66 Epub 2008 Aug 11
Reason for exclusion Not population and intervention of interest
Mustian KM Morrow GR Carroll JK Figueroa-Moseley CD Pascal JP Williams GC Integrative
nonpharmacologic behavioral interventions for the management of Cancer-Related fatigue The
Oncologist 2007 12(1)52-67
Reason for exclusion Not population of interest
Neill J Belan I Ried K Effectiveness of non-pharmacological interventions for fatigue in adults with
multiple sclerosis rheumatoid arthritis or systemic lupus erythematosus a systematic review
Journal of Advanced Nursing 2006 Dec 56(6)617-35
Reason for exclusion Not population of interest
Rheingans JI A systematic review of nonpharmacologic adjunctive therapies for symptom management
Journal of Pediatric Oncology Nursing 2007 24(2) 81-94
683
52
Reason for exclusion Not outcome of interest
Rheingans JI Pediatric oncology nursesrsquo management of patients symptoms Journal of Pediatric
Oncology Nursing 2008 Nov 25(6) 303-11
Reason for exclusion Not outcome of interest
San Juan AF Fleck SJ Chamorro-Vintildea C Mateacute-Muntildeoz JL Moral S Peacuterez M Cardona C Del Valle MF
Hernaacutendez M Ramiacuterez M Madero L Lucia A Effects of an intrahospital exercise program
intervention for children with leukemia Medicine amp Science in Sports amp Exercise 2007 Jan
39(1)13-21
Reason for exclusion Not outcome of interest
Sanford SD Okuma JO Pan J Srivastava DK West N Farr L Hinds PS Gender differences in sleep
fatigue and daytime activity in a pediatric oncology sample receiving dexamethasone Journal of
Pediatric Psychology 2008 Apr 33(3)298-306 Epub 2007 Nov 17
Reason for exclusion Not experimental or quasi-experimental study
Schmitz KH Holtzman J Courneya KS Macircsse LC Duval S Kane R Controlled physical activity trials in
cancer survivors a systematic review and meta-analysis Cancer Epidemiol Biomarkers Prev
2005 Jul 14(7)1588-95
Reason for exclusion Not population of interest
van Brussel M Takken T Lucia A van der Net J Helders PJ Is physical fitness decreased in survivors of
childhood leukemia A systematic review Leukemia 2005 Jan 19(1)13-7
Reason for exclusion Not population of interest
Whiting P Bagnall AM Snowden AJ Cornell JE Mulrow CD Ramirez G Interventions for the treatment
and management of chronic fatigue syndrome JAMA 2001 Sep 19 286(11)1360-8
Reason for exclusion Not intervention of interest
Whitsett SF Gudmundsdottir M Davies B McCarthy P Friedman D Chemotherapy-related fatigue in
childhood cancer correlates consequences and coping strategies Journal of Pediatric
Oncology Nursing 2008 Mar-Apr 25(2)86-96 Epub 2008 Feb 29
Reason for exclusion Not experimental or quasi-experimental study
Winner C Muumlller C Hoffmann C Boos J Rosenbaum D Physical activity and childhood cancer Pediatr
Blood Cancer 2010 Apr 54(4)501-10
Reason for exclusion Not research study
684
53
Wu M Hsu L Zhang B Shen N Lu H Li S The experiences of cancer-related fatigue among Chinese
children with leukaemia A phenomenological study Journal of Nursing Studies 2010 Jan
47(1)49-59 Epub 2009 Aug 25
Reason for exclusion Not experimental or quasi-experimental study
Yeh CH Chiang YC Lin L Yang CP Chien LC Weaver MA Chuang HL Clinical factors associated with
fatigue over time in paediatric oncology patients receiving chemotherapy British Journal of
Cancer 2008 Jul 8 99(1)23-9 Epub 2008 Jun 24
Reason for exclusion Not experimental or quasi-experimental study
685
26
Fig 4 Meta-analysis results of exercise intervention for sleep rest fatigue
The effectiveness of exercise intervention for cognitive fatigue Lastly the following data reports the results of meta-analysis of the effectiveness of
exercise interventions for cognitive fatigue The heterogeneity was p>005 then the
fixed effects model was used The effect size is -035 indicating no statistically significant
differences (p = 024 95 CI-092 023 Fig 5)
Fig 5 Meta-analysis results of exercise intervention for cognitive fatigue
Narrative presentation of remaining included studies
Three studies were not included in meta-analysis Post-White et al7 one of the aims in
this study was to examine the effect of massage therapy on fatigue in children with
cancer The study was a quasi-experimental design Twenty-three childrenparent dyads
were enrolled 17completed all data points Children with cancer ages 7 to 18 years
received at least 2 identical cycles of chemotherapy and one parent participated in the
2-period crossover design in which 4 weekly massage sessions (MT) alternated with 4
659
27
weekly quiet-time (QT) control sessions There were no significant changes in fatigue in
children over the 4-week MT or QT conditions either independently (change over time) or
when we compared fatigue by condition
The lack of effect of massage on fatigue may be the difficulty some children had in
differentiating fatigue from being relaxed underscores the challenge of measuring fatigue
in children Some children interpreted being tired or relaxed as having greater fatigue
because they felt like lying around and sleeping or felt unmotivated to do their usual
activities all measures of fatigue in the instrument used in the study
Hinds et al24conducted a prospective two-site randomized controlled pilot study to
assess the feasibility of an enhanced physical activity (EPA) intervention in hospitalized
children and adolescents receiving treatment for a solid tumor or for acute myeloid
leukemia (AML) Twenty-nine patients (25 with a solid tumor and 4 with AML) participated
age range from 736 to 1816 (mean 1248 y) The EPA intervention selected was
pedaling a stationary bicycle-style exerciser (Chattanooga Peddler Deluxe Bio-Teck
Medical Memphis TN) for 30 minutes twice daily for 2 to 4 days of hospitalization The
mixed model analysis revealed no significant differences in patient reports of fatigue
between the two study arms or over time
Genc et al2 conducted a RCT involving children with cancer who are 7 to 12 years of age
and receiving chemotherapy treatment to determine the impact of educational
intervention by nurses on decreasing the fatigue syndrome The research sample was
composed of a total of 60 children with cancer with 30 children being included in the
660
28
experimental group (mean age 923)and 30 children included in the control group (mean
age 937) with their mothers In the experimental group after the 7th to 10th day of the
chemotherapy treatment throughout a week the researcher conducted the nursing
interventions every day for 45 to 60 minutes In the control group routine nursing
interventions were carried out The experimental group received education about the
fatigue with the chemotherapy and fatigue handbook was given which was developed by
the authors Children and mothers were consulted for including activities that could
decrease fatigue which were described as effective interventions A statistically
significant difference was found between the Fatigue Scale-Child mean scores of the
experimental (2723) and the control group (4213) The results suggest that fatigue of
children with cancer can be reduced by implementing appropriate nursing interventions
(t=567 Plt00)
Discussion The purpose of this systematic review was to determine the effectiveness of
non-pharmacological interventions specifically targeting fatigue for children and
adolescents with cancer undergoing chemotherapy or after receiving chemotherapy
Included articles about the effectiveness of non-pharmacological interventions for
children and adolescents with cancer were published between the years of 2007 and
2009 Although interventions for cancer fatigue for adults have been extensively studied
it can be seen from either the title of the paper or related content that an intervention
study on children was a pilot study or a feasibility study Representing a field in its early
stage these studies show that the fatigue issues with young cancer patients have only
recently been taken seriously
661
29
The results of our meta-analysis include measurement of the four performance indicators
fatigue and general fatigue sleep rest fatigue and cognitive fatigue The results show
that there is a statistically significant difference only in the domain of general fatigue
using an exercise intervention for children with cancer can improve the degree of fatigue
with the effect size reaching 0671 Other results do not indicate significant differences
The reasons may include the following
1 Characteristics of the cancer The exhaustion from cancer occurs not only during cancer treatment but also in during
long-term survival a time during which patients may continue to be affected by this
symptom 8 26 Therefore when using intervention measures to improve fatigue
circumstances should be considered such as the process of the treatment and the course
or stage of the disease Because cancer patients will experience different forms of
treatment or courses of treatment the disease itself or treatment differences should be
considered in the choice of intervention Even chemotherapy drugs should be taken into
consideration For example a period of general steroid treatment can increase patientsrsquo
fatigue In those studies of children with cancer few studies looked solely at one type of
cancer most studies included a variety of cancer patients Furthermore most studies do
not clearly explain the stage of the disease or course of treatment and most do not
include treatment variables in the control group Moreover children with cancer may
have different levels of physical function
2 Research design The sample size Currently there are few studies with large sample size and a rigorous
RCT design due to the small number of papers available for analysis The sample size
included in our studyrsquos data analysis is between 20 and 42 people this small sample size
will affect the power available to evaluate outcome variables
Although most of the non-pharmacological interventions still use exercise and physical
activity and these studies overall show better results for fatigue as compared with
controls more research is still needed to further confirm the efficacy of these findings
662
30
The dropout rate in the evaluated research varies a great deal ranging from 5 to 45
these dropout rates may result from the characteristics of the research subjects or the
lengthy time involved in participating in these studies The research data with a high
turnover rate might not reflect the actual outcomes of participation in exercise and the
quality of the research contained in articles with high subject turnover rates may be
lower
Exercise doses and time The exercise doses needed to reduce fatigue cannot be
determined additionally the amount of exercise completed by the patient is also
inconsistent interventions vary between 2-3 times per week and two times a day and
exercise duration varies between 10 and 45 minutes each time Furthermore the study
interventions vary in length between a couple of days and a long period of 16 weeks The
data collection times are different some were measured 12 weeks after the intervention
began some were measured during the 6 weeks of intervention some were measured
three months after the intervention was finished and some were measured after one
year
In addition disease-related symptoms decrease childrenrsquos willingness to participate in
exercise interventions inappropriate exercise intervention programs may actually
increase childrens fatigue In addition the children in the study are still developing
physically it is important to consider ways to design an interesting exercise intervention
to increase the compliance of patients in order to improve the effectiveness Although
intervention programs in the hospital or in a community sports center can improve the
effectiveness because they provide supervision the feasibility of these programs is
questionable However if the program is home-based the children need to be
supervised by parents in order to improve their compliance in doing the exercises
Furthermore regarding the nature of the intervention the results from this study indicate
that the researched non-pharmacological interventions include the following exercise
training programs physical activity massage therapy and health education interventions
However according to the National Comprehensive Cancer Network 1 clinical guidelines
663
31
for cancer non-drug measures for cancer fatigue can be separated into five categories
(1) activity enhancement (2) psychosocial interventions such as cognitive behavioral
therapy (CBT) stress management relaxation techniques and support groups (3)
attention-restoring therapy (4) nutritional consultation and (5) cognitive behavioral
therapy specifically targeting sleep disturbance Researchers have also suggested that
psychosocial interventions should be included in the future research for children with
cancer-related fatigue 22
(2) The measurement tools in the study The assessment of fatigue can be
one-dimensional or multidimensional One-dimensional assessment can help understand
the severity of fatigue symptoms however multidimensional scales are often more
credible Therefore when measuring cancer-related fatigue researchers should consider
whether there is a uniform definition of fatigue or a standardized tool for measuring
fatigue in order to facilitate further systematic meta-analyses and further develop the
clinical care guidelines
Limitations of the review The present review has some potential limitations First the low methodological quality
may influence the result Although exercise intervention seems promising quality of the
RCTs was generally quite low Future studies require better design and reporting if
methodological issues to establish evidence-based nonpharmcologic intervention
Second the identified studies covered only a limited types of nonpharmcological
intervention especially in exercise intervention The guidelines for cancer-related fatigue
in NCCN (2011)1 referred to more interventions than the ones included in this review
such as cognitive behavioral therapy and nutrition consultation Thirdly the small sample
size and effect size could be potentially having led to underpowered approach for
detecting the effects on fatigue Therefore we recommend that as research continues to
grow a re-analysis can be undertaken Fourthly Combining data in meta analysis from
664
32
studies where the ages were quite different is a potential source of heterogeneity and
may affect the interpretation of the results
Conclusion At present clinical treatment is widely used for cancer patients However child and
adolescent cancer patients often experience various side effects which cause short-term
or long-term discomfort both physically and psychologically In particular with the
increasing cure rate cancer related fatigue during or after treatment has become an
important issue This study result provided positive effect of exercise intervention on
general fatigue
Implications for practice The results of this systematic review and meta-analysis show that exercise interventions
can effectively improve the level of general fatigue In particular although the articles
were self-reported feasibility studies their results all indicate that exercise interventions
for fatigue are feasible and safe there was no conclusion to be made for the use of
massage therapy or health education measures because there was only one article for
each of these interventions
Recommendations for practice
Cancer-related fatigue is one of the most severe and frequent symptoms by pediatric
oncology children and adolescent suffered during treatment and the symptom existed
even after treatment has ended Until now no golden standard of treatment to fatigue is
established The findings call for more attention to how to reduce patientrsquos levels of
fatigue Based on the available information evaluated in this review the following
recommendations for practice are provided
665
33
bull For children aged 7 to 18 who has cancer (eg Lymphoma leukemia CNS tumor
germ cell tumor) an effective progressive aerobic exercise program is recommended to
be at least 2-3 times per week 20 to 45 minute for each session and last for 6-16 weeks
in order to reduce their general fatigue (tiredness physically weakness) In addition
adults should be involved in accompanying children while they are performing physical
exercise of which should be able to improve the adherence rate (level 2 ) ( Grade of
recommendation A)
bull For children aged 7 to 18 who has cancer (eg Lymphoma leukemia CNS tumor
germ cell tumor) an progressive aerobic exercise program will not be effective to reduce
their sleep andor rest (sleeping or resting a lot) or cognitive fatigue (problems with
thinking quickly or problems with remembering) (level 2 ) ( Grade of recommendation C)
bull Nursing interventions in educating treatment of fatigue include information about
activity nutrition energy preservation consulting and providing a useful fatigue
handbook will benefit those children who are 7 to 12 years have a new diagnosis of ALL
AML or lymphoma and receive for the first time after being diagnosed a 7- to 10-day
chemotherapy treatment (level 2) ( Grade of recommendation A)
bull A 4-week massage therapy program (the therapists massage childrenrsquos back legs
arms stomachchest and face) is not effective for children who are aged 7 to 18 and
have acute lymphoblastic leukemia brain tumors lymphoma rhabdomyosarcoma
Wilms tumor or Ewing sarcoma(level 2)( Grade of recommendation C)
bull Using a 12-week aerobic and strength exercise (45-min exercise sessions twice a
week) is not effective for children who are aged 6-14 and survived acute lymphoblaststic
leukemia age from 6 to 14(level 2) ( Grade of recommendation C)
bull Using a physical activity intervention (30minutestwice daily for 2-4days) is not
effective for children who are 7 to 18 years of age with soild tumor or AML(level 2)
( Grade of recommendation C)
666
34
Implications for research According to this systematic review and meta-analysis results there are suggestions to
improve the effectiveness of future research on non-pharmacological interventions for
children and young peoplersquos cancer-related fatigue
As the majority of included non-pharmacological interventions for the fatigue of cancer
patients consist of exercise programs future research should also consider various
non-pharmacological interventions in order to understand the effectiveness of different
methods
Regarding the exercise intervention methods and studies should consider multiple
factors including the age or personal condition of the subject the disease stage and the
amount of daily activities Studies should use design prescriptions (eg frequency
intensity duration and type of exercise) and consider the adherence to the measures in
order to enhance the study strength
In measuring the results of non-pharmacological interventions there should be standard
definitions or standard measurement tools to facilitate the following systematic review
and meta-analysis that can subsequently be developed into clinical care guidelines
Reviewing the effectiveness of the current non-pharmacological management of children
and adolescent cancer patients there is still a lack of rigorous RCT research Limited by
the characteristics of cancer there is still a lack of large sample sizes
Potential conflicts of interest There is no conflict of interest
Acknowledgements
Thank you to Dr Rie Konno Research Fellow Joanna Briggs Institute for her help in
assessing studies
667
35
References 1 National Comprehensive Cancer Network( NCCN) in USA NCCN clinical practice
guideline in oncology cancer-related fatigue 2011 2 Ekti Genc R amp Conk Z Impact of effective nursing interventions to the fatigue
syndrome in children who receive chemotherapy Cancer Nursing 200831(4)312-317
3 Childhood Cancer Foundation of ROC (2009March) The classification of diseases
and age sex statistical tables of case Childhood Cancer Foundation of ROC newsletter103105-106
4 Department of Health Executive Yuan ROC (TAIWAN)(2009 March 20)2009 cause of death statistic Health and National Health Insurance Annual Statistics Information Service 2010 June 28Available httpwwwdohgovtwstatisticdatavital statists9898health statistic--lifepdf
5 Chang TK (2007December 8) Common childhood cancer and its treatment Status
Childhood Cancer Foundation of ROC (TAIWAN) 2010 September 23 Available httpwwwccfrocorgtwchildchild_events_readphpe_id=45
6 Hockenberry MJ amp Wilson D Wongs nursing care of infants and children (8th ed) St
Louis MO Mosby 2007
7 Post-White J Fitzgerald M Savik K Hooke MC Hannahan AB amp Sencer SF
Massage therapy for children with cancer Journal of Pediatric Oncology Nursing 2009 26(1)16-28
8Chiang YC Yeh CH Wang WKamp Yang CP The experience of cancer-related fatigue
in Taiwanese children European Journal of Cancer Care 2009 18(1)43-49 9Langeveld NE Grootenhuis M A Voute P A de Haan RJ amp van den Bos C No excess
fatigue in young adult survivors of childhood cancer European Journal of Cancer 200339(2)204-214
10Piper BF Lindsey AM amp Dodd MJ Fatigue mechanisms in cancer patients
developing nursing theory Oncology Nursing Forum 1987 14(6)17-23 11Nail LM amp Winningham ML Fatigue In S L Groenwald M H Forgge M Goodman
amp C H Yarbro (Eds) Cancer Nursing Principles and practice (4 th ed) Boston Jones and Bartlett1997
12Irvine D Vincent L Graydon JE Bubela N amp Thompson L The prevalence and
correlates of fatigue in patients receiving treatment with chemotherapy and
668
36
radiotherapy A comparison with the fatigue experienced by healthy individuals Cancer Nursing 199417(5)367-378
13Hinds PS amp Hockenberry-Eaton M Developing a research program on fatigue in
children and adloescents diagnosed with cancer Journal of Pediatric Oncology Nursing 200118(2)3-12
14Aaronson LS Teel CS Cassmeyer V Neuberger GB Pallikkathayil L Pierce J Press
AN Williams DP amp Wingate A Defining and measuring fatigue Journal of Nursing scholarship 1999 31(1)45-50
15Yeh CH Wang CH Chiang YC Lin Lamp Chien LC Assessment of symptoms reported
by 10- to 18-year-old cancer patients in Taiwan 2009 38(5)738-746 16 Okuyama T Akechi T Kugaya A Okamura H Shima Yamp Maruguchi M
Development and validation of the cancer fatigue scale a brief three-dimensional self-rating scale for assessment of fatigue in cancer patients Journal of Pain amp Symptom Management 2000 19(1) 5-14
17Gibson F Mulhall AB Richardson A Edwards JL Ream E amp Sepion BJ A
phenomenologic study of fatigue in adolescents receiving treatment for cancer Oncology Nursing Forum200532(3)651-660
18Wolfe J Grier HE Klar N Levin SB Ellenbogen JMamp Salem-Schatz S et al
Symptoms and suffering at the end of life in children with cancer New England Journal of Medicine 2000342(5)326-333
19Whiting P Bagnall AM Sowden AJ Cornell JE Mulrow CD amp Ramirez G
Interventions for the treatment and management of chronic fatigue syndrome a systematic review JAMA the Journal of the American Medical Association 2001286(11)1360-1368
20 Kangas M Bovbjerg DHamp Montgomery G H Cancer-related fatigue a systematic
and meta-analytic review of non-pharmacological therapies for cancer patients Psychological Bulletin 2008134 (5)700-741
21Williams PD Schmideskamp J Ridder EL amp Williams AR Symptom monitoring and
dependent care during cancer treatment in children pilot study Cancer Nursing 200629(3)188-197
22Takken T van der Torre P Zwerink M Hulzebos EH Bierings M Helders PJMamp van
der Net J Development feasibility and efficacy of a community-based exercise training
669
37
program in pediatric cancer survivors Psycho-Oncology 200918(4)440-448
23Keats MR amp Culos-Reed SN A community-based physical activity program for
adolescents with cancer (project TREK) program feasibility and preliminary findings
Pediatric hematology and oncology 200830(4) 272-280
24Hinds PS Hockenberry M Rai SN Zhang L Razzouk B I Cremer L McCarthy K amp
Rodriguez-Galindo C Clinical field testing of an enhanced-activity intervention in
hospitalized children with cancer Journal of Pain amp Symptom Management 2007
33(6)686-697
25Chiang YC The effects of ldquo a home-based aerobic exercise interventionrdquo on fatigue
and cardiorespiratory fitness in children with acute lymphoblastic leukemia during the
maintenance stage of chemotherapy Unpublished thesis Taiwan Tao-Yuan 2007
26Langeveld N Ubbink M amp Smets E I dont have any energy The experience of
fatigue in young adult survivors of childhood cancer European journal of oncology
nursing 20004(1)20-28
27 Kisner C Colby L Therapeutic exercise Foundations and techniques 2nd ed Philadelphia PAFA Davies 2007
670
38
Appendix I JBI Critical Appraisal Checklist for Experimental studies
Author__________ Year_________ Record Number__________________
Questions 1 to 4 must be answered ldquoyesrdquo for study to be included in the metashyanalysis
1 Were the participants randomized to study groups
Yes No Not clear
2 Other than research intervention were participants in each groups treated the same
Yes No Not clear
3 Were the outcomes measured in the same manner for all participants
Yes No Not clear
4 Were groups comparable at entry
Yes No Not clear
5 Was randomization of participants blinded
Yes No Not clear
6 Were those assessing outcome blinded to treatment allocation (if outcome not objective such as survival or length of hospitalization)
Yes No Not clear
7 Was allocation to treatment groups concealed from the allocator
Yes No Not clear
8 Was an appropriate statistical analysis used
671
39
Yes No Not clear
9 Were outcomes measured in a reliable way
Yes No Not clear
10 Was there adequate followshyup of participants
Yes No Not clear
Summary
TOTAL
Yes No Not clear
DECISION
Use Reject
Narrative summary only Further information needed
COMMENTS
672
40
Appendix II JBI Data Extraction Tool for Quantitative Studies Authors and Year
Journal Title
Record NumberArticle Reference No
Reviewer
Method
Settings
Participants
Number of participants
Group A Group B Group C
Control Intervention 1 Intervention 2
Interventions
Group A
Control
Group B
Intervention 1
Group C
Intervention 2
Outcome measures
Definition
673
41
Other outcome measures
Outcome description ScaleMeasure
Results
Dichotomous Data
Outcome Control Group
Numbertotal number
Treatment Group
Numbertotal number
Continuous Data
Authorrsquos Conclusions
Comments
Outcome Control Group
Mean amp SD
Treatment Group
Mean amp SD
674
43
Appendix III Details of included studies (N=6)(2720212223) RefNo Author(s)
(years) Title Study question Research
method Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
22 Takken T van der Torre P Zwerink M Hulzebos E H Bierings M Helders P J Mamp van der Net J (2009)
Development feasibility and efficacy of a community-based exercise training program in pediatric cancer survivors
To develop a 12-week home-based exercise training program (comprising aerobic and strength exercises) for children who survived ALL and to study itrsquos feasibility and efficacy
Pre-post test design
No comparsion group
Survived ALL(N=9)ages 6-14 years
1anthropometry 2 muscle strength 3functional mobility 4cardio-pulmonary
exercise test 5Fatigue
1 Feasibility questionnaire 2 anthropometry electronic scale and a wallmounted stadiometerHarpenden skin fold calipers 3 muscle strength handheld dynamometer 4functional mobility Timed Up
and Go test (TUG) 5cardio-pulmonary exercise test electronically braked cycle ergometer 6Fatigue(mean)CSI-20 (subjective experience of fatigueconcentrationmotivationphysical activity)
112-week exercise training program
2 Patients were assessed before (T0) and after (T1) 12 weeks of training
1 muscle strength execapacity functional moand fatigue showed nosignificant differences between pre(meanplusmnSD415plusmn147) and post training(meanplusmnSD3687)
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
7 Post-White J Fitzgerald M Savik K Hooke M C Hannahan A B amp Sencer S F (2009)
Massage therapy for children with cancer
To determine whether 4 weekly sessions of massage compared with 4 quiet-time control conditions would reduce anxiety cortisol levels fatigue nausea and pain in children with cancer undergoing chemotherapy and would reduce anxiety fatigue and mood disturbance in a parent
2-period crossover design (Randomized)
quiet-time
control
sessions
Children with cancer 1 to 18 years of age Twenty-three childrenparent dyads were enrolled 17 completed all data points
children 1relaxation 2symptoms 3 fatigue
parents
1anxiety 2 fatigue
children 1relaxation (heart and respiratory rates blood pressure and salivary cortisol level)
2symptoms (pain nausea anxiety 3 fatigue 1-2y3-6yLansky Play Performance Scale (PPS) 7-13y
1 4 weekly massage (MT) sessions alternated with 4 weekly quiet-time(QT) control sessions
2 children included presession and postsession vital signs (heart rate respiratory rate blood pressure) and self-report (parent proxy report for age 1-2 years) of pain nausea and anxiety Fatigue was measured before sessions 1 and 4 and at each follow-up Parent measures
included anxiety fatigue and mood states
1Massage was moreeffective than quiet tireducing heart rate inchildren anxiety in cless than age 14 yeaparent anxiety 2There were no sign
changes in blood pcortisol pain naufatigue (no state d
3 Children reported tmassage helped thebetter lessened theirand worries and hadlasting effects than q
675
44
14-18yChild Fatigue Scale (CFS) (frequency
intensity) 2 parents anxiety and fatigue
676
45
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
24 Hinds P S Hockenberry M Rai S N Zhang L Razzouk B I Cremer L McCarthy K amp Rodriguez-Galindo C (2007)
Clinical field testing of an enhanced-activity intervention in hospitalized children with cancer
To determine the feasibility of an
enhanced physical activity EPA intervention in children and adolescents hospitalized to receive chemotherapy for a solid tumor or AML and to assess the sleep and fatigue outcomes of the intervention using two different statistical approaches to analyze the longitudinal symptom data
randomized prospective two-site and two-group pilot study
Standard care Twenty nine patients (25 with a solid tumor and 4 with AML)ages 7-18 years
1 sleep duration 2 sleep efficiency 3 fatigue
1sleep duration sleep efficiency The
Wrist Actigraph The Daily Sleep Diary-Parent 2 fatigue (mean) The Fatigue Scale(FS-C) for 7-12 (intensity) The Fatigue Scale(FS-A) for 13-18 The Fatigue Scale Parent Version (FS-P) The Fatigue Scale Staff Version (FS-S)
1enhanced physical activity (EPA) (hospital-based 30 minutes
twice daily for 2-4 days) 2 T0On the day of admission
(Day 0 or baseline)patient and parents completed the fatigue instruments and a team member applied the actigraph Patients wore the wrist actigraph T1 from Day 0 to 2 or 3 consecutive days (Days 0e3) In addition the patient same parent and staff nurses completed the daily sleep and fatigue reports in the late afternoons of Days 1-3
1 ANOVA model slesignificantly more the experimental athe control arm whdifferences from bsleep efficiency vaaveraged and com
2 The patient-reported mean fatigue scoresarms were higher amadolescents than for
3 The mixed model anarevealed no significandifferences in patientfatigue between
the two study arms otime( no final result iSD only give mixed result)
677
46
23 Keats M
R amp Culos-Reed S N (2008)
A community-based physical activity program for adolescents with cancer (project TREK) program feasibility and preliminary findings
To examine the
feasibility of a
theoretically-based
physical activity (PA)
intervention in
adolescents with
cancerand
examination of the
impact of the
program on
participant QOL
including social
emotional and
physical
well-being(including fatigue)
Repeat measures longitudinal design
No comparsion group
10 adolescents(Lymphoma(4)leukemia(4)CNS tumor(1)germ cell tumor(1)) ages 14-18 years
1physical fitness 2quality of life (QOL) 3PA behavior 4fatigue
1 Feasibility was assessed by participant recruitment attendance and adherence
2physical fitness Fitnessgram 3quality of life (QOL) Pediatric Quality of Life Inventory (PedsQL) 4PA behavior leisure score index (LSI) 5fatigue (mean) pediatric Quality of life
Multidimensional Fatigue Scale (Peds QL-MFS)
(Generalsleepcognitive fatigue)
116week physical activity (PA)
2 total PA physical fitness and overall QOL was assessed at 5 different intervals T0 preintervention (baseline) T1midintervention (after the
first 8 wk) T2 postintervention
(16 wk) T3 3-months
postintervention T4 1-year poststudy
initiation
1 from baseline -wkssig Improvementstotal PA physfitness and Qgeneral fatigue(meanplusmnSD 796plusmn135)
2 from baseline to 3FUsig Improvin general fatigue(meanplusmnSD824plusmn131)slefatigue(meanplusmnSD755plusmn191)totafatigue(meanplusmnSD778plusmn150)
3at 1 years FUsImprovements in sleeprest fatigue(meanplusmnSD725plusmn203)total (meanplusmnSD 763plusmn
678
47
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
2 Gene R E amp Conk Z (2008)
Impact of Effective Nursing Interventions to the Fatigue Syndrome in Children Who Receive Chemotherapy
1 to examine the effects of an effective nursing intervention to the fatigue syndrome of children 7 to 12 years of age who receive chemotherapy 2Tto examine the relationship between fatigue and demographic variables (age sex) diagnoses ([ALL AML] lymphoma) and therapy-related variables (eg level of hemoglobin
experimental randomized controlled study
Routine nursing care
A total of 60 children who are 7-12 years of age(a new diagnosis of ALL AML or lymphoma and receiving for the first time after being diagnosed a 7- to 10-day chemotherapy treatment )
fatigue The Fatigue Scale(FS-C) for 7-12 (intensity)
The Fatigue Scale Parent Version (FS-P)
1 effective nursing interventions(45- 60mdaya week)education about the fatigue with the chemotherapy and fatigue handbook 2 T1 After a 7-day period the children
and parent were evaluated with the Fatigue Scale
1The difference betwthe 2 mean values wafound to be statisticallsignificant 2 statistically significadifference was found between the Fatigue Scale-Child mean scothe experimental (272the control group (4213)children
679
48
25 Chiang et
al(2007)
The effects of ldquo a home ndashbased aerobic exercise interventionrdquo on fatigue and cardiorespiratory fitness in children with Acute Lymphoblastic Leukemia during the maintenance stage of chemotherapy
To examine the effect of ldquo a home ndashbased aerobic exercise interventionrdquo on fatigue and cardiorespiratory fitness in children with Acute Lymphoblastic Leukemia during the maintenance stage of chemotherapy
Quasi-experi -mental
Routine
nursing care
14 pediatric oncology patients in the experimental group and 10 in control group who were matched by age and sex ages7-18 years
1Cardiorespiratory fitness
2Fatigue
1Cardiorespiratory fitness Physical Activity Recall
VO2maxHR peak 6MWT
2 Fatigue PedsQL-MFS(Generalsleepcognitive fatigue)
1A six-week home-based aerobic exercise intervention 2 8 time points T0 baseline T1-T6 every week during the
intervention(6 weeks) T7 post intervention T8 follow-up (one month after
the end of the home-based exercise program)
1 For intent-to ndash treatthe findings indicated are no intervention efftime differences by anon the subscale of fat2 For per-protocol angeneral fatigue( mean422plusmn402) was the osubscale that was siglower for children whothe exercise interventthose in control groupfollow-up assessmentmonth after the compintervention) 3 The VO2peak are significantly improvingexperimental group atbaseline- and post-intassessment The VO2was significantly highechildren who were in experimental group thcontrol subjects at post-intervention assefor the per-protocol an
680
49
Appendix IV Instrument used to measure fatigue
Name Instrument
developers
Description Used in
age in
ref
Reliability
Consistency of
instrument
Checklist Individual Strength
(CIS)22
Vercoulen et
al1996
20 items using 7-point Likert scale of
fatigue To measure four aspects of
fatiguesubjective experience
contractionmotivation physical
Activity
6-14 Not reported
Child Fatigue Scale (CFS)7 Hockenberry
et al2003
14 items 2 part questionnaire frequency
(yes or no) 5-point Likert scale of the
intensity of any yes responses
7-13
14-18 α073-o84
The Fatigue Scale for 7-12
year Olds (FS-C)224
Hockenberry
et al
14 items provide a fatigue intensity score
5-point Likert scale
7-12 αo84
The Fatigue Scale for 13-18
year Olds (FS-A)24
Hockenberry
et al
14 items provide a fatigue intensity score
5-point Likert scale
13-18 α076-o96
Pediatric Quality of life
Multidimensional Fatigue
Scale (Peds QL-MFS)2325
Varni2002 18 items to measure three aspects of
fatigueGeneralsleepcognitive
14-18 Not reported
681
50
Appendix V Excluded studies and reasons for exclusion
Baggott C Dodd M Kennedy C Marina N Miaskowski C Multiple Symptoms in Pediatric Oncology
Patients A Systematic Review Journal of Pediatric Oncology Nursing 2009 Nov-Dec 27(6)
325-339
Reason for exclusion Not outcome of interest
Barlow JH Ellard DR Psycho-educational interventions for children with chronic disease parents and
siblings an overview of the research evidence base Care Health amp Development 2004 Nov
30(6)637-45
Reason for exclusion Not outcome of interest
Bedider S Moyer CA Randomized controlled trials of pediatric massage A review Evid Based
Complement Alternat Med 2007 Mar 4(1)23-34 Epub 2006 Nov 3
Reason for exclusion Not outcome of interest
de Nijs EJ Ros W Grijpdonck MH Nursing intervention for fatigue during the treatment for cancer Cancer
Nursing 2008 31(3)191-206
Reason for exclusion Not population of interest
Edwards JL Gibson F Richardson A Sepion B Ream E Fatigue in adolescents with and following a
cancer diagnosis developing an evidence base for practice European Journal of Cancer 2003
Dec 39(18)2671-80
Reason for exclusion Not experimental or quasi-experimental study
Hinds PS Hockenberry-Eatan M Developing a research program on fatigue in children and adolescents
diagnosed with cancer Journal of Pediatric Oncology Nursing 2001 Mar-Apr 18(2 Suppl
1)3-12
Reason for exclusion Not experimental or quasi-experimental study
Hockenberry-Eaton M Hinds PS Alcoser P ONeill JB Euell K Howard V Gattuso J Taylor J Fatigue in
Children and Adolescents With Cancer Journal of Pediatric Oncology Nursing 1998 July
15(3)172-182
Reason for exclusion Not experimental or quasi-experimental study
Jean-Pierre P Mustian K Kohli S Roscoe JA Hickok JT Morrow GR Community-based clinical oncology
research trials for cancer-related fatigue The Journal of Supportive Oncology 2006 Nov-Dec
4(10)511-6
682
51
Reason for exclusion Not population of interest
Kangas M Bovbjerg DH Montgomery GH Cancer-Related Fatigue A Systematic and Meta-Analytic
Review of Non-Pharmacological Therapies for Cancer Patients Psychological Bulletin 2008 Sep
134(5)700-41
Reason for exclusion Not population of interest
Lotfi-Jam K Carey M Jefford M Schofield P Charleson C Aranda S Nonpharmacologic strategies for
managing common chemotherapy adverse effects A systematic review Journal of Clinical
Oncology 2008 Dec 1 26(34)5618-29 Epub 2008 Nov 3
Reason for exclusion Not outcome of interest
Marchese VG Chiarello LA Lange BJ Effects of physical therapy intervention for children with acute
lymphoblastic leukemia Pediatr Blood Cancer 2004 Feb42(2)127-33
Reason for exclusion Not outcome of interest
Meeske KA Siegel SE Globe DR Mack WJ Bernstein L Prevalence and correlates of fatigue in
long-term survivors of childhood leukemia Journal of Clinical Oncology 2005 Aug 20
23(24)5501-10
Reason for exclusion Not intervention study
Minton O Richardson A Sharpe M Hotopf Stone P A systematic review and meta-analysis of the
pharmacological treatment of cancer-related fatigue J Natl Cancer Inst 2008 Aug 20
100(16)1155-66 Epub 2008 Aug 11
Reason for exclusion Not population and intervention of interest
Mustian KM Morrow GR Carroll JK Figueroa-Moseley CD Pascal JP Williams GC Integrative
nonpharmacologic behavioral interventions for the management of Cancer-Related fatigue The
Oncologist 2007 12(1)52-67
Reason for exclusion Not population of interest
Neill J Belan I Ried K Effectiveness of non-pharmacological interventions for fatigue in adults with
multiple sclerosis rheumatoid arthritis or systemic lupus erythematosus a systematic review
Journal of Advanced Nursing 2006 Dec 56(6)617-35
Reason for exclusion Not population of interest
Rheingans JI A systematic review of nonpharmacologic adjunctive therapies for symptom management
Journal of Pediatric Oncology Nursing 2007 24(2) 81-94
683
52
Reason for exclusion Not outcome of interest
Rheingans JI Pediatric oncology nursesrsquo management of patients symptoms Journal of Pediatric
Oncology Nursing 2008 Nov 25(6) 303-11
Reason for exclusion Not outcome of interest
San Juan AF Fleck SJ Chamorro-Vintildea C Mateacute-Muntildeoz JL Moral S Peacuterez M Cardona C Del Valle MF
Hernaacutendez M Ramiacuterez M Madero L Lucia A Effects of an intrahospital exercise program
intervention for children with leukemia Medicine amp Science in Sports amp Exercise 2007 Jan
39(1)13-21
Reason for exclusion Not outcome of interest
Sanford SD Okuma JO Pan J Srivastava DK West N Farr L Hinds PS Gender differences in sleep
fatigue and daytime activity in a pediatric oncology sample receiving dexamethasone Journal of
Pediatric Psychology 2008 Apr 33(3)298-306 Epub 2007 Nov 17
Reason for exclusion Not experimental or quasi-experimental study
Schmitz KH Holtzman J Courneya KS Macircsse LC Duval S Kane R Controlled physical activity trials in
cancer survivors a systematic review and meta-analysis Cancer Epidemiol Biomarkers Prev
2005 Jul 14(7)1588-95
Reason for exclusion Not population of interest
van Brussel M Takken T Lucia A van der Net J Helders PJ Is physical fitness decreased in survivors of
childhood leukemia A systematic review Leukemia 2005 Jan 19(1)13-7
Reason for exclusion Not population of interest
Whiting P Bagnall AM Snowden AJ Cornell JE Mulrow CD Ramirez G Interventions for the treatment
and management of chronic fatigue syndrome JAMA 2001 Sep 19 286(11)1360-8
Reason for exclusion Not intervention of interest
Whitsett SF Gudmundsdottir M Davies B McCarthy P Friedman D Chemotherapy-related fatigue in
childhood cancer correlates consequences and coping strategies Journal of Pediatric
Oncology Nursing 2008 Mar-Apr 25(2)86-96 Epub 2008 Feb 29
Reason for exclusion Not experimental or quasi-experimental study
Winner C Muumlller C Hoffmann C Boos J Rosenbaum D Physical activity and childhood cancer Pediatr
Blood Cancer 2010 Apr 54(4)501-10
Reason for exclusion Not research study
684
53
Wu M Hsu L Zhang B Shen N Lu H Li S The experiences of cancer-related fatigue among Chinese
children with leukaemia A phenomenological study Journal of Nursing Studies 2010 Jan
47(1)49-59 Epub 2009 Aug 25
Reason for exclusion Not experimental or quasi-experimental study
Yeh CH Chiang YC Lin L Yang CP Chien LC Weaver MA Chuang HL Clinical factors associated with
fatigue over time in paediatric oncology patients receiving chemotherapy British Journal of
Cancer 2008 Jul 8 99(1)23-9 Epub 2008 Jun 24
Reason for exclusion Not experimental or quasi-experimental study
685
27
weekly quiet-time (QT) control sessions There were no significant changes in fatigue in
children over the 4-week MT or QT conditions either independently (change over time) or
when we compared fatigue by condition
The lack of effect of massage on fatigue may be the difficulty some children had in
differentiating fatigue from being relaxed underscores the challenge of measuring fatigue
in children Some children interpreted being tired or relaxed as having greater fatigue
because they felt like lying around and sleeping or felt unmotivated to do their usual
activities all measures of fatigue in the instrument used in the study
Hinds et al24conducted a prospective two-site randomized controlled pilot study to
assess the feasibility of an enhanced physical activity (EPA) intervention in hospitalized
children and adolescents receiving treatment for a solid tumor or for acute myeloid
leukemia (AML) Twenty-nine patients (25 with a solid tumor and 4 with AML) participated
age range from 736 to 1816 (mean 1248 y) The EPA intervention selected was
pedaling a stationary bicycle-style exerciser (Chattanooga Peddler Deluxe Bio-Teck
Medical Memphis TN) for 30 minutes twice daily for 2 to 4 days of hospitalization The
mixed model analysis revealed no significant differences in patient reports of fatigue
between the two study arms or over time
Genc et al2 conducted a RCT involving children with cancer who are 7 to 12 years of age
and receiving chemotherapy treatment to determine the impact of educational
intervention by nurses on decreasing the fatigue syndrome The research sample was
composed of a total of 60 children with cancer with 30 children being included in the
660
28
experimental group (mean age 923)and 30 children included in the control group (mean
age 937) with their mothers In the experimental group after the 7th to 10th day of the
chemotherapy treatment throughout a week the researcher conducted the nursing
interventions every day for 45 to 60 minutes In the control group routine nursing
interventions were carried out The experimental group received education about the
fatigue with the chemotherapy and fatigue handbook was given which was developed by
the authors Children and mothers were consulted for including activities that could
decrease fatigue which were described as effective interventions A statistically
significant difference was found between the Fatigue Scale-Child mean scores of the
experimental (2723) and the control group (4213) The results suggest that fatigue of
children with cancer can be reduced by implementing appropriate nursing interventions
(t=567 Plt00)
Discussion The purpose of this systematic review was to determine the effectiveness of
non-pharmacological interventions specifically targeting fatigue for children and
adolescents with cancer undergoing chemotherapy or after receiving chemotherapy
Included articles about the effectiveness of non-pharmacological interventions for
children and adolescents with cancer were published between the years of 2007 and
2009 Although interventions for cancer fatigue for adults have been extensively studied
it can be seen from either the title of the paper or related content that an intervention
study on children was a pilot study or a feasibility study Representing a field in its early
stage these studies show that the fatigue issues with young cancer patients have only
recently been taken seriously
661
29
The results of our meta-analysis include measurement of the four performance indicators
fatigue and general fatigue sleep rest fatigue and cognitive fatigue The results show
that there is a statistically significant difference only in the domain of general fatigue
using an exercise intervention for children with cancer can improve the degree of fatigue
with the effect size reaching 0671 Other results do not indicate significant differences
The reasons may include the following
1 Characteristics of the cancer The exhaustion from cancer occurs not only during cancer treatment but also in during
long-term survival a time during which patients may continue to be affected by this
symptom 8 26 Therefore when using intervention measures to improve fatigue
circumstances should be considered such as the process of the treatment and the course
or stage of the disease Because cancer patients will experience different forms of
treatment or courses of treatment the disease itself or treatment differences should be
considered in the choice of intervention Even chemotherapy drugs should be taken into
consideration For example a period of general steroid treatment can increase patientsrsquo
fatigue In those studies of children with cancer few studies looked solely at one type of
cancer most studies included a variety of cancer patients Furthermore most studies do
not clearly explain the stage of the disease or course of treatment and most do not
include treatment variables in the control group Moreover children with cancer may
have different levels of physical function
2 Research design The sample size Currently there are few studies with large sample size and a rigorous
RCT design due to the small number of papers available for analysis The sample size
included in our studyrsquos data analysis is between 20 and 42 people this small sample size
will affect the power available to evaluate outcome variables
Although most of the non-pharmacological interventions still use exercise and physical
activity and these studies overall show better results for fatigue as compared with
controls more research is still needed to further confirm the efficacy of these findings
662
30
The dropout rate in the evaluated research varies a great deal ranging from 5 to 45
these dropout rates may result from the characteristics of the research subjects or the
lengthy time involved in participating in these studies The research data with a high
turnover rate might not reflect the actual outcomes of participation in exercise and the
quality of the research contained in articles with high subject turnover rates may be
lower
Exercise doses and time The exercise doses needed to reduce fatigue cannot be
determined additionally the amount of exercise completed by the patient is also
inconsistent interventions vary between 2-3 times per week and two times a day and
exercise duration varies between 10 and 45 minutes each time Furthermore the study
interventions vary in length between a couple of days and a long period of 16 weeks The
data collection times are different some were measured 12 weeks after the intervention
began some were measured during the 6 weeks of intervention some were measured
three months after the intervention was finished and some were measured after one
year
In addition disease-related symptoms decrease childrenrsquos willingness to participate in
exercise interventions inappropriate exercise intervention programs may actually
increase childrens fatigue In addition the children in the study are still developing
physically it is important to consider ways to design an interesting exercise intervention
to increase the compliance of patients in order to improve the effectiveness Although
intervention programs in the hospital or in a community sports center can improve the
effectiveness because they provide supervision the feasibility of these programs is
questionable However if the program is home-based the children need to be
supervised by parents in order to improve their compliance in doing the exercises
Furthermore regarding the nature of the intervention the results from this study indicate
that the researched non-pharmacological interventions include the following exercise
training programs physical activity massage therapy and health education interventions
However according to the National Comprehensive Cancer Network 1 clinical guidelines
663
31
for cancer non-drug measures for cancer fatigue can be separated into five categories
(1) activity enhancement (2) psychosocial interventions such as cognitive behavioral
therapy (CBT) stress management relaxation techniques and support groups (3)
attention-restoring therapy (4) nutritional consultation and (5) cognitive behavioral
therapy specifically targeting sleep disturbance Researchers have also suggested that
psychosocial interventions should be included in the future research for children with
cancer-related fatigue 22
(2) The measurement tools in the study The assessment of fatigue can be
one-dimensional or multidimensional One-dimensional assessment can help understand
the severity of fatigue symptoms however multidimensional scales are often more
credible Therefore when measuring cancer-related fatigue researchers should consider
whether there is a uniform definition of fatigue or a standardized tool for measuring
fatigue in order to facilitate further systematic meta-analyses and further develop the
clinical care guidelines
Limitations of the review The present review has some potential limitations First the low methodological quality
may influence the result Although exercise intervention seems promising quality of the
RCTs was generally quite low Future studies require better design and reporting if
methodological issues to establish evidence-based nonpharmcologic intervention
Second the identified studies covered only a limited types of nonpharmcological
intervention especially in exercise intervention The guidelines for cancer-related fatigue
in NCCN (2011)1 referred to more interventions than the ones included in this review
such as cognitive behavioral therapy and nutrition consultation Thirdly the small sample
size and effect size could be potentially having led to underpowered approach for
detecting the effects on fatigue Therefore we recommend that as research continues to
grow a re-analysis can be undertaken Fourthly Combining data in meta analysis from
664
32
studies where the ages were quite different is a potential source of heterogeneity and
may affect the interpretation of the results
Conclusion At present clinical treatment is widely used for cancer patients However child and
adolescent cancer patients often experience various side effects which cause short-term
or long-term discomfort both physically and psychologically In particular with the
increasing cure rate cancer related fatigue during or after treatment has become an
important issue This study result provided positive effect of exercise intervention on
general fatigue
Implications for practice The results of this systematic review and meta-analysis show that exercise interventions
can effectively improve the level of general fatigue In particular although the articles
were self-reported feasibility studies their results all indicate that exercise interventions
for fatigue are feasible and safe there was no conclusion to be made for the use of
massage therapy or health education measures because there was only one article for
each of these interventions
Recommendations for practice
Cancer-related fatigue is one of the most severe and frequent symptoms by pediatric
oncology children and adolescent suffered during treatment and the symptom existed
even after treatment has ended Until now no golden standard of treatment to fatigue is
established The findings call for more attention to how to reduce patientrsquos levels of
fatigue Based on the available information evaluated in this review the following
recommendations for practice are provided
665
33
bull For children aged 7 to 18 who has cancer (eg Lymphoma leukemia CNS tumor
germ cell tumor) an effective progressive aerobic exercise program is recommended to
be at least 2-3 times per week 20 to 45 minute for each session and last for 6-16 weeks
in order to reduce their general fatigue (tiredness physically weakness) In addition
adults should be involved in accompanying children while they are performing physical
exercise of which should be able to improve the adherence rate (level 2 ) ( Grade of
recommendation A)
bull For children aged 7 to 18 who has cancer (eg Lymphoma leukemia CNS tumor
germ cell tumor) an progressive aerobic exercise program will not be effective to reduce
their sleep andor rest (sleeping or resting a lot) or cognitive fatigue (problems with
thinking quickly or problems with remembering) (level 2 ) ( Grade of recommendation C)
bull Nursing interventions in educating treatment of fatigue include information about
activity nutrition energy preservation consulting and providing a useful fatigue
handbook will benefit those children who are 7 to 12 years have a new diagnosis of ALL
AML or lymphoma and receive for the first time after being diagnosed a 7- to 10-day
chemotherapy treatment (level 2) ( Grade of recommendation A)
bull A 4-week massage therapy program (the therapists massage childrenrsquos back legs
arms stomachchest and face) is not effective for children who are aged 7 to 18 and
have acute lymphoblastic leukemia brain tumors lymphoma rhabdomyosarcoma
Wilms tumor or Ewing sarcoma(level 2)( Grade of recommendation C)
bull Using a 12-week aerobic and strength exercise (45-min exercise sessions twice a
week) is not effective for children who are aged 6-14 and survived acute lymphoblaststic
leukemia age from 6 to 14(level 2) ( Grade of recommendation C)
bull Using a physical activity intervention (30minutestwice daily for 2-4days) is not
effective for children who are 7 to 18 years of age with soild tumor or AML(level 2)
( Grade of recommendation C)
666
34
Implications for research According to this systematic review and meta-analysis results there are suggestions to
improve the effectiveness of future research on non-pharmacological interventions for
children and young peoplersquos cancer-related fatigue
As the majority of included non-pharmacological interventions for the fatigue of cancer
patients consist of exercise programs future research should also consider various
non-pharmacological interventions in order to understand the effectiveness of different
methods
Regarding the exercise intervention methods and studies should consider multiple
factors including the age or personal condition of the subject the disease stage and the
amount of daily activities Studies should use design prescriptions (eg frequency
intensity duration and type of exercise) and consider the adherence to the measures in
order to enhance the study strength
In measuring the results of non-pharmacological interventions there should be standard
definitions or standard measurement tools to facilitate the following systematic review
and meta-analysis that can subsequently be developed into clinical care guidelines
Reviewing the effectiveness of the current non-pharmacological management of children
and adolescent cancer patients there is still a lack of rigorous RCT research Limited by
the characteristics of cancer there is still a lack of large sample sizes
Potential conflicts of interest There is no conflict of interest
Acknowledgements
Thank you to Dr Rie Konno Research Fellow Joanna Briggs Institute for her help in
assessing studies
667
35
References 1 National Comprehensive Cancer Network( NCCN) in USA NCCN clinical practice
guideline in oncology cancer-related fatigue 2011 2 Ekti Genc R amp Conk Z Impact of effective nursing interventions to the fatigue
syndrome in children who receive chemotherapy Cancer Nursing 200831(4)312-317
3 Childhood Cancer Foundation of ROC (2009March) The classification of diseases
and age sex statistical tables of case Childhood Cancer Foundation of ROC newsletter103105-106
4 Department of Health Executive Yuan ROC (TAIWAN)(2009 March 20)2009 cause of death statistic Health and National Health Insurance Annual Statistics Information Service 2010 June 28Available httpwwwdohgovtwstatisticdatavital statists9898health statistic--lifepdf
5 Chang TK (2007December 8) Common childhood cancer and its treatment Status
Childhood Cancer Foundation of ROC (TAIWAN) 2010 September 23 Available httpwwwccfrocorgtwchildchild_events_readphpe_id=45
6 Hockenberry MJ amp Wilson D Wongs nursing care of infants and children (8th ed) St
Louis MO Mosby 2007
7 Post-White J Fitzgerald M Savik K Hooke MC Hannahan AB amp Sencer SF
Massage therapy for children with cancer Journal of Pediatric Oncology Nursing 2009 26(1)16-28
8Chiang YC Yeh CH Wang WKamp Yang CP The experience of cancer-related fatigue
in Taiwanese children European Journal of Cancer Care 2009 18(1)43-49 9Langeveld NE Grootenhuis M A Voute P A de Haan RJ amp van den Bos C No excess
fatigue in young adult survivors of childhood cancer European Journal of Cancer 200339(2)204-214
10Piper BF Lindsey AM amp Dodd MJ Fatigue mechanisms in cancer patients
developing nursing theory Oncology Nursing Forum 1987 14(6)17-23 11Nail LM amp Winningham ML Fatigue In S L Groenwald M H Forgge M Goodman
amp C H Yarbro (Eds) Cancer Nursing Principles and practice (4 th ed) Boston Jones and Bartlett1997
12Irvine D Vincent L Graydon JE Bubela N amp Thompson L The prevalence and
correlates of fatigue in patients receiving treatment with chemotherapy and
668
36
radiotherapy A comparison with the fatigue experienced by healthy individuals Cancer Nursing 199417(5)367-378
13Hinds PS amp Hockenberry-Eaton M Developing a research program on fatigue in
children and adloescents diagnosed with cancer Journal of Pediatric Oncology Nursing 200118(2)3-12
14Aaronson LS Teel CS Cassmeyer V Neuberger GB Pallikkathayil L Pierce J Press
AN Williams DP amp Wingate A Defining and measuring fatigue Journal of Nursing scholarship 1999 31(1)45-50
15Yeh CH Wang CH Chiang YC Lin Lamp Chien LC Assessment of symptoms reported
by 10- to 18-year-old cancer patients in Taiwan 2009 38(5)738-746 16 Okuyama T Akechi T Kugaya A Okamura H Shima Yamp Maruguchi M
Development and validation of the cancer fatigue scale a brief three-dimensional self-rating scale for assessment of fatigue in cancer patients Journal of Pain amp Symptom Management 2000 19(1) 5-14
17Gibson F Mulhall AB Richardson A Edwards JL Ream E amp Sepion BJ A
phenomenologic study of fatigue in adolescents receiving treatment for cancer Oncology Nursing Forum200532(3)651-660
18Wolfe J Grier HE Klar N Levin SB Ellenbogen JMamp Salem-Schatz S et al
Symptoms and suffering at the end of life in children with cancer New England Journal of Medicine 2000342(5)326-333
19Whiting P Bagnall AM Sowden AJ Cornell JE Mulrow CD amp Ramirez G
Interventions for the treatment and management of chronic fatigue syndrome a systematic review JAMA the Journal of the American Medical Association 2001286(11)1360-1368
20 Kangas M Bovbjerg DHamp Montgomery G H Cancer-related fatigue a systematic
and meta-analytic review of non-pharmacological therapies for cancer patients Psychological Bulletin 2008134 (5)700-741
21Williams PD Schmideskamp J Ridder EL amp Williams AR Symptom monitoring and
dependent care during cancer treatment in children pilot study Cancer Nursing 200629(3)188-197
22Takken T van der Torre P Zwerink M Hulzebos EH Bierings M Helders PJMamp van
der Net J Development feasibility and efficacy of a community-based exercise training
669
37
program in pediatric cancer survivors Psycho-Oncology 200918(4)440-448
23Keats MR amp Culos-Reed SN A community-based physical activity program for
adolescents with cancer (project TREK) program feasibility and preliminary findings
Pediatric hematology and oncology 200830(4) 272-280
24Hinds PS Hockenberry M Rai SN Zhang L Razzouk B I Cremer L McCarthy K amp
Rodriguez-Galindo C Clinical field testing of an enhanced-activity intervention in
hospitalized children with cancer Journal of Pain amp Symptom Management 2007
33(6)686-697
25Chiang YC The effects of ldquo a home-based aerobic exercise interventionrdquo on fatigue
and cardiorespiratory fitness in children with acute lymphoblastic leukemia during the
maintenance stage of chemotherapy Unpublished thesis Taiwan Tao-Yuan 2007
26Langeveld N Ubbink M amp Smets E I dont have any energy The experience of
fatigue in young adult survivors of childhood cancer European journal of oncology
nursing 20004(1)20-28
27 Kisner C Colby L Therapeutic exercise Foundations and techniques 2nd ed Philadelphia PAFA Davies 2007
670
38
Appendix I JBI Critical Appraisal Checklist for Experimental studies
Author__________ Year_________ Record Number__________________
Questions 1 to 4 must be answered ldquoyesrdquo for study to be included in the metashyanalysis
1 Were the participants randomized to study groups
Yes No Not clear
2 Other than research intervention were participants in each groups treated the same
Yes No Not clear
3 Were the outcomes measured in the same manner for all participants
Yes No Not clear
4 Were groups comparable at entry
Yes No Not clear
5 Was randomization of participants blinded
Yes No Not clear
6 Were those assessing outcome blinded to treatment allocation (if outcome not objective such as survival or length of hospitalization)
Yes No Not clear
7 Was allocation to treatment groups concealed from the allocator
Yes No Not clear
8 Was an appropriate statistical analysis used
671
39
Yes No Not clear
9 Were outcomes measured in a reliable way
Yes No Not clear
10 Was there adequate followshyup of participants
Yes No Not clear
Summary
TOTAL
Yes No Not clear
DECISION
Use Reject
Narrative summary only Further information needed
COMMENTS
672
40
Appendix II JBI Data Extraction Tool for Quantitative Studies Authors and Year
Journal Title
Record NumberArticle Reference No
Reviewer
Method
Settings
Participants
Number of participants
Group A Group B Group C
Control Intervention 1 Intervention 2
Interventions
Group A
Control
Group B
Intervention 1
Group C
Intervention 2
Outcome measures
Definition
673
41
Other outcome measures
Outcome description ScaleMeasure
Results
Dichotomous Data
Outcome Control Group
Numbertotal number
Treatment Group
Numbertotal number
Continuous Data
Authorrsquos Conclusions
Comments
Outcome Control Group
Mean amp SD
Treatment Group
Mean amp SD
674
43
Appendix III Details of included studies (N=6)(2720212223) RefNo Author(s)
(years) Title Study question Research
method Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
22 Takken T van der Torre P Zwerink M Hulzebos E H Bierings M Helders P J Mamp van der Net J (2009)
Development feasibility and efficacy of a community-based exercise training program in pediatric cancer survivors
To develop a 12-week home-based exercise training program (comprising aerobic and strength exercises) for children who survived ALL and to study itrsquos feasibility and efficacy
Pre-post test design
No comparsion group
Survived ALL(N=9)ages 6-14 years
1anthropometry 2 muscle strength 3functional mobility 4cardio-pulmonary
exercise test 5Fatigue
1 Feasibility questionnaire 2 anthropometry electronic scale and a wallmounted stadiometerHarpenden skin fold calipers 3 muscle strength handheld dynamometer 4functional mobility Timed Up
and Go test (TUG) 5cardio-pulmonary exercise test electronically braked cycle ergometer 6Fatigue(mean)CSI-20 (subjective experience of fatigueconcentrationmotivationphysical activity)
112-week exercise training program
2 Patients were assessed before (T0) and after (T1) 12 weeks of training
1 muscle strength execapacity functional moand fatigue showed nosignificant differences between pre(meanplusmnSD415plusmn147) and post training(meanplusmnSD3687)
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
7 Post-White J Fitzgerald M Savik K Hooke M C Hannahan A B amp Sencer S F (2009)
Massage therapy for children with cancer
To determine whether 4 weekly sessions of massage compared with 4 quiet-time control conditions would reduce anxiety cortisol levels fatigue nausea and pain in children with cancer undergoing chemotherapy and would reduce anxiety fatigue and mood disturbance in a parent
2-period crossover design (Randomized)
quiet-time
control
sessions
Children with cancer 1 to 18 years of age Twenty-three childrenparent dyads were enrolled 17 completed all data points
children 1relaxation 2symptoms 3 fatigue
parents
1anxiety 2 fatigue
children 1relaxation (heart and respiratory rates blood pressure and salivary cortisol level)
2symptoms (pain nausea anxiety 3 fatigue 1-2y3-6yLansky Play Performance Scale (PPS) 7-13y
1 4 weekly massage (MT) sessions alternated with 4 weekly quiet-time(QT) control sessions
2 children included presession and postsession vital signs (heart rate respiratory rate blood pressure) and self-report (parent proxy report for age 1-2 years) of pain nausea and anxiety Fatigue was measured before sessions 1 and 4 and at each follow-up Parent measures
included anxiety fatigue and mood states
1Massage was moreeffective than quiet tireducing heart rate inchildren anxiety in cless than age 14 yeaparent anxiety 2There were no sign
changes in blood pcortisol pain naufatigue (no state d
3 Children reported tmassage helped thebetter lessened theirand worries and hadlasting effects than q
675
44
14-18yChild Fatigue Scale (CFS) (frequency
intensity) 2 parents anxiety and fatigue
676
45
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
24 Hinds P S Hockenberry M Rai S N Zhang L Razzouk B I Cremer L McCarthy K amp Rodriguez-Galindo C (2007)
Clinical field testing of an enhanced-activity intervention in hospitalized children with cancer
To determine the feasibility of an
enhanced physical activity EPA intervention in children and adolescents hospitalized to receive chemotherapy for a solid tumor or AML and to assess the sleep and fatigue outcomes of the intervention using two different statistical approaches to analyze the longitudinal symptom data
randomized prospective two-site and two-group pilot study
Standard care Twenty nine patients (25 with a solid tumor and 4 with AML)ages 7-18 years
1 sleep duration 2 sleep efficiency 3 fatigue
1sleep duration sleep efficiency The
Wrist Actigraph The Daily Sleep Diary-Parent 2 fatigue (mean) The Fatigue Scale(FS-C) for 7-12 (intensity) The Fatigue Scale(FS-A) for 13-18 The Fatigue Scale Parent Version (FS-P) The Fatigue Scale Staff Version (FS-S)
1enhanced physical activity (EPA) (hospital-based 30 minutes
twice daily for 2-4 days) 2 T0On the day of admission
(Day 0 or baseline)patient and parents completed the fatigue instruments and a team member applied the actigraph Patients wore the wrist actigraph T1 from Day 0 to 2 or 3 consecutive days (Days 0e3) In addition the patient same parent and staff nurses completed the daily sleep and fatigue reports in the late afternoons of Days 1-3
1 ANOVA model slesignificantly more the experimental athe control arm whdifferences from bsleep efficiency vaaveraged and com
2 The patient-reported mean fatigue scoresarms were higher amadolescents than for
3 The mixed model anarevealed no significandifferences in patientfatigue between
the two study arms otime( no final result iSD only give mixed result)
677
46
23 Keats M
R amp Culos-Reed S N (2008)
A community-based physical activity program for adolescents with cancer (project TREK) program feasibility and preliminary findings
To examine the
feasibility of a
theoretically-based
physical activity (PA)
intervention in
adolescents with
cancerand
examination of the
impact of the
program on
participant QOL
including social
emotional and
physical
well-being(including fatigue)
Repeat measures longitudinal design
No comparsion group
10 adolescents(Lymphoma(4)leukemia(4)CNS tumor(1)germ cell tumor(1)) ages 14-18 years
1physical fitness 2quality of life (QOL) 3PA behavior 4fatigue
1 Feasibility was assessed by participant recruitment attendance and adherence
2physical fitness Fitnessgram 3quality of life (QOL) Pediatric Quality of Life Inventory (PedsQL) 4PA behavior leisure score index (LSI) 5fatigue (mean) pediatric Quality of life
Multidimensional Fatigue Scale (Peds QL-MFS)
(Generalsleepcognitive fatigue)
116week physical activity (PA)
2 total PA physical fitness and overall QOL was assessed at 5 different intervals T0 preintervention (baseline) T1midintervention (after the
first 8 wk) T2 postintervention
(16 wk) T3 3-months
postintervention T4 1-year poststudy
initiation
1 from baseline -wkssig Improvementstotal PA physfitness and Qgeneral fatigue(meanplusmnSD 796plusmn135)
2 from baseline to 3FUsig Improvin general fatigue(meanplusmnSD824plusmn131)slefatigue(meanplusmnSD755plusmn191)totafatigue(meanplusmnSD778plusmn150)
3at 1 years FUsImprovements in sleeprest fatigue(meanplusmnSD725plusmn203)total (meanplusmnSD 763plusmn
678
47
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
2 Gene R E amp Conk Z (2008)
Impact of Effective Nursing Interventions to the Fatigue Syndrome in Children Who Receive Chemotherapy
1 to examine the effects of an effective nursing intervention to the fatigue syndrome of children 7 to 12 years of age who receive chemotherapy 2Tto examine the relationship between fatigue and demographic variables (age sex) diagnoses ([ALL AML] lymphoma) and therapy-related variables (eg level of hemoglobin
experimental randomized controlled study
Routine nursing care
A total of 60 children who are 7-12 years of age(a new diagnosis of ALL AML or lymphoma and receiving for the first time after being diagnosed a 7- to 10-day chemotherapy treatment )
fatigue The Fatigue Scale(FS-C) for 7-12 (intensity)
The Fatigue Scale Parent Version (FS-P)
1 effective nursing interventions(45- 60mdaya week)education about the fatigue with the chemotherapy and fatigue handbook 2 T1 After a 7-day period the children
and parent were evaluated with the Fatigue Scale
1The difference betwthe 2 mean values wafound to be statisticallsignificant 2 statistically significadifference was found between the Fatigue Scale-Child mean scothe experimental (272the control group (4213)children
679
48
25 Chiang et
al(2007)
The effects of ldquo a home ndashbased aerobic exercise interventionrdquo on fatigue and cardiorespiratory fitness in children with Acute Lymphoblastic Leukemia during the maintenance stage of chemotherapy
To examine the effect of ldquo a home ndashbased aerobic exercise interventionrdquo on fatigue and cardiorespiratory fitness in children with Acute Lymphoblastic Leukemia during the maintenance stage of chemotherapy
Quasi-experi -mental
Routine
nursing care
14 pediatric oncology patients in the experimental group and 10 in control group who were matched by age and sex ages7-18 years
1Cardiorespiratory fitness
2Fatigue
1Cardiorespiratory fitness Physical Activity Recall
VO2maxHR peak 6MWT
2 Fatigue PedsQL-MFS(Generalsleepcognitive fatigue)
1A six-week home-based aerobic exercise intervention 2 8 time points T0 baseline T1-T6 every week during the
intervention(6 weeks) T7 post intervention T8 follow-up (one month after
the end of the home-based exercise program)
1 For intent-to ndash treatthe findings indicated are no intervention efftime differences by anon the subscale of fat2 For per-protocol angeneral fatigue( mean422plusmn402) was the osubscale that was siglower for children whothe exercise interventthose in control groupfollow-up assessmentmonth after the compintervention) 3 The VO2peak are significantly improvingexperimental group atbaseline- and post-intassessment The VO2was significantly highechildren who were in experimental group thcontrol subjects at post-intervention assefor the per-protocol an
680
49
Appendix IV Instrument used to measure fatigue
Name Instrument
developers
Description Used in
age in
ref
Reliability
Consistency of
instrument
Checklist Individual Strength
(CIS)22
Vercoulen et
al1996
20 items using 7-point Likert scale of
fatigue To measure four aspects of
fatiguesubjective experience
contractionmotivation physical
Activity
6-14 Not reported
Child Fatigue Scale (CFS)7 Hockenberry
et al2003
14 items 2 part questionnaire frequency
(yes or no) 5-point Likert scale of the
intensity of any yes responses
7-13
14-18 α073-o84
The Fatigue Scale for 7-12
year Olds (FS-C)224
Hockenberry
et al
14 items provide a fatigue intensity score
5-point Likert scale
7-12 αo84
The Fatigue Scale for 13-18
year Olds (FS-A)24
Hockenberry
et al
14 items provide a fatigue intensity score
5-point Likert scale
13-18 α076-o96
Pediatric Quality of life
Multidimensional Fatigue
Scale (Peds QL-MFS)2325
Varni2002 18 items to measure three aspects of
fatigueGeneralsleepcognitive
14-18 Not reported
681
50
Appendix V Excluded studies and reasons for exclusion
Baggott C Dodd M Kennedy C Marina N Miaskowski C Multiple Symptoms in Pediatric Oncology
Patients A Systematic Review Journal of Pediatric Oncology Nursing 2009 Nov-Dec 27(6)
325-339
Reason for exclusion Not outcome of interest
Barlow JH Ellard DR Psycho-educational interventions for children with chronic disease parents and
siblings an overview of the research evidence base Care Health amp Development 2004 Nov
30(6)637-45
Reason for exclusion Not outcome of interest
Bedider S Moyer CA Randomized controlled trials of pediatric massage A review Evid Based
Complement Alternat Med 2007 Mar 4(1)23-34 Epub 2006 Nov 3
Reason for exclusion Not outcome of interest
de Nijs EJ Ros W Grijpdonck MH Nursing intervention for fatigue during the treatment for cancer Cancer
Nursing 2008 31(3)191-206
Reason for exclusion Not population of interest
Edwards JL Gibson F Richardson A Sepion B Ream E Fatigue in adolescents with and following a
cancer diagnosis developing an evidence base for practice European Journal of Cancer 2003
Dec 39(18)2671-80
Reason for exclusion Not experimental or quasi-experimental study
Hinds PS Hockenberry-Eatan M Developing a research program on fatigue in children and adolescents
diagnosed with cancer Journal of Pediatric Oncology Nursing 2001 Mar-Apr 18(2 Suppl
1)3-12
Reason for exclusion Not experimental or quasi-experimental study
Hockenberry-Eaton M Hinds PS Alcoser P ONeill JB Euell K Howard V Gattuso J Taylor J Fatigue in
Children and Adolescents With Cancer Journal of Pediatric Oncology Nursing 1998 July
15(3)172-182
Reason for exclusion Not experimental or quasi-experimental study
Jean-Pierre P Mustian K Kohli S Roscoe JA Hickok JT Morrow GR Community-based clinical oncology
research trials for cancer-related fatigue The Journal of Supportive Oncology 2006 Nov-Dec
4(10)511-6
682
51
Reason for exclusion Not population of interest
Kangas M Bovbjerg DH Montgomery GH Cancer-Related Fatigue A Systematic and Meta-Analytic
Review of Non-Pharmacological Therapies for Cancer Patients Psychological Bulletin 2008 Sep
134(5)700-41
Reason for exclusion Not population of interest
Lotfi-Jam K Carey M Jefford M Schofield P Charleson C Aranda S Nonpharmacologic strategies for
managing common chemotherapy adverse effects A systematic review Journal of Clinical
Oncology 2008 Dec 1 26(34)5618-29 Epub 2008 Nov 3
Reason for exclusion Not outcome of interest
Marchese VG Chiarello LA Lange BJ Effects of physical therapy intervention for children with acute
lymphoblastic leukemia Pediatr Blood Cancer 2004 Feb42(2)127-33
Reason for exclusion Not outcome of interest
Meeske KA Siegel SE Globe DR Mack WJ Bernstein L Prevalence and correlates of fatigue in
long-term survivors of childhood leukemia Journal of Clinical Oncology 2005 Aug 20
23(24)5501-10
Reason for exclusion Not intervention study
Minton O Richardson A Sharpe M Hotopf Stone P A systematic review and meta-analysis of the
pharmacological treatment of cancer-related fatigue J Natl Cancer Inst 2008 Aug 20
100(16)1155-66 Epub 2008 Aug 11
Reason for exclusion Not population and intervention of interest
Mustian KM Morrow GR Carroll JK Figueroa-Moseley CD Pascal JP Williams GC Integrative
nonpharmacologic behavioral interventions for the management of Cancer-Related fatigue The
Oncologist 2007 12(1)52-67
Reason for exclusion Not population of interest
Neill J Belan I Ried K Effectiveness of non-pharmacological interventions for fatigue in adults with
multiple sclerosis rheumatoid arthritis or systemic lupus erythematosus a systematic review
Journal of Advanced Nursing 2006 Dec 56(6)617-35
Reason for exclusion Not population of interest
Rheingans JI A systematic review of nonpharmacologic adjunctive therapies for symptom management
Journal of Pediatric Oncology Nursing 2007 24(2) 81-94
683
52
Reason for exclusion Not outcome of interest
Rheingans JI Pediatric oncology nursesrsquo management of patients symptoms Journal of Pediatric
Oncology Nursing 2008 Nov 25(6) 303-11
Reason for exclusion Not outcome of interest
San Juan AF Fleck SJ Chamorro-Vintildea C Mateacute-Muntildeoz JL Moral S Peacuterez M Cardona C Del Valle MF
Hernaacutendez M Ramiacuterez M Madero L Lucia A Effects of an intrahospital exercise program
intervention for children with leukemia Medicine amp Science in Sports amp Exercise 2007 Jan
39(1)13-21
Reason for exclusion Not outcome of interest
Sanford SD Okuma JO Pan J Srivastava DK West N Farr L Hinds PS Gender differences in sleep
fatigue and daytime activity in a pediatric oncology sample receiving dexamethasone Journal of
Pediatric Psychology 2008 Apr 33(3)298-306 Epub 2007 Nov 17
Reason for exclusion Not experimental or quasi-experimental study
Schmitz KH Holtzman J Courneya KS Macircsse LC Duval S Kane R Controlled physical activity trials in
cancer survivors a systematic review and meta-analysis Cancer Epidemiol Biomarkers Prev
2005 Jul 14(7)1588-95
Reason for exclusion Not population of interest
van Brussel M Takken T Lucia A van der Net J Helders PJ Is physical fitness decreased in survivors of
childhood leukemia A systematic review Leukemia 2005 Jan 19(1)13-7
Reason for exclusion Not population of interest
Whiting P Bagnall AM Snowden AJ Cornell JE Mulrow CD Ramirez G Interventions for the treatment
and management of chronic fatigue syndrome JAMA 2001 Sep 19 286(11)1360-8
Reason for exclusion Not intervention of interest
Whitsett SF Gudmundsdottir M Davies B McCarthy P Friedman D Chemotherapy-related fatigue in
childhood cancer correlates consequences and coping strategies Journal of Pediatric
Oncology Nursing 2008 Mar-Apr 25(2)86-96 Epub 2008 Feb 29
Reason for exclusion Not experimental or quasi-experimental study
Winner C Muumlller C Hoffmann C Boos J Rosenbaum D Physical activity and childhood cancer Pediatr
Blood Cancer 2010 Apr 54(4)501-10
Reason for exclusion Not research study
684
53
Wu M Hsu L Zhang B Shen N Lu H Li S The experiences of cancer-related fatigue among Chinese
children with leukaemia A phenomenological study Journal of Nursing Studies 2010 Jan
47(1)49-59 Epub 2009 Aug 25
Reason for exclusion Not experimental or quasi-experimental study
Yeh CH Chiang YC Lin L Yang CP Chien LC Weaver MA Chuang HL Clinical factors associated with
fatigue over time in paediatric oncology patients receiving chemotherapy British Journal of
Cancer 2008 Jul 8 99(1)23-9 Epub 2008 Jun 24
Reason for exclusion Not experimental or quasi-experimental study
685
28
experimental group (mean age 923)and 30 children included in the control group (mean
age 937) with their mothers In the experimental group after the 7th to 10th day of the
chemotherapy treatment throughout a week the researcher conducted the nursing
interventions every day for 45 to 60 minutes In the control group routine nursing
interventions were carried out The experimental group received education about the
fatigue with the chemotherapy and fatigue handbook was given which was developed by
the authors Children and mothers were consulted for including activities that could
decrease fatigue which were described as effective interventions A statistically
significant difference was found between the Fatigue Scale-Child mean scores of the
experimental (2723) and the control group (4213) The results suggest that fatigue of
children with cancer can be reduced by implementing appropriate nursing interventions
(t=567 Plt00)
Discussion The purpose of this systematic review was to determine the effectiveness of
non-pharmacological interventions specifically targeting fatigue for children and
adolescents with cancer undergoing chemotherapy or after receiving chemotherapy
Included articles about the effectiveness of non-pharmacological interventions for
children and adolescents with cancer were published between the years of 2007 and
2009 Although interventions for cancer fatigue for adults have been extensively studied
it can be seen from either the title of the paper or related content that an intervention
study on children was a pilot study or a feasibility study Representing a field in its early
stage these studies show that the fatigue issues with young cancer patients have only
recently been taken seriously
661
29
The results of our meta-analysis include measurement of the four performance indicators
fatigue and general fatigue sleep rest fatigue and cognitive fatigue The results show
that there is a statistically significant difference only in the domain of general fatigue
using an exercise intervention for children with cancer can improve the degree of fatigue
with the effect size reaching 0671 Other results do not indicate significant differences
The reasons may include the following
1 Characteristics of the cancer The exhaustion from cancer occurs not only during cancer treatment but also in during
long-term survival a time during which patients may continue to be affected by this
symptom 8 26 Therefore when using intervention measures to improve fatigue
circumstances should be considered such as the process of the treatment and the course
or stage of the disease Because cancer patients will experience different forms of
treatment or courses of treatment the disease itself or treatment differences should be
considered in the choice of intervention Even chemotherapy drugs should be taken into
consideration For example a period of general steroid treatment can increase patientsrsquo
fatigue In those studies of children with cancer few studies looked solely at one type of
cancer most studies included a variety of cancer patients Furthermore most studies do
not clearly explain the stage of the disease or course of treatment and most do not
include treatment variables in the control group Moreover children with cancer may
have different levels of physical function
2 Research design The sample size Currently there are few studies with large sample size and a rigorous
RCT design due to the small number of papers available for analysis The sample size
included in our studyrsquos data analysis is between 20 and 42 people this small sample size
will affect the power available to evaluate outcome variables
Although most of the non-pharmacological interventions still use exercise and physical
activity and these studies overall show better results for fatigue as compared with
controls more research is still needed to further confirm the efficacy of these findings
662
30
The dropout rate in the evaluated research varies a great deal ranging from 5 to 45
these dropout rates may result from the characteristics of the research subjects or the
lengthy time involved in participating in these studies The research data with a high
turnover rate might not reflect the actual outcomes of participation in exercise and the
quality of the research contained in articles with high subject turnover rates may be
lower
Exercise doses and time The exercise doses needed to reduce fatigue cannot be
determined additionally the amount of exercise completed by the patient is also
inconsistent interventions vary between 2-3 times per week and two times a day and
exercise duration varies between 10 and 45 minutes each time Furthermore the study
interventions vary in length between a couple of days and a long period of 16 weeks The
data collection times are different some were measured 12 weeks after the intervention
began some were measured during the 6 weeks of intervention some were measured
three months after the intervention was finished and some were measured after one
year
In addition disease-related symptoms decrease childrenrsquos willingness to participate in
exercise interventions inappropriate exercise intervention programs may actually
increase childrens fatigue In addition the children in the study are still developing
physically it is important to consider ways to design an interesting exercise intervention
to increase the compliance of patients in order to improve the effectiveness Although
intervention programs in the hospital or in a community sports center can improve the
effectiveness because they provide supervision the feasibility of these programs is
questionable However if the program is home-based the children need to be
supervised by parents in order to improve their compliance in doing the exercises
Furthermore regarding the nature of the intervention the results from this study indicate
that the researched non-pharmacological interventions include the following exercise
training programs physical activity massage therapy and health education interventions
However according to the National Comprehensive Cancer Network 1 clinical guidelines
663
31
for cancer non-drug measures for cancer fatigue can be separated into five categories
(1) activity enhancement (2) psychosocial interventions such as cognitive behavioral
therapy (CBT) stress management relaxation techniques and support groups (3)
attention-restoring therapy (4) nutritional consultation and (5) cognitive behavioral
therapy specifically targeting sleep disturbance Researchers have also suggested that
psychosocial interventions should be included in the future research for children with
cancer-related fatigue 22
(2) The measurement tools in the study The assessment of fatigue can be
one-dimensional or multidimensional One-dimensional assessment can help understand
the severity of fatigue symptoms however multidimensional scales are often more
credible Therefore when measuring cancer-related fatigue researchers should consider
whether there is a uniform definition of fatigue or a standardized tool for measuring
fatigue in order to facilitate further systematic meta-analyses and further develop the
clinical care guidelines
Limitations of the review The present review has some potential limitations First the low methodological quality
may influence the result Although exercise intervention seems promising quality of the
RCTs was generally quite low Future studies require better design and reporting if
methodological issues to establish evidence-based nonpharmcologic intervention
Second the identified studies covered only a limited types of nonpharmcological
intervention especially in exercise intervention The guidelines for cancer-related fatigue
in NCCN (2011)1 referred to more interventions than the ones included in this review
such as cognitive behavioral therapy and nutrition consultation Thirdly the small sample
size and effect size could be potentially having led to underpowered approach for
detecting the effects on fatigue Therefore we recommend that as research continues to
grow a re-analysis can be undertaken Fourthly Combining data in meta analysis from
664
32
studies where the ages were quite different is a potential source of heterogeneity and
may affect the interpretation of the results
Conclusion At present clinical treatment is widely used for cancer patients However child and
adolescent cancer patients often experience various side effects which cause short-term
or long-term discomfort both physically and psychologically In particular with the
increasing cure rate cancer related fatigue during or after treatment has become an
important issue This study result provided positive effect of exercise intervention on
general fatigue
Implications for practice The results of this systematic review and meta-analysis show that exercise interventions
can effectively improve the level of general fatigue In particular although the articles
were self-reported feasibility studies their results all indicate that exercise interventions
for fatigue are feasible and safe there was no conclusion to be made for the use of
massage therapy or health education measures because there was only one article for
each of these interventions
Recommendations for practice
Cancer-related fatigue is one of the most severe and frequent symptoms by pediatric
oncology children and adolescent suffered during treatment and the symptom existed
even after treatment has ended Until now no golden standard of treatment to fatigue is
established The findings call for more attention to how to reduce patientrsquos levels of
fatigue Based on the available information evaluated in this review the following
recommendations for practice are provided
665
33
bull For children aged 7 to 18 who has cancer (eg Lymphoma leukemia CNS tumor
germ cell tumor) an effective progressive aerobic exercise program is recommended to
be at least 2-3 times per week 20 to 45 minute for each session and last for 6-16 weeks
in order to reduce their general fatigue (tiredness physically weakness) In addition
adults should be involved in accompanying children while they are performing physical
exercise of which should be able to improve the adherence rate (level 2 ) ( Grade of
recommendation A)
bull For children aged 7 to 18 who has cancer (eg Lymphoma leukemia CNS tumor
germ cell tumor) an progressive aerobic exercise program will not be effective to reduce
their sleep andor rest (sleeping or resting a lot) or cognitive fatigue (problems with
thinking quickly or problems with remembering) (level 2 ) ( Grade of recommendation C)
bull Nursing interventions in educating treatment of fatigue include information about
activity nutrition energy preservation consulting and providing a useful fatigue
handbook will benefit those children who are 7 to 12 years have a new diagnosis of ALL
AML or lymphoma and receive for the first time after being diagnosed a 7- to 10-day
chemotherapy treatment (level 2) ( Grade of recommendation A)
bull A 4-week massage therapy program (the therapists massage childrenrsquos back legs
arms stomachchest and face) is not effective for children who are aged 7 to 18 and
have acute lymphoblastic leukemia brain tumors lymphoma rhabdomyosarcoma
Wilms tumor or Ewing sarcoma(level 2)( Grade of recommendation C)
bull Using a 12-week aerobic and strength exercise (45-min exercise sessions twice a
week) is not effective for children who are aged 6-14 and survived acute lymphoblaststic
leukemia age from 6 to 14(level 2) ( Grade of recommendation C)
bull Using a physical activity intervention (30minutestwice daily for 2-4days) is not
effective for children who are 7 to 18 years of age with soild tumor or AML(level 2)
( Grade of recommendation C)
666
34
Implications for research According to this systematic review and meta-analysis results there are suggestions to
improve the effectiveness of future research on non-pharmacological interventions for
children and young peoplersquos cancer-related fatigue
As the majority of included non-pharmacological interventions for the fatigue of cancer
patients consist of exercise programs future research should also consider various
non-pharmacological interventions in order to understand the effectiveness of different
methods
Regarding the exercise intervention methods and studies should consider multiple
factors including the age or personal condition of the subject the disease stage and the
amount of daily activities Studies should use design prescriptions (eg frequency
intensity duration and type of exercise) and consider the adherence to the measures in
order to enhance the study strength
In measuring the results of non-pharmacological interventions there should be standard
definitions or standard measurement tools to facilitate the following systematic review
and meta-analysis that can subsequently be developed into clinical care guidelines
Reviewing the effectiveness of the current non-pharmacological management of children
and adolescent cancer patients there is still a lack of rigorous RCT research Limited by
the characteristics of cancer there is still a lack of large sample sizes
Potential conflicts of interest There is no conflict of interest
Acknowledgements
Thank you to Dr Rie Konno Research Fellow Joanna Briggs Institute for her help in
assessing studies
667
35
References 1 National Comprehensive Cancer Network( NCCN) in USA NCCN clinical practice
guideline in oncology cancer-related fatigue 2011 2 Ekti Genc R amp Conk Z Impact of effective nursing interventions to the fatigue
syndrome in children who receive chemotherapy Cancer Nursing 200831(4)312-317
3 Childhood Cancer Foundation of ROC (2009March) The classification of diseases
and age sex statistical tables of case Childhood Cancer Foundation of ROC newsletter103105-106
4 Department of Health Executive Yuan ROC (TAIWAN)(2009 March 20)2009 cause of death statistic Health and National Health Insurance Annual Statistics Information Service 2010 June 28Available httpwwwdohgovtwstatisticdatavital statists9898health statistic--lifepdf
5 Chang TK (2007December 8) Common childhood cancer and its treatment Status
Childhood Cancer Foundation of ROC (TAIWAN) 2010 September 23 Available httpwwwccfrocorgtwchildchild_events_readphpe_id=45
6 Hockenberry MJ amp Wilson D Wongs nursing care of infants and children (8th ed) St
Louis MO Mosby 2007
7 Post-White J Fitzgerald M Savik K Hooke MC Hannahan AB amp Sencer SF
Massage therapy for children with cancer Journal of Pediatric Oncology Nursing 2009 26(1)16-28
8Chiang YC Yeh CH Wang WKamp Yang CP The experience of cancer-related fatigue
in Taiwanese children European Journal of Cancer Care 2009 18(1)43-49 9Langeveld NE Grootenhuis M A Voute P A de Haan RJ amp van den Bos C No excess
fatigue in young adult survivors of childhood cancer European Journal of Cancer 200339(2)204-214
10Piper BF Lindsey AM amp Dodd MJ Fatigue mechanisms in cancer patients
developing nursing theory Oncology Nursing Forum 1987 14(6)17-23 11Nail LM amp Winningham ML Fatigue In S L Groenwald M H Forgge M Goodman
amp C H Yarbro (Eds) Cancer Nursing Principles and practice (4 th ed) Boston Jones and Bartlett1997
12Irvine D Vincent L Graydon JE Bubela N amp Thompson L The prevalence and
correlates of fatigue in patients receiving treatment with chemotherapy and
668
36
radiotherapy A comparison with the fatigue experienced by healthy individuals Cancer Nursing 199417(5)367-378
13Hinds PS amp Hockenberry-Eaton M Developing a research program on fatigue in
children and adloescents diagnosed with cancer Journal of Pediatric Oncology Nursing 200118(2)3-12
14Aaronson LS Teel CS Cassmeyer V Neuberger GB Pallikkathayil L Pierce J Press
AN Williams DP amp Wingate A Defining and measuring fatigue Journal of Nursing scholarship 1999 31(1)45-50
15Yeh CH Wang CH Chiang YC Lin Lamp Chien LC Assessment of symptoms reported
by 10- to 18-year-old cancer patients in Taiwan 2009 38(5)738-746 16 Okuyama T Akechi T Kugaya A Okamura H Shima Yamp Maruguchi M
Development and validation of the cancer fatigue scale a brief three-dimensional self-rating scale for assessment of fatigue in cancer patients Journal of Pain amp Symptom Management 2000 19(1) 5-14
17Gibson F Mulhall AB Richardson A Edwards JL Ream E amp Sepion BJ A
phenomenologic study of fatigue in adolescents receiving treatment for cancer Oncology Nursing Forum200532(3)651-660
18Wolfe J Grier HE Klar N Levin SB Ellenbogen JMamp Salem-Schatz S et al
Symptoms and suffering at the end of life in children with cancer New England Journal of Medicine 2000342(5)326-333
19Whiting P Bagnall AM Sowden AJ Cornell JE Mulrow CD amp Ramirez G
Interventions for the treatment and management of chronic fatigue syndrome a systematic review JAMA the Journal of the American Medical Association 2001286(11)1360-1368
20 Kangas M Bovbjerg DHamp Montgomery G H Cancer-related fatigue a systematic
and meta-analytic review of non-pharmacological therapies for cancer patients Psychological Bulletin 2008134 (5)700-741
21Williams PD Schmideskamp J Ridder EL amp Williams AR Symptom monitoring and
dependent care during cancer treatment in children pilot study Cancer Nursing 200629(3)188-197
22Takken T van der Torre P Zwerink M Hulzebos EH Bierings M Helders PJMamp van
der Net J Development feasibility and efficacy of a community-based exercise training
669
37
program in pediatric cancer survivors Psycho-Oncology 200918(4)440-448
23Keats MR amp Culos-Reed SN A community-based physical activity program for
adolescents with cancer (project TREK) program feasibility and preliminary findings
Pediatric hematology and oncology 200830(4) 272-280
24Hinds PS Hockenberry M Rai SN Zhang L Razzouk B I Cremer L McCarthy K amp
Rodriguez-Galindo C Clinical field testing of an enhanced-activity intervention in
hospitalized children with cancer Journal of Pain amp Symptom Management 2007
33(6)686-697
25Chiang YC The effects of ldquo a home-based aerobic exercise interventionrdquo on fatigue
and cardiorespiratory fitness in children with acute lymphoblastic leukemia during the
maintenance stage of chemotherapy Unpublished thesis Taiwan Tao-Yuan 2007
26Langeveld N Ubbink M amp Smets E I dont have any energy The experience of
fatigue in young adult survivors of childhood cancer European journal of oncology
nursing 20004(1)20-28
27 Kisner C Colby L Therapeutic exercise Foundations and techniques 2nd ed Philadelphia PAFA Davies 2007
670
38
Appendix I JBI Critical Appraisal Checklist for Experimental studies
Author__________ Year_________ Record Number__________________
Questions 1 to 4 must be answered ldquoyesrdquo for study to be included in the metashyanalysis
1 Were the participants randomized to study groups
Yes No Not clear
2 Other than research intervention were participants in each groups treated the same
Yes No Not clear
3 Were the outcomes measured in the same manner for all participants
Yes No Not clear
4 Were groups comparable at entry
Yes No Not clear
5 Was randomization of participants blinded
Yes No Not clear
6 Were those assessing outcome blinded to treatment allocation (if outcome not objective such as survival or length of hospitalization)
Yes No Not clear
7 Was allocation to treatment groups concealed from the allocator
Yes No Not clear
8 Was an appropriate statistical analysis used
671
39
Yes No Not clear
9 Were outcomes measured in a reliable way
Yes No Not clear
10 Was there adequate followshyup of participants
Yes No Not clear
Summary
TOTAL
Yes No Not clear
DECISION
Use Reject
Narrative summary only Further information needed
COMMENTS
672
40
Appendix II JBI Data Extraction Tool for Quantitative Studies Authors and Year
Journal Title
Record NumberArticle Reference No
Reviewer
Method
Settings
Participants
Number of participants
Group A Group B Group C
Control Intervention 1 Intervention 2
Interventions
Group A
Control
Group B
Intervention 1
Group C
Intervention 2
Outcome measures
Definition
673
41
Other outcome measures
Outcome description ScaleMeasure
Results
Dichotomous Data
Outcome Control Group
Numbertotal number
Treatment Group
Numbertotal number
Continuous Data
Authorrsquos Conclusions
Comments
Outcome Control Group
Mean amp SD
Treatment Group
Mean amp SD
674
43
Appendix III Details of included studies (N=6)(2720212223) RefNo Author(s)
(years) Title Study question Research
method Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
22 Takken T van der Torre P Zwerink M Hulzebos E H Bierings M Helders P J Mamp van der Net J (2009)
Development feasibility and efficacy of a community-based exercise training program in pediatric cancer survivors
To develop a 12-week home-based exercise training program (comprising aerobic and strength exercises) for children who survived ALL and to study itrsquos feasibility and efficacy
Pre-post test design
No comparsion group
Survived ALL(N=9)ages 6-14 years
1anthropometry 2 muscle strength 3functional mobility 4cardio-pulmonary
exercise test 5Fatigue
1 Feasibility questionnaire 2 anthropometry electronic scale and a wallmounted stadiometerHarpenden skin fold calipers 3 muscle strength handheld dynamometer 4functional mobility Timed Up
and Go test (TUG) 5cardio-pulmonary exercise test electronically braked cycle ergometer 6Fatigue(mean)CSI-20 (subjective experience of fatigueconcentrationmotivationphysical activity)
112-week exercise training program
2 Patients were assessed before (T0) and after (T1) 12 weeks of training
1 muscle strength execapacity functional moand fatigue showed nosignificant differences between pre(meanplusmnSD415plusmn147) and post training(meanplusmnSD3687)
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
7 Post-White J Fitzgerald M Savik K Hooke M C Hannahan A B amp Sencer S F (2009)
Massage therapy for children with cancer
To determine whether 4 weekly sessions of massage compared with 4 quiet-time control conditions would reduce anxiety cortisol levels fatigue nausea and pain in children with cancer undergoing chemotherapy and would reduce anxiety fatigue and mood disturbance in a parent
2-period crossover design (Randomized)
quiet-time
control
sessions
Children with cancer 1 to 18 years of age Twenty-three childrenparent dyads were enrolled 17 completed all data points
children 1relaxation 2symptoms 3 fatigue
parents
1anxiety 2 fatigue
children 1relaxation (heart and respiratory rates blood pressure and salivary cortisol level)
2symptoms (pain nausea anxiety 3 fatigue 1-2y3-6yLansky Play Performance Scale (PPS) 7-13y
1 4 weekly massage (MT) sessions alternated with 4 weekly quiet-time(QT) control sessions
2 children included presession and postsession vital signs (heart rate respiratory rate blood pressure) and self-report (parent proxy report for age 1-2 years) of pain nausea and anxiety Fatigue was measured before sessions 1 and 4 and at each follow-up Parent measures
included anxiety fatigue and mood states
1Massage was moreeffective than quiet tireducing heart rate inchildren anxiety in cless than age 14 yeaparent anxiety 2There were no sign
changes in blood pcortisol pain naufatigue (no state d
3 Children reported tmassage helped thebetter lessened theirand worries and hadlasting effects than q
675
44
14-18yChild Fatigue Scale (CFS) (frequency
intensity) 2 parents anxiety and fatigue
676
45
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
24 Hinds P S Hockenberry M Rai S N Zhang L Razzouk B I Cremer L McCarthy K amp Rodriguez-Galindo C (2007)
Clinical field testing of an enhanced-activity intervention in hospitalized children with cancer
To determine the feasibility of an
enhanced physical activity EPA intervention in children and adolescents hospitalized to receive chemotherapy for a solid tumor or AML and to assess the sleep and fatigue outcomes of the intervention using two different statistical approaches to analyze the longitudinal symptom data
randomized prospective two-site and two-group pilot study
Standard care Twenty nine patients (25 with a solid tumor and 4 with AML)ages 7-18 years
1 sleep duration 2 sleep efficiency 3 fatigue
1sleep duration sleep efficiency The
Wrist Actigraph The Daily Sleep Diary-Parent 2 fatigue (mean) The Fatigue Scale(FS-C) for 7-12 (intensity) The Fatigue Scale(FS-A) for 13-18 The Fatigue Scale Parent Version (FS-P) The Fatigue Scale Staff Version (FS-S)
1enhanced physical activity (EPA) (hospital-based 30 minutes
twice daily for 2-4 days) 2 T0On the day of admission
(Day 0 or baseline)patient and parents completed the fatigue instruments and a team member applied the actigraph Patients wore the wrist actigraph T1 from Day 0 to 2 or 3 consecutive days (Days 0e3) In addition the patient same parent and staff nurses completed the daily sleep and fatigue reports in the late afternoons of Days 1-3
1 ANOVA model slesignificantly more the experimental athe control arm whdifferences from bsleep efficiency vaaveraged and com
2 The patient-reported mean fatigue scoresarms were higher amadolescents than for
3 The mixed model anarevealed no significandifferences in patientfatigue between
the two study arms otime( no final result iSD only give mixed result)
677
46
23 Keats M
R amp Culos-Reed S N (2008)
A community-based physical activity program for adolescents with cancer (project TREK) program feasibility and preliminary findings
To examine the
feasibility of a
theoretically-based
physical activity (PA)
intervention in
adolescents with
cancerand
examination of the
impact of the
program on
participant QOL
including social
emotional and
physical
well-being(including fatigue)
Repeat measures longitudinal design
No comparsion group
10 adolescents(Lymphoma(4)leukemia(4)CNS tumor(1)germ cell tumor(1)) ages 14-18 years
1physical fitness 2quality of life (QOL) 3PA behavior 4fatigue
1 Feasibility was assessed by participant recruitment attendance and adherence
2physical fitness Fitnessgram 3quality of life (QOL) Pediatric Quality of Life Inventory (PedsQL) 4PA behavior leisure score index (LSI) 5fatigue (mean) pediatric Quality of life
Multidimensional Fatigue Scale (Peds QL-MFS)
(Generalsleepcognitive fatigue)
116week physical activity (PA)
2 total PA physical fitness and overall QOL was assessed at 5 different intervals T0 preintervention (baseline) T1midintervention (after the
first 8 wk) T2 postintervention
(16 wk) T3 3-months
postintervention T4 1-year poststudy
initiation
1 from baseline -wkssig Improvementstotal PA physfitness and Qgeneral fatigue(meanplusmnSD 796plusmn135)
2 from baseline to 3FUsig Improvin general fatigue(meanplusmnSD824plusmn131)slefatigue(meanplusmnSD755plusmn191)totafatigue(meanplusmnSD778plusmn150)
3at 1 years FUsImprovements in sleeprest fatigue(meanplusmnSD725plusmn203)total (meanplusmnSD 763plusmn
678
47
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
2 Gene R E amp Conk Z (2008)
Impact of Effective Nursing Interventions to the Fatigue Syndrome in Children Who Receive Chemotherapy
1 to examine the effects of an effective nursing intervention to the fatigue syndrome of children 7 to 12 years of age who receive chemotherapy 2Tto examine the relationship between fatigue and demographic variables (age sex) diagnoses ([ALL AML] lymphoma) and therapy-related variables (eg level of hemoglobin
experimental randomized controlled study
Routine nursing care
A total of 60 children who are 7-12 years of age(a new diagnosis of ALL AML or lymphoma and receiving for the first time after being diagnosed a 7- to 10-day chemotherapy treatment )
fatigue The Fatigue Scale(FS-C) for 7-12 (intensity)
The Fatigue Scale Parent Version (FS-P)
1 effective nursing interventions(45- 60mdaya week)education about the fatigue with the chemotherapy and fatigue handbook 2 T1 After a 7-day period the children
and parent were evaluated with the Fatigue Scale
1The difference betwthe 2 mean values wafound to be statisticallsignificant 2 statistically significadifference was found between the Fatigue Scale-Child mean scothe experimental (272the control group (4213)children
679
48
25 Chiang et
al(2007)
The effects of ldquo a home ndashbased aerobic exercise interventionrdquo on fatigue and cardiorespiratory fitness in children with Acute Lymphoblastic Leukemia during the maintenance stage of chemotherapy
To examine the effect of ldquo a home ndashbased aerobic exercise interventionrdquo on fatigue and cardiorespiratory fitness in children with Acute Lymphoblastic Leukemia during the maintenance stage of chemotherapy
Quasi-experi -mental
Routine
nursing care
14 pediatric oncology patients in the experimental group and 10 in control group who were matched by age and sex ages7-18 years
1Cardiorespiratory fitness
2Fatigue
1Cardiorespiratory fitness Physical Activity Recall
VO2maxHR peak 6MWT
2 Fatigue PedsQL-MFS(Generalsleepcognitive fatigue)
1A six-week home-based aerobic exercise intervention 2 8 time points T0 baseline T1-T6 every week during the
intervention(6 weeks) T7 post intervention T8 follow-up (one month after
the end of the home-based exercise program)
1 For intent-to ndash treatthe findings indicated are no intervention efftime differences by anon the subscale of fat2 For per-protocol angeneral fatigue( mean422plusmn402) was the osubscale that was siglower for children whothe exercise interventthose in control groupfollow-up assessmentmonth after the compintervention) 3 The VO2peak are significantly improvingexperimental group atbaseline- and post-intassessment The VO2was significantly highechildren who were in experimental group thcontrol subjects at post-intervention assefor the per-protocol an
680
49
Appendix IV Instrument used to measure fatigue
Name Instrument
developers
Description Used in
age in
ref
Reliability
Consistency of
instrument
Checklist Individual Strength
(CIS)22
Vercoulen et
al1996
20 items using 7-point Likert scale of
fatigue To measure four aspects of
fatiguesubjective experience
contractionmotivation physical
Activity
6-14 Not reported
Child Fatigue Scale (CFS)7 Hockenberry
et al2003
14 items 2 part questionnaire frequency
(yes or no) 5-point Likert scale of the
intensity of any yes responses
7-13
14-18 α073-o84
The Fatigue Scale for 7-12
year Olds (FS-C)224
Hockenberry
et al
14 items provide a fatigue intensity score
5-point Likert scale
7-12 αo84
The Fatigue Scale for 13-18
year Olds (FS-A)24
Hockenberry
et al
14 items provide a fatigue intensity score
5-point Likert scale
13-18 α076-o96
Pediatric Quality of life
Multidimensional Fatigue
Scale (Peds QL-MFS)2325
Varni2002 18 items to measure three aspects of
fatigueGeneralsleepcognitive
14-18 Not reported
681
50
Appendix V Excluded studies and reasons for exclusion
Baggott C Dodd M Kennedy C Marina N Miaskowski C Multiple Symptoms in Pediatric Oncology
Patients A Systematic Review Journal of Pediatric Oncology Nursing 2009 Nov-Dec 27(6)
325-339
Reason for exclusion Not outcome of interest
Barlow JH Ellard DR Psycho-educational interventions for children with chronic disease parents and
siblings an overview of the research evidence base Care Health amp Development 2004 Nov
30(6)637-45
Reason for exclusion Not outcome of interest
Bedider S Moyer CA Randomized controlled trials of pediatric massage A review Evid Based
Complement Alternat Med 2007 Mar 4(1)23-34 Epub 2006 Nov 3
Reason for exclusion Not outcome of interest
de Nijs EJ Ros W Grijpdonck MH Nursing intervention for fatigue during the treatment for cancer Cancer
Nursing 2008 31(3)191-206
Reason for exclusion Not population of interest
Edwards JL Gibson F Richardson A Sepion B Ream E Fatigue in adolescents with and following a
cancer diagnosis developing an evidence base for practice European Journal of Cancer 2003
Dec 39(18)2671-80
Reason for exclusion Not experimental or quasi-experimental study
Hinds PS Hockenberry-Eatan M Developing a research program on fatigue in children and adolescents
diagnosed with cancer Journal of Pediatric Oncology Nursing 2001 Mar-Apr 18(2 Suppl
1)3-12
Reason for exclusion Not experimental or quasi-experimental study
Hockenberry-Eaton M Hinds PS Alcoser P ONeill JB Euell K Howard V Gattuso J Taylor J Fatigue in
Children and Adolescents With Cancer Journal of Pediatric Oncology Nursing 1998 July
15(3)172-182
Reason for exclusion Not experimental or quasi-experimental study
Jean-Pierre P Mustian K Kohli S Roscoe JA Hickok JT Morrow GR Community-based clinical oncology
research trials for cancer-related fatigue The Journal of Supportive Oncology 2006 Nov-Dec
4(10)511-6
682
51
Reason for exclusion Not population of interest
Kangas M Bovbjerg DH Montgomery GH Cancer-Related Fatigue A Systematic and Meta-Analytic
Review of Non-Pharmacological Therapies for Cancer Patients Psychological Bulletin 2008 Sep
134(5)700-41
Reason for exclusion Not population of interest
Lotfi-Jam K Carey M Jefford M Schofield P Charleson C Aranda S Nonpharmacologic strategies for
managing common chemotherapy adverse effects A systematic review Journal of Clinical
Oncology 2008 Dec 1 26(34)5618-29 Epub 2008 Nov 3
Reason for exclusion Not outcome of interest
Marchese VG Chiarello LA Lange BJ Effects of physical therapy intervention for children with acute
lymphoblastic leukemia Pediatr Blood Cancer 2004 Feb42(2)127-33
Reason for exclusion Not outcome of interest
Meeske KA Siegel SE Globe DR Mack WJ Bernstein L Prevalence and correlates of fatigue in
long-term survivors of childhood leukemia Journal of Clinical Oncology 2005 Aug 20
23(24)5501-10
Reason for exclusion Not intervention study
Minton O Richardson A Sharpe M Hotopf Stone P A systematic review and meta-analysis of the
pharmacological treatment of cancer-related fatigue J Natl Cancer Inst 2008 Aug 20
100(16)1155-66 Epub 2008 Aug 11
Reason for exclusion Not population and intervention of interest
Mustian KM Morrow GR Carroll JK Figueroa-Moseley CD Pascal JP Williams GC Integrative
nonpharmacologic behavioral interventions for the management of Cancer-Related fatigue The
Oncologist 2007 12(1)52-67
Reason for exclusion Not population of interest
Neill J Belan I Ried K Effectiveness of non-pharmacological interventions for fatigue in adults with
multiple sclerosis rheumatoid arthritis or systemic lupus erythematosus a systematic review
Journal of Advanced Nursing 2006 Dec 56(6)617-35
Reason for exclusion Not population of interest
Rheingans JI A systematic review of nonpharmacologic adjunctive therapies for symptom management
Journal of Pediatric Oncology Nursing 2007 24(2) 81-94
683
52
Reason for exclusion Not outcome of interest
Rheingans JI Pediatric oncology nursesrsquo management of patients symptoms Journal of Pediatric
Oncology Nursing 2008 Nov 25(6) 303-11
Reason for exclusion Not outcome of interest
San Juan AF Fleck SJ Chamorro-Vintildea C Mateacute-Muntildeoz JL Moral S Peacuterez M Cardona C Del Valle MF
Hernaacutendez M Ramiacuterez M Madero L Lucia A Effects of an intrahospital exercise program
intervention for children with leukemia Medicine amp Science in Sports amp Exercise 2007 Jan
39(1)13-21
Reason for exclusion Not outcome of interest
Sanford SD Okuma JO Pan J Srivastava DK West N Farr L Hinds PS Gender differences in sleep
fatigue and daytime activity in a pediatric oncology sample receiving dexamethasone Journal of
Pediatric Psychology 2008 Apr 33(3)298-306 Epub 2007 Nov 17
Reason for exclusion Not experimental or quasi-experimental study
Schmitz KH Holtzman J Courneya KS Macircsse LC Duval S Kane R Controlled physical activity trials in
cancer survivors a systematic review and meta-analysis Cancer Epidemiol Biomarkers Prev
2005 Jul 14(7)1588-95
Reason for exclusion Not population of interest
van Brussel M Takken T Lucia A van der Net J Helders PJ Is physical fitness decreased in survivors of
childhood leukemia A systematic review Leukemia 2005 Jan 19(1)13-7
Reason for exclusion Not population of interest
Whiting P Bagnall AM Snowden AJ Cornell JE Mulrow CD Ramirez G Interventions for the treatment
and management of chronic fatigue syndrome JAMA 2001 Sep 19 286(11)1360-8
Reason for exclusion Not intervention of interest
Whitsett SF Gudmundsdottir M Davies B McCarthy P Friedman D Chemotherapy-related fatigue in
childhood cancer correlates consequences and coping strategies Journal of Pediatric
Oncology Nursing 2008 Mar-Apr 25(2)86-96 Epub 2008 Feb 29
Reason for exclusion Not experimental or quasi-experimental study
Winner C Muumlller C Hoffmann C Boos J Rosenbaum D Physical activity and childhood cancer Pediatr
Blood Cancer 2010 Apr 54(4)501-10
Reason for exclusion Not research study
684
53
Wu M Hsu L Zhang B Shen N Lu H Li S The experiences of cancer-related fatigue among Chinese
children with leukaemia A phenomenological study Journal of Nursing Studies 2010 Jan
47(1)49-59 Epub 2009 Aug 25
Reason for exclusion Not experimental or quasi-experimental study
Yeh CH Chiang YC Lin L Yang CP Chien LC Weaver MA Chuang HL Clinical factors associated with
fatigue over time in paediatric oncology patients receiving chemotherapy British Journal of
Cancer 2008 Jul 8 99(1)23-9 Epub 2008 Jun 24
Reason for exclusion Not experimental or quasi-experimental study
685
29
The results of our meta-analysis include measurement of the four performance indicators
fatigue and general fatigue sleep rest fatigue and cognitive fatigue The results show
that there is a statistically significant difference only in the domain of general fatigue
using an exercise intervention for children with cancer can improve the degree of fatigue
with the effect size reaching 0671 Other results do not indicate significant differences
The reasons may include the following
1 Characteristics of the cancer The exhaustion from cancer occurs not only during cancer treatment but also in during
long-term survival a time during which patients may continue to be affected by this
symptom 8 26 Therefore when using intervention measures to improve fatigue
circumstances should be considered such as the process of the treatment and the course
or stage of the disease Because cancer patients will experience different forms of
treatment or courses of treatment the disease itself or treatment differences should be
considered in the choice of intervention Even chemotherapy drugs should be taken into
consideration For example a period of general steroid treatment can increase patientsrsquo
fatigue In those studies of children with cancer few studies looked solely at one type of
cancer most studies included a variety of cancer patients Furthermore most studies do
not clearly explain the stage of the disease or course of treatment and most do not
include treatment variables in the control group Moreover children with cancer may
have different levels of physical function
2 Research design The sample size Currently there are few studies with large sample size and a rigorous
RCT design due to the small number of papers available for analysis The sample size
included in our studyrsquos data analysis is between 20 and 42 people this small sample size
will affect the power available to evaluate outcome variables
Although most of the non-pharmacological interventions still use exercise and physical
activity and these studies overall show better results for fatigue as compared with
controls more research is still needed to further confirm the efficacy of these findings
662
30
The dropout rate in the evaluated research varies a great deal ranging from 5 to 45
these dropout rates may result from the characteristics of the research subjects or the
lengthy time involved in participating in these studies The research data with a high
turnover rate might not reflect the actual outcomes of participation in exercise and the
quality of the research contained in articles with high subject turnover rates may be
lower
Exercise doses and time The exercise doses needed to reduce fatigue cannot be
determined additionally the amount of exercise completed by the patient is also
inconsistent interventions vary between 2-3 times per week and two times a day and
exercise duration varies between 10 and 45 minutes each time Furthermore the study
interventions vary in length between a couple of days and a long period of 16 weeks The
data collection times are different some were measured 12 weeks after the intervention
began some were measured during the 6 weeks of intervention some were measured
three months after the intervention was finished and some were measured after one
year
In addition disease-related symptoms decrease childrenrsquos willingness to participate in
exercise interventions inappropriate exercise intervention programs may actually
increase childrens fatigue In addition the children in the study are still developing
physically it is important to consider ways to design an interesting exercise intervention
to increase the compliance of patients in order to improve the effectiveness Although
intervention programs in the hospital or in a community sports center can improve the
effectiveness because they provide supervision the feasibility of these programs is
questionable However if the program is home-based the children need to be
supervised by parents in order to improve their compliance in doing the exercises
Furthermore regarding the nature of the intervention the results from this study indicate
that the researched non-pharmacological interventions include the following exercise
training programs physical activity massage therapy and health education interventions
However according to the National Comprehensive Cancer Network 1 clinical guidelines
663
31
for cancer non-drug measures for cancer fatigue can be separated into five categories
(1) activity enhancement (2) psychosocial interventions such as cognitive behavioral
therapy (CBT) stress management relaxation techniques and support groups (3)
attention-restoring therapy (4) nutritional consultation and (5) cognitive behavioral
therapy specifically targeting sleep disturbance Researchers have also suggested that
psychosocial interventions should be included in the future research for children with
cancer-related fatigue 22
(2) The measurement tools in the study The assessment of fatigue can be
one-dimensional or multidimensional One-dimensional assessment can help understand
the severity of fatigue symptoms however multidimensional scales are often more
credible Therefore when measuring cancer-related fatigue researchers should consider
whether there is a uniform definition of fatigue or a standardized tool for measuring
fatigue in order to facilitate further systematic meta-analyses and further develop the
clinical care guidelines
Limitations of the review The present review has some potential limitations First the low methodological quality
may influence the result Although exercise intervention seems promising quality of the
RCTs was generally quite low Future studies require better design and reporting if
methodological issues to establish evidence-based nonpharmcologic intervention
Second the identified studies covered only a limited types of nonpharmcological
intervention especially in exercise intervention The guidelines for cancer-related fatigue
in NCCN (2011)1 referred to more interventions than the ones included in this review
such as cognitive behavioral therapy and nutrition consultation Thirdly the small sample
size and effect size could be potentially having led to underpowered approach for
detecting the effects on fatigue Therefore we recommend that as research continues to
grow a re-analysis can be undertaken Fourthly Combining data in meta analysis from
664
32
studies where the ages were quite different is a potential source of heterogeneity and
may affect the interpretation of the results
Conclusion At present clinical treatment is widely used for cancer patients However child and
adolescent cancer patients often experience various side effects which cause short-term
or long-term discomfort both physically and psychologically In particular with the
increasing cure rate cancer related fatigue during or after treatment has become an
important issue This study result provided positive effect of exercise intervention on
general fatigue
Implications for practice The results of this systematic review and meta-analysis show that exercise interventions
can effectively improve the level of general fatigue In particular although the articles
were self-reported feasibility studies their results all indicate that exercise interventions
for fatigue are feasible and safe there was no conclusion to be made for the use of
massage therapy or health education measures because there was only one article for
each of these interventions
Recommendations for practice
Cancer-related fatigue is one of the most severe and frequent symptoms by pediatric
oncology children and adolescent suffered during treatment and the symptom existed
even after treatment has ended Until now no golden standard of treatment to fatigue is
established The findings call for more attention to how to reduce patientrsquos levels of
fatigue Based on the available information evaluated in this review the following
recommendations for practice are provided
665
33
bull For children aged 7 to 18 who has cancer (eg Lymphoma leukemia CNS tumor
germ cell tumor) an effective progressive aerobic exercise program is recommended to
be at least 2-3 times per week 20 to 45 minute for each session and last for 6-16 weeks
in order to reduce their general fatigue (tiredness physically weakness) In addition
adults should be involved in accompanying children while they are performing physical
exercise of which should be able to improve the adherence rate (level 2 ) ( Grade of
recommendation A)
bull For children aged 7 to 18 who has cancer (eg Lymphoma leukemia CNS tumor
germ cell tumor) an progressive aerobic exercise program will not be effective to reduce
their sleep andor rest (sleeping or resting a lot) or cognitive fatigue (problems with
thinking quickly or problems with remembering) (level 2 ) ( Grade of recommendation C)
bull Nursing interventions in educating treatment of fatigue include information about
activity nutrition energy preservation consulting and providing a useful fatigue
handbook will benefit those children who are 7 to 12 years have a new diagnosis of ALL
AML or lymphoma and receive for the first time after being diagnosed a 7- to 10-day
chemotherapy treatment (level 2) ( Grade of recommendation A)
bull A 4-week massage therapy program (the therapists massage childrenrsquos back legs
arms stomachchest and face) is not effective for children who are aged 7 to 18 and
have acute lymphoblastic leukemia brain tumors lymphoma rhabdomyosarcoma
Wilms tumor or Ewing sarcoma(level 2)( Grade of recommendation C)
bull Using a 12-week aerobic and strength exercise (45-min exercise sessions twice a
week) is not effective for children who are aged 6-14 and survived acute lymphoblaststic
leukemia age from 6 to 14(level 2) ( Grade of recommendation C)
bull Using a physical activity intervention (30minutestwice daily for 2-4days) is not
effective for children who are 7 to 18 years of age with soild tumor or AML(level 2)
( Grade of recommendation C)
666
34
Implications for research According to this systematic review and meta-analysis results there are suggestions to
improve the effectiveness of future research on non-pharmacological interventions for
children and young peoplersquos cancer-related fatigue
As the majority of included non-pharmacological interventions for the fatigue of cancer
patients consist of exercise programs future research should also consider various
non-pharmacological interventions in order to understand the effectiveness of different
methods
Regarding the exercise intervention methods and studies should consider multiple
factors including the age or personal condition of the subject the disease stage and the
amount of daily activities Studies should use design prescriptions (eg frequency
intensity duration and type of exercise) and consider the adherence to the measures in
order to enhance the study strength
In measuring the results of non-pharmacological interventions there should be standard
definitions or standard measurement tools to facilitate the following systematic review
and meta-analysis that can subsequently be developed into clinical care guidelines
Reviewing the effectiveness of the current non-pharmacological management of children
and adolescent cancer patients there is still a lack of rigorous RCT research Limited by
the characteristics of cancer there is still a lack of large sample sizes
Potential conflicts of interest There is no conflict of interest
Acknowledgements
Thank you to Dr Rie Konno Research Fellow Joanna Briggs Institute for her help in
assessing studies
667
35
References 1 National Comprehensive Cancer Network( NCCN) in USA NCCN clinical practice
guideline in oncology cancer-related fatigue 2011 2 Ekti Genc R amp Conk Z Impact of effective nursing interventions to the fatigue
syndrome in children who receive chemotherapy Cancer Nursing 200831(4)312-317
3 Childhood Cancer Foundation of ROC (2009March) The classification of diseases
and age sex statistical tables of case Childhood Cancer Foundation of ROC newsletter103105-106
4 Department of Health Executive Yuan ROC (TAIWAN)(2009 March 20)2009 cause of death statistic Health and National Health Insurance Annual Statistics Information Service 2010 June 28Available httpwwwdohgovtwstatisticdatavital statists9898health statistic--lifepdf
5 Chang TK (2007December 8) Common childhood cancer and its treatment Status
Childhood Cancer Foundation of ROC (TAIWAN) 2010 September 23 Available httpwwwccfrocorgtwchildchild_events_readphpe_id=45
6 Hockenberry MJ amp Wilson D Wongs nursing care of infants and children (8th ed) St
Louis MO Mosby 2007
7 Post-White J Fitzgerald M Savik K Hooke MC Hannahan AB amp Sencer SF
Massage therapy for children with cancer Journal of Pediatric Oncology Nursing 2009 26(1)16-28
8Chiang YC Yeh CH Wang WKamp Yang CP The experience of cancer-related fatigue
in Taiwanese children European Journal of Cancer Care 2009 18(1)43-49 9Langeveld NE Grootenhuis M A Voute P A de Haan RJ amp van den Bos C No excess
fatigue in young adult survivors of childhood cancer European Journal of Cancer 200339(2)204-214
10Piper BF Lindsey AM amp Dodd MJ Fatigue mechanisms in cancer patients
developing nursing theory Oncology Nursing Forum 1987 14(6)17-23 11Nail LM amp Winningham ML Fatigue In S L Groenwald M H Forgge M Goodman
amp C H Yarbro (Eds) Cancer Nursing Principles and practice (4 th ed) Boston Jones and Bartlett1997
12Irvine D Vincent L Graydon JE Bubela N amp Thompson L The prevalence and
correlates of fatigue in patients receiving treatment with chemotherapy and
668
36
radiotherapy A comparison with the fatigue experienced by healthy individuals Cancer Nursing 199417(5)367-378
13Hinds PS amp Hockenberry-Eaton M Developing a research program on fatigue in
children and adloescents diagnosed with cancer Journal of Pediatric Oncology Nursing 200118(2)3-12
14Aaronson LS Teel CS Cassmeyer V Neuberger GB Pallikkathayil L Pierce J Press
AN Williams DP amp Wingate A Defining and measuring fatigue Journal of Nursing scholarship 1999 31(1)45-50
15Yeh CH Wang CH Chiang YC Lin Lamp Chien LC Assessment of symptoms reported
by 10- to 18-year-old cancer patients in Taiwan 2009 38(5)738-746 16 Okuyama T Akechi T Kugaya A Okamura H Shima Yamp Maruguchi M
Development and validation of the cancer fatigue scale a brief three-dimensional self-rating scale for assessment of fatigue in cancer patients Journal of Pain amp Symptom Management 2000 19(1) 5-14
17Gibson F Mulhall AB Richardson A Edwards JL Ream E amp Sepion BJ A
phenomenologic study of fatigue in adolescents receiving treatment for cancer Oncology Nursing Forum200532(3)651-660
18Wolfe J Grier HE Klar N Levin SB Ellenbogen JMamp Salem-Schatz S et al
Symptoms and suffering at the end of life in children with cancer New England Journal of Medicine 2000342(5)326-333
19Whiting P Bagnall AM Sowden AJ Cornell JE Mulrow CD amp Ramirez G
Interventions for the treatment and management of chronic fatigue syndrome a systematic review JAMA the Journal of the American Medical Association 2001286(11)1360-1368
20 Kangas M Bovbjerg DHamp Montgomery G H Cancer-related fatigue a systematic
and meta-analytic review of non-pharmacological therapies for cancer patients Psychological Bulletin 2008134 (5)700-741
21Williams PD Schmideskamp J Ridder EL amp Williams AR Symptom monitoring and
dependent care during cancer treatment in children pilot study Cancer Nursing 200629(3)188-197
22Takken T van der Torre P Zwerink M Hulzebos EH Bierings M Helders PJMamp van
der Net J Development feasibility and efficacy of a community-based exercise training
669
37
program in pediatric cancer survivors Psycho-Oncology 200918(4)440-448
23Keats MR amp Culos-Reed SN A community-based physical activity program for
adolescents with cancer (project TREK) program feasibility and preliminary findings
Pediatric hematology and oncology 200830(4) 272-280
24Hinds PS Hockenberry M Rai SN Zhang L Razzouk B I Cremer L McCarthy K amp
Rodriguez-Galindo C Clinical field testing of an enhanced-activity intervention in
hospitalized children with cancer Journal of Pain amp Symptom Management 2007
33(6)686-697
25Chiang YC The effects of ldquo a home-based aerobic exercise interventionrdquo on fatigue
and cardiorespiratory fitness in children with acute lymphoblastic leukemia during the
maintenance stage of chemotherapy Unpublished thesis Taiwan Tao-Yuan 2007
26Langeveld N Ubbink M amp Smets E I dont have any energy The experience of
fatigue in young adult survivors of childhood cancer European journal of oncology
nursing 20004(1)20-28
27 Kisner C Colby L Therapeutic exercise Foundations and techniques 2nd ed Philadelphia PAFA Davies 2007
670
38
Appendix I JBI Critical Appraisal Checklist for Experimental studies
Author__________ Year_________ Record Number__________________
Questions 1 to 4 must be answered ldquoyesrdquo for study to be included in the metashyanalysis
1 Were the participants randomized to study groups
Yes No Not clear
2 Other than research intervention were participants in each groups treated the same
Yes No Not clear
3 Were the outcomes measured in the same manner for all participants
Yes No Not clear
4 Were groups comparable at entry
Yes No Not clear
5 Was randomization of participants blinded
Yes No Not clear
6 Were those assessing outcome blinded to treatment allocation (if outcome not objective such as survival or length of hospitalization)
Yes No Not clear
7 Was allocation to treatment groups concealed from the allocator
Yes No Not clear
8 Was an appropriate statistical analysis used
671
39
Yes No Not clear
9 Were outcomes measured in a reliable way
Yes No Not clear
10 Was there adequate followshyup of participants
Yes No Not clear
Summary
TOTAL
Yes No Not clear
DECISION
Use Reject
Narrative summary only Further information needed
COMMENTS
672
40
Appendix II JBI Data Extraction Tool for Quantitative Studies Authors and Year
Journal Title
Record NumberArticle Reference No
Reviewer
Method
Settings
Participants
Number of participants
Group A Group B Group C
Control Intervention 1 Intervention 2
Interventions
Group A
Control
Group B
Intervention 1
Group C
Intervention 2
Outcome measures
Definition
673
41
Other outcome measures
Outcome description ScaleMeasure
Results
Dichotomous Data
Outcome Control Group
Numbertotal number
Treatment Group
Numbertotal number
Continuous Data
Authorrsquos Conclusions
Comments
Outcome Control Group
Mean amp SD
Treatment Group
Mean amp SD
674
43
Appendix III Details of included studies (N=6)(2720212223) RefNo Author(s)
(years) Title Study question Research
method Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
22 Takken T van der Torre P Zwerink M Hulzebos E H Bierings M Helders P J Mamp van der Net J (2009)
Development feasibility and efficacy of a community-based exercise training program in pediatric cancer survivors
To develop a 12-week home-based exercise training program (comprising aerobic and strength exercises) for children who survived ALL and to study itrsquos feasibility and efficacy
Pre-post test design
No comparsion group
Survived ALL(N=9)ages 6-14 years
1anthropometry 2 muscle strength 3functional mobility 4cardio-pulmonary
exercise test 5Fatigue
1 Feasibility questionnaire 2 anthropometry electronic scale and a wallmounted stadiometerHarpenden skin fold calipers 3 muscle strength handheld dynamometer 4functional mobility Timed Up
and Go test (TUG) 5cardio-pulmonary exercise test electronically braked cycle ergometer 6Fatigue(mean)CSI-20 (subjective experience of fatigueconcentrationmotivationphysical activity)
112-week exercise training program
2 Patients were assessed before (T0) and after (T1) 12 weeks of training
1 muscle strength execapacity functional moand fatigue showed nosignificant differences between pre(meanplusmnSD415plusmn147) and post training(meanplusmnSD3687)
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
7 Post-White J Fitzgerald M Savik K Hooke M C Hannahan A B amp Sencer S F (2009)
Massage therapy for children with cancer
To determine whether 4 weekly sessions of massage compared with 4 quiet-time control conditions would reduce anxiety cortisol levels fatigue nausea and pain in children with cancer undergoing chemotherapy and would reduce anxiety fatigue and mood disturbance in a parent
2-period crossover design (Randomized)
quiet-time
control
sessions
Children with cancer 1 to 18 years of age Twenty-three childrenparent dyads were enrolled 17 completed all data points
children 1relaxation 2symptoms 3 fatigue
parents
1anxiety 2 fatigue
children 1relaxation (heart and respiratory rates blood pressure and salivary cortisol level)
2symptoms (pain nausea anxiety 3 fatigue 1-2y3-6yLansky Play Performance Scale (PPS) 7-13y
1 4 weekly massage (MT) sessions alternated with 4 weekly quiet-time(QT) control sessions
2 children included presession and postsession vital signs (heart rate respiratory rate blood pressure) and self-report (parent proxy report for age 1-2 years) of pain nausea and anxiety Fatigue was measured before sessions 1 and 4 and at each follow-up Parent measures
included anxiety fatigue and mood states
1Massage was moreeffective than quiet tireducing heart rate inchildren anxiety in cless than age 14 yeaparent anxiety 2There were no sign
changes in blood pcortisol pain naufatigue (no state d
3 Children reported tmassage helped thebetter lessened theirand worries and hadlasting effects than q
675
44
14-18yChild Fatigue Scale (CFS) (frequency
intensity) 2 parents anxiety and fatigue
676
45
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
24 Hinds P S Hockenberry M Rai S N Zhang L Razzouk B I Cremer L McCarthy K amp Rodriguez-Galindo C (2007)
Clinical field testing of an enhanced-activity intervention in hospitalized children with cancer
To determine the feasibility of an
enhanced physical activity EPA intervention in children and adolescents hospitalized to receive chemotherapy for a solid tumor or AML and to assess the sleep and fatigue outcomes of the intervention using two different statistical approaches to analyze the longitudinal symptom data
randomized prospective two-site and two-group pilot study
Standard care Twenty nine patients (25 with a solid tumor and 4 with AML)ages 7-18 years
1 sleep duration 2 sleep efficiency 3 fatigue
1sleep duration sleep efficiency The
Wrist Actigraph The Daily Sleep Diary-Parent 2 fatigue (mean) The Fatigue Scale(FS-C) for 7-12 (intensity) The Fatigue Scale(FS-A) for 13-18 The Fatigue Scale Parent Version (FS-P) The Fatigue Scale Staff Version (FS-S)
1enhanced physical activity (EPA) (hospital-based 30 minutes
twice daily for 2-4 days) 2 T0On the day of admission
(Day 0 or baseline)patient and parents completed the fatigue instruments and a team member applied the actigraph Patients wore the wrist actigraph T1 from Day 0 to 2 or 3 consecutive days (Days 0e3) In addition the patient same parent and staff nurses completed the daily sleep and fatigue reports in the late afternoons of Days 1-3
1 ANOVA model slesignificantly more the experimental athe control arm whdifferences from bsleep efficiency vaaveraged and com
2 The patient-reported mean fatigue scoresarms were higher amadolescents than for
3 The mixed model anarevealed no significandifferences in patientfatigue between
the two study arms otime( no final result iSD only give mixed result)
677
46
23 Keats M
R amp Culos-Reed S N (2008)
A community-based physical activity program for adolescents with cancer (project TREK) program feasibility and preliminary findings
To examine the
feasibility of a
theoretically-based
physical activity (PA)
intervention in
adolescents with
cancerand
examination of the
impact of the
program on
participant QOL
including social
emotional and
physical
well-being(including fatigue)
Repeat measures longitudinal design
No comparsion group
10 adolescents(Lymphoma(4)leukemia(4)CNS tumor(1)germ cell tumor(1)) ages 14-18 years
1physical fitness 2quality of life (QOL) 3PA behavior 4fatigue
1 Feasibility was assessed by participant recruitment attendance and adherence
2physical fitness Fitnessgram 3quality of life (QOL) Pediatric Quality of Life Inventory (PedsQL) 4PA behavior leisure score index (LSI) 5fatigue (mean) pediatric Quality of life
Multidimensional Fatigue Scale (Peds QL-MFS)
(Generalsleepcognitive fatigue)
116week physical activity (PA)
2 total PA physical fitness and overall QOL was assessed at 5 different intervals T0 preintervention (baseline) T1midintervention (after the
first 8 wk) T2 postintervention
(16 wk) T3 3-months
postintervention T4 1-year poststudy
initiation
1 from baseline -wkssig Improvementstotal PA physfitness and Qgeneral fatigue(meanplusmnSD 796plusmn135)
2 from baseline to 3FUsig Improvin general fatigue(meanplusmnSD824plusmn131)slefatigue(meanplusmnSD755plusmn191)totafatigue(meanplusmnSD778plusmn150)
3at 1 years FUsImprovements in sleeprest fatigue(meanplusmnSD725plusmn203)total (meanplusmnSD 763plusmn
678
47
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
2 Gene R E amp Conk Z (2008)
Impact of Effective Nursing Interventions to the Fatigue Syndrome in Children Who Receive Chemotherapy
1 to examine the effects of an effective nursing intervention to the fatigue syndrome of children 7 to 12 years of age who receive chemotherapy 2Tto examine the relationship between fatigue and demographic variables (age sex) diagnoses ([ALL AML] lymphoma) and therapy-related variables (eg level of hemoglobin
experimental randomized controlled study
Routine nursing care
A total of 60 children who are 7-12 years of age(a new diagnosis of ALL AML or lymphoma and receiving for the first time after being diagnosed a 7- to 10-day chemotherapy treatment )
fatigue The Fatigue Scale(FS-C) for 7-12 (intensity)
The Fatigue Scale Parent Version (FS-P)
1 effective nursing interventions(45- 60mdaya week)education about the fatigue with the chemotherapy and fatigue handbook 2 T1 After a 7-day period the children
and parent were evaluated with the Fatigue Scale
1The difference betwthe 2 mean values wafound to be statisticallsignificant 2 statistically significadifference was found between the Fatigue Scale-Child mean scothe experimental (272the control group (4213)children
679
48
25 Chiang et
al(2007)
The effects of ldquo a home ndashbased aerobic exercise interventionrdquo on fatigue and cardiorespiratory fitness in children with Acute Lymphoblastic Leukemia during the maintenance stage of chemotherapy
To examine the effect of ldquo a home ndashbased aerobic exercise interventionrdquo on fatigue and cardiorespiratory fitness in children with Acute Lymphoblastic Leukemia during the maintenance stage of chemotherapy
Quasi-experi -mental
Routine
nursing care
14 pediatric oncology patients in the experimental group and 10 in control group who were matched by age and sex ages7-18 years
1Cardiorespiratory fitness
2Fatigue
1Cardiorespiratory fitness Physical Activity Recall
VO2maxHR peak 6MWT
2 Fatigue PedsQL-MFS(Generalsleepcognitive fatigue)
1A six-week home-based aerobic exercise intervention 2 8 time points T0 baseline T1-T6 every week during the
intervention(6 weeks) T7 post intervention T8 follow-up (one month after
the end of the home-based exercise program)
1 For intent-to ndash treatthe findings indicated are no intervention efftime differences by anon the subscale of fat2 For per-protocol angeneral fatigue( mean422plusmn402) was the osubscale that was siglower for children whothe exercise interventthose in control groupfollow-up assessmentmonth after the compintervention) 3 The VO2peak are significantly improvingexperimental group atbaseline- and post-intassessment The VO2was significantly highechildren who were in experimental group thcontrol subjects at post-intervention assefor the per-protocol an
680
49
Appendix IV Instrument used to measure fatigue
Name Instrument
developers
Description Used in
age in
ref
Reliability
Consistency of
instrument
Checklist Individual Strength
(CIS)22
Vercoulen et
al1996
20 items using 7-point Likert scale of
fatigue To measure four aspects of
fatiguesubjective experience
contractionmotivation physical
Activity
6-14 Not reported
Child Fatigue Scale (CFS)7 Hockenberry
et al2003
14 items 2 part questionnaire frequency
(yes or no) 5-point Likert scale of the
intensity of any yes responses
7-13
14-18 α073-o84
The Fatigue Scale for 7-12
year Olds (FS-C)224
Hockenberry
et al
14 items provide a fatigue intensity score
5-point Likert scale
7-12 αo84
The Fatigue Scale for 13-18
year Olds (FS-A)24
Hockenberry
et al
14 items provide a fatigue intensity score
5-point Likert scale
13-18 α076-o96
Pediatric Quality of life
Multidimensional Fatigue
Scale (Peds QL-MFS)2325
Varni2002 18 items to measure three aspects of
fatigueGeneralsleepcognitive
14-18 Not reported
681
50
Appendix V Excluded studies and reasons for exclusion
Baggott C Dodd M Kennedy C Marina N Miaskowski C Multiple Symptoms in Pediatric Oncology
Patients A Systematic Review Journal of Pediatric Oncology Nursing 2009 Nov-Dec 27(6)
325-339
Reason for exclusion Not outcome of interest
Barlow JH Ellard DR Psycho-educational interventions for children with chronic disease parents and
siblings an overview of the research evidence base Care Health amp Development 2004 Nov
30(6)637-45
Reason for exclusion Not outcome of interest
Bedider S Moyer CA Randomized controlled trials of pediatric massage A review Evid Based
Complement Alternat Med 2007 Mar 4(1)23-34 Epub 2006 Nov 3
Reason for exclusion Not outcome of interest
de Nijs EJ Ros W Grijpdonck MH Nursing intervention for fatigue during the treatment for cancer Cancer
Nursing 2008 31(3)191-206
Reason for exclusion Not population of interest
Edwards JL Gibson F Richardson A Sepion B Ream E Fatigue in adolescents with and following a
cancer diagnosis developing an evidence base for practice European Journal of Cancer 2003
Dec 39(18)2671-80
Reason for exclusion Not experimental or quasi-experimental study
Hinds PS Hockenberry-Eatan M Developing a research program on fatigue in children and adolescents
diagnosed with cancer Journal of Pediatric Oncology Nursing 2001 Mar-Apr 18(2 Suppl
1)3-12
Reason for exclusion Not experimental or quasi-experimental study
Hockenberry-Eaton M Hinds PS Alcoser P ONeill JB Euell K Howard V Gattuso J Taylor J Fatigue in
Children and Adolescents With Cancer Journal of Pediatric Oncology Nursing 1998 July
15(3)172-182
Reason for exclusion Not experimental or quasi-experimental study
Jean-Pierre P Mustian K Kohli S Roscoe JA Hickok JT Morrow GR Community-based clinical oncology
research trials for cancer-related fatigue The Journal of Supportive Oncology 2006 Nov-Dec
4(10)511-6
682
51
Reason for exclusion Not population of interest
Kangas M Bovbjerg DH Montgomery GH Cancer-Related Fatigue A Systematic and Meta-Analytic
Review of Non-Pharmacological Therapies for Cancer Patients Psychological Bulletin 2008 Sep
134(5)700-41
Reason for exclusion Not population of interest
Lotfi-Jam K Carey M Jefford M Schofield P Charleson C Aranda S Nonpharmacologic strategies for
managing common chemotherapy adverse effects A systematic review Journal of Clinical
Oncology 2008 Dec 1 26(34)5618-29 Epub 2008 Nov 3
Reason for exclusion Not outcome of interest
Marchese VG Chiarello LA Lange BJ Effects of physical therapy intervention for children with acute
lymphoblastic leukemia Pediatr Blood Cancer 2004 Feb42(2)127-33
Reason for exclusion Not outcome of interest
Meeske KA Siegel SE Globe DR Mack WJ Bernstein L Prevalence and correlates of fatigue in
long-term survivors of childhood leukemia Journal of Clinical Oncology 2005 Aug 20
23(24)5501-10
Reason for exclusion Not intervention study
Minton O Richardson A Sharpe M Hotopf Stone P A systematic review and meta-analysis of the
pharmacological treatment of cancer-related fatigue J Natl Cancer Inst 2008 Aug 20
100(16)1155-66 Epub 2008 Aug 11
Reason for exclusion Not population and intervention of interest
Mustian KM Morrow GR Carroll JK Figueroa-Moseley CD Pascal JP Williams GC Integrative
nonpharmacologic behavioral interventions for the management of Cancer-Related fatigue The
Oncologist 2007 12(1)52-67
Reason for exclusion Not population of interest
Neill J Belan I Ried K Effectiveness of non-pharmacological interventions for fatigue in adults with
multiple sclerosis rheumatoid arthritis or systemic lupus erythematosus a systematic review
Journal of Advanced Nursing 2006 Dec 56(6)617-35
Reason for exclusion Not population of interest
Rheingans JI A systematic review of nonpharmacologic adjunctive therapies for symptom management
Journal of Pediatric Oncology Nursing 2007 24(2) 81-94
683
52
Reason for exclusion Not outcome of interest
Rheingans JI Pediatric oncology nursesrsquo management of patients symptoms Journal of Pediatric
Oncology Nursing 2008 Nov 25(6) 303-11
Reason for exclusion Not outcome of interest
San Juan AF Fleck SJ Chamorro-Vintildea C Mateacute-Muntildeoz JL Moral S Peacuterez M Cardona C Del Valle MF
Hernaacutendez M Ramiacuterez M Madero L Lucia A Effects of an intrahospital exercise program
intervention for children with leukemia Medicine amp Science in Sports amp Exercise 2007 Jan
39(1)13-21
Reason for exclusion Not outcome of interest
Sanford SD Okuma JO Pan J Srivastava DK West N Farr L Hinds PS Gender differences in sleep
fatigue and daytime activity in a pediatric oncology sample receiving dexamethasone Journal of
Pediatric Psychology 2008 Apr 33(3)298-306 Epub 2007 Nov 17
Reason for exclusion Not experimental or quasi-experimental study
Schmitz KH Holtzman J Courneya KS Macircsse LC Duval S Kane R Controlled physical activity trials in
cancer survivors a systematic review and meta-analysis Cancer Epidemiol Biomarkers Prev
2005 Jul 14(7)1588-95
Reason for exclusion Not population of interest
van Brussel M Takken T Lucia A van der Net J Helders PJ Is physical fitness decreased in survivors of
childhood leukemia A systematic review Leukemia 2005 Jan 19(1)13-7
Reason for exclusion Not population of interest
Whiting P Bagnall AM Snowden AJ Cornell JE Mulrow CD Ramirez G Interventions for the treatment
and management of chronic fatigue syndrome JAMA 2001 Sep 19 286(11)1360-8
Reason for exclusion Not intervention of interest
Whitsett SF Gudmundsdottir M Davies B McCarthy P Friedman D Chemotherapy-related fatigue in
childhood cancer correlates consequences and coping strategies Journal of Pediatric
Oncology Nursing 2008 Mar-Apr 25(2)86-96 Epub 2008 Feb 29
Reason for exclusion Not experimental or quasi-experimental study
Winner C Muumlller C Hoffmann C Boos J Rosenbaum D Physical activity and childhood cancer Pediatr
Blood Cancer 2010 Apr 54(4)501-10
Reason for exclusion Not research study
684
53
Wu M Hsu L Zhang B Shen N Lu H Li S The experiences of cancer-related fatigue among Chinese
children with leukaemia A phenomenological study Journal of Nursing Studies 2010 Jan
47(1)49-59 Epub 2009 Aug 25
Reason for exclusion Not experimental or quasi-experimental study
Yeh CH Chiang YC Lin L Yang CP Chien LC Weaver MA Chuang HL Clinical factors associated with
fatigue over time in paediatric oncology patients receiving chemotherapy British Journal of
Cancer 2008 Jul 8 99(1)23-9 Epub 2008 Jun 24
Reason for exclusion Not experimental or quasi-experimental study
685
30
The dropout rate in the evaluated research varies a great deal ranging from 5 to 45
these dropout rates may result from the characteristics of the research subjects or the
lengthy time involved in participating in these studies The research data with a high
turnover rate might not reflect the actual outcomes of participation in exercise and the
quality of the research contained in articles with high subject turnover rates may be
lower
Exercise doses and time The exercise doses needed to reduce fatigue cannot be
determined additionally the amount of exercise completed by the patient is also
inconsistent interventions vary between 2-3 times per week and two times a day and
exercise duration varies between 10 and 45 minutes each time Furthermore the study
interventions vary in length between a couple of days and a long period of 16 weeks The
data collection times are different some were measured 12 weeks after the intervention
began some were measured during the 6 weeks of intervention some were measured
three months after the intervention was finished and some were measured after one
year
In addition disease-related symptoms decrease childrenrsquos willingness to participate in
exercise interventions inappropriate exercise intervention programs may actually
increase childrens fatigue In addition the children in the study are still developing
physically it is important to consider ways to design an interesting exercise intervention
to increase the compliance of patients in order to improve the effectiveness Although
intervention programs in the hospital or in a community sports center can improve the
effectiveness because they provide supervision the feasibility of these programs is
questionable However if the program is home-based the children need to be
supervised by parents in order to improve their compliance in doing the exercises
Furthermore regarding the nature of the intervention the results from this study indicate
that the researched non-pharmacological interventions include the following exercise
training programs physical activity massage therapy and health education interventions
However according to the National Comprehensive Cancer Network 1 clinical guidelines
663
31
for cancer non-drug measures for cancer fatigue can be separated into five categories
(1) activity enhancement (2) psychosocial interventions such as cognitive behavioral
therapy (CBT) stress management relaxation techniques and support groups (3)
attention-restoring therapy (4) nutritional consultation and (5) cognitive behavioral
therapy specifically targeting sleep disturbance Researchers have also suggested that
psychosocial interventions should be included in the future research for children with
cancer-related fatigue 22
(2) The measurement tools in the study The assessment of fatigue can be
one-dimensional or multidimensional One-dimensional assessment can help understand
the severity of fatigue symptoms however multidimensional scales are often more
credible Therefore when measuring cancer-related fatigue researchers should consider
whether there is a uniform definition of fatigue or a standardized tool for measuring
fatigue in order to facilitate further systematic meta-analyses and further develop the
clinical care guidelines
Limitations of the review The present review has some potential limitations First the low methodological quality
may influence the result Although exercise intervention seems promising quality of the
RCTs was generally quite low Future studies require better design and reporting if
methodological issues to establish evidence-based nonpharmcologic intervention
Second the identified studies covered only a limited types of nonpharmcological
intervention especially in exercise intervention The guidelines for cancer-related fatigue
in NCCN (2011)1 referred to more interventions than the ones included in this review
such as cognitive behavioral therapy and nutrition consultation Thirdly the small sample
size and effect size could be potentially having led to underpowered approach for
detecting the effects on fatigue Therefore we recommend that as research continues to
grow a re-analysis can be undertaken Fourthly Combining data in meta analysis from
664
32
studies where the ages were quite different is a potential source of heterogeneity and
may affect the interpretation of the results
Conclusion At present clinical treatment is widely used for cancer patients However child and
adolescent cancer patients often experience various side effects which cause short-term
or long-term discomfort both physically and psychologically In particular with the
increasing cure rate cancer related fatigue during or after treatment has become an
important issue This study result provided positive effect of exercise intervention on
general fatigue
Implications for practice The results of this systematic review and meta-analysis show that exercise interventions
can effectively improve the level of general fatigue In particular although the articles
were self-reported feasibility studies their results all indicate that exercise interventions
for fatigue are feasible and safe there was no conclusion to be made for the use of
massage therapy or health education measures because there was only one article for
each of these interventions
Recommendations for practice
Cancer-related fatigue is one of the most severe and frequent symptoms by pediatric
oncology children and adolescent suffered during treatment and the symptom existed
even after treatment has ended Until now no golden standard of treatment to fatigue is
established The findings call for more attention to how to reduce patientrsquos levels of
fatigue Based on the available information evaluated in this review the following
recommendations for practice are provided
665
33
bull For children aged 7 to 18 who has cancer (eg Lymphoma leukemia CNS tumor
germ cell tumor) an effective progressive aerobic exercise program is recommended to
be at least 2-3 times per week 20 to 45 minute for each session and last for 6-16 weeks
in order to reduce their general fatigue (tiredness physically weakness) In addition
adults should be involved in accompanying children while they are performing physical
exercise of which should be able to improve the adherence rate (level 2 ) ( Grade of
recommendation A)
bull For children aged 7 to 18 who has cancer (eg Lymphoma leukemia CNS tumor
germ cell tumor) an progressive aerobic exercise program will not be effective to reduce
their sleep andor rest (sleeping or resting a lot) or cognitive fatigue (problems with
thinking quickly or problems with remembering) (level 2 ) ( Grade of recommendation C)
bull Nursing interventions in educating treatment of fatigue include information about
activity nutrition energy preservation consulting and providing a useful fatigue
handbook will benefit those children who are 7 to 12 years have a new diagnosis of ALL
AML or lymphoma and receive for the first time after being diagnosed a 7- to 10-day
chemotherapy treatment (level 2) ( Grade of recommendation A)
bull A 4-week massage therapy program (the therapists massage childrenrsquos back legs
arms stomachchest and face) is not effective for children who are aged 7 to 18 and
have acute lymphoblastic leukemia brain tumors lymphoma rhabdomyosarcoma
Wilms tumor or Ewing sarcoma(level 2)( Grade of recommendation C)
bull Using a 12-week aerobic and strength exercise (45-min exercise sessions twice a
week) is not effective for children who are aged 6-14 and survived acute lymphoblaststic
leukemia age from 6 to 14(level 2) ( Grade of recommendation C)
bull Using a physical activity intervention (30minutestwice daily for 2-4days) is not
effective for children who are 7 to 18 years of age with soild tumor or AML(level 2)
( Grade of recommendation C)
666
34
Implications for research According to this systematic review and meta-analysis results there are suggestions to
improve the effectiveness of future research on non-pharmacological interventions for
children and young peoplersquos cancer-related fatigue
As the majority of included non-pharmacological interventions for the fatigue of cancer
patients consist of exercise programs future research should also consider various
non-pharmacological interventions in order to understand the effectiveness of different
methods
Regarding the exercise intervention methods and studies should consider multiple
factors including the age or personal condition of the subject the disease stage and the
amount of daily activities Studies should use design prescriptions (eg frequency
intensity duration and type of exercise) and consider the adherence to the measures in
order to enhance the study strength
In measuring the results of non-pharmacological interventions there should be standard
definitions or standard measurement tools to facilitate the following systematic review
and meta-analysis that can subsequently be developed into clinical care guidelines
Reviewing the effectiveness of the current non-pharmacological management of children
and adolescent cancer patients there is still a lack of rigorous RCT research Limited by
the characteristics of cancer there is still a lack of large sample sizes
Potential conflicts of interest There is no conflict of interest
Acknowledgements
Thank you to Dr Rie Konno Research Fellow Joanna Briggs Institute for her help in
assessing studies
667
35
References 1 National Comprehensive Cancer Network( NCCN) in USA NCCN clinical practice
guideline in oncology cancer-related fatigue 2011 2 Ekti Genc R amp Conk Z Impact of effective nursing interventions to the fatigue
syndrome in children who receive chemotherapy Cancer Nursing 200831(4)312-317
3 Childhood Cancer Foundation of ROC (2009March) The classification of diseases
and age sex statistical tables of case Childhood Cancer Foundation of ROC newsletter103105-106
4 Department of Health Executive Yuan ROC (TAIWAN)(2009 March 20)2009 cause of death statistic Health and National Health Insurance Annual Statistics Information Service 2010 June 28Available httpwwwdohgovtwstatisticdatavital statists9898health statistic--lifepdf
5 Chang TK (2007December 8) Common childhood cancer and its treatment Status
Childhood Cancer Foundation of ROC (TAIWAN) 2010 September 23 Available httpwwwccfrocorgtwchildchild_events_readphpe_id=45
6 Hockenberry MJ amp Wilson D Wongs nursing care of infants and children (8th ed) St
Louis MO Mosby 2007
7 Post-White J Fitzgerald M Savik K Hooke MC Hannahan AB amp Sencer SF
Massage therapy for children with cancer Journal of Pediatric Oncology Nursing 2009 26(1)16-28
8Chiang YC Yeh CH Wang WKamp Yang CP The experience of cancer-related fatigue
in Taiwanese children European Journal of Cancer Care 2009 18(1)43-49 9Langeveld NE Grootenhuis M A Voute P A de Haan RJ amp van den Bos C No excess
fatigue in young adult survivors of childhood cancer European Journal of Cancer 200339(2)204-214
10Piper BF Lindsey AM amp Dodd MJ Fatigue mechanisms in cancer patients
developing nursing theory Oncology Nursing Forum 1987 14(6)17-23 11Nail LM amp Winningham ML Fatigue In S L Groenwald M H Forgge M Goodman
amp C H Yarbro (Eds) Cancer Nursing Principles and practice (4 th ed) Boston Jones and Bartlett1997
12Irvine D Vincent L Graydon JE Bubela N amp Thompson L The prevalence and
correlates of fatigue in patients receiving treatment with chemotherapy and
668
36
radiotherapy A comparison with the fatigue experienced by healthy individuals Cancer Nursing 199417(5)367-378
13Hinds PS amp Hockenberry-Eaton M Developing a research program on fatigue in
children and adloescents diagnosed with cancer Journal of Pediatric Oncology Nursing 200118(2)3-12
14Aaronson LS Teel CS Cassmeyer V Neuberger GB Pallikkathayil L Pierce J Press
AN Williams DP amp Wingate A Defining and measuring fatigue Journal of Nursing scholarship 1999 31(1)45-50
15Yeh CH Wang CH Chiang YC Lin Lamp Chien LC Assessment of symptoms reported
by 10- to 18-year-old cancer patients in Taiwan 2009 38(5)738-746 16 Okuyama T Akechi T Kugaya A Okamura H Shima Yamp Maruguchi M
Development and validation of the cancer fatigue scale a brief three-dimensional self-rating scale for assessment of fatigue in cancer patients Journal of Pain amp Symptom Management 2000 19(1) 5-14
17Gibson F Mulhall AB Richardson A Edwards JL Ream E amp Sepion BJ A
phenomenologic study of fatigue in adolescents receiving treatment for cancer Oncology Nursing Forum200532(3)651-660
18Wolfe J Grier HE Klar N Levin SB Ellenbogen JMamp Salem-Schatz S et al
Symptoms and suffering at the end of life in children with cancer New England Journal of Medicine 2000342(5)326-333
19Whiting P Bagnall AM Sowden AJ Cornell JE Mulrow CD amp Ramirez G
Interventions for the treatment and management of chronic fatigue syndrome a systematic review JAMA the Journal of the American Medical Association 2001286(11)1360-1368
20 Kangas M Bovbjerg DHamp Montgomery G H Cancer-related fatigue a systematic
and meta-analytic review of non-pharmacological therapies for cancer patients Psychological Bulletin 2008134 (5)700-741
21Williams PD Schmideskamp J Ridder EL amp Williams AR Symptom monitoring and
dependent care during cancer treatment in children pilot study Cancer Nursing 200629(3)188-197
22Takken T van der Torre P Zwerink M Hulzebos EH Bierings M Helders PJMamp van
der Net J Development feasibility and efficacy of a community-based exercise training
669
37
program in pediatric cancer survivors Psycho-Oncology 200918(4)440-448
23Keats MR amp Culos-Reed SN A community-based physical activity program for
adolescents with cancer (project TREK) program feasibility and preliminary findings
Pediatric hematology and oncology 200830(4) 272-280
24Hinds PS Hockenberry M Rai SN Zhang L Razzouk B I Cremer L McCarthy K amp
Rodriguez-Galindo C Clinical field testing of an enhanced-activity intervention in
hospitalized children with cancer Journal of Pain amp Symptom Management 2007
33(6)686-697
25Chiang YC The effects of ldquo a home-based aerobic exercise interventionrdquo on fatigue
and cardiorespiratory fitness in children with acute lymphoblastic leukemia during the
maintenance stage of chemotherapy Unpublished thesis Taiwan Tao-Yuan 2007
26Langeveld N Ubbink M amp Smets E I dont have any energy The experience of
fatigue in young adult survivors of childhood cancer European journal of oncology
nursing 20004(1)20-28
27 Kisner C Colby L Therapeutic exercise Foundations and techniques 2nd ed Philadelphia PAFA Davies 2007
670
38
Appendix I JBI Critical Appraisal Checklist for Experimental studies
Author__________ Year_________ Record Number__________________
Questions 1 to 4 must be answered ldquoyesrdquo for study to be included in the metashyanalysis
1 Were the participants randomized to study groups
Yes No Not clear
2 Other than research intervention were participants in each groups treated the same
Yes No Not clear
3 Were the outcomes measured in the same manner for all participants
Yes No Not clear
4 Were groups comparable at entry
Yes No Not clear
5 Was randomization of participants blinded
Yes No Not clear
6 Were those assessing outcome blinded to treatment allocation (if outcome not objective such as survival or length of hospitalization)
Yes No Not clear
7 Was allocation to treatment groups concealed from the allocator
Yes No Not clear
8 Was an appropriate statistical analysis used
671
39
Yes No Not clear
9 Were outcomes measured in a reliable way
Yes No Not clear
10 Was there adequate followshyup of participants
Yes No Not clear
Summary
TOTAL
Yes No Not clear
DECISION
Use Reject
Narrative summary only Further information needed
COMMENTS
672
40
Appendix II JBI Data Extraction Tool for Quantitative Studies Authors and Year
Journal Title
Record NumberArticle Reference No
Reviewer
Method
Settings
Participants
Number of participants
Group A Group B Group C
Control Intervention 1 Intervention 2
Interventions
Group A
Control
Group B
Intervention 1
Group C
Intervention 2
Outcome measures
Definition
673
41
Other outcome measures
Outcome description ScaleMeasure
Results
Dichotomous Data
Outcome Control Group
Numbertotal number
Treatment Group
Numbertotal number
Continuous Data
Authorrsquos Conclusions
Comments
Outcome Control Group
Mean amp SD
Treatment Group
Mean amp SD
674
43
Appendix III Details of included studies (N=6)(2720212223) RefNo Author(s)
(years) Title Study question Research
method Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
22 Takken T van der Torre P Zwerink M Hulzebos E H Bierings M Helders P J Mamp van der Net J (2009)
Development feasibility and efficacy of a community-based exercise training program in pediatric cancer survivors
To develop a 12-week home-based exercise training program (comprising aerobic and strength exercises) for children who survived ALL and to study itrsquos feasibility and efficacy
Pre-post test design
No comparsion group
Survived ALL(N=9)ages 6-14 years
1anthropometry 2 muscle strength 3functional mobility 4cardio-pulmonary
exercise test 5Fatigue
1 Feasibility questionnaire 2 anthropometry electronic scale and a wallmounted stadiometerHarpenden skin fold calipers 3 muscle strength handheld dynamometer 4functional mobility Timed Up
and Go test (TUG) 5cardio-pulmonary exercise test electronically braked cycle ergometer 6Fatigue(mean)CSI-20 (subjective experience of fatigueconcentrationmotivationphysical activity)
112-week exercise training program
2 Patients were assessed before (T0) and after (T1) 12 weeks of training
1 muscle strength execapacity functional moand fatigue showed nosignificant differences between pre(meanplusmnSD415plusmn147) and post training(meanplusmnSD3687)
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
7 Post-White J Fitzgerald M Savik K Hooke M C Hannahan A B amp Sencer S F (2009)
Massage therapy for children with cancer
To determine whether 4 weekly sessions of massage compared with 4 quiet-time control conditions would reduce anxiety cortisol levels fatigue nausea and pain in children with cancer undergoing chemotherapy and would reduce anxiety fatigue and mood disturbance in a parent
2-period crossover design (Randomized)
quiet-time
control
sessions
Children with cancer 1 to 18 years of age Twenty-three childrenparent dyads were enrolled 17 completed all data points
children 1relaxation 2symptoms 3 fatigue
parents
1anxiety 2 fatigue
children 1relaxation (heart and respiratory rates blood pressure and salivary cortisol level)
2symptoms (pain nausea anxiety 3 fatigue 1-2y3-6yLansky Play Performance Scale (PPS) 7-13y
1 4 weekly massage (MT) sessions alternated with 4 weekly quiet-time(QT) control sessions
2 children included presession and postsession vital signs (heart rate respiratory rate blood pressure) and self-report (parent proxy report for age 1-2 years) of pain nausea and anxiety Fatigue was measured before sessions 1 and 4 and at each follow-up Parent measures
included anxiety fatigue and mood states
1Massage was moreeffective than quiet tireducing heart rate inchildren anxiety in cless than age 14 yeaparent anxiety 2There were no sign
changes in blood pcortisol pain naufatigue (no state d
3 Children reported tmassage helped thebetter lessened theirand worries and hadlasting effects than q
675
44
14-18yChild Fatigue Scale (CFS) (frequency
intensity) 2 parents anxiety and fatigue
676
45
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
24 Hinds P S Hockenberry M Rai S N Zhang L Razzouk B I Cremer L McCarthy K amp Rodriguez-Galindo C (2007)
Clinical field testing of an enhanced-activity intervention in hospitalized children with cancer
To determine the feasibility of an
enhanced physical activity EPA intervention in children and adolescents hospitalized to receive chemotherapy for a solid tumor or AML and to assess the sleep and fatigue outcomes of the intervention using two different statistical approaches to analyze the longitudinal symptom data
randomized prospective two-site and two-group pilot study
Standard care Twenty nine patients (25 with a solid tumor and 4 with AML)ages 7-18 years
1 sleep duration 2 sleep efficiency 3 fatigue
1sleep duration sleep efficiency The
Wrist Actigraph The Daily Sleep Diary-Parent 2 fatigue (mean) The Fatigue Scale(FS-C) for 7-12 (intensity) The Fatigue Scale(FS-A) for 13-18 The Fatigue Scale Parent Version (FS-P) The Fatigue Scale Staff Version (FS-S)
1enhanced physical activity (EPA) (hospital-based 30 minutes
twice daily for 2-4 days) 2 T0On the day of admission
(Day 0 or baseline)patient and parents completed the fatigue instruments and a team member applied the actigraph Patients wore the wrist actigraph T1 from Day 0 to 2 or 3 consecutive days (Days 0e3) In addition the patient same parent and staff nurses completed the daily sleep and fatigue reports in the late afternoons of Days 1-3
1 ANOVA model slesignificantly more the experimental athe control arm whdifferences from bsleep efficiency vaaveraged and com
2 The patient-reported mean fatigue scoresarms were higher amadolescents than for
3 The mixed model anarevealed no significandifferences in patientfatigue between
the two study arms otime( no final result iSD only give mixed result)
677
46
23 Keats M
R amp Culos-Reed S N (2008)
A community-based physical activity program for adolescents with cancer (project TREK) program feasibility and preliminary findings
To examine the
feasibility of a
theoretically-based
physical activity (PA)
intervention in
adolescents with
cancerand
examination of the
impact of the
program on
participant QOL
including social
emotional and
physical
well-being(including fatigue)
Repeat measures longitudinal design
No comparsion group
10 adolescents(Lymphoma(4)leukemia(4)CNS tumor(1)germ cell tumor(1)) ages 14-18 years
1physical fitness 2quality of life (QOL) 3PA behavior 4fatigue
1 Feasibility was assessed by participant recruitment attendance and adherence
2physical fitness Fitnessgram 3quality of life (QOL) Pediatric Quality of Life Inventory (PedsQL) 4PA behavior leisure score index (LSI) 5fatigue (mean) pediatric Quality of life
Multidimensional Fatigue Scale (Peds QL-MFS)
(Generalsleepcognitive fatigue)
116week physical activity (PA)
2 total PA physical fitness and overall QOL was assessed at 5 different intervals T0 preintervention (baseline) T1midintervention (after the
first 8 wk) T2 postintervention
(16 wk) T3 3-months
postintervention T4 1-year poststudy
initiation
1 from baseline -wkssig Improvementstotal PA physfitness and Qgeneral fatigue(meanplusmnSD 796plusmn135)
2 from baseline to 3FUsig Improvin general fatigue(meanplusmnSD824plusmn131)slefatigue(meanplusmnSD755plusmn191)totafatigue(meanplusmnSD778plusmn150)
3at 1 years FUsImprovements in sleeprest fatigue(meanplusmnSD725plusmn203)total (meanplusmnSD 763plusmn
678
47
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
2 Gene R E amp Conk Z (2008)
Impact of Effective Nursing Interventions to the Fatigue Syndrome in Children Who Receive Chemotherapy
1 to examine the effects of an effective nursing intervention to the fatigue syndrome of children 7 to 12 years of age who receive chemotherapy 2Tto examine the relationship between fatigue and demographic variables (age sex) diagnoses ([ALL AML] lymphoma) and therapy-related variables (eg level of hemoglobin
experimental randomized controlled study
Routine nursing care
A total of 60 children who are 7-12 years of age(a new diagnosis of ALL AML or lymphoma and receiving for the first time after being diagnosed a 7- to 10-day chemotherapy treatment )
fatigue The Fatigue Scale(FS-C) for 7-12 (intensity)
The Fatigue Scale Parent Version (FS-P)
1 effective nursing interventions(45- 60mdaya week)education about the fatigue with the chemotherapy and fatigue handbook 2 T1 After a 7-day period the children
and parent were evaluated with the Fatigue Scale
1The difference betwthe 2 mean values wafound to be statisticallsignificant 2 statistically significadifference was found between the Fatigue Scale-Child mean scothe experimental (272the control group (4213)children
679
48
25 Chiang et
al(2007)
The effects of ldquo a home ndashbased aerobic exercise interventionrdquo on fatigue and cardiorespiratory fitness in children with Acute Lymphoblastic Leukemia during the maintenance stage of chemotherapy
To examine the effect of ldquo a home ndashbased aerobic exercise interventionrdquo on fatigue and cardiorespiratory fitness in children with Acute Lymphoblastic Leukemia during the maintenance stage of chemotherapy
Quasi-experi -mental
Routine
nursing care
14 pediatric oncology patients in the experimental group and 10 in control group who were matched by age and sex ages7-18 years
1Cardiorespiratory fitness
2Fatigue
1Cardiorespiratory fitness Physical Activity Recall
VO2maxHR peak 6MWT
2 Fatigue PedsQL-MFS(Generalsleepcognitive fatigue)
1A six-week home-based aerobic exercise intervention 2 8 time points T0 baseline T1-T6 every week during the
intervention(6 weeks) T7 post intervention T8 follow-up (one month after
the end of the home-based exercise program)
1 For intent-to ndash treatthe findings indicated are no intervention efftime differences by anon the subscale of fat2 For per-protocol angeneral fatigue( mean422plusmn402) was the osubscale that was siglower for children whothe exercise interventthose in control groupfollow-up assessmentmonth after the compintervention) 3 The VO2peak are significantly improvingexperimental group atbaseline- and post-intassessment The VO2was significantly highechildren who were in experimental group thcontrol subjects at post-intervention assefor the per-protocol an
680
49
Appendix IV Instrument used to measure fatigue
Name Instrument
developers
Description Used in
age in
ref
Reliability
Consistency of
instrument
Checklist Individual Strength
(CIS)22
Vercoulen et
al1996
20 items using 7-point Likert scale of
fatigue To measure four aspects of
fatiguesubjective experience
contractionmotivation physical
Activity
6-14 Not reported
Child Fatigue Scale (CFS)7 Hockenberry
et al2003
14 items 2 part questionnaire frequency
(yes or no) 5-point Likert scale of the
intensity of any yes responses
7-13
14-18 α073-o84
The Fatigue Scale for 7-12
year Olds (FS-C)224
Hockenberry
et al
14 items provide a fatigue intensity score
5-point Likert scale
7-12 αo84
The Fatigue Scale for 13-18
year Olds (FS-A)24
Hockenberry
et al
14 items provide a fatigue intensity score
5-point Likert scale
13-18 α076-o96
Pediatric Quality of life
Multidimensional Fatigue
Scale (Peds QL-MFS)2325
Varni2002 18 items to measure three aspects of
fatigueGeneralsleepcognitive
14-18 Not reported
681
50
Appendix V Excluded studies and reasons for exclusion
Baggott C Dodd M Kennedy C Marina N Miaskowski C Multiple Symptoms in Pediatric Oncology
Patients A Systematic Review Journal of Pediatric Oncology Nursing 2009 Nov-Dec 27(6)
325-339
Reason for exclusion Not outcome of interest
Barlow JH Ellard DR Psycho-educational interventions for children with chronic disease parents and
siblings an overview of the research evidence base Care Health amp Development 2004 Nov
30(6)637-45
Reason for exclusion Not outcome of interest
Bedider S Moyer CA Randomized controlled trials of pediatric massage A review Evid Based
Complement Alternat Med 2007 Mar 4(1)23-34 Epub 2006 Nov 3
Reason for exclusion Not outcome of interest
de Nijs EJ Ros W Grijpdonck MH Nursing intervention for fatigue during the treatment for cancer Cancer
Nursing 2008 31(3)191-206
Reason for exclusion Not population of interest
Edwards JL Gibson F Richardson A Sepion B Ream E Fatigue in adolescents with and following a
cancer diagnosis developing an evidence base for practice European Journal of Cancer 2003
Dec 39(18)2671-80
Reason for exclusion Not experimental or quasi-experimental study
Hinds PS Hockenberry-Eatan M Developing a research program on fatigue in children and adolescents
diagnosed with cancer Journal of Pediatric Oncology Nursing 2001 Mar-Apr 18(2 Suppl
1)3-12
Reason for exclusion Not experimental or quasi-experimental study
Hockenberry-Eaton M Hinds PS Alcoser P ONeill JB Euell K Howard V Gattuso J Taylor J Fatigue in
Children and Adolescents With Cancer Journal of Pediatric Oncology Nursing 1998 July
15(3)172-182
Reason for exclusion Not experimental or quasi-experimental study
Jean-Pierre P Mustian K Kohli S Roscoe JA Hickok JT Morrow GR Community-based clinical oncology
research trials for cancer-related fatigue The Journal of Supportive Oncology 2006 Nov-Dec
4(10)511-6
682
51
Reason for exclusion Not population of interest
Kangas M Bovbjerg DH Montgomery GH Cancer-Related Fatigue A Systematic and Meta-Analytic
Review of Non-Pharmacological Therapies for Cancer Patients Psychological Bulletin 2008 Sep
134(5)700-41
Reason for exclusion Not population of interest
Lotfi-Jam K Carey M Jefford M Schofield P Charleson C Aranda S Nonpharmacologic strategies for
managing common chemotherapy adverse effects A systematic review Journal of Clinical
Oncology 2008 Dec 1 26(34)5618-29 Epub 2008 Nov 3
Reason for exclusion Not outcome of interest
Marchese VG Chiarello LA Lange BJ Effects of physical therapy intervention for children with acute
lymphoblastic leukemia Pediatr Blood Cancer 2004 Feb42(2)127-33
Reason for exclusion Not outcome of interest
Meeske KA Siegel SE Globe DR Mack WJ Bernstein L Prevalence and correlates of fatigue in
long-term survivors of childhood leukemia Journal of Clinical Oncology 2005 Aug 20
23(24)5501-10
Reason for exclusion Not intervention study
Minton O Richardson A Sharpe M Hotopf Stone P A systematic review and meta-analysis of the
pharmacological treatment of cancer-related fatigue J Natl Cancer Inst 2008 Aug 20
100(16)1155-66 Epub 2008 Aug 11
Reason for exclusion Not population and intervention of interest
Mustian KM Morrow GR Carroll JK Figueroa-Moseley CD Pascal JP Williams GC Integrative
nonpharmacologic behavioral interventions for the management of Cancer-Related fatigue The
Oncologist 2007 12(1)52-67
Reason for exclusion Not population of interest
Neill J Belan I Ried K Effectiveness of non-pharmacological interventions for fatigue in adults with
multiple sclerosis rheumatoid arthritis or systemic lupus erythematosus a systematic review
Journal of Advanced Nursing 2006 Dec 56(6)617-35
Reason for exclusion Not population of interest
Rheingans JI A systematic review of nonpharmacologic adjunctive therapies for symptom management
Journal of Pediatric Oncology Nursing 2007 24(2) 81-94
683
52
Reason for exclusion Not outcome of interest
Rheingans JI Pediatric oncology nursesrsquo management of patients symptoms Journal of Pediatric
Oncology Nursing 2008 Nov 25(6) 303-11
Reason for exclusion Not outcome of interest
San Juan AF Fleck SJ Chamorro-Vintildea C Mateacute-Muntildeoz JL Moral S Peacuterez M Cardona C Del Valle MF
Hernaacutendez M Ramiacuterez M Madero L Lucia A Effects of an intrahospital exercise program
intervention for children with leukemia Medicine amp Science in Sports amp Exercise 2007 Jan
39(1)13-21
Reason for exclusion Not outcome of interest
Sanford SD Okuma JO Pan J Srivastava DK West N Farr L Hinds PS Gender differences in sleep
fatigue and daytime activity in a pediatric oncology sample receiving dexamethasone Journal of
Pediatric Psychology 2008 Apr 33(3)298-306 Epub 2007 Nov 17
Reason for exclusion Not experimental or quasi-experimental study
Schmitz KH Holtzman J Courneya KS Macircsse LC Duval S Kane R Controlled physical activity trials in
cancer survivors a systematic review and meta-analysis Cancer Epidemiol Biomarkers Prev
2005 Jul 14(7)1588-95
Reason for exclusion Not population of interest
van Brussel M Takken T Lucia A van der Net J Helders PJ Is physical fitness decreased in survivors of
childhood leukemia A systematic review Leukemia 2005 Jan 19(1)13-7
Reason for exclusion Not population of interest
Whiting P Bagnall AM Snowden AJ Cornell JE Mulrow CD Ramirez G Interventions for the treatment
and management of chronic fatigue syndrome JAMA 2001 Sep 19 286(11)1360-8
Reason for exclusion Not intervention of interest
Whitsett SF Gudmundsdottir M Davies B McCarthy P Friedman D Chemotherapy-related fatigue in
childhood cancer correlates consequences and coping strategies Journal of Pediatric
Oncology Nursing 2008 Mar-Apr 25(2)86-96 Epub 2008 Feb 29
Reason for exclusion Not experimental or quasi-experimental study
Winner C Muumlller C Hoffmann C Boos J Rosenbaum D Physical activity and childhood cancer Pediatr
Blood Cancer 2010 Apr 54(4)501-10
Reason for exclusion Not research study
684
53
Wu M Hsu L Zhang B Shen N Lu H Li S The experiences of cancer-related fatigue among Chinese
children with leukaemia A phenomenological study Journal of Nursing Studies 2010 Jan
47(1)49-59 Epub 2009 Aug 25
Reason for exclusion Not experimental or quasi-experimental study
Yeh CH Chiang YC Lin L Yang CP Chien LC Weaver MA Chuang HL Clinical factors associated with
fatigue over time in paediatric oncology patients receiving chemotherapy British Journal of
Cancer 2008 Jul 8 99(1)23-9 Epub 2008 Jun 24
Reason for exclusion Not experimental or quasi-experimental study
685
31
for cancer non-drug measures for cancer fatigue can be separated into five categories
(1) activity enhancement (2) psychosocial interventions such as cognitive behavioral
therapy (CBT) stress management relaxation techniques and support groups (3)
attention-restoring therapy (4) nutritional consultation and (5) cognitive behavioral
therapy specifically targeting sleep disturbance Researchers have also suggested that
psychosocial interventions should be included in the future research for children with
cancer-related fatigue 22
(2) The measurement tools in the study The assessment of fatigue can be
one-dimensional or multidimensional One-dimensional assessment can help understand
the severity of fatigue symptoms however multidimensional scales are often more
credible Therefore when measuring cancer-related fatigue researchers should consider
whether there is a uniform definition of fatigue or a standardized tool for measuring
fatigue in order to facilitate further systematic meta-analyses and further develop the
clinical care guidelines
Limitations of the review The present review has some potential limitations First the low methodological quality
may influence the result Although exercise intervention seems promising quality of the
RCTs was generally quite low Future studies require better design and reporting if
methodological issues to establish evidence-based nonpharmcologic intervention
Second the identified studies covered only a limited types of nonpharmcological
intervention especially in exercise intervention The guidelines for cancer-related fatigue
in NCCN (2011)1 referred to more interventions than the ones included in this review
such as cognitive behavioral therapy and nutrition consultation Thirdly the small sample
size and effect size could be potentially having led to underpowered approach for
detecting the effects on fatigue Therefore we recommend that as research continues to
grow a re-analysis can be undertaken Fourthly Combining data in meta analysis from
664
32
studies where the ages were quite different is a potential source of heterogeneity and
may affect the interpretation of the results
Conclusion At present clinical treatment is widely used for cancer patients However child and
adolescent cancer patients often experience various side effects which cause short-term
or long-term discomfort both physically and psychologically In particular with the
increasing cure rate cancer related fatigue during or after treatment has become an
important issue This study result provided positive effect of exercise intervention on
general fatigue
Implications for practice The results of this systematic review and meta-analysis show that exercise interventions
can effectively improve the level of general fatigue In particular although the articles
were self-reported feasibility studies their results all indicate that exercise interventions
for fatigue are feasible and safe there was no conclusion to be made for the use of
massage therapy or health education measures because there was only one article for
each of these interventions
Recommendations for practice
Cancer-related fatigue is one of the most severe and frequent symptoms by pediatric
oncology children and adolescent suffered during treatment and the symptom existed
even after treatment has ended Until now no golden standard of treatment to fatigue is
established The findings call for more attention to how to reduce patientrsquos levels of
fatigue Based on the available information evaluated in this review the following
recommendations for practice are provided
665
33
bull For children aged 7 to 18 who has cancer (eg Lymphoma leukemia CNS tumor
germ cell tumor) an effective progressive aerobic exercise program is recommended to
be at least 2-3 times per week 20 to 45 minute for each session and last for 6-16 weeks
in order to reduce their general fatigue (tiredness physically weakness) In addition
adults should be involved in accompanying children while they are performing physical
exercise of which should be able to improve the adherence rate (level 2 ) ( Grade of
recommendation A)
bull For children aged 7 to 18 who has cancer (eg Lymphoma leukemia CNS tumor
germ cell tumor) an progressive aerobic exercise program will not be effective to reduce
their sleep andor rest (sleeping or resting a lot) or cognitive fatigue (problems with
thinking quickly or problems with remembering) (level 2 ) ( Grade of recommendation C)
bull Nursing interventions in educating treatment of fatigue include information about
activity nutrition energy preservation consulting and providing a useful fatigue
handbook will benefit those children who are 7 to 12 years have a new diagnosis of ALL
AML or lymphoma and receive for the first time after being diagnosed a 7- to 10-day
chemotherapy treatment (level 2) ( Grade of recommendation A)
bull A 4-week massage therapy program (the therapists massage childrenrsquos back legs
arms stomachchest and face) is not effective for children who are aged 7 to 18 and
have acute lymphoblastic leukemia brain tumors lymphoma rhabdomyosarcoma
Wilms tumor or Ewing sarcoma(level 2)( Grade of recommendation C)
bull Using a 12-week aerobic and strength exercise (45-min exercise sessions twice a
week) is not effective for children who are aged 6-14 and survived acute lymphoblaststic
leukemia age from 6 to 14(level 2) ( Grade of recommendation C)
bull Using a physical activity intervention (30minutestwice daily for 2-4days) is not
effective for children who are 7 to 18 years of age with soild tumor or AML(level 2)
( Grade of recommendation C)
666
34
Implications for research According to this systematic review and meta-analysis results there are suggestions to
improve the effectiveness of future research on non-pharmacological interventions for
children and young peoplersquos cancer-related fatigue
As the majority of included non-pharmacological interventions for the fatigue of cancer
patients consist of exercise programs future research should also consider various
non-pharmacological interventions in order to understand the effectiveness of different
methods
Regarding the exercise intervention methods and studies should consider multiple
factors including the age or personal condition of the subject the disease stage and the
amount of daily activities Studies should use design prescriptions (eg frequency
intensity duration and type of exercise) and consider the adherence to the measures in
order to enhance the study strength
In measuring the results of non-pharmacological interventions there should be standard
definitions or standard measurement tools to facilitate the following systematic review
and meta-analysis that can subsequently be developed into clinical care guidelines
Reviewing the effectiveness of the current non-pharmacological management of children
and adolescent cancer patients there is still a lack of rigorous RCT research Limited by
the characteristics of cancer there is still a lack of large sample sizes
Potential conflicts of interest There is no conflict of interest
Acknowledgements
Thank you to Dr Rie Konno Research Fellow Joanna Briggs Institute for her help in
assessing studies
667
35
References 1 National Comprehensive Cancer Network( NCCN) in USA NCCN clinical practice
guideline in oncology cancer-related fatigue 2011 2 Ekti Genc R amp Conk Z Impact of effective nursing interventions to the fatigue
syndrome in children who receive chemotherapy Cancer Nursing 200831(4)312-317
3 Childhood Cancer Foundation of ROC (2009March) The classification of diseases
and age sex statistical tables of case Childhood Cancer Foundation of ROC newsletter103105-106
4 Department of Health Executive Yuan ROC (TAIWAN)(2009 March 20)2009 cause of death statistic Health and National Health Insurance Annual Statistics Information Service 2010 June 28Available httpwwwdohgovtwstatisticdatavital statists9898health statistic--lifepdf
5 Chang TK (2007December 8) Common childhood cancer and its treatment Status
Childhood Cancer Foundation of ROC (TAIWAN) 2010 September 23 Available httpwwwccfrocorgtwchildchild_events_readphpe_id=45
6 Hockenberry MJ amp Wilson D Wongs nursing care of infants and children (8th ed) St
Louis MO Mosby 2007
7 Post-White J Fitzgerald M Savik K Hooke MC Hannahan AB amp Sencer SF
Massage therapy for children with cancer Journal of Pediatric Oncology Nursing 2009 26(1)16-28
8Chiang YC Yeh CH Wang WKamp Yang CP The experience of cancer-related fatigue
in Taiwanese children European Journal of Cancer Care 2009 18(1)43-49 9Langeveld NE Grootenhuis M A Voute P A de Haan RJ amp van den Bos C No excess
fatigue in young adult survivors of childhood cancer European Journal of Cancer 200339(2)204-214
10Piper BF Lindsey AM amp Dodd MJ Fatigue mechanisms in cancer patients
developing nursing theory Oncology Nursing Forum 1987 14(6)17-23 11Nail LM amp Winningham ML Fatigue In S L Groenwald M H Forgge M Goodman
amp C H Yarbro (Eds) Cancer Nursing Principles and practice (4 th ed) Boston Jones and Bartlett1997
12Irvine D Vincent L Graydon JE Bubela N amp Thompson L The prevalence and
correlates of fatigue in patients receiving treatment with chemotherapy and
668
36
radiotherapy A comparison with the fatigue experienced by healthy individuals Cancer Nursing 199417(5)367-378
13Hinds PS amp Hockenberry-Eaton M Developing a research program on fatigue in
children and adloescents diagnosed with cancer Journal of Pediatric Oncology Nursing 200118(2)3-12
14Aaronson LS Teel CS Cassmeyer V Neuberger GB Pallikkathayil L Pierce J Press
AN Williams DP amp Wingate A Defining and measuring fatigue Journal of Nursing scholarship 1999 31(1)45-50
15Yeh CH Wang CH Chiang YC Lin Lamp Chien LC Assessment of symptoms reported
by 10- to 18-year-old cancer patients in Taiwan 2009 38(5)738-746 16 Okuyama T Akechi T Kugaya A Okamura H Shima Yamp Maruguchi M
Development and validation of the cancer fatigue scale a brief three-dimensional self-rating scale for assessment of fatigue in cancer patients Journal of Pain amp Symptom Management 2000 19(1) 5-14
17Gibson F Mulhall AB Richardson A Edwards JL Ream E amp Sepion BJ A
phenomenologic study of fatigue in adolescents receiving treatment for cancer Oncology Nursing Forum200532(3)651-660
18Wolfe J Grier HE Klar N Levin SB Ellenbogen JMamp Salem-Schatz S et al
Symptoms and suffering at the end of life in children with cancer New England Journal of Medicine 2000342(5)326-333
19Whiting P Bagnall AM Sowden AJ Cornell JE Mulrow CD amp Ramirez G
Interventions for the treatment and management of chronic fatigue syndrome a systematic review JAMA the Journal of the American Medical Association 2001286(11)1360-1368
20 Kangas M Bovbjerg DHamp Montgomery G H Cancer-related fatigue a systematic
and meta-analytic review of non-pharmacological therapies for cancer patients Psychological Bulletin 2008134 (5)700-741
21Williams PD Schmideskamp J Ridder EL amp Williams AR Symptom monitoring and
dependent care during cancer treatment in children pilot study Cancer Nursing 200629(3)188-197
22Takken T van der Torre P Zwerink M Hulzebos EH Bierings M Helders PJMamp van
der Net J Development feasibility and efficacy of a community-based exercise training
669
37
program in pediatric cancer survivors Psycho-Oncology 200918(4)440-448
23Keats MR amp Culos-Reed SN A community-based physical activity program for
adolescents with cancer (project TREK) program feasibility and preliminary findings
Pediatric hematology and oncology 200830(4) 272-280
24Hinds PS Hockenberry M Rai SN Zhang L Razzouk B I Cremer L McCarthy K amp
Rodriguez-Galindo C Clinical field testing of an enhanced-activity intervention in
hospitalized children with cancer Journal of Pain amp Symptom Management 2007
33(6)686-697
25Chiang YC The effects of ldquo a home-based aerobic exercise interventionrdquo on fatigue
and cardiorespiratory fitness in children with acute lymphoblastic leukemia during the
maintenance stage of chemotherapy Unpublished thesis Taiwan Tao-Yuan 2007
26Langeveld N Ubbink M amp Smets E I dont have any energy The experience of
fatigue in young adult survivors of childhood cancer European journal of oncology
nursing 20004(1)20-28
27 Kisner C Colby L Therapeutic exercise Foundations and techniques 2nd ed Philadelphia PAFA Davies 2007
670
38
Appendix I JBI Critical Appraisal Checklist for Experimental studies
Author__________ Year_________ Record Number__________________
Questions 1 to 4 must be answered ldquoyesrdquo for study to be included in the metashyanalysis
1 Were the participants randomized to study groups
Yes No Not clear
2 Other than research intervention were participants in each groups treated the same
Yes No Not clear
3 Were the outcomes measured in the same manner for all participants
Yes No Not clear
4 Were groups comparable at entry
Yes No Not clear
5 Was randomization of participants blinded
Yes No Not clear
6 Were those assessing outcome blinded to treatment allocation (if outcome not objective such as survival or length of hospitalization)
Yes No Not clear
7 Was allocation to treatment groups concealed from the allocator
Yes No Not clear
8 Was an appropriate statistical analysis used
671
39
Yes No Not clear
9 Were outcomes measured in a reliable way
Yes No Not clear
10 Was there adequate followshyup of participants
Yes No Not clear
Summary
TOTAL
Yes No Not clear
DECISION
Use Reject
Narrative summary only Further information needed
COMMENTS
672
40
Appendix II JBI Data Extraction Tool for Quantitative Studies Authors and Year
Journal Title
Record NumberArticle Reference No
Reviewer
Method
Settings
Participants
Number of participants
Group A Group B Group C
Control Intervention 1 Intervention 2
Interventions
Group A
Control
Group B
Intervention 1
Group C
Intervention 2
Outcome measures
Definition
673
41
Other outcome measures
Outcome description ScaleMeasure
Results
Dichotomous Data
Outcome Control Group
Numbertotal number
Treatment Group
Numbertotal number
Continuous Data
Authorrsquos Conclusions
Comments
Outcome Control Group
Mean amp SD
Treatment Group
Mean amp SD
674
43
Appendix III Details of included studies (N=6)(2720212223) RefNo Author(s)
(years) Title Study question Research
method Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
22 Takken T van der Torre P Zwerink M Hulzebos E H Bierings M Helders P J Mamp van der Net J (2009)
Development feasibility and efficacy of a community-based exercise training program in pediatric cancer survivors
To develop a 12-week home-based exercise training program (comprising aerobic and strength exercises) for children who survived ALL and to study itrsquos feasibility and efficacy
Pre-post test design
No comparsion group
Survived ALL(N=9)ages 6-14 years
1anthropometry 2 muscle strength 3functional mobility 4cardio-pulmonary
exercise test 5Fatigue
1 Feasibility questionnaire 2 anthropometry electronic scale and a wallmounted stadiometerHarpenden skin fold calipers 3 muscle strength handheld dynamometer 4functional mobility Timed Up
and Go test (TUG) 5cardio-pulmonary exercise test electronically braked cycle ergometer 6Fatigue(mean)CSI-20 (subjective experience of fatigueconcentrationmotivationphysical activity)
112-week exercise training program
2 Patients were assessed before (T0) and after (T1) 12 weeks of training
1 muscle strength execapacity functional moand fatigue showed nosignificant differences between pre(meanplusmnSD415plusmn147) and post training(meanplusmnSD3687)
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
7 Post-White J Fitzgerald M Savik K Hooke M C Hannahan A B amp Sencer S F (2009)
Massage therapy for children with cancer
To determine whether 4 weekly sessions of massage compared with 4 quiet-time control conditions would reduce anxiety cortisol levels fatigue nausea and pain in children with cancer undergoing chemotherapy and would reduce anxiety fatigue and mood disturbance in a parent
2-period crossover design (Randomized)
quiet-time
control
sessions
Children with cancer 1 to 18 years of age Twenty-three childrenparent dyads were enrolled 17 completed all data points
children 1relaxation 2symptoms 3 fatigue
parents
1anxiety 2 fatigue
children 1relaxation (heart and respiratory rates blood pressure and salivary cortisol level)
2symptoms (pain nausea anxiety 3 fatigue 1-2y3-6yLansky Play Performance Scale (PPS) 7-13y
1 4 weekly massage (MT) sessions alternated with 4 weekly quiet-time(QT) control sessions
2 children included presession and postsession vital signs (heart rate respiratory rate blood pressure) and self-report (parent proxy report for age 1-2 years) of pain nausea and anxiety Fatigue was measured before sessions 1 and 4 and at each follow-up Parent measures
included anxiety fatigue and mood states
1Massage was moreeffective than quiet tireducing heart rate inchildren anxiety in cless than age 14 yeaparent anxiety 2There were no sign
changes in blood pcortisol pain naufatigue (no state d
3 Children reported tmassage helped thebetter lessened theirand worries and hadlasting effects than q
675
44
14-18yChild Fatigue Scale (CFS) (frequency
intensity) 2 parents anxiety and fatigue
676
45
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
24 Hinds P S Hockenberry M Rai S N Zhang L Razzouk B I Cremer L McCarthy K amp Rodriguez-Galindo C (2007)
Clinical field testing of an enhanced-activity intervention in hospitalized children with cancer
To determine the feasibility of an
enhanced physical activity EPA intervention in children and adolescents hospitalized to receive chemotherapy for a solid tumor or AML and to assess the sleep and fatigue outcomes of the intervention using two different statistical approaches to analyze the longitudinal symptom data
randomized prospective two-site and two-group pilot study
Standard care Twenty nine patients (25 with a solid tumor and 4 with AML)ages 7-18 years
1 sleep duration 2 sleep efficiency 3 fatigue
1sleep duration sleep efficiency The
Wrist Actigraph The Daily Sleep Diary-Parent 2 fatigue (mean) The Fatigue Scale(FS-C) for 7-12 (intensity) The Fatigue Scale(FS-A) for 13-18 The Fatigue Scale Parent Version (FS-P) The Fatigue Scale Staff Version (FS-S)
1enhanced physical activity (EPA) (hospital-based 30 minutes
twice daily for 2-4 days) 2 T0On the day of admission
(Day 0 or baseline)patient and parents completed the fatigue instruments and a team member applied the actigraph Patients wore the wrist actigraph T1 from Day 0 to 2 or 3 consecutive days (Days 0e3) In addition the patient same parent and staff nurses completed the daily sleep and fatigue reports in the late afternoons of Days 1-3
1 ANOVA model slesignificantly more the experimental athe control arm whdifferences from bsleep efficiency vaaveraged and com
2 The patient-reported mean fatigue scoresarms were higher amadolescents than for
3 The mixed model anarevealed no significandifferences in patientfatigue between
the two study arms otime( no final result iSD only give mixed result)
677
46
23 Keats M
R amp Culos-Reed S N (2008)
A community-based physical activity program for adolescents with cancer (project TREK) program feasibility and preliminary findings
To examine the
feasibility of a
theoretically-based
physical activity (PA)
intervention in
adolescents with
cancerand
examination of the
impact of the
program on
participant QOL
including social
emotional and
physical
well-being(including fatigue)
Repeat measures longitudinal design
No comparsion group
10 adolescents(Lymphoma(4)leukemia(4)CNS tumor(1)germ cell tumor(1)) ages 14-18 years
1physical fitness 2quality of life (QOL) 3PA behavior 4fatigue
1 Feasibility was assessed by participant recruitment attendance and adherence
2physical fitness Fitnessgram 3quality of life (QOL) Pediatric Quality of Life Inventory (PedsQL) 4PA behavior leisure score index (LSI) 5fatigue (mean) pediatric Quality of life
Multidimensional Fatigue Scale (Peds QL-MFS)
(Generalsleepcognitive fatigue)
116week physical activity (PA)
2 total PA physical fitness and overall QOL was assessed at 5 different intervals T0 preintervention (baseline) T1midintervention (after the
first 8 wk) T2 postintervention
(16 wk) T3 3-months
postintervention T4 1-year poststudy
initiation
1 from baseline -wkssig Improvementstotal PA physfitness and Qgeneral fatigue(meanplusmnSD 796plusmn135)
2 from baseline to 3FUsig Improvin general fatigue(meanplusmnSD824plusmn131)slefatigue(meanplusmnSD755plusmn191)totafatigue(meanplusmnSD778plusmn150)
3at 1 years FUsImprovements in sleeprest fatigue(meanplusmnSD725plusmn203)total (meanplusmnSD 763plusmn
678
47
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
2 Gene R E amp Conk Z (2008)
Impact of Effective Nursing Interventions to the Fatigue Syndrome in Children Who Receive Chemotherapy
1 to examine the effects of an effective nursing intervention to the fatigue syndrome of children 7 to 12 years of age who receive chemotherapy 2Tto examine the relationship between fatigue and demographic variables (age sex) diagnoses ([ALL AML] lymphoma) and therapy-related variables (eg level of hemoglobin
experimental randomized controlled study
Routine nursing care
A total of 60 children who are 7-12 years of age(a new diagnosis of ALL AML or lymphoma and receiving for the first time after being diagnosed a 7- to 10-day chemotherapy treatment )
fatigue The Fatigue Scale(FS-C) for 7-12 (intensity)
The Fatigue Scale Parent Version (FS-P)
1 effective nursing interventions(45- 60mdaya week)education about the fatigue with the chemotherapy and fatigue handbook 2 T1 After a 7-day period the children
and parent were evaluated with the Fatigue Scale
1The difference betwthe 2 mean values wafound to be statisticallsignificant 2 statistically significadifference was found between the Fatigue Scale-Child mean scothe experimental (272the control group (4213)children
679
48
25 Chiang et
al(2007)
The effects of ldquo a home ndashbased aerobic exercise interventionrdquo on fatigue and cardiorespiratory fitness in children with Acute Lymphoblastic Leukemia during the maintenance stage of chemotherapy
To examine the effect of ldquo a home ndashbased aerobic exercise interventionrdquo on fatigue and cardiorespiratory fitness in children with Acute Lymphoblastic Leukemia during the maintenance stage of chemotherapy
Quasi-experi -mental
Routine
nursing care
14 pediatric oncology patients in the experimental group and 10 in control group who were matched by age and sex ages7-18 years
1Cardiorespiratory fitness
2Fatigue
1Cardiorespiratory fitness Physical Activity Recall
VO2maxHR peak 6MWT
2 Fatigue PedsQL-MFS(Generalsleepcognitive fatigue)
1A six-week home-based aerobic exercise intervention 2 8 time points T0 baseline T1-T6 every week during the
intervention(6 weeks) T7 post intervention T8 follow-up (one month after
the end of the home-based exercise program)
1 For intent-to ndash treatthe findings indicated are no intervention efftime differences by anon the subscale of fat2 For per-protocol angeneral fatigue( mean422plusmn402) was the osubscale that was siglower for children whothe exercise interventthose in control groupfollow-up assessmentmonth after the compintervention) 3 The VO2peak are significantly improvingexperimental group atbaseline- and post-intassessment The VO2was significantly highechildren who were in experimental group thcontrol subjects at post-intervention assefor the per-protocol an
680
49
Appendix IV Instrument used to measure fatigue
Name Instrument
developers
Description Used in
age in
ref
Reliability
Consistency of
instrument
Checklist Individual Strength
(CIS)22
Vercoulen et
al1996
20 items using 7-point Likert scale of
fatigue To measure four aspects of
fatiguesubjective experience
contractionmotivation physical
Activity
6-14 Not reported
Child Fatigue Scale (CFS)7 Hockenberry
et al2003
14 items 2 part questionnaire frequency
(yes or no) 5-point Likert scale of the
intensity of any yes responses
7-13
14-18 α073-o84
The Fatigue Scale for 7-12
year Olds (FS-C)224
Hockenberry
et al
14 items provide a fatigue intensity score
5-point Likert scale
7-12 αo84
The Fatigue Scale for 13-18
year Olds (FS-A)24
Hockenberry
et al
14 items provide a fatigue intensity score
5-point Likert scale
13-18 α076-o96
Pediatric Quality of life
Multidimensional Fatigue
Scale (Peds QL-MFS)2325
Varni2002 18 items to measure three aspects of
fatigueGeneralsleepcognitive
14-18 Not reported
681
50
Appendix V Excluded studies and reasons for exclusion
Baggott C Dodd M Kennedy C Marina N Miaskowski C Multiple Symptoms in Pediatric Oncology
Patients A Systematic Review Journal of Pediatric Oncology Nursing 2009 Nov-Dec 27(6)
325-339
Reason for exclusion Not outcome of interest
Barlow JH Ellard DR Psycho-educational interventions for children with chronic disease parents and
siblings an overview of the research evidence base Care Health amp Development 2004 Nov
30(6)637-45
Reason for exclusion Not outcome of interest
Bedider S Moyer CA Randomized controlled trials of pediatric massage A review Evid Based
Complement Alternat Med 2007 Mar 4(1)23-34 Epub 2006 Nov 3
Reason for exclusion Not outcome of interest
de Nijs EJ Ros W Grijpdonck MH Nursing intervention for fatigue during the treatment for cancer Cancer
Nursing 2008 31(3)191-206
Reason for exclusion Not population of interest
Edwards JL Gibson F Richardson A Sepion B Ream E Fatigue in adolescents with and following a
cancer diagnosis developing an evidence base for practice European Journal of Cancer 2003
Dec 39(18)2671-80
Reason for exclusion Not experimental or quasi-experimental study
Hinds PS Hockenberry-Eatan M Developing a research program on fatigue in children and adolescents
diagnosed with cancer Journal of Pediatric Oncology Nursing 2001 Mar-Apr 18(2 Suppl
1)3-12
Reason for exclusion Not experimental or quasi-experimental study
Hockenberry-Eaton M Hinds PS Alcoser P ONeill JB Euell K Howard V Gattuso J Taylor J Fatigue in
Children and Adolescents With Cancer Journal of Pediatric Oncology Nursing 1998 July
15(3)172-182
Reason for exclusion Not experimental or quasi-experimental study
Jean-Pierre P Mustian K Kohli S Roscoe JA Hickok JT Morrow GR Community-based clinical oncology
research trials for cancer-related fatigue The Journal of Supportive Oncology 2006 Nov-Dec
4(10)511-6
682
51
Reason for exclusion Not population of interest
Kangas M Bovbjerg DH Montgomery GH Cancer-Related Fatigue A Systematic and Meta-Analytic
Review of Non-Pharmacological Therapies for Cancer Patients Psychological Bulletin 2008 Sep
134(5)700-41
Reason for exclusion Not population of interest
Lotfi-Jam K Carey M Jefford M Schofield P Charleson C Aranda S Nonpharmacologic strategies for
managing common chemotherapy adverse effects A systematic review Journal of Clinical
Oncology 2008 Dec 1 26(34)5618-29 Epub 2008 Nov 3
Reason for exclusion Not outcome of interest
Marchese VG Chiarello LA Lange BJ Effects of physical therapy intervention for children with acute
lymphoblastic leukemia Pediatr Blood Cancer 2004 Feb42(2)127-33
Reason for exclusion Not outcome of interest
Meeske KA Siegel SE Globe DR Mack WJ Bernstein L Prevalence and correlates of fatigue in
long-term survivors of childhood leukemia Journal of Clinical Oncology 2005 Aug 20
23(24)5501-10
Reason for exclusion Not intervention study
Minton O Richardson A Sharpe M Hotopf Stone P A systematic review and meta-analysis of the
pharmacological treatment of cancer-related fatigue J Natl Cancer Inst 2008 Aug 20
100(16)1155-66 Epub 2008 Aug 11
Reason for exclusion Not population and intervention of interest
Mustian KM Morrow GR Carroll JK Figueroa-Moseley CD Pascal JP Williams GC Integrative
nonpharmacologic behavioral interventions for the management of Cancer-Related fatigue The
Oncologist 2007 12(1)52-67
Reason for exclusion Not population of interest
Neill J Belan I Ried K Effectiveness of non-pharmacological interventions for fatigue in adults with
multiple sclerosis rheumatoid arthritis or systemic lupus erythematosus a systematic review
Journal of Advanced Nursing 2006 Dec 56(6)617-35
Reason for exclusion Not population of interest
Rheingans JI A systematic review of nonpharmacologic adjunctive therapies for symptom management
Journal of Pediatric Oncology Nursing 2007 24(2) 81-94
683
52
Reason for exclusion Not outcome of interest
Rheingans JI Pediatric oncology nursesrsquo management of patients symptoms Journal of Pediatric
Oncology Nursing 2008 Nov 25(6) 303-11
Reason for exclusion Not outcome of interest
San Juan AF Fleck SJ Chamorro-Vintildea C Mateacute-Muntildeoz JL Moral S Peacuterez M Cardona C Del Valle MF
Hernaacutendez M Ramiacuterez M Madero L Lucia A Effects of an intrahospital exercise program
intervention for children with leukemia Medicine amp Science in Sports amp Exercise 2007 Jan
39(1)13-21
Reason for exclusion Not outcome of interest
Sanford SD Okuma JO Pan J Srivastava DK West N Farr L Hinds PS Gender differences in sleep
fatigue and daytime activity in a pediatric oncology sample receiving dexamethasone Journal of
Pediatric Psychology 2008 Apr 33(3)298-306 Epub 2007 Nov 17
Reason for exclusion Not experimental or quasi-experimental study
Schmitz KH Holtzman J Courneya KS Macircsse LC Duval S Kane R Controlled physical activity trials in
cancer survivors a systematic review and meta-analysis Cancer Epidemiol Biomarkers Prev
2005 Jul 14(7)1588-95
Reason for exclusion Not population of interest
van Brussel M Takken T Lucia A van der Net J Helders PJ Is physical fitness decreased in survivors of
childhood leukemia A systematic review Leukemia 2005 Jan 19(1)13-7
Reason for exclusion Not population of interest
Whiting P Bagnall AM Snowden AJ Cornell JE Mulrow CD Ramirez G Interventions for the treatment
and management of chronic fatigue syndrome JAMA 2001 Sep 19 286(11)1360-8
Reason for exclusion Not intervention of interest
Whitsett SF Gudmundsdottir M Davies B McCarthy P Friedman D Chemotherapy-related fatigue in
childhood cancer correlates consequences and coping strategies Journal of Pediatric
Oncology Nursing 2008 Mar-Apr 25(2)86-96 Epub 2008 Feb 29
Reason for exclusion Not experimental or quasi-experimental study
Winner C Muumlller C Hoffmann C Boos J Rosenbaum D Physical activity and childhood cancer Pediatr
Blood Cancer 2010 Apr 54(4)501-10
Reason for exclusion Not research study
684
53
Wu M Hsu L Zhang B Shen N Lu H Li S The experiences of cancer-related fatigue among Chinese
children with leukaemia A phenomenological study Journal of Nursing Studies 2010 Jan
47(1)49-59 Epub 2009 Aug 25
Reason for exclusion Not experimental or quasi-experimental study
Yeh CH Chiang YC Lin L Yang CP Chien LC Weaver MA Chuang HL Clinical factors associated with
fatigue over time in paediatric oncology patients receiving chemotherapy British Journal of
Cancer 2008 Jul 8 99(1)23-9 Epub 2008 Jun 24
Reason for exclusion Not experimental or quasi-experimental study
685
32
studies where the ages were quite different is a potential source of heterogeneity and
may affect the interpretation of the results
Conclusion At present clinical treatment is widely used for cancer patients However child and
adolescent cancer patients often experience various side effects which cause short-term
or long-term discomfort both physically and psychologically In particular with the
increasing cure rate cancer related fatigue during or after treatment has become an
important issue This study result provided positive effect of exercise intervention on
general fatigue
Implications for practice The results of this systematic review and meta-analysis show that exercise interventions
can effectively improve the level of general fatigue In particular although the articles
were self-reported feasibility studies their results all indicate that exercise interventions
for fatigue are feasible and safe there was no conclusion to be made for the use of
massage therapy or health education measures because there was only one article for
each of these interventions
Recommendations for practice
Cancer-related fatigue is one of the most severe and frequent symptoms by pediatric
oncology children and adolescent suffered during treatment and the symptom existed
even after treatment has ended Until now no golden standard of treatment to fatigue is
established The findings call for more attention to how to reduce patientrsquos levels of
fatigue Based on the available information evaluated in this review the following
recommendations for practice are provided
665
33
bull For children aged 7 to 18 who has cancer (eg Lymphoma leukemia CNS tumor
germ cell tumor) an effective progressive aerobic exercise program is recommended to
be at least 2-3 times per week 20 to 45 minute for each session and last for 6-16 weeks
in order to reduce their general fatigue (tiredness physically weakness) In addition
adults should be involved in accompanying children while they are performing physical
exercise of which should be able to improve the adherence rate (level 2 ) ( Grade of
recommendation A)
bull For children aged 7 to 18 who has cancer (eg Lymphoma leukemia CNS tumor
germ cell tumor) an progressive aerobic exercise program will not be effective to reduce
their sleep andor rest (sleeping or resting a lot) or cognitive fatigue (problems with
thinking quickly or problems with remembering) (level 2 ) ( Grade of recommendation C)
bull Nursing interventions in educating treatment of fatigue include information about
activity nutrition energy preservation consulting and providing a useful fatigue
handbook will benefit those children who are 7 to 12 years have a new diagnosis of ALL
AML or lymphoma and receive for the first time after being diagnosed a 7- to 10-day
chemotherapy treatment (level 2) ( Grade of recommendation A)
bull A 4-week massage therapy program (the therapists massage childrenrsquos back legs
arms stomachchest and face) is not effective for children who are aged 7 to 18 and
have acute lymphoblastic leukemia brain tumors lymphoma rhabdomyosarcoma
Wilms tumor or Ewing sarcoma(level 2)( Grade of recommendation C)
bull Using a 12-week aerobic and strength exercise (45-min exercise sessions twice a
week) is not effective for children who are aged 6-14 and survived acute lymphoblaststic
leukemia age from 6 to 14(level 2) ( Grade of recommendation C)
bull Using a physical activity intervention (30minutestwice daily for 2-4days) is not
effective for children who are 7 to 18 years of age with soild tumor or AML(level 2)
( Grade of recommendation C)
666
34
Implications for research According to this systematic review and meta-analysis results there are suggestions to
improve the effectiveness of future research on non-pharmacological interventions for
children and young peoplersquos cancer-related fatigue
As the majority of included non-pharmacological interventions for the fatigue of cancer
patients consist of exercise programs future research should also consider various
non-pharmacological interventions in order to understand the effectiveness of different
methods
Regarding the exercise intervention methods and studies should consider multiple
factors including the age or personal condition of the subject the disease stage and the
amount of daily activities Studies should use design prescriptions (eg frequency
intensity duration and type of exercise) and consider the adherence to the measures in
order to enhance the study strength
In measuring the results of non-pharmacological interventions there should be standard
definitions or standard measurement tools to facilitate the following systematic review
and meta-analysis that can subsequently be developed into clinical care guidelines
Reviewing the effectiveness of the current non-pharmacological management of children
and adolescent cancer patients there is still a lack of rigorous RCT research Limited by
the characteristics of cancer there is still a lack of large sample sizes
Potential conflicts of interest There is no conflict of interest
Acknowledgements
Thank you to Dr Rie Konno Research Fellow Joanna Briggs Institute for her help in
assessing studies
667
35
References 1 National Comprehensive Cancer Network( NCCN) in USA NCCN clinical practice
guideline in oncology cancer-related fatigue 2011 2 Ekti Genc R amp Conk Z Impact of effective nursing interventions to the fatigue
syndrome in children who receive chemotherapy Cancer Nursing 200831(4)312-317
3 Childhood Cancer Foundation of ROC (2009March) The classification of diseases
and age sex statistical tables of case Childhood Cancer Foundation of ROC newsletter103105-106
4 Department of Health Executive Yuan ROC (TAIWAN)(2009 March 20)2009 cause of death statistic Health and National Health Insurance Annual Statistics Information Service 2010 June 28Available httpwwwdohgovtwstatisticdatavital statists9898health statistic--lifepdf
5 Chang TK (2007December 8) Common childhood cancer and its treatment Status
Childhood Cancer Foundation of ROC (TAIWAN) 2010 September 23 Available httpwwwccfrocorgtwchildchild_events_readphpe_id=45
6 Hockenberry MJ amp Wilson D Wongs nursing care of infants and children (8th ed) St
Louis MO Mosby 2007
7 Post-White J Fitzgerald M Savik K Hooke MC Hannahan AB amp Sencer SF
Massage therapy for children with cancer Journal of Pediatric Oncology Nursing 2009 26(1)16-28
8Chiang YC Yeh CH Wang WKamp Yang CP The experience of cancer-related fatigue
in Taiwanese children European Journal of Cancer Care 2009 18(1)43-49 9Langeveld NE Grootenhuis M A Voute P A de Haan RJ amp van den Bos C No excess
fatigue in young adult survivors of childhood cancer European Journal of Cancer 200339(2)204-214
10Piper BF Lindsey AM amp Dodd MJ Fatigue mechanisms in cancer patients
developing nursing theory Oncology Nursing Forum 1987 14(6)17-23 11Nail LM amp Winningham ML Fatigue In S L Groenwald M H Forgge M Goodman
amp C H Yarbro (Eds) Cancer Nursing Principles and practice (4 th ed) Boston Jones and Bartlett1997
12Irvine D Vincent L Graydon JE Bubela N amp Thompson L The prevalence and
correlates of fatigue in patients receiving treatment with chemotherapy and
668
36
radiotherapy A comparison with the fatigue experienced by healthy individuals Cancer Nursing 199417(5)367-378
13Hinds PS amp Hockenberry-Eaton M Developing a research program on fatigue in
children and adloescents diagnosed with cancer Journal of Pediatric Oncology Nursing 200118(2)3-12
14Aaronson LS Teel CS Cassmeyer V Neuberger GB Pallikkathayil L Pierce J Press
AN Williams DP amp Wingate A Defining and measuring fatigue Journal of Nursing scholarship 1999 31(1)45-50
15Yeh CH Wang CH Chiang YC Lin Lamp Chien LC Assessment of symptoms reported
by 10- to 18-year-old cancer patients in Taiwan 2009 38(5)738-746 16 Okuyama T Akechi T Kugaya A Okamura H Shima Yamp Maruguchi M
Development and validation of the cancer fatigue scale a brief three-dimensional self-rating scale for assessment of fatigue in cancer patients Journal of Pain amp Symptom Management 2000 19(1) 5-14
17Gibson F Mulhall AB Richardson A Edwards JL Ream E amp Sepion BJ A
phenomenologic study of fatigue in adolescents receiving treatment for cancer Oncology Nursing Forum200532(3)651-660
18Wolfe J Grier HE Klar N Levin SB Ellenbogen JMamp Salem-Schatz S et al
Symptoms and suffering at the end of life in children with cancer New England Journal of Medicine 2000342(5)326-333
19Whiting P Bagnall AM Sowden AJ Cornell JE Mulrow CD amp Ramirez G
Interventions for the treatment and management of chronic fatigue syndrome a systematic review JAMA the Journal of the American Medical Association 2001286(11)1360-1368
20 Kangas M Bovbjerg DHamp Montgomery G H Cancer-related fatigue a systematic
and meta-analytic review of non-pharmacological therapies for cancer patients Psychological Bulletin 2008134 (5)700-741
21Williams PD Schmideskamp J Ridder EL amp Williams AR Symptom monitoring and
dependent care during cancer treatment in children pilot study Cancer Nursing 200629(3)188-197
22Takken T van der Torre P Zwerink M Hulzebos EH Bierings M Helders PJMamp van
der Net J Development feasibility and efficacy of a community-based exercise training
669
37
program in pediatric cancer survivors Psycho-Oncology 200918(4)440-448
23Keats MR amp Culos-Reed SN A community-based physical activity program for
adolescents with cancer (project TREK) program feasibility and preliminary findings
Pediatric hematology and oncology 200830(4) 272-280
24Hinds PS Hockenberry M Rai SN Zhang L Razzouk B I Cremer L McCarthy K amp
Rodriguez-Galindo C Clinical field testing of an enhanced-activity intervention in
hospitalized children with cancer Journal of Pain amp Symptom Management 2007
33(6)686-697
25Chiang YC The effects of ldquo a home-based aerobic exercise interventionrdquo on fatigue
and cardiorespiratory fitness in children with acute lymphoblastic leukemia during the
maintenance stage of chemotherapy Unpublished thesis Taiwan Tao-Yuan 2007
26Langeveld N Ubbink M amp Smets E I dont have any energy The experience of
fatigue in young adult survivors of childhood cancer European journal of oncology
nursing 20004(1)20-28
27 Kisner C Colby L Therapeutic exercise Foundations and techniques 2nd ed Philadelphia PAFA Davies 2007
670
38
Appendix I JBI Critical Appraisal Checklist for Experimental studies
Author__________ Year_________ Record Number__________________
Questions 1 to 4 must be answered ldquoyesrdquo for study to be included in the metashyanalysis
1 Were the participants randomized to study groups
Yes No Not clear
2 Other than research intervention were participants in each groups treated the same
Yes No Not clear
3 Were the outcomes measured in the same manner for all participants
Yes No Not clear
4 Were groups comparable at entry
Yes No Not clear
5 Was randomization of participants blinded
Yes No Not clear
6 Were those assessing outcome blinded to treatment allocation (if outcome not objective such as survival or length of hospitalization)
Yes No Not clear
7 Was allocation to treatment groups concealed from the allocator
Yes No Not clear
8 Was an appropriate statistical analysis used
671
39
Yes No Not clear
9 Were outcomes measured in a reliable way
Yes No Not clear
10 Was there adequate followshyup of participants
Yes No Not clear
Summary
TOTAL
Yes No Not clear
DECISION
Use Reject
Narrative summary only Further information needed
COMMENTS
672
40
Appendix II JBI Data Extraction Tool for Quantitative Studies Authors and Year
Journal Title
Record NumberArticle Reference No
Reviewer
Method
Settings
Participants
Number of participants
Group A Group B Group C
Control Intervention 1 Intervention 2
Interventions
Group A
Control
Group B
Intervention 1
Group C
Intervention 2
Outcome measures
Definition
673
41
Other outcome measures
Outcome description ScaleMeasure
Results
Dichotomous Data
Outcome Control Group
Numbertotal number
Treatment Group
Numbertotal number
Continuous Data
Authorrsquos Conclusions
Comments
Outcome Control Group
Mean amp SD
Treatment Group
Mean amp SD
674
43
Appendix III Details of included studies (N=6)(2720212223) RefNo Author(s)
(years) Title Study question Research
method Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
22 Takken T van der Torre P Zwerink M Hulzebos E H Bierings M Helders P J Mamp van der Net J (2009)
Development feasibility and efficacy of a community-based exercise training program in pediatric cancer survivors
To develop a 12-week home-based exercise training program (comprising aerobic and strength exercises) for children who survived ALL and to study itrsquos feasibility and efficacy
Pre-post test design
No comparsion group
Survived ALL(N=9)ages 6-14 years
1anthropometry 2 muscle strength 3functional mobility 4cardio-pulmonary
exercise test 5Fatigue
1 Feasibility questionnaire 2 anthropometry electronic scale and a wallmounted stadiometerHarpenden skin fold calipers 3 muscle strength handheld dynamometer 4functional mobility Timed Up
and Go test (TUG) 5cardio-pulmonary exercise test electronically braked cycle ergometer 6Fatigue(mean)CSI-20 (subjective experience of fatigueconcentrationmotivationphysical activity)
112-week exercise training program
2 Patients were assessed before (T0) and after (T1) 12 weeks of training
1 muscle strength execapacity functional moand fatigue showed nosignificant differences between pre(meanplusmnSD415plusmn147) and post training(meanplusmnSD3687)
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
7 Post-White J Fitzgerald M Savik K Hooke M C Hannahan A B amp Sencer S F (2009)
Massage therapy for children with cancer
To determine whether 4 weekly sessions of massage compared with 4 quiet-time control conditions would reduce anxiety cortisol levels fatigue nausea and pain in children with cancer undergoing chemotherapy and would reduce anxiety fatigue and mood disturbance in a parent
2-period crossover design (Randomized)
quiet-time
control
sessions
Children with cancer 1 to 18 years of age Twenty-three childrenparent dyads were enrolled 17 completed all data points
children 1relaxation 2symptoms 3 fatigue
parents
1anxiety 2 fatigue
children 1relaxation (heart and respiratory rates blood pressure and salivary cortisol level)
2symptoms (pain nausea anxiety 3 fatigue 1-2y3-6yLansky Play Performance Scale (PPS) 7-13y
1 4 weekly massage (MT) sessions alternated with 4 weekly quiet-time(QT) control sessions
2 children included presession and postsession vital signs (heart rate respiratory rate blood pressure) and self-report (parent proxy report for age 1-2 years) of pain nausea and anxiety Fatigue was measured before sessions 1 and 4 and at each follow-up Parent measures
included anxiety fatigue and mood states
1Massage was moreeffective than quiet tireducing heart rate inchildren anxiety in cless than age 14 yeaparent anxiety 2There were no sign
changes in blood pcortisol pain naufatigue (no state d
3 Children reported tmassage helped thebetter lessened theirand worries and hadlasting effects than q
675
44
14-18yChild Fatigue Scale (CFS) (frequency
intensity) 2 parents anxiety and fatigue
676
45
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
24 Hinds P S Hockenberry M Rai S N Zhang L Razzouk B I Cremer L McCarthy K amp Rodriguez-Galindo C (2007)
Clinical field testing of an enhanced-activity intervention in hospitalized children with cancer
To determine the feasibility of an
enhanced physical activity EPA intervention in children and adolescents hospitalized to receive chemotherapy for a solid tumor or AML and to assess the sleep and fatigue outcomes of the intervention using two different statistical approaches to analyze the longitudinal symptom data
randomized prospective two-site and two-group pilot study
Standard care Twenty nine patients (25 with a solid tumor and 4 with AML)ages 7-18 years
1 sleep duration 2 sleep efficiency 3 fatigue
1sleep duration sleep efficiency The
Wrist Actigraph The Daily Sleep Diary-Parent 2 fatigue (mean) The Fatigue Scale(FS-C) for 7-12 (intensity) The Fatigue Scale(FS-A) for 13-18 The Fatigue Scale Parent Version (FS-P) The Fatigue Scale Staff Version (FS-S)
1enhanced physical activity (EPA) (hospital-based 30 minutes
twice daily for 2-4 days) 2 T0On the day of admission
(Day 0 or baseline)patient and parents completed the fatigue instruments and a team member applied the actigraph Patients wore the wrist actigraph T1 from Day 0 to 2 or 3 consecutive days (Days 0e3) In addition the patient same parent and staff nurses completed the daily sleep and fatigue reports in the late afternoons of Days 1-3
1 ANOVA model slesignificantly more the experimental athe control arm whdifferences from bsleep efficiency vaaveraged and com
2 The patient-reported mean fatigue scoresarms were higher amadolescents than for
3 The mixed model anarevealed no significandifferences in patientfatigue between
the two study arms otime( no final result iSD only give mixed result)
677
46
23 Keats M
R amp Culos-Reed S N (2008)
A community-based physical activity program for adolescents with cancer (project TREK) program feasibility and preliminary findings
To examine the
feasibility of a
theoretically-based
physical activity (PA)
intervention in
adolescents with
cancerand
examination of the
impact of the
program on
participant QOL
including social
emotional and
physical
well-being(including fatigue)
Repeat measures longitudinal design
No comparsion group
10 adolescents(Lymphoma(4)leukemia(4)CNS tumor(1)germ cell tumor(1)) ages 14-18 years
1physical fitness 2quality of life (QOL) 3PA behavior 4fatigue
1 Feasibility was assessed by participant recruitment attendance and adherence
2physical fitness Fitnessgram 3quality of life (QOL) Pediatric Quality of Life Inventory (PedsQL) 4PA behavior leisure score index (LSI) 5fatigue (mean) pediatric Quality of life
Multidimensional Fatigue Scale (Peds QL-MFS)
(Generalsleepcognitive fatigue)
116week physical activity (PA)
2 total PA physical fitness and overall QOL was assessed at 5 different intervals T0 preintervention (baseline) T1midintervention (after the
first 8 wk) T2 postintervention
(16 wk) T3 3-months
postintervention T4 1-year poststudy
initiation
1 from baseline -wkssig Improvementstotal PA physfitness and Qgeneral fatigue(meanplusmnSD 796plusmn135)
2 from baseline to 3FUsig Improvin general fatigue(meanplusmnSD824plusmn131)slefatigue(meanplusmnSD755plusmn191)totafatigue(meanplusmnSD778plusmn150)
3at 1 years FUsImprovements in sleeprest fatigue(meanplusmnSD725plusmn203)total (meanplusmnSD 763plusmn
678
47
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
2 Gene R E amp Conk Z (2008)
Impact of Effective Nursing Interventions to the Fatigue Syndrome in Children Who Receive Chemotherapy
1 to examine the effects of an effective nursing intervention to the fatigue syndrome of children 7 to 12 years of age who receive chemotherapy 2Tto examine the relationship between fatigue and demographic variables (age sex) diagnoses ([ALL AML] lymphoma) and therapy-related variables (eg level of hemoglobin
experimental randomized controlled study
Routine nursing care
A total of 60 children who are 7-12 years of age(a new diagnosis of ALL AML or lymphoma and receiving for the first time after being diagnosed a 7- to 10-day chemotherapy treatment )
fatigue The Fatigue Scale(FS-C) for 7-12 (intensity)
The Fatigue Scale Parent Version (FS-P)
1 effective nursing interventions(45- 60mdaya week)education about the fatigue with the chemotherapy and fatigue handbook 2 T1 After a 7-day period the children
and parent were evaluated with the Fatigue Scale
1The difference betwthe 2 mean values wafound to be statisticallsignificant 2 statistically significadifference was found between the Fatigue Scale-Child mean scothe experimental (272the control group (4213)children
679
48
25 Chiang et
al(2007)
The effects of ldquo a home ndashbased aerobic exercise interventionrdquo on fatigue and cardiorespiratory fitness in children with Acute Lymphoblastic Leukemia during the maintenance stage of chemotherapy
To examine the effect of ldquo a home ndashbased aerobic exercise interventionrdquo on fatigue and cardiorespiratory fitness in children with Acute Lymphoblastic Leukemia during the maintenance stage of chemotherapy
Quasi-experi -mental
Routine
nursing care
14 pediatric oncology patients in the experimental group and 10 in control group who were matched by age and sex ages7-18 years
1Cardiorespiratory fitness
2Fatigue
1Cardiorespiratory fitness Physical Activity Recall
VO2maxHR peak 6MWT
2 Fatigue PedsQL-MFS(Generalsleepcognitive fatigue)
1A six-week home-based aerobic exercise intervention 2 8 time points T0 baseline T1-T6 every week during the
intervention(6 weeks) T7 post intervention T8 follow-up (one month after
the end of the home-based exercise program)
1 For intent-to ndash treatthe findings indicated are no intervention efftime differences by anon the subscale of fat2 For per-protocol angeneral fatigue( mean422plusmn402) was the osubscale that was siglower for children whothe exercise interventthose in control groupfollow-up assessmentmonth after the compintervention) 3 The VO2peak are significantly improvingexperimental group atbaseline- and post-intassessment The VO2was significantly highechildren who were in experimental group thcontrol subjects at post-intervention assefor the per-protocol an
680
49
Appendix IV Instrument used to measure fatigue
Name Instrument
developers
Description Used in
age in
ref
Reliability
Consistency of
instrument
Checklist Individual Strength
(CIS)22
Vercoulen et
al1996
20 items using 7-point Likert scale of
fatigue To measure four aspects of
fatiguesubjective experience
contractionmotivation physical
Activity
6-14 Not reported
Child Fatigue Scale (CFS)7 Hockenberry
et al2003
14 items 2 part questionnaire frequency
(yes or no) 5-point Likert scale of the
intensity of any yes responses
7-13
14-18 α073-o84
The Fatigue Scale for 7-12
year Olds (FS-C)224
Hockenberry
et al
14 items provide a fatigue intensity score
5-point Likert scale
7-12 αo84
The Fatigue Scale for 13-18
year Olds (FS-A)24
Hockenberry
et al
14 items provide a fatigue intensity score
5-point Likert scale
13-18 α076-o96
Pediatric Quality of life
Multidimensional Fatigue
Scale (Peds QL-MFS)2325
Varni2002 18 items to measure three aspects of
fatigueGeneralsleepcognitive
14-18 Not reported
681
50
Appendix V Excluded studies and reasons for exclusion
Baggott C Dodd M Kennedy C Marina N Miaskowski C Multiple Symptoms in Pediatric Oncology
Patients A Systematic Review Journal of Pediatric Oncology Nursing 2009 Nov-Dec 27(6)
325-339
Reason for exclusion Not outcome of interest
Barlow JH Ellard DR Psycho-educational interventions for children with chronic disease parents and
siblings an overview of the research evidence base Care Health amp Development 2004 Nov
30(6)637-45
Reason for exclusion Not outcome of interest
Bedider S Moyer CA Randomized controlled trials of pediatric massage A review Evid Based
Complement Alternat Med 2007 Mar 4(1)23-34 Epub 2006 Nov 3
Reason for exclusion Not outcome of interest
de Nijs EJ Ros W Grijpdonck MH Nursing intervention for fatigue during the treatment for cancer Cancer
Nursing 2008 31(3)191-206
Reason for exclusion Not population of interest
Edwards JL Gibson F Richardson A Sepion B Ream E Fatigue in adolescents with and following a
cancer diagnosis developing an evidence base for practice European Journal of Cancer 2003
Dec 39(18)2671-80
Reason for exclusion Not experimental or quasi-experimental study
Hinds PS Hockenberry-Eatan M Developing a research program on fatigue in children and adolescents
diagnosed with cancer Journal of Pediatric Oncology Nursing 2001 Mar-Apr 18(2 Suppl
1)3-12
Reason for exclusion Not experimental or quasi-experimental study
Hockenberry-Eaton M Hinds PS Alcoser P ONeill JB Euell K Howard V Gattuso J Taylor J Fatigue in
Children and Adolescents With Cancer Journal of Pediatric Oncology Nursing 1998 July
15(3)172-182
Reason for exclusion Not experimental or quasi-experimental study
Jean-Pierre P Mustian K Kohli S Roscoe JA Hickok JT Morrow GR Community-based clinical oncology
research trials for cancer-related fatigue The Journal of Supportive Oncology 2006 Nov-Dec
4(10)511-6
682
51
Reason for exclusion Not population of interest
Kangas M Bovbjerg DH Montgomery GH Cancer-Related Fatigue A Systematic and Meta-Analytic
Review of Non-Pharmacological Therapies for Cancer Patients Psychological Bulletin 2008 Sep
134(5)700-41
Reason for exclusion Not population of interest
Lotfi-Jam K Carey M Jefford M Schofield P Charleson C Aranda S Nonpharmacologic strategies for
managing common chemotherapy adverse effects A systematic review Journal of Clinical
Oncology 2008 Dec 1 26(34)5618-29 Epub 2008 Nov 3
Reason for exclusion Not outcome of interest
Marchese VG Chiarello LA Lange BJ Effects of physical therapy intervention for children with acute
lymphoblastic leukemia Pediatr Blood Cancer 2004 Feb42(2)127-33
Reason for exclusion Not outcome of interest
Meeske KA Siegel SE Globe DR Mack WJ Bernstein L Prevalence and correlates of fatigue in
long-term survivors of childhood leukemia Journal of Clinical Oncology 2005 Aug 20
23(24)5501-10
Reason for exclusion Not intervention study
Minton O Richardson A Sharpe M Hotopf Stone P A systematic review and meta-analysis of the
pharmacological treatment of cancer-related fatigue J Natl Cancer Inst 2008 Aug 20
100(16)1155-66 Epub 2008 Aug 11
Reason for exclusion Not population and intervention of interest
Mustian KM Morrow GR Carroll JK Figueroa-Moseley CD Pascal JP Williams GC Integrative
nonpharmacologic behavioral interventions for the management of Cancer-Related fatigue The
Oncologist 2007 12(1)52-67
Reason for exclusion Not population of interest
Neill J Belan I Ried K Effectiveness of non-pharmacological interventions for fatigue in adults with
multiple sclerosis rheumatoid arthritis or systemic lupus erythematosus a systematic review
Journal of Advanced Nursing 2006 Dec 56(6)617-35
Reason for exclusion Not population of interest
Rheingans JI A systematic review of nonpharmacologic adjunctive therapies for symptom management
Journal of Pediatric Oncology Nursing 2007 24(2) 81-94
683
52
Reason for exclusion Not outcome of interest
Rheingans JI Pediatric oncology nursesrsquo management of patients symptoms Journal of Pediatric
Oncology Nursing 2008 Nov 25(6) 303-11
Reason for exclusion Not outcome of interest
San Juan AF Fleck SJ Chamorro-Vintildea C Mateacute-Muntildeoz JL Moral S Peacuterez M Cardona C Del Valle MF
Hernaacutendez M Ramiacuterez M Madero L Lucia A Effects of an intrahospital exercise program
intervention for children with leukemia Medicine amp Science in Sports amp Exercise 2007 Jan
39(1)13-21
Reason for exclusion Not outcome of interest
Sanford SD Okuma JO Pan J Srivastava DK West N Farr L Hinds PS Gender differences in sleep
fatigue and daytime activity in a pediatric oncology sample receiving dexamethasone Journal of
Pediatric Psychology 2008 Apr 33(3)298-306 Epub 2007 Nov 17
Reason for exclusion Not experimental or quasi-experimental study
Schmitz KH Holtzman J Courneya KS Macircsse LC Duval S Kane R Controlled physical activity trials in
cancer survivors a systematic review and meta-analysis Cancer Epidemiol Biomarkers Prev
2005 Jul 14(7)1588-95
Reason for exclusion Not population of interest
van Brussel M Takken T Lucia A van der Net J Helders PJ Is physical fitness decreased in survivors of
childhood leukemia A systematic review Leukemia 2005 Jan 19(1)13-7
Reason for exclusion Not population of interest
Whiting P Bagnall AM Snowden AJ Cornell JE Mulrow CD Ramirez G Interventions for the treatment
and management of chronic fatigue syndrome JAMA 2001 Sep 19 286(11)1360-8
Reason for exclusion Not intervention of interest
Whitsett SF Gudmundsdottir M Davies B McCarthy P Friedman D Chemotherapy-related fatigue in
childhood cancer correlates consequences and coping strategies Journal of Pediatric
Oncology Nursing 2008 Mar-Apr 25(2)86-96 Epub 2008 Feb 29
Reason for exclusion Not experimental or quasi-experimental study
Winner C Muumlller C Hoffmann C Boos J Rosenbaum D Physical activity and childhood cancer Pediatr
Blood Cancer 2010 Apr 54(4)501-10
Reason for exclusion Not research study
684
53
Wu M Hsu L Zhang B Shen N Lu H Li S The experiences of cancer-related fatigue among Chinese
children with leukaemia A phenomenological study Journal of Nursing Studies 2010 Jan
47(1)49-59 Epub 2009 Aug 25
Reason for exclusion Not experimental or quasi-experimental study
Yeh CH Chiang YC Lin L Yang CP Chien LC Weaver MA Chuang HL Clinical factors associated with
fatigue over time in paediatric oncology patients receiving chemotherapy British Journal of
Cancer 2008 Jul 8 99(1)23-9 Epub 2008 Jun 24
Reason for exclusion Not experimental or quasi-experimental study
685
33
bull For children aged 7 to 18 who has cancer (eg Lymphoma leukemia CNS tumor
germ cell tumor) an effective progressive aerobic exercise program is recommended to
be at least 2-3 times per week 20 to 45 minute for each session and last for 6-16 weeks
in order to reduce their general fatigue (tiredness physically weakness) In addition
adults should be involved in accompanying children while they are performing physical
exercise of which should be able to improve the adherence rate (level 2 ) ( Grade of
recommendation A)
bull For children aged 7 to 18 who has cancer (eg Lymphoma leukemia CNS tumor
germ cell tumor) an progressive aerobic exercise program will not be effective to reduce
their sleep andor rest (sleeping or resting a lot) or cognitive fatigue (problems with
thinking quickly or problems with remembering) (level 2 ) ( Grade of recommendation C)
bull Nursing interventions in educating treatment of fatigue include information about
activity nutrition energy preservation consulting and providing a useful fatigue
handbook will benefit those children who are 7 to 12 years have a new diagnosis of ALL
AML or lymphoma and receive for the first time after being diagnosed a 7- to 10-day
chemotherapy treatment (level 2) ( Grade of recommendation A)
bull A 4-week massage therapy program (the therapists massage childrenrsquos back legs
arms stomachchest and face) is not effective for children who are aged 7 to 18 and
have acute lymphoblastic leukemia brain tumors lymphoma rhabdomyosarcoma
Wilms tumor or Ewing sarcoma(level 2)( Grade of recommendation C)
bull Using a 12-week aerobic and strength exercise (45-min exercise sessions twice a
week) is not effective for children who are aged 6-14 and survived acute lymphoblaststic
leukemia age from 6 to 14(level 2) ( Grade of recommendation C)
bull Using a physical activity intervention (30minutestwice daily for 2-4days) is not
effective for children who are 7 to 18 years of age with soild tumor or AML(level 2)
( Grade of recommendation C)
666
34
Implications for research According to this systematic review and meta-analysis results there are suggestions to
improve the effectiveness of future research on non-pharmacological interventions for
children and young peoplersquos cancer-related fatigue
As the majority of included non-pharmacological interventions for the fatigue of cancer
patients consist of exercise programs future research should also consider various
non-pharmacological interventions in order to understand the effectiveness of different
methods
Regarding the exercise intervention methods and studies should consider multiple
factors including the age or personal condition of the subject the disease stage and the
amount of daily activities Studies should use design prescriptions (eg frequency
intensity duration and type of exercise) and consider the adherence to the measures in
order to enhance the study strength
In measuring the results of non-pharmacological interventions there should be standard
definitions or standard measurement tools to facilitate the following systematic review
and meta-analysis that can subsequently be developed into clinical care guidelines
Reviewing the effectiveness of the current non-pharmacological management of children
and adolescent cancer patients there is still a lack of rigorous RCT research Limited by
the characteristics of cancer there is still a lack of large sample sizes
Potential conflicts of interest There is no conflict of interest
Acknowledgements
Thank you to Dr Rie Konno Research Fellow Joanna Briggs Institute for her help in
assessing studies
667
35
References 1 National Comprehensive Cancer Network( NCCN) in USA NCCN clinical practice
guideline in oncology cancer-related fatigue 2011 2 Ekti Genc R amp Conk Z Impact of effective nursing interventions to the fatigue
syndrome in children who receive chemotherapy Cancer Nursing 200831(4)312-317
3 Childhood Cancer Foundation of ROC (2009March) The classification of diseases
and age sex statistical tables of case Childhood Cancer Foundation of ROC newsletter103105-106
4 Department of Health Executive Yuan ROC (TAIWAN)(2009 March 20)2009 cause of death statistic Health and National Health Insurance Annual Statistics Information Service 2010 June 28Available httpwwwdohgovtwstatisticdatavital statists9898health statistic--lifepdf
5 Chang TK (2007December 8) Common childhood cancer and its treatment Status
Childhood Cancer Foundation of ROC (TAIWAN) 2010 September 23 Available httpwwwccfrocorgtwchildchild_events_readphpe_id=45
6 Hockenberry MJ amp Wilson D Wongs nursing care of infants and children (8th ed) St
Louis MO Mosby 2007
7 Post-White J Fitzgerald M Savik K Hooke MC Hannahan AB amp Sencer SF
Massage therapy for children with cancer Journal of Pediatric Oncology Nursing 2009 26(1)16-28
8Chiang YC Yeh CH Wang WKamp Yang CP The experience of cancer-related fatigue
in Taiwanese children European Journal of Cancer Care 2009 18(1)43-49 9Langeveld NE Grootenhuis M A Voute P A de Haan RJ amp van den Bos C No excess
fatigue in young adult survivors of childhood cancer European Journal of Cancer 200339(2)204-214
10Piper BF Lindsey AM amp Dodd MJ Fatigue mechanisms in cancer patients
developing nursing theory Oncology Nursing Forum 1987 14(6)17-23 11Nail LM amp Winningham ML Fatigue In S L Groenwald M H Forgge M Goodman
amp C H Yarbro (Eds) Cancer Nursing Principles and practice (4 th ed) Boston Jones and Bartlett1997
12Irvine D Vincent L Graydon JE Bubela N amp Thompson L The prevalence and
correlates of fatigue in patients receiving treatment with chemotherapy and
668
36
radiotherapy A comparison with the fatigue experienced by healthy individuals Cancer Nursing 199417(5)367-378
13Hinds PS amp Hockenberry-Eaton M Developing a research program on fatigue in
children and adloescents diagnosed with cancer Journal of Pediatric Oncology Nursing 200118(2)3-12
14Aaronson LS Teel CS Cassmeyer V Neuberger GB Pallikkathayil L Pierce J Press
AN Williams DP amp Wingate A Defining and measuring fatigue Journal of Nursing scholarship 1999 31(1)45-50
15Yeh CH Wang CH Chiang YC Lin Lamp Chien LC Assessment of symptoms reported
by 10- to 18-year-old cancer patients in Taiwan 2009 38(5)738-746 16 Okuyama T Akechi T Kugaya A Okamura H Shima Yamp Maruguchi M
Development and validation of the cancer fatigue scale a brief three-dimensional self-rating scale for assessment of fatigue in cancer patients Journal of Pain amp Symptom Management 2000 19(1) 5-14
17Gibson F Mulhall AB Richardson A Edwards JL Ream E amp Sepion BJ A
phenomenologic study of fatigue in adolescents receiving treatment for cancer Oncology Nursing Forum200532(3)651-660
18Wolfe J Grier HE Klar N Levin SB Ellenbogen JMamp Salem-Schatz S et al
Symptoms and suffering at the end of life in children with cancer New England Journal of Medicine 2000342(5)326-333
19Whiting P Bagnall AM Sowden AJ Cornell JE Mulrow CD amp Ramirez G
Interventions for the treatment and management of chronic fatigue syndrome a systematic review JAMA the Journal of the American Medical Association 2001286(11)1360-1368
20 Kangas M Bovbjerg DHamp Montgomery G H Cancer-related fatigue a systematic
and meta-analytic review of non-pharmacological therapies for cancer patients Psychological Bulletin 2008134 (5)700-741
21Williams PD Schmideskamp J Ridder EL amp Williams AR Symptom monitoring and
dependent care during cancer treatment in children pilot study Cancer Nursing 200629(3)188-197
22Takken T van der Torre P Zwerink M Hulzebos EH Bierings M Helders PJMamp van
der Net J Development feasibility and efficacy of a community-based exercise training
669
37
program in pediatric cancer survivors Psycho-Oncology 200918(4)440-448
23Keats MR amp Culos-Reed SN A community-based physical activity program for
adolescents with cancer (project TREK) program feasibility and preliminary findings
Pediatric hematology and oncology 200830(4) 272-280
24Hinds PS Hockenberry M Rai SN Zhang L Razzouk B I Cremer L McCarthy K amp
Rodriguez-Galindo C Clinical field testing of an enhanced-activity intervention in
hospitalized children with cancer Journal of Pain amp Symptom Management 2007
33(6)686-697
25Chiang YC The effects of ldquo a home-based aerobic exercise interventionrdquo on fatigue
and cardiorespiratory fitness in children with acute lymphoblastic leukemia during the
maintenance stage of chemotherapy Unpublished thesis Taiwan Tao-Yuan 2007
26Langeveld N Ubbink M amp Smets E I dont have any energy The experience of
fatigue in young adult survivors of childhood cancer European journal of oncology
nursing 20004(1)20-28
27 Kisner C Colby L Therapeutic exercise Foundations and techniques 2nd ed Philadelphia PAFA Davies 2007
670
38
Appendix I JBI Critical Appraisal Checklist for Experimental studies
Author__________ Year_________ Record Number__________________
Questions 1 to 4 must be answered ldquoyesrdquo for study to be included in the metashyanalysis
1 Were the participants randomized to study groups
Yes No Not clear
2 Other than research intervention were participants in each groups treated the same
Yes No Not clear
3 Were the outcomes measured in the same manner for all participants
Yes No Not clear
4 Were groups comparable at entry
Yes No Not clear
5 Was randomization of participants blinded
Yes No Not clear
6 Were those assessing outcome blinded to treatment allocation (if outcome not objective such as survival or length of hospitalization)
Yes No Not clear
7 Was allocation to treatment groups concealed from the allocator
Yes No Not clear
8 Was an appropriate statistical analysis used
671
39
Yes No Not clear
9 Were outcomes measured in a reliable way
Yes No Not clear
10 Was there adequate followshyup of participants
Yes No Not clear
Summary
TOTAL
Yes No Not clear
DECISION
Use Reject
Narrative summary only Further information needed
COMMENTS
672
40
Appendix II JBI Data Extraction Tool for Quantitative Studies Authors and Year
Journal Title
Record NumberArticle Reference No
Reviewer
Method
Settings
Participants
Number of participants
Group A Group B Group C
Control Intervention 1 Intervention 2
Interventions
Group A
Control
Group B
Intervention 1
Group C
Intervention 2
Outcome measures
Definition
673
41
Other outcome measures
Outcome description ScaleMeasure
Results
Dichotomous Data
Outcome Control Group
Numbertotal number
Treatment Group
Numbertotal number
Continuous Data
Authorrsquos Conclusions
Comments
Outcome Control Group
Mean amp SD
Treatment Group
Mean amp SD
674
43
Appendix III Details of included studies (N=6)(2720212223) RefNo Author(s)
(years) Title Study question Research
method Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
22 Takken T van der Torre P Zwerink M Hulzebos E H Bierings M Helders P J Mamp van der Net J (2009)
Development feasibility and efficacy of a community-based exercise training program in pediatric cancer survivors
To develop a 12-week home-based exercise training program (comprising aerobic and strength exercises) for children who survived ALL and to study itrsquos feasibility and efficacy
Pre-post test design
No comparsion group
Survived ALL(N=9)ages 6-14 years
1anthropometry 2 muscle strength 3functional mobility 4cardio-pulmonary
exercise test 5Fatigue
1 Feasibility questionnaire 2 anthropometry electronic scale and a wallmounted stadiometerHarpenden skin fold calipers 3 muscle strength handheld dynamometer 4functional mobility Timed Up
and Go test (TUG) 5cardio-pulmonary exercise test electronically braked cycle ergometer 6Fatigue(mean)CSI-20 (subjective experience of fatigueconcentrationmotivationphysical activity)
112-week exercise training program
2 Patients were assessed before (T0) and after (T1) 12 weeks of training
1 muscle strength execapacity functional moand fatigue showed nosignificant differences between pre(meanplusmnSD415plusmn147) and post training(meanplusmnSD3687)
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
7 Post-White J Fitzgerald M Savik K Hooke M C Hannahan A B amp Sencer S F (2009)
Massage therapy for children with cancer
To determine whether 4 weekly sessions of massage compared with 4 quiet-time control conditions would reduce anxiety cortisol levels fatigue nausea and pain in children with cancer undergoing chemotherapy and would reduce anxiety fatigue and mood disturbance in a parent
2-period crossover design (Randomized)
quiet-time
control
sessions
Children with cancer 1 to 18 years of age Twenty-three childrenparent dyads were enrolled 17 completed all data points
children 1relaxation 2symptoms 3 fatigue
parents
1anxiety 2 fatigue
children 1relaxation (heart and respiratory rates blood pressure and salivary cortisol level)
2symptoms (pain nausea anxiety 3 fatigue 1-2y3-6yLansky Play Performance Scale (PPS) 7-13y
1 4 weekly massage (MT) sessions alternated with 4 weekly quiet-time(QT) control sessions
2 children included presession and postsession vital signs (heart rate respiratory rate blood pressure) and self-report (parent proxy report for age 1-2 years) of pain nausea and anxiety Fatigue was measured before sessions 1 and 4 and at each follow-up Parent measures
included anxiety fatigue and mood states
1Massage was moreeffective than quiet tireducing heart rate inchildren anxiety in cless than age 14 yeaparent anxiety 2There were no sign
changes in blood pcortisol pain naufatigue (no state d
3 Children reported tmassage helped thebetter lessened theirand worries and hadlasting effects than q
675
44
14-18yChild Fatigue Scale (CFS) (frequency
intensity) 2 parents anxiety and fatigue
676
45
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
24 Hinds P S Hockenberry M Rai S N Zhang L Razzouk B I Cremer L McCarthy K amp Rodriguez-Galindo C (2007)
Clinical field testing of an enhanced-activity intervention in hospitalized children with cancer
To determine the feasibility of an
enhanced physical activity EPA intervention in children and adolescents hospitalized to receive chemotherapy for a solid tumor or AML and to assess the sleep and fatigue outcomes of the intervention using two different statistical approaches to analyze the longitudinal symptom data
randomized prospective two-site and two-group pilot study
Standard care Twenty nine patients (25 with a solid tumor and 4 with AML)ages 7-18 years
1 sleep duration 2 sleep efficiency 3 fatigue
1sleep duration sleep efficiency The
Wrist Actigraph The Daily Sleep Diary-Parent 2 fatigue (mean) The Fatigue Scale(FS-C) for 7-12 (intensity) The Fatigue Scale(FS-A) for 13-18 The Fatigue Scale Parent Version (FS-P) The Fatigue Scale Staff Version (FS-S)
1enhanced physical activity (EPA) (hospital-based 30 minutes
twice daily for 2-4 days) 2 T0On the day of admission
(Day 0 or baseline)patient and parents completed the fatigue instruments and a team member applied the actigraph Patients wore the wrist actigraph T1 from Day 0 to 2 or 3 consecutive days (Days 0e3) In addition the patient same parent and staff nurses completed the daily sleep and fatigue reports in the late afternoons of Days 1-3
1 ANOVA model slesignificantly more the experimental athe control arm whdifferences from bsleep efficiency vaaveraged and com
2 The patient-reported mean fatigue scoresarms were higher amadolescents than for
3 The mixed model anarevealed no significandifferences in patientfatigue between
the two study arms otime( no final result iSD only give mixed result)
677
46
23 Keats M
R amp Culos-Reed S N (2008)
A community-based physical activity program for adolescents with cancer (project TREK) program feasibility and preliminary findings
To examine the
feasibility of a
theoretically-based
physical activity (PA)
intervention in
adolescents with
cancerand
examination of the
impact of the
program on
participant QOL
including social
emotional and
physical
well-being(including fatigue)
Repeat measures longitudinal design
No comparsion group
10 adolescents(Lymphoma(4)leukemia(4)CNS tumor(1)germ cell tumor(1)) ages 14-18 years
1physical fitness 2quality of life (QOL) 3PA behavior 4fatigue
1 Feasibility was assessed by participant recruitment attendance and adherence
2physical fitness Fitnessgram 3quality of life (QOL) Pediatric Quality of Life Inventory (PedsQL) 4PA behavior leisure score index (LSI) 5fatigue (mean) pediatric Quality of life
Multidimensional Fatigue Scale (Peds QL-MFS)
(Generalsleepcognitive fatigue)
116week physical activity (PA)
2 total PA physical fitness and overall QOL was assessed at 5 different intervals T0 preintervention (baseline) T1midintervention (after the
first 8 wk) T2 postintervention
(16 wk) T3 3-months
postintervention T4 1-year poststudy
initiation
1 from baseline -wkssig Improvementstotal PA physfitness and Qgeneral fatigue(meanplusmnSD 796plusmn135)
2 from baseline to 3FUsig Improvin general fatigue(meanplusmnSD824plusmn131)slefatigue(meanplusmnSD755plusmn191)totafatigue(meanplusmnSD778plusmn150)
3at 1 years FUsImprovements in sleeprest fatigue(meanplusmnSD725plusmn203)total (meanplusmnSD 763plusmn
678
47
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
2 Gene R E amp Conk Z (2008)
Impact of Effective Nursing Interventions to the Fatigue Syndrome in Children Who Receive Chemotherapy
1 to examine the effects of an effective nursing intervention to the fatigue syndrome of children 7 to 12 years of age who receive chemotherapy 2Tto examine the relationship between fatigue and demographic variables (age sex) diagnoses ([ALL AML] lymphoma) and therapy-related variables (eg level of hemoglobin
experimental randomized controlled study
Routine nursing care
A total of 60 children who are 7-12 years of age(a new diagnosis of ALL AML or lymphoma and receiving for the first time after being diagnosed a 7- to 10-day chemotherapy treatment )
fatigue The Fatigue Scale(FS-C) for 7-12 (intensity)
The Fatigue Scale Parent Version (FS-P)
1 effective nursing interventions(45- 60mdaya week)education about the fatigue with the chemotherapy and fatigue handbook 2 T1 After a 7-day period the children
and parent were evaluated with the Fatigue Scale
1The difference betwthe 2 mean values wafound to be statisticallsignificant 2 statistically significadifference was found between the Fatigue Scale-Child mean scothe experimental (272the control group (4213)children
679
48
25 Chiang et
al(2007)
The effects of ldquo a home ndashbased aerobic exercise interventionrdquo on fatigue and cardiorespiratory fitness in children with Acute Lymphoblastic Leukemia during the maintenance stage of chemotherapy
To examine the effect of ldquo a home ndashbased aerobic exercise interventionrdquo on fatigue and cardiorespiratory fitness in children with Acute Lymphoblastic Leukemia during the maintenance stage of chemotherapy
Quasi-experi -mental
Routine
nursing care
14 pediatric oncology patients in the experimental group and 10 in control group who were matched by age and sex ages7-18 years
1Cardiorespiratory fitness
2Fatigue
1Cardiorespiratory fitness Physical Activity Recall
VO2maxHR peak 6MWT
2 Fatigue PedsQL-MFS(Generalsleepcognitive fatigue)
1A six-week home-based aerobic exercise intervention 2 8 time points T0 baseline T1-T6 every week during the
intervention(6 weeks) T7 post intervention T8 follow-up (one month after
the end of the home-based exercise program)
1 For intent-to ndash treatthe findings indicated are no intervention efftime differences by anon the subscale of fat2 For per-protocol angeneral fatigue( mean422plusmn402) was the osubscale that was siglower for children whothe exercise interventthose in control groupfollow-up assessmentmonth after the compintervention) 3 The VO2peak are significantly improvingexperimental group atbaseline- and post-intassessment The VO2was significantly highechildren who were in experimental group thcontrol subjects at post-intervention assefor the per-protocol an
680
49
Appendix IV Instrument used to measure fatigue
Name Instrument
developers
Description Used in
age in
ref
Reliability
Consistency of
instrument
Checklist Individual Strength
(CIS)22
Vercoulen et
al1996
20 items using 7-point Likert scale of
fatigue To measure four aspects of
fatiguesubjective experience
contractionmotivation physical
Activity
6-14 Not reported
Child Fatigue Scale (CFS)7 Hockenberry
et al2003
14 items 2 part questionnaire frequency
(yes or no) 5-point Likert scale of the
intensity of any yes responses
7-13
14-18 α073-o84
The Fatigue Scale for 7-12
year Olds (FS-C)224
Hockenberry
et al
14 items provide a fatigue intensity score
5-point Likert scale
7-12 αo84
The Fatigue Scale for 13-18
year Olds (FS-A)24
Hockenberry
et al
14 items provide a fatigue intensity score
5-point Likert scale
13-18 α076-o96
Pediatric Quality of life
Multidimensional Fatigue
Scale (Peds QL-MFS)2325
Varni2002 18 items to measure three aspects of
fatigueGeneralsleepcognitive
14-18 Not reported
681
50
Appendix V Excluded studies and reasons for exclusion
Baggott C Dodd M Kennedy C Marina N Miaskowski C Multiple Symptoms in Pediatric Oncology
Patients A Systematic Review Journal of Pediatric Oncology Nursing 2009 Nov-Dec 27(6)
325-339
Reason for exclusion Not outcome of interest
Barlow JH Ellard DR Psycho-educational interventions for children with chronic disease parents and
siblings an overview of the research evidence base Care Health amp Development 2004 Nov
30(6)637-45
Reason for exclusion Not outcome of interest
Bedider S Moyer CA Randomized controlled trials of pediatric massage A review Evid Based
Complement Alternat Med 2007 Mar 4(1)23-34 Epub 2006 Nov 3
Reason for exclusion Not outcome of interest
de Nijs EJ Ros W Grijpdonck MH Nursing intervention for fatigue during the treatment for cancer Cancer
Nursing 2008 31(3)191-206
Reason for exclusion Not population of interest
Edwards JL Gibson F Richardson A Sepion B Ream E Fatigue in adolescents with and following a
cancer diagnosis developing an evidence base for practice European Journal of Cancer 2003
Dec 39(18)2671-80
Reason for exclusion Not experimental or quasi-experimental study
Hinds PS Hockenberry-Eatan M Developing a research program on fatigue in children and adolescents
diagnosed with cancer Journal of Pediatric Oncology Nursing 2001 Mar-Apr 18(2 Suppl
1)3-12
Reason for exclusion Not experimental or quasi-experimental study
Hockenberry-Eaton M Hinds PS Alcoser P ONeill JB Euell K Howard V Gattuso J Taylor J Fatigue in
Children and Adolescents With Cancer Journal of Pediatric Oncology Nursing 1998 July
15(3)172-182
Reason for exclusion Not experimental or quasi-experimental study
Jean-Pierre P Mustian K Kohli S Roscoe JA Hickok JT Morrow GR Community-based clinical oncology
research trials for cancer-related fatigue The Journal of Supportive Oncology 2006 Nov-Dec
4(10)511-6
682
51
Reason for exclusion Not population of interest
Kangas M Bovbjerg DH Montgomery GH Cancer-Related Fatigue A Systematic and Meta-Analytic
Review of Non-Pharmacological Therapies for Cancer Patients Psychological Bulletin 2008 Sep
134(5)700-41
Reason for exclusion Not population of interest
Lotfi-Jam K Carey M Jefford M Schofield P Charleson C Aranda S Nonpharmacologic strategies for
managing common chemotherapy adverse effects A systematic review Journal of Clinical
Oncology 2008 Dec 1 26(34)5618-29 Epub 2008 Nov 3
Reason for exclusion Not outcome of interest
Marchese VG Chiarello LA Lange BJ Effects of physical therapy intervention for children with acute
lymphoblastic leukemia Pediatr Blood Cancer 2004 Feb42(2)127-33
Reason for exclusion Not outcome of interest
Meeske KA Siegel SE Globe DR Mack WJ Bernstein L Prevalence and correlates of fatigue in
long-term survivors of childhood leukemia Journal of Clinical Oncology 2005 Aug 20
23(24)5501-10
Reason for exclusion Not intervention study
Minton O Richardson A Sharpe M Hotopf Stone P A systematic review and meta-analysis of the
pharmacological treatment of cancer-related fatigue J Natl Cancer Inst 2008 Aug 20
100(16)1155-66 Epub 2008 Aug 11
Reason for exclusion Not population and intervention of interest
Mustian KM Morrow GR Carroll JK Figueroa-Moseley CD Pascal JP Williams GC Integrative
nonpharmacologic behavioral interventions for the management of Cancer-Related fatigue The
Oncologist 2007 12(1)52-67
Reason for exclusion Not population of interest
Neill J Belan I Ried K Effectiveness of non-pharmacological interventions for fatigue in adults with
multiple sclerosis rheumatoid arthritis or systemic lupus erythematosus a systematic review
Journal of Advanced Nursing 2006 Dec 56(6)617-35
Reason for exclusion Not population of interest
Rheingans JI A systematic review of nonpharmacologic adjunctive therapies for symptom management
Journal of Pediatric Oncology Nursing 2007 24(2) 81-94
683
52
Reason for exclusion Not outcome of interest
Rheingans JI Pediatric oncology nursesrsquo management of patients symptoms Journal of Pediatric
Oncology Nursing 2008 Nov 25(6) 303-11
Reason for exclusion Not outcome of interest
San Juan AF Fleck SJ Chamorro-Vintildea C Mateacute-Muntildeoz JL Moral S Peacuterez M Cardona C Del Valle MF
Hernaacutendez M Ramiacuterez M Madero L Lucia A Effects of an intrahospital exercise program
intervention for children with leukemia Medicine amp Science in Sports amp Exercise 2007 Jan
39(1)13-21
Reason for exclusion Not outcome of interest
Sanford SD Okuma JO Pan J Srivastava DK West N Farr L Hinds PS Gender differences in sleep
fatigue and daytime activity in a pediatric oncology sample receiving dexamethasone Journal of
Pediatric Psychology 2008 Apr 33(3)298-306 Epub 2007 Nov 17
Reason for exclusion Not experimental or quasi-experimental study
Schmitz KH Holtzman J Courneya KS Macircsse LC Duval S Kane R Controlled physical activity trials in
cancer survivors a systematic review and meta-analysis Cancer Epidemiol Biomarkers Prev
2005 Jul 14(7)1588-95
Reason for exclusion Not population of interest
van Brussel M Takken T Lucia A van der Net J Helders PJ Is physical fitness decreased in survivors of
childhood leukemia A systematic review Leukemia 2005 Jan 19(1)13-7
Reason for exclusion Not population of interest
Whiting P Bagnall AM Snowden AJ Cornell JE Mulrow CD Ramirez G Interventions for the treatment
and management of chronic fatigue syndrome JAMA 2001 Sep 19 286(11)1360-8
Reason for exclusion Not intervention of interest
Whitsett SF Gudmundsdottir M Davies B McCarthy P Friedman D Chemotherapy-related fatigue in
childhood cancer correlates consequences and coping strategies Journal of Pediatric
Oncology Nursing 2008 Mar-Apr 25(2)86-96 Epub 2008 Feb 29
Reason for exclusion Not experimental or quasi-experimental study
Winner C Muumlller C Hoffmann C Boos J Rosenbaum D Physical activity and childhood cancer Pediatr
Blood Cancer 2010 Apr 54(4)501-10
Reason for exclusion Not research study
684
53
Wu M Hsu L Zhang B Shen N Lu H Li S The experiences of cancer-related fatigue among Chinese
children with leukaemia A phenomenological study Journal of Nursing Studies 2010 Jan
47(1)49-59 Epub 2009 Aug 25
Reason for exclusion Not experimental or quasi-experimental study
Yeh CH Chiang YC Lin L Yang CP Chien LC Weaver MA Chuang HL Clinical factors associated with
fatigue over time in paediatric oncology patients receiving chemotherapy British Journal of
Cancer 2008 Jul 8 99(1)23-9 Epub 2008 Jun 24
Reason for exclusion Not experimental or quasi-experimental study
685
34
Implications for research According to this systematic review and meta-analysis results there are suggestions to
improve the effectiveness of future research on non-pharmacological interventions for
children and young peoplersquos cancer-related fatigue
As the majority of included non-pharmacological interventions for the fatigue of cancer
patients consist of exercise programs future research should also consider various
non-pharmacological interventions in order to understand the effectiveness of different
methods
Regarding the exercise intervention methods and studies should consider multiple
factors including the age or personal condition of the subject the disease stage and the
amount of daily activities Studies should use design prescriptions (eg frequency
intensity duration and type of exercise) and consider the adherence to the measures in
order to enhance the study strength
In measuring the results of non-pharmacological interventions there should be standard
definitions or standard measurement tools to facilitate the following systematic review
and meta-analysis that can subsequently be developed into clinical care guidelines
Reviewing the effectiveness of the current non-pharmacological management of children
and adolescent cancer patients there is still a lack of rigorous RCT research Limited by
the characteristics of cancer there is still a lack of large sample sizes
Potential conflicts of interest There is no conflict of interest
Acknowledgements
Thank you to Dr Rie Konno Research Fellow Joanna Briggs Institute for her help in
assessing studies
667
35
References 1 National Comprehensive Cancer Network( NCCN) in USA NCCN clinical practice
guideline in oncology cancer-related fatigue 2011 2 Ekti Genc R amp Conk Z Impact of effective nursing interventions to the fatigue
syndrome in children who receive chemotherapy Cancer Nursing 200831(4)312-317
3 Childhood Cancer Foundation of ROC (2009March) The classification of diseases
and age sex statistical tables of case Childhood Cancer Foundation of ROC newsletter103105-106
4 Department of Health Executive Yuan ROC (TAIWAN)(2009 March 20)2009 cause of death statistic Health and National Health Insurance Annual Statistics Information Service 2010 June 28Available httpwwwdohgovtwstatisticdatavital statists9898health statistic--lifepdf
5 Chang TK (2007December 8) Common childhood cancer and its treatment Status
Childhood Cancer Foundation of ROC (TAIWAN) 2010 September 23 Available httpwwwccfrocorgtwchildchild_events_readphpe_id=45
6 Hockenberry MJ amp Wilson D Wongs nursing care of infants and children (8th ed) St
Louis MO Mosby 2007
7 Post-White J Fitzgerald M Savik K Hooke MC Hannahan AB amp Sencer SF
Massage therapy for children with cancer Journal of Pediatric Oncology Nursing 2009 26(1)16-28
8Chiang YC Yeh CH Wang WKamp Yang CP The experience of cancer-related fatigue
in Taiwanese children European Journal of Cancer Care 2009 18(1)43-49 9Langeveld NE Grootenhuis M A Voute P A de Haan RJ amp van den Bos C No excess
fatigue in young adult survivors of childhood cancer European Journal of Cancer 200339(2)204-214
10Piper BF Lindsey AM amp Dodd MJ Fatigue mechanisms in cancer patients
developing nursing theory Oncology Nursing Forum 1987 14(6)17-23 11Nail LM amp Winningham ML Fatigue In S L Groenwald M H Forgge M Goodman
amp C H Yarbro (Eds) Cancer Nursing Principles and practice (4 th ed) Boston Jones and Bartlett1997
12Irvine D Vincent L Graydon JE Bubela N amp Thompson L The prevalence and
correlates of fatigue in patients receiving treatment with chemotherapy and
668
36
radiotherapy A comparison with the fatigue experienced by healthy individuals Cancer Nursing 199417(5)367-378
13Hinds PS amp Hockenberry-Eaton M Developing a research program on fatigue in
children and adloescents diagnosed with cancer Journal of Pediatric Oncology Nursing 200118(2)3-12
14Aaronson LS Teel CS Cassmeyer V Neuberger GB Pallikkathayil L Pierce J Press
AN Williams DP amp Wingate A Defining and measuring fatigue Journal of Nursing scholarship 1999 31(1)45-50
15Yeh CH Wang CH Chiang YC Lin Lamp Chien LC Assessment of symptoms reported
by 10- to 18-year-old cancer patients in Taiwan 2009 38(5)738-746 16 Okuyama T Akechi T Kugaya A Okamura H Shima Yamp Maruguchi M
Development and validation of the cancer fatigue scale a brief three-dimensional self-rating scale for assessment of fatigue in cancer patients Journal of Pain amp Symptom Management 2000 19(1) 5-14
17Gibson F Mulhall AB Richardson A Edwards JL Ream E amp Sepion BJ A
phenomenologic study of fatigue in adolescents receiving treatment for cancer Oncology Nursing Forum200532(3)651-660
18Wolfe J Grier HE Klar N Levin SB Ellenbogen JMamp Salem-Schatz S et al
Symptoms and suffering at the end of life in children with cancer New England Journal of Medicine 2000342(5)326-333
19Whiting P Bagnall AM Sowden AJ Cornell JE Mulrow CD amp Ramirez G
Interventions for the treatment and management of chronic fatigue syndrome a systematic review JAMA the Journal of the American Medical Association 2001286(11)1360-1368
20 Kangas M Bovbjerg DHamp Montgomery G H Cancer-related fatigue a systematic
and meta-analytic review of non-pharmacological therapies for cancer patients Psychological Bulletin 2008134 (5)700-741
21Williams PD Schmideskamp J Ridder EL amp Williams AR Symptom monitoring and
dependent care during cancer treatment in children pilot study Cancer Nursing 200629(3)188-197
22Takken T van der Torre P Zwerink M Hulzebos EH Bierings M Helders PJMamp van
der Net J Development feasibility and efficacy of a community-based exercise training
669
37
program in pediatric cancer survivors Psycho-Oncology 200918(4)440-448
23Keats MR amp Culos-Reed SN A community-based physical activity program for
adolescents with cancer (project TREK) program feasibility and preliminary findings
Pediatric hematology and oncology 200830(4) 272-280
24Hinds PS Hockenberry M Rai SN Zhang L Razzouk B I Cremer L McCarthy K amp
Rodriguez-Galindo C Clinical field testing of an enhanced-activity intervention in
hospitalized children with cancer Journal of Pain amp Symptom Management 2007
33(6)686-697
25Chiang YC The effects of ldquo a home-based aerobic exercise interventionrdquo on fatigue
and cardiorespiratory fitness in children with acute lymphoblastic leukemia during the
maintenance stage of chemotherapy Unpublished thesis Taiwan Tao-Yuan 2007
26Langeveld N Ubbink M amp Smets E I dont have any energy The experience of
fatigue in young adult survivors of childhood cancer European journal of oncology
nursing 20004(1)20-28
27 Kisner C Colby L Therapeutic exercise Foundations and techniques 2nd ed Philadelphia PAFA Davies 2007
670
38
Appendix I JBI Critical Appraisal Checklist for Experimental studies
Author__________ Year_________ Record Number__________________
Questions 1 to 4 must be answered ldquoyesrdquo for study to be included in the metashyanalysis
1 Were the participants randomized to study groups
Yes No Not clear
2 Other than research intervention were participants in each groups treated the same
Yes No Not clear
3 Were the outcomes measured in the same manner for all participants
Yes No Not clear
4 Were groups comparable at entry
Yes No Not clear
5 Was randomization of participants blinded
Yes No Not clear
6 Were those assessing outcome blinded to treatment allocation (if outcome not objective such as survival or length of hospitalization)
Yes No Not clear
7 Was allocation to treatment groups concealed from the allocator
Yes No Not clear
8 Was an appropriate statistical analysis used
671
39
Yes No Not clear
9 Were outcomes measured in a reliable way
Yes No Not clear
10 Was there adequate followshyup of participants
Yes No Not clear
Summary
TOTAL
Yes No Not clear
DECISION
Use Reject
Narrative summary only Further information needed
COMMENTS
672
40
Appendix II JBI Data Extraction Tool for Quantitative Studies Authors and Year
Journal Title
Record NumberArticle Reference No
Reviewer
Method
Settings
Participants
Number of participants
Group A Group B Group C
Control Intervention 1 Intervention 2
Interventions
Group A
Control
Group B
Intervention 1
Group C
Intervention 2
Outcome measures
Definition
673
41
Other outcome measures
Outcome description ScaleMeasure
Results
Dichotomous Data
Outcome Control Group
Numbertotal number
Treatment Group
Numbertotal number
Continuous Data
Authorrsquos Conclusions
Comments
Outcome Control Group
Mean amp SD
Treatment Group
Mean amp SD
674
43
Appendix III Details of included studies (N=6)(2720212223) RefNo Author(s)
(years) Title Study question Research
method Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
22 Takken T van der Torre P Zwerink M Hulzebos E H Bierings M Helders P J Mamp van der Net J (2009)
Development feasibility and efficacy of a community-based exercise training program in pediatric cancer survivors
To develop a 12-week home-based exercise training program (comprising aerobic and strength exercises) for children who survived ALL and to study itrsquos feasibility and efficacy
Pre-post test design
No comparsion group
Survived ALL(N=9)ages 6-14 years
1anthropometry 2 muscle strength 3functional mobility 4cardio-pulmonary
exercise test 5Fatigue
1 Feasibility questionnaire 2 anthropometry electronic scale and a wallmounted stadiometerHarpenden skin fold calipers 3 muscle strength handheld dynamometer 4functional mobility Timed Up
and Go test (TUG) 5cardio-pulmonary exercise test electronically braked cycle ergometer 6Fatigue(mean)CSI-20 (subjective experience of fatigueconcentrationmotivationphysical activity)
112-week exercise training program
2 Patients were assessed before (T0) and after (T1) 12 weeks of training
1 muscle strength execapacity functional moand fatigue showed nosignificant differences between pre(meanplusmnSD415plusmn147) and post training(meanplusmnSD3687)
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
7 Post-White J Fitzgerald M Savik K Hooke M C Hannahan A B amp Sencer S F (2009)
Massage therapy for children with cancer
To determine whether 4 weekly sessions of massage compared with 4 quiet-time control conditions would reduce anxiety cortisol levels fatigue nausea and pain in children with cancer undergoing chemotherapy and would reduce anxiety fatigue and mood disturbance in a parent
2-period crossover design (Randomized)
quiet-time
control
sessions
Children with cancer 1 to 18 years of age Twenty-three childrenparent dyads were enrolled 17 completed all data points
children 1relaxation 2symptoms 3 fatigue
parents
1anxiety 2 fatigue
children 1relaxation (heart and respiratory rates blood pressure and salivary cortisol level)
2symptoms (pain nausea anxiety 3 fatigue 1-2y3-6yLansky Play Performance Scale (PPS) 7-13y
1 4 weekly massage (MT) sessions alternated with 4 weekly quiet-time(QT) control sessions
2 children included presession and postsession vital signs (heart rate respiratory rate blood pressure) and self-report (parent proxy report for age 1-2 years) of pain nausea and anxiety Fatigue was measured before sessions 1 and 4 and at each follow-up Parent measures
included anxiety fatigue and mood states
1Massage was moreeffective than quiet tireducing heart rate inchildren anxiety in cless than age 14 yeaparent anxiety 2There were no sign
changes in blood pcortisol pain naufatigue (no state d
3 Children reported tmassage helped thebetter lessened theirand worries and hadlasting effects than q
675
44
14-18yChild Fatigue Scale (CFS) (frequency
intensity) 2 parents anxiety and fatigue
676
45
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
24 Hinds P S Hockenberry M Rai S N Zhang L Razzouk B I Cremer L McCarthy K amp Rodriguez-Galindo C (2007)
Clinical field testing of an enhanced-activity intervention in hospitalized children with cancer
To determine the feasibility of an
enhanced physical activity EPA intervention in children and adolescents hospitalized to receive chemotherapy for a solid tumor or AML and to assess the sleep and fatigue outcomes of the intervention using two different statistical approaches to analyze the longitudinal symptom data
randomized prospective two-site and two-group pilot study
Standard care Twenty nine patients (25 with a solid tumor and 4 with AML)ages 7-18 years
1 sleep duration 2 sleep efficiency 3 fatigue
1sleep duration sleep efficiency The
Wrist Actigraph The Daily Sleep Diary-Parent 2 fatigue (mean) The Fatigue Scale(FS-C) for 7-12 (intensity) The Fatigue Scale(FS-A) for 13-18 The Fatigue Scale Parent Version (FS-P) The Fatigue Scale Staff Version (FS-S)
1enhanced physical activity (EPA) (hospital-based 30 minutes
twice daily for 2-4 days) 2 T0On the day of admission
(Day 0 or baseline)patient and parents completed the fatigue instruments and a team member applied the actigraph Patients wore the wrist actigraph T1 from Day 0 to 2 or 3 consecutive days (Days 0e3) In addition the patient same parent and staff nurses completed the daily sleep and fatigue reports in the late afternoons of Days 1-3
1 ANOVA model slesignificantly more the experimental athe control arm whdifferences from bsleep efficiency vaaveraged and com
2 The patient-reported mean fatigue scoresarms were higher amadolescents than for
3 The mixed model anarevealed no significandifferences in patientfatigue between
the two study arms otime( no final result iSD only give mixed result)
677
46
23 Keats M
R amp Culos-Reed S N (2008)
A community-based physical activity program for adolescents with cancer (project TREK) program feasibility and preliminary findings
To examine the
feasibility of a
theoretically-based
physical activity (PA)
intervention in
adolescents with
cancerand
examination of the
impact of the
program on
participant QOL
including social
emotional and
physical
well-being(including fatigue)
Repeat measures longitudinal design
No comparsion group
10 adolescents(Lymphoma(4)leukemia(4)CNS tumor(1)germ cell tumor(1)) ages 14-18 years
1physical fitness 2quality of life (QOL) 3PA behavior 4fatigue
1 Feasibility was assessed by participant recruitment attendance and adherence
2physical fitness Fitnessgram 3quality of life (QOL) Pediatric Quality of Life Inventory (PedsQL) 4PA behavior leisure score index (LSI) 5fatigue (mean) pediatric Quality of life
Multidimensional Fatigue Scale (Peds QL-MFS)
(Generalsleepcognitive fatigue)
116week physical activity (PA)
2 total PA physical fitness and overall QOL was assessed at 5 different intervals T0 preintervention (baseline) T1midintervention (after the
first 8 wk) T2 postintervention
(16 wk) T3 3-months
postintervention T4 1-year poststudy
initiation
1 from baseline -wkssig Improvementstotal PA physfitness and Qgeneral fatigue(meanplusmnSD 796plusmn135)
2 from baseline to 3FUsig Improvin general fatigue(meanplusmnSD824plusmn131)slefatigue(meanplusmnSD755plusmn191)totafatigue(meanplusmnSD778plusmn150)
3at 1 years FUsImprovements in sleeprest fatigue(meanplusmnSD725plusmn203)total (meanplusmnSD 763plusmn
678
47
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
2 Gene R E amp Conk Z (2008)
Impact of Effective Nursing Interventions to the Fatigue Syndrome in Children Who Receive Chemotherapy
1 to examine the effects of an effective nursing intervention to the fatigue syndrome of children 7 to 12 years of age who receive chemotherapy 2Tto examine the relationship between fatigue and demographic variables (age sex) diagnoses ([ALL AML] lymphoma) and therapy-related variables (eg level of hemoglobin
experimental randomized controlled study
Routine nursing care
A total of 60 children who are 7-12 years of age(a new diagnosis of ALL AML or lymphoma and receiving for the first time after being diagnosed a 7- to 10-day chemotherapy treatment )
fatigue The Fatigue Scale(FS-C) for 7-12 (intensity)
The Fatigue Scale Parent Version (FS-P)
1 effective nursing interventions(45- 60mdaya week)education about the fatigue with the chemotherapy and fatigue handbook 2 T1 After a 7-day period the children
and parent were evaluated with the Fatigue Scale
1The difference betwthe 2 mean values wafound to be statisticallsignificant 2 statistically significadifference was found between the Fatigue Scale-Child mean scothe experimental (272the control group (4213)children
679
48
25 Chiang et
al(2007)
The effects of ldquo a home ndashbased aerobic exercise interventionrdquo on fatigue and cardiorespiratory fitness in children with Acute Lymphoblastic Leukemia during the maintenance stage of chemotherapy
To examine the effect of ldquo a home ndashbased aerobic exercise interventionrdquo on fatigue and cardiorespiratory fitness in children with Acute Lymphoblastic Leukemia during the maintenance stage of chemotherapy
Quasi-experi -mental
Routine
nursing care
14 pediatric oncology patients in the experimental group and 10 in control group who were matched by age and sex ages7-18 years
1Cardiorespiratory fitness
2Fatigue
1Cardiorespiratory fitness Physical Activity Recall
VO2maxHR peak 6MWT
2 Fatigue PedsQL-MFS(Generalsleepcognitive fatigue)
1A six-week home-based aerobic exercise intervention 2 8 time points T0 baseline T1-T6 every week during the
intervention(6 weeks) T7 post intervention T8 follow-up (one month after
the end of the home-based exercise program)
1 For intent-to ndash treatthe findings indicated are no intervention efftime differences by anon the subscale of fat2 For per-protocol angeneral fatigue( mean422plusmn402) was the osubscale that was siglower for children whothe exercise interventthose in control groupfollow-up assessmentmonth after the compintervention) 3 The VO2peak are significantly improvingexperimental group atbaseline- and post-intassessment The VO2was significantly highechildren who were in experimental group thcontrol subjects at post-intervention assefor the per-protocol an
680
49
Appendix IV Instrument used to measure fatigue
Name Instrument
developers
Description Used in
age in
ref
Reliability
Consistency of
instrument
Checklist Individual Strength
(CIS)22
Vercoulen et
al1996
20 items using 7-point Likert scale of
fatigue To measure four aspects of
fatiguesubjective experience
contractionmotivation physical
Activity
6-14 Not reported
Child Fatigue Scale (CFS)7 Hockenberry
et al2003
14 items 2 part questionnaire frequency
(yes or no) 5-point Likert scale of the
intensity of any yes responses
7-13
14-18 α073-o84
The Fatigue Scale for 7-12
year Olds (FS-C)224
Hockenberry
et al
14 items provide a fatigue intensity score
5-point Likert scale
7-12 αo84
The Fatigue Scale for 13-18
year Olds (FS-A)24
Hockenberry
et al
14 items provide a fatigue intensity score
5-point Likert scale
13-18 α076-o96
Pediatric Quality of life
Multidimensional Fatigue
Scale (Peds QL-MFS)2325
Varni2002 18 items to measure three aspects of
fatigueGeneralsleepcognitive
14-18 Not reported
681
50
Appendix V Excluded studies and reasons for exclusion
Baggott C Dodd M Kennedy C Marina N Miaskowski C Multiple Symptoms in Pediatric Oncology
Patients A Systematic Review Journal of Pediatric Oncology Nursing 2009 Nov-Dec 27(6)
325-339
Reason for exclusion Not outcome of interest
Barlow JH Ellard DR Psycho-educational interventions for children with chronic disease parents and
siblings an overview of the research evidence base Care Health amp Development 2004 Nov
30(6)637-45
Reason for exclusion Not outcome of interest
Bedider S Moyer CA Randomized controlled trials of pediatric massage A review Evid Based
Complement Alternat Med 2007 Mar 4(1)23-34 Epub 2006 Nov 3
Reason for exclusion Not outcome of interest
de Nijs EJ Ros W Grijpdonck MH Nursing intervention for fatigue during the treatment for cancer Cancer
Nursing 2008 31(3)191-206
Reason for exclusion Not population of interest
Edwards JL Gibson F Richardson A Sepion B Ream E Fatigue in adolescents with and following a
cancer diagnosis developing an evidence base for practice European Journal of Cancer 2003
Dec 39(18)2671-80
Reason for exclusion Not experimental or quasi-experimental study
Hinds PS Hockenberry-Eatan M Developing a research program on fatigue in children and adolescents
diagnosed with cancer Journal of Pediatric Oncology Nursing 2001 Mar-Apr 18(2 Suppl
1)3-12
Reason for exclusion Not experimental or quasi-experimental study
Hockenberry-Eaton M Hinds PS Alcoser P ONeill JB Euell K Howard V Gattuso J Taylor J Fatigue in
Children and Adolescents With Cancer Journal of Pediatric Oncology Nursing 1998 July
15(3)172-182
Reason for exclusion Not experimental or quasi-experimental study
Jean-Pierre P Mustian K Kohli S Roscoe JA Hickok JT Morrow GR Community-based clinical oncology
research trials for cancer-related fatigue The Journal of Supportive Oncology 2006 Nov-Dec
4(10)511-6
682
51
Reason for exclusion Not population of interest
Kangas M Bovbjerg DH Montgomery GH Cancer-Related Fatigue A Systematic and Meta-Analytic
Review of Non-Pharmacological Therapies for Cancer Patients Psychological Bulletin 2008 Sep
134(5)700-41
Reason for exclusion Not population of interest
Lotfi-Jam K Carey M Jefford M Schofield P Charleson C Aranda S Nonpharmacologic strategies for
managing common chemotherapy adverse effects A systematic review Journal of Clinical
Oncology 2008 Dec 1 26(34)5618-29 Epub 2008 Nov 3
Reason for exclusion Not outcome of interest
Marchese VG Chiarello LA Lange BJ Effects of physical therapy intervention for children with acute
lymphoblastic leukemia Pediatr Blood Cancer 2004 Feb42(2)127-33
Reason for exclusion Not outcome of interest
Meeske KA Siegel SE Globe DR Mack WJ Bernstein L Prevalence and correlates of fatigue in
long-term survivors of childhood leukemia Journal of Clinical Oncology 2005 Aug 20
23(24)5501-10
Reason for exclusion Not intervention study
Minton O Richardson A Sharpe M Hotopf Stone P A systematic review and meta-analysis of the
pharmacological treatment of cancer-related fatigue J Natl Cancer Inst 2008 Aug 20
100(16)1155-66 Epub 2008 Aug 11
Reason for exclusion Not population and intervention of interest
Mustian KM Morrow GR Carroll JK Figueroa-Moseley CD Pascal JP Williams GC Integrative
nonpharmacologic behavioral interventions for the management of Cancer-Related fatigue The
Oncologist 2007 12(1)52-67
Reason for exclusion Not population of interest
Neill J Belan I Ried K Effectiveness of non-pharmacological interventions for fatigue in adults with
multiple sclerosis rheumatoid arthritis or systemic lupus erythematosus a systematic review
Journal of Advanced Nursing 2006 Dec 56(6)617-35
Reason for exclusion Not population of interest
Rheingans JI A systematic review of nonpharmacologic adjunctive therapies for symptom management
Journal of Pediatric Oncology Nursing 2007 24(2) 81-94
683
52
Reason for exclusion Not outcome of interest
Rheingans JI Pediatric oncology nursesrsquo management of patients symptoms Journal of Pediatric
Oncology Nursing 2008 Nov 25(6) 303-11
Reason for exclusion Not outcome of interest
San Juan AF Fleck SJ Chamorro-Vintildea C Mateacute-Muntildeoz JL Moral S Peacuterez M Cardona C Del Valle MF
Hernaacutendez M Ramiacuterez M Madero L Lucia A Effects of an intrahospital exercise program
intervention for children with leukemia Medicine amp Science in Sports amp Exercise 2007 Jan
39(1)13-21
Reason for exclusion Not outcome of interest
Sanford SD Okuma JO Pan J Srivastava DK West N Farr L Hinds PS Gender differences in sleep
fatigue and daytime activity in a pediatric oncology sample receiving dexamethasone Journal of
Pediatric Psychology 2008 Apr 33(3)298-306 Epub 2007 Nov 17
Reason for exclusion Not experimental or quasi-experimental study
Schmitz KH Holtzman J Courneya KS Macircsse LC Duval S Kane R Controlled physical activity trials in
cancer survivors a systematic review and meta-analysis Cancer Epidemiol Biomarkers Prev
2005 Jul 14(7)1588-95
Reason for exclusion Not population of interest
van Brussel M Takken T Lucia A van der Net J Helders PJ Is physical fitness decreased in survivors of
childhood leukemia A systematic review Leukemia 2005 Jan 19(1)13-7
Reason for exclusion Not population of interest
Whiting P Bagnall AM Snowden AJ Cornell JE Mulrow CD Ramirez G Interventions for the treatment
and management of chronic fatigue syndrome JAMA 2001 Sep 19 286(11)1360-8
Reason for exclusion Not intervention of interest
Whitsett SF Gudmundsdottir M Davies B McCarthy P Friedman D Chemotherapy-related fatigue in
childhood cancer correlates consequences and coping strategies Journal of Pediatric
Oncology Nursing 2008 Mar-Apr 25(2)86-96 Epub 2008 Feb 29
Reason for exclusion Not experimental or quasi-experimental study
Winner C Muumlller C Hoffmann C Boos J Rosenbaum D Physical activity and childhood cancer Pediatr
Blood Cancer 2010 Apr 54(4)501-10
Reason for exclusion Not research study
684
53
Wu M Hsu L Zhang B Shen N Lu H Li S The experiences of cancer-related fatigue among Chinese
children with leukaemia A phenomenological study Journal of Nursing Studies 2010 Jan
47(1)49-59 Epub 2009 Aug 25
Reason for exclusion Not experimental or quasi-experimental study
Yeh CH Chiang YC Lin L Yang CP Chien LC Weaver MA Chuang HL Clinical factors associated with
fatigue over time in paediatric oncology patients receiving chemotherapy British Journal of
Cancer 2008 Jul 8 99(1)23-9 Epub 2008 Jun 24
Reason for exclusion Not experimental or quasi-experimental study
685
35
References 1 National Comprehensive Cancer Network( NCCN) in USA NCCN clinical practice
guideline in oncology cancer-related fatigue 2011 2 Ekti Genc R amp Conk Z Impact of effective nursing interventions to the fatigue
syndrome in children who receive chemotherapy Cancer Nursing 200831(4)312-317
3 Childhood Cancer Foundation of ROC (2009March) The classification of diseases
and age sex statistical tables of case Childhood Cancer Foundation of ROC newsletter103105-106
4 Department of Health Executive Yuan ROC (TAIWAN)(2009 March 20)2009 cause of death statistic Health and National Health Insurance Annual Statistics Information Service 2010 June 28Available httpwwwdohgovtwstatisticdatavital statists9898health statistic--lifepdf
5 Chang TK (2007December 8) Common childhood cancer and its treatment Status
Childhood Cancer Foundation of ROC (TAIWAN) 2010 September 23 Available httpwwwccfrocorgtwchildchild_events_readphpe_id=45
6 Hockenberry MJ amp Wilson D Wongs nursing care of infants and children (8th ed) St
Louis MO Mosby 2007
7 Post-White J Fitzgerald M Savik K Hooke MC Hannahan AB amp Sencer SF
Massage therapy for children with cancer Journal of Pediatric Oncology Nursing 2009 26(1)16-28
8Chiang YC Yeh CH Wang WKamp Yang CP The experience of cancer-related fatigue
in Taiwanese children European Journal of Cancer Care 2009 18(1)43-49 9Langeveld NE Grootenhuis M A Voute P A de Haan RJ amp van den Bos C No excess
fatigue in young adult survivors of childhood cancer European Journal of Cancer 200339(2)204-214
10Piper BF Lindsey AM amp Dodd MJ Fatigue mechanisms in cancer patients
developing nursing theory Oncology Nursing Forum 1987 14(6)17-23 11Nail LM amp Winningham ML Fatigue In S L Groenwald M H Forgge M Goodman
amp C H Yarbro (Eds) Cancer Nursing Principles and practice (4 th ed) Boston Jones and Bartlett1997
12Irvine D Vincent L Graydon JE Bubela N amp Thompson L The prevalence and
correlates of fatigue in patients receiving treatment with chemotherapy and
668
36
radiotherapy A comparison with the fatigue experienced by healthy individuals Cancer Nursing 199417(5)367-378
13Hinds PS amp Hockenberry-Eaton M Developing a research program on fatigue in
children and adloescents diagnosed with cancer Journal of Pediatric Oncology Nursing 200118(2)3-12
14Aaronson LS Teel CS Cassmeyer V Neuberger GB Pallikkathayil L Pierce J Press
AN Williams DP amp Wingate A Defining and measuring fatigue Journal of Nursing scholarship 1999 31(1)45-50
15Yeh CH Wang CH Chiang YC Lin Lamp Chien LC Assessment of symptoms reported
by 10- to 18-year-old cancer patients in Taiwan 2009 38(5)738-746 16 Okuyama T Akechi T Kugaya A Okamura H Shima Yamp Maruguchi M
Development and validation of the cancer fatigue scale a brief three-dimensional self-rating scale for assessment of fatigue in cancer patients Journal of Pain amp Symptom Management 2000 19(1) 5-14
17Gibson F Mulhall AB Richardson A Edwards JL Ream E amp Sepion BJ A
phenomenologic study of fatigue in adolescents receiving treatment for cancer Oncology Nursing Forum200532(3)651-660
18Wolfe J Grier HE Klar N Levin SB Ellenbogen JMamp Salem-Schatz S et al
Symptoms and suffering at the end of life in children with cancer New England Journal of Medicine 2000342(5)326-333
19Whiting P Bagnall AM Sowden AJ Cornell JE Mulrow CD amp Ramirez G
Interventions for the treatment and management of chronic fatigue syndrome a systematic review JAMA the Journal of the American Medical Association 2001286(11)1360-1368
20 Kangas M Bovbjerg DHamp Montgomery G H Cancer-related fatigue a systematic
and meta-analytic review of non-pharmacological therapies for cancer patients Psychological Bulletin 2008134 (5)700-741
21Williams PD Schmideskamp J Ridder EL amp Williams AR Symptom monitoring and
dependent care during cancer treatment in children pilot study Cancer Nursing 200629(3)188-197
22Takken T van der Torre P Zwerink M Hulzebos EH Bierings M Helders PJMamp van
der Net J Development feasibility and efficacy of a community-based exercise training
669
37
program in pediatric cancer survivors Psycho-Oncology 200918(4)440-448
23Keats MR amp Culos-Reed SN A community-based physical activity program for
adolescents with cancer (project TREK) program feasibility and preliminary findings
Pediatric hematology and oncology 200830(4) 272-280
24Hinds PS Hockenberry M Rai SN Zhang L Razzouk B I Cremer L McCarthy K amp
Rodriguez-Galindo C Clinical field testing of an enhanced-activity intervention in
hospitalized children with cancer Journal of Pain amp Symptom Management 2007
33(6)686-697
25Chiang YC The effects of ldquo a home-based aerobic exercise interventionrdquo on fatigue
and cardiorespiratory fitness in children with acute lymphoblastic leukemia during the
maintenance stage of chemotherapy Unpublished thesis Taiwan Tao-Yuan 2007
26Langeveld N Ubbink M amp Smets E I dont have any energy The experience of
fatigue in young adult survivors of childhood cancer European journal of oncology
nursing 20004(1)20-28
27 Kisner C Colby L Therapeutic exercise Foundations and techniques 2nd ed Philadelphia PAFA Davies 2007
670
38
Appendix I JBI Critical Appraisal Checklist for Experimental studies
Author__________ Year_________ Record Number__________________
Questions 1 to 4 must be answered ldquoyesrdquo for study to be included in the metashyanalysis
1 Were the participants randomized to study groups
Yes No Not clear
2 Other than research intervention were participants in each groups treated the same
Yes No Not clear
3 Were the outcomes measured in the same manner for all participants
Yes No Not clear
4 Were groups comparable at entry
Yes No Not clear
5 Was randomization of participants blinded
Yes No Not clear
6 Were those assessing outcome blinded to treatment allocation (if outcome not objective such as survival or length of hospitalization)
Yes No Not clear
7 Was allocation to treatment groups concealed from the allocator
Yes No Not clear
8 Was an appropriate statistical analysis used
671
39
Yes No Not clear
9 Were outcomes measured in a reliable way
Yes No Not clear
10 Was there adequate followshyup of participants
Yes No Not clear
Summary
TOTAL
Yes No Not clear
DECISION
Use Reject
Narrative summary only Further information needed
COMMENTS
672
40
Appendix II JBI Data Extraction Tool for Quantitative Studies Authors and Year
Journal Title
Record NumberArticle Reference No
Reviewer
Method
Settings
Participants
Number of participants
Group A Group B Group C
Control Intervention 1 Intervention 2
Interventions
Group A
Control
Group B
Intervention 1
Group C
Intervention 2
Outcome measures
Definition
673
41
Other outcome measures
Outcome description ScaleMeasure
Results
Dichotomous Data
Outcome Control Group
Numbertotal number
Treatment Group
Numbertotal number
Continuous Data
Authorrsquos Conclusions
Comments
Outcome Control Group
Mean amp SD
Treatment Group
Mean amp SD
674
43
Appendix III Details of included studies (N=6)(2720212223) RefNo Author(s)
(years) Title Study question Research
method Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
22 Takken T van der Torre P Zwerink M Hulzebos E H Bierings M Helders P J Mamp van der Net J (2009)
Development feasibility and efficacy of a community-based exercise training program in pediatric cancer survivors
To develop a 12-week home-based exercise training program (comprising aerobic and strength exercises) for children who survived ALL and to study itrsquos feasibility and efficacy
Pre-post test design
No comparsion group
Survived ALL(N=9)ages 6-14 years
1anthropometry 2 muscle strength 3functional mobility 4cardio-pulmonary
exercise test 5Fatigue
1 Feasibility questionnaire 2 anthropometry electronic scale and a wallmounted stadiometerHarpenden skin fold calipers 3 muscle strength handheld dynamometer 4functional mobility Timed Up
and Go test (TUG) 5cardio-pulmonary exercise test electronically braked cycle ergometer 6Fatigue(mean)CSI-20 (subjective experience of fatigueconcentrationmotivationphysical activity)
112-week exercise training program
2 Patients were assessed before (T0) and after (T1) 12 weeks of training
1 muscle strength execapacity functional moand fatigue showed nosignificant differences between pre(meanplusmnSD415plusmn147) and post training(meanplusmnSD3687)
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
7 Post-White J Fitzgerald M Savik K Hooke M C Hannahan A B amp Sencer S F (2009)
Massage therapy for children with cancer
To determine whether 4 weekly sessions of massage compared with 4 quiet-time control conditions would reduce anxiety cortisol levels fatigue nausea and pain in children with cancer undergoing chemotherapy and would reduce anxiety fatigue and mood disturbance in a parent
2-period crossover design (Randomized)
quiet-time
control
sessions
Children with cancer 1 to 18 years of age Twenty-three childrenparent dyads were enrolled 17 completed all data points
children 1relaxation 2symptoms 3 fatigue
parents
1anxiety 2 fatigue
children 1relaxation (heart and respiratory rates blood pressure and salivary cortisol level)
2symptoms (pain nausea anxiety 3 fatigue 1-2y3-6yLansky Play Performance Scale (PPS) 7-13y
1 4 weekly massage (MT) sessions alternated with 4 weekly quiet-time(QT) control sessions
2 children included presession and postsession vital signs (heart rate respiratory rate blood pressure) and self-report (parent proxy report for age 1-2 years) of pain nausea and anxiety Fatigue was measured before sessions 1 and 4 and at each follow-up Parent measures
included anxiety fatigue and mood states
1Massage was moreeffective than quiet tireducing heart rate inchildren anxiety in cless than age 14 yeaparent anxiety 2There were no sign
changes in blood pcortisol pain naufatigue (no state d
3 Children reported tmassage helped thebetter lessened theirand worries and hadlasting effects than q
675
44
14-18yChild Fatigue Scale (CFS) (frequency
intensity) 2 parents anxiety and fatigue
676
45
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
24 Hinds P S Hockenberry M Rai S N Zhang L Razzouk B I Cremer L McCarthy K amp Rodriguez-Galindo C (2007)
Clinical field testing of an enhanced-activity intervention in hospitalized children with cancer
To determine the feasibility of an
enhanced physical activity EPA intervention in children and adolescents hospitalized to receive chemotherapy for a solid tumor or AML and to assess the sleep and fatigue outcomes of the intervention using two different statistical approaches to analyze the longitudinal symptom data
randomized prospective two-site and two-group pilot study
Standard care Twenty nine patients (25 with a solid tumor and 4 with AML)ages 7-18 years
1 sleep duration 2 sleep efficiency 3 fatigue
1sleep duration sleep efficiency The
Wrist Actigraph The Daily Sleep Diary-Parent 2 fatigue (mean) The Fatigue Scale(FS-C) for 7-12 (intensity) The Fatigue Scale(FS-A) for 13-18 The Fatigue Scale Parent Version (FS-P) The Fatigue Scale Staff Version (FS-S)
1enhanced physical activity (EPA) (hospital-based 30 minutes
twice daily for 2-4 days) 2 T0On the day of admission
(Day 0 or baseline)patient and parents completed the fatigue instruments and a team member applied the actigraph Patients wore the wrist actigraph T1 from Day 0 to 2 or 3 consecutive days (Days 0e3) In addition the patient same parent and staff nurses completed the daily sleep and fatigue reports in the late afternoons of Days 1-3
1 ANOVA model slesignificantly more the experimental athe control arm whdifferences from bsleep efficiency vaaveraged and com
2 The patient-reported mean fatigue scoresarms were higher amadolescents than for
3 The mixed model anarevealed no significandifferences in patientfatigue between
the two study arms otime( no final result iSD only give mixed result)
677
46
23 Keats M
R amp Culos-Reed S N (2008)
A community-based physical activity program for adolescents with cancer (project TREK) program feasibility and preliminary findings
To examine the
feasibility of a
theoretically-based
physical activity (PA)
intervention in
adolescents with
cancerand
examination of the
impact of the
program on
participant QOL
including social
emotional and
physical
well-being(including fatigue)
Repeat measures longitudinal design
No comparsion group
10 adolescents(Lymphoma(4)leukemia(4)CNS tumor(1)germ cell tumor(1)) ages 14-18 years
1physical fitness 2quality of life (QOL) 3PA behavior 4fatigue
1 Feasibility was assessed by participant recruitment attendance and adherence
2physical fitness Fitnessgram 3quality of life (QOL) Pediatric Quality of Life Inventory (PedsQL) 4PA behavior leisure score index (LSI) 5fatigue (mean) pediatric Quality of life
Multidimensional Fatigue Scale (Peds QL-MFS)
(Generalsleepcognitive fatigue)
116week physical activity (PA)
2 total PA physical fitness and overall QOL was assessed at 5 different intervals T0 preintervention (baseline) T1midintervention (after the
first 8 wk) T2 postintervention
(16 wk) T3 3-months
postintervention T4 1-year poststudy
initiation
1 from baseline -wkssig Improvementstotal PA physfitness and Qgeneral fatigue(meanplusmnSD 796plusmn135)
2 from baseline to 3FUsig Improvin general fatigue(meanplusmnSD824plusmn131)slefatigue(meanplusmnSD755plusmn191)totafatigue(meanplusmnSD778plusmn150)
3at 1 years FUsImprovements in sleeprest fatigue(meanplusmnSD725plusmn203)total (meanplusmnSD 763plusmn
678
47
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
2 Gene R E amp Conk Z (2008)
Impact of Effective Nursing Interventions to the Fatigue Syndrome in Children Who Receive Chemotherapy
1 to examine the effects of an effective nursing intervention to the fatigue syndrome of children 7 to 12 years of age who receive chemotherapy 2Tto examine the relationship between fatigue and demographic variables (age sex) diagnoses ([ALL AML] lymphoma) and therapy-related variables (eg level of hemoglobin
experimental randomized controlled study
Routine nursing care
A total of 60 children who are 7-12 years of age(a new diagnosis of ALL AML or lymphoma and receiving for the first time after being diagnosed a 7- to 10-day chemotherapy treatment )
fatigue The Fatigue Scale(FS-C) for 7-12 (intensity)
The Fatigue Scale Parent Version (FS-P)
1 effective nursing interventions(45- 60mdaya week)education about the fatigue with the chemotherapy and fatigue handbook 2 T1 After a 7-day period the children
and parent were evaluated with the Fatigue Scale
1The difference betwthe 2 mean values wafound to be statisticallsignificant 2 statistically significadifference was found between the Fatigue Scale-Child mean scothe experimental (272the control group (4213)children
679
48
25 Chiang et
al(2007)
The effects of ldquo a home ndashbased aerobic exercise interventionrdquo on fatigue and cardiorespiratory fitness in children with Acute Lymphoblastic Leukemia during the maintenance stage of chemotherapy
To examine the effect of ldquo a home ndashbased aerobic exercise interventionrdquo on fatigue and cardiorespiratory fitness in children with Acute Lymphoblastic Leukemia during the maintenance stage of chemotherapy
Quasi-experi -mental
Routine
nursing care
14 pediatric oncology patients in the experimental group and 10 in control group who were matched by age and sex ages7-18 years
1Cardiorespiratory fitness
2Fatigue
1Cardiorespiratory fitness Physical Activity Recall
VO2maxHR peak 6MWT
2 Fatigue PedsQL-MFS(Generalsleepcognitive fatigue)
1A six-week home-based aerobic exercise intervention 2 8 time points T0 baseline T1-T6 every week during the
intervention(6 weeks) T7 post intervention T8 follow-up (one month after
the end of the home-based exercise program)
1 For intent-to ndash treatthe findings indicated are no intervention efftime differences by anon the subscale of fat2 For per-protocol angeneral fatigue( mean422plusmn402) was the osubscale that was siglower for children whothe exercise interventthose in control groupfollow-up assessmentmonth after the compintervention) 3 The VO2peak are significantly improvingexperimental group atbaseline- and post-intassessment The VO2was significantly highechildren who were in experimental group thcontrol subjects at post-intervention assefor the per-protocol an
680
49
Appendix IV Instrument used to measure fatigue
Name Instrument
developers
Description Used in
age in
ref
Reliability
Consistency of
instrument
Checklist Individual Strength
(CIS)22
Vercoulen et
al1996
20 items using 7-point Likert scale of
fatigue To measure four aspects of
fatiguesubjective experience
contractionmotivation physical
Activity
6-14 Not reported
Child Fatigue Scale (CFS)7 Hockenberry
et al2003
14 items 2 part questionnaire frequency
(yes or no) 5-point Likert scale of the
intensity of any yes responses
7-13
14-18 α073-o84
The Fatigue Scale for 7-12
year Olds (FS-C)224
Hockenberry
et al
14 items provide a fatigue intensity score
5-point Likert scale
7-12 αo84
The Fatigue Scale for 13-18
year Olds (FS-A)24
Hockenberry
et al
14 items provide a fatigue intensity score
5-point Likert scale
13-18 α076-o96
Pediatric Quality of life
Multidimensional Fatigue
Scale (Peds QL-MFS)2325
Varni2002 18 items to measure three aspects of
fatigueGeneralsleepcognitive
14-18 Not reported
681
50
Appendix V Excluded studies and reasons for exclusion
Baggott C Dodd M Kennedy C Marina N Miaskowski C Multiple Symptoms in Pediatric Oncology
Patients A Systematic Review Journal of Pediatric Oncology Nursing 2009 Nov-Dec 27(6)
325-339
Reason for exclusion Not outcome of interest
Barlow JH Ellard DR Psycho-educational interventions for children with chronic disease parents and
siblings an overview of the research evidence base Care Health amp Development 2004 Nov
30(6)637-45
Reason for exclusion Not outcome of interest
Bedider S Moyer CA Randomized controlled trials of pediatric massage A review Evid Based
Complement Alternat Med 2007 Mar 4(1)23-34 Epub 2006 Nov 3
Reason for exclusion Not outcome of interest
de Nijs EJ Ros W Grijpdonck MH Nursing intervention for fatigue during the treatment for cancer Cancer
Nursing 2008 31(3)191-206
Reason for exclusion Not population of interest
Edwards JL Gibson F Richardson A Sepion B Ream E Fatigue in adolescents with and following a
cancer diagnosis developing an evidence base for practice European Journal of Cancer 2003
Dec 39(18)2671-80
Reason for exclusion Not experimental or quasi-experimental study
Hinds PS Hockenberry-Eatan M Developing a research program on fatigue in children and adolescents
diagnosed with cancer Journal of Pediatric Oncology Nursing 2001 Mar-Apr 18(2 Suppl
1)3-12
Reason for exclusion Not experimental or quasi-experimental study
Hockenberry-Eaton M Hinds PS Alcoser P ONeill JB Euell K Howard V Gattuso J Taylor J Fatigue in
Children and Adolescents With Cancer Journal of Pediatric Oncology Nursing 1998 July
15(3)172-182
Reason for exclusion Not experimental or quasi-experimental study
Jean-Pierre P Mustian K Kohli S Roscoe JA Hickok JT Morrow GR Community-based clinical oncology
research trials for cancer-related fatigue The Journal of Supportive Oncology 2006 Nov-Dec
4(10)511-6
682
51
Reason for exclusion Not population of interest
Kangas M Bovbjerg DH Montgomery GH Cancer-Related Fatigue A Systematic and Meta-Analytic
Review of Non-Pharmacological Therapies for Cancer Patients Psychological Bulletin 2008 Sep
134(5)700-41
Reason for exclusion Not population of interest
Lotfi-Jam K Carey M Jefford M Schofield P Charleson C Aranda S Nonpharmacologic strategies for
managing common chemotherapy adverse effects A systematic review Journal of Clinical
Oncology 2008 Dec 1 26(34)5618-29 Epub 2008 Nov 3
Reason for exclusion Not outcome of interest
Marchese VG Chiarello LA Lange BJ Effects of physical therapy intervention for children with acute
lymphoblastic leukemia Pediatr Blood Cancer 2004 Feb42(2)127-33
Reason for exclusion Not outcome of interest
Meeske KA Siegel SE Globe DR Mack WJ Bernstein L Prevalence and correlates of fatigue in
long-term survivors of childhood leukemia Journal of Clinical Oncology 2005 Aug 20
23(24)5501-10
Reason for exclusion Not intervention study
Minton O Richardson A Sharpe M Hotopf Stone P A systematic review and meta-analysis of the
pharmacological treatment of cancer-related fatigue J Natl Cancer Inst 2008 Aug 20
100(16)1155-66 Epub 2008 Aug 11
Reason for exclusion Not population and intervention of interest
Mustian KM Morrow GR Carroll JK Figueroa-Moseley CD Pascal JP Williams GC Integrative
nonpharmacologic behavioral interventions for the management of Cancer-Related fatigue The
Oncologist 2007 12(1)52-67
Reason for exclusion Not population of interest
Neill J Belan I Ried K Effectiveness of non-pharmacological interventions for fatigue in adults with
multiple sclerosis rheumatoid arthritis or systemic lupus erythematosus a systematic review
Journal of Advanced Nursing 2006 Dec 56(6)617-35
Reason for exclusion Not population of interest
Rheingans JI A systematic review of nonpharmacologic adjunctive therapies for symptom management
Journal of Pediatric Oncology Nursing 2007 24(2) 81-94
683
52
Reason for exclusion Not outcome of interest
Rheingans JI Pediatric oncology nursesrsquo management of patients symptoms Journal of Pediatric
Oncology Nursing 2008 Nov 25(6) 303-11
Reason for exclusion Not outcome of interest
San Juan AF Fleck SJ Chamorro-Vintildea C Mateacute-Muntildeoz JL Moral S Peacuterez M Cardona C Del Valle MF
Hernaacutendez M Ramiacuterez M Madero L Lucia A Effects of an intrahospital exercise program
intervention for children with leukemia Medicine amp Science in Sports amp Exercise 2007 Jan
39(1)13-21
Reason for exclusion Not outcome of interest
Sanford SD Okuma JO Pan J Srivastava DK West N Farr L Hinds PS Gender differences in sleep
fatigue and daytime activity in a pediatric oncology sample receiving dexamethasone Journal of
Pediatric Psychology 2008 Apr 33(3)298-306 Epub 2007 Nov 17
Reason for exclusion Not experimental or quasi-experimental study
Schmitz KH Holtzman J Courneya KS Macircsse LC Duval S Kane R Controlled physical activity trials in
cancer survivors a systematic review and meta-analysis Cancer Epidemiol Biomarkers Prev
2005 Jul 14(7)1588-95
Reason for exclusion Not population of interest
van Brussel M Takken T Lucia A van der Net J Helders PJ Is physical fitness decreased in survivors of
childhood leukemia A systematic review Leukemia 2005 Jan 19(1)13-7
Reason for exclusion Not population of interest
Whiting P Bagnall AM Snowden AJ Cornell JE Mulrow CD Ramirez G Interventions for the treatment
and management of chronic fatigue syndrome JAMA 2001 Sep 19 286(11)1360-8
Reason for exclusion Not intervention of interest
Whitsett SF Gudmundsdottir M Davies B McCarthy P Friedman D Chemotherapy-related fatigue in
childhood cancer correlates consequences and coping strategies Journal of Pediatric
Oncology Nursing 2008 Mar-Apr 25(2)86-96 Epub 2008 Feb 29
Reason for exclusion Not experimental or quasi-experimental study
Winner C Muumlller C Hoffmann C Boos J Rosenbaum D Physical activity and childhood cancer Pediatr
Blood Cancer 2010 Apr 54(4)501-10
Reason for exclusion Not research study
684
53
Wu M Hsu L Zhang B Shen N Lu H Li S The experiences of cancer-related fatigue among Chinese
children with leukaemia A phenomenological study Journal of Nursing Studies 2010 Jan
47(1)49-59 Epub 2009 Aug 25
Reason for exclusion Not experimental or quasi-experimental study
Yeh CH Chiang YC Lin L Yang CP Chien LC Weaver MA Chuang HL Clinical factors associated with
fatigue over time in paediatric oncology patients receiving chemotherapy British Journal of
Cancer 2008 Jul 8 99(1)23-9 Epub 2008 Jun 24
Reason for exclusion Not experimental or quasi-experimental study
685
36
radiotherapy A comparison with the fatigue experienced by healthy individuals Cancer Nursing 199417(5)367-378
13Hinds PS amp Hockenberry-Eaton M Developing a research program on fatigue in
children and adloescents diagnosed with cancer Journal of Pediatric Oncology Nursing 200118(2)3-12
14Aaronson LS Teel CS Cassmeyer V Neuberger GB Pallikkathayil L Pierce J Press
AN Williams DP amp Wingate A Defining and measuring fatigue Journal of Nursing scholarship 1999 31(1)45-50
15Yeh CH Wang CH Chiang YC Lin Lamp Chien LC Assessment of symptoms reported
by 10- to 18-year-old cancer patients in Taiwan 2009 38(5)738-746 16 Okuyama T Akechi T Kugaya A Okamura H Shima Yamp Maruguchi M
Development and validation of the cancer fatigue scale a brief three-dimensional self-rating scale for assessment of fatigue in cancer patients Journal of Pain amp Symptom Management 2000 19(1) 5-14
17Gibson F Mulhall AB Richardson A Edwards JL Ream E amp Sepion BJ A
phenomenologic study of fatigue in adolescents receiving treatment for cancer Oncology Nursing Forum200532(3)651-660
18Wolfe J Grier HE Klar N Levin SB Ellenbogen JMamp Salem-Schatz S et al
Symptoms and suffering at the end of life in children with cancer New England Journal of Medicine 2000342(5)326-333
19Whiting P Bagnall AM Sowden AJ Cornell JE Mulrow CD amp Ramirez G
Interventions for the treatment and management of chronic fatigue syndrome a systematic review JAMA the Journal of the American Medical Association 2001286(11)1360-1368
20 Kangas M Bovbjerg DHamp Montgomery G H Cancer-related fatigue a systematic
and meta-analytic review of non-pharmacological therapies for cancer patients Psychological Bulletin 2008134 (5)700-741
21Williams PD Schmideskamp J Ridder EL amp Williams AR Symptom monitoring and
dependent care during cancer treatment in children pilot study Cancer Nursing 200629(3)188-197
22Takken T van der Torre P Zwerink M Hulzebos EH Bierings M Helders PJMamp van
der Net J Development feasibility and efficacy of a community-based exercise training
669
37
program in pediatric cancer survivors Psycho-Oncology 200918(4)440-448
23Keats MR amp Culos-Reed SN A community-based physical activity program for
adolescents with cancer (project TREK) program feasibility and preliminary findings
Pediatric hematology and oncology 200830(4) 272-280
24Hinds PS Hockenberry M Rai SN Zhang L Razzouk B I Cremer L McCarthy K amp
Rodriguez-Galindo C Clinical field testing of an enhanced-activity intervention in
hospitalized children with cancer Journal of Pain amp Symptom Management 2007
33(6)686-697
25Chiang YC The effects of ldquo a home-based aerobic exercise interventionrdquo on fatigue
and cardiorespiratory fitness in children with acute lymphoblastic leukemia during the
maintenance stage of chemotherapy Unpublished thesis Taiwan Tao-Yuan 2007
26Langeveld N Ubbink M amp Smets E I dont have any energy The experience of
fatigue in young adult survivors of childhood cancer European journal of oncology
nursing 20004(1)20-28
27 Kisner C Colby L Therapeutic exercise Foundations and techniques 2nd ed Philadelphia PAFA Davies 2007
670
38
Appendix I JBI Critical Appraisal Checklist for Experimental studies
Author__________ Year_________ Record Number__________________
Questions 1 to 4 must be answered ldquoyesrdquo for study to be included in the metashyanalysis
1 Were the participants randomized to study groups
Yes No Not clear
2 Other than research intervention were participants in each groups treated the same
Yes No Not clear
3 Were the outcomes measured in the same manner for all participants
Yes No Not clear
4 Were groups comparable at entry
Yes No Not clear
5 Was randomization of participants blinded
Yes No Not clear
6 Were those assessing outcome blinded to treatment allocation (if outcome not objective such as survival or length of hospitalization)
Yes No Not clear
7 Was allocation to treatment groups concealed from the allocator
Yes No Not clear
8 Was an appropriate statistical analysis used
671
39
Yes No Not clear
9 Were outcomes measured in a reliable way
Yes No Not clear
10 Was there adequate followshyup of participants
Yes No Not clear
Summary
TOTAL
Yes No Not clear
DECISION
Use Reject
Narrative summary only Further information needed
COMMENTS
672
40
Appendix II JBI Data Extraction Tool for Quantitative Studies Authors and Year
Journal Title
Record NumberArticle Reference No
Reviewer
Method
Settings
Participants
Number of participants
Group A Group B Group C
Control Intervention 1 Intervention 2
Interventions
Group A
Control
Group B
Intervention 1
Group C
Intervention 2
Outcome measures
Definition
673
41
Other outcome measures
Outcome description ScaleMeasure
Results
Dichotomous Data
Outcome Control Group
Numbertotal number
Treatment Group
Numbertotal number
Continuous Data
Authorrsquos Conclusions
Comments
Outcome Control Group
Mean amp SD
Treatment Group
Mean amp SD
674
43
Appendix III Details of included studies (N=6)(2720212223) RefNo Author(s)
(years) Title Study question Research
method Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
22 Takken T van der Torre P Zwerink M Hulzebos E H Bierings M Helders P J Mamp van der Net J (2009)
Development feasibility and efficacy of a community-based exercise training program in pediatric cancer survivors
To develop a 12-week home-based exercise training program (comprising aerobic and strength exercises) for children who survived ALL and to study itrsquos feasibility and efficacy
Pre-post test design
No comparsion group
Survived ALL(N=9)ages 6-14 years
1anthropometry 2 muscle strength 3functional mobility 4cardio-pulmonary
exercise test 5Fatigue
1 Feasibility questionnaire 2 anthropometry electronic scale and a wallmounted stadiometerHarpenden skin fold calipers 3 muscle strength handheld dynamometer 4functional mobility Timed Up
and Go test (TUG) 5cardio-pulmonary exercise test electronically braked cycle ergometer 6Fatigue(mean)CSI-20 (subjective experience of fatigueconcentrationmotivationphysical activity)
112-week exercise training program
2 Patients were assessed before (T0) and after (T1) 12 weeks of training
1 muscle strength execapacity functional moand fatigue showed nosignificant differences between pre(meanplusmnSD415plusmn147) and post training(meanplusmnSD3687)
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
7 Post-White J Fitzgerald M Savik K Hooke M C Hannahan A B amp Sencer S F (2009)
Massage therapy for children with cancer
To determine whether 4 weekly sessions of massage compared with 4 quiet-time control conditions would reduce anxiety cortisol levels fatigue nausea and pain in children with cancer undergoing chemotherapy and would reduce anxiety fatigue and mood disturbance in a parent
2-period crossover design (Randomized)
quiet-time
control
sessions
Children with cancer 1 to 18 years of age Twenty-three childrenparent dyads were enrolled 17 completed all data points
children 1relaxation 2symptoms 3 fatigue
parents
1anxiety 2 fatigue
children 1relaxation (heart and respiratory rates blood pressure and salivary cortisol level)
2symptoms (pain nausea anxiety 3 fatigue 1-2y3-6yLansky Play Performance Scale (PPS) 7-13y
1 4 weekly massage (MT) sessions alternated with 4 weekly quiet-time(QT) control sessions
2 children included presession and postsession vital signs (heart rate respiratory rate blood pressure) and self-report (parent proxy report for age 1-2 years) of pain nausea and anxiety Fatigue was measured before sessions 1 and 4 and at each follow-up Parent measures
included anxiety fatigue and mood states
1Massage was moreeffective than quiet tireducing heart rate inchildren anxiety in cless than age 14 yeaparent anxiety 2There were no sign
changes in blood pcortisol pain naufatigue (no state d
3 Children reported tmassage helped thebetter lessened theirand worries and hadlasting effects than q
675
44
14-18yChild Fatigue Scale (CFS) (frequency
intensity) 2 parents anxiety and fatigue
676
45
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
24 Hinds P S Hockenberry M Rai S N Zhang L Razzouk B I Cremer L McCarthy K amp Rodriguez-Galindo C (2007)
Clinical field testing of an enhanced-activity intervention in hospitalized children with cancer
To determine the feasibility of an
enhanced physical activity EPA intervention in children and adolescents hospitalized to receive chemotherapy for a solid tumor or AML and to assess the sleep and fatigue outcomes of the intervention using two different statistical approaches to analyze the longitudinal symptom data
randomized prospective two-site and two-group pilot study
Standard care Twenty nine patients (25 with a solid tumor and 4 with AML)ages 7-18 years
1 sleep duration 2 sleep efficiency 3 fatigue
1sleep duration sleep efficiency The
Wrist Actigraph The Daily Sleep Diary-Parent 2 fatigue (mean) The Fatigue Scale(FS-C) for 7-12 (intensity) The Fatigue Scale(FS-A) for 13-18 The Fatigue Scale Parent Version (FS-P) The Fatigue Scale Staff Version (FS-S)
1enhanced physical activity (EPA) (hospital-based 30 minutes
twice daily for 2-4 days) 2 T0On the day of admission
(Day 0 or baseline)patient and parents completed the fatigue instruments and a team member applied the actigraph Patients wore the wrist actigraph T1 from Day 0 to 2 or 3 consecutive days (Days 0e3) In addition the patient same parent and staff nurses completed the daily sleep and fatigue reports in the late afternoons of Days 1-3
1 ANOVA model slesignificantly more the experimental athe control arm whdifferences from bsleep efficiency vaaveraged and com
2 The patient-reported mean fatigue scoresarms were higher amadolescents than for
3 The mixed model anarevealed no significandifferences in patientfatigue between
the two study arms otime( no final result iSD only give mixed result)
677
46
23 Keats M
R amp Culos-Reed S N (2008)
A community-based physical activity program for adolescents with cancer (project TREK) program feasibility and preliminary findings
To examine the
feasibility of a
theoretically-based
physical activity (PA)
intervention in
adolescents with
cancerand
examination of the
impact of the
program on
participant QOL
including social
emotional and
physical
well-being(including fatigue)
Repeat measures longitudinal design
No comparsion group
10 adolescents(Lymphoma(4)leukemia(4)CNS tumor(1)germ cell tumor(1)) ages 14-18 years
1physical fitness 2quality of life (QOL) 3PA behavior 4fatigue
1 Feasibility was assessed by participant recruitment attendance and adherence
2physical fitness Fitnessgram 3quality of life (QOL) Pediatric Quality of Life Inventory (PedsQL) 4PA behavior leisure score index (LSI) 5fatigue (mean) pediatric Quality of life
Multidimensional Fatigue Scale (Peds QL-MFS)
(Generalsleepcognitive fatigue)
116week physical activity (PA)
2 total PA physical fitness and overall QOL was assessed at 5 different intervals T0 preintervention (baseline) T1midintervention (after the
first 8 wk) T2 postintervention
(16 wk) T3 3-months
postintervention T4 1-year poststudy
initiation
1 from baseline -wkssig Improvementstotal PA physfitness and Qgeneral fatigue(meanplusmnSD 796plusmn135)
2 from baseline to 3FUsig Improvin general fatigue(meanplusmnSD824plusmn131)slefatigue(meanplusmnSD755plusmn191)totafatigue(meanplusmnSD778plusmn150)
3at 1 years FUsImprovements in sleeprest fatigue(meanplusmnSD725plusmn203)total (meanplusmnSD 763plusmn
678
47
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
2 Gene R E amp Conk Z (2008)
Impact of Effective Nursing Interventions to the Fatigue Syndrome in Children Who Receive Chemotherapy
1 to examine the effects of an effective nursing intervention to the fatigue syndrome of children 7 to 12 years of age who receive chemotherapy 2Tto examine the relationship between fatigue and demographic variables (age sex) diagnoses ([ALL AML] lymphoma) and therapy-related variables (eg level of hemoglobin
experimental randomized controlled study
Routine nursing care
A total of 60 children who are 7-12 years of age(a new diagnosis of ALL AML or lymphoma and receiving for the first time after being diagnosed a 7- to 10-day chemotherapy treatment )
fatigue The Fatigue Scale(FS-C) for 7-12 (intensity)
The Fatigue Scale Parent Version (FS-P)
1 effective nursing interventions(45- 60mdaya week)education about the fatigue with the chemotherapy and fatigue handbook 2 T1 After a 7-day period the children
and parent were evaluated with the Fatigue Scale
1The difference betwthe 2 mean values wafound to be statisticallsignificant 2 statistically significadifference was found between the Fatigue Scale-Child mean scothe experimental (272the control group (4213)children
679
48
25 Chiang et
al(2007)
The effects of ldquo a home ndashbased aerobic exercise interventionrdquo on fatigue and cardiorespiratory fitness in children with Acute Lymphoblastic Leukemia during the maintenance stage of chemotherapy
To examine the effect of ldquo a home ndashbased aerobic exercise interventionrdquo on fatigue and cardiorespiratory fitness in children with Acute Lymphoblastic Leukemia during the maintenance stage of chemotherapy
Quasi-experi -mental
Routine
nursing care
14 pediatric oncology patients in the experimental group and 10 in control group who were matched by age and sex ages7-18 years
1Cardiorespiratory fitness
2Fatigue
1Cardiorespiratory fitness Physical Activity Recall
VO2maxHR peak 6MWT
2 Fatigue PedsQL-MFS(Generalsleepcognitive fatigue)
1A six-week home-based aerobic exercise intervention 2 8 time points T0 baseline T1-T6 every week during the
intervention(6 weeks) T7 post intervention T8 follow-up (one month after
the end of the home-based exercise program)
1 For intent-to ndash treatthe findings indicated are no intervention efftime differences by anon the subscale of fat2 For per-protocol angeneral fatigue( mean422plusmn402) was the osubscale that was siglower for children whothe exercise interventthose in control groupfollow-up assessmentmonth after the compintervention) 3 The VO2peak are significantly improvingexperimental group atbaseline- and post-intassessment The VO2was significantly highechildren who were in experimental group thcontrol subjects at post-intervention assefor the per-protocol an
680
49
Appendix IV Instrument used to measure fatigue
Name Instrument
developers
Description Used in
age in
ref
Reliability
Consistency of
instrument
Checklist Individual Strength
(CIS)22
Vercoulen et
al1996
20 items using 7-point Likert scale of
fatigue To measure four aspects of
fatiguesubjective experience
contractionmotivation physical
Activity
6-14 Not reported
Child Fatigue Scale (CFS)7 Hockenberry
et al2003
14 items 2 part questionnaire frequency
(yes or no) 5-point Likert scale of the
intensity of any yes responses
7-13
14-18 α073-o84
The Fatigue Scale for 7-12
year Olds (FS-C)224
Hockenberry
et al
14 items provide a fatigue intensity score
5-point Likert scale
7-12 αo84
The Fatigue Scale for 13-18
year Olds (FS-A)24
Hockenberry
et al
14 items provide a fatigue intensity score
5-point Likert scale
13-18 α076-o96
Pediatric Quality of life
Multidimensional Fatigue
Scale (Peds QL-MFS)2325
Varni2002 18 items to measure three aspects of
fatigueGeneralsleepcognitive
14-18 Not reported
681
50
Appendix V Excluded studies and reasons for exclusion
Baggott C Dodd M Kennedy C Marina N Miaskowski C Multiple Symptoms in Pediatric Oncology
Patients A Systematic Review Journal of Pediatric Oncology Nursing 2009 Nov-Dec 27(6)
325-339
Reason for exclusion Not outcome of interest
Barlow JH Ellard DR Psycho-educational interventions for children with chronic disease parents and
siblings an overview of the research evidence base Care Health amp Development 2004 Nov
30(6)637-45
Reason for exclusion Not outcome of interest
Bedider S Moyer CA Randomized controlled trials of pediatric massage A review Evid Based
Complement Alternat Med 2007 Mar 4(1)23-34 Epub 2006 Nov 3
Reason for exclusion Not outcome of interest
de Nijs EJ Ros W Grijpdonck MH Nursing intervention for fatigue during the treatment for cancer Cancer
Nursing 2008 31(3)191-206
Reason for exclusion Not population of interest
Edwards JL Gibson F Richardson A Sepion B Ream E Fatigue in adolescents with and following a
cancer diagnosis developing an evidence base for practice European Journal of Cancer 2003
Dec 39(18)2671-80
Reason for exclusion Not experimental or quasi-experimental study
Hinds PS Hockenberry-Eatan M Developing a research program on fatigue in children and adolescents
diagnosed with cancer Journal of Pediatric Oncology Nursing 2001 Mar-Apr 18(2 Suppl
1)3-12
Reason for exclusion Not experimental or quasi-experimental study
Hockenberry-Eaton M Hinds PS Alcoser P ONeill JB Euell K Howard V Gattuso J Taylor J Fatigue in
Children and Adolescents With Cancer Journal of Pediatric Oncology Nursing 1998 July
15(3)172-182
Reason for exclusion Not experimental or quasi-experimental study
Jean-Pierre P Mustian K Kohli S Roscoe JA Hickok JT Morrow GR Community-based clinical oncology
research trials for cancer-related fatigue The Journal of Supportive Oncology 2006 Nov-Dec
4(10)511-6
682
51
Reason for exclusion Not population of interest
Kangas M Bovbjerg DH Montgomery GH Cancer-Related Fatigue A Systematic and Meta-Analytic
Review of Non-Pharmacological Therapies for Cancer Patients Psychological Bulletin 2008 Sep
134(5)700-41
Reason for exclusion Not population of interest
Lotfi-Jam K Carey M Jefford M Schofield P Charleson C Aranda S Nonpharmacologic strategies for
managing common chemotherapy adverse effects A systematic review Journal of Clinical
Oncology 2008 Dec 1 26(34)5618-29 Epub 2008 Nov 3
Reason for exclusion Not outcome of interest
Marchese VG Chiarello LA Lange BJ Effects of physical therapy intervention for children with acute
lymphoblastic leukemia Pediatr Blood Cancer 2004 Feb42(2)127-33
Reason for exclusion Not outcome of interest
Meeske KA Siegel SE Globe DR Mack WJ Bernstein L Prevalence and correlates of fatigue in
long-term survivors of childhood leukemia Journal of Clinical Oncology 2005 Aug 20
23(24)5501-10
Reason for exclusion Not intervention study
Minton O Richardson A Sharpe M Hotopf Stone P A systematic review and meta-analysis of the
pharmacological treatment of cancer-related fatigue J Natl Cancer Inst 2008 Aug 20
100(16)1155-66 Epub 2008 Aug 11
Reason for exclusion Not population and intervention of interest
Mustian KM Morrow GR Carroll JK Figueroa-Moseley CD Pascal JP Williams GC Integrative
nonpharmacologic behavioral interventions for the management of Cancer-Related fatigue The
Oncologist 2007 12(1)52-67
Reason for exclusion Not population of interest
Neill J Belan I Ried K Effectiveness of non-pharmacological interventions for fatigue in adults with
multiple sclerosis rheumatoid arthritis or systemic lupus erythematosus a systematic review
Journal of Advanced Nursing 2006 Dec 56(6)617-35
Reason for exclusion Not population of interest
Rheingans JI A systematic review of nonpharmacologic adjunctive therapies for symptom management
Journal of Pediatric Oncology Nursing 2007 24(2) 81-94
683
52
Reason for exclusion Not outcome of interest
Rheingans JI Pediatric oncology nursesrsquo management of patients symptoms Journal of Pediatric
Oncology Nursing 2008 Nov 25(6) 303-11
Reason for exclusion Not outcome of interest
San Juan AF Fleck SJ Chamorro-Vintildea C Mateacute-Muntildeoz JL Moral S Peacuterez M Cardona C Del Valle MF
Hernaacutendez M Ramiacuterez M Madero L Lucia A Effects of an intrahospital exercise program
intervention for children with leukemia Medicine amp Science in Sports amp Exercise 2007 Jan
39(1)13-21
Reason for exclusion Not outcome of interest
Sanford SD Okuma JO Pan J Srivastava DK West N Farr L Hinds PS Gender differences in sleep
fatigue and daytime activity in a pediatric oncology sample receiving dexamethasone Journal of
Pediatric Psychology 2008 Apr 33(3)298-306 Epub 2007 Nov 17
Reason for exclusion Not experimental or quasi-experimental study
Schmitz KH Holtzman J Courneya KS Macircsse LC Duval S Kane R Controlled physical activity trials in
cancer survivors a systematic review and meta-analysis Cancer Epidemiol Biomarkers Prev
2005 Jul 14(7)1588-95
Reason for exclusion Not population of interest
van Brussel M Takken T Lucia A van der Net J Helders PJ Is physical fitness decreased in survivors of
childhood leukemia A systematic review Leukemia 2005 Jan 19(1)13-7
Reason for exclusion Not population of interest
Whiting P Bagnall AM Snowden AJ Cornell JE Mulrow CD Ramirez G Interventions for the treatment
and management of chronic fatigue syndrome JAMA 2001 Sep 19 286(11)1360-8
Reason for exclusion Not intervention of interest
Whitsett SF Gudmundsdottir M Davies B McCarthy P Friedman D Chemotherapy-related fatigue in
childhood cancer correlates consequences and coping strategies Journal of Pediatric
Oncology Nursing 2008 Mar-Apr 25(2)86-96 Epub 2008 Feb 29
Reason for exclusion Not experimental or quasi-experimental study
Winner C Muumlller C Hoffmann C Boos J Rosenbaum D Physical activity and childhood cancer Pediatr
Blood Cancer 2010 Apr 54(4)501-10
Reason for exclusion Not research study
684
53
Wu M Hsu L Zhang B Shen N Lu H Li S The experiences of cancer-related fatigue among Chinese
children with leukaemia A phenomenological study Journal of Nursing Studies 2010 Jan
47(1)49-59 Epub 2009 Aug 25
Reason for exclusion Not experimental or quasi-experimental study
Yeh CH Chiang YC Lin L Yang CP Chien LC Weaver MA Chuang HL Clinical factors associated with
fatigue over time in paediatric oncology patients receiving chemotherapy British Journal of
Cancer 2008 Jul 8 99(1)23-9 Epub 2008 Jun 24
Reason for exclusion Not experimental or quasi-experimental study
685
37
program in pediatric cancer survivors Psycho-Oncology 200918(4)440-448
23Keats MR amp Culos-Reed SN A community-based physical activity program for
adolescents with cancer (project TREK) program feasibility and preliminary findings
Pediatric hematology and oncology 200830(4) 272-280
24Hinds PS Hockenberry M Rai SN Zhang L Razzouk B I Cremer L McCarthy K amp
Rodriguez-Galindo C Clinical field testing of an enhanced-activity intervention in
hospitalized children with cancer Journal of Pain amp Symptom Management 2007
33(6)686-697
25Chiang YC The effects of ldquo a home-based aerobic exercise interventionrdquo on fatigue
and cardiorespiratory fitness in children with acute lymphoblastic leukemia during the
maintenance stage of chemotherapy Unpublished thesis Taiwan Tao-Yuan 2007
26Langeveld N Ubbink M amp Smets E I dont have any energy The experience of
fatigue in young adult survivors of childhood cancer European journal of oncology
nursing 20004(1)20-28
27 Kisner C Colby L Therapeutic exercise Foundations and techniques 2nd ed Philadelphia PAFA Davies 2007
670
38
Appendix I JBI Critical Appraisal Checklist for Experimental studies
Author__________ Year_________ Record Number__________________
Questions 1 to 4 must be answered ldquoyesrdquo for study to be included in the metashyanalysis
1 Were the participants randomized to study groups
Yes No Not clear
2 Other than research intervention were participants in each groups treated the same
Yes No Not clear
3 Were the outcomes measured in the same manner for all participants
Yes No Not clear
4 Were groups comparable at entry
Yes No Not clear
5 Was randomization of participants blinded
Yes No Not clear
6 Were those assessing outcome blinded to treatment allocation (if outcome not objective such as survival or length of hospitalization)
Yes No Not clear
7 Was allocation to treatment groups concealed from the allocator
Yes No Not clear
8 Was an appropriate statistical analysis used
671
39
Yes No Not clear
9 Were outcomes measured in a reliable way
Yes No Not clear
10 Was there adequate followshyup of participants
Yes No Not clear
Summary
TOTAL
Yes No Not clear
DECISION
Use Reject
Narrative summary only Further information needed
COMMENTS
672
40
Appendix II JBI Data Extraction Tool for Quantitative Studies Authors and Year
Journal Title
Record NumberArticle Reference No
Reviewer
Method
Settings
Participants
Number of participants
Group A Group B Group C
Control Intervention 1 Intervention 2
Interventions
Group A
Control
Group B
Intervention 1
Group C
Intervention 2
Outcome measures
Definition
673
41
Other outcome measures
Outcome description ScaleMeasure
Results
Dichotomous Data
Outcome Control Group
Numbertotal number
Treatment Group
Numbertotal number
Continuous Data
Authorrsquos Conclusions
Comments
Outcome Control Group
Mean amp SD
Treatment Group
Mean amp SD
674
43
Appendix III Details of included studies (N=6)(2720212223) RefNo Author(s)
(years) Title Study question Research
method Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
22 Takken T van der Torre P Zwerink M Hulzebos E H Bierings M Helders P J Mamp van der Net J (2009)
Development feasibility and efficacy of a community-based exercise training program in pediatric cancer survivors
To develop a 12-week home-based exercise training program (comprising aerobic and strength exercises) for children who survived ALL and to study itrsquos feasibility and efficacy
Pre-post test design
No comparsion group
Survived ALL(N=9)ages 6-14 years
1anthropometry 2 muscle strength 3functional mobility 4cardio-pulmonary
exercise test 5Fatigue
1 Feasibility questionnaire 2 anthropometry electronic scale and a wallmounted stadiometerHarpenden skin fold calipers 3 muscle strength handheld dynamometer 4functional mobility Timed Up
and Go test (TUG) 5cardio-pulmonary exercise test electronically braked cycle ergometer 6Fatigue(mean)CSI-20 (subjective experience of fatigueconcentrationmotivationphysical activity)
112-week exercise training program
2 Patients were assessed before (T0) and after (T1) 12 weeks of training
1 muscle strength execapacity functional moand fatigue showed nosignificant differences between pre(meanplusmnSD415plusmn147) and post training(meanplusmnSD3687)
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
7 Post-White J Fitzgerald M Savik K Hooke M C Hannahan A B amp Sencer S F (2009)
Massage therapy for children with cancer
To determine whether 4 weekly sessions of massage compared with 4 quiet-time control conditions would reduce anxiety cortisol levels fatigue nausea and pain in children with cancer undergoing chemotherapy and would reduce anxiety fatigue and mood disturbance in a parent
2-period crossover design (Randomized)
quiet-time
control
sessions
Children with cancer 1 to 18 years of age Twenty-three childrenparent dyads were enrolled 17 completed all data points
children 1relaxation 2symptoms 3 fatigue
parents
1anxiety 2 fatigue
children 1relaxation (heart and respiratory rates blood pressure and salivary cortisol level)
2symptoms (pain nausea anxiety 3 fatigue 1-2y3-6yLansky Play Performance Scale (PPS) 7-13y
1 4 weekly massage (MT) sessions alternated with 4 weekly quiet-time(QT) control sessions
2 children included presession and postsession vital signs (heart rate respiratory rate blood pressure) and self-report (parent proxy report for age 1-2 years) of pain nausea and anxiety Fatigue was measured before sessions 1 and 4 and at each follow-up Parent measures
included anxiety fatigue and mood states
1Massage was moreeffective than quiet tireducing heart rate inchildren anxiety in cless than age 14 yeaparent anxiety 2There were no sign
changes in blood pcortisol pain naufatigue (no state d
3 Children reported tmassage helped thebetter lessened theirand worries and hadlasting effects than q
675
44
14-18yChild Fatigue Scale (CFS) (frequency
intensity) 2 parents anxiety and fatigue
676
45
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
24 Hinds P S Hockenberry M Rai S N Zhang L Razzouk B I Cremer L McCarthy K amp Rodriguez-Galindo C (2007)
Clinical field testing of an enhanced-activity intervention in hospitalized children with cancer
To determine the feasibility of an
enhanced physical activity EPA intervention in children and adolescents hospitalized to receive chemotherapy for a solid tumor or AML and to assess the sleep and fatigue outcomes of the intervention using two different statistical approaches to analyze the longitudinal symptom data
randomized prospective two-site and two-group pilot study
Standard care Twenty nine patients (25 with a solid tumor and 4 with AML)ages 7-18 years
1 sleep duration 2 sleep efficiency 3 fatigue
1sleep duration sleep efficiency The
Wrist Actigraph The Daily Sleep Diary-Parent 2 fatigue (mean) The Fatigue Scale(FS-C) for 7-12 (intensity) The Fatigue Scale(FS-A) for 13-18 The Fatigue Scale Parent Version (FS-P) The Fatigue Scale Staff Version (FS-S)
1enhanced physical activity (EPA) (hospital-based 30 minutes
twice daily for 2-4 days) 2 T0On the day of admission
(Day 0 or baseline)patient and parents completed the fatigue instruments and a team member applied the actigraph Patients wore the wrist actigraph T1 from Day 0 to 2 or 3 consecutive days (Days 0e3) In addition the patient same parent and staff nurses completed the daily sleep and fatigue reports in the late afternoons of Days 1-3
1 ANOVA model slesignificantly more the experimental athe control arm whdifferences from bsleep efficiency vaaveraged and com
2 The patient-reported mean fatigue scoresarms were higher amadolescents than for
3 The mixed model anarevealed no significandifferences in patientfatigue between
the two study arms otime( no final result iSD only give mixed result)
677
46
23 Keats M
R amp Culos-Reed S N (2008)
A community-based physical activity program for adolescents with cancer (project TREK) program feasibility and preliminary findings
To examine the
feasibility of a
theoretically-based
physical activity (PA)
intervention in
adolescents with
cancerand
examination of the
impact of the
program on
participant QOL
including social
emotional and
physical
well-being(including fatigue)
Repeat measures longitudinal design
No comparsion group
10 adolescents(Lymphoma(4)leukemia(4)CNS tumor(1)germ cell tumor(1)) ages 14-18 years
1physical fitness 2quality of life (QOL) 3PA behavior 4fatigue
1 Feasibility was assessed by participant recruitment attendance and adherence
2physical fitness Fitnessgram 3quality of life (QOL) Pediatric Quality of Life Inventory (PedsQL) 4PA behavior leisure score index (LSI) 5fatigue (mean) pediatric Quality of life
Multidimensional Fatigue Scale (Peds QL-MFS)
(Generalsleepcognitive fatigue)
116week physical activity (PA)
2 total PA physical fitness and overall QOL was assessed at 5 different intervals T0 preintervention (baseline) T1midintervention (after the
first 8 wk) T2 postintervention
(16 wk) T3 3-months
postintervention T4 1-year poststudy
initiation
1 from baseline -wkssig Improvementstotal PA physfitness and Qgeneral fatigue(meanplusmnSD 796plusmn135)
2 from baseline to 3FUsig Improvin general fatigue(meanplusmnSD824plusmn131)slefatigue(meanplusmnSD755plusmn191)totafatigue(meanplusmnSD778plusmn150)
3at 1 years FUsImprovements in sleeprest fatigue(meanplusmnSD725plusmn203)total (meanplusmnSD 763plusmn
678
47
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
2 Gene R E amp Conk Z (2008)
Impact of Effective Nursing Interventions to the Fatigue Syndrome in Children Who Receive Chemotherapy
1 to examine the effects of an effective nursing intervention to the fatigue syndrome of children 7 to 12 years of age who receive chemotherapy 2Tto examine the relationship between fatigue and demographic variables (age sex) diagnoses ([ALL AML] lymphoma) and therapy-related variables (eg level of hemoglobin
experimental randomized controlled study
Routine nursing care
A total of 60 children who are 7-12 years of age(a new diagnosis of ALL AML or lymphoma and receiving for the first time after being diagnosed a 7- to 10-day chemotherapy treatment )
fatigue The Fatigue Scale(FS-C) for 7-12 (intensity)
The Fatigue Scale Parent Version (FS-P)
1 effective nursing interventions(45- 60mdaya week)education about the fatigue with the chemotherapy and fatigue handbook 2 T1 After a 7-day period the children
and parent were evaluated with the Fatigue Scale
1The difference betwthe 2 mean values wafound to be statisticallsignificant 2 statistically significadifference was found between the Fatigue Scale-Child mean scothe experimental (272the control group (4213)children
679
48
25 Chiang et
al(2007)
The effects of ldquo a home ndashbased aerobic exercise interventionrdquo on fatigue and cardiorespiratory fitness in children with Acute Lymphoblastic Leukemia during the maintenance stage of chemotherapy
To examine the effect of ldquo a home ndashbased aerobic exercise interventionrdquo on fatigue and cardiorespiratory fitness in children with Acute Lymphoblastic Leukemia during the maintenance stage of chemotherapy
Quasi-experi -mental
Routine
nursing care
14 pediatric oncology patients in the experimental group and 10 in control group who were matched by age and sex ages7-18 years
1Cardiorespiratory fitness
2Fatigue
1Cardiorespiratory fitness Physical Activity Recall
VO2maxHR peak 6MWT
2 Fatigue PedsQL-MFS(Generalsleepcognitive fatigue)
1A six-week home-based aerobic exercise intervention 2 8 time points T0 baseline T1-T6 every week during the
intervention(6 weeks) T7 post intervention T8 follow-up (one month after
the end of the home-based exercise program)
1 For intent-to ndash treatthe findings indicated are no intervention efftime differences by anon the subscale of fat2 For per-protocol angeneral fatigue( mean422plusmn402) was the osubscale that was siglower for children whothe exercise interventthose in control groupfollow-up assessmentmonth after the compintervention) 3 The VO2peak are significantly improvingexperimental group atbaseline- and post-intassessment The VO2was significantly highechildren who were in experimental group thcontrol subjects at post-intervention assefor the per-protocol an
680
49
Appendix IV Instrument used to measure fatigue
Name Instrument
developers
Description Used in
age in
ref
Reliability
Consistency of
instrument
Checklist Individual Strength
(CIS)22
Vercoulen et
al1996
20 items using 7-point Likert scale of
fatigue To measure four aspects of
fatiguesubjective experience
contractionmotivation physical
Activity
6-14 Not reported
Child Fatigue Scale (CFS)7 Hockenberry
et al2003
14 items 2 part questionnaire frequency
(yes or no) 5-point Likert scale of the
intensity of any yes responses
7-13
14-18 α073-o84
The Fatigue Scale for 7-12
year Olds (FS-C)224
Hockenberry
et al
14 items provide a fatigue intensity score
5-point Likert scale
7-12 αo84
The Fatigue Scale for 13-18
year Olds (FS-A)24
Hockenberry
et al
14 items provide a fatigue intensity score
5-point Likert scale
13-18 α076-o96
Pediatric Quality of life
Multidimensional Fatigue
Scale (Peds QL-MFS)2325
Varni2002 18 items to measure three aspects of
fatigueGeneralsleepcognitive
14-18 Not reported
681
50
Appendix V Excluded studies and reasons for exclusion
Baggott C Dodd M Kennedy C Marina N Miaskowski C Multiple Symptoms in Pediatric Oncology
Patients A Systematic Review Journal of Pediatric Oncology Nursing 2009 Nov-Dec 27(6)
325-339
Reason for exclusion Not outcome of interest
Barlow JH Ellard DR Psycho-educational interventions for children with chronic disease parents and
siblings an overview of the research evidence base Care Health amp Development 2004 Nov
30(6)637-45
Reason for exclusion Not outcome of interest
Bedider S Moyer CA Randomized controlled trials of pediatric massage A review Evid Based
Complement Alternat Med 2007 Mar 4(1)23-34 Epub 2006 Nov 3
Reason for exclusion Not outcome of interest
de Nijs EJ Ros W Grijpdonck MH Nursing intervention for fatigue during the treatment for cancer Cancer
Nursing 2008 31(3)191-206
Reason for exclusion Not population of interest
Edwards JL Gibson F Richardson A Sepion B Ream E Fatigue in adolescents with and following a
cancer diagnosis developing an evidence base for practice European Journal of Cancer 2003
Dec 39(18)2671-80
Reason for exclusion Not experimental or quasi-experimental study
Hinds PS Hockenberry-Eatan M Developing a research program on fatigue in children and adolescents
diagnosed with cancer Journal of Pediatric Oncology Nursing 2001 Mar-Apr 18(2 Suppl
1)3-12
Reason for exclusion Not experimental or quasi-experimental study
Hockenberry-Eaton M Hinds PS Alcoser P ONeill JB Euell K Howard V Gattuso J Taylor J Fatigue in
Children and Adolescents With Cancer Journal of Pediatric Oncology Nursing 1998 July
15(3)172-182
Reason for exclusion Not experimental or quasi-experimental study
Jean-Pierre P Mustian K Kohli S Roscoe JA Hickok JT Morrow GR Community-based clinical oncology
research trials for cancer-related fatigue The Journal of Supportive Oncology 2006 Nov-Dec
4(10)511-6
682
51
Reason for exclusion Not population of interest
Kangas M Bovbjerg DH Montgomery GH Cancer-Related Fatigue A Systematic and Meta-Analytic
Review of Non-Pharmacological Therapies for Cancer Patients Psychological Bulletin 2008 Sep
134(5)700-41
Reason for exclusion Not population of interest
Lotfi-Jam K Carey M Jefford M Schofield P Charleson C Aranda S Nonpharmacologic strategies for
managing common chemotherapy adverse effects A systematic review Journal of Clinical
Oncology 2008 Dec 1 26(34)5618-29 Epub 2008 Nov 3
Reason for exclusion Not outcome of interest
Marchese VG Chiarello LA Lange BJ Effects of physical therapy intervention for children with acute
lymphoblastic leukemia Pediatr Blood Cancer 2004 Feb42(2)127-33
Reason for exclusion Not outcome of interest
Meeske KA Siegel SE Globe DR Mack WJ Bernstein L Prevalence and correlates of fatigue in
long-term survivors of childhood leukemia Journal of Clinical Oncology 2005 Aug 20
23(24)5501-10
Reason for exclusion Not intervention study
Minton O Richardson A Sharpe M Hotopf Stone P A systematic review and meta-analysis of the
pharmacological treatment of cancer-related fatigue J Natl Cancer Inst 2008 Aug 20
100(16)1155-66 Epub 2008 Aug 11
Reason for exclusion Not population and intervention of interest
Mustian KM Morrow GR Carroll JK Figueroa-Moseley CD Pascal JP Williams GC Integrative
nonpharmacologic behavioral interventions for the management of Cancer-Related fatigue The
Oncologist 2007 12(1)52-67
Reason for exclusion Not population of interest
Neill J Belan I Ried K Effectiveness of non-pharmacological interventions for fatigue in adults with
multiple sclerosis rheumatoid arthritis or systemic lupus erythematosus a systematic review
Journal of Advanced Nursing 2006 Dec 56(6)617-35
Reason for exclusion Not population of interest
Rheingans JI A systematic review of nonpharmacologic adjunctive therapies for symptom management
Journal of Pediatric Oncology Nursing 2007 24(2) 81-94
683
52
Reason for exclusion Not outcome of interest
Rheingans JI Pediatric oncology nursesrsquo management of patients symptoms Journal of Pediatric
Oncology Nursing 2008 Nov 25(6) 303-11
Reason for exclusion Not outcome of interest
San Juan AF Fleck SJ Chamorro-Vintildea C Mateacute-Muntildeoz JL Moral S Peacuterez M Cardona C Del Valle MF
Hernaacutendez M Ramiacuterez M Madero L Lucia A Effects of an intrahospital exercise program
intervention for children with leukemia Medicine amp Science in Sports amp Exercise 2007 Jan
39(1)13-21
Reason for exclusion Not outcome of interest
Sanford SD Okuma JO Pan J Srivastava DK West N Farr L Hinds PS Gender differences in sleep
fatigue and daytime activity in a pediatric oncology sample receiving dexamethasone Journal of
Pediatric Psychology 2008 Apr 33(3)298-306 Epub 2007 Nov 17
Reason for exclusion Not experimental or quasi-experimental study
Schmitz KH Holtzman J Courneya KS Macircsse LC Duval S Kane R Controlled physical activity trials in
cancer survivors a systematic review and meta-analysis Cancer Epidemiol Biomarkers Prev
2005 Jul 14(7)1588-95
Reason for exclusion Not population of interest
van Brussel M Takken T Lucia A van der Net J Helders PJ Is physical fitness decreased in survivors of
childhood leukemia A systematic review Leukemia 2005 Jan 19(1)13-7
Reason for exclusion Not population of interest
Whiting P Bagnall AM Snowden AJ Cornell JE Mulrow CD Ramirez G Interventions for the treatment
and management of chronic fatigue syndrome JAMA 2001 Sep 19 286(11)1360-8
Reason for exclusion Not intervention of interest
Whitsett SF Gudmundsdottir M Davies B McCarthy P Friedman D Chemotherapy-related fatigue in
childhood cancer correlates consequences and coping strategies Journal of Pediatric
Oncology Nursing 2008 Mar-Apr 25(2)86-96 Epub 2008 Feb 29
Reason for exclusion Not experimental or quasi-experimental study
Winner C Muumlller C Hoffmann C Boos J Rosenbaum D Physical activity and childhood cancer Pediatr
Blood Cancer 2010 Apr 54(4)501-10
Reason for exclusion Not research study
684
53
Wu M Hsu L Zhang B Shen N Lu H Li S The experiences of cancer-related fatigue among Chinese
children with leukaemia A phenomenological study Journal of Nursing Studies 2010 Jan
47(1)49-59 Epub 2009 Aug 25
Reason for exclusion Not experimental or quasi-experimental study
Yeh CH Chiang YC Lin L Yang CP Chien LC Weaver MA Chuang HL Clinical factors associated with
fatigue over time in paediatric oncology patients receiving chemotherapy British Journal of
Cancer 2008 Jul 8 99(1)23-9 Epub 2008 Jun 24
Reason for exclusion Not experimental or quasi-experimental study
685
38
Appendix I JBI Critical Appraisal Checklist for Experimental studies
Author__________ Year_________ Record Number__________________
Questions 1 to 4 must be answered ldquoyesrdquo for study to be included in the metashyanalysis
1 Were the participants randomized to study groups
Yes No Not clear
2 Other than research intervention were participants in each groups treated the same
Yes No Not clear
3 Were the outcomes measured in the same manner for all participants
Yes No Not clear
4 Were groups comparable at entry
Yes No Not clear
5 Was randomization of participants blinded
Yes No Not clear
6 Were those assessing outcome blinded to treatment allocation (if outcome not objective such as survival or length of hospitalization)
Yes No Not clear
7 Was allocation to treatment groups concealed from the allocator
Yes No Not clear
8 Was an appropriate statistical analysis used
671
39
Yes No Not clear
9 Were outcomes measured in a reliable way
Yes No Not clear
10 Was there adequate followshyup of participants
Yes No Not clear
Summary
TOTAL
Yes No Not clear
DECISION
Use Reject
Narrative summary only Further information needed
COMMENTS
672
40
Appendix II JBI Data Extraction Tool for Quantitative Studies Authors and Year
Journal Title
Record NumberArticle Reference No
Reviewer
Method
Settings
Participants
Number of participants
Group A Group B Group C
Control Intervention 1 Intervention 2
Interventions
Group A
Control
Group B
Intervention 1
Group C
Intervention 2
Outcome measures
Definition
673
41
Other outcome measures
Outcome description ScaleMeasure
Results
Dichotomous Data
Outcome Control Group
Numbertotal number
Treatment Group
Numbertotal number
Continuous Data
Authorrsquos Conclusions
Comments
Outcome Control Group
Mean amp SD
Treatment Group
Mean amp SD
674
43
Appendix III Details of included studies (N=6)(2720212223) RefNo Author(s)
(years) Title Study question Research
method Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
22 Takken T van der Torre P Zwerink M Hulzebos E H Bierings M Helders P J Mamp van der Net J (2009)
Development feasibility and efficacy of a community-based exercise training program in pediatric cancer survivors
To develop a 12-week home-based exercise training program (comprising aerobic and strength exercises) for children who survived ALL and to study itrsquos feasibility and efficacy
Pre-post test design
No comparsion group
Survived ALL(N=9)ages 6-14 years
1anthropometry 2 muscle strength 3functional mobility 4cardio-pulmonary
exercise test 5Fatigue
1 Feasibility questionnaire 2 anthropometry electronic scale and a wallmounted stadiometerHarpenden skin fold calipers 3 muscle strength handheld dynamometer 4functional mobility Timed Up
and Go test (TUG) 5cardio-pulmonary exercise test electronically braked cycle ergometer 6Fatigue(mean)CSI-20 (subjective experience of fatigueconcentrationmotivationphysical activity)
112-week exercise training program
2 Patients were assessed before (T0) and after (T1) 12 weeks of training
1 muscle strength execapacity functional moand fatigue showed nosignificant differences between pre(meanplusmnSD415plusmn147) and post training(meanplusmnSD3687)
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
7 Post-White J Fitzgerald M Savik K Hooke M C Hannahan A B amp Sencer S F (2009)
Massage therapy for children with cancer
To determine whether 4 weekly sessions of massage compared with 4 quiet-time control conditions would reduce anxiety cortisol levels fatigue nausea and pain in children with cancer undergoing chemotherapy and would reduce anxiety fatigue and mood disturbance in a parent
2-period crossover design (Randomized)
quiet-time
control
sessions
Children with cancer 1 to 18 years of age Twenty-three childrenparent dyads were enrolled 17 completed all data points
children 1relaxation 2symptoms 3 fatigue
parents
1anxiety 2 fatigue
children 1relaxation (heart and respiratory rates blood pressure and salivary cortisol level)
2symptoms (pain nausea anxiety 3 fatigue 1-2y3-6yLansky Play Performance Scale (PPS) 7-13y
1 4 weekly massage (MT) sessions alternated with 4 weekly quiet-time(QT) control sessions
2 children included presession and postsession vital signs (heart rate respiratory rate blood pressure) and self-report (parent proxy report for age 1-2 years) of pain nausea and anxiety Fatigue was measured before sessions 1 and 4 and at each follow-up Parent measures
included anxiety fatigue and mood states
1Massage was moreeffective than quiet tireducing heart rate inchildren anxiety in cless than age 14 yeaparent anxiety 2There were no sign
changes in blood pcortisol pain naufatigue (no state d
3 Children reported tmassage helped thebetter lessened theirand worries and hadlasting effects than q
675
44
14-18yChild Fatigue Scale (CFS) (frequency
intensity) 2 parents anxiety and fatigue
676
45
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
24 Hinds P S Hockenberry M Rai S N Zhang L Razzouk B I Cremer L McCarthy K amp Rodriguez-Galindo C (2007)
Clinical field testing of an enhanced-activity intervention in hospitalized children with cancer
To determine the feasibility of an
enhanced physical activity EPA intervention in children and adolescents hospitalized to receive chemotherapy for a solid tumor or AML and to assess the sleep and fatigue outcomes of the intervention using two different statistical approaches to analyze the longitudinal symptom data
randomized prospective two-site and two-group pilot study
Standard care Twenty nine patients (25 with a solid tumor and 4 with AML)ages 7-18 years
1 sleep duration 2 sleep efficiency 3 fatigue
1sleep duration sleep efficiency The
Wrist Actigraph The Daily Sleep Diary-Parent 2 fatigue (mean) The Fatigue Scale(FS-C) for 7-12 (intensity) The Fatigue Scale(FS-A) for 13-18 The Fatigue Scale Parent Version (FS-P) The Fatigue Scale Staff Version (FS-S)
1enhanced physical activity (EPA) (hospital-based 30 minutes
twice daily for 2-4 days) 2 T0On the day of admission
(Day 0 or baseline)patient and parents completed the fatigue instruments and a team member applied the actigraph Patients wore the wrist actigraph T1 from Day 0 to 2 or 3 consecutive days (Days 0e3) In addition the patient same parent and staff nurses completed the daily sleep and fatigue reports in the late afternoons of Days 1-3
1 ANOVA model slesignificantly more the experimental athe control arm whdifferences from bsleep efficiency vaaveraged and com
2 The patient-reported mean fatigue scoresarms were higher amadolescents than for
3 The mixed model anarevealed no significandifferences in patientfatigue between
the two study arms otime( no final result iSD only give mixed result)
677
46
23 Keats M
R amp Culos-Reed S N (2008)
A community-based physical activity program for adolescents with cancer (project TREK) program feasibility and preliminary findings
To examine the
feasibility of a
theoretically-based
physical activity (PA)
intervention in
adolescents with
cancerand
examination of the
impact of the
program on
participant QOL
including social
emotional and
physical
well-being(including fatigue)
Repeat measures longitudinal design
No comparsion group
10 adolescents(Lymphoma(4)leukemia(4)CNS tumor(1)germ cell tumor(1)) ages 14-18 years
1physical fitness 2quality of life (QOL) 3PA behavior 4fatigue
1 Feasibility was assessed by participant recruitment attendance and adherence
2physical fitness Fitnessgram 3quality of life (QOL) Pediatric Quality of Life Inventory (PedsQL) 4PA behavior leisure score index (LSI) 5fatigue (mean) pediatric Quality of life
Multidimensional Fatigue Scale (Peds QL-MFS)
(Generalsleepcognitive fatigue)
116week physical activity (PA)
2 total PA physical fitness and overall QOL was assessed at 5 different intervals T0 preintervention (baseline) T1midintervention (after the
first 8 wk) T2 postintervention
(16 wk) T3 3-months
postintervention T4 1-year poststudy
initiation
1 from baseline -wkssig Improvementstotal PA physfitness and Qgeneral fatigue(meanplusmnSD 796plusmn135)
2 from baseline to 3FUsig Improvin general fatigue(meanplusmnSD824plusmn131)slefatigue(meanplusmnSD755plusmn191)totafatigue(meanplusmnSD778plusmn150)
3at 1 years FUsImprovements in sleeprest fatigue(meanplusmnSD725plusmn203)total (meanplusmnSD 763plusmn
678
47
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
2 Gene R E amp Conk Z (2008)
Impact of Effective Nursing Interventions to the Fatigue Syndrome in Children Who Receive Chemotherapy
1 to examine the effects of an effective nursing intervention to the fatigue syndrome of children 7 to 12 years of age who receive chemotherapy 2Tto examine the relationship between fatigue and demographic variables (age sex) diagnoses ([ALL AML] lymphoma) and therapy-related variables (eg level of hemoglobin
experimental randomized controlled study
Routine nursing care
A total of 60 children who are 7-12 years of age(a new diagnosis of ALL AML or lymphoma and receiving for the first time after being diagnosed a 7- to 10-day chemotherapy treatment )
fatigue The Fatigue Scale(FS-C) for 7-12 (intensity)
The Fatigue Scale Parent Version (FS-P)
1 effective nursing interventions(45- 60mdaya week)education about the fatigue with the chemotherapy and fatigue handbook 2 T1 After a 7-day period the children
and parent were evaluated with the Fatigue Scale
1The difference betwthe 2 mean values wafound to be statisticallsignificant 2 statistically significadifference was found between the Fatigue Scale-Child mean scothe experimental (272the control group (4213)children
679
48
25 Chiang et
al(2007)
The effects of ldquo a home ndashbased aerobic exercise interventionrdquo on fatigue and cardiorespiratory fitness in children with Acute Lymphoblastic Leukemia during the maintenance stage of chemotherapy
To examine the effect of ldquo a home ndashbased aerobic exercise interventionrdquo on fatigue and cardiorespiratory fitness in children with Acute Lymphoblastic Leukemia during the maintenance stage of chemotherapy
Quasi-experi -mental
Routine
nursing care
14 pediatric oncology patients in the experimental group and 10 in control group who were matched by age and sex ages7-18 years
1Cardiorespiratory fitness
2Fatigue
1Cardiorespiratory fitness Physical Activity Recall
VO2maxHR peak 6MWT
2 Fatigue PedsQL-MFS(Generalsleepcognitive fatigue)
1A six-week home-based aerobic exercise intervention 2 8 time points T0 baseline T1-T6 every week during the
intervention(6 weeks) T7 post intervention T8 follow-up (one month after
the end of the home-based exercise program)
1 For intent-to ndash treatthe findings indicated are no intervention efftime differences by anon the subscale of fat2 For per-protocol angeneral fatigue( mean422plusmn402) was the osubscale that was siglower for children whothe exercise interventthose in control groupfollow-up assessmentmonth after the compintervention) 3 The VO2peak are significantly improvingexperimental group atbaseline- and post-intassessment The VO2was significantly highechildren who were in experimental group thcontrol subjects at post-intervention assefor the per-protocol an
680
49
Appendix IV Instrument used to measure fatigue
Name Instrument
developers
Description Used in
age in
ref
Reliability
Consistency of
instrument
Checklist Individual Strength
(CIS)22
Vercoulen et
al1996
20 items using 7-point Likert scale of
fatigue To measure four aspects of
fatiguesubjective experience
contractionmotivation physical
Activity
6-14 Not reported
Child Fatigue Scale (CFS)7 Hockenberry
et al2003
14 items 2 part questionnaire frequency
(yes or no) 5-point Likert scale of the
intensity of any yes responses
7-13
14-18 α073-o84
The Fatigue Scale for 7-12
year Olds (FS-C)224
Hockenberry
et al
14 items provide a fatigue intensity score
5-point Likert scale
7-12 αo84
The Fatigue Scale for 13-18
year Olds (FS-A)24
Hockenberry
et al
14 items provide a fatigue intensity score
5-point Likert scale
13-18 α076-o96
Pediatric Quality of life
Multidimensional Fatigue
Scale (Peds QL-MFS)2325
Varni2002 18 items to measure three aspects of
fatigueGeneralsleepcognitive
14-18 Not reported
681
50
Appendix V Excluded studies and reasons for exclusion
Baggott C Dodd M Kennedy C Marina N Miaskowski C Multiple Symptoms in Pediatric Oncology
Patients A Systematic Review Journal of Pediatric Oncology Nursing 2009 Nov-Dec 27(6)
325-339
Reason for exclusion Not outcome of interest
Barlow JH Ellard DR Psycho-educational interventions for children with chronic disease parents and
siblings an overview of the research evidence base Care Health amp Development 2004 Nov
30(6)637-45
Reason for exclusion Not outcome of interest
Bedider S Moyer CA Randomized controlled trials of pediatric massage A review Evid Based
Complement Alternat Med 2007 Mar 4(1)23-34 Epub 2006 Nov 3
Reason for exclusion Not outcome of interest
de Nijs EJ Ros W Grijpdonck MH Nursing intervention for fatigue during the treatment for cancer Cancer
Nursing 2008 31(3)191-206
Reason for exclusion Not population of interest
Edwards JL Gibson F Richardson A Sepion B Ream E Fatigue in adolescents with and following a
cancer diagnosis developing an evidence base for practice European Journal of Cancer 2003
Dec 39(18)2671-80
Reason for exclusion Not experimental or quasi-experimental study
Hinds PS Hockenberry-Eatan M Developing a research program on fatigue in children and adolescents
diagnosed with cancer Journal of Pediatric Oncology Nursing 2001 Mar-Apr 18(2 Suppl
1)3-12
Reason for exclusion Not experimental or quasi-experimental study
Hockenberry-Eaton M Hinds PS Alcoser P ONeill JB Euell K Howard V Gattuso J Taylor J Fatigue in
Children and Adolescents With Cancer Journal of Pediatric Oncology Nursing 1998 July
15(3)172-182
Reason for exclusion Not experimental or quasi-experimental study
Jean-Pierre P Mustian K Kohli S Roscoe JA Hickok JT Morrow GR Community-based clinical oncology
research trials for cancer-related fatigue The Journal of Supportive Oncology 2006 Nov-Dec
4(10)511-6
682
51
Reason for exclusion Not population of interest
Kangas M Bovbjerg DH Montgomery GH Cancer-Related Fatigue A Systematic and Meta-Analytic
Review of Non-Pharmacological Therapies for Cancer Patients Psychological Bulletin 2008 Sep
134(5)700-41
Reason for exclusion Not population of interest
Lotfi-Jam K Carey M Jefford M Schofield P Charleson C Aranda S Nonpharmacologic strategies for
managing common chemotherapy adverse effects A systematic review Journal of Clinical
Oncology 2008 Dec 1 26(34)5618-29 Epub 2008 Nov 3
Reason for exclusion Not outcome of interest
Marchese VG Chiarello LA Lange BJ Effects of physical therapy intervention for children with acute
lymphoblastic leukemia Pediatr Blood Cancer 2004 Feb42(2)127-33
Reason for exclusion Not outcome of interest
Meeske KA Siegel SE Globe DR Mack WJ Bernstein L Prevalence and correlates of fatigue in
long-term survivors of childhood leukemia Journal of Clinical Oncology 2005 Aug 20
23(24)5501-10
Reason for exclusion Not intervention study
Minton O Richardson A Sharpe M Hotopf Stone P A systematic review and meta-analysis of the
pharmacological treatment of cancer-related fatigue J Natl Cancer Inst 2008 Aug 20
100(16)1155-66 Epub 2008 Aug 11
Reason for exclusion Not population and intervention of interest
Mustian KM Morrow GR Carroll JK Figueroa-Moseley CD Pascal JP Williams GC Integrative
nonpharmacologic behavioral interventions for the management of Cancer-Related fatigue The
Oncologist 2007 12(1)52-67
Reason for exclusion Not population of interest
Neill J Belan I Ried K Effectiveness of non-pharmacological interventions for fatigue in adults with
multiple sclerosis rheumatoid arthritis or systemic lupus erythematosus a systematic review
Journal of Advanced Nursing 2006 Dec 56(6)617-35
Reason for exclusion Not population of interest
Rheingans JI A systematic review of nonpharmacologic adjunctive therapies for symptom management
Journal of Pediatric Oncology Nursing 2007 24(2) 81-94
683
52
Reason for exclusion Not outcome of interest
Rheingans JI Pediatric oncology nursesrsquo management of patients symptoms Journal of Pediatric
Oncology Nursing 2008 Nov 25(6) 303-11
Reason for exclusion Not outcome of interest
San Juan AF Fleck SJ Chamorro-Vintildea C Mateacute-Muntildeoz JL Moral S Peacuterez M Cardona C Del Valle MF
Hernaacutendez M Ramiacuterez M Madero L Lucia A Effects of an intrahospital exercise program
intervention for children with leukemia Medicine amp Science in Sports amp Exercise 2007 Jan
39(1)13-21
Reason for exclusion Not outcome of interest
Sanford SD Okuma JO Pan J Srivastava DK West N Farr L Hinds PS Gender differences in sleep
fatigue and daytime activity in a pediatric oncology sample receiving dexamethasone Journal of
Pediatric Psychology 2008 Apr 33(3)298-306 Epub 2007 Nov 17
Reason for exclusion Not experimental or quasi-experimental study
Schmitz KH Holtzman J Courneya KS Macircsse LC Duval S Kane R Controlled physical activity trials in
cancer survivors a systematic review and meta-analysis Cancer Epidemiol Biomarkers Prev
2005 Jul 14(7)1588-95
Reason for exclusion Not population of interest
van Brussel M Takken T Lucia A van der Net J Helders PJ Is physical fitness decreased in survivors of
childhood leukemia A systematic review Leukemia 2005 Jan 19(1)13-7
Reason for exclusion Not population of interest
Whiting P Bagnall AM Snowden AJ Cornell JE Mulrow CD Ramirez G Interventions for the treatment
and management of chronic fatigue syndrome JAMA 2001 Sep 19 286(11)1360-8
Reason for exclusion Not intervention of interest
Whitsett SF Gudmundsdottir M Davies B McCarthy P Friedman D Chemotherapy-related fatigue in
childhood cancer correlates consequences and coping strategies Journal of Pediatric
Oncology Nursing 2008 Mar-Apr 25(2)86-96 Epub 2008 Feb 29
Reason for exclusion Not experimental or quasi-experimental study
Winner C Muumlller C Hoffmann C Boos J Rosenbaum D Physical activity and childhood cancer Pediatr
Blood Cancer 2010 Apr 54(4)501-10
Reason for exclusion Not research study
684
53
Wu M Hsu L Zhang B Shen N Lu H Li S The experiences of cancer-related fatigue among Chinese
children with leukaemia A phenomenological study Journal of Nursing Studies 2010 Jan
47(1)49-59 Epub 2009 Aug 25
Reason for exclusion Not experimental or quasi-experimental study
Yeh CH Chiang YC Lin L Yang CP Chien LC Weaver MA Chuang HL Clinical factors associated with
fatigue over time in paediatric oncology patients receiving chemotherapy British Journal of
Cancer 2008 Jul 8 99(1)23-9 Epub 2008 Jun 24
Reason for exclusion Not experimental or quasi-experimental study
685
39
Yes No Not clear
9 Were outcomes measured in a reliable way
Yes No Not clear
10 Was there adequate followshyup of participants
Yes No Not clear
Summary
TOTAL
Yes No Not clear
DECISION
Use Reject
Narrative summary only Further information needed
COMMENTS
672
40
Appendix II JBI Data Extraction Tool for Quantitative Studies Authors and Year
Journal Title
Record NumberArticle Reference No
Reviewer
Method
Settings
Participants
Number of participants
Group A Group B Group C
Control Intervention 1 Intervention 2
Interventions
Group A
Control
Group B
Intervention 1
Group C
Intervention 2
Outcome measures
Definition
673
41
Other outcome measures
Outcome description ScaleMeasure
Results
Dichotomous Data
Outcome Control Group
Numbertotal number
Treatment Group
Numbertotal number
Continuous Data
Authorrsquos Conclusions
Comments
Outcome Control Group
Mean amp SD
Treatment Group
Mean amp SD
674
43
Appendix III Details of included studies (N=6)(2720212223) RefNo Author(s)
(years) Title Study question Research
method Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
22 Takken T van der Torre P Zwerink M Hulzebos E H Bierings M Helders P J Mamp van der Net J (2009)
Development feasibility and efficacy of a community-based exercise training program in pediatric cancer survivors
To develop a 12-week home-based exercise training program (comprising aerobic and strength exercises) for children who survived ALL and to study itrsquos feasibility and efficacy
Pre-post test design
No comparsion group
Survived ALL(N=9)ages 6-14 years
1anthropometry 2 muscle strength 3functional mobility 4cardio-pulmonary
exercise test 5Fatigue
1 Feasibility questionnaire 2 anthropometry electronic scale and a wallmounted stadiometerHarpenden skin fold calipers 3 muscle strength handheld dynamometer 4functional mobility Timed Up
and Go test (TUG) 5cardio-pulmonary exercise test electronically braked cycle ergometer 6Fatigue(mean)CSI-20 (subjective experience of fatigueconcentrationmotivationphysical activity)
112-week exercise training program
2 Patients were assessed before (T0) and after (T1) 12 weeks of training
1 muscle strength execapacity functional moand fatigue showed nosignificant differences between pre(meanplusmnSD415plusmn147) and post training(meanplusmnSD3687)
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
7 Post-White J Fitzgerald M Savik K Hooke M C Hannahan A B amp Sencer S F (2009)
Massage therapy for children with cancer
To determine whether 4 weekly sessions of massage compared with 4 quiet-time control conditions would reduce anxiety cortisol levels fatigue nausea and pain in children with cancer undergoing chemotherapy and would reduce anxiety fatigue and mood disturbance in a parent
2-period crossover design (Randomized)
quiet-time
control
sessions
Children with cancer 1 to 18 years of age Twenty-three childrenparent dyads were enrolled 17 completed all data points
children 1relaxation 2symptoms 3 fatigue
parents
1anxiety 2 fatigue
children 1relaxation (heart and respiratory rates blood pressure and salivary cortisol level)
2symptoms (pain nausea anxiety 3 fatigue 1-2y3-6yLansky Play Performance Scale (PPS) 7-13y
1 4 weekly massage (MT) sessions alternated with 4 weekly quiet-time(QT) control sessions
2 children included presession and postsession vital signs (heart rate respiratory rate blood pressure) and self-report (parent proxy report for age 1-2 years) of pain nausea and anxiety Fatigue was measured before sessions 1 and 4 and at each follow-up Parent measures
included anxiety fatigue and mood states
1Massage was moreeffective than quiet tireducing heart rate inchildren anxiety in cless than age 14 yeaparent anxiety 2There were no sign
changes in blood pcortisol pain naufatigue (no state d
3 Children reported tmassage helped thebetter lessened theirand worries and hadlasting effects than q
675
44
14-18yChild Fatigue Scale (CFS) (frequency
intensity) 2 parents anxiety and fatigue
676
45
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
24 Hinds P S Hockenberry M Rai S N Zhang L Razzouk B I Cremer L McCarthy K amp Rodriguez-Galindo C (2007)
Clinical field testing of an enhanced-activity intervention in hospitalized children with cancer
To determine the feasibility of an
enhanced physical activity EPA intervention in children and adolescents hospitalized to receive chemotherapy for a solid tumor or AML and to assess the sleep and fatigue outcomes of the intervention using two different statistical approaches to analyze the longitudinal symptom data
randomized prospective two-site and two-group pilot study
Standard care Twenty nine patients (25 with a solid tumor and 4 with AML)ages 7-18 years
1 sleep duration 2 sleep efficiency 3 fatigue
1sleep duration sleep efficiency The
Wrist Actigraph The Daily Sleep Diary-Parent 2 fatigue (mean) The Fatigue Scale(FS-C) for 7-12 (intensity) The Fatigue Scale(FS-A) for 13-18 The Fatigue Scale Parent Version (FS-P) The Fatigue Scale Staff Version (FS-S)
1enhanced physical activity (EPA) (hospital-based 30 minutes
twice daily for 2-4 days) 2 T0On the day of admission
(Day 0 or baseline)patient and parents completed the fatigue instruments and a team member applied the actigraph Patients wore the wrist actigraph T1 from Day 0 to 2 or 3 consecutive days (Days 0e3) In addition the patient same parent and staff nurses completed the daily sleep and fatigue reports in the late afternoons of Days 1-3
1 ANOVA model slesignificantly more the experimental athe control arm whdifferences from bsleep efficiency vaaveraged and com
2 The patient-reported mean fatigue scoresarms were higher amadolescents than for
3 The mixed model anarevealed no significandifferences in patientfatigue between
the two study arms otime( no final result iSD only give mixed result)
677
46
23 Keats M
R amp Culos-Reed S N (2008)
A community-based physical activity program for adolescents with cancer (project TREK) program feasibility and preliminary findings
To examine the
feasibility of a
theoretically-based
physical activity (PA)
intervention in
adolescents with
cancerand
examination of the
impact of the
program on
participant QOL
including social
emotional and
physical
well-being(including fatigue)
Repeat measures longitudinal design
No comparsion group
10 adolescents(Lymphoma(4)leukemia(4)CNS tumor(1)germ cell tumor(1)) ages 14-18 years
1physical fitness 2quality of life (QOL) 3PA behavior 4fatigue
1 Feasibility was assessed by participant recruitment attendance and adherence
2physical fitness Fitnessgram 3quality of life (QOL) Pediatric Quality of Life Inventory (PedsQL) 4PA behavior leisure score index (LSI) 5fatigue (mean) pediatric Quality of life
Multidimensional Fatigue Scale (Peds QL-MFS)
(Generalsleepcognitive fatigue)
116week physical activity (PA)
2 total PA physical fitness and overall QOL was assessed at 5 different intervals T0 preintervention (baseline) T1midintervention (after the
first 8 wk) T2 postintervention
(16 wk) T3 3-months
postintervention T4 1-year poststudy
initiation
1 from baseline -wkssig Improvementstotal PA physfitness and Qgeneral fatigue(meanplusmnSD 796plusmn135)
2 from baseline to 3FUsig Improvin general fatigue(meanplusmnSD824plusmn131)slefatigue(meanplusmnSD755plusmn191)totafatigue(meanplusmnSD778plusmn150)
3at 1 years FUsImprovements in sleeprest fatigue(meanplusmnSD725plusmn203)total (meanplusmnSD 763plusmn
678
47
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
2 Gene R E amp Conk Z (2008)
Impact of Effective Nursing Interventions to the Fatigue Syndrome in Children Who Receive Chemotherapy
1 to examine the effects of an effective nursing intervention to the fatigue syndrome of children 7 to 12 years of age who receive chemotherapy 2Tto examine the relationship between fatigue and demographic variables (age sex) diagnoses ([ALL AML] lymphoma) and therapy-related variables (eg level of hemoglobin
experimental randomized controlled study
Routine nursing care
A total of 60 children who are 7-12 years of age(a new diagnosis of ALL AML or lymphoma and receiving for the first time after being diagnosed a 7- to 10-day chemotherapy treatment )
fatigue The Fatigue Scale(FS-C) for 7-12 (intensity)
The Fatigue Scale Parent Version (FS-P)
1 effective nursing interventions(45- 60mdaya week)education about the fatigue with the chemotherapy and fatigue handbook 2 T1 After a 7-day period the children
and parent were evaluated with the Fatigue Scale
1The difference betwthe 2 mean values wafound to be statisticallsignificant 2 statistically significadifference was found between the Fatigue Scale-Child mean scothe experimental (272the control group (4213)children
679
48
25 Chiang et
al(2007)
The effects of ldquo a home ndashbased aerobic exercise interventionrdquo on fatigue and cardiorespiratory fitness in children with Acute Lymphoblastic Leukemia during the maintenance stage of chemotherapy
To examine the effect of ldquo a home ndashbased aerobic exercise interventionrdquo on fatigue and cardiorespiratory fitness in children with Acute Lymphoblastic Leukemia during the maintenance stage of chemotherapy
Quasi-experi -mental
Routine
nursing care
14 pediatric oncology patients in the experimental group and 10 in control group who were matched by age and sex ages7-18 years
1Cardiorespiratory fitness
2Fatigue
1Cardiorespiratory fitness Physical Activity Recall
VO2maxHR peak 6MWT
2 Fatigue PedsQL-MFS(Generalsleepcognitive fatigue)
1A six-week home-based aerobic exercise intervention 2 8 time points T0 baseline T1-T6 every week during the
intervention(6 weeks) T7 post intervention T8 follow-up (one month after
the end of the home-based exercise program)
1 For intent-to ndash treatthe findings indicated are no intervention efftime differences by anon the subscale of fat2 For per-protocol angeneral fatigue( mean422plusmn402) was the osubscale that was siglower for children whothe exercise interventthose in control groupfollow-up assessmentmonth after the compintervention) 3 The VO2peak are significantly improvingexperimental group atbaseline- and post-intassessment The VO2was significantly highechildren who were in experimental group thcontrol subjects at post-intervention assefor the per-protocol an
680
49
Appendix IV Instrument used to measure fatigue
Name Instrument
developers
Description Used in
age in
ref
Reliability
Consistency of
instrument
Checklist Individual Strength
(CIS)22
Vercoulen et
al1996
20 items using 7-point Likert scale of
fatigue To measure four aspects of
fatiguesubjective experience
contractionmotivation physical
Activity
6-14 Not reported
Child Fatigue Scale (CFS)7 Hockenberry
et al2003
14 items 2 part questionnaire frequency
(yes or no) 5-point Likert scale of the
intensity of any yes responses
7-13
14-18 α073-o84
The Fatigue Scale for 7-12
year Olds (FS-C)224
Hockenberry
et al
14 items provide a fatigue intensity score
5-point Likert scale
7-12 αo84
The Fatigue Scale for 13-18
year Olds (FS-A)24
Hockenberry
et al
14 items provide a fatigue intensity score
5-point Likert scale
13-18 α076-o96
Pediatric Quality of life
Multidimensional Fatigue
Scale (Peds QL-MFS)2325
Varni2002 18 items to measure three aspects of
fatigueGeneralsleepcognitive
14-18 Not reported
681
50
Appendix V Excluded studies and reasons for exclusion
Baggott C Dodd M Kennedy C Marina N Miaskowski C Multiple Symptoms in Pediatric Oncology
Patients A Systematic Review Journal of Pediatric Oncology Nursing 2009 Nov-Dec 27(6)
325-339
Reason for exclusion Not outcome of interest
Barlow JH Ellard DR Psycho-educational interventions for children with chronic disease parents and
siblings an overview of the research evidence base Care Health amp Development 2004 Nov
30(6)637-45
Reason for exclusion Not outcome of interest
Bedider S Moyer CA Randomized controlled trials of pediatric massage A review Evid Based
Complement Alternat Med 2007 Mar 4(1)23-34 Epub 2006 Nov 3
Reason for exclusion Not outcome of interest
de Nijs EJ Ros W Grijpdonck MH Nursing intervention for fatigue during the treatment for cancer Cancer
Nursing 2008 31(3)191-206
Reason for exclusion Not population of interest
Edwards JL Gibson F Richardson A Sepion B Ream E Fatigue in adolescents with and following a
cancer diagnosis developing an evidence base for practice European Journal of Cancer 2003
Dec 39(18)2671-80
Reason for exclusion Not experimental or quasi-experimental study
Hinds PS Hockenberry-Eatan M Developing a research program on fatigue in children and adolescents
diagnosed with cancer Journal of Pediatric Oncology Nursing 2001 Mar-Apr 18(2 Suppl
1)3-12
Reason for exclusion Not experimental or quasi-experimental study
Hockenberry-Eaton M Hinds PS Alcoser P ONeill JB Euell K Howard V Gattuso J Taylor J Fatigue in
Children and Adolescents With Cancer Journal of Pediatric Oncology Nursing 1998 July
15(3)172-182
Reason for exclusion Not experimental or quasi-experimental study
Jean-Pierre P Mustian K Kohli S Roscoe JA Hickok JT Morrow GR Community-based clinical oncology
research trials for cancer-related fatigue The Journal of Supportive Oncology 2006 Nov-Dec
4(10)511-6
682
51
Reason for exclusion Not population of interest
Kangas M Bovbjerg DH Montgomery GH Cancer-Related Fatigue A Systematic and Meta-Analytic
Review of Non-Pharmacological Therapies for Cancer Patients Psychological Bulletin 2008 Sep
134(5)700-41
Reason for exclusion Not population of interest
Lotfi-Jam K Carey M Jefford M Schofield P Charleson C Aranda S Nonpharmacologic strategies for
managing common chemotherapy adverse effects A systematic review Journal of Clinical
Oncology 2008 Dec 1 26(34)5618-29 Epub 2008 Nov 3
Reason for exclusion Not outcome of interest
Marchese VG Chiarello LA Lange BJ Effects of physical therapy intervention for children with acute
lymphoblastic leukemia Pediatr Blood Cancer 2004 Feb42(2)127-33
Reason for exclusion Not outcome of interest
Meeske KA Siegel SE Globe DR Mack WJ Bernstein L Prevalence and correlates of fatigue in
long-term survivors of childhood leukemia Journal of Clinical Oncology 2005 Aug 20
23(24)5501-10
Reason for exclusion Not intervention study
Minton O Richardson A Sharpe M Hotopf Stone P A systematic review and meta-analysis of the
pharmacological treatment of cancer-related fatigue J Natl Cancer Inst 2008 Aug 20
100(16)1155-66 Epub 2008 Aug 11
Reason for exclusion Not population and intervention of interest
Mustian KM Morrow GR Carroll JK Figueroa-Moseley CD Pascal JP Williams GC Integrative
nonpharmacologic behavioral interventions for the management of Cancer-Related fatigue The
Oncologist 2007 12(1)52-67
Reason for exclusion Not population of interest
Neill J Belan I Ried K Effectiveness of non-pharmacological interventions for fatigue in adults with
multiple sclerosis rheumatoid arthritis or systemic lupus erythematosus a systematic review
Journal of Advanced Nursing 2006 Dec 56(6)617-35
Reason for exclusion Not population of interest
Rheingans JI A systematic review of nonpharmacologic adjunctive therapies for symptom management
Journal of Pediatric Oncology Nursing 2007 24(2) 81-94
683
52
Reason for exclusion Not outcome of interest
Rheingans JI Pediatric oncology nursesrsquo management of patients symptoms Journal of Pediatric
Oncology Nursing 2008 Nov 25(6) 303-11
Reason for exclusion Not outcome of interest
San Juan AF Fleck SJ Chamorro-Vintildea C Mateacute-Muntildeoz JL Moral S Peacuterez M Cardona C Del Valle MF
Hernaacutendez M Ramiacuterez M Madero L Lucia A Effects of an intrahospital exercise program
intervention for children with leukemia Medicine amp Science in Sports amp Exercise 2007 Jan
39(1)13-21
Reason for exclusion Not outcome of interest
Sanford SD Okuma JO Pan J Srivastava DK West N Farr L Hinds PS Gender differences in sleep
fatigue and daytime activity in a pediatric oncology sample receiving dexamethasone Journal of
Pediatric Psychology 2008 Apr 33(3)298-306 Epub 2007 Nov 17
Reason for exclusion Not experimental or quasi-experimental study
Schmitz KH Holtzman J Courneya KS Macircsse LC Duval S Kane R Controlled physical activity trials in
cancer survivors a systematic review and meta-analysis Cancer Epidemiol Biomarkers Prev
2005 Jul 14(7)1588-95
Reason for exclusion Not population of interest
van Brussel M Takken T Lucia A van der Net J Helders PJ Is physical fitness decreased in survivors of
childhood leukemia A systematic review Leukemia 2005 Jan 19(1)13-7
Reason for exclusion Not population of interest
Whiting P Bagnall AM Snowden AJ Cornell JE Mulrow CD Ramirez G Interventions for the treatment
and management of chronic fatigue syndrome JAMA 2001 Sep 19 286(11)1360-8
Reason for exclusion Not intervention of interest
Whitsett SF Gudmundsdottir M Davies B McCarthy P Friedman D Chemotherapy-related fatigue in
childhood cancer correlates consequences and coping strategies Journal of Pediatric
Oncology Nursing 2008 Mar-Apr 25(2)86-96 Epub 2008 Feb 29
Reason for exclusion Not experimental or quasi-experimental study
Winner C Muumlller C Hoffmann C Boos J Rosenbaum D Physical activity and childhood cancer Pediatr
Blood Cancer 2010 Apr 54(4)501-10
Reason for exclusion Not research study
684
53
Wu M Hsu L Zhang B Shen N Lu H Li S The experiences of cancer-related fatigue among Chinese
children with leukaemia A phenomenological study Journal of Nursing Studies 2010 Jan
47(1)49-59 Epub 2009 Aug 25
Reason for exclusion Not experimental or quasi-experimental study
Yeh CH Chiang YC Lin L Yang CP Chien LC Weaver MA Chuang HL Clinical factors associated with
fatigue over time in paediatric oncology patients receiving chemotherapy British Journal of
Cancer 2008 Jul 8 99(1)23-9 Epub 2008 Jun 24
Reason for exclusion Not experimental or quasi-experimental study
685
40
Appendix II JBI Data Extraction Tool for Quantitative Studies Authors and Year
Journal Title
Record NumberArticle Reference No
Reviewer
Method
Settings
Participants
Number of participants
Group A Group B Group C
Control Intervention 1 Intervention 2
Interventions
Group A
Control
Group B
Intervention 1
Group C
Intervention 2
Outcome measures
Definition
673
41
Other outcome measures
Outcome description ScaleMeasure
Results
Dichotomous Data
Outcome Control Group
Numbertotal number
Treatment Group
Numbertotal number
Continuous Data
Authorrsquos Conclusions
Comments
Outcome Control Group
Mean amp SD
Treatment Group
Mean amp SD
674
43
Appendix III Details of included studies (N=6)(2720212223) RefNo Author(s)
(years) Title Study question Research
method Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
22 Takken T van der Torre P Zwerink M Hulzebos E H Bierings M Helders P J Mamp van der Net J (2009)
Development feasibility and efficacy of a community-based exercise training program in pediatric cancer survivors
To develop a 12-week home-based exercise training program (comprising aerobic and strength exercises) for children who survived ALL and to study itrsquos feasibility and efficacy
Pre-post test design
No comparsion group
Survived ALL(N=9)ages 6-14 years
1anthropometry 2 muscle strength 3functional mobility 4cardio-pulmonary
exercise test 5Fatigue
1 Feasibility questionnaire 2 anthropometry electronic scale and a wallmounted stadiometerHarpenden skin fold calipers 3 muscle strength handheld dynamometer 4functional mobility Timed Up
and Go test (TUG) 5cardio-pulmonary exercise test electronically braked cycle ergometer 6Fatigue(mean)CSI-20 (subjective experience of fatigueconcentrationmotivationphysical activity)
112-week exercise training program
2 Patients were assessed before (T0) and after (T1) 12 weeks of training
1 muscle strength execapacity functional moand fatigue showed nosignificant differences between pre(meanplusmnSD415plusmn147) and post training(meanplusmnSD3687)
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
7 Post-White J Fitzgerald M Savik K Hooke M C Hannahan A B amp Sencer S F (2009)
Massage therapy for children with cancer
To determine whether 4 weekly sessions of massage compared with 4 quiet-time control conditions would reduce anxiety cortisol levels fatigue nausea and pain in children with cancer undergoing chemotherapy and would reduce anxiety fatigue and mood disturbance in a parent
2-period crossover design (Randomized)
quiet-time
control
sessions
Children with cancer 1 to 18 years of age Twenty-three childrenparent dyads were enrolled 17 completed all data points
children 1relaxation 2symptoms 3 fatigue
parents
1anxiety 2 fatigue
children 1relaxation (heart and respiratory rates blood pressure and salivary cortisol level)
2symptoms (pain nausea anxiety 3 fatigue 1-2y3-6yLansky Play Performance Scale (PPS) 7-13y
1 4 weekly massage (MT) sessions alternated with 4 weekly quiet-time(QT) control sessions
2 children included presession and postsession vital signs (heart rate respiratory rate blood pressure) and self-report (parent proxy report for age 1-2 years) of pain nausea and anxiety Fatigue was measured before sessions 1 and 4 and at each follow-up Parent measures
included anxiety fatigue and mood states
1Massage was moreeffective than quiet tireducing heart rate inchildren anxiety in cless than age 14 yeaparent anxiety 2There were no sign
changes in blood pcortisol pain naufatigue (no state d
3 Children reported tmassage helped thebetter lessened theirand worries and hadlasting effects than q
675
44
14-18yChild Fatigue Scale (CFS) (frequency
intensity) 2 parents anxiety and fatigue
676
45
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
24 Hinds P S Hockenberry M Rai S N Zhang L Razzouk B I Cremer L McCarthy K amp Rodriguez-Galindo C (2007)
Clinical field testing of an enhanced-activity intervention in hospitalized children with cancer
To determine the feasibility of an
enhanced physical activity EPA intervention in children and adolescents hospitalized to receive chemotherapy for a solid tumor or AML and to assess the sleep and fatigue outcomes of the intervention using two different statistical approaches to analyze the longitudinal symptom data
randomized prospective two-site and two-group pilot study
Standard care Twenty nine patients (25 with a solid tumor and 4 with AML)ages 7-18 years
1 sleep duration 2 sleep efficiency 3 fatigue
1sleep duration sleep efficiency The
Wrist Actigraph The Daily Sleep Diary-Parent 2 fatigue (mean) The Fatigue Scale(FS-C) for 7-12 (intensity) The Fatigue Scale(FS-A) for 13-18 The Fatigue Scale Parent Version (FS-P) The Fatigue Scale Staff Version (FS-S)
1enhanced physical activity (EPA) (hospital-based 30 minutes
twice daily for 2-4 days) 2 T0On the day of admission
(Day 0 or baseline)patient and parents completed the fatigue instruments and a team member applied the actigraph Patients wore the wrist actigraph T1 from Day 0 to 2 or 3 consecutive days (Days 0e3) In addition the patient same parent and staff nurses completed the daily sleep and fatigue reports in the late afternoons of Days 1-3
1 ANOVA model slesignificantly more the experimental athe control arm whdifferences from bsleep efficiency vaaveraged and com
2 The patient-reported mean fatigue scoresarms were higher amadolescents than for
3 The mixed model anarevealed no significandifferences in patientfatigue between
the two study arms otime( no final result iSD only give mixed result)
677
46
23 Keats M
R amp Culos-Reed S N (2008)
A community-based physical activity program for adolescents with cancer (project TREK) program feasibility and preliminary findings
To examine the
feasibility of a
theoretically-based
physical activity (PA)
intervention in
adolescents with
cancerand
examination of the
impact of the
program on
participant QOL
including social
emotional and
physical
well-being(including fatigue)
Repeat measures longitudinal design
No comparsion group
10 adolescents(Lymphoma(4)leukemia(4)CNS tumor(1)germ cell tumor(1)) ages 14-18 years
1physical fitness 2quality of life (QOL) 3PA behavior 4fatigue
1 Feasibility was assessed by participant recruitment attendance and adherence
2physical fitness Fitnessgram 3quality of life (QOL) Pediatric Quality of Life Inventory (PedsQL) 4PA behavior leisure score index (LSI) 5fatigue (mean) pediatric Quality of life
Multidimensional Fatigue Scale (Peds QL-MFS)
(Generalsleepcognitive fatigue)
116week physical activity (PA)
2 total PA physical fitness and overall QOL was assessed at 5 different intervals T0 preintervention (baseline) T1midintervention (after the
first 8 wk) T2 postintervention
(16 wk) T3 3-months
postintervention T4 1-year poststudy
initiation
1 from baseline -wkssig Improvementstotal PA physfitness and Qgeneral fatigue(meanplusmnSD 796plusmn135)
2 from baseline to 3FUsig Improvin general fatigue(meanplusmnSD824plusmn131)slefatigue(meanplusmnSD755plusmn191)totafatigue(meanplusmnSD778plusmn150)
3at 1 years FUsImprovements in sleeprest fatigue(meanplusmnSD725plusmn203)total (meanplusmnSD 763plusmn
678
47
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
2 Gene R E amp Conk Z (2008)
Impact of Effective Nursing Interventions to the Fatigue Syndrome in Children Who Receive Chemotherapy
1 to examine the effects of an effective nursing intervention to the fatigue syndrome of children 7 to 12 years of age who receive chemotherapy 2Tto examine the relationship between fatigue and demographic variables (age sex) diagnoses ([ALL AML] lymphoma) and therapy-related variables (eg level of hemoglobin
experimental randomized controlled study
Routine nursing care
A total of 60 children who are 7-12 years of age(a new diagnosis of ALL AML or lymphoma and receiving for the first time after being diagnosed a 7- to 10-day chemotherapy treatment )
fatigue The Fatigue Scale(FS-C) for 7-12 (intensity)
The Fatigue Scale Parent Version (FS-P)
1 effective nursing interventions(45- 60mdaya week)education about the fatigue with the chemotherapy and fatigue handbook 2 T1 After a 7-day period the children
and parent were evaluated with the Fatigue Scale
1The difference betwthe 2 mean values wafound to be statisticallsignificant 2 statistically significadifference was found between the Fatigue Scale-Child mean scothe experimental (272the control group (4213)children
679
48
25 Chiang et
al(2007)
The effects of ldquo a home ndashbased aerobic exercise interventionrdquo on fatigue and cardiorespiratory fitness in children with Acute Lymphoblastic Leukemia during the maintenance stage of chemotherapy
To examine the effect of ldquo a home ndashbased aerobic exercise interventionrdquo on fatigue and cardiorespiratory fitness in children with Acute Lymphoblastic Leukemia during the maintenance stage of chemotherapy
Quasi-experi -mental
Routine
nursing care
14 pediatric oncology patients in the experimental group and 10 in control group who were matched by age and sex ages7-18 years
1Cardiorespiratory fitness
2Fatigue
1Cardiorespiratory fitness Physical Activity Recall
VO2maxHR peak 6MWT
2 Fatigue PedsQL-MFS(Generalsleepcognitive fatigue)
1A six-week home-based aerobic exercise intervention 2 8 time points T0 baseline T1-T6 every week during the
intervention(6 weeks) T7 post intervention T8 follow-up (one month after
the end of the home-based exercise program)
1 For intent-to ndash treatthe findings indicated are no intervention efftime differences by anon the subscale of fat2 For per-protocol angeneral fatigue( mean422plusmn402) was the osubscale that was siglower for children whothe exercise interventthose in control groupfollow-up assessmentmonth after the compintervention) 3 The VO2peak are significantly improvingexperimental group atbaseline- and post-intassessment The VO2was significantly highechildren who were in experimental group thcontrol subjects at post-intervention assefor the per-protocol an
680
49
Appendix IV Instrument used to measure fatigue
Name Instrument
developers
Description Used in
age in
ref
Reliability
Consistency of
instrument
Checklist Individual Strength
(CIS)22
Vercoulen et
al1996
20 items using 7-point Likert scale of
fatigue To measure four aspects of
fatiguesubjective experience
contractionmotivation physical
Activity
6-14 Not reported
Child Fatigue Scale (CFS)7 Hockenberry
et al2003
14 items 2 part questionnaire frequency
(yes or no) 5-point Likert scale of the
intensity of any yes responses
7-13
14-18 α073-o84
The Fatigue Scale for 7-12
year Olds (FS-C)224
Hockenberry
et al
14 items provide a fatigue intensity score
5-point Likert scale
7-12 αo84
The Fatigue Scale for 13-18
year Olds (FS-A)24
Hockenberry
et al
14 items provide a fatigue intensity score
5-point Likert scale
13-18 α076-o96
Pediatric Quality of life
Multidimensional Fatigue
Scale (Peds QL-MFS)2325
Varni2002 18 items to measure three aspects of
fatigueGeneralsleepcognitive
14-18 Not reported
681
50
Appendix V Excluded studies and reasons for exclusion
Baggott C Dodd M Kennedy C Marina N Miaskowski C Multiple Symptoms in Pediatric Oncology
Patients A Systematic Review Journal of Pediatric Oncology Nursing 2009 Nov-Dec 27(6)
325-339
Reason for exclusion Not outcome of interest
Barlow JH Ellard DR Psycho-educational interventions for children with chronic disease parents and
siblings an overview of the research evidence base Care Health amp Development 2004 Nov
30(6)637-45
Reason for exclusion Not outcome of interest
Bedider S Moyer CA Randomized controlled trials of pediatric massage A review Evid Based
Complement Alternat Med 2007 Mar 4(1)23-34 Epub 2006 Nov 3
Reason for exclusion Not outcome of interest
de Nijs EJ Ros W Grijpdonck MH Nursing intervention for fatigue during the treatment for cancer Cancer
Nursing 2008 31(3)191-206
Reason for exclusion Not population of interest
Edwards JL Gibson F Richardson A Sepion B Ream E Fatigue in adolescents with and following a
cancer diagnosis developing an evidence base for practice European Journal of Cancer 2003
Dec 39(18)2671-80
Reason for exclusion Not experimental or quasi-experimental study
Hinds PS Hockenberry-Eatan M Developing a research program on fatigue in children and adolescents
diagnosed with cancer Journal of Pediatric Oncology Nursing 2001 Mar-Apr 18(2 Suppl
1)3-12
Reason for exclusion Not experimental or quasi-experimental study
Hockenberry-Eaton M Hinds PS Alcoser P ONeill JB Euell K Howard V Gattuso J Taylor J Fatigue in
Children and Adolescents With Cancer Journal of Pediatric Oncology Nursing 1998 July
15(3)172-182
Reason for exclusion Not experimental or quasi-experimental study
Jean-Pierre P Mustian K Kohli S Roscoe JA Hickok JT Morrow GR Community-based clinical oncology
research trials for cancer-related fatigue The Journal of Supportive Oncology 2006 Nov-Dec
4(10)511-6
682
51
Reason for exclusion Not population of interest
Kangas M Bovbjerg DH Montgomery GH Cancer-Related Fatigue A Systematic and Meta-Analytic
Review of Non-Pharmacological Therapies for Cancer Patients Psychological Bulletin 2008 Sep
134(5)700-41
Reason for exclusion Not population of interest
Lotfi-Jam K Carey M Jefford M Schofield P Charleson C Aranda S Nonpharmacologic strategies for
managing common chemotherapy adverse effects A systematic review Journal of Clinical
Oncology 2008 Dec 1 26(34)5618-29 Epub 2008 Nov 3
Reason for exclusion Not outcome of interest
Marchese VG Chiarello LA Lange BJ Effects of physical therapy intervention for children with acute
lymphoblastic leukemia Pediatr Blood Cancer 2004 Feb42(2)127-33
Reason for exclusion Not outcome of interest
Meeske KA Siegel SE Globe DR Mack WJ Bernstein L Prevalence and correlates of fatigue in
long-term survivors of childhood leukemia Journal of Clinical Oncology 2005 Aug 20
23(24)5501-10
Reason for exclusion Not intervention study
Minton O Richardson A Sharpe M Hotopf Stone P A systematic review and meta-analysis of the
pharmacological treatment of cancer-related fatigue J Natl Cancer Inst 2008 Aug 20
100(16)1155-66 Epub 2008 Aug 11
Reason for exclusion Not population and intervention of interest
Mustian KM Morrow GR Carroll JK Figueroa-Moseley CD Pascal JP Williams GC Integrative
nonpharmacologic behavioral interventions for the management of Cancer-Related fatigue The
Oncologist 2007 12(1)52-67
Reason for exclusion Not population of interest
Neill J Belan I Ried K Effectiveness of non-pharmacological interventions for fatigue in adults with
multiple sclerosis rheumatoid arthritis or systemic lupus erythematosus a systematic review
Journal of Advanced Nursing 2006 Dec 56(6)617-35
Reason for exclusion Not population of interest
Rheingans JI A systematic review of nonpharmacologic adjunctive therapies for symptom management
Journal of Pediatric Oncology Nursing 2007 24(2) 81-94
683
52
Reason for exclusion Not outcome of interest
Rheingans JI Pediatric oncology nursesrsquo management of patients symptoms Journal of Pediatric
Oncology Nursing 2008 Nov 25(6) 303-11
Reason for exclusion Not outcome of interest
San Juan AF Fleck SJ Chamorro-Vintildea C Mateacute-Muntildeoz JL Moral S Peacuterez M Cardona C Del Valle MF
Hernaacutendez M Ramiacuterez M Madero L Lucia A Effects of an intrahospital exercise program
intervention for children with leukemia Medicine amp Science in Sports amp Exercise 2007 Jan
39(1)13-21
Reason for exclusion Not outcome of interest
Sanford SD Okuma JO Pan J Srivastava DK West N Farr L Hinds PS Gender differences in sleep
fatigue and daytime activity in a pediatric oncology sample receiving dexamethasone Journal of
Pediatric Psychology 2008 Apr 33(3)298-306 Epub 2007 Nov 17
Reason for exclusion Not experimental or quasi-experimental study
Schmitz KH Holtzman J Courneya KS Macircsse LC Duval S Kane R Controlled physical activity trials in
cancer survivors a systematic review and meta-analysis Cancer Epidemiol Biomarkers Prev
2005 Jul 14(7)1588-95
Reason for exclusion Not population of interest
van Brussel M Takken T Lucia A van der Net J Helders PJ Is physical fitness decreased in survivors of
childhood leukemia A systematic review Leukemia 2005 Jan 19(1)13-7
Reason for exclusion Not population of interest
Whiting P Bagnall AM Snowden AJ Cornell JE Mulrow CD Ramirez G Interventions for the treatment
and management of chronic fatigue syndrome JAMA 2001 Sep 19 286(11)1360-8
Reason for exclusion Not intervention of interest
Whitsett SF Gudmundsdottir M Davies B McCarthy P Friedman D Chemotherapy-related fatigue in
childhood cancer correlates consequences and coping strategies Journal of Pediatric
Oncology Nursing 2008 Mar-Apr 25(2)86-96 Epub 2008 Feb 29
Reason for exclusion Not experimental or quasi-experimental study
Winner C Muumlller C Hoffmann C Boos J Rosenbaum D Physical activity and childhood cancer Pediatr
Blood Cancer 2010 Apr 54(4)501-10
Reason for exclusion Not research study
684
53
Wu M Hsu L Zhang B Shen N Lu H Li S The experiences of cancer-related fatigue among Chinese
children with leukaemia A phenomenological study Journal of Nursing Studies 2010 Jan
47(1)49-59 Epub 2009 Aug 25
Reason for exclusion Not experimental or quasi-experimental study
Yeh CH Chiang YC Lin L Yang CP Chien LC Weaver MA Chuang HL Clinical factors associated with
fatigue over time in paediatric oncology patients receiving chemotherapy British Journal of
Cancer 2008 Jul 8 99(1)23-9 Epub 2008 Jun 24
Reason for exclusion Not experimental or quasi-experimental study
685
41
Other outcome measures
Outcome description ScaleMeasure
Results
Dichotomous Data
Outcome Control Group
Numbertotal number
Treatment Group
Numbertotal number
Continuous Data
Authorrsquos Conclusions
Comments
Outcome Control Group
Mean amp SD
Treatment Group
Mean amp SD
674
43
Appendix III Details of included studies (N=6)(2720212223) RefNo Author(s)
(years) Title Study question Research
method Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
22 Takken T van der Torre P Zwerink M Hulzebos E H Bierings M Helders P J Mamp van der Net J (2009)
Development feasibility and efficacy of a community-based exercise training program in pediatric cancer survivors
To develop a 12-week home-based exercise training program (comprising aerobic and strength exercises) for children who survived ALL and to study itrsquos feasibility and efficacy
Pre-post test design
No comparsion group
Survived ALL(N=9)ages 6-14 years
1anthropometry 2 muscle strength 3functional mobility 4cardio-pulmonary
exercise test 5Fatigue
1 Feasibility questionnaire 2 anthropometry electronic scale and a wallmounted stadiometerHarpenden skin fold calipers 3 muscle strength handheld dynamometer 4functional mobility Timed Up
and Go test (TUG) 5cardio-pulmonary exercise test electronically braked cycle ergometer 6Fatigue(mean)CSI-20 (subjective experience of fatigueconcentrationmotivationphysical activity)
112-week exercise training program
2 Patients were assessed before (T0) and after (T1) 12 weeks of training
1 muscle strength execapacity functional moand fatigue showed nosignificant differences between pre(meanplusmnSD415plusmn147) and post training(meanplusmnSD3687)
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
7 Post-White J Fitzgerald M Savik K Hooke M C Hannahan A B amp Sencer S F (2009)
Massage therapy for children with cancer
To determine whether 4 weekly sessions of massage compared with 4 quiet-time control conditions would reduce anxiety cortisol levels fatigue nausea and pain in children with cancer undergoing chemotherapy and would reduce anxiety fatigue and mood disturbance in a parent
2-period crossover design (Randomized)
quiet-time
control
sessions
Children with cancer 1 to 18 years of age Twenty-three childrenparent dyads were enrolled 17 completed all data points
children 1relaxation 2symptoms 3 fatigue
parents
1anxiety 2 fatigue
children 1relaxation (heart and respiratory rates blood pressure and salivary cortisol level)
2symptoms (pain nausea anxiety 3 fatigue 1-2y3-6yLansky Play Performance Scale (PPS) 7-13y
1 4 weekly massage (MT) sessions alternated with 4 weekly quiet-time(QT) control sessions
2 children included presession and postsession vital signs (heart rate respiratory rate blood pressure) and self-report (parent proxy report for age 1-2 years) of pain nausea and anxiety Fatigue was measured before sessions 1 and 4 and at each follow-up Parent measures
included anxiety fatigue and mood states
1Massage was moreeffective than quiet tireducing heart rate inchildren anxiety in cless than age 14 yeaparent anxiety 2There were no sign
changes in blood pcortisol pain naufatigue (no state d
3 Children reported tmassage helped thebetter lessened theirand worries and hadlasting effects than q
675
44
14-18yChild Fatigue Scale (CFS) (frequency
intensity) 2 parents anxiety and fatigue
676
45
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
24 Hinds P S Hockenberry M Rai S N Zhang L Razzouk B I Cremer L McCarthy K amp Rodriguez-Galindo C (2007)
Clinical field testing of an enhanced-activity intervention in hospitalized children with cancer
To determine the feasibility of an
enhanced physical activity EPA intervention in children and adolescents hospitalized to receive chemotherapy for a solid tumor or AML and to assess the sleep and fatigue outcomes of the intervention using two different statistical approaches to analyze the longitudinal symptom data
randomized prospective two-site and two-group pilot study
Standard care Twenty nine patients (25 with a solid tumor and 4 with AML)ages 7-18 years
1 sleep duration 2 sleep efficiency 3 fatigue
1sleep duration sleep efficiency The
Wrist Actigraph The Daily Sleep Diary-Parent 2 fatigue (mean) The Fatigue Scale(FS-C) for 7-12 (intensity) The Fatigue Scale(FS-A) for 13-18 The Fatigue Scale Parent Version (FS-P) The Fatigue Scale Staff Version (FS-S)
1enhanced physical activity (EPA) (hospital-based 30 minutes
twice daily for 2-4 days) 2 T0On the day of admission
(Day 0 or baseline)patient and parents completed the fatigue instruments and a team member applied the actigraph Patients wore the wrist actigraph T1 from Day 0 to 2 or 3 consecutive days (Days 0e3) In addition the patient same parent and staff nurses completed the daily sleep and fatigue reports in the late afternoons of Days 1-3
1 ANOVA model slesignificantly more the experimental athe control arm whdifferences from bsleep efficiency vaaveraged and com
2 The patient-reported mean fatigue scoresarms were higher amadolescents than for
3 The mixed model anarevealed no significandifferences in patientfatigue between
the two study arms otime( no final result iSD only give mixed result)
677
46
23 Keats M
R amp Culos-Reed S N (2008)
A community-based physical activity program for adolescents with cancer (project TREK) program feasibility and preliminary findings
To examine the
feasibility of a
theoretically-based
physical activity (PA)
intervention in
adolescents with
cancerand
examination of the
impact of the
program on
participant QOL
including social
emotional and
physical
well-being(including fatigue)
Repeat measures longitudinal design
No comparsion group
10 adolescents(Lymphoma(4)leukemia(4)CNS tumor(1)germ cell tumor(1)) ages 14-18 years
1physical fitness 2quality of life (QOL) 3PA behavior 4fatigue
1 Feasibility was assessed by participant recruitment attendance and adherence
2physical fitness Fitnessgram 3quality of life (QOL) Pediatric Quality of Life Inventory (PedsQL) 4PA behavior leisure score index (LSI) 5fatigue (mean) pediatric Quality of life
Multidimensional Fatigue Scale (Peds QL-MFS)
(Generalsleepcognitive fatigue)
116week physical activity (PA)
2 total PA physical fitness and overall QOL was assessed at 5 different intervals T0 preintervention (baseline) T1midintervention (after the
first 8 wk) T2 postintervention
(16 wk) T3 3-months
postintervention T4 1-year poststudy
initiation
1 from baseline -wkssig Improvementstotal PA physfitness and Qgeneral fatigue(meanplusmnSD 796plusmn135)
2 from baseline to 3FUsig Improvin general fatigue(meanplusmnSD824plusmn131)slefatigue(meanplusmnSD755plusmn191)totafatigue(meanplusmnSD778plusmn150)
3at 1 years FUsImprovements in sleeprest fatigue(meanplusmnSD725plusmn203)total (meanplusmnSD 763plusmn
678
47
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
2 Gene R E amp Conk Z (2008)
Impact of Effective Nursing Interventions to the Fatigue Syndrome in Children Who Receive Chemotherapy
1 to examine the effects of an effective nursing intervention to the fatigue syndrome of children 7 to 12 years of age who receive chemotherapy 2Tto examine the relationship between fatigue and demographic variables (age sex) diagnoses ([ALL AML] lymphoma) and therapy-related variables (eg level of hemoglobin
experimental randomized controlled study
Routine nursing care
A total of 60 children who are 7-12 years of age(a new diagnosis of ALL AML or lymphoma and receiving for the first time after being diagnosed a 7- to 10-day chemotherapy treatment )
fatigue The Fatigue Scale(FS-C) for 7-12 (intensity)
The Fatigue Scale Parent Version (FS-P)
1 effective nursing interventions(45- 60mdaya week)education about the fatigue with the chemotherapy and fatigue handbook 2 T1 After a 7-day period the children
and parent were evaluated with the Fatigue Scale
1The difference betwthe 2 mean values wafound to be statisticallsignificant 2 statistically significadifference was found between the Fatigue Scale-Child mean scothe experimental (272the control group (4213)children
679
48
25 Chiang et
al(2007)
The effects of ldquo a home ndashbased aerobic exercise interventionrdquo on fatigue and cardiorespiratory fitness in children with Acute Lymphoblastic Leukemia during the maintenance stage of chemotherapy
To examine the effect of ldquo a home ndashbased aerobic exercise interventionrdquo on fatigue and cardiorespiratory fitness in children with Acute Lymphoblastic Leukemia during the maintenance stage of chemotherapy
Quasi-experi -mental
Routine
nursing care
14 pediatric oncology patients in the experimental group and 10 in control group who were matched by age and sex ages7-18 years
1Cardiorespiratory fitness
2Fatigue
1Cardiorespiratory fitness Physical Activity Recall
VO2maxHR peak 6MWT
2 Fatigue PedsQL-MFS(Generalsleepcognitive fatigue)
1A six-week home-based aerobic exercise intervention 2 8 time points T0 baseline T1-T6 every week during the
intervention(6 weeks) T7 post intervention T8 follow-up (one month after
the end of the home-based exercise program)
1 For intent-to ndash treatthe findings indicated are no intervention efftime differences by anon the subscale of fat2 For per-protocol angeneral fatigue( mean422plusmn402) was the osubscale that was siglower for children whothe exercise interventthose in control groupfollow-up assessmentmonth after the compintervention) 3 The VO2peak are significantly improvingexperimental group atbaseline- and post-intassessment The VO2was significantly highechildren who were in experimental group thcontrol subjects at post-intervention assefor the per-protocol an
680
49
Appendix IV Instrument used to measure fatigue
Name Instrument
developers
Description Used in
age in
ref
Reliability
Consistency of
instrument
Checklist Individual Strength
(CIS)22
Vercoulen et
al1996
20 items using 7-point Likert scale of
fatigue To measure four aspects of
fatiguesubjective experience
contractionmotivation physical
Activity
6-14 Not reported
Child Fatigue Scale (CFS)7 Hockenberry
et al2003
14 items 2 part questionnaire frequency
(yes or no) 5-point Likert scale of the
intensity of any yes responses
7-13
14-18 α073-o84
The Fatigue Scale for 7-12
year Olds (FS-C)224
Hockenberry
et al
14 items provide a fatigue intensity score
5-point Likert scale
7-12 αo84
The Fatigue Scale for 13-18
year Olds (FS-A)24
Hockenberry
et al
14 items provide a fatigue intensity score
5-point Likert scale
13-18 α076-o96
Pediatric Quality of life
Multidimensional Fatigue
Scale (Peds QL-MFS)2325
Varni2002 18 items to measure three aspects of
fatigueGeneralsleepcognitive
14-18 Not reported
681
50
Appendix V Excluded studies and reasons for exclusion
Baggott C Dodd M Kennedy C Marina N Miaskowski C Multiple Symptoms in Pediatric Oncology
Patients A Systematic Review Journal of Pediatric Oncology Nursing 2009 Nov-Dec 27(6)
325-339
Reason for exclusion Not outcome of interest
Barlow JH Ellard DR Psycho-educational interventions for children with chronic disease parents and
siblings an overview of the research evidence base Care Health amp Development 2004 Nov
30(6)637-45
Reason for exclusion Not outcome of interest
Bedider S Moyer CA Randomized controlled trials of pediatric massage A review Evid Based
Complement Alternat Med 2007 Mar 4(1)23-34 Epub 2006 Nov 3
Reason for exclusion Not outcome of interest
de Nijs EJ Ros W Grijpdonck MH Nursing intervention for fatigue during the treatment for cancer Cancer
Nursing 2008 31(3)191-206
Reason for exclusion Not population of interest
Edwards JL Gibson F Richardson A Sepion B Ream E Fatigue in adolescents with and following a
cancer diagnosis developing an evidence base for practice European Journal of Cancer 2003
Dec 39(18)2671-80
Reason for exclusion Not experimental or quasi-experimental study
Hinds PS Hockenberry-Eatan M Developing a research program on fatigue in children and adolescents
diagnosed with cancer Journal of Pediatric Oncology Nursing 2001 Mar-Apr 18(2 Suppl
1)3-12
Reason for exclusion Not experimental or quasi-experimental study
Hockenberry-Eaton M Hinds PS Alcoser P ONeill JB Euell K Howard V Gattuso J Taylor J Fatigue in
Children and Adolescents With Cancer Journal of Pediatric Oncology Nursing 1998 July
15(3)172-182
Reason for exclusion Not experimental or quasi-experimental study
Jean-Pierre P Mustian K Kohli S Roscoe JA Hickok JT Morrow GR Community-based clinical oncology
research trials for cancer-related fatigue The Journal of Supportive Oncology 2006 Nov-Dec
4(10)511-6
682
51
Reason for exclusion Not population of interest
Kangas M Bovbjerg DH Montgomery GH Cancer-Related Fatigue A Systematic and Meta-Analytic
Review of Non-Pharmacological Therapies for Cancer Patients Psychological Bulletin 2008 Sep
134(5)700-41
Reason for exclusion Not population of interest
Lotfi-Jam K Carey M Jefford M Schofield P Charleson C Aranda S Nonpharmacologic strategies for
managing common chemotherapy adverse effects A systematic review Journal of Clinical
Oncology 2008 Dec 1 26(34)5618-29 Epub 2008 Nov 3
Reason for exclusion Not outcome of interest
Marchese VG Chiarello LA Lange BJ Effects of physical therapy intervention for children with acute
lymphoblastic leukemia Pediatr Blood Cancer 2004 Feb42(2)127-33
Reason for exclusion Not outcome of interest
Meeske KA Siegel SE Globe DR Mack WJ Bernstein L Prevalence and correlates of fatigue in
long-term survivors of childhood leukemia Journal of Clinical Oncology 2005 Aug 20
23(24)5501-10
Reason for exclusion Not intervention study
Minton O Richardson A Sharpe M Hotopf Stone P A systematic review and meta-analysis of the
pharmacological treatment of cancer-related fatigue J Natl Cancer Inst 2008 Aug 20
100(16)1155-66 Epub 2008 Aug 11
Reason for exclusion Not population and intervention of interest
Mustian KM Morrow GR Carroll JK Figueroa-Moseley CD Pascal JP Williams GC Integrative
nonpharmacologic behavioral interventions for the management of Cancer-Related fatigue The
Oncologist 2007 12(1)52-67
Reason for exclusion Not population of interest
Neill J Belan I Ried K Effectiveness of non-pharmacological interventions for fatigue in adults with
multiple sclerosis rheumatoid arthritis or systemic lupus erythematosus a systematic review
Journal of Advanced Nursing 2006 Dec 56(6)617-35
Reason for exclusion Not population of interest
Rheingans JI A systematic review of nonpharmacologic adjunctive therapies for symptom management
Journal of Pediatric Oncology Nursing 2007 24(2) 81-94
683
52
Reason for exclusion Not outcome of interest
Rheingans JI Pediatric oncology nursesrsquo management of patients symptoms Journal of Pediatric
Oncology Nursing 2008 Nov 25(6) 303-11
Reason for exclusion Not outcome of interest
San Juan AF Fleck SJ Chamorro-Vintildea C Mateacute-Muntildeoz JL Moral S Peacuterez M Cardona C Del Valle MF
Hernaacutendez M Ramiacuterez M Madero L Lucia A Effects of an intrahospital exercise program
intervention for children with leukemia Medicine amp Science in Sports amp Exercise 2007 Jan
39(1)13-21
Reason for exclusion Not outcome of interest
Sanford SD Okuma JO Pan J Srivastava DK West N Farr L Hinds PS Gender differences in sleep
fatigue and daytime activity in a pediatric oncology sample receiving dexamethasone Journal of
Pediatric Psychology 2008 Apr 33(3)298-306 Epub 2007 Nov 17
Reason for exclusion Not experimental or quasi-experimental study
Schmitz KH Holtzman J Courneya KS Macircsse LC Duval S Kane R Controlled physical activity trials in
cancer survivors a systematic review and meta-analysis Cancer Epidemiol Biomarkers Prev
2005 Jul 14(7)1588-95
Reason for exclusion Not population of interest
van Brussel M Takken T Lucia A van der Net J Helders PJ Is physical fitness decreased in survivors of
childhood leukemia A systematic review Leukemia 2005 Jan 19(1)13-7
Reason for exclusion Not population of interest
Whiting P Bagnall AM Snowden AJ Cornell JE Mulrow CD Ramirez G Interventions for the treatment
and management of chronic fatigue syndrome JAMA 2001 Sep 19 286(11)1360-8
Reason for exclusion Not intervention of interest
Whitsett SF Gudmundsdottir M Davies B McCarthy P Friedman D Chemotherapy-related fatigue in
childhood cancer correlates consequences and coping strategies Journal of Pediatric
Oncology Nursing 2008 Mar-Apr 25(2)86-96 Epub 2008 Feb 29
Reason for exclusion Not experimental or quasi-experimental study
Winner C Muumlller C Hoffmann C Boos J Rosenbaum D Physical activity and childhood cancer Pediatr
Blood Cancer 2010 Apr 54(4)501-10
Reason for exclusion Not research study
684
53
Wu M Hsu L Zhang B Shen N Lu H Li S The experiences of cancer-related fatigue among Chinese
children with leukaemia A phenomenological study Journal of Nursing Studies 2010 Jan
47(1)49-59 Epub 2009 Aug 25
Reason for exclusion Not experimental or quasi-experimental study
Yeh CH Chiang YC Lin L Yang CP Chien LC Weaver MA Chuang HL Clinical factors associated with
fatigue over time in paediatric oncology patients receiving chemotherapy British Journal of
Cancer 2008 Jul 8 99(1)23-9 Epub 2008 Jun 24
Reason for exclusion Not experimental or quasi-experimental study
685
43
Appendix III Details of included studies (N=6)(2720212223) RefNo Author(s)
(years) Title Study question Research
method Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
22 Takken T van der Torre P Zwerink M Hulzebos E H Bierings M Helders P J Mamp van der Net J (2009)
Development feasibility and efficacy of a community-based exercise training program in pediatric cancer survivors
To develop a 12-week home-based exercise training program (comprising aerobic and strength exercises) for children who survived ALL and to study itrsquos feasibility and efficacy
Pre-post test design
No comparsion group
Survived ALL(N=9)ages 6-14 years
1anthropometry 2 muscle strength 3functional mobility 4cardio-pulmonary
exercise test 5Fatigue
1 Feasibility questionnaire 2 anthropometry electronic scale and a wallmounted stadiometerHarpenden skin fold calipers 3 muscle strength handheld dynamometer 4functional mobility Timed Up
and Go test (TUG) 5cardio-pulmonary exercise test electronically braked cycle ergometer 6Fatigue(mean)CSI-20 (subjective experience of fatigueconcentrationmotivationphysical activity)
112-week exercise training program
2 Patients were assessed before (T0) and after (T1) 12 weeks of training
1 muscle strength execapacity functional moand fatigue showed nosignificant differences between pre(meanplusmnSD415plusmn147) and post training(meanplusmnSD3687)
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
7 Post-White J Fitzgerald M Savik K Hooke M C Hannahan A B amp Sencer S F (2009)
Massage therapy for children with cancer
To determine whether 4 weekly sessions of massage compared with 4 quiet-time control conditions would reduce anxiety cortisol levels fatigue nausea and pain in children with cancer undergoing chemotherapy and would reduce anxiety fatigue and mood disturbance in a parent
2-period crossover design (Randomized)
quiet-time
control
sessions
Children with cancer 1 to 18 years of age Twenty-three childrenparent dyads were enrolled 17 completed all data points
children 1relaxation 2symptoms 3 fatigue
parents
1anxiety 2 fatigue
children 1relaxation (heart and respiratory rates blood pressure and salivary cortisol level)
2symptoms (pain nausea anxiety 3 fatigue 1-2y3-6yLansky Play Performance Scale (PPS) 7-13y
1 4 weekly massage (MT) sessions alternated with 4 weekly quiet-time(QT) control sessions
2 children included presession and postsession vital signs (heart rate respiratory rate blood pressure) and self-report (parent proxy report for age 1-2 years) of pain nausea and anxiety Fatigue was measured before sessions 1 and 4 and at each follow-up Parent measures
included anxiety fatigue and mood states
1Massage was moreeffective than quiet tireducing heart rate inchildren anxiety in cless than age 14 yeaparent anxiety 2There were no sign
changes in blood pcortisol pain naufatigue (no state d
3 Children reported tmassage helped thebetter lessened theirand worries and hadlasting effects than q
675
44
14-18yChild Fatigue Scale (CFS) (frequency
intensity) 2 parents anxiety and fatigue
676
45
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
24 Hinds P S Hockenberry M Rai S N Zhang L Razzouk B I Cremer L McCarthy K amp Rodriguez-Galindo C (2007)
Clinical field testing of an enhanced-activity intervention in hospitalized children with cancer
To determine the feasibility of an
enhanced physical activity EPA intervention in children and adolescents hospitalized to receive chemotherapy for a solid tumor or AML and to assess the sleep and fatigue outcomes of the intervention using two different statistical approaches to analyze the longitudinal symptom data
randomized prospective two-site and two-group pilot study
Standard care Twenty nine patients (25 with a solid tumor and 4 with AML)ages 7-18 years
1 sleep duration 2 sleep efficiency 3 fatigue
1sleep duration sleep efficiency The
Wrist Actigraph The Daily Sleep Diary-Parent 2 fatigue (mean) The Fatigue Scale(FS-C) for 7-12 (intensity) The Fatigue Scale(FS-A) for 13-18 The Fatigue Scale Parent Version (FS-P) The Fatigue Scale Staff Version (FS-S)
1enhanced physical activity (EPA) (hospital-based 30 minutes
twice daily for 2-4 days) 2 T0On the day of admission
(Day 0 or baseline)patient and parents completed the fatigue instruments and a team member applied the actigraph Patients wore the wrist actigraph T1 from Day 0 to 2 or 3 consecutive days (Days 0e3) In addition the patient same parent and staff nurses completed the daily sleep and fatigue reports in the late afternoons of Days 1-3
1 ANOVA model slesignificantly more the experimental athe control arm whdifferences from bsleep efficiency vaaveraged and com
2 The patient-reported mean fatigue scoresarms were higher amadolescents than for
3 The mixed model anarevealed no significandifferences in patientfatigue between
the two study arms otime( no final result iSD only give mixed result)
677
46
23 Keats M
R amp Culos-Reed S N (2008)
A community-based physical activity program for adolescents with cancer (project TREK) program feasibility and preliminary findings
To examine the
feasibility of a
theoretically-based
physical activity (PA)
intervention in
adolescents with
cancerand
examination of the
impact of the
program on
participant QOL
including social
emotional and
physical
well-being(including fatigue)
Repeat measures longitudinal design
No comparsion group
10 adolescents(Lymphoma(4)leukemia(4)CNS tumor(1)germ cell tumor(1)) ages 14-18 years
1physical fitness 2quality of life (QOL) 3PA behavior 4fatigue
1 Feasibility was assessed by participant recruitment attendance and adherence
2physical fitness Fitnessgram 3quality of life (QOL) Pediatric Quality of Life Inventory (PedsQL) 4PA behavior leisure score index (LSI) 5fatigue (mean) pediatric Quality of life
Multidimensional Fatigue Scale (Peds QL-MFS)
(Generalsleepcognitive fatigue)
116week physical activity (PA)
2 total PA physical fitness and overall QOL was assessed at 5 different intervals T0 preintervention (baseline) T1midintervention (after the
first 8 wk) T2 postintervention
(16 wk) T3 3-months
postintervention T4 1-year poststudy
initiation
1 from baseline -wkssig Improvementstotal PA physfitness and Qgeneral fatigue(meanplusmnSD 796plusmn135)
2 from baseline to 3FUsig Improvin general fatigue(meanplusmnSD824plusmn131)slefatigue(meanplusmnSD755plusmn191)totafatigue(meanplusmnSD778plusmn150)
3at 1 years FUsImprovements in sleeprest fatigue(meanplusmnSD725plusmn203)total (meanplusmnSD 763plusmn
678
47
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
2 Gene R E amp Conk Z (2008)
Impact of Effective Nursing Interventions to the Fatigue Syndrome in Children Who Receive Chemotherapy
1 to examine the effects of an effective nursing intervention to the fatigue syndrome of children 7 to 12 years of age who receive chemotherapy 2Tto examine the relationship between fatigue and demographic variables (age sex) diagnoses ([ALL AML] lymphoma) and therapy-related variables (eg level of hemoglobin
experimental randomized controlled study
Routine nursing care
A total of 60 children who are 7-12 years of age(a new diagnosis of ALL AML or lymphoma and receiving for the first time after being diagnosed a 7- to 10-day chemotherapy treatment )
fatigue The Fatigue Scale(FS-C) for 7-12 (intensity)
The Fatigue Scale Parent Version (FS-P)
1 effective nursing interventions(45- 60mdaya week)education about the fatigue with the chemotherapy and fatigue handbook 2 T1 After a 7-day period the children
and parent were evaluated with the Fatigue Scale
1The difference betwthe 2 mean values wafound to be statisticallsignificant 2 statistically significadifference was found between the Fatigue Scale-Child mean scothe experimental (272the control group (4213)children
679
48
25 Chiang et
al(2007)
The effects of ldquo a home ndashbased aerobic exercise interventionrdquo on fatigue and cardiorespiratory fitness in children with Acute Lymphoblastic Leukemia during the maintenance stage of chemotherapy
To examine the effect of ldquo a home ndashbased aerobic exercise interventionrdquo on fatigue and cardiorespiratory fitness in children with Acute Lymphoblastic Leukemia during the maintenance stage of chemotherapy
Quasi-experi -mental
Routine
nursing care
14 pediatric oncology patients in the experimental group and 10 in control group who were matched by age and sex ages7-18 years
1Cardiorespiratory fitness
2Fatigue
1Cardiorespiratory fitness Physical Activity Recall
VO2maxHR peak 6MWT
2 Fatigue PedsQL-MFS(Generalsleepcognitive fatigue)
1A six-week home-based aerobic exercise intervention 2 8 time points T0 baseline T1-T6 every week during the
intervention(6 weeks) T7 post intervention T8 follow-up (one month after
the end of the home-based exercise program)
1 For intent-to ndash treatthe findings indicated are no intervention efftime differences by anon the subscale of fat2 For per-protocol angeneral fatigue( mean422plusmn402) was the osubscale that was siglower for children whothe exercise interventthose in control groupfollow-up assessmentmonth after the compintervention) 3 The VO2peak are significantly improvingexperimental group atbaseline- and post-intassessment The VO2was significantly highechildren who were in experimental group thcontrol subjects at post-intervention assefor the per-protocol an
680
49
Appendix IV Instrument used to measure fatigue
Name Instrument
developers
Description Used in
age in
ref
Reliability
Consistency of
instrument
Checklist Individual Strength
(CIS)22
Vercoulen et
al1996
20 items using 7-point Likert scale of
fatigue To measure four aspects of
fatiguesubjective experience
contractionmotivation physical
Activity
6-14 Not reported
Child Fatigue Scale (CFS)7 Hockenberry
et al2003
14 items 2 part questionnaire frequency
(yes or no) 5-point Likert scale of the
intensity of any yes responses
7-13
14-18 α073-o84
The Fatigue Scale for 7-12
year Olds (FS-C)224
Hockenberry
et al
14 items provide a fatigue intensity score
5-point Likert scale
7-12 αo84
The Fatigue Scale for 13-18
year Olds (FS-A)24
Hockenberry
et al
14 items provide a fatigue intensity score
5-point Likert scale
13-18 α076-o96
Pediatric Quality of life
Multidimensional Fatigue
Scale (Peds QL-MFS)2325
Varni2002 18 items to measure three aspects of
fatigueGeneralsleepcognitive
14-18 Not reported
681
50
Appendix V Excluded studies and reasons for exclusion
Baggott C Dodd M Kennedy C Marina N Miaskowski C Multiple Symptoms in Pediatric Oncology
Patients A Systematic Review Journal of Pediatric Oncology Nursing 2009 Nov-Dec 27(6)
325-339
Reason for exclusion Not outcome of interest
Barlow JH Ellard DR Psycho-educational interventions for children with chronic disease parents and
siblings an overview of the research evidence base Care Health amp Development 2004 Nov
30(6)637-45
Reason for exclusion Not outcome of interest
Bedider S Moyer CA Randomized controlled trials of pediatric massage A review Evid Based
Complement Alternat Med 2007 Mar 4(1)23-34 Epub 2006 Nov 3
Reason for exclusion Not outcome of interest
de Nijs EJ Ros W Grijpdonck MH Nursing intervention for fatigue during the treatment for cancer Cancer
Nursing 2008 31(3)191-206
Reason for exclusion Not population of interest
Edwards JL Gibson F Richardson A Sepion B Ream E Fatigue in adolescents with and following a
cancer diagnosis developing an evidence base for practice European Journal of Cancer 2003
Dec 39(18)2671-80
Reason for exclusion Not experimental or quasi-experimental study
Hinds PS Hockenberry-Eatan M Developing a research program on fatigue in children and adolescents
diagnosed with cancer Journal of Pediatric Oncology Nursing 2001 Mar-Apr 18(2 Suppl
1)3-12
Reason for exclusion Not experimental or quasi-experimental study
Hockenberry-Eaton M Hinds PS Alcoser P ONeill JB Euell K Howard V Gattuso J Taylor J Fatigue in
Children and Adolescents With Cancer Journal of Pediatric Oncology Nursing 1998 July
15(3)172-182
Reason for exclusion Not experimental or quasi-experimental study
Jean-Pierre P Mustian K Kohli S Roscoe JA Hickok JT Morrow GR Community-based clinical oncology
research trials for cancer-related fatigue The Journal of Supportive Oncology 2006 Nov-Dec
4(10)511-6
682
51
Reason for exclusion Not population of interest
Kangas M Bovbjerg DH Montgomery GH Cancer-Related Fatigue A Systematic and Meta-Analytic
Review of Non-Pharmacological Therapies for Cancer Patients Psychological Bulletin 2008 Sep
134(5)700-41
Reason for exclusion Not population of interest
Lotfi-Jam K Carey M Jefford M Schofield P Charleson C Aranda S Nonpharmacologic strategies for
managing common chemotherapy adverse effects A systematic review Journal of Clinical
Oncology 2008 Dec 1 26(34)5618-29 Epub 2008 Nov 3
Reason for exclusion Not outcome of interest
Marchese VG Chiarello LA Lange BJ Effects of physical therapy intervention for children with acute
lymphoblastic leukemia Pediatr Blood Cancer 2004 Feb42(2)127-33
Reason for exclusion Not outcome of interest
Meeske KA Siegel SE Globe DR Mack WJ Bernstein L Prevalence and correlates of fatigue in
long-term survivors of childhood leukemia Journal of Clinical Oncology 2005 Aug 20
23(24)5501-10
Reason for exclusion Not intervention study
Minton O Richardson A Sharpe M Hotopf Stone P A systematic review and meta-analysis of the
pharmacological treatment of cancer-related fatigue J Natl Cancer Inst 2008 Aug 20
100(16)1155-66 Epub 2008 Aug 11
Reason for exclusion Not population and intervention of interest
Mustian KM Morrow GR Carroll JK Figueroa-Moseley CD Pascal JP Williams GC Integrative
nonpharmacologic behavioral interventions for the management of Cancer-Related fatigue The
Oncologist 2007 12(1)52-67
Reason for exclusion Not population of interest
Neill J Belan I Ried K Effectiveness of non-pharmacological interventions for fatigue in adults with
multiple sclerosis rheumatoid arthritis or systemic lupus erythematosus a systematic review
Journal of Advanced Nursing 2006 Dec 56(6)617-35
Reason for exclusion Not population of interest
Rheingans JI A systematic review of nonpharmacologic adjunctive therapies for symptom management
Journal of Pediatric Oncology Nursing 2007 24(2) 81-94
683
52
Reason for exclusion Not outcome of interest
Rheingans JI Pediatric oncology nursesrsquo management of patients symptoms Journal of Pediatric
Oncology Nursing 2008 Nov 25(6) 303-11
Reason for exclusion Not outcome of interest
San Juan AF Fleck SJ Chamorro-Vintildea C Mateacute-Muntildeoz JL Moral S Peacuterez M Cardona C Del Valle MF
Hernaacutendez M Ramiacuterez M Madero L Lucia A Effects of an intrahospital exercise program
intervention for children with leukemia Medicine amp Science in Sports amp Exercise 2007 Jan
39(1)13-21
Reason for exclusion Not outcome of interest
Sanford SD Okuma JO Pan J Srivastava DK West N Farr L Hinds PS Gender differences in sleep
fatigue and daytime activity in a pediatric oncology sample receiving dexamethasone Journal of
Pediatric Psychology 2008 Apr 33(3)298-306 Epub 2007 Nov 17
Reason for exclusion Not experimental or quasi-experimental study
Schmitz KH Holtzman J Courneya KS Macircsse LC Duval S Kane R Controlled physical activity trials in
cancer survivors a systematic review and meta-analysis Cancer Epidemiol Biomarkers Prev
2005 Jul 14(7)1588-95
Reason for exclusion Not population of interest
van Brussel M Takken T Lucia A van der Net J Helders PJ Is physical fitness decreased in survivors of
childhood leukemia A systematic review Leukemia 2005 Jan 19(1)13-7
Reason for exclusion Not population of interest
Whiting P Bagnall AM Snowden AJ Cornell JE Mulrow CD Ramirez G Interventions for the treatment
and management of chronic fatigue syndrome JAMA 2001 Sep 19 286(11)1360-8
Reason for exclusion Not intervention of interest
Whitsett SF Gudmundsdottir M Davies B McCarthy P Friedman D Chemotherapy-related fatigue in
childhood cancer correlates consequences and coping strategies Journal of Pediatric
Oncology Nursing 2008 Mar-Apr 25(2)86-96 Epub 2008 Feb 29
Reason for exclusion Not experimental or quasi-experimental study
Winner C Muumlller C Hoffmann C Boos J Rosenbaum D Physical activity and childhood cancer Pediatr
Blood Cancer 2010 Apr 54(4)501-10
Reason for exclusion Not research study
684
53
Wu M Hsu L Zhang B Shen N Lu H Li S The experiences of cancer-related fatigue among Chinese
children with leukaemia A phenomenological study Journal of Nursing Studies 2010 Jan
47(1)49-59 Epub 2009 Aug 25
Reason for exclusion Not experimental or quasi-experimental study
Yeh CH Chiang YC Lin L Yang CP Chien LC Weaver MA Chuang HL Clinical factors associated with
fatigue over time in paediatric oncology patients receiving chemotherapy British Journal of
Cancer 2008 Jul 8 99(1)23-9 Epub 2008 Jun 24
Reason for exclusion Not experimental or quasi-experimental study
685
44
14-18yChild Fatigue Scale (CFS) (frequency
intensity) 2 parents anxiety and fatigue
676
45
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
24 Hinds P S Hockenberry M Rai S N Zhang L Razzouk B I Cremer L McCarthy K amp Rodriguez-Galindo C (2007)
Clinical field testing of an enhanced-activity intervention in hospitalized children with cancer
To determine the feasibility of an
enhanced physical activity EPA intervention in children and adolescents hospitalized to receive chemotherapy for a solid tumor or AML and to assess the sleep and fatigue outcomes of the intervention using two different statistical approaches to analyze the longitudinal symptom data
randomized prospective two-site and two-group pilot study
Standard care Twenty nine patients (25 with a solid tumor and 4 with AML)ages 7-18 years
1 sleep duration 2 sleep efficiency 3 fatigue
1sleep duration sleep efficiency The
Wrist Actigraph The Daily Sleep Diary-Parent 2 fatigue (mean) The Fatigue Scale(FS-C) for 7-12 (intensity) The Fatigue Scale(FS-A) for 13-18 The Fatigue Scale Parent Version (FS-P) The Fatigue Scale Staff Version (FS-S)
1enhanced physical activity (EPA) (hospital-based 30 minutes
twice daily for 2-4 days) 2 T0On the day of admission
(Day 0 or baseline)patient and parents completed the fatigue instruments and a team member applied the actigraph Patients wore the wrist actigraph T1 from Day 0 to 2 or 3 consecutive days (Days 0e3) In addition the patient same parent and staff nurses completed the daily sleep and fatigue reports in the late afternoons of Days 1-3
1 ANOVA model slesignificantly more the experimental athe control arm whdifferences from bsleep efficiency vaaveraged and com
2 The patient-reported mean fatigue scoresarms were higher amadolescents than for
3 The mixed model anarevealed no significandifferences in patientfatigue between
the two study arms otime( no final result iSD only give mixed result)
677
46
23 Keats M
R amp Culos-Reed S N (2008)
A community-based physical activity program for adolescents with cancer (project TREK) program feasibility and preliminary findings
To examine the
feasibility of a
theoretically-based
physical activity (PA)
intervention in
adolescents with
cancerand
examination of the
impact of the
program on
participant QOL
including social
emotional and
physical
well-being(including fatigue)
Repeat measures longitudinal design
No comparsion group
10 adolescents(Lymphoma(4)leukemia(4)CNS tumor(1)germ cell tumor(1)) ages 14-18 years
1physical fitness 2quality of life (QOL) 3PA behavior 4fatigue
1 Feasibility was assessed by participant recruitment attendance and adherence
2physical fitness Fitnessgram 3quality of life (QOL) Pediatric Quality of Life Inventory (PedsQL) 4PA behavior leisure score index (LSI) 5fatigue (mean) pediatric Quality of life
Multidimensional Fatigue Scale (Peds QL-MFS)
(Generalsleepcognitive fatigue)
116week physical activity (PA)
2 total PA physical fitness and overall QOL was assessed at 5 different intervals T0 preintervention (baseline) T1midintervention (after the
first 8 wk) T2 postintervention
(16 wk) T3 3-months
postintervention T4 1-year poststudy
initiation
1 from baseline -wkssig Improvementstotal PA physfitness and Qgeneral fatigue(meanplusmnSD 796plusmn135)
2 from baseline to 3FUsig Improvin general fatigue(meanplusmnSD824plusmn131)slefatigue(meanplusmnSD755plusmn191)totafatigue(meanplusmnSD778plusmn150)
3at 1 years FUsImprovements in sleeprest fatigue(meanplusmnSD725plusmn203)total (meanplusmnSD 763plusmn
678
47
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
2 Gene R E amp Conk Z (2008)
Impact of Effective Nursing Interventions to the Fatigue Syndrome in Children Who Receive Chemotherapy
1 to examine the effects of an effective nursing intervention to the fatigue syndrome of children 7 to 12 years of age who receive chemotherapy 2Tto examine the relationship between fatigue and demographic variables (age sex) diagnoses ([ALL AML] lymphoma) and therapy-related variables (eg level of hemoglobin
experimental randomized controlled study
Routine nursing care
A total of 60 children who are 7-12 years of age(a new diagnosis of ALL AML or lymphoma and receiving for the first time after being diagnosed a 7- to 10-day chemotherapy treatment )
fatigue The Fatigue Scale(FS-C) for 7-12 (intensity)
The Fatigue Scale Parent Version (FS-P)
1 effective nursing interventions(45- 60mdaya week)education about the fatigue with the chemotherapy and fatigue handbook 2 T1 After a 7-day period the children
and parent were evaluated with the Fatigue Scale
1The difference betwthe 2 mean values wafound to be statisticallsignificant 2 statistically significadifference was found between the Fatigue Scale-Child mean scothe experimental (272the control group (4213)children
679
48
25 Chiang et
al(2007)
The effects of ldquo a home ndashbased aerobic exercise interventionrdquo on fatigue and cardiorespiratory fitness in children with Acute Lymphoblastic Leukemia during the maintenance stage of chemotherapy
To examine the effect of ldquo a home ndashbased aerobic exercise interventionrdquo on fatigue and cardiorespiratory fitness in children with Acute Lymphoblastic Leukemia during the maintenance stage of chemotherapy
Quasi-experi -mental
Routine
nursing care
14 pediatric oncology patients in the experimental group and 10 in control group who were matched by age and sex ages7-18 years
1Cardiorespiratory fitness
2Fatigue
1Cardiorespiratory fitness Physical Activity Recall
VO2maxHR peak 6MWT
2 Fatigue PedsQL-MFS(Generalsleepcognitive fatigue)
1A six-week home-based aerobic exercise intervention 2 8 time points T0 baseline T1-T6 every week during the
intervention(6 weeks) T7 post intervention T8 follow-up (one month after
the end of the home-based exercise program)
1 For intent-to ndash treatthe findings indicated are no intervention efftime differences by anon the subscale of fat2 For per-protocol angeneral fatigue( mean422plusmn402) was the osubscale that was siglower for children whothe exercise interventthose in control groupfollow-up assessmentmonth after the compintervention) 3 The VO2peak are significantly improvingexperimental group atbaseline- and post-intassessment The VO2was significantly highechildren who were in experimental group thcontrol subjects at post-intervention assefor the per-protocol an
680
49
Appendix IV Instrument used to measure fatigue
Name Instrument
developers
Description Used in
age in
ref
Reliability
Consistency of
instrument
Checklist Individual Strength
(CIS)22
Vercoulen et
al1996
20 items using 7-point Likert scale of
fatigue To measure four aspects of
fatiguesubjective experience
contractionmotivation physical
Activity
6-14 Not reported
Child Fatigue Scale (CFS)7 Hockenberry
et al2003
14 items 2 part questionnaire frequency
(yes or no) 5-point Likert scale of the
intensity of any yes responses
7-13
14-18 α073-o84
The Fatigue Scale for 7-12
year Olds (FS-C)224
Hockenberry
et al
14 items provide a fatigue intensity score
5-point Likert scale
7-12 αo84
The Fatigue Scale for 13-18
year Olds (FS-A)24
Hockenberry
et al
14 items provide a fatigue intensity score
5-point Likert scale
13-18 α076-o96
Pediatric Quality of life
Multidimensional Fatigue
Scale (Peds QL-MFS)2325
Varni2002 18 items to measure three aspects of
fatigueGeneralsleepcognitive
14-18 Not reported
681
50
Appendix V Excluded studies and reasons for exclusion
Baggott C Dodd M Kennedy C Marina N Miaskowski C Multiple Symptoms in Pediatric Oncology
Patients A Systematic Review Journal of Pediatric Oncology Nursing 2009 Nov-Dec 27(6)
325-339
Reason for exclusion Not outcome of interest
Barlow JH Ellard DR Psycho-educational interventions for children with chronic disease parents and
siblings an overview of the research evidence base Care Health amp Development 2004 Nov
30(6)637-45
Reason for exclusion Not outcome of interest
Bedider S Moyer CA Randomized controlled trials of pediatric massage A review Evid Based
Complement Alternat Med 2007 Mar 4(1)23-34 Epub 2006 Nov 3
Reason for exclusion Not outcome of interest
de Nijs EJ Ros W Grijpdonck MH Nursing intervention for fatigue during the treatment for cancer Cancer
Nursing 2008 31(3)191-206
Reason for exclusion Not population of interest
Edwards JL Gibson F Richardson A Sepion B Ream E Fatigue in adolescents with and following a
cancer diagnosis developing an evidence base for practice European Journal of Cancer 2003
Dec 39(18)2671-80
Reason for exclusion Not experimental or quasi-experimental study
Hinds PS Hockenberry-Eatan M Developing a research program on fatigue in children and adolescents
diagnosed with cancer Journal of Pediatric Oncology Nursing 2001 Mar-Apr 18(2 Suppl
1)3-12
Reason for exclusion Not experimental or quasi-experimental study
Hockenberry-Eaton M Hinds PS Alcoser P ONeill JB Euell K Howard V Gattuso J Taylor J Fatigue in
Children and Adolescents With Cancer Journal of Pediatric Oncology Nursing 1998 July
15(3)172-182
Reason for exclusion Not experimental or quasi-experimental study
Jean-Pierre P Mustian K Kohli S Roscoe JA Hickok JT Morrow GR Community-based clinical oncology
research trials for cancer-related fatigue The Journal of Supportive Oncology 2006 Nov-Dec
4(10)511-6
682
51
Reason for exclusion Not population of interest
Kangas M Bovbjerg DH Montgomery GH Cancer-Related Fatigue A Systematic and Meta-Analytic
Review of Non-Pharmacological Therapies for Cancer Patients Psychological Bulletin 2008 Sep
134(5)700-41
Reason for exclusion Not population of interest
Lotfi-Jam K Carey M Jefford M Schofield P Charleson C Aranda S Nonpharmacologic strategies for
managing common chemotherapy adverse effects A systematic review Journal of Clinical
Oncology 2008 Dec 1 26(34)5618-29 Epub 2008 Nov 3
Reason for exclusion Not outcome of interest
Marchese VG Chiarello LA Lange BJ Effects of physical therapy intervention for children with acute
lymphoblastic leukemia Pediatr Blood Cancer 2004 Feb42(2)127-33
Reason for exclusion Not outcome of interest
Meeske KA Siegel SE Globe DR Mack WJ Bernstein L Prevalence and correlates of fatigue in
long-term survivors of childhood leukemia Journal of Clinical Oncology 2005 Aug 20
23(24)5501-10
Reason for exclusion Not intervention study
Minton O Richardson A Sharpe M Hotopf Stone P A systematic review and meta-analysis of the
pharmacological treatment of cancer-related fatigue J Natl Cancer Inst 2008 Aug 20
100(16)1155-66 Epub 2008 Aug 11
Reason for exclusion Not population and intervention of interest
Mustian KM Morrow GR Carroll JK Figueroa-Moseley CD Pascal JP Williams GC Integrative
nonpharmacologic behavioral interventions for the management of Cancer-Related fatigue The
Oncologist 2007 12(1)52-67
Reason for exclusion Not population of interest
Neill J Belan I Ried K Effectiveness of non-pharmacological interventions for fatigue in adults with
multiple sclerosis rheumatoid arthritis or systemic lupus erythematosus a systematic review
Journal of Advanced Nursing 2006 Dec 56(6)617-35
Reason for exclusion Not population of interest
Rheingans JI A systematic review of nonpharmacologic adjunctive therapies for symptom management
Journal of Pediatric Oncology Nursing 2007 24(2) 81-94
683
52
Reason for exclusion Not outcome of interest
Rheingans JI Pediatric oncology nursesrsquo management of patients symptoms Journal of Pediatric
Oncology Nursing 2008 Nov 25(6) 303-11
Reason for exclusion Not outcome of interest
San Juan AF Fleck SJ Chamorro-Vintildea C Mateacute-Muntildeoz JL Moral S Peacuterez M Cardona C Del Valle MF
Hernaacutendez M Ramiacuterez M Madero L Lucia A Effects of an intrahospital exercise program
intervention for children with leukemia Medicine amp Science in Sports amp Exercise 2007 Jan
39(1)13-21
Reason for exclusion Not outcome of interest
Sanford SD Okuma JO Pan J Srivastava DK West N Farr L Hinds PS Gender differences in sleep
fatigue and daytime activity in a pediatric oncology sample receiving dexamethasone Journal of
Pediatric Psychology 2008 Apr 33(3)298-306 Epub 2007 Nov 17
Reason for exclusion Not experimental or quasi-experimental study
Schmitz KH Holtzman J Courneya KS Macircsse LC Duval S Kane R Controlled physical activity trials in
cancer survivors a systematic review and meta-analysis Cancer Epidemiol Biomarkers Prev
2005 Jul 14(7)1588-95
Reason for exclusion Not population of interest
van Brussel M Takken T Lucia A van der Net J Helders PJ Is physical fitness decreased in survivors of
childhood leukemia A systematic review Leukemia 2005 Jan 19(1)13-7
Reason for exclusion Not population of interest
Whiting P Bagnall AM Snowden AJ Cornell JE Mulrow CD Ramirez G Interventions for the treatment
and management of chronic fatigue syndrome JAMA 2001 Sep 19 286(11)1360-8
Reason for exclusion Not intervention of interest
Whitsett SF Gudmundsdottir M Davies B McCarthy P Friedman D Chemotherapy-related fatigue in
childhood cancer correlates consequences and coping strategies Journal of Pediatric
Oncology Nursing 2008 Mar-Apr 25(2)86-96 Epub 2008 Feb 29
Reason for exclusion Not experimental or quasi-experimental study
Winner C Muumlller C Hoffmann C Boos J Rosenbaum D Physical activity and childhood cancer Pediatr
Blood Cancer 2010 Apr 54(4)501-10
Reason for exclusion Not research study
684
53
Wu M Hsu L Zhang B Shen N Lu H Li S The experiences of cancer-related fatigue among Chinese
children with leukaemia A phenomenological study Journal of Nursing Studies 2010 Jan
47(1)49-59 Epub 2009 Aug 25
Reason for exclusion Not experimental or quasi-experimental study
Yeh CH Chiang YC Lin L Yang CP Chien LC Weaver MA Chuang HL Clinical factors associated with
fatigue over time in paediatric oncology patients receiving chemotherapy British Journal of
Cancer 2008 Jul 8 99(1)23-9 Epub 2008 Jun 24
Reason for exclusion Not experimental or quasi-experimental study
685
45
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling
Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
24 Hinds P S Hockenberry M Rai S N Zhang L Razzouk B I Cremer L McCarthy K amp Rodriguez-Galindo C (2007)
Clinical field testing of an enhanced-activity intervention in hospitalized children with cancer
To determine the feasibility of an
enhanced physical activity EPA intervention in children and adolescents hospitalized to receive chemotherapy for a solid tumor or AML and to assess the sleep and fatigue outcomes of the intervention using two different statistical approaches to analyze the longitudinal symptom data
randomized prospective two-site and two-group pilot study
Standard care Twenty nine patients (25 with a solid tumor and 4 with AML)ages 7-18 years
1 sleep duration 2 sleep efficiency 3 fatigue
1sleep duration sleep efficiency The
Wrist Actigraph The Daily Sleep Diary-Parent 2 fatigue (mean) The Fatigue Scale(FS-C) for 7-12 (intensity) The Fatigue Scale(FS-A) for 13-18 The Fatigue Scale Parent Version (FS-P) The Fatigue Scale Staff Version (FS-S)
1enhanced physical activity (EPA) (hospital-based 30 minutes
twice daily for 2-4 days) 2 T0On the day of admission
(Day 0 or baseline)patient and parents completed the fatigue instruments and a team member applied the actigraph Patients wore the wrist actigraph T1 from Day 0 to 2 or 3 consecutive days (Days 0e3) In addition the patient same parent and staff nurses completed the daily sleep and fatigue reports in the late afternoons of Days 1-3
1 ANOVA model slesignificantly more the experimental athe control arm whdifferences from bsleep efficiency vaaveraged and com
2 The patient-reported mean fatigue scoresarms were higher amadolescents than for
3 The mixed model anarevealed no significandifferences in patientfatigue between
the two study arms otime( no final result iSD only give mixed result)
677
46
23 Keats M
R amp Culos-Reed S N (2008)
A community-based physical activity program for adolescents with cancer (project TREK) program feasibility and preliminary findings
To examine the
feasibility of a
theoretically-based
physical activity (PA)
intervention in
adolescents with
cancerand
examination of the
impact of the
program on
participant QOL
including social
emotional and
physical
well-being(including fatigue)
Repeat measures longitudinal design
No comparsion group
10 adolescents(Lymphoma(4)leukemia(4)CNS tumor(1)germ cell tumor(1)) ages 14-18 years
1physical fitness 2quality of life (QOL) 3PA behavior 4fatigue
1 Feasibility was assessed by participant recruitment attendance and adherence
2physical fitness Fitnessgram 3quality of life (QOL) Pediatric Quality of Life Inventory (PedsQL) 4PA behavior leisure score index (LSI) 5fatigue (mean) pediatric Quality of life
Multidimensional Fatigue Scale (Peds QL-MFS)
(Generalsleepcognitive fatigue)
116week physical activity (PA)
2 total PA physical fitness and overall QOL was assessed at 5 different intervals T0 preintervention (baseline) T1midintervention (after the
first 8 wk) T2 postintervention
(16 wk) T3 3-months
postintervention T4 1-year poststudy
initiation
1 from baseline -wkssig Improvementstotal PA physfitness and Qgeneral fatigue(meanplusmnSD 796plusmn135)
2 from baseline to 3FUsig Improvin general fatigue(meanplusmnSD824plusmn131)slefatigue(meanplusmnSD755plusmn191)totafatigue(meanplusmnSD778plusmn150)
3at 1 years FUsImprovements in sleeprest fatigue(meanplusmnSD725plusmn203)total (meanplusmnSD 763plusmn
678
47
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
2 Gene R E amp Conk Z (2008)
Impact of Effective Nursing Interventions to the Fatigue Syndrome in Children Who Receive Chemotherapy
1 to examine the effects of an effective nursing intervention to the fatigue syndrome of children 7 to 12 years of age who receive chemotherapy 2Tto examine the relationship between fatigue and demographic variables (age sex) diagnoses ([ALL AML] lymphoma) and therapy-related variables (eg level of hemoglobin
experimental randomized controlled study
Routine nursing care
A total of 60 children who are 7-12 years of age(a new diagnosis of ALL AML or lymphoma and receiving for the first time after being diagnosed a 7- to 10-day chemotherapy treatment )
fatigue The Fatigue Scale(FS-C) for 7-12 (intensity)
The Fatigue Scale Parent Version (FS-P)
1 effective nursing interventions(45- 60mdaya week)education about the fatigue with the chemotherapy and fatigue handbook 2 T1 After a 7-day period the children
and parent were evaluated with the Fatigue Scale
1The difference betwthe 2 mean values wafound to be statisticallsignificant 2 statistically significadifference was found between the Fatigue Scale-Child mean scothe experimental (272the control group (4213)children
679
48
25 Chiang et
al(2007)
The effects of ldquo a home ndashbased aerobic exercise interventionrdquo on fatigue and cardiorespiratory fitness in children with Acute Lymphoblastic Leukemia during the maintenance stage of chemotherapy
To examine the effect of ldquo a home ndashbased aerobic exercise interventionrdquo on fatigue and cardiorespiratory fitness in children with Acute Lymphoblastic Leukemia during the maintenance stage of chemotherapy
Quasi-experi -mental
Routine
nursing care
14 pediatric oncology patients in the experimental group and 10 in control group who were matched by age and sex ages7-18 years
1Cardiorespiratory fitness
2Fatigue
1Cardiorespiratory fitness Physical Activity Recall
VO2maxHR peak 6MWT
2 Fatigue PedsQL-MFS(Generalsleepcognitive fatigue)
1A six-week home-based aerobic exercise intervention 2 8 time points T0 baseline T1-T6 every week during the
intervention(6 weeks) T7 post intervention T8 follow-up (one month after
the end of the home-based exercise program)
1 For intent-to ndash treatthe findings indicated are no intervention efftime differences by anon the subscale of fat2 For per-protocol angeneral fatigue( mean422plusmn402) was the osubscale that was siglower for children whothe exercise interventthose in control groupfollow-up assessmentmonth after the compintervention) 3 The VO2peak are significantly improvingexperimental group atbaseline- and post-intassessment The VO2was significantly highechildren who were in experimental group thcontrol subjects at post-intervention assefor the per-protocol an
680
49
Appendix IV Instrument used to measure fatigue
Name Instrument
developers
Description Used in
age in
ref
Reliability
Consistency of
instrument
Checklist Individual Strength
(CIS)22
Vercoulen et
al1996
20 items using 7-point Likert scale of
fatigue To measure four aspects of
fatiguesubjective experience
contractionmotivation physical
Activity
6-14 Not reported
Child Fatigue Scale (CFS)7 Hockenberry
et al2003
14 items 2 part questionnaire frequency
(yes or no) 5-point Likert scale of the
intensity of any yes responses
7-13
14-18 α073-o84
The Fatigue Scale for 7-12
year Olds (FS-C)224
Hockenberry
et al
14 items provide a fatigue intensity score
5-point Likert scale
7-12 αo84
The Fatigue Scale for 13-18
year Olds (FS-A)24
Hockenberry
et al
14 items provide a fatigue intensity score
5-point Likert scale
13-18 α076-o96
Pediatric Quality of life
Multidimensional Fatigue
Scale (Peds QL-MFS)2325
Varni2002 18 items to measure three aspects of
fatigueGeneralsleepcognitive
14-18 Not reported
681
50
Appendix V Excluded studies and reasons for exclusion
Baggott C Dodd M Kennedy C Marina N Miaskowski C Multiple Symptoms in Pediatric Oncology
Patients A Systematic Review Journal of Pediatric Oncology Nursing 2009 Nov-Dec 27(6)
325-339
Reason for exclusion Not outcome of interest
Barlow JH Ellard DR Psycho-educational interventions for children with chronic disease parents and
siblings an overview of the research evidence base Care Health amp Development 2004 Nov
30(6)637-45
Reason for exclusion Not outcome of interest
Bedider S Moyer CA Randomized controlled trials of pediatric massage A review Evid Based
Complement Alternat Med 2007 Mar 4(1)23-34 Epub 2006 Nov 3
Reason for exclusion Not outcome of interest
de Nijs EJ Ros W Grijpdonck MH Nursing intervention for fatigue during the treatment for cancer Cancer
Nursing 2008 31(3)191-206
Reason for exclusion Not population of interest
Edwards JL Gibson F Richardson A Sepion B Ream E Fatigue in adolescents with and following a
cancer diagnosis developing an evidence base for practice European Journal of Cancer 2003
Dec 39(18)2671-80
Reason for exclusion Not experimental or quasi-experimental study
Hinds PS Hockenberry-Eatan M Developing a research program on fatigue in children and adolescents
diagnosed with cancer Journal of Pediatric Oncology Nursing 2001 Mar-Apr 18(2 Suppl
1)3-12
Reason for exclusion Not experimental or quasi-experimental study
Hockenberry-Eaton M Hinds PS Alcoser P ONeill JB Euell K Howard V Gattuso J Taylor J Fatigue in
Children and Adolescents With Cancer Journal of Pediatric Oncology Nursing 1998 July
15(3)172-182
Reason for exclusion Not experimental or quasi-experimental study
Jean-Pierre P Mustian K Kohli S Roscoe JA Hickok JT Morrow GR Community-based clinical oncology
research trials for cancer-related fatigue The Journal of Supportive Oncology 2006 Nov-Dec
4(10)511-6
682
51
Reason for exclusion Not population of interest
Kangas M Bovbjerg DH Montgomery GH Cancer-Related Fatigue A Systematic and Meta-Analytic
Review of Non-Pharmacological Therapies for Cancer Patients Psychological Bulletin 2008 Sep
134(5)700-41
Reason for exclusion Not population of interest
Lotfi-Jam K Carey M Jefford M Schofield P Charleson C Aranda S Nonpharmacologic strategies for
managing common chemotherapy adverse effects A systematic review Journal of Clinical
Oncology 2008 Dec 1 26(34)5618-29 Epub 2008 Nov 3
Reason for exclusion Not outcome of interest
Marchese VG Chiarello LA Lange BJ Effects of physical therapy intervention for children with acute
lymphoblastic leukemia Pediatr Blood Cancer 2004 Feb42(2)127-33
Reason for exclusion Not outcome of interest
Meeske KA Siegel SE Globe DR Mack WJ Bernstein L Prevalence and correlates of fatigue in
long-term survivors of childhood leukemia Journal of Clinical Oncology 2005 Aug 20
23(24)5501-10
Reason for exclusion Not intervention study
Minton O Richardson A Sharpe M Hotopf Stone P A systematic review and meta-analysis of the
pharmacological treatment of cancer-related fatigue J Natl Cancer Inst 2008 Aug 20
100(16)1155-66 Epub 2008 Aug 11
Reason for exclusion Not population and intervention of interest
Mustian KM Morrow GR Carroll JK Figueroa-Moseley CD Pascal JP Williams GC Integrative
nonpharmacologic behavioral interventions for the management of Cancer-Related fatigue The
Oncologist 2007 12(1)52-67
Reason for exclusion Not population of interest
Neill J Belan I Ried K Effectiveness of non-pharmacological interventions for fatigue in adults with
multiple sclerosis rheumatoid arthritis or systemic lupus erythematosus a systematic review
Journal of Advanced Nursing 2006 Dec 56(6)617-35
Reason for exclusion Not population of interest
Rheingans JI A systematic review of nonpharmacologic adjunctive therapies for symptom management
Journal of Pediatric Oncology Nursing 2007 24(2) 81-94
683
52
Reason for exclusion Not outcome of interest
Rheingans JI Pediatric oncology nursesrsquo management of patients symptoms Journal of Pediatric
Oncology Nursing 2008 Nov 25(6) 303-11
Reason for exclusion Not outcome of interest
San Juan AF Fleck SJ Chamorro-Vintildea C Mateacute-Muntildeoz JL Moral S Peacuterez M Cardona C Del Valle MF
Hernaacutendez M Ramiacuterez M Madero L Lucia A Effects of an intrahospital exercise program
intervention for children with leukemia Medicine amp Science in Sports amp Exercise 2007 Jan
39(1)13-21
Reason for exclusion Not outcome of interest
Sanford SD Okuma JO Pan J Srivastava DK West N Farr L Hinds PS Gender differences in sleep
fatigue and daytime activity in a pediatric oncology sample receiving dexamethasone Journal of
Pediatric Psychology 2008 Apr 33(3)298-306 Epub 2007 Nov 17
Reason for exclusion Not experimental or quasi-experimental study
Schmitz KH Holtzman J Courneya KS Macircsse LC Duval S Kane R Controlled physical activity trials in
cancer survivors a systematic review and meta-analysis Cancer Epidemiol Biomarkers Prev
2005 Jul 14(7)1588-95
Reason for exclusion Not population of interest
van Brussel M Takken T Lucia A van der Net J Helders PJ Is physical fitness decreased in survivors of
childhood leukemia A systematic review Leukemia 2005 Jan 19(1)13-7
Reason for exclusion Not population of interest
Whiting P Bagnall AM Snowden AJ Cornell JE Mulrow CD Ramirez G Interventions for the treatment
and management of chronic fatigue syndrome JAMA 2001 Sep 19 286(11)1360-8
Reason for exclusion Not intervention of interest
Whitsett SF Gudmundsdottir M Davies B McCarthy P Friedman D Chemotherapy-related fatigue in
childhood cancer correlates consequences and coping strategies Journal of Pediatric
Oncology Nursing 2008 Mar-Apr 25(2)86-96 Epub 2008 Feb 29
Reason for exclusion Not experimental or quasi-experimental study
Winner C Muumlller C Hoffmann C Boos J Rosenbaum D Physical activity and childhood cancer Pediatr
Blood Cancer 2010 Apr 54(4)501-10
Reason for exclusion Not research study
684
53
Wu M Hsu L Zhang B Shen N Lu H Li S The experiences of cancer-related fatigue among Chinese
children with leukaemia A phenomenological study Journal of Nursing Studies 2010 Jan
47(1)49-59 Epub 2009 Aug 25
Reason for exclusion Not experimental or quasi-experimental study
Yeh CH Chiang YC Lin L Yang CP Chien LC Weaver MA Chuang HL Clinical factors associated with
fatigue over time in paediatric oncology patients receiving chemotherapy British Journal of
Cancer 2008 Jul 8 99(1)23-9 Epub 2008 Jun 24
Reason for exclusion Not experimental or quasi-experimental study
685
46
23 Keats M
R amp Culos-Reed S N (2008)
A community-based physical activity program for adolescents with cancer (project TREK) program feasibility and preliminary findings
To examine the
feasibility of a
theoretically-based
physical activity (PA)
intervention in
adolescents with
cancerand
examination of the
impact of the
program on
participant QOL
including social
emotional and
physical
well-being(including fatigue)
Repeat measures longitudinal design
No comparsion group
10 adolescents(Lymphoma(4)leukemia(4)CNS tumor(1)germ cell tumor(1)) ages 14-18 years
1physical fitness 2quality of life (QOL) 3PA behavior 4fatigue
1 Feasibility was assessed by participant recruitment attendance and adherence
2physical fitness Fitnessgram 3quality of life (QOL) Pediatric Quality of Life Inventory (PedsQL) 4PA behavior leisure score index (LSI) 5fatigue (mean) pediatric Quality of life
Multidimensional Fatigue Scale (Peds QL-MFS)
(Generalsleepcognitive fatigue)
116week physical activity (PA)
2 total PA physical fitness and overall QOL was assessed at 5 different intervals T0 preintervention (baseline) T1midintervention (after the
first 8 wk) T2 postintervention
(16 wk) T3 3-months
postintervention T4 1-year poststudy
initiation
1 from baseline -wkssig Improvementstotal PA physfitness and Qgeneral fatigue(meanplusmnSD 796plusmn135)
2 from baseline to 3FUsig Improvin general fatigue(meanplusmnSD824plusmn131)slefatigue(meanplusmnSD755plusmn191)totafatigue(meanplusmnSD778plusmn150)
3at 1 years FUsImprovements in sleeprest fatigue(meanplusmnSD725plusmn203)total (meanplusmnSD 763plusmn
678
47
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
2 Gene R E amp Conk Z (2008)
Impact of Effective Nursing Interventions to the Fatigue Syndrome in Children Who Receive Chemotherapy
1 to examine the effects of an effective nursing intervention to the fatigue syndrome of children 7 to 12 years of age who receive chemotherapy 2Tto examine the relationship between fatigue and demographic variables (age sex) diagnoses ([ALL AML] lymphoma) and therapy-related variables (eg level of hemoglobin
experimental randomized controlled study
Routine nursing care
A total of 60 children who are 7-12 years of age(a new diagnosis of ALL AML or lymphoma and receiving for the first time after being diagnosed a 7- to 10-day chemotherapy treatment )
fatigue The Fatigue Scale(FS-C) for 7-12 (intensity)
The Fatigue Scale Parent Version (FS-P)
1 effective nursing interventions(45- 60mdaya week)education about the fatigue with the chemotherapy and fatigue handbook 2 T1 After a 7-day period the children
and parent were evaluated with the Fatigue Scale
1The difference betwthe 2 mean values wafound to be statisticallsignificant 2 statistically significadifference was found between the Fatigue Scale-Child mean scothe experimental (272the control group (4213)children
679
48
25 Chiang et
al(2007)
The effects of ldquo a home ndashbased aerobic exercise interventionrdquo on fatigue and cardiorespiratory fitness in children with Acute Lymphoblastic Leukemia during the maintenance stage of chemotherapy
To examine the effect of ldquo a home ndashbased aerobic exercise interventionrdquo on fatigue and cardiorespiratory fitness in children with Acute Lymphoblastic Leukemia during the maintenance stage of chemotherapy
Quasi-experi -mental
Routine
nursing care
14 pediatric oncology patients in the experimental group and 10 in control group who were matched by age and sex ages7-18 years
1Cardiorespiratory fitness
2Fatigue
1Cardiorespiratory fitness Physical Activity Recall
VO2maxHR peak 6MWT
2 Fatigue PedsQL-MFS(Generalsleepcognitive fatigue)
1A six-week home-based aerobic exercise intervention 2 8 time points T0 baseline T1-T6 every week during the
intervention(6 weeks) T7 post intervention T8 follow-up (one month after
the end of the home-based exercise program)
1 For intent-to ndash treatthe findings indicated are no intervention efftime differences by anon the subscale of fat2 For per-protocol angeneral fatigue( mean422plusmn402) was the osubscale that was siglower for children whothe exercise interventthose in control groupfollow-up assessmentmonth after the compintervention) 3 The VO2peak are significantly improvingexperimental group atbaseline- and post-intassessment The VO2was significantly highechildren who were in experimental group thcontrol subjects at post-intervention assefor the per-protocol an
680
49
Appendix IV Instrument used to measure fatigue
Name Instrument
developers
Description Used in
age in
ref
Reliability
Consistency of
instrument
Checklist Individual Strength
(CIS)22
Vercoulen et
al1996
20 items using 7-point Likert scale of
fatigue To measure four aspects of
fatiguesubjective experience
contractionmotivation physical
Activity
6-14 Not reported
Child Fatigue Scale (CFS)7 Hockenberry
et al2003
14 items 2 part questionnaire frequency
(yes or no) 5-point Likert scale of the
intensity of any yes responses
7-13
14-18 α073-o84
The Fatigue Scale for 7-12
year Olds (FS-C)224
Hockenberry
et al
14 items provide a fatigue intensity score
5-point Likert scale
7-12 αo84
The Fatigue Scale for 13-18
year Olds (FS-A)24
Hockenberry
et al
14 items provide a fatigue intensity score
5-point Likert scale
13-18 α076-o96
Pediatric Quality of life
Multidimensional Fatigue
Scale (Peds QL-MFS)2325
Varni2002 18 items to measure three aspects of
fatigueGeneralsleepcognitive
14-18 Not reported
681
50
Appendix V Excluded studies and reasons for exclusion
Baggott C Dodd M Kennedy C Marina N Miaskowski C Multiple Symptoms in Pediatric Oncology
Patients A Systematic Review Journal of Pediatric Oncology Nursing 2009 Nov-Dec 27(6)
325-339
Reason for exclusion Not outcome of interest
Barlow JH Ellard DR Psycho-educational interventions for children with chronic disease parents and
siblings an overview of the research evidence base Care Health amp Development 2004 Nov
30(6)637-45
Reason for exclusion Not outcome of interest
Bedider S Moyer CA Randomized controlled trials of pediatric massage A review Evid Based
Complement Alternat Med 2007 Mar 4(1)23-34 Epub 2006 Nov 3
Reason for exclusion Not outcome of interest
de Nijs EJ Ros W Grijpdonck MH Nursing intervention for fatigue during the treatment for cancer Cancer
Nursing 2008 31(3)191-206
Reason for exclusion Not population of interest
Edwards JL Gibson F Richardson A Sepion B Ream E Fatigue in adolescents with and following a
cancer diagnosis developing an evidence base for practice European Journal of Cancer 2003
Dec 39(18)2671-80
Reason for exclusion Not experimental or quasi-experimental study
Hinds PS Hockenberry-Eatan M Developing a research program on fatigue in children and adolescents
diagnosed with cancer Journal of Pediatric Oncology Nursing 2001 Mar-Apr 18(2 Suppl
1)3-12
Reason for exclusion Not experimental or quasi-experimental study
Hockenberry-Eaton M Hinds PS Alcoser P ONeill JB Euell K Howard V Gattuso J Taylor J Fatigue in
Children and Adolescents With Cancer Journal of Pediatric Oncology Nursing 1998 July
15(3)172-182
Reason for exclusion Not experimental or quasi-experimental study
Jean-Pierre P Mustian K Kohli S Roscoe JA Hickok JT Morrow GR Community-based clinical oncology
research trials for cancer-related fatigue The Journal of Supportive Oncology 2006 Nov-Dec
4(10)511-6
682
51
Reason for exclusion Not population of interest
Kangas M Bovbjerg DH Montgomery GH Cancer-Related Fatigue A Systematic and Meta-Analytic
Review of Non-Pharmacological Therapies for Cancer Patients Psychological Bulletin 2008 Sep
134(5)700-41
Reason for exclusion Not population of interest
Lotfi-Jam K Carey M Jefford M Schofield P Charleson C Aranda S Nonpharmacologic strategies for
managing common chemotherapy adverse effects A systematic review Journal of Clinical
Oncology 2008 Dec 1 26(34)5618-29 Epub 2008 Nov 3
Reason for exclusion Not outcome of interest
Marchese VG Chiarello LA Lange BJ Effects of physical therapy intervention for children with acute
lymphoblastic leukemia Pediatr Blood Cancer 2004 Feb42(2)127-33
Reason for exclusion Not outcome of interest
Meeske KA Siegel SE Globe DR Mack WJ Bernstein L Prevalence and correlates of fatigue in
long-term survivors of childhood leukemia Journal of Clinical Oncology 2005 Aug 20
23(24)5501-10
Reason for exclusion Not intervention study
Minton O Richardson A Sharpe M Hotopf Stone P A systematic review and meta-analysis of the
pharmacological treatment of cancer-related fatigue J Natl Cancer Inst 2008 Aug 20
100(16)1155-66 Epub 2008 Aug 11
Reason for exclusion Not population and intervention of interest
Mustian KM Morrow GR Carroll JK Figueroa-Moseley CD Pascal JP Williams GC Integrative
nonpharmacologic behavioral interventions for the management of Cancer-Related fatigue The
Oncologist 2007 12(1)52-67
Reason for exclusion Not population of interest
Neill J Belan I Ried K Effectiveness of non-pharmacological interventions for fatigue in adults with
multiple sclerosis rheumatoid arthritis or systemic lupus erythematosus a systematic review
Journal of Advanced Nursing 2006 Dec 56(6)617-35
Reason for exclusion Not population of interest
Rheingans JI A systematic review of nonpharmacologic adjunctive therapies for symptom management
Journal of Pediatric Oncology Nursing 2007 24(2) 81-94
683
52
Reason for exclusion Not outcome of interest
Rheingans JI Pediatric oncology nursesrsquo management of patients symptoms Journal of Pediatric
Oncology Nursing 2008 Nov 25(6) 303-11
Reason for exclusion Not outcome of interest
San Juan AF Fleck SJ Chamorro-Vintildea C Mateacute-Muntildeoz JL Moral S Peacuterez M Cardona C Del Valle MF
Hernaacutendez M Ramiacuterez M Madero L Lucia A Effects of an intrahospital exercise program
intervention for children with leukemia Medicine amp Science in Sports amp Exercise 2007 Jan
39(1)13-21
Reason for exclusion Not outcome of interest
Sanford SD Okuma JO Pan J Srivastava DK West N Farr L Hinds PS Gender differences in sleep
fatigue and daytime activity in a pediatric oncology sample receiving dexamethasone Journal of
Pediatric Psychology 2008 Apr 33(3)298-306 Epub 2007 Nov 17
Reason for exclusion Not experimental or quasi-experimental study
Schmitz KH Holtzman J Courneya KS Macircsse LC Duval S Kane R Controlled physical activity trials in
cancer survivors a systematic review and meta-analysis Cancer Epidemiol Biomarkers Prev
2005 Jul 14(7)1588-95
Reason for exclusion Not population of interest
van Brussel M Takken T Lucia A van der Net J Helders PJ Is physical fitness decreased in survivors of
childhood leukemia A systematic review Leukemia 2005 Jan 19(1)13-7
Reason for exclusion Not population of interest
Whiting P Bagnall AM Snowden AJ Cornell JE Mulrow CD Ramirez G Interventions for the treatment
and management of chronic fatigue syndrome JAMA 2001 Sep 19 286(11)1360-8
Reason for exclusion Not intervention of interest
Whitsett SF Gudmundsdottir M Davies B McCarthy P Friedman D Chemotherapy-related fatigue in
childhood cancer correlates consequences and coping strategies Journal of Pediatric
Oncology Nursing 2008 Mar-Apr 25(2)86-96 Epub 2008 Feb 29
Reason for exclusion Not experimental or quasi-experimental study
Winner C Muumlller C Hoffmann C Boos J Rosenbaum D Physical activity and childhood cancer Pediatr
Blood Cancer 2010 Apr 54(4)501-10
Reason for exclusion Not research study
684
53
Wu M Hsu L Zhang B Shen N Lu H Li S The experiences of cancer-related fatigue among Chinese
children with leukaemia A phenomenological study Journal of Nursing Studies 2010 Jan
47(1)49-59 Epub 2009 Aug 25
Reason for exclusion Not experimental or quasi-experimental study
Yeh CH Chiang YC Lin L Yang CP Chien LC Weaver MA Chuang HL Clinical factors associated with
fatigue over time in paediatric oncology patients receiving chemotherapy British Journal of
Cancer 2008 Jul 8 99(1)23-9 Epub 2008 Jun 24
Reason for exclusion Not experimental or quasi-experimental study
685
47
RefNo
Author(s) (years)
Title Study question Research method
Comparison group
Sampling Measurement variables
Data collection
Intervention Data collection time
OutcomesResults
2 Gene R E amp Conk Z (2008)
Impact of Effective Nursing Interventions to the Fatigue Syndrome in Children Who Receive Chemotherapy
1 to examine the effects of an effective nursing intervention to the fatigue syndrome of children 7 to 12 years of age who receive chemotherapy 2Tto examine the relationship between fatigue and demographic variables (age sex) diagnoses ([ALL AML] lymphoma) and therapy-related variables (eg level of hemoglobin
experimental randomized controlled study
Routine nursing care
A total of 60 children who are 7-12 years of age(a new diagnosis of ALL AML or lymphoma and receiving for the first time after being diagnosed a 7- to 10-day chemotherapy treatment )
fatigue The Fatigue Scale(FS-C) for 7-12 (intensity)
The Fatigue Scale Parent Version (FS-P)
1 effective nursing interventions(45- 60mdaya week)education about the fatigue with the chemotherapy and fatigue handbook 2 T1 After a 7-day period the children
and parent were evaluated with the Fatigue Scale
1The difference betwthe 2 mean values wafound to be statisticallsignificant 2 statistically significadifference was found between the Fatigue Scale-Child mean scothe experimental (272the control group (4213)children
679
48
25 Chiang et
al(2007)
The effects of ldquo a home ndashbased aerobic exercise interventionrdquo on fatigue and cardiorespiratory fitness in children with Acute Lymphoblastic Leukemia during the maintenance stage of chemotherapy
To examine the effect of ldquo a home ndashbased aerobic exercise interventionrdquo on fatigue and cardiorespiratory fitness in children with Acute Lymphoblastic Leukemia during the maintenance stage of chemotherapy
Quasi-experi -mental
Routine
nursing care
14 pediatric oncology patients in the experimental group and 10 in control group who were matched by age and sex ages7-18 years
1Cardiorespiratory fitness
2Fatigue
1Cardiorespiratory fitness Physical Activity Recall
VO2maxHR peak 6MWT
2 Fatigue PedsQL-MFS(Generalsleepcognitive fatigue)
1A six-week home-based aerobic exercise intervention 2 8 time points T0 baseline T1-T6 every week during the
intervention(6 weeks) T7 post intervention T8 follow-up (one month after
the end of the home-based exercise program)
1 For intent-to ndash treatthe findings indicated are no intervention efftime differences by anon the subscale of fat2 For per-protocol angeneral fatigue( mean422plusmn402) was the osubscale that was siglower for children whothe exercise interventthose in control groupfollow-up assessmentmonth after the compintervention) 3 The VO2peak are significantly improvingexperimental group atbaseline- and post-intassessment The VO2was significantly highechildren who were in experimental group thcontrol subjects at post-intervention assefor the per-protocol an
680
49
Appendix IV Instrument used to measure fatigue
Name Instrument
developers
Description Used in
age in
ref
Reliability
Consistency of
instrument
Checklist Individual Strength
(CIS)22
Vercoulen et
al1996
20 items using 7-point Likert scale of
fatigue To measure four aspects of
fatiguesubjective experience
contractionmotivation physical
Activity
6-14 Not reported
Child Fatigue Scale (CFS)7 Hockenberry
et al2003
14 items 2 part questionnaire frequency
(yes or no) 5-point Likert scale of the
intensity of any yes responses
7-13
14-18 α073-o84
The Fatigue Scale for 7-12
year Olds (FS-C)224
Hockenberry
et al
14 items provide a fatigue intensity score
5-point Likert scale
7-12 αo84
The Fatigue Scale for 13-18
year Olds (FS-A)24
Hockenberry
et al
14 items provide a fatigue intensity score
5-point Likert scale
13-18 α076-o96
Pediatric Quality of life
Multidimensional Fatigue
Scale (Peds QL-MFS)2325
Varni2002 18 items to measure three aspects of
fatigueGeneralsleepcognitive
14-18 Not reported
681
50
Appendix V Excluded studies and reasons for exclusion
Baggott C Dodd M Kennedy C Marina N Miaskowski C Multiple Symptoms in Pediatric Oncology
Patients A Systematic Review Journal of Pediatric Oncology Nursing 2009 Nov-Dec 27(6)
325-339
Reason for exclusion Not outcome of interest
Barlow JH Ellard DR Psycho-educational interventions for children with chronic disease parents and
siblings an overview of the research evidence base Care Health amp Development 2004 Nov
30(6)637-45
Reason for exclusion Not outcome of interest
Bedider S Moyer CA Randomized controlled trials of pediatric massage A review Evid Based
Complement Alternat Med 2007 Mar 4(1)23-34 Epub 2006 Nov 3
Reason for exclusion Not outcome of interest
de Nijs EJ Ros W Grijpdonck MH Nursing intervention for fatigue during the treatment for cancer Cancer
Nursing 2008 31(3)191-206
Reason for exclusion Not population of interest
Edwards JL Gibson F Richardson A Sepion B Ream E Fatigue in adolescents with and following a
cancer diagnosis developing an evidence base for practice European Journal of Cancer 2003
Dec 39(18)2671-80
Reason for exclusion Not experimental or quasi-experimental study
Hinds PS Hockenberry-Eatan M Developing a research program on fatigue in children and adolescents
diagnosed with cancer Journal of Pediatric Oncology Nursing 2001 Mar-Apr 18(2 Suppl
1)3-12
Reason for exclusion Not experimental or quasi-experimental study
Hockenberry-Eaton M Hinds PS Alcoser P ONeill JB Euell K Howard V Gattuso J Taylor J Fatigue in
Children and Adolescents With Cancer Journal of Pediatric Oncology Nursing 1998 July
15(3)172-182
Reason for exclusion Not experimental or quasi-experimental study
Jean-Pierre P Mustian K Kohli S Roscoe JA Hickok JT Morrow GR Community-based clinical oncology
research trials for cancer-related fatigue The Journal of Supportive Oncology 2006 Nov-Dec
4(10)511-6
682
51
Reason for exclusion Not population of interest
Kangas M Bovbjerg DH Montgomery GH Cancer-Related Fatigue A Systematic and Meta-Analytic
Review of Non-Pharmacological Therapies for Cancer Patients Psychological Bulletin 2008 Sep
134(5)700-41
Reason for exclusion Not population of interest
Lotfi-Jam K Carey M Jefford M Schofield P Charleson C Aranda S Nonpharmacologic strategies for
managing common chemotherapy adverse effects A systematic review Journal of Clinical
Oncology 2008 Dec 1 26(34)5618-29 Epub 2008 Nov 3
Reason for exclusion Not outcome of interest
Marchese VG Chiarello LA Lange BJ Effects of physical therapy intervention for children with acute
lymphoblastic leukemia Pediatr Blood Cancer 2004 Feb42(2)127-33
Reason for exclusion Not outcome of interest
Meeske KA Siegel SE Globe DR Mack WJ Bernstein L Prevalence and correlates of fatigue in
long-term survivors of childhood leukemia Journal of Clinical Oncology 2005 Aug 20
23(24)5501-10
Reason for exclusion Not intervention study
Minton O Richardson A Sharpe M Hotopf Stone P A systematic review and meta-analysis of the
pharmacological treatment of cancer-related fatigue J Natl Cancer Inst 2008 Aug 20
100(16)1155-66 Epub 2008 Aug 11
Reason for exclusion Not population and intervention of interest
Mustian KM Morrow GR Carroll JK Figueroa-Moseley CD Pascal JP Williams GC Integrative
nonpharmacologic behavioral interventions for the management of Cancer-Related fatigue The
Oncologist 2007 12(1)52-67
Reason for exclusion Not population of interest
Neill J Belan I Ried K Effectiveness of non-pharmacological interventions for fatigue in adults with
multiple sclerosis rheumatoid arthritis or systemic lupus erythematosus a systematic review
Journal of Advanced Nursing 2006 Dec 56(6)617-35
Reason for exclusion Not population of interest
Rheingans JI A systematic review of nonpharmacologic adjunctive therapies for symptom management
Journal of Pediatric Oncology Nursing 2007 24(2) 81-94
683
52
Reason for exclusion Not outcome of interest
Rheingans JI Pediatric oncology nursesrsquo management of patients symptoms Journal of Pediatric
Oncology Nursing 2008 Nov 25(6) 303-11
Reason for exclusion Not outcome of interest
San Juan AF Fleck SJ Chamorro-Vintildea C Mateacute-Muntildeoz JL Moral S Peacuterez M Cardona C Del Valle MF
Hernaacutendez M Ramiacuterez M Madero L Lucia A Effects of an intrahospital exercise program
intervention for children with leukemia Medicine amp Science in Sports amp Exercise 2007 Jan
39(1)13-21
Reason for exclusion Not outcome of interest
Sanford SD Okuma JO Pan J Srivastava DK West N Farr L Hinds PS Gender differences in sleep
fatigue and daytime activity in a pediatric oncology sample receiving dexamethasone Journal of
Pediatric Psychology 2008 Apr 33(3)298-306 Epub 2007 Nov 17
Reason for exclusion Not experimental or quasi-experimental study
Schmitz KH Holtzman J Courneya KS Macircsse LC Duval S Kane R Controlled physical activity trials in
cancer survivors a systematic review and meta-analysis Cancer Epidemiol Biomarkers Prev
2005 Jul 14(7)1588-95
Reason for exclusion Not population of interest
van Brussel M Takken T Lucia A van der Net J Helders PJ Is physical fitness decreased in survivors of
childhood leukemia A systematic review Leukemia 2005 Jan 19(1)13-7
Reason for exclusion Not population of interest
Whiting P Bagnall AM Snowden AJ Cornell JE Mulrow CD Ramirez G Interventions for the treatment
and management of chronic fatigue syndrome JAMA 2001 Sep 19 286(11)1360-8
Reason for exclusion Not intervention of interest
Whitsett SF Gudmundsdottir M Davies B McCarthy P Friedman D Chemotherapy-related fatigue in
childhood cancer correlates consequences and coping strategies Journal of Pediatric
Oncology Nursing 2008 Mar-Apr 25(2)86-96 Epub 2008 Feb 29
Reason for exclusion Not experimental or quasi-experimental study
Winner C Muumlller C Hoffmann C Boos J Rosenbaum D Physical activity and childhood cancer Pediatr
Blood Cancer 2010 Apr 54(4)501-10
Reason for exclusion Not research study
684
53
Wu M Hsu L Zhang B Shen N Lu H Li S The experiences of cancer-related fatigue among Chinese
children with leukaemia A phenomenological study Journal of Nursing Studies 2010 Jan
47(1)49-59 Epub 2009 Aug 25
Reason for exclusion Not experimental or quasi-experimental study
Yeh CH Chiang YC Lin L Yang CP Chien LC Weaver MA Chuang HL Clinical factors associated with
fatigue over time in paediatric oncology patients receiving chemotherapy British Journal of
Cancer 2008 Jul 8 99(1)23-9 Epub 2008 Jun 24
Reason for exclusion Not experimental or quasi-experimental study
685
48
25 Chiang et
al(2007)
The effects of ldquo a home ndashbased aerobic exercise interventionrdquo on fatigue and cardiorespiratory fitness in children with Acute Lymphoblastic Leukemia during the maintenance stage of chemotherapy
To examine the effect of ldquo a home ndashbased aerobic exercise interventionrdquo on fatigue and cardiorespiratory fitness in children with Acute Lymphoblastic Leukemia during the maintenance stage of chemotherapy
Quasi-experi -mental
Routine
nursing care
14 pediatric oncology patients in the experimental group and 10 in control group who were matched by age and sex ages7-18 years
1Cardiorespiratory fitness
2Fatigue
1Cardiorespiratory fitness Physical Activity Recall
VO2maxHR peak 6MWT
2 Fatigue PedsQL-MFS(Generalsleepcognitive fatigue)
1A six-week home-based aerobic exercise intervention 2 8 time points T0 baseline T1-T6 every week during the
intervention(6 weeks) T7 post intervention T8 follow-up (one month after
the end of the home-based exercise program)
1 For intent-to ndash treatthe findings indicated are no intervention efftime differences by anon the subscale of fat2 For per-protocol angeneral fatigue( mean422plusmn402) was the osubscale that was siglower for children whothe exercise interventthose in control groupfollow-up assessmentmonth after the compintervention) 3 The VO2peak are significantly improvingexperimental group atbaseline- and post-intassessment The VO2was significantly highechildren who were in experimental group thcontrol subjects at post-intervention assefor the per-protocol an
680
49
Appendix IV Instrument used to measure fatigue
Name Instrument
developers
Description Used in
age in
ref
Reliability
Consistency of
instrument
Checklist Individual Strength
(CIS)22
Vercoulen et
al1996
20 items using 7-point Likert scale of
fatigue To measure four aspects of
fatiguesubjective experience
contractionmotivation physical
Activity
6-14 Not reported
Child Fatigue Scale (CFS)7 Hockenberry
et al2003
14 items 2 part questionnaire frequency
(yes or no) 5-point Likert scale of the
intensity of any yes responses
7-13
14-18 α073-o84
The Fatigue Scale for 7-12
year Olds (FS-C)224
Hockenberry
et al
14 items provide a fatigue intensity score
5-point Likert scale
7-12 αo84
The Fatigue Scale for 13-18
year Olds (FS-A)24
Hockenberry
et al
14 items provide a fatigue intensity score
5-point Likert scale
13-18 α076-o96
Pediatric Quality of life
Multidimensional Fatigue
Scale (Peds QL-MFS)2325
Varni2002 18 items to measure three aspects of
fatigueGeneralsleepcognitive
14-18 Not reported
681
50
Appendix V Excluded studies and reasons for exclusion
Baggott C Dodd M Kennedy C Marina N Miaskowski C Multiple Symptoms in Pediatric Oncology
Patients A Systematic Review Journal of Pediatric Oncology Nursing 2009 Nov-Dec 27(6)
325-339
Reason for exclusion Not outcome of interest
Barlow JH Ellard DR Psycho-educational interventions for children with chronic disease parents and
siblings an overview of the research evidence base Care Health amp Development 2004 Nov
30(6)637-45
Reason for exclusion Not outcome of interest
Bedider S Moyer CA Randomized controlled trials of pediatric massage A review Evid Based
Complement Alternat Med 2007 Mar 4(1)23-34 Epub 2006 Nov 3
Reason for exclusion Not outcome of interest
de Nijs EJ Ros W Grijpdonck MH Nursing intervention for fatigue during the treatment for cancer Cancer
Nursing 2008 31(3)191-206
Reason for exclusion Not population of interest
Edwards JL Gibson F Richardson A Sepion B Ream E Fatigue in adolescents with and following a
cancer diagnosis developing an evidence base for practice European Journal of Cancer 2003
Dec 39(18)2671-80
Reason for exclusion Not experimental or quasi-experimental study
Hinds PS Hockenberry-Eatan M Developing a research program on fatigue in children and adolescents
diagnosed with cancer Journal of Pediatric Oncology Nursing 2001 Mar-Apr 18(2 Suppl
1)3-12
Reason for exclusion Not experimental or quasi-experimental study
Hockenberry-Eaton M Hinds PS Alcoser P ONeill JB Euell K Howard V Gattuso J Taylor J Fatigue in
Children and Adolescents With Cancer Journal of Pediatric Oncology Nursing 1998 July
15(3)172-182
Reason for exclusion Not experimental or quasi-experimental study
Jean-Pierre P Mustian K Kohli S Roscoe JA Hickok JT Morrow GR Community-based clinical oncology
research trials for cancer-related fatigue The Journal of Supportive Oncology 2006 Nov-Dec
4(10)511-6
682
51
Reason for exclusion Not population of interest
Kangas M Bovbjerg DH Montgomery GH Cancer-Related Fatigue A Systematic and Meta-Analytic
Review of Non-Pharmacological Therapies for Cancer Patients Psychological Bulletin 2008 Sep
134(5)700-41
Reason for exclusion Not population of interest
Lotfi-Jam K Carey M Jefford M Schofield P Charleson C Aranda S Nonpharmacologic strategies for
managing common chemotherapy adverse effects A systematic review Journal of Clinical
Oncology 2008 Dec 1 26(34)5618-29 Epub 2008 Nov 3
Reason for exclusion Not outcome of interest
Marchese VG Chiarello LA Lange BJ Effects of physical therapy intervention for children with acute
lymphoblastic leukemia Pediatr Blood Cancer 2004 Feb42(2)127-33
Reason for exclusion Not outcome of interest
Meeske KA Siegel SE Globe DR Mack WJ Bernstein L Prevalence and correlates of fatigue in
long-term survivors of childhood leukemia Journal of Clinical Oncology 2005 Aug 20
23(24)5501-10
Reason for exclusion Not intervention study
Minton O Richardson A Sharpe M Hotopf Stone P A systematic review and meta-analysis of the
pharmacological treatment of cancer-related fatigue J Natl Cancer Inst 2008 Aug 20
100(16)1155-66 Epub 2008 Aug 11
Reason for exclusion Not population and intervention of interest
Mustian KM Morrow GR Carroll JK Figueroa-Moseley CD Pascal JP Williams GC Integrative
nonpharmacologic behavioral interventions for the management of Cancer-Related fatigue The
Oncologist 2007 12(1)52-67
Reason for exclusion Not population of interest
Neill J Belan I Ried K Effectiveness of non-pharmacological interventions for fatigue in adults with
multiple sclerosis rheumatoid arthritis or systemic lupus erythematosus a systematic review
Journal of Advanced Nursing 2006 Dec 56(6)617-35
Reason for exclusion Not population of interest
Rheingans JI A systematic review of nonpharmacologic adjunctive therapies for symptom management
Journal of Pediatric Oncology Nursing 2007 24(2) 81-94
683
52
Reason for exclusion Not outcome of interest
Rheingans JI Pediatric oncology nursesrsquo management of patients symptoms Journal of Pediatric
Oncology Nursing 2008 Nov 25(6) 303-11
Reason for exclusion Not outcome of interest
San Juan AF Fleck SJ Chamorro-Vintildea C Mateacute-Muntildeoz JL Moral S Peacuterez M Cardona C Del Valle MF
Hernaacutendez M Ramiacuterez M Madero L Lucia A Effects of an intrahospital exercise program
intervention for children with leukemia Medicine amp Science in Sports amp Exercise 2007 Jan
39(1)13-21
Reason for exclusion Not outcome of interest
Sanford SD Okuma JO Pan J Srivastava DK West N Farr L Hinds PS Gender differences in sleep
fatigue and daytime activity in a pediatric oncology sample receiving dexamethasone Journal of
Pediatric Psychology 2008 Apr 33(3)298-306 Epub 2007 Nov 17
Reason for exclusion Not experimental or quasi-experimental study
Schmitz KH Holtzman J Courneya KS Macircsse LC Duval S Kane R Controlled physical activity trials in
cancer survivors a systematic review and meta-analysis Cancer Epidemiol Biomarkers Prev
2005 Jul 14(7)1588-95
Reason for exclusion Not population of interest
van Brussel M Takken T Lucia A van der Net J Helders PJ Is physical fitness decreased in survivors of
childhood leukemia A systematic review Leukemia 2005 Jan 19(1)13-7
Reason for exclusion Not population of interest
Whiting P Bagnall AM Snowden AJ Cornell JE Mulrow CD Ramirez G Interventions for the treatment
and management of chronic fatigue syndrome JAMA 2001 Sep 19 286(11)1360-8
Reason for exclusion Not intervention of interest
Whitsett SF Gudmundsdottir M Davies B McCarthy P Friedman D Chemotherapy-related fatigue in
childhood cancer correlates consequences and coping strategies Journal of Pediatric
Oncology Nursing 2008 Mar-Apr 25(2)86-96 Epub 2008 Feb 29
Reason for exclusion Not experimental or quasi-experimental study
Winner C Muumlller C Hoffmann C Boos J Rosenbaum D Physical activity and childhood cancer Pediatr
Blood Cancer 2010 Apr 54(4)501-10
Reason for exclusion Not research study
684
53
Wu M Hsu L Zhang B Shen N Lu H Li S The experiences of cancer-related fatigue among Chinese
children with leukaemia A phenomenological study Journal of Nursing Studies 2010 Jan
47(1)49-59 Epub 2009 Aug 25
Reason for exclusion Not experimental or quasi-experimental study
Yeh CH Chiang YC Lin L Yang CP Chien LC Weaver MA Chuang HL Clinical factors associated with
fatigue over time in paediatric oncology patients receiving chemotherapy British Journal of
Cancer 2008 Jul 8 99(1)23-9 Epub 2008 Jun 24
Reason for exclusion Not experimental or quasi-experimental study
685
49
Appendix IV Instrument used to measure fatigue
Name Instrument
developers
Description Used in
age in
ref
Reliability
Consistency of
instrument
Checklist Individual Strength
(CIS)22
Vercoulen et
al1996
20 items using 7-point Likert scale of
fatigue To measure four aspects of
fatiguesubjective experience
contractionmotivation physical
Activity
6-14 Not reported
Child Fatigue Scale (CFS)7 Hockenberry
et al2003
14 items 2 part questionnaire frequency
(yes or no) 5-point Likert scale of the
intensity of any yes responses
7-13
14-18 α073-o84
The Fatigue Scale for 7-12
year Olds (FS-C)224
Hockenberry
et al
14 items provide a fatigue intensity score
5-point Likert scale
7-12 αo84
The Fatigue Scale for 13-18
year Olds (FS-A)24
Hockenberry
et al
14 items provide a fatigue intensity score
5-point Likert scale
13-18 α076-o96
Pediatric Quality of life
Multidimensional Fatigue
Scale (Peds QL-MFS)2325
Varni2002 18 items to measure three aspects of
fatigueGeneralsleepcognitive
14-18 Not reported
681
50
Appendix V Excluded studies and reasons for exclusion
Baggott C Dodd M Kennedy C Marina N Miaskowski C Multiple Symptoms in Pediatric Oncology
Patients A Systematic Review Journal of Pediatric Oncology Nursing 2009 Nov-Dec 27(6)
325-339
Reason for exclusion Not outcome of interest
Barlow JH Ellard DR Psycho-educational interventions for children with chronic disease parents and
siblings an overview of the research evidence base Care Health amp Development 2004 Nov
30(6)637-45
Reason for exclusion Not outcome of interest
Bedider S Moyer CA Randomized controlled trials of pediatric massage A review Evid Based
Complement Alternat Med 2007 Mar 4(1)23-34 Epub 2006 Nov 3
Reason for exclusion Not outcome of interest
de Nijs EJ Ros W Grijpdonck MH Nursing intervention for fatigue during the treatment for cancer Cancer
Nursing 2008 31(3)191-206
Reason for exclusion Not population of interest
Edwards JL Gibson F Richardson A Sepion B Ream E Fatigue in adolescents with and following a
cancer diagnosis developing an evidence base for practice European Journal of Cancer 2003
Dec 39(18)2671-80
Reason for exclusion Not experimental or quasi-experimental study
Hinds PS Hockenberry-Eatan M Developing a research program on fatigue in children and adolescents
diagnosed with cancer Journal of Pediatric Oncology Nursing 2001 Mar-Apr 18(2 Suppl
1)3-12
Reason for exclusion Not experimental or quasi-experimental study
Hockenberry-Eaton M Hinds PS Alcoser P ONeill JB Euell K Howard V Gattuso J Taylor J Fatigue in
Children and Adolescents With Cancer Journal of Pediatric Oncology Nursing 1998 July
15(3)172-182
Reason for exclusion Not experimental or quasi-experimental study
Jean-Pierre P Mustian K Kohli S Roscoe JA Hickok JT Morrow GR Community-based clinical oncology
research trials for cancer-related fatigue The Journal of Supportive Oncology 2006 Nov-Dec
4(10)511-6
682
51
Reason for exclusion Not population of interest
Kangas M Bovbjerg DH Montgomery GH Cancer-Related Fatigue A Systematic and Meta-Analytic
Review of Non-Pharmacological Therapies for Cancer Patients Psychological Bulletin 2008 Sep
134(5)700-41
Reason for exclusion Not population of interest
Lotfi-Jam K Carey M Jefford M Schofield P Charleson C Aranda S Nonpharmacologic strategies for
managing common chemotherapy adverse effects A systematic review Journal of Clinical
Oncology 2008 Dec 1 26(34)5618-29 Epub 2008 Nov 3
Reason for exclusion Not outcome of interest
Marchese VG Chiarello LA Lange BJ Effects of physical therapy intervention for children with acute
lymphoblastic leukemia Pediatr Blood Cancer 2004 Feb42(2)127-33
Reason for exclusion Not outcome of interest
Meeske KA Siegel SE Globe DR Mack WJ Bernstein L Prevalence and correlates of fatigue in
long-term survivors of childhood leukemia Journal of Clinical Oncology 2005 Aug 20
23(24)5501-10
Reason for exclusion Not intervention study
Minton O Richardson A Sharpe M Hotopf Stone P A systematic review and meta-analysis of the
pharmacological treatment of cancer-related fatigue J Natl Cancer Inst 2008 Aug 20
100(16)1155-66 Epub 2008 Aug 11
Reason for exclusion Not population and intervention of interest
Mustian KM Morrow GR Carroll JK Figueroa-Moseley CD Pascal JP Williams GC Integrative
nonpharmacologic behavioral interventions for the management of Cancer-Related fatigue The
Oncologist 2007 12(1)52-67
Reason for exclusion Not population of interest
Neill J Belan I Ried K Effectiveness of non-pharmacological interventions for fatigue in adults with
multiple sclerosis rheumatoid arthritis or systemic lupus erythematosus a systematic review
Journal of Advanced Nursing 2006 Dec 56(6)617-35
Reason for exclusion Not population of interest
Rheingans JI A systematic review of nonpharmacologic adjunctive therapies for symptom management
Journal of Pediatric Oncology Nursing 2007 24(2) 81-94
683
52
Reason for exclusion Not outcome of interest
Rheingans JI Pediatric oncology nursesrsquo management of patients symptoms Journal of Pediatric
Oncology Nursing 2008 Nov 25(6) 303-11
Reason for exclusion Not outcome of interest
San Juan AF Fleck SJ Chamorro-Vintildea C Mateacute-Muntildeoz JL Moral S Peacuterez M Cardona C Del Valle MF
Hernaacutendez M Ramiacuterez M Madero L Lucia A Effects of an intrahospital exercise program
intervention for children with leukemia Medicine amp Science in Sports amp Exercise 2007 Jan
39(1)13-21
Reason for exclusion Not outcome of interest
Sanford SD Okuma JO Pan J Srivastava DK West N Farr L Hinds PS Gender differences in sleep
fatigue and daytime activity in a pediatric oncology sample receiving dexamethasone Journal of
Pediatric Psychology 2008 Apr 33(3)298-306 Epub 2007 Nov 17
Reason for exclusion Not experimental or quasi-experimental study
Schmitz KH Holtzman J Courneya KS Macircsse LC Duval S Kane R Controlled physical activity trials in
cancer survivors a systematic review and meta-analysis Cancer Epidemiol Biomarkers Prev
2005 Jul 14(7)1588-95
Reason for exclusion Not population of interest
van Brussel M Takken T Lucia A van der Net J Helders PJ Is physical fitness decreased in survivors of
childhood leukemia A systematic review Leukemia 2005 Jan 19(1)13-7
Reason for exclusion Not population of interest
Whiting P Bagnall AM Snowden AJ Cornell JE Mulrow CD Ramirez G Interventions for the treatment
and management of chronic fatigue syndrome JAMA 2001 Sep 19 286(11)1360-8
Reason for exclusion Not intervention of interest
Whitsett SF Gudmundsdottir M Davies B McCarthy P Friedman D Chemotherapy-related fatigue in
childhood cancer correlates consequences and coping strategies Journal of Pediatric
Oncology Nursing 2008 Mar-Apr 25(2)86-96 Epub 2008 Feb 29
Reason for exclusion Not experimental or quasi-experimental study
Winner C Muumlller C Hoffmann C Boos J Rosenbaum D Physical activity and childhood cancer Pediatr
Blood Cancer 2010 Apr 54(4)501-10
Reason for exclusion Not research study
684
53
Wu M Hsu L Zhang B Shen N Lu H Li S The experiences of cancer-related fatigue among Chinese
children with leukaemia A phenomenological study Journal of Nursing Studies 2010 Jan
47(1)49-59 Epub 2009 Aug 25
Reason for exclusion Not experimental or quasi-experimental study
Yeh CH Chiang YC Lin L Yang CP Chien LC Weaver MA Chuang HL Clinical factors associated with
fatigue over time in paediatric oncology patients receiving chemotherapy British Journal of
Cancer 2008 Jul 8 99(1)23-9 Epub 2008 Jun 24
Reason for exclusion Not experimental or quasi-experimental study
685
50
Appendix V Excluded studies and reasons for exclusion
Baggott C Dodd M Kennedy C Marina N Miaskowski C Multiple Symptoms in Pediatric Oncology
Patients A Systematic Review Journal of Pediatric Oncology Nursing 2009 Nov-Dec 27(6)
325-339
Reason for exclusion Not outcome of interest
Barlow JH Ellard DR Psycho-educational interventions for children with chronic disease parents and
siblings an overview of the research evidence base Care Health amp Development 2004 Nov
30(6)637-45
Reason for exclusion Not outcome of interest
Bedider S Moyer CA Randomized controlled trials of pediatric massage A review Evid Based
Complement Alternat Med 2007 Mar 4(1)23-34 Epub 2006 Nov 3
Reason for exclusion Not outcome of interest
de Nijs EJ Ros W Grijpdonck MH Nursing intervention for fatigue during the treatment for cancer Cancer
Nursing 2008 31(3)191-206
Reason for exclusion Not population of interest
Edwards JL Gibson F Richardson A Sepion B Ream E Fatigue in adolescents with and following a
cancer diagnosis developing an evidence base for practice European Journal of Cancer 2003
Dec 39(18)2671-80
Reason for exclusion Not experimental or quasi-experimental study
Hinds PS Hockenberry-Eatan M Developing a research program on fatigue in children and adolescents
diagnosed with cancer Journal of Pediatric Oncology Nursing 2001 Mar-Apr 18(2 Suppl
1)3-12
Reason for exclusion Not experimental or quasi-experimental study
Hockenberry-Eaton M Hinds PS Alcoser P ONeill JB Euell K Howard V Gattuso J Taylor J Fatigue in
Children and Adolescents With Cancer Journal of Pediatric Oncology Nursing 1998 July
15(3)172-182
Reason for exclusion Not experimental or quasi-experimental study
Jean-Pierre P Mustian K Kohli S Roscoe JA Hickok JT Morrow GR Community-based clinical oncology
research trials for cancer-related fatigue The Journal of Supportive Oncology 2006 Nov-Dec
4(10)511-6
682
51
Reason for exclusion Not population of interest
Kangas M Bovbjerg DH Montgomery GH Cancer-Related Fatigue A Systematic and Meta-Analytic
Review of Non-Pharmacological Therapies for Cancer Patients Psychological Bulletin 2008 Sep
134(5)700-41
Reason for exclusion Not population of interest
Lotfi-Jam K Carey M Jefford M Schofield P Charleson C Aranda S Nonpharmacologic strategies for
managing common chemotherapy adverse effects A systematic review Journal of Clinical
Oncology 2008 Dec 1 26(34)5618-29 Epub 2008 Nov 3
Reason for exclusion Not outcome of interest
Marchese VG Chiarello LA Lange BJ Effects of physical therapy intervention for children with acute
lymphoblastic leukemia Pediatr Blood Cancer 2004 Feb42(2)127-33
Reason for exclusion Not outcome of interest
Meeske KA Siegel SE Globe DR Mack WJ Bernstein L Prevalence and correlates of fatigue in
long-term survivors of childhood leukemia Journal of Clinical Oncology 2005 Aug 20
23(24)5501-10
Reason for exclusion Not intervention study
Minton O Richardson A Sharpe M Hotopf Stone P A systematic review and meta-analysis of the
pharmacological treatment of cancer-related fatigue J Natl Cancer Inst 2008 Aug 20
100(16)1155-66 Epub 2008 Aug 11
Reason for exclusion Not population and intervention of interest
Mustian KM Morrow GR Carroll JK Figueroa-Moseley CD Pascal JP Williams GC Integrative
nonpharmacologic behavioral interventions for the management of Cancer-Related fatigue The
Oncologist 2007 12(1)52-67
Reason for exclusion Not population of interest
Neill J Belan I Ried K Effectiveness of non-pharmacological interventions for fatigue in adults with
multiple sclerosis rheumatoid arthritis or systemic lupus erythematosus a systematic review
Journal of Advanced Nursing 2006 Dec 56(6)617-35
Reason for exclusion Not population of interest
Rheingans JI A systematic review of nonpharmacologic adjunctive therapies for symptom management
Journal of Pediatric Oncology Nursing 2007 24(2) 81-94
683
52
Reason for exclusion Not outcome of interest
Rheingans JI Pediatric oncology nursesrsquo management of patients symptoms Journal of Pediatric
Oncology Nursing 2008 Nov 25(6) 303-11
Reason for exclusion Not outcome of interest
San Juan AF Fleck SJ Chamorro-Vintildea C Mateacute-Muntildeoz JL Moral S Peacuterez M Cardona C Del Valle MF
Hernaacutendez M Ramiacuterez M Madero L Lucia A Effects of an intrahospital exercise program
intervention for children with leukemia Medicine amp Science in Sports amp Exercise 2007 Jan
39(1)13-21
Reason for exclusion Not outcome of interest
Sanford SD Okuma JO Pan J Srivastava DK West N Farr L Hinds PS Gender differences in sleep
fatigue and daytime activity in a pediatric oncology sample receiving dexamethasone Journal of
Pediatric Psychology 2008 Apr 33(3)298-306 Epub 2007 Nov 17
Reason for exclusion Not experimental or quasi-experimental study
Schmitz KH Holtzman J Courneya KS Macircsse LC Duval S Kane R Controlled physical activity trials in
cancer survivors a systematic review and meta-analysis Cancer Epidemiol Biomarkers Prev
2005 Jul 14(7)1588-95
Reason for exclusion Not population of interest
van Brussel M Takken T Lucia A van der Net J Helders PJ Is physical fitness decreased in survivors of
childhood leukemia A systematic review Leukemia 2005 Jan 19(1)13-7
Reason for exclusion Not population of interest
Whiting P Bagnall AM Snowden AJ Cornell JE Mulrow CD Ramirez G Interventions for the treatment
and management of chronic fatigue syndrome JAMA 2001 Sep 19 286(11)1360-8
Reason for exclusion Not intervention of interest
Whitsett SF Gudmundsdottir M Davies B McCarthy P Friedman D Chemotherapy-related fatigue in
childhood cancer correlates consequences and coping strategies Journal of Pediatric
Oncology Nursing 2008 Mar-Apr 25(2)86-96 Epub 2008 Feb 29
Reason for exclusion Not experimental or quasi-experimental study
Winner C Muumlller C Hoffmann C Boos J Rosenbaum D Physical activity and childhood cancer Pediatr
Blood Cancer 2010 Apr 54(4)501-10
Reason for exclusion Not research study
684
53
Wu M Hsu L Zhang B Shen N Lu H Li S The experiences of cancer-related fatigue among Chinese
children with leukaemia A phenomenological study Journal of Nursing Studies 2010 Jan
47(1)49-59 Epub 2009 Aug 25
Reason for exclusion Not experimental or quasi-experimental study
Yeh CH Chiang YC Lin L Yang CP Chien LC Weaver MA Chuang HL Clinical factors associated with
fatigue over time in paediatric oncology patients receiving chemotherapy British Journal of
Cancer 2008 Jul 8 99(1)23-9 Epub 2008 Jun 24
Reason for exclusion Not experimental or quasi-experimental study
685
51
Reason for exclusion Not population of interest
Kangas M Bovbjerg DH Montgomery GH Cancer-Related Fatigue A Systematic and Meta-Analytic
Review of Non-Pharmacological Therapies for Cancer Patients Psychological Bulletin 2008 Sep
134(5)700-41
Reason for exclusion Not population of interest
Lotfi-Jam K Carey M Jefford M Schofield P Charleson C Aranda S Nonpharmacologic strategies for
managing common chemotherapy adverse effects A systematic review Journal of Clinical
Oncology 2008 Dec 1 26(34)5618-29 Epub 2008 Nov 3
Reason for exclusion Not outcome of interest
Marchese VG Chiarello LA Lange BJ Effects of physical therapy intervention for children with acute
lymphoblastic leukemia Pediatr Blood Cancer 2004 Feb42(2)127-33
Reason for exclusion Not outcome of interest
Meeske KA Siegel SE Globe DR Mack WJ Bernstein L Prevalence and correlates of fatigue in
long-term survivors of childhood leukemia Journal of Clinical Oncology 2005 Aug 20
23(24)5501-10
Reason for exclusion Not intervention study
Minton O Richardson A Sharpe M Hotopf Stone P A systematic review and meta-analysis of the
pharmacological treatment of cancer-related fatigue J Natl Cancer Inst 2008 Aug 20
100(16)1155-66 Epub 2008 Aug 11
Reason for exclusion Not population and intervention of interest
Mustian KM Morrow GR Carroll JK Figueroa-Moseley CD Pascal JP Williams GC Integrative
nonpharmacologic behavioral interventions for the management of Cancer-Related fatigue The
Oncologist 2007 12(1)52-67
Reason for exclusion Not population of interest
Neill J Belan I Ried K Effectiveness of non-pharmacological interventions for fatigue in adults with
multiple sclerosis rheumatoid arthritis or systemic lupus erythematosus a systematic review
Journal of Advanced Nursing 2006 Dec 56(6)617-35
Reason for exclusion Not population of interest
Rheingans JI A systematic review of nonpharmacologic adjunctive therapies for symptom management
Journal of Pediatric Oncology Nursing 2007 24(2) 81-94
683
52
Reason for exclusion Not outcome of interest
Rheingans JI Pediatric oncology nursesrsquo management of patients symptoms Journal of Pediatric
Oncology Nursing 2008 Nov 25(6) 303-11
Reason for exclusion Not outcome of interest
San Juan AF Fleck SJ Chamorro-Vintildea C Mateacute-Muntildeoz JL Moral S Peacuterez M Cardona C Del Valle MF
Hernaacutendez M Ramiacuterez M Madero L Lucia A Effects of an intrahospital exercise program
intervention for children with leukemia Medicine amp Science in Sports amp Exercise 2007 Jan
39(1)13-21
Reason for exclusion Not outcome of interest
Sanford SD Okuma JO Pan J Srivastava DK West N Farr L Hinds PS Gender differences in sleep
fatigue and daytime activity in a pediatric oncology sample receiving dexamethasone Journal of
Pediatric Psychology 2008 Apr 33(3)298-306 Epub 2007 Nov 17
Reason for exclusion Not experimental or quasi-experimental study
Schmitz KH Holtzman J Courneya KS Macircsse LC Duval S Kane R Controlled physical activity trials in
cancer survivors a systematic review and meta-analysis Cancer Epidemiol Biomarkers Prev
2005 Jul 14(7)1588-95
Reason for exclusion Not population of interest
van Brussel M Takken T Lucia A van der Net J Helders PJ Is physical fitness decreased in survivors of
childhood leukemia A systematic review Leukemia 2005 Jan 19(1)13-7
Reason for exclusion Not population of interest
Whiting P Bagnall AM Snowden AJ Cornell JE Mulrow CD Ramirez G Interventions for the treatment
and management of chronic fatigue syndrome JAMA 2001 Sep 19 286(11)1360-8
Reason for exclusion Not intervention of interest
Whitsett SF Gudmundsdottir M Davies B McCarthy P Friedman D Chemotherapy-related fatigue in
childhood cancer correlates consequences and coping strategies Journal of Pediatric
Oncology Nursing 2008 Mar-Apr 25(2)86-96 Epub 2008 Feb 29
Reason for exclusion Not experimental or quasi-experimental study
Winner C Muumlller C Hoffmann C Boos J Rosenbaum D Physical activity and childhood cancer Pediatr
Blood Cancer 2010 Apr 54(4)501-10
Reason for exclusion Not research study
684
53
Wu M Hsu L Zhang B Shen N Lu H Li S The experiences of cancer-related fatigue among Chinese
children with leukaemia A phenomenological study Journal of Nursing Studies 2010 Jan
47(1)49-59 Epub 2009 Aug 25
Reason for exclusion Not experimental or quasi-experimental study
Yeh CH Chiang YC Lin L Yang CP Chien LC Weaver MA Chuang HL Clinical factors associated with
fatigue over time in paediatric oncology patients receiving chemotherapy British Journal of
Cancer 2008 Jul 8 99(1)23-9 Epub 2008 Jun 24
Reason for exclusion Not experimental or quasi-experimental study
685
52
Reason for exclusion Not outcome of interest
Rheingans JI Pediatric oncology nursesrsquo management of patients symptoms Journal of Pediatric
Oncology Nursing 2008 Nov 25(6) 303-11
Reason for exclusion Not outcome of interest
San Juan AF Fleck SJ Chamorro-Vintildea C Mateacute-Muntildeoz JL Moral S Peacuterez M Cardona C Del Valle MF
Hernaacutendez M Ramiacuterez M Madero L Lucia A Effects of an intrahospital exercise program
intervention for children with leukemia Medicine amp Science in Sports amp Exercise 2007 Jan
39(1)13-21
Reason for exclusion Not outcome of interest
Sanford SD Okuma JO Pan J Srivastava DK West N Farr L Hinds PS Gender differences in sleep
fatigue and daytime activity in a pediatric oncology sample receiving dexamethasone Journal of
Pediatric Psychology 2008 Apr 33(3)298-306 Epub 2007 Nov 17
Reason for exclusion Not experimental or quasi-experimental study
Schmitz KH Holtzman J Courneya KS Macircsse LC Duval S Kane R Controlled physical activity trials in
cancer survivors a systematic review and meta-analysis Cancer Epidemiol Biomarkers Prev
2005 Jul 14(7)1588-95
Reason for exclusion Not population of interest
van Brussel M Takken T Lucia A van der Net J Helders PJ Is physical fitness decreased in survivors of
childhood leukemia A systematic review Leukemia 2005 Jan 19(1)13-7
Reason for exclusion Not population of interest
Whiting P Bagnall AM Snowden AJ Cornell JE Mulrow CD Ramirez G Interventions for the treatment
and management of chronic fatigue syndrome JAMA 2001 Sep 19 286(11)1360-8
Reason for exclusion Not intervention of interest
Whitsett SF Gudmundsdottir M Davies B McCarthy P Friedman D Chemotherapy-related fatigue in
childhood cancer correlates consequences and coping strategies Journal of Pediatric
Oncology Nursing 2008 Mar-Apr 25(2)86-96 Epub 2008 Feb 29
Reason for exclusion Not experimental or quasi-experimental study
Winner C Muumlller C Hoffmann C Boos J Rosenbaum D Physical activity and childhood cancer Pediatr
Blood Cancer 2010 Apr 54(4)501-10
Reason for exclusion Not research study
684
53
Wu M Hsu L Zhang B Shen N Lu H Li S The experiences of cancer-related fatigue among Chinese
children with leukaemia A phenomenological study Journal of Nursing Studies 2010 Jan
47(1)49-59 Epub 2009 Aug 25
Reason for exclusion Not experimental or quasi-experimental study
Yeh CH Chiang YC Lin L Yang CP Chien LC Weaver MA Chuang HL Clinical factors associated with
fatigue over time in paediatric oncology patients receiving chemotherapy British Journal of
Cancer 2008 Jul 8 99(1)23-9 Epub 2008 Jun 24
Reason for exclusion Not experimental or quasi-experimental study
685
53
Wu M Hsu L Zhang B Shen N Lu H Li S The experiences of cancer-related fatigue among Chinese
children with leukaemia A phenomenological study Journal of Nursing Studies 2010 Jan
47(1)49-59 Epub 2009 Aug 25
Reason for exclusion Not experimental or quasi-experimental study
Yeh CH Chiang YC Lin L Yang CP Chien LC Weaver MA Chuang HL Clinical factors associated with
fatigue over time in paediatric oncology patients receiving chemotherapy British Journal of
Cancer 2008 Jul 8 99(1)23-9 Epub 2008 Jun 24
Reason for exclusion Not experimental or quasi-experimental study
685