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Cancer survivorship Helen Hatcher and TV Ajithkumar

Cambridge University Hospitals NHS Trust

What is survivorship?

• Issues after cancer treatment

• Cancer and beyond

• Co-survivorship

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Survivorship

• The time from the understanding of being given a diagnosis of cancer

• Previously used to relate to the “cure” “remission” terms that can be used after successful treatment

• However…the effects start from the point of diagnosis and are unrelated to a clinical opinion of the severity of that diagnosis

Impact of successful cancer treatment

• 1 in 250 adults of working age are survivors of childhood or TYA cancer

• More than 70% adults with cancer survive 5 years or more

• Late effects are often multiple

• 30% of survivors report 2-3 long term effects

• The “new normal”

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The many facets of survivorship

Physical Psychosocial

Health behaviours

https://cancercontrol.cancer.gov/ocs/about/staff.html

Medical late effects

• Cancer

• Treatment

• Family genetics

• Developmental stage of individual

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Paediatric Radiation Oncology:

Are children small adults?

Target volumes

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Beam arrangement

Beam size

Beam shape

Beam weight

Beam energy

Human brain development Neural connection for different functions develop sequentially

https://developingchild.harvard.edu/resources/inbrief-science-of-ecd/

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Persistent stress changes brain architecture

https://developingchild.harvard.edu/resources/inbrief-science-of-ecd/

40-90% develop cognitive dysfuntion

• Global cognitive functioning (IQ)

• Academic achievement

• Executive function

– High level task goals

• Psychomotor skills

Ullrich et al. Seminars Pediatr Neurol 2012, 19:35 Padovani et al. Nat Rev Neurol 2012, 8:578 Ajithkumar et al. Lancet Oncol, 2017,18:e91-e100.

Neurocognitive dysfunction

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Neurocognitve dysfunction

Risk factors

Correlation between individual genetic characteristics and cognition e.g. GST, COMT, MTR genes

Wefel et al. Lancet Oncol, 2016; 17: e97

Acute (during and within 6 weeks of treatment)

Predominantly fast proliferating tissues

Skin, mucosa and haemopoetic system

Late (6 weeks after treatment)

Slow proliferating

Lung, kidney, heart, liver & CNS

Side-effects of radiotherapy

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Skin Erythema, desquamation, ulceration

Atrophy, fibrosis, telangiectasia

Mucosa Mucositis

Ulceration, atrophy, fibrosis, necrosis

Lung Pneumonitis, fibrosis

Heart Pericarditis, cardiomyopathy

CNS Somnolence, myelitis, necrosis

Radiotherapy for radiologists

Side-effects of radiotherapy

RADIOTHERAPY IN CHILDREN

Challenges of

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Childhood tumours

https://www.childrenwithcancer.org.uk/childhood-cancer-info/types-of-cancer/

Challenges of Radiotherapy

Larger tumour

Radiation tolerance

Normal organs

Growth

Epiphyseal plates (18 Gy), muscle

Hormone: Pituitary (20 Gy)

Fertility

Testis and ovary (5 Gy)

Other organs

Brain, heart, lung, genital system etc.

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Challenges of radiotherapy

Conformal plan to cover PTV can lead

to asymmetrical growth

Target near vertebrae: include vertebrae in

the field leading to compromise with

sparing

Issue of second cancer

Craniospinal radiotherapy

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Reality…………

5 10 cm Depth

Dose

(%)

Ideally………

T

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Why protons?

Spreading of Bragg peak (SOBP)

65MeV 140meV 200MeV

5 10 cm Depth

Dose

(%)

Effective range varies with proton Energy

The Bragg Peak

Proton beam energies

Wilson R. Radiological use of fast protons Radiology 1946;47, 487-491

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Proton therapy

IMRT Proton Conventional

Late effects

• Nervous system • Chemo-brain

• Respiratory system

• Cardiovascular • Coronary disease • Cardiomyopathy

• Renal

• Reproductive system • Infertility

• Skeletal • Osteronecrosis • Osteoporosis

BMJ. 2016 Sep 7;354:i4567.

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Late-mortality among 5-year survivors

• Primary cancer:58%

• Second cancer: 19%

• Cardiac: 7%

• Respiratory: ~3%

Ann C. Mertens et al. JNCI J Natl Cancer Inst 2008;100:1368-1379

Second cancer

• 2nd most common cause of death after curative treatment

Second cancer Identified or potential risk factors

Leukaemia Chemotherapy e.g. etoposide, anthracyclines

Sarcoma Radiotherapy for e.g. previous sarcoma or retroperitoneal lymph nodes

Genetics e.g. Li Fraumeni, hereditary retinoblastoma

Lung Radiotherapy especially in smokers

Potential risk from multiple CT scans for follow up

Breast Radiotherapy e.g. mantle or hemi thorax especially if given in late teens or early

twenties (up to 4-7 times the standardised mortality ratio)

Uterine Tamoxifen (risk 1 in 100 000), increased in those with HNPCC

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Psychosocial issues

• Psychological • Anxiety, depression

• Fear of recurrence

• Survivorship guilt

• Post-traumatic stress

• Social • Isolation

• Relationships

• Employment/training

“I just don’t know what to do with myself now. I thought I was going to die, but I think

I’m okay. I keep wondering-who would I have been if this hadn’t happened?”

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A systematic approach to survivorship

• Palliation

• Prevention or Preservation

• Health Promotion

Ganz PA. BMC Med. 2011 Feb 10;9:14.

Individualised treatment summaries and care plans

Palliation

• Fatigue

• Pain

• Depression

• Physical limitations

• Cognitive changes

• Sexual dysfunction

• Body Image

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Fatigue

• “a distressing, persistent, subjective sense of physical, emotional, and/or cognitive tiredness or exhaustion related to cancer or cancer treatment that is not proportional to recent activity, interferes with usual functioning and is not improved by rest.”

• Affects 30% cancer survivors long term and over 90% during Tx

• Measures • Manage reversible causes (thyroid/testosterone/anaemia)

• CBT

• Short burst of exertion – structured exercise routine

Prevention

• Early detection and early intervention

• Chemoprevention

• Life style modifications

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Preservation Fertility

• Female • Cryopreservation

• Embryo

• Mature oocyte

• Ovarian tissue

• (LHRH analogues)

• Male • Sperm cryopreservation

• Microsurgical testicular sperm extraction followed by ICSI

“I was treated at the ages of 13 and 17. I only recently found out, from the internet, that it can make you infertile.”

Health Promotion

• To minimise problems of second cancer, cardiac problems and others

• Encourage healthy-life style • Diet

• Weight

• Regular exercise

• Avoid risky behaviour – alcohol, substance abuse

• Compliance with screening visits

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BMJ. 2016 Sep 7;354:i4567.

Adult tumours

PROSTATE

MELANOMA UTERINE

BREAST

COLORECTAL

Slide courtesy A Milano

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Pelvic tumours

• Local treatment • urinary incontinence (50%)

• sexual dysfunction (95%)

• bowel dysfunction (50%)

Hormonal treatment

• Women • hot flashes, night sweats, atrophic

vaginitis, arthralgia and osteoporosis

• Male • ‘menopause’ : loss of libido, hot flashes,

night sweats, irritability, and gynaecomastia

• risk of osteoporosis, obesity, diabetes

• Sexual dysfunction

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Challenges of survivorship plans

• Lack of clear understanding of mechanisms

• Limited research leading to weak evidence-based approach

• Poor focus on survivorship

• Financial constraints

Key components of survivorship plan

• Follow-up plan • For detection of recurrence

• For screening of second primaries

• Any new, usual and/or persistent symptoms (to detect recurrence)

• List of likely or rare but clinically significant late and/or long-term effects

• Emotional or mental health, parenting, work/employment

• Life style modification: healthy diet, exercise, smoking cessation and alcohol use reduction

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Summary

• Start addressing issues of survivorship at diagnosis • Choosing the optimal treatment

• Ensure optimal preventative/ preservation strategies

• Individualised treatment summaries and survivorship advice

• Participate in research

The future for a survivor…

“I have come to learn that cancer is not something I will get over, but something I live with. For some reason I thought I could put it in a neat box and forget about it. But actually when it has been part of your life for so long you should (a) be proud of what you have accomplished and (b) take all you have learned and have fun!”