prognostic factors of patients with spinal chondrosarcoma: a retrospective analysis of 98...

ORIGINAL ARTICLE – BONE AND SOFT TISSUE SARCOMAS

Prognostic Factors of Patients with Spinal Chondrosarcoma:A Retrospective Analysis of 98 Consecutive Patients in a SingleCenter

Huabin Yin, MD1,4, Wang Zhou, MD1, Jia Meng, MD2, Dan Zhang, MD1, Zhipeng Wu, MD1, Ting Wang, MD1,

Jing Wang, MD1, Peng Wang, MD3, Xin Shi, MD2, Sujia Wu, MD2, Jianning Zhao, MD2, and Jianru Xiao, MD1

1Department of Bone Tumor Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, China;2Department of Orthopaedics, Jinling Hospital, Clinical School of Medical College, Nanjing University, Nanjing, Jiangsu,

China; 3Department of Radiology, Changzheng Hospital, Second Military Medical University, Shanghai, China;4Department of Orthopedics, 149 Hospital, Lianyungang, Jiangsu, China

ABSTRACT

Purpose. Chondrosarcoma (CHS) in the spine is relatively

rare and minimal information has been published in the

literature regarding this subject. The objective of our study

was to discuss the factors that may affect outcomes of

patients with spinal CHS.

Methods. Univariate and multivariate analyses were per-

formed to identify prognostic factors for recurrence, distant

metastasis, and survival of spinal CHS. T test, v2 test and

rank sum test were used to analyze a single factor for

recurrence and metastasis, while survival rate was esti-

mated using the Kaplan–Meier method. Factors with p

values of B0.1 were subjected to multivariate analyses by

binary logistic regression analyses or Cox regression

analyses. p Values of B0.05 were considered statistically

significant.

Results. A total of 98 patients with spinal CHS were

included in the study. The mean follow-up period was

49.7 months (range 6–178). Recurrence was detected in 42

patients after initial surgery in our center, while distant

metastasis and death occurred in 24 and 32 cases, respec-

tively. The statistical analyses suggested that pathology

grade III was closely related with distant metastasis which

was an independent prognostic factor for overall survival.

Total en bloc spondylectomy could significantly decrease

the risk of recurrence, distant metastasis, and death of

patients with spinal CHS.

Conclusions. Total en bloc spondylectomy could signifi-

cantly decrease the risk of recurrence and distant

metastasis, and meanwhile improve overall survival of

spinal CHS. Distant metastasis which was closely associ-

ated with pathology grade III was an adverse prognostic

factor for overall survival of spinal CHS.

Chondrosarcoma (CHS) is one of the most common types

of malignant bone tumor and usually occurs in patients

between 30 and 70 years of age.1,2 According to the World

Health Organization (WHO), CHS is a family of malignant

tumors characterized by their ability for cartilage formation.3

Pelvis, femur, and shoulder girdle are the most frequent sites

of CHS, while the incidence of spinal CHSs is estimated to be

less than 12 %.4–7 Spinal CHS is generally a slowly-growing

tumor, but it exhibits strong local aggressiveness.2,5,8 Com-

plete resection is advocated for spinal CHS, but anatomic

constraints hinder such efforts and local recurrence rates

range from 40 to 75 %.5,9,10 Distant metastasis is sparsely

reported in the literature and considered to be associated with

Huabin Yin, Wang Zhou, and Jia Meng contributed equally to this

work, and all should be considered first author.

Electronic supplementary material The online version of thisarticle (doi:10.1245/s10434-014-3745-z) contains supplementarymaterial, which is available to authorized users.

� Society of Surgical Oncology 2014

First Received: 21 February 2014

S. Wu, MD

e-mail: [email protected]

J. Zhao, MD


J. Xiao, MD


Ann Surg Oncol

DOI 10.1245/s10434-014-3745-z

http://dx.doi.org/10.1245/s10434-014-3745-z

higher tumor grade and local recurrence.2,9–11 Regarding

survival, it is difficult to extract exact information due to the

lack of large series in the existing literature.

In the literature, there are only some case series of spinal

CHS with small sample sizes and most of the published

information was about the relationship between different

surgical options and recurrence.2,4–7,9,10,12 We previously

reported a series of CHS in the cervical and cervicothoracic

spine, but sample size and short follow-up limited its ability

to provide much information.2 As for distant metastasis and

overall survival of spinal CHS, any convincing information

in the literature is scarce. In addition, bisphosphonate treat-

ment, which is widely used and believed to control CHS in

both clinical treatment and experimental research, was not

evaluated in the previous studies.13–16 Therefore, a system-

atic analysis of a large case series to analyze the prognostic

factors for recurrence, distant metastasis, and overall sur-

vival of spinal CHS is very essential. The objective of our

study was to identify the prognostic factors of spinal CHS by

analyzing a large case series undergoing surgery.

MATERIALS AND METHODS

Patients

From August 1998 to January 2011, 98 cases of spinal

CHS were surgically treated and documented in our center.

This study was approved by the hospital Ethics Committee

and informed consent was obtained from the surviving

patients or family members of those who had died.

A diagnosis of CHS was confirmed by pathology in all

patients. Preoperative neurologic status was classified

according to the Frankel score.17 The pathologic feature

was classified into WHO grades I–III according to histo-

logical appearance.18–20 Surgical strategy was decided for

each patient according to Tomita classification, Enneking

stage, and Weinstein–Boriani–Biagini systems.21–23 Sur-

geries were performed by posterior approach, anterior

approach, or a combination.24,25

The research tried to identify the prognostic factors for

patients with spinal CHS after the initial surgery in our

center. All patients were followed up at 3, 6, and

12 months after surgery, every 6 months for the next

2 years, and then annually for life.26 The follow-up period

was defined as the interval from the date of surgery to

death, or until December 2013 for alive patients. The

recurrence and distant metastasis status was confirmed on

the basis of clinical manifestations and imaging findings in

outpatient follow-up, or pathologic evaluation of second

surgery. Death status and time of death were acquired

through telephone interviews.

Statistical Method

Quantitative data are described by median (range), and

qualitative data are described as counts and percentages.

The univariate and multivariate analyses of various clinical

factors were performed to identify independent variables

that could predict prognosis. Patient factors were age, sex,

treatment history, and preoperative Frankel score. Tumor

factors were location, number of involved segments,

Enneking stage, Tomita classification, and pathologic fea-

tures. Treatment factors were preoperative selective artery

embolism (PAE), surgical approach, resection mode and

local treatment with cisplatin or methotrexate, intraopera-

tive blood loss, bisphosphonate treatment with zoledronic

acid or incadronate disodium, and adjuvant radiotherapy.

Recurrence was also evaluated as a possible factor for

distant metastasis, while the impact of recurrence and

distant metastasis were tested for overall survival.

Data were analyzed using SPSS version 17.0. (SPSS,

Inc., Chicago, IL, USA). T test, v2 test, and rank sum test

were used to analyze the single factors for recurrence and

metastasis, with factors of p B 0.1 subjected to multivari-

ate analysis by binary logistic regression analysis. The

Kaplan–Meier method was used to estimate postoperative

survival, and survival curves were compared using a log-

rank test. Factors with p values B0.1 were subjected to

multivariate analysis by Cox regression analysis. p Values

B0.05 were considered statistically significant.

RESULTS

The series was comprised of 66 men and 32 women,

with a mean age of 43.4 years (median 44, range 17–71).

Of these patients, 67 were admitted for primary CHS, and

the remaining 31 were recurrent CHS after surgical treat-

ment in other institutions. The mean follow-up period was

49.7 (median 41.0, range 6–178) months. Recurrence was

detected in 42 patients after initial surgery in our center,

while distant metastasis and death occurred in 24 and 32

cases, respectively. The mean time from surgery to recur-

rence was 15.4 months (median 14.0, range 3–40), while

follow-up for the dead patients was 31.3 months (median

32.0, range 6–68). Of these patients, 38 (90.4 %) devel-

oped recurrence within 24 months, and 21 (67.7 %) died of

disease progression or lung metastasis within 36 months.

Univariate and Multivariate Analysis of Prognostic

Factors for Recurrence

Postoperative recurrence is not uncommon for CHS; the

recurrence rate for spinal CHS is considered to be higher

due to anatomic constraints of the spine.5,9,10 Overall

recurrence rates were 42.9 % in our series, and the

H. Yin et al.

univariate analysis of clinical factors is shown in Table 1.

In this study, patients with Enneking stages II and III had a

higher recurrence rate than those of Enneking stage I

(p B 0.0005). Recurrence rate was significantly different

between patients with pathology grades I–III (p B 0.0005).

Patients with lesions evaluated as Tomita I–III had an

obviously lower recurrence rate than those evaluated as

Tomita IV–VII (p = 0.031).

Subtotal resection was applied in 21 patients, piecemeal

total spondylectomy in 48 patients, and total en bloc

spondylectomy in 29 cases. Recurrence rate was obviously

different between patients with three different resection

modes (p B 0.0005). Cisplatin and methotrexate were used

as local treatment to soak the surgery field after tumor

resection.27 There was no significant difference of recur-

rence rate in patients who received local treatment

(p = 0.276). The mean intraoperative blood loss was

2,173 ml (median 2,000, range 200–6,000). Patients with

intraoperative blood loss[2,000 ml had a lower recurrence

rate than those with intraoperative blood loss B2,000 ml

(p = 0.047). PAE was used in 32 patients to reduce

intraoperative blood loss, but no significant difference in

recurrence rate was observed (p = 0.802).

Zoledronic acid and incadronate disodium, which are

bisphosphonates, are used to control osteolytic lesions of

bone tumors in our center.27 Fifteen patients received

zoledronic acid and incadronate disodium was used in 34

cases; however, no significant difference in recurrence rate

was found (p = 0.336). Adjuvant radiotherapy (30–55 Gy)

was administered postoperatively in 52 patients. Patients

with adjuvant radiotherapy had a higher recurrence rate

than those without (p B 0.0005). There was no significant

difference in other factors of age, sex, treatment history,

location, number of involved segments, preoperative

Frankel score, and surgical approach.

Potential prognostic factors extracted by univariate

analysis were submitted to multivariate analysis by binary

logistic regression. Resection mode was evaluated as an

effective variate for recurrence. The risk of recurrence was

significantly decreased in patients who accepted total

spondylectomy [piecemeal total spondylectomy: hazard

ratio (HR) 0.033, p = 0.001; total en bloc spondylectomy:

HR 0.006, p \ 0.0005].

The above results showed that resection mode had

effective factors for recurrence, and total spondylectomy

by either en bloc or piecemeal strategy was associated with

a lower recurrence rate. Details are listed in Table 2.

Statistical Analysis of Factors Related to Distant

Metastasis

Distant metastasis is another important event for CHS,

with lungs as the most frequent site.28 Twenty-four patients

(24.5 %) experienced distant metastasis, and lung metastasis

was found in 16 (66.7 %) patients. The univariate analysis of

the prognostic factors for distant metastasis is shown in

Table 1. According to univariate analysis, single factors

for distant metastasis were number of segments involve-

ment (p = 0.007), Enneking stage (p = 0.001), Tomita

classification (p = 0.027), adjuvant radiotherapy

(p = 0.003), and recurrence (p B 0.0005). There was also

significant difference in metastasis rate between pathology

grade (p B 0.0005) and resection mode (p B 0.0005).

Multivariate analysis by binary logistic regression was

carried out to identify independent prognostic factors. Total

en bloc spondylectomy and pathology grade III were eval-

uated as effective variates for distant metastasis. The risk of

distant metastasis was significantly lower in patients who

accepted total en bloc spondylectomy (p = 0.018; HR

0.056), while patients with CHS pathology grade III had a

significantly higher metastasis rate (p = 0.008; HR 10.530).

The above results showed that total en bloc spondylec-

tomy and pathology grade III were independent prognostic

factors for distant metastasis. Details are listed in Table 3.

Survival Analysis of Patients with Spinal CHS

Thirty-two patients (32.7 %) suffered death in our series;

univariate analysis of prognostic factors affecting survival is

shown in Table 1. According to statistical analysis using the

Kaplan–Meier method, worse survival was found in patients

with CHS Enneking stages II and III (p = 0.001), adjuvant

radiotherapy (p = 0.011), recurrence (p B 0.0005), and

distant metastasis (p B 0.0005). There was a significant

difference of survival between pathology grades I–III

(p B 0.0005) and resection mode (p B 0.0005).

The above factors, along with Tomita classification

(p = 0.098) and number of involved segments (p = 0.072),

were submitted to the multivariate Cox regression model for

survival analysis. The risk of death from disease was closely

related with total en bloc spondylectomy and distant

metastasis. The HR of distant metastasis was 16.333 for

survival (p B 0.0005). Total en bloc spondylectomy signif-

icantly decreased the risk of death (p = 0.004; HR 0.047).

The Kaplan–Meier curves of survival for total en bloc

spondylectomy and distant metastasis are shown in Fig. 1.

The result of survival analysis showed total en bloc

spondylectomy and distant metastasis were independent

prognostic factors for overall survival of spinal CHS.

Details are listed in Table 4.

DISCUSSION

CHS is the third most common primary malignant bone

tumor.26,39 The spine is a relatively rare site but poses great

challenge for the treatment of CHS.2,4–7 How to prevent

Prognostic Factors for Spinal Chondrosarcoma

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H. Yin et al.

postoperative recurrence is a hot issue of spinal CHS,

whereas distant metastasis and overall survival after surgery

are still unclear. In this research, we performed univariate

and multivariate analyses to investigate prognostic factors

for recurrence, distant metastasis, and overall survival of

patients with spinal CHS. The results suggested that

pathology grade III was closely related with distant metas-

tasis which was an independent prognostic factor for

survival. Total en bloc spondylectomy could significantly

decrease the risk of recurrence, distant metastasis and death.

In our series, the mean age was 43.4 years, with 73.5 %

of cases occurring between 30 and 70 years of age, which

was similar to the findings of previous reports.4–7 The male

to female ratio was 2.1:1, which is quite different from the

equal sex representation reported by Boriani et al.5 and

York et al.10 In our series, age was not an independent

prognostic factor for postoperative recurrence, distant

metastasis, and overall survival of spinal CHS. The same

results were achieved for sex, treatment history, location,

number of involved segments, preoperative Frankel score,

intraoperative blood loss, and surgical approach.

Histopathologically, CHS can be classified into con-

ventional CHS and variant types. Meanwhile, conventional

CHS can be further classified into primary and secondary.8

The histopathological classification of spinal CHS is quite

complex and confusing, whereas pathology features of

three different grades were widely recognized and con-

sidered to be reliable predictors of clinical behavior.19,20,29

The findings in our study suggested that pathology grade

was not an independent prognostic factor for recurrence

and overall survival, but pathology grade III was closely

associated with distant metastasis.

Surgery is the foundational treatment strategy for spinal

CHS, with the aim of preserving or even improving func-

tionality, relieving pain, controlling local recurrence, and

promising prolonged survival.5,8,30 The spectrum of sur-

gical procedures applicable to the spinal column varies

from the simplest subtotal resection (curettage) to the most

complex total en bloc spondylectomy.8,23 The findings in

our research suggest that total spondylectomy, by either en

bloc or piecemeal methods, could significantly decrease the

recurrence rate of spinal CHS.

Although piecemeal total spondylectomy is confirmed to

be superior to subtotal spondylectomy for spinal CHS, it is

associated with a possibility of tumor cell contamination in

the surgical field.27 Total en bloc spondylectomy, which is

hard to achieve because of the anatomical complexity of

the spine, is reported to have excellent prognosis.2,5,7,8,24

The findings in our study showed that total en bloc

spondylectomy could not only minimize recurrence but

also significantly decrease distant metastasis and improve

survival.

Total en bloc spondylectomy is a procedure aimed at

surgically removing a tumor in a single, intact piece, fully

encased by a continuous shell of healthy tissue (margin).23

Anatomical complexity of the spine makes it technically

demanding, and careful surgical planning according to the

Tomita classification, Enneking stage, and Weinstein–Bo-

riani–Biagini systems is of great importance. Basically,

most tumors of Tomita types I–IV, and some tumors of

types V and VI, are suitable for total en bloc spondylec-

tomy, but it is not recommended for tumors of Tomita type

VII. Meanwhile, total en bloc spondylectomy is appropri-

ate for most tumors of Enneking stages I and II, but is not

adopted for tumors of Enneking stage III. As anatomical

structures, especially nerve roots, should be sacrificed to

achieve appropriate margins, the upper cervical and lower

lumbar spine cannot be excised in an ideal en bloc manner

owing to its proximity to vital neurovascular structures.2,31

Total en bloc spondylectomy is considered to have more

complications than the other two surgical procedures and

its complications in the spine, which have been widely

discussed in the literature, can be divided into major and

minor according to McDonnell et al.32–34

TABLE 2 Multivariate analysis of prognostic factors for recurrence

Factors B HR p Value

Enneking stage 0.199

Pathology grade II 0.905

Pathology grade III 0.104

Tomita classification 0.967

Total piecemeal spondylectomy -3.419 0.033 0.001*

Total en bloc spondylectomy -5.155 0.006 \0.0005*

Intraoperative blood loss 0.102

Adjuvant radiotherapy 0.728

HR hazard ratio, B coefficient value

* p B 0.05

TABLE 3 Multivariate analysis of prognostic factors for distant

metastasis



Number of involved segments 0.259


Pathology grade III 2.354 10.53 0.008*


Total piecemeal spondylectomy 0.064

Total en bloc spondylectomy -2.878 0.056 0.018*


Recurrence 0.541


* p B 0.05


Distant metastasis is not uncommon for CHS and the

lung serves as the most frequent site.28 Due to the rarity of

spinal CHS, detailed data about distant metastasis was not

covered in the literature. About 24.5 % of patients in our

series suffered distant metastasis, with two-thirds involving

the lung. We found that pathology grade III was closely

associated with it; meanwhile, distant metastasis signifi-

cantly increased the risk of death.

Radiotherapy and chemotherapy were used as adjuvant

therapies for spinal CHS, but their positive effect on

recurrence and overall survival seemed to be of little

importance.4,5,8,10,35,36 We further confirmed that intraop-

erative local chemotherapy and postoperative radiotherapy

could not improve recurrence, distant metastasis, and

overall survival of spinal CHS.

In our study, it was found that PAE and bisphosphonate

treatment were not independent prognostic factors for

spinal CHS. PAE could reduce intraoperative blood loss

and improve the excision rate and safety of surgery,37,38

but it could not improve the prognosis, including recur-

rence, distant metastasis, and overall survival.

Bisphosphonates are confirmed to control human CHS cells

in in vitro studies,13,14,16 and could significantly relieve

cancer pain in clinical treatment.15 The pain control effect

of bisphosphonates was also verified in the treatment of

spinal CHS in our center, but its positive effect for recur-

rence, distant metastasis, and overall survival was not

confirmed in our series.

As far as we know, our series is the largest to date of

spinal CHS, with the almost longest follow-up until now;

meanwhile, it is the first to focus on prognostic factors for

distant metastasis and overall survival. However, the nature

of a retrospective study is a limitation of this study, and the

duration of follow-up might not be long enough because

late (3 years or more) local recurrence was sparsely

reported.5,8

CONCLUSIONS

Total en bloc spondylectomy significantly decreased the

risk of recurrence, distant metastasis, and improve overall

survival of spinal CHS. Distant metastasis which was

closely associated with pathology grade III was an adverse

prognostic factor for overall survival of spinal CHS.

ACKNOWLEDGMENT This work was supported by the Shang-

hai Science Foundation of China (12DZ2295103).

0.00

0.0

0.2

0.4

0.6

0.8

1.0

50.0 100.0

Survival time(m)

Per

cent

Sur

viva

lBA

0.0

0.2

0.4

0.6

0.8

1.0

Per

cent

Sur

viva

l

150.00 200.00

Resection modeSubtotal

Piecemeal total

Total en bloc

Subtotal-censored

Piecemeal total-censoredTotal en bloc-censored

0.00 50.0 100.0

Survival time(m)

150.00 200.00

Distant metastasisNoYesNo-censoredYes-censored

FIG. 1 Kaplan–Meier curves of survival for a resection mode and b distant metastasis

TABLE 4 Multivariate analysis of prognostic factors affecting

survival



Number of involved segments 0.243


Pathology grade III 0.687


Total piecemeal spondylectomy 0.228

Total en bloc spondylectomy -3.053 0.047 0.004*


Recurrence 0.111

Distant metastasis 2.793 16.333 \0.0005*


* p B 0.05

H. Yin et al.

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