Pediatr Blood Cancer 2014;61:1925–1931

Evaluation of Outcome and Prognostic Factors in Extraosseous Ewing Sarcoma

Bivas Biswas, MD,1 N.K. Shukla, MD,2 S.V.S. Deo, MD,2 Sandeep Agarwala, MD,3 D.N. Sharma, MD,4
Sreenivas Vishnubhatla, PhD,5 and Sameer Bakhshi, MD1*

Background. Data on extraosseous Ewing sarcoma (EES) with analysis, hemoglobin 10 g/dl (P ¼ 0.03), and white blood cell count
uniform chemotherapy protocol are minimal. We aimed to examine (WBC) >11  109/L (P ¼ 0.009) predicted inferior EFS for the entire
this aspect in our patients, identify prognostic factors and compare EES cohort. Low hemoglobin (P ¼ 0.05) and high LDH (P ¼ 0.01)
the same with osseous Ewing sarcoma. Procedures. A single predicted inferior OS for the entire EES cohort on multivariate
institutional data review of patients with EES treated between analysis. As compared to the cohort of skeletal primary (n ¼ 314),
June 2003 and November 2011 with uniform chemotherapy and higher proportion of patients underwent surgery in the cohort of EES
evaluated on intent-to-treat analysis was done. Results. Of 374 (P ¼ 0.003); EFS (P ¼ 0.004) and OS (P ¼ 0.08) were superior for
patients with Ewing sarcoma, 60 (16%) were EES with median age patients with EES than patients with skeletal Ewing sarcoma.
16 years; 20 (33%) had metastases. After median follow-up of Conclusion. These data of EES suggests that low hemoglobin and
25 months (range: 1.7–104.4), 5-year event free survival (EFS), OS, high WBC count adversely affect EFS. Overall outcome was
and local-control-rate were 47.1
7.9%, 61.6
7.8%, and significantly better for EES than skeletal primary tumors. Pediatr
77.9
8.6%, respectively for entire EES cohort. In multivariate Blood Cancer 2014;61:1925–1931. # 2014 Wiley Periodicals, Inc.

Key words: chemotherapy; outcome; primitive neuroectodermal tumor; prognostic factors; soft tissue

INTRODUCTION positivity for CD99 (MIC 2), and/or synaptophysin or chromog-

ranin. Other round cell tumors were ruled out by performing IHC
Ewing sarcoma can arise from bone or soft tissue. Extraosseous with leucocyte common antigen, desmin, and myogenin. Evalua-
Ewing sarcoma (EES) is rare and incidence varies from 6% to 47% tion for translocation [t(11;22)(q24;q11.2–12)] was not performed
of all Ewing sarcoma [1–5]. Historically they had been included in in this cohort as it was not available routinely in our institute.
rhabdomyosarcoma protocols [6]. As the incidence is low, Diagnosis of Ewing sarcoma was made after review of pathology
chemotherapy protocol has been extrapolated from that of skeletal slides with IHC panel. Extent of lesion was determined by
Ewing sarcoma. computed tomography (CT) or magnetic resonance imaging of the
There are few studies that evaluated prognostic factors in EES, local site. All patients underwent metastatic work up including bone
and the majority of the studies have included patients treated over scan, CT chest, and bone marrow biopsy.
long-span of time with small sample size, heterogeneous
chemotherapy protocol, lack of prognostication and conflicting
Treatment and Response Evaluation
results of outcome [4,6–24]. Here, we have analyzed the baseline
clinicopathological characteristics, outcome and prognostic factors Treatment protocol consisted of three phases: neoadjuvant
of 60 cases of EES treated at our institute over 8 years with uniform chemotherapy for 9–12 weeks, local therapy, which was then
chemotherapy protocol, and compared the same with skeletal followed with adjuvant chemotherapy. Chemotherapy was given
Ewing sarcoma. alternating 3-weekly cycle of VAC (vincristine at 1.4 mg/m2,

MATERIALS AND METHODS 1

Department of Medical Oncology, Dr. B. R. A. Institute Rotary Cancer
Patients Hospital, All India Institute of Medical Sciences, New Delhi, India;
2
Department of Surgical Oncology, Dr. B. R. A. Institute Rotary Cancer
This study involves data review of all patients with a proven Hospital, All India Institute of Medical Sciences, New Delhi, India;
diagnosis of Ewing sarcoma that were treated in our department 3
Department of Pediatric Surgery, Dr. B. R. A. Institute Rotary Cancer
from June 2003 to November 2011. Data of patients treated between Hospital, All India Institute of Medical Sciences, New Delhi, India;
4
January 2011 and November 2011 was collected prospectively. Department of Radiotherapy, Dr. B. R. A. Institute Rotary Cancer
Specifically, Ewing sarcoma of soft tissue origin (without any Hospital, All India Institute of Medical Sciences, New Delhi, India;
5
cortical bone involvement) was selected for this analysis. Ewing Department of Biostatistics, Dr. B. R. A. Institute Rotary Cancer
sarcoma arising from brain was excluded from this analysis. Hospital, All India Institute of Medical Sciences, New Delhi, India
Patient’s baseline clinic-pathological features, metastatic work up, Conflict of interest: Nothing to declare.
treatment modality, and outcome data were collected. Ethical Additional supporting information may be found in the online version
clearance was taken from institutional ethical and review of this article at the publisher’s web-site.
committee. Informed consent was taken from patient or guardian
Presentations: This was presented as an oral paper in 45th Annual SIOP
(in case of minor) in patients enrolled prospectively. Meeting at Hong Kong in Sept 2013.

Correspondence to: Sameer Bakhshi, Department of Medical
Diagnostic Work Up Oncology, Dr. B. R. Ambedkar Institute Rotary Cancer Hospital, All
All patients underwent biopsy (trucut or incisional) of primary India Institute of Medical Sciences, New Delhi-110029, India.
lesion with immunohistochemistry (IHC). Diagnosis of Ewing E-mail: [email protected]
sarcoma required presence of small blue round cell tumor and Received 25 February 2014; Accepted 21 April 2014

C 2014 Wiley Periodicals, Inc.
DOI 10.1002/pbc.25095
Published online 17 August 2014 in Wiley Online Library
(wileyonlinelibrary.com).
1926 Biswas et al.

max ¼ 2 mg; doxorubicin at 75 mg/m2 or actinomycin D at patients with Ewing sarcoma, 65 (16%) had EES. Five patients did
1.25 mg/m2 and cyclophosphamide at 1.2 gm/m2 with MESNA) not take therapy and so here we have analyzed baseline character-
with IE (ifosfamide at 9 gm/m2 with MESNA and etoposide at istics and survival of 60/374 (16%) patients. Median age was
500 mg/m2) [25] for total 48 weeks. Local therapy was radiotherapy 16 years (range: 0.1–48) with median symptom duration was 3.5
or surgery with or without post-operative radiotherapy. The choice months (range: 0.5–12 months). Median tumor diameter was 9.8 cm
of local therapy was made on an individual basis depending on (range: 2–24 cm) and tumor size >8 cm was observed in 28 (53%)
primary tumor site and resectability of tumor after neoadjuvant patients. Most common primary regions of disease included
chemotherapy with care to avoid long term morbidity and abdomen in 16 (27%), extremity in 14 (23%), head and neck in
disfigurement. Surgery was preferred wherever wide local excision 11 (18%), and thorax in 12 (11%) patients. Diagnostic work up
was possible with clear surgical margin and without a mutilating revealed metastases in 20 (33%) patients. Patients with EES had
surgery. The decision for surgical resection was taken by the shorter symptom duration (P ¼ 0.01) and higher prevalence in the
treating surgeon. In general, patients with pathological CR were not axial region (P ¼ 0.001) as compared to skeletal primary; further,
subjected to adjuvant radiotherapy although decisions for adjuvant higher proportion of patients with EES underwent surgical
radiotherapy were taken on an individual case to case basis after resection (P ¼ 0.003) as compared to skeletal primary (Table I).
discussion in the multidisciplinary clinic. After local therapy all
patients were subjected to receive adjuvant chemotherapy up to Treatment
planned total 48 weeks. Disease response was assessed by radiology
after neoadjuvant chemotherapy and after completion of local All 60 patients were subjected to neoadjuvant chemotherapy and
therapy. Complete remission (CR), partial response (PR), stable a median of six cycles (range: 4–7) of neoadjuvant chemotherapy
disease (SD), and progressive disease (PD) were defined as per was administered to all patients. Nine patients discontinued
RECIST criteria [26] wherever applicable. All patients without neoadjuvant chemotherapy (PR-5, SD-1 and not evaluated-3);
metastases underwent local therapy if they were in CR/PR/SD post six patients had PD while receiving neoadjuvant chemotherapy.
neoadjuvant chemotherapy while all patients with metastases Thus, 45 patients (75%) received local therapy: surgery was done in
received local therapy if they were in CR/PR at both primary and/or 30 (67%) patients of which 18 received adjuvant radiotherapy;
site(s) of metastases. definitive radiotherapy alone was administered in 15 (33%)
patients. Out of the 30 patients who underwent surgical resection,
R0 resection was achieved in 26 patients. Radiotherapy was given at
Statistical Analysis
a median dose of 50 Gy (range: 50–60 Gy) in 1.8–2 Gy/day, 5-days a
Descriptive statistics were used for demographics and clinical week and over 5–6 weeks. Seven patients were LFU (PR-3, CR-2,
characteristics. Chi-square test was used to detect association
between categorical variables. Student t-test test were applied to
compare continuous variables between groups. Survival was TABLE I. Comparison of Baseline Patients’ and Tumor
estimated by the Kaplan–Meier method and compared using log- Characteristics Between Skeletal and EES
rank test. Data were censored on June 30, 2013. Univariate Cox
proportional hazard model followed by stepwise multivariate Cox Skeletal Soft tissue
Variables (n ¼ 314) (n ¼ 60) P
regression analysis was done to identify the predictors of outcome.
Factors with significance (P value) of up to 0.1 in univariate analysis Mean age (years) 15.5 15.1 0.71
were taken into multivariate analysis. Event free survival (EFS) was Sex
calculated from date of diagnosis to date of disease relapse or Male 228 (73) 42 (70)
progression, death from any cause. Overall survival (OS) was Female 86 (27) 18 (30) 0.68
calculated from date of diagnosis to date of death from any cause. Systemic symptoms
No 216 (69) 48 (80)
Combined local and distant site failure was taken as local failure for
Yes 98 (31) 12 (20) 0.08
analysis of local control rate (LCR). Patients who were lost to
Mean symptom duration (months) 6.5 4.3 0.01
follow-up (LFU) or had treatment abandonment were also included Mean tumor diameter (cm) 9.8 9.2 0.4
for EFS and OS analysis and outcome in these patients was Tumor site
confirmed by telephonic contact. Treatment abandonment was Axial 170 (54) 46 (77)
included for survival analysis in the present study as it has been Appendicular 144 (46) 14 (23) 0.001
proposed that non-compliant and treatment abandonment patients Mean hemoglobin (g/dl) 11.8 11.5 0.2
should be included in survival analysis for studies from developing Mean WBC (/ml) 9,613 9,515 0.86
nations to provide a true picture of outcome from these countries Mean albumin (g/dl) 4.2 4.3 0.33
[27]. STATA/SE 9.0 (StataCorp LP, College Station, TX) was used Mean SAP (IU/L) 353 330 0.55
Mean LDH (U/L) 465 458 0.92
for statistical analysis.
Metastatic
No 184 (59) 40 (67)
RESULTS Yes 130 (41) 20 (33) 0.24
Local treatment type
Clinicopathological Profile Surgery 48 (23) 12 (26)
The clinical findings are summarized in Supplemental Table SI. Surgery þ radiotherapy 41 (20) 18 (41)
Radiotherapy 119 (57) 15 (33) 0.003
During the study period, 403 patients with Ewing sarcoma were
registered at our centre, and as per our intention-to-treat analysis LDH, lactate dehydrogenase; SAP, serum alkaline phosphatase; WBC,
374 patients were evaluable for survival analysis. Of the 403 white blood cell count.
Pediatr Blood Cancer DOI 10.1002/pbc
 Extraosseous Ewing sarcoma 1927

not evaluable-2) during or after receiving local treatment. Thus, could not be ascertained). After a median follow-up of 25 months
remaining 38 patients received adjuvant chemotherapy (Fig. 1). (range: 1.7–104.4), 5-year EFS, OS and LCR were 47.1
7.9%,
61.6
7.8%, and 77.9
8.6%, respectively for the entire cohort of
Response to Neoadjuvant Chemotherapy and Local EES. The 5-year LCR in surgery group, surgery plus radiotherapy
Therapy group, and definitive radiotherapy group was 43.6%, 87.5%, and
77.9%, respectively.
Out of 60 patients, re-evaluation after neoadjuvant chemotherapy
was performed in 57 patients (discontinued therapy-3) and response
Comparison of Outcome of EES With Skeletal Ewing
was as follows: CR-14, PR-34, SD-3, and PD-6 with overall response
Sarcoma
rate (ORR) of 84% (n ¼ 48/57). Of the 45 patients who underwent
either surgery and/or radiotherapy, post local therapy response was EES patients had significantly higher EFS (5-year estimate of
CR-31, PR-12, and not evaluated-2 with ORR of 100% (n ¼ 43/43). 48.5% vs. 22.4%, P ¼ 0.004) and a trend towards higher OS (61.5%
vs. 36%, P ¼ 0.08) when compared with skeletal Ewing sarcoma
Treatment Failure and Outcome cohort (Figs. 2A and B). The findings were similar for EFS (5-year
EFS of 62% vs. 31.7%, P ¼ 0.01), but not for OS (5-year OS of
Treatment failure was observed in 16 (27%) patients: 68.3% vs. 48.2%, P ¼ 0.29) when localized cohort (extraosseous vs.
recurrences after achieving CR in six patients and PD during or skeletal) was compared (Figs. 2C and D).
post therapy in 10 patients (post neoadjuvant chemotherapy PD-6,
and during/post adjuvant chemotherapy PD—4). Site of failure was
EES With Metastasis
local site alone in eight patients, distant metastasis in five patients,
and combined failure in three patients. Median time to local failure Twenty (33%) patients had metastatic disease at baseline. All
was 12.1 months (range: 3.7–40.2). patients received neoadjuvant chemotherapy and achieved ORR of
Seventeen (28%) patients died during or after treatment (PD—7, 75% (CR-3, PR-12), while only 11 patients received local therapy
toxic deaths—4, and six patients died at home, the cause of which (radiotherapy only—6, Surgery with or without radiotherapy—5).

Fig. 1. Flow diagram showing treatment and outcome of study patients. CR, complete response; LFU, lost to follow up; N, number; PD,
progressive disease; PR, partial response.
Pediatr Blood Cancer DOI 10.1002/pbc
1928 Biswas et al.

Fig. 2. Five-year EFS was 48.5% for EES (n ¼ 60) versus 22.4% for skeletal primary (n ¼ 314) (A). Five year OS was 61.5% for EES (n ¼ 60)
versus 36% for skeletal primary (n ¼ 314) (B). Five-year EFS was 62% for EES (n ¼ 40) versus 31.7% for skeletal primary (localized cohort,
n ¼ 184) (C). Five-year OS was 68.3% for EES (localized cohort, n ¼ 40) versus 48.2% for skeletal primary (localized cohort, n ¼ 184) (D).

There was no difference in baseline clinical and tumor-related DISCUSSION

factors between localized and metastatic disease. After median
EES constituted 16% of all Ewing sarcoma. This is consistent
follow up 16.6 months (range:2.5–37.4), the 3-year EFS, OS and
with previous published literature wherein EES comprised 6–47%
LCR rates were 15.8
12.7%, 43.9
15.3%, and 71.4
17.1%,
of total Ewing sarcoma cohort [1–5]. In the above cohort, most
respectively.
common site of EES was abdomen which is also in consistence with
previous published data [6,9,11,19]. Pelvic location of EES was
Prognostic Factors 19.8% in report by Applebaum et al. [28] as compared to only 7% in
Univariate analysis. Univariate analysis showed primary of our cohort, whereas axial location was 72.9% in previous report
spine, abdomen and pelvis (P ¼ 0.02), hemoglobin 10 g/dl which is similar to our observation of 77%. One-third of our patients
(P ¼ 0.004), white blood cell (WBC) count >11  109/L had metastatic disease; this may have been due to referral bias.
(P ¼ 0.001), lactate dehydrogenase (LDH) >2  N U/L Our analysis revealed low hemoglobin and high WBC count to
(P ¼ 0.002), and metastases (P ¼ 0.008) adversely predicted EFS adversely affect EFS, whereas low hemoglobin and raised LDH
(Table II). Primary of spine, abdomen and pelvis (P ¼ 0.04), tumor adversely affected OS on multivariate analysis. High serum LDH
size >8 cm (P ¼ 0.02), hemoglobin 10 g/dl (P ¼ 0.003), WBC may reflect a high tumor burden and has been shown to be a poor
count >11  109/L (P ¼ 0.04), and LDH >2  N U/L (P ¼ 0.03) prognostic factor in previous reports of EES [9,11]. However, the
were found to have adverse outcome for OS. (Table II). Age 15 years observation of low hemoglobin and high WBC count to affect
(P ¼ 0.09), WBC count >11  109/L (P ¼ 0.07), and LDH >2  N outcome was unique. High WBC count may reflect systemic
U/L had a trend towards inferior LCR (Supplemental Table SII). nature of the disease with possible micrometastatic pathology
Multivariate analysis. Multivariate analysis showed hemo- without over metastasis, or may be a paraneoplastic phenomenon.
globin 10 g/dl (P ¼ 0.03) and WBC count >11  109/L Patients of EES presenting with low hemoglobin had higher number
(P ¼ 0.009) to predict inferior EFS (Table III) (Figs. 3A and B). of patients with systemic symptoms (42% vs. 10%, P ¼ 0.01),
For OS, hemoglobin 10 g/dl (P ¼ 0.006) and LDH >2  N U/L higher axial primary (585% vs. 29%, P ¼ 0.06), lower serum
(P ¼ 0.03) independently predicted inferior outcome (Table III) albumin level (3.7 gm% vs. 4.5 gm%, P ¼ 0.0001); this may explain
(Figs. 3C and D). the poorer prognosis in this subgroup of patients with EES.

Pediatr Blood Cancer DOI 10.1002/pbc

 Extraosseous Ewing sarcoma 1929

TABLE II. Univariate Analysis for Event Free Survival (EFS) and Overall Survival (OS) in Entire EES Cohort (n ¼ 60)

EFS OS

5-year EFS 5-year OS

Variables Category estimate (%) HR P estimate (%) HR P
Age (years) 15 (n ¼ 29) 38.2 1 0.15 55.5 1 0.6
>15 (n ¼ 31) 55.4 0.55 69.8 0.77
Sex Male (n ¼ 42) 45.1 1 0.98 63.8 1 0.5
Female (n ¼ 18) 58.2 1.01 60.9 1.42
Systemic symptoms No (n ¼ 48) 49.2 1 0.21 63.7 1 0.26
Yes (n ¼ 12) 36.1 1.8 50.1 1.93
Symptom duration 4 months (n ¼ 38) 51.7 1 0.35 62.8 1 0.69
>4 months (n ¼ 22) 39.2 1.45 58.8 1.22
Tumor site HN, chest, limb (n ¼ 37) 62.3 1 0.02 78.5 1 0.04
Spine & pelvis, abdomen (n ¼ 23) 25.4 2.55 36.3 2.7
Tumor location Axial (n ¼ 46) 40.7 1 0.13 56.7 1 0.25
Appendicular (n ¼ 14) 73.3 0.4 81.5 0.42
Tumor diameter 8 cm (n ¼ 25) 66.7 1 0.1 91.7 1 0.02
>8 cm (n ¼ 28) 40.5 2.12 46.4 6.12
Hemoglobin (g/dl) 10 (n ¼ 12) 13.7 1 0.004 14.6 1 0.003
>10 (n ¼ 41) 59 0.27 73 0.22
WBC (/mL) 11,000 (n ¼ 36) 63.1 1 0.001 67.6 1 0.04
>11,000 (n ¼ 16) 18.2 4.89 39.8 2.82
LDH (U/L) 2  N (n ¼ 25) 75.1 1 0.002 73.5 1 0.03
>2  N (n ¼ 18) 15.7 5.36 45.9 3.43
Albumin (g/dl) 3.4 (n ¼ 6) 22.2 1 0.1 27.8 1
>3.4 (n ¼ 40) 59.3 0.39 71.1 0.35 0.1
Metastasisa No (n ¼ 40) 64.3 1 0.008 68.3 1
Yes (n ¼ 20) 15.8 3.04 43.9 2.27 0.1
Local treatment Sx þ RT (n ¼ 30) 50.3 1 0.52 68.8 1
RT only (n ¼ 15) 65.9 0.69 72.5 0.84 0.8
a
HR, hazard ratio; LDH, lactate dehydrogenase; RT, radiotherapy; Sx, surgery; WBC, white blood cell. 3-year estimated value.

There was a higher proportion of patients who underwent there was no difference in baseline tumor size between the two
surgical resection as primary local therapy (77% vs. 43%, groups.
P ¼ 0.003) in comparison with the patients of skeletal Ewing EES had significantly higher EFS and better OS when
sarcoma. Post neoadjuvant chemotherapy response was slightly compared with that of skeletal primary in our cohort. This was
higher in EES as compared to skeletal primary (ORR of 84.5% vs. in contrast to the observation in various published stud-
73%, P ¼ 0.07). This is similar to the observation of Applebaum ies [10,16,18,19,21,29], where there was no difference in outcome
et al. [28] who also observed the same finding when analyzing EES between skeletal Ewing sarcoma and EES. Two recently published
from the SEER data. It is difficult to explain this finding because studies reported improved survival of EES in comparison to

TABLE III. Multivariate Analysis

Entire group

Entire cohort (n ¼ 60) After excluding patients whose status unknown for OS (n ¼ 38)

Variables Category HR P HR P
A. Event free survival
Hb (g/dl) 10 1
>10 0.28 0.03
WBC count (/ml) 11,000 1
>11,000 4.31 0.009
C. Overall survival (OS)
Hb (g/dl) 10 1 1
>10 0.16 0.006 0.26 0.05
LDH (U/L) 2  N 1 1
>2  N 5.98 0.03 8.25 0.01
Hb, hemoglobin; HR, hazard ratio; LDH, lactate dehydrogenase; WBC, white blood cell.
Pediatr Blood Cancer DOI 10.1002/pbc
1930 Biswas et al.

Fig. 3. Five-year EFS was 13.7% for patients with hemoglobin 10 g/dl versus 59% for patients with hemoglobin >10 g/dl (n ¼ 60) (A). Five-year
EFS in was 63.1% for patients with WBC 11  109/L versus 18.2% for patients with WBC >11  109/L (n ¼ 60) (B). Five-year OS in was 14.6%
for patients with hemoglobin 10 g/dl versus 73% for patients with hemoglobin >10 g/dl (n ¼ 60) (C). Five-year OS was 73.5% for patients with
LDH 2  N U/L versus 45.9% for patients with LDH >2  N U/L (n ¼ 60) (D).

skeletal Ewing sarcoma [13,28], as was seen in our cohort. For The limitations of our study include the lack of translocation
initial 18 months after diagnosis, the hazard ratio for event for (EWS-FLI) analysis in our patients at diagnosis. Further approxi-
patients with EES was 0.72 (95% CI 0.44–1.16, P ¼ 0.17) as mately 23% (n ¼ 14) of our patients stopped therapy prematurely
compared to patients with skeletal primary tumors. After 18 months for whom the final survival status could be not ascertained. Further
from initial diagnosis, hazard ratio for event for patients with EES since the above is not a randomized study, it was not designed to
was 0.34 (95% CI 0.14–0.84, P ¼ 0.02) as compared to patients detect the difference between surgery and radical radiotherapy as
with skeletal primary tumors. This result indicates that extraoss- local treatment modality in EES.
eous origin of Ewing sarcoma has a greater chance of having an The strength of our study is that it included all patients with
event in the initial period after diagnosis (first 18 months) than after intention-to-treat analysis and received a uniform chemotherapy
18 months of diagnosis as compared to skeletal Ewing sarcoma; protocol. Hemoglobin and serum LDH adversely affected OS in
this was also observed in the study of EES by Applebaum entire EES cohort and continued to be independent prognostic
et al. [28]. The EES group had short mean symptom duration factors for OS even after exclusion of patients whose final survival
(4.3 days vs. 6.5 days, P ¼ 0.01), higher tumors of pelvic/spinal status for OS could not be ascertained. Low hemoglobin and high
region (38% vs. 23.9%, P ¼ 0.02), higher number of axial tumors WBC count were associated with adverse EFS. In comparison to the
(76.7% vs. 54%, P ¼ 0.001), and higher number of surgical cohort with skeletal primary tumors, the outcome was superior in
resection as local treatment (67.4% vs. 42.5%, P ¼ 0.002) as the cohort with EES, and most events tend to occur early in the
compared to skeletal primary group. Other clinic-pathological course of disease in the cohort with EES as compared to the cohort
characteristics did not differ between the two groups. Though the with skeletal Ewing sarcoma.
group with EES had higher axial or pelvic/spinal tumor location, it
is possible that the disease biology of these tumors may be more
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Pediatr Blood Cancer DOI 10.1002/pbc