Pediatr Blood Cancer 2013;60:E97–E99
BRIEF REPORT
High Burden of Metastases and Poor Outcome in Pelvic PNET
1
Bivas Biswas, MD, Sandeep Agarwala, MD,2 Shishir Rastogi, MD,3 Shah Alam Khan, MD,3 B.K. Mohanti, MD,4
D.N. Sharma, MD,4 Sushmita Pathy, MD,4 and Sameer Bakhshi, MD1*
Data on prognostic factors in pelvic PNET are minimal. We
analyzed patients with pelvic PNET treated between June 2003 and
November 2011 for prognostic factors. Forty-eight (13%) of 374
patients with PNET were pelvic PNET with median age 14.5 years
(range: 5–33); 31 (65%) had metastases. After median follow-up of
20.4 months (range: 1.3–64.9), 3-year EFS, OS, and local-control-rate
Key words: chemotherapy; outcome; pelvic EWING’s sarcoma; prognostic factors; radical radiotherapy
INTRODUCTION
Pelvic primitive neuroectodermal tumor (PNET) do worse as
compared to PNET of other sites [1–4]. Most studies wherein those
with pelvic PNET underwent surgery have had selection bias;
further, heterogeneous treatment over long period of time and small
sample size [3–11] makes data between studies incomparable and
there is lack of prognostication. At our center we used local
radiotherapy as preferred mode of therapy for pelvic PNET. In view
of paucity of prognostic factors, we analyzed patients with pelvic
PNET treated at our institute with uniform treatment protocol for
outcome and prognostic factors.
MATERIALS AND METHODS
Patients
This study involves data review of patients with histologically
proven PNET of pelvic bone (arising from ilium, ischium,
acetabulam, and pubis) treated in our department between
June 2003 and November 2011. Ethical clearance was taken
from institutional ethical review committee. All patients had
computed tomography (CT) or magnetic resonance imaging of
abdomen and pelvis, and underwent metastatic work-up including
bone scan, CT chest and bone marrow biopsy.
Treatment and Response Evaluation
Treatment consisted of three phases: neoadjuvant chemotherapy
(NACT) for 9–12 weeks, local therapy, followed with adjuvant
chemotherapy (ACT) [12]. Complete remission (CR), partial
response (PR), stable disease (SD), and progressive disease (PD)
were defined as per RECIST criteria [13]. All patients without
metastases underwent local therapy if they were in CR/PR/SD post-
NACT while all patients with metastases received local therapy if
they were in CR/PR at both primary and/or metastatic site.
Statistical Analysis
Chi-square/Fischer’s exact test and Student’s t-test/Wilcoxon
Rank-Sum test was used to detect association between baseline
characteristics. Survival was estimated by Kaplan–Meier method
and compared using log-rank test. Data were censored on 30th
November 2012. Univariate Cox proportional hazard model
C 2013 Wiley Periodicals, Inc.
DOI 10.1002/pbc.24552
Published online 26 April 2013 in Wiley Online Library
(wileyonlinelibrary.com).
were 13.5
5.5%, 15.4
9%, and 41.3
14.9%, respectively.
Hypoalbuminemia (3.4 g/dl) predicted inferior EFS and OS for
both entire cohort and metastatic group. All patients with hypo-
albuminemia (n ¼ 10) had low BMI as compared to 23/38 without
hypoalbuminemia (P ¼ 0.02). Pediatr Blood Cancer 2013;60:E97–
E99. # 2013 Wiley Periodicals, Inc.
followed by stepwise multivariate Cox regression analysis was
done to identify predictors of outcome. Factors with significance
(P-value) up to 0.25 in univariate analysis were taken into
multivariate analysis. Event-free-survival (EFS) was calculated
from date of diagnosis to date of disease relapse or progression,
death from any cause. Overall-survival (OS) was calculated from
date of diagnosis to date of death from any cause. Combined local
and distant site failure was taken as local failure for analysis of local
control rate (LCR). Patients who were lost to follow-up or had
treatment abandonment were also included for EFS and OS
analysis. STATA/SE 9.0 (StataCorp LP, College Station, TX) was
used for statistical analysis.
RESULTS
Clinicopathological Profile
Forty-eight (13%) of total 374 patients with PNET who
underwent treatment were pelvic PNET. Median symptom duration
was 4.5 months (range: 1–24 months). Median tumor diameter was
10 cm (range: 4–18.6 cm) and tumor size >8 cm was observed in 30
(68%) patients. Metastatic disease was observed in 31 patients
(65%) (Supplementary Table I).
1
Department of Medical Oncology, Dr. B. R. A. Institute Rotary Cancer
Hospital, All India Institute of Medical Sciences, New Delhi, India;
2
Department of Pediatric Surgery, Dr. B. R. A. Institute Rotary Cancer
Hospital, All India Institute of Medical Sciences, New Delhi, India;
3
Departments of Orthopedic Surgery, Dr. B. R. A. Institute Rotary
Cancer Hospital, All India Institute of Medical Sciences, New Delhi,
India; 4Department of Radiotherapy, Dr. B. R. A. Institute Rotary
Cancer Hospital, All India Institute of Medical Sciences, New Delhi,
India
Conflict of interest: Nothing to declare.

Correspondence to: Sameer Bakhshi, Department of Medical
Oncology, Dr. B. R Ambedkar Institute Rotary Cancer Hospital, All
India Institute of Medical Sciences, New Delhi 110029, India.
E-mail: sambakh@hotmail.com
Received 12 February 2013; Accepted 8 March 2013
E98 Biswas et al.

Response, Failure, and Outcome
Out of 48 patients, re-evaluation post-NACT in 47 patients (one
defaulted) revealed: CR-4, PR-30, SD-4, and PD-9 with overall
response rate (ORR) of 72% (n ¼ 34/47). Of these, 30 received local
treatment (surgical resection-1, radical radiotherapy-29); 17
patients did not take local treatment (PD-9, LFU-8 patients of
which seven were in PR and one had SD). Of these 30 patients, post-
local therapy response was CR-10, PR-18, SD-1, and PD-1 with
ORR of 93% (n ¼ 28/30).
Treatment failure was observed in 27 patients (56%):
recurrences after achieving CR in nine patients and PD during or
post-therapy in 18 patients (post-NACT PD-9, post-local therapy
PD-1, and during/post-ACT PD-8). Site of treatment failure was
local site alone in 12 patients, distant metastasis in 10 patients, and
combined failure in 5 patients.
Although EFS and LCR could be assessed in all patients yet final
survival status of 11 (23%) patients could not be assessed for OS
(defaulted therapy-8; PD-3). After median follow-up of 20.4
months (range: 1.3–64.9), 3-year EFS, OS, and LCR were 13.5

5.5%, 15.4
9%, and 41.3
14.9%, respectively for entire
cohort. In those with localized disease (n ¼ 17), 2-year EFS, OS and
LCR were 21
12.9%, 70.7
12.4%, and 30
17.6%, respective-
ly. In the group with metastatic disease, 3-year EFS, OS, and LCR
were 10.5
8.6%, 12
10.4%, and 50.8
21.8%, respectively.
Prognostic Factors
Entire cohort. Univariate analysis showed that serum albumin
level 3.4 g/dl predicted adverse EFS (P ¼ 0.001) and OS
(P ¼ 0.04) (Supplementary Fig. 1A,B and Table I). For LCR, ilium
as a primary site had slightly improved outcome as compared to
other sites (P ¼ 0.08) (Supplementary Fig. 1C and Supplementary
Table II). After excluding patients whose survival status could not
be assessed (n ¼ 11), serum albumin 3.4 g/dl continued to
adversely affect OS (2-year OS: 0% vs. 54%, P ¼ 0.006)
(Supplementary Fig. 1D). Hypoalbuminemia emerged as an
independent poor prognostic factor for both EFS (P ¼ 0.001) and
OS (P ¼ 0.04) on multivariate analysis (Supplementary Table III).
Localized disease. No factor affected either EFS or OS, though
patients with age >15 years had slightly higher EFS (2-years EFS:
53% vs. 0%, P ¼ 0.07) (Supplementary Fig. 2A and Supplementary
Table IV). None of the factor influenced LCR on univariate
analysis.
Metastatic disease. Univariate analysis showed that patients
with serum albumin level 3.4 g/dl had adverse EFS (P ¼ 0.004)
and OS (P ¼ 0.05) in metastatic group (Supplementary Fig. 2B,C
and Table II). No factor significantly affected LCR, though male
patients had slightly higher LCR (P ¼ 0.09) (Supplementary Fig.
2D and Supplementary Table II). Multivariate analysis showed that
albumin level 3.4 g/dl (P ¼ 0.001) and age >15 years (P ¼ 0.04)
adversely predicted EFS while hypoalbuminemia alone predicted
poor OS (P ¼ 0.045) (Supplementary Table III).
DISCUSSION
We observed a 65% incidence of metastatic disease in our cohort
of pelvic PNET. This was higher as compared to published literature
for pelvic PNET; notably Hoffman et al. [1] reported 241 cases of
pelvic PNET with 36% metastatic disease. Incidence of metastatic
disease at presentation in PNET is 20–25% in literature [12] while
40% of patients treated at our institution (n ¼ 150/374) had
metastatic disease at presentation possibly because of referral bias

TABLE I. Univariate Analysis for Event Free Survival (EFS) and Overall Survival (OS) in Entire Cohort (n ¼ 48)

EFS OS

Variables Category 3-Year EFS estimate (%) HR P 3-Year OS estimate (%) HR P

Age (years) 15 (n¼29) 16 17.2
>15 (n¼19) 0 1.11 0.77 13.6 1.3 0.51
Sex Male (n¼37) 11.8 22.7
Female (n¼11) 0 0.94 0.78 0 1.33 0.53
Systemic symptoms No (n¼31) 0 0
Yes (n¼17) 17.5 0.72 0.38 38.3 0.5 0.13
Symptom duration (months) 4 (n¼24) 8.4 16.4
>4 (n¼14) 0 0.91 0.78 14.4 1.23 0.6
Tumor site Iliac (n¼37) 10.3 22
Non-iliac (n¼11) 0 1.35 0.46 0 1.25 0.63
Tumor diameter (cm) 8cm (n¼14) 24.2 17.4
>8cm (n¼30) 0 1.06 0.89 0 0.83 0.68
Hemoglobin (g/dl) 10 (n¼21) 0 0.14 0
>10 (n¼27) 11.7 0.58 28 0.62 0.23
White blood cell count (l) 11,000 (n¼30) 29.6 52.7
>11,000 (n¼18) 9.4 1.23 0.57 44.8 1.66 0.23
LDH (U/L) 500 (n¼20) 7.5 9.8
>500 (n¼17) 0 1.3 0.53 0 1.6 0.32
Serum albumin (g/dl) 3.4 (n¼10) 0 0
>3.4 (n¼34) 10.8 0.24 0.001 17.7 0.34 0.04
Metastases No (n¼17) 0 0.39 17.1
Yes (n¼31) 10.5 1.4 12 1.12 0.79
CI, confidence interval; HR, hazard ratio; LDH, lactate dehydrogenase.

Two-year estimate value.
Pediatr Blood Cancer DOI 10.1002/pbc
 Primitive Neuroectodermal Tumor of Pelvis E99

TABLE II. Univariate Analysis for Event FREE Survival (EFS) and Overall Survival (OS) in Patients With Metastatic Disease (n ¼ 31)

EFS OS

Variables Category 3-year EFS estimate (%) HR P 3-year OS estimate (%) HR P

Age (years )
15 (n¼18) 28.7 27.9
>15 (n¼13) 0 1.71 0.21 0 1.85 0.2
Sex Male (n¼25) 14.8 19
Female (n¼6) 0 0.98 0.97 0 1.17 0.77
Systemic symptoms No (n¼18) 0 0
Yes (n¼13) 21 0.74 0.49 23.9 0.7 0.46
Symptom duration (months) 4 (n¼15) 18.3 23.2
>4 (n¼16) 0 1 0.99 0 1.33 0.56
Tumor site Iliac (n¼22) 13.5 19.1
Non-iliac (n¼9) 0 1.56 0.36 0 1.36 0.55
Tumor diameter (cm) 8cm (n¼7) 21.4 21.4
>8cm (n¼23) 0 0.87 0.8 0 0.99 0.99
Hemoglobin (g/dl) 10 (n¼18) 0 0
>10 (n¼13) 24.9 0.63 0.3 40.3 0.62 0.35
White blood cell count (l) 11,000 (n¼20) 21.5 46.4
>11,000 (n¼11) 24.6 1.15 0.76 28.6 1 0.87
LDH (U/L) 500 (n¼13) 10 38.7
>500 (n¼12) 0 1 0.93 20 1 0.96
Serum albumin (g/dl) 3.4 (n¼9) 0 0
>3.4 (n¼20) 17.8 0.27 0.004 15.5 0.32 0.05
HR, hazard ratio; LDH, lactate dehydrogenase.

Two-year estimate value for both EFS and OS.

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Pediatr Blood Cancer DOI 10.1002/pbc