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and IORT, patients received standard adjuvant therapy,
consisting of concomitant external-beam radiotherapy
(EBRT; 60 Gy) and temozolomide followed by cycling
maintenance temozolomide chemotherapy (5/28
schedule). The primary endpoint was safety as per the
occurrence of dose-limiting toxicities (DLT) within 3
months after IORT. Secondary endpoints were progression-
free survival (PFS) and overall survival (OS). In addition,
we performed an exploratory analysis of the local PFS
(defined as tumor recurrence within 1 cm of the resection
cavity border). The trial is registered at ClinicalTrials.gov,
number NCT02104882.
Results
Fifteen patients were treated (n=7 at 20 Gy, n=4 at 30 Gy,
n=4 at 40 Gy) during surgery. The majority of patients
(n=13) underwent incomplete resection. Six patients had
unresected multifocal tumors and 3 did not receive per-
protocol adjuvant treatment (PPT). Hypermethylation of
the MGMT promoter was absent in 10 patients. The median
follow-up was 13.8 months. The majority of grade 3-5
adverse events (23 of 27) were deemed related to EBRT,
chemotherapy or tumor progression. No DLT occurred and
thus the IORT dose was escalated to 40 Gy. Suspected or
confirmed radionecrosis was detected in 5 patients of all
3 dose levels. The median PFS was 11.2 months (95%CI:
5.4-17.0) in all and 11.3 months (95%CI: 10.9-11.6) with
PPT. The median local PFS was 14.3 m (95%CI: 8.4-20.2) in
all and 17.8 m (95%CI: 9.7-25.9) with PPT. The median OS
was 16.2 m (95%CI: 11.1-21.4) for all and 17.8 m (95%CI:
13.9-21.7) with PPT. One patient unexpectedly showed
distant response of a satellite lesion that was initially not
targeted with IORT.
Conclusion
IORT resulted in a highly relevant increase in PFS and
exhibited a manageable safety profile in a cohort with
mostly incompletely resected GBM and unfavorable
prognostic factors. A multinational randomized phase III
trial has been set up to test IORT plus standard of care
versus standard of care alone (INTRAGO II; NCT02685605).
PO-0633 Randomized study of adjuvant temozolomide
(6 vs.12 cycle) in newly diagnosed glioblastoma
multiforme
A.K. Gandhi
1
, M. Bhandari
1
, D.N. Sharma
1
, P. Julka
1
, G.K.
Rath
1
1
All India Institute of Medical Sciences, Radiation
oncology, New Delhi, India
Purpose or Objective
The role of adjuvant temozolomide (TMZ) beyond 6 cycles
in newly diagnosed glioblastoma multiforme (GBM) is not
clear. We did this prospective randomized study with a
hypothesis that E-TMZ for a total of 12 adjuvant cycles
would improve survival of patients with newly diagnosed
GBM as compared to conventional 6 cycles of TMZ (C-
TMZ).
Material and Methods
Between January 2012 and July 2013, 40 post-operative
patients of GBM between age 18-65 years and Karnofsky
Performance Score (KPS) ≥ 70 were included. Patients
were randomized to receive radiation (60 Gray in 30
fractions over 6 weeks) with concomitant TMZ (75
mg/m
2
/day) and adjuvant therapy with either 6 (C-TMZ
arm) or 12 cycles (E-TMZ arm) of TMZ (150-200 mg/m
2
for
5 days, repeated 4 weekly). Toxicity was assessed using
CTCAE (common terminology criteria for adverse events)
version 3.0. Progression free survival (PFS) was calculated
from the time of diagnosis to the time of progression or
death. Overall survival (OS) was calculated from the time
of diagnosis to the time of death from any cause. Kaplan
Meier method was used for survival analysis. P value of <
0.05 was taken as significant and SPSS version 12.0 [SPSS
Inc., Chicago, IL, USA] was used for all statistical analysis.
All patients signed informed consent before entry into the
study and the study was approved by Institutional ethics
committee (IESC/T-027/2011).
Results
20 patients were treated in each arm. Median age was 49
years and 44 years and median KPS was 90 and 80
respectively in C-TMZ and E-TMZ arms. Gross total
resection was possible in 60% and 55% patients and
subtotal resection was done in 40% and 45% patients
respectively in C-TMZ and E-TMZ arm. 10 and 9 patients
respectively in C-TMZ and E-TMZ arm had grade 2 and no
patient suffered from grade 3 non-hematological
toxicities. 2 patients each had grade 2 hematological
toxicity in C-TMZ (both thrombocytopenia) and E-TMZ arm
(one neutropenia and one thrombocytopenia) and 1
patient in E-TMZ arm had grade 4 (neutropenia)
hematological toxicity during concurrent radiotherapy.
Overall, 0% and 5% respectively in C-TMZ and E-TMZ arm
had hematological toxicity ≥ 3 in grade during concurrent
phase.
Median follow up in C-TMZ and E-TMZ arm were 14.65 and
19.85 months. Median PFS was 12.8 months and 16.8
months in C-TMZ and E-TMZ arm respectively (p=0.069). 2
year PFS was 16.4% vs. 18.7% in C-TMZ and E-TMZ arm
respectively (Figure 1). Median OS was 15.4 months vs.
23.8 months in C-TMZ and E-TMZ arm respectively
(p=0.044). 2-year OS was 12.9% vs. 35.5% respectively in
C-TMZ and E-TMZ arm (Figure 2).
Conclusion
The result of our study suggests that E-TMZ is safe,
tolerable as well as confers significant survival advantage
as compared to conventional duration of TMZ. Pending
results from larger, phase III, multi-institutional studies,
it appears prudent for us to suggest use of at least 12
cycles of adjuvant TMZ in patients with newly diagnosed
GBM.
PO-0634 Irradiation of Subventricular Zone in
Glioblastoma: Its Impact on Tumor Progression and
Survival