Annual Meeting Proceedings Part 1 - American Society of Clinical ...

2047 General Poster Session (Board #13B), Sat, 1:15 PM-5:15 PM
The effect of the addition of chemotherapy to radiotherapy on cognitive
function in patients with low-grade glioma: Secondary analysis of RTOG
98-02. Presenting Author: Roshan Sudhir Prabhu, Winship Cancer Institute,
Emory University, Atlanta, GA
Background: The addition of PCV chemotherapy to radiotherapy (RT) for
patients with WHO grade II glioma improves progression free survival (PFS)
and overall survival (OS), for patients surviving at least 2 years (Shaw, J Clin
Oncol 26: 2008). The effect of therapy intensification on cognitive function
(CF) remains a concern in this population with substantial long term
survival. Methods: 251patients with WHO grade II glioma and age � 40
with any extent of resection, or age � 40 with subtotal resection/biopsy
were randomized to RT (54Gy) or RT � PCV. 111 patients with age � 40
and gross total resection were observed. CF was assessed by mini-mental
status exam (MMSE)at baseline and years 1, 3, and 5 for patients without
progression. Change in MMSE score from baseline of � 3 points was
considered clinically significant. Results: Overall, very few patients experienced
significant decline in MMSE score, with a median follow-up time of
9.7 years for alive patients. There were no significant differences in the
proportion of patients experiencing MMSE decline between study arms at
any time point. The table below summarizes MMSE change from baseline
over time. Neither baseline MMSE score nor change in MMSE at year 1
significantly predicted for OS or PFS, but there was a trend towards worse
OS for patients with MMSE loss of � 2 points [HR 1.73, 95% CI (0.86,
3.47), p�0.12]. Conclusions: The MMSE is a relatively insensitive tool that
has not been validated in patients receiving cranial RT, and subtle changes
in CF may have been missed. However, the addition of PCV to RT for low
grade glioma did not result in significantly higher rates of MMSE decline
than RT alone or observation. There was a trend towards an MMSE decline
of � 2 points at year 1 predicting for worse OS.
Observation (%) RT (%) RT � PCV (%)
Significant MMSE decline
Year 1 0 / 62 (0) 5 / 74 (6.8) 2 / 51 (3.9)
Year 3 0 / 44 (0) 1 / 48 (2.1) 0 / 43 (0)
Year 5
No MMSE change
0/27(0) 0/22(0) 2/25(8)
Year 1 60 / 62 (96.8) 66 / 74 (89.2) 44 / 51 (86.3)
Year 3 44 / 44 (100) 45 / 48 (93.8) 38 / 43 (88.4)
Year 5
Significant MMSE gain
27 / 27 (100) 21 / 22 (95.5) 20 / 25 (80)
Year 1 2 / 62 (3.2) 3 / 74 (4.1) 5 / 51 (9.8)
Year 3 0 / 44 (0) 2 / 48 (4.2) 5 / 43 (11.6)
Year 5 0 / 27 (0) 1 / 22 (4.5) 3 / 25 (12)
2049 General Poster Session (Board #13D), Sat, 1:15 PM-5:15 PM
Predictive role of MGMT status in recurrent glioblastoma (GBM) patients
(PTS) treated with antiangiogenic drug (AD) plus temozolomide (TMZ) or
CPT-11. Presenting Author: Giuseppe Lombardi, Medical Oncology 1,
Istituto Oncologico Veneto-IRCCS, Padua, Italy
Background: Methylation and silencing of MGMT promoter is a favourable
predictive factor in PTS with GBM treated with single alkylating agent such
as TMZ. Yet, MGMT is an important resistance determinant to CPT-11
activity. AD can be administered in second line treatment as single agent or
in combination to cytotoxic drugs. We analyzed the predictive role of MGMT
status in PTS treated with AD plus TMZ or CPT-11 as second line
treatment. Methods: Retrospectively, 55 PTS were analyzed: 36 (65%) with
unmethlyated MGMT, 19 (35%) with methylated MGMT; 3 (5%) PTS with
IDH1 mutations. 17 (31%) PTS performed a reoperation before the second
line treatment and MGMT status was changed in 2 (18%) PTS, IDH1 status
was unchanged in all PTS. 32 PTS were treated with sorafenib 800mg/die
plus TMZ 40mg/m2/die, 23 with bevacizumab 10mg/Kg plus irinotecan
every two weeks. Tumor response was evaluated by clinician assessment
and by MRI according to RANO criteria every two months or when clinically
indicated. Results: Among all PTS, median PFS was 2.7 months (95%CI
1.5-3.5), median OS from start of AD was 7.3 months (95%CI 6.02-8.5),
6-month PFS was 32%; no significant differences were observed and
MGMT status was balanced between the two AD groups (p�0.05).
Analyzing MGMT status at first surgery, according to univariate analyses
there were no significant differences in terms of PFS (3.5ms vs 2.1ms;
p�0.2), OS (6.5ms vs 7.2ms; p�0.1) and 6-PFS (HR�0.2, CI95%
0.05-1.07) between PTS with unmethylated and methylated MGMT,
respectively. On multivariate analysis, adjusted for performance status, age
and cytotoxic drug, MGMT status was not statistically significant in terms of
PFS (p�0.8) and OS (p�0.1). Yet, no significant differences emerged with
MGMT status at second surgery as well as analyzing the two AD groups,
separately. Conclusions: MGMT status might not be a predictive factor in
recurrent GBM patients treated with AD plus TMZ or CPT-11 as second line
treatment, although MGMT status may change in some PTS between first
and second surgery. In conclusion, the outcome of patients with recurrent
GBM receiving AD plus TMZ or CPT-11 is not significantly influenced by
MGMT methylation status.
Central Nervous System Tumors
127s
2048 General Poster Session (Board #13C), Sat, 1:15 PM-5:15 PM
First results of radiotherapy after hyperbaric oxygenation with temozolomide
for high-grade gliomas. Presenting Author: David Hamid Khelif,
Service de Radiothérapie Groupe Hospitalier sud Reunion, Saint Pierre,
Reunion
Background: The outcome of patients with high-grade gliomas remains poor
despite modern therapeutic arsenal. The objective of this study was to
assess the feasibility and efficacy of radiotherapy (RT) given immediately
after hyperbaric oxygenation (HBO) with Stupp protocol. Methods: All
patients with histologically confirmed high-grade gliomas from 2008 till
2011 coveraged at GHSR hospital were enrolled. Patients underwent
Stupp protocol consisting in 60 Gy RT with a daily dose of 2 Gy for 5 days
per week administrated immediately after HBO. Temozolomide (TMZ) was
administrated at the daily dose 75 mg/m², 7 days per week followed by 6
cycles of TMZ 150 to 200 mg/m² for 5 days each 28 day-cycle. HBO
schedule was approximately 15 min of compression with air, 60 min of
100% oxygen inhalation and 10 min of decompression with oxygen.
Results: A total of 21 patients were diagnosed and histologically confirmed
high grade gliomas. Five were excluded because of HBO contraindications.
Twelve patients (75%) had undergone debulking surgery. The time interval
from completion of decompression to start of irradiation was less than 15
minutes (mean 14.25, range 8-18). Twelve patients (75%) received the
complete dose of RT and TMZ. HBO was completed for 7 (43.75%). Five
(31.25%) were temporarily stopped and 4 (25%) were definitively stopped.
One patient (6.25%) suffered from pancytopenia with grade 4 thrombopenia
and grade 3 neutropenia. The median follow up was 46.95 weeks
(range 5.7-108.3). Nine patients (56.25%) are still alive. Four (25%) have
a survival more than 16 months. Conclusions: HBO with Stupp protocol is
feasible and promising but requiring a large multicentric study.
2050 General Poster Session (Board #13E), Sat, 1:15 PM-5:15 PM
Phase II trial of sunitinib malate and lomustine in patients with temozolomide
refractory recurrent low-grade and anaplastic gliomas. Presenting
Author: Johnny Duerinck, UZ Brussel, Brussels, Belgium
Background: Recurrent low-grade and anaplastic gliomas eventually transform
to a higher grade that is characterized by neo-angiogenesis. Sunitinib
inhibits multiple tyrosine kinase receptors (including VEGFR, PDGFR and
c-Kit) but has no meaningful activity as a mono-therapy for recurrent
glioblastoma when given at a daily dose of 37,5 mg (Neyns et al. J
Neurooncol. 2011). We investigated sunitinib in combination with lomustine
(CCNU) for the treatment of patients (pts) with temozolomide (TMZ)
refractory recurrent low-grade or anaplastic glioma. Methods: Pts received a
daily dose of 25 mg sunitinib for 28 consecutive days followed by a 14 days
treatment-free interval. CCNU was administered as a single dose (80
mg/m²) on day 14 of a 6w cycle. T1 � Gd and T2/FLAIR weighted MRI
images were obtained q6 wks. 18FET-PET was performed at baseline and
reassessed in responding pts. Results: 13 pts were enrolled (mean age 40
[range 33-49]; M/F 8/5; KPS 80-90/70-60: 8/5 pts). All pts had PD
following surgery, RT and TMZ. In 7 pts, treatment was initiated at 2nd
recurrence, in 4 pts at 3rd recurrence and in 2 pts at the 4th recurrence.
Most frequent AEs where fatigue (gr 2: n� 3; gr 3: n� 1), thrombopenia (gr
2: n� 1gr3:n�3 gr4: n� 1), neutropenia (gr 2: n� 2; gr3: n� 2; gr4: n�
2) and lymphopenia (gr 2: n�1; gr 3: n�2; gr 4: n�1). In 5/13 pts CCNU
had to be discontinued because of AEs. Treatment with sunitinib was
continued in these cases without reoccurrence of AEs. BOR according to
RANO criteria: 1 CR, 1 PR (not-confirmed) and 2 SD (DCR: 4/13� 31%).
In the patient with CR, FET-PET indicated a complete metabolic response.
After a mean FU of 7 mths (range 2 -19), 5 pts are alive. The 6-month PFS
is 23% (3/13 pts); median PFS is 1,8 mths (95%CI 1.0 - 2,7). A durable
disease control was obtained in 3 pts (TTP respectively 14.8, 11.8� and
19.2� mths). Conclusions: in this heavily pretreated population with
recurrent low-grade and anaplastic glioma the combination of sunitinib and
CCNU is associated with acceptable toxicity and offers a durable progressionfree
survival in a subgroup of pts. Molecular predictive factors identifying
the sensitive population would be needed to justify further clinical
investigation of this combination.
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