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

2090^ General Poster Session (Board #18E), Sat, 1:15 PM-5:15 PM
The addition of bevacizumab to temozolomide and radiation therapy
followed by bevacizumab, temozolomide, and oral topotecan for newly
diagnosed glioblastoma multiforme (GBM). Presenting Author: Henry S.
Friedman, Duke University Medical Center, Durham, NC
Background: The prognosis for newly-diagnosed GBM is dismal. The
addition of temozolomide to radiation therapy improved the median overall
survival (OS) to 14.6 months (mos). GBM’s have the highest levels of
vascular endothelial growth factor (VEGF). Hypoxia inducing factor-1 alpha
(HIF-1 alpha) is an important regulator of VEGF, and topotecan may inhibit
HIF-1 alpha. Methods: We performed a phase II trial in newly diagnosed
GBM by adding bevacizumab and topotecan to standard therapy. 80 newly
diagnosed GBM patients were enrolled between January 2010 and January
2011. Patients received standard radiation therapy and temozolomide.
Bevacizumab at 10 mg/kg every 14 days was added a minimum of 4 weeks
post-op. Two weeks after radiation therapy was completed, 12 monthly
cycles of temozolomide at 150 mg/m2 /d days 1-5, oral topotecan at 1.5
mg/m2 for patients not on an enzyme inducing anti-epileptic drug (EIAED)
and 2.0 mg/m2 for patients on an EIAED days 2-6, and bevacizumab at 10
mg/kg on days 1 and 15. Results: The addition of bevacizumab to standard
radiation therapy and daily temozolomide was safe. Of the 80 patients, 76
completed radiation therapy. Four patients did not complete radiation, two
with clinical decline, one each with a bone flap infection, and a pulmonary
embolus. Fifteen patients came off study for toxicity, five with recurrent
grade IV thrombocytopenia, three with grade III fatigue, two each with
grade 2 CNS hemorrhage, and wound dehiscence requiring surgery and one
each with GI perforation, pulmonary embolism and an aortic thrombus. Of
the 80 patients, 56 have progressed and 37 have died. The median
progression-free survival (PFS) and OS are 11.1 mos (95% CI: 9.4-13.6)
and 17.2 mos (95% CI: 15.2) at a median follow-up of 18.4 months. The
two year OS is 45.3%. Conclusions: The addition of bevacizumab to
temozolomide and radiation followed by temozolomide, bevacizumab and
oral topotecan is tolerable. The median PFS and OS are encouraging. The
randomized phase III trials with bevacizumab for newly diagnosed GBM
patients are essential.
2092 General Poster Session (Board #18G), Sat, 1:15 PM-5:15 PM
Primary central nervous system lymphoma: The Cleveland Clinic experience.
Presenting Author: Manmeet Singh Ahluwalia, Cleveland Clinic,
Cleveland, OH
Background: Primary central nervous system lymphoma (PCNSL) is an
uncommon variant of extranodal non-Hodgkin lymphoma that involves the
brain, leptomeninges, eyes, or spinal cord without evidence of systemic
disease. Untreated PCNSL has a rapidly fatal course, with survival of
approximately 1.5 months from the time of diagnosis. In this study, we
sought to describe the demographics, diagnoses, management, and outcomes
of patients with PCNSL at a single institution. Methods: After
obtaining IRB approval, the Cleveland Clinic Brain Tumor and Neuro-
Oncology Center’s database was used to identify patients with histologically
proven PCNSL at the Cleveland Clinic between 1986 and 2010. Data were
subjected univariate and multivariate analysis followed by recursive partitioning
analysis in order to generate a prognostic model. Results: 153
patients were diagnosed with PCNSL with a median age of 61 and
Karnofsky performance status (KPS) of 70. The progression-free survival
(PFS) was 9.3 months; the overall survival (OS) was 27 months. The
treatment regimen included methotrexate-based chemotherapy (MTX) or a
combination of methotrexate-based chemotherapy and whole brain radiation
therapy (WBRT). Patients treated with the MTX regimen had an OS of
65 months; those treated with the MTX � WBRT regimen had an OS of 74
months. The Cox proportional hazards regression identified age and KPS as
the only prognostic indicators to OS and PFS. Recursive partitioning
analysis categorized the patients into three groups according to these
prognostic factors. Patients with KPS � 70 had a favorable outcome
compared to patients with KPS � 70. This held true especially for patients
age 60 and younger, whose median OS was 100 months. Conclusions: The
survival and prognostic indicators approximate those reported previously
and provide independent validation for a simple yet powerful prognostic
model that uses age and KPS to predict survival.
PFS and OS of patients in different groups based on age and performance
status.
Outcome PFS (months) OS (months)
All patients 9.3 27
Group 1 17 100
Group 2 18 41
Group 3 2.3 6.0
Group 1: age � 60 years and KPS � 70; group 2: age � 60 years and KPS � 70;
group 3: KPS � 70 (p � 0.0001).
Central Nervous System Tumors
137s
2091 General Poster Session (Board #18F), Sat, 1:15 PM-5:15 PM
Comparison of fractionated and single session radiosurgery for radiation
resistant brain metastases. Presenting Author: Eric Karl Oermann, University
of North Carolina at Chapel Hill, Chapel Hill, NC
Background: Melanoma and renal cell carcinoma are commonly called
radiation resistant tumors due to the decreased response rate to traditional
radiation (1.8-2 Gy /Fraction). Large brain metastases from radioresistant
primaries are clinical challenges. This study examines the impact of
fractionation on the treatment of intracranial metastases from radiation
resistant tumors. Methods: Patients with a primary diagnosis of melanoma
or renal cell carcinoma and intracranial metastases who completed
treatment at The University of North Carolina with frameless robotic
radiosurgery between 2007-2011 were retrospectively analyzed. Patients
were treated with either single or 3-5 fractions depending on volume. The
study’s primary endpoints were overall survival (OS) and local control (LC),
and its secondary endpoint was patient steroid requirements. Outcomes
data and pre-treatment variables were analyzed for significance using
appropriate non-parametric tests. Results: 25 patients were included in the
single fraction arm and 13 patients in the multi-fraction arm, and both had
equivalent pre-treatment characteristics with the exception of tumor
volume which was larger in the multi-fraction arm (p�0.01). At a median
follow-up of 4.7 months (range, 1.8-11.6), the median OS for all patients
was 6.2 months. One year survival was 35.1% and 5 patients (13%) had
local failures at a median time to local failure of 5.5 months. Patients in the
multi-fraction arm failed at a higher rate (10.5%) than patients in the
single fraction arm (2.6%) (p�0.04), but there was no difference in OS
(p�0.34). There was no difference between pre-treatment and posttreatment
steroid requirements between the two arms (p�0.351).
Conclusions: Fractionation is intended to facilitate radiosurgery in large
tumors by limiting high doses of radiation to a large portion of normal brain.
In our study of radioresistant intracranial metastases, large tumors receiving
multi-fraction radiosurgery had decreased local control with no difference
in toxicity or OS. These results suggest a need for either dose
escalation, or combination therapy designed to reduce tumor size (resection
or aspiration) in order to facilitate single fraction treatment.
2093 General Poster Session (Board #18H), Sat, 1:15 PM-5:15 PM
Low-grade gliomas in older patients. Presenting Author: Adewale Alade
Fawole, Fairview Hospital, Cleveland, OH
Background: Low grade gliomas account for 10-20% of all primary brain
tumors. The outcomes of older patients with low-grade glioma (LGG) are not
well known. Methods: After obtaining IRB approval, the Cleveland Clinic
Brain Tumor and Neuro-Oncology Center’s database was used to identify
older patients defined as those �55 years of age with histologically
confirmed grade 2 glioma at the time of diagnosis. Multivariable analysis
was conducted with use of a Cox proportional hazards model and a stepwise
selection algorithm that used p�.10 as the criteria for entry and p�0.05 as
retention in the model to identify independent predictors of survival.
Results: Chart records of 61 patients diagnosed between 1991 and 2010
were included for final analysis. In contrast to patients �55 years, older
patients are more likely to be male (p�.06), have poorer performance
status at presentation (p�.0001), more comorbid conditions (p�.0001),
present with more neurologic symptoms (p�.0001), have a prior history of
cancer (p�.0001). They are more likely to have astrocytic histology
(p�.008) and present with multifocal tumors more frequently (p�.001).
Older patients received radiation (RT) upfront more frequently (p�.07) and
undergo gross total resection less frequently (p�.003). Median Progression
free survival (PFS) and median overall survival (OS) was 1.9 and 4.3 years,
respectively in these patients. On univariate analysis, patients with poor
performance status have worse PFS (p�.01) and OS (p�.003). Patients
with memory impairment have worse PFS (p�.009) and OS (p�.0001).
Patients treated with adjuvant chemotherapy had better OS (p�.01).
Tumor related characteristics associated with poor survival included, �pure�
or mixed astrocytoma histology (OS, p�.06), multifocal tumors (OS,
p�.08), left-sided tumors (p�.07). In multivariable analysis, performance
status was the only independent predictor of either PFS or OS. Conclusions:
Older patients with low grade gliomas have less favorable outcomes as
compared to younger patients. They have more comorbid conditions and
symptoms at presentation. Use of chemotherapy in this patient group was
associated with improved survival. Performance status was the only
independent predictor of either PFS or OS.
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