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

2081 General Poster Session (Board #17D), Sat, 1:15 PM-5:15 PM
The impact of bevacizumab on the occurrence and recurrence of intracranial
brain metastases in non-small cell lung cancer (NSCLC) patients.
Presenting Author: Mohamed E. Salem, Karmanos Cancer Institute, Wayne
State University School of Medicine, Dertoit, MI
Background: Patients (pts) with brain metastases (BM) have a poor
prognosis and limited treatment options. Approximately 40-50% of pts
with NSCLC will develop BM during the course of their disease. A better
understanding of the pathobiology of BM and the development of targeted
agents hold promise for improved prophylaxis and therapy of BM which
could have significant impact on disease progression and pt’s survival.
Vascular Endothelial Growth Factor has been implicated in setting up a
metastatic niche allowing cells to seed and grow in the brain parenchyma.
Inhibition of this signaling has been studied and shown to be effective in
reducing BM in animal models. Methods: The objective of this retrospective
study was to determine whether bevacizumab decreases the incidence and
or the recurrence of BM in pts with NSCLC. We retrospectively identified
NSCLC pts with and without BM treated with bevacizumab. The primary
endpoint was the proportion of patients who developed BM on or after
bevacizumab therapy. Secondary endpoints were rate of local or regional
recurrence after stereotactic radiosurgery (SRS). Occurrence of BM was
evaluated by retrospectively reviewing MRI and or CT scans. Results: A total
of 30 pts with stage IV non-squamous NSCLC who had no BM at diagnosis
treated with bevacizumab (Non-BM group, NBMG) and 85 pts with
non-squamous NSCLC who had BM and underwent SRS (BM group, BMG)
were studied (46%M; median age 60 years (range 32-84). In the NBMG,
28% of pts developed BM. Median time to development of BM was 10.5
months. In the BMG, 4 pts were treated with bevacizumab following SRS.
Of these 4 pts, 3 pts (75%) had no recurrence while 1 pt (25%) developed
local then regional recurrence at 7 and 9 months, respectively. Of the
remaining 81 pts who underwent SRS but never received bevacizumab,
27% of pts had local recurrence and 41% had regional recurrence at
median time of 4 and 4.5 months, respectively. Conclusions: Bevacizumab
may have a role in the treatment of NSCLC in regards to development and
recurrence of brain metastases. These results support the need for further
prospective investigation in a larger patient population with matched
controls.
2083 General Poster Session (Board #17F), Sat, 1:15 PM-5:15 PM
Plasma levels of IL-8 and g-CSF in high-grade gliomas treated with
bevacizumab. Presenting Author: Marica Eoli, Fondazione IRCCS Istituto
Neurologico Carlo Besta, Milan, Italy
Background: Bevacizumab, an anti-VEGF antibody, has shown significant
activity in high grade gliomas (HGG). However, tumor recurrence inevitably
occurs. Methods: We treated 63 recurrent HGG patients with poor prognostic
factors with bevacizumab (10 mg/kg) and irinotecan (125 or 340
mg/m2 ) every 2 weeks, and investigated IL-12, IL-13, IL-17, FGF basic,
G-CSF, MIP-1b, PDGF-beta, plasma levels before starting treatment and
every 8 weeks by Bioplex. Ten age- and sex-matched healthy controls were
used for comparison. Results: After a median follow-up of 27 weeks,
median OS and PFS were 33 and 18 weeks, respectively. PFS at 6 and 12
months were 32% and 12%, respectively. OS at 6 months was 60%.
Toxicity was mild. Baseline higher amounts of IL-13 (48�174 pg/ml vs
3.44�0.9 pg/ml, p�0.0001) and lower amounts of MIP-1b (35.3�20.9
pg/ml vs 67.2�18.8 pg/ml, p�0.0002), PDGF-beta (1585.5�1585
pg/ml vs 7098�1585 pg/ml, p�0.0001) and VEGF (27�39.8 pg/ml vs
54.5�32 pg/ml, p�0.001) were detected in patients than in healthy
controls. In a cohort of 15 non-responders (patients who progressed 8
weeks after treatment onset), baseline IL-8 (15.7�10.8 pg/ml vs 10.9�9.4
pg/ml, p�0.03) and G-CSF (113.3�54 pg/ml vs 84.9�59.2 pg/ml,
p�0.03) were significantly higher than in patients responding to treatment.
In the same cohort no significant reduction of VEGF and other
cytokines was observed after 8 weeks of treatment, while a decrease of
plasma VEGF was observed in the remaining patients (26�32 pg/ml vs
13.3�28.5 pg/ml, p�0.001). Furthermore, in a cohort of 22 long-term
responders (patients who progressed after more than 18 weeks of treatment),
levels of VEGF decreased after 8 weeks of treatment when compared
to baseline, whereas no difference was observed in baseline levels
(23.9�22.6 pg/ml vs 9.8�9.4 pg/ml, p�0.001). Conclusions: Data
suggest that high levels of IL-8 and G-CSF at baseline associated with a
lack of VEGF decrease after 8 weeks of treatment identify patients who are
resistant to bevacizumab. This hypothesis should be tested in a large
number of patients.
Central Nervous System Tumors
135s
2082 General Poster Session (Board #17E), Sat, 1:15 PM-5:15 PM
Relationship between IDH1 mutation status and magnetic resonance
imaging features in WHO grade II and III oligodendroglial tumors. Presenting
Author: Frederique Toulgoat, Neuroradiologie CHU Nantes, Nantes,
France
Background: In gliomas, relationship between radiological characteristics
and several biomarkers was the subject of numerous publications. Mutations
in the isocitrate dehydrogenase 1 (IDH1) gene have been identified
recently to play a key role in these tumors occuring in up to 75% of
low-grade diffuse (WHO grade II) and anaplastic (WHO grade III) astrocytic,
oligodendroglial and mixed oligodendroglial neoplasms. However, the
correlation with magnetic resonance imaging (MRI) features has been little
studied. Methods: Patients treated for WHO grade II and III oligodendroglial
tumors between 2005 and 2011 were retrospectively identified. Each case
has been reviewed by the same neuropathologist. IDH1 and IDH2 mutations
were available. Preoperative MRI, including T1 weighted, T2 weighted,
T1 contrast enhanced, FLAIR, T2* weighted, diffusion weighted (ADC
ratio), perfusion weighted (CBV ratio) and MR spectroscopy, were analyzed
by two radiologists blinded from molecular data. Logistic regression
analysis and Fisher’s test were used to develop predictive models of genetic
profile from imaging. Results: Sixty eight patients, WHO grade II (n� 37)
and grade III (n�31) patients were identified. Mean age at diagnosis was
46 years; ratio male/female was 40/28. IDH1 mutations were identified in
42 patients (62 %), IDH2 in 4 patients (6 %). Analysis of tumor location,
size, borders, morphological aspect, and signal did not shown any significant
difference between IDH1 mutated group and IDH1 non mutated group
neither in grade II nor in grade III oligodendroglial tumors. In the same way,
MR spectroscopy (Choline/NAA ratio and detection of lipid and lactate) was
not relevant to discern the two groups. As well, ADC ratio (1,5 versus 1,4;
p�0,35) and CBV ratio (3,4 versus 4,2; p� 0,46) did not reveal any
difference between mutated group and non mutated group. Conclusions: In
our study, IDH1 mutations were not correlated with MRI features available
during routine MRI. Nevertheless, recent studies suggest the ability of MR
spectroscopy to detect 2-hydroxyglutarate as an MRI marker of IDH1
mutated tumors, which encourage carrying on research in molecular
imaging.
2084 General Poster Session (Board #17G), Sat, 1:15 PM-5:15 PM
The final report of a phase I trial of surgical resection with biodegradable
carmustine (BCNU) wafer placement followed by vaccination with
dendritic cells pulsed with tumor lysate for patients with glioblastoma.
Presenting Author: Jeremy Rudnick, Neuro-Oncology Program, Cedars-
Sinai Medical Center, Los Angeles, CA
Background: Our prior immunotherapy trials demonstrated efficacy in
generating a tumor specific immune response in malignant glioma and the
potential for high tumor-specific toxicity and sustained tumoricidal activity.
Immunotherapy may synergize with chemotherapy and biodegradable
carmustine (BCNU) wafers and have a modest impact to extend overall
survival. We exploited this synergistic effect to maintain a cytotoxic
environment around the tumor milieu, and this is a presentation of the final
results of our clinical trial. Methods: Patients with glioblastoma were
eligible after maximal resection with biodegradable carmustine (BCNU)
wafer placement. Screening leukapheresis was used to isolate mononuclear
cells which were differentiated into dendritic cells, pulsed with tumor
lysate, and then 3 intradermal vaccines administered at 2-week intervals.
Patients continued systemic chemotherapy after vaccine or at progression.
Results: Twenty three patient with glioblastoma received therapy including
8 with newly diagnosed disease (35%) and 15 with recurrent disease
(65%) were evaluable. Immune response data is available for 20/23
patients although survival data is present for all. One grade 3 SAE of fever
and chills was noted otherwise therapy was well tolerated. Within the newly
diagnosed GBM cohort the median overall survival (OS) was 25.5 months
(15,31�), and within the recurrent GBM cohort, the median OS was 16
months (8,23�). Among the recurrent GBM an increase of �1.5 X baseline
interferon gamma production post vaccination was associated with a
prolonged median OS 22 months (8,40) in 4/12 patients versus 17 months
(9,27) in 8/12 patients. Conclusions: We were able to generate an immune
response in 25% of patients which is lower than what we have seen in
previous trials and suggests a limited synergy with local control. However,
within the recurrent GBM cohort we did find prolonged survival in both
groups with an increased survival noted in immune responders demonstrating
the potential for this therapy.
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