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

2098 General Poster Session (Board #19E), Sat, 1:15 PM-5:15 PM
Effects of lazaroid U-74389G liposomes in a glioblastoma mouse model.
Presenting Author: Fady Ibrahim, University of British Columbia, Vancouver,
BC, Canada
Background: Lazaroid U-74389G (LAZ) is a 21-aminosteroid that has
radioprotective effects against radiation-induced lipid peroxidation. Also in
vitro antiproliferative effects have been reported against glioblastoma cell
lines. The aim of this study was to use a liposomal formulation to evaluate
LAZ radioprotective and antiproliferative effects in a glioblastoma mouse
model. Methods: LAZ PEGylated liposomes (Lipo G) were developed at the
University of Houston, College of Pharmacy. Glioblastoma cell line U87expressing
firefly luciferase reporter gene (100,000 cells in 2 �L) was
injected intracranially in each male SCID hairless outbred mouse. There
were 4 treatment groups (n�8-9, each): brain model (M) without treatment
(control), radiation 2Gy weekly (M�R), Lipo G at 5 mg/kg dose IP twice per
week (M�L) and radiation with Lipo G (M�R�L). Treatment lasted three
weeks. Tumor size was monitored using non-invasive bioluminescence
imaging (BLI), in each mouse. Mice were sacrificed after 3 weeks. Brain
was harvested for immunohistochemistry examinations. Lipid peroxidation
of brain tissues was quantified by measuring malondialdehyde (MDA) as a
surrogate biomarker. Survival was evaluated using Kaplan Meier analysis at
P� 0.05. Results: The relative BLI intensity was 4002.03�1737.67,
2034�737.72, 1387.36�684.53 and 2498.89�2521.32 % for M,
M�R, M�L and M�R�L, respectively. The tumor size of the M�L group
was reduced by 65% compared to control . For the radiation treated groups
(M�R and M�R�L), there was no significant difference in tumor size
compared to control group. MDA brain concentration in M�L and M�R�L
groups was significantly less than in M�R group (8.27�0.78 and
10.37�3.30 �M/gm vs. 23.09� 3.79 �M/gm). The survival mean was
22.67, 25.33, 25.22 and 27.13 days for M, M�R, M�R�L and M�L
groups, respectively. Mean survival of LAZ treated groups (M�L and
M�R�L) was significantly longer than that of the control group Conclusions:
LAZ liposomal formulations administered at 5 mg/kg dose reduced tumor
growth by 65%. LAZ also protected brain tissue from radiation-induced
lipid peroxidation by reducing MDA concentration by 50%. These provocative
data warrant further investigation of LAZ as a radiation protectant and
chemotherapeutic agent.
2100 General Poster Session (Board #19G), Sat, 1:15 PM-5:15 PM
Anaplastic oligodendroglial tumors: The Cleveland Clinic experience.
Presenting Author: Neda Hashemi-Sadraei, Cleveland Clinic, Cleveland,
OH
Background: Anaplastic oligodendroglial tumors include both anaplastic
oligodendroglioma (AO), and anaplastic oligoastrocytoma (AOA), histological
categories of WHO grade 3 gliomas. There is limited data on specific
prognostic factors for patients with these tumors. Methods: After obtaining
IRB approval, the Cleveland Clinic Brain Tumor and Neuro-Oncology
Center’s database was used to identify patients with histologically confirmed
AO and AOA 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�0.05 both as the criteria for entry and
retention in the model to identify independent predictors of survival.
Results: Chart records of 139 patients, 52% of whom were male, diagnosed
between 1992 and 2009 were included for analysis. Median age at
presentation was 47 years (range, 18-83 years). 22% of patients had
biopsy only, 35% had gross total resection, 43% had near total resection or
subtotal resection. Following surgery, 30% of patients were treated with
chemotherapy (CT) alone, 14% were treated with radiotherapy (RT) and
47% received both CT and RT. Median progression free survival and
median overall survival (OS) were 29.0 and 58.7 months respectively. On
multivariate analysis, four factors were identified as independent predictors
of OS: age at diagnosis (�50 vs. �50, p�0.004), Hypothyroidism
(p�0.009), multifocal disease (p�0.005) and 1p 19q co-deletion
(p�0.001). Choice of initial therapy did not impact survival in this cohort
of patients. Conclusions: Older age, hypothyroidism and multifocal disease
were associated with higher mortality. 1p, 19q co-deletion was associated
with lower mortality.
Risk factors for mortality: Multivariable Cox proportional hazards analysis.
Factor Hazard ratio (95% C.I.) p2 Age at diagnosis, years
(>50 vs.