Date of Award

January 2016

Document Type

Thesis

Degree Name

Medical Doctor (MD)

Department

Medicine

First Advisor

Joseph N. Contessa

Abstract

Glioblastoma is the most common and highest-grade primary malignancy of the central nervous system. Prognosis is typically poor, but significant heterogeneity within the patient population makes prediction of individual outcomes difficult. We performed a multi-institutional study to identify prognostic factors for patients with glioblastoma treated with concurrent temozolomide-based chemoradiotherapy (CRT). Particular attention was given to O6-methylguanine DNA methyltransferase (MGMT) as a factor whose interaction with other known prognostic factors is unknown.

A total of 162 patients with glioblastoma were identified from three institutions. Patients were eligible only if MGMT status was available. All received concurrent temozolomide-based chemoradiation after surgical intervention. Estimates for overall survival (OS) were determined and prognostic factors were identified using the Kaplan-Meier log rank test and Cox proportional hazards regression modeling.

Median OS after tissue diagnosis was 27.7 months (range, 2.50 to 77.5 months; 95% CI, 22.5 to 33.0 months). Kaplan-Meier estimate of 2-year OS was 59%. On multivariable analysis, younger age, MGMT methylated tumors, frontal tumors, and gross total resection compared to biopsy were found to be independent predictors of OS. Tumor side and gross total resection (GTR) compared to subtotal resection (STR) were not significantly associated with overall survival. On univariable analysis for unmethylated patients (n = 87), GTR was not associated with significantly longer OS than STR (medians, 18.7 and 22.5 months, respectively; p = 0.829). The same analysis among MGMT methylated patients (n = 57) yielded a significant survival benefit for GTR compared to STR (medians, 34.0 and 54.5 months, respectively; p = 0.041). Multivariable analysis of unmethylated patients revealed

a non-significance of GTR compared to STR (p = 0.347) while the same analysis of MGMT methylated patients showed a trend toward significant OS benefit for GTR compared to STR (p = 0.058).

Patients with MGMT methylated glioblastoma have significantly prolonged survival, and there may be a synergistic effect with gross total resection compared to subtotal resection. These patients may represent a population in which improved local control via re-resection, dose escalation, or laser-induced thermal therapy may be especially beneficial.

Comments

This thesis is restricted to Yale network users only. This thesis is permanently embargoed from public release.

Download

Share

COinS