O6-Methylguanine-DNA Methyltransferase (MGMT) Promoter Methylation and Low MGMT-Encoded Protein Expression as Prognostic Markers in Glioblastoma Patients Treated with Biodegradable Carmustine Wafer Implants after Initial Surgery Followed by Radiotherapy with Concomitant and Adjuvant Temozolomide (P06.004)

Abstract

Objective: To study the prognostic impact of O 6 -methylguanine-DNA methyltransferase (MGMT) on newly diagnosed glioblastoma patients being treated with carmustine-releasing wafers (Gliadel®) along with temozolomide (TMZ). Background MGMT promoter methylation status was proposed as a prognostic biomarker for glioblastoma patients. However, the prognostic impact of MGMT on newly diagnosed glioblastoma patients treated using surgical resection and Gliadel® implants followed by Stupp9s protocol is still unknown. Design/Methods: MGMT promoter methylation status and protein expression were analyzed in formalin-fixed, paraffin-embedded tumor specimens obtained from 111 French patients with newly diagnosed glioblastoma. Patients received Gliadel® followed by radiotherapy plus concomitant and adjuvant TMZ chemotherapy, while being enrolled in a French multicenter prospective study. Results: For the whole cohort, median overall survival (OS) and progression-free survival (PFS) were 17.5 and 10.3 months, respectively. Patients with tumors harboring MGMT methylation displayed a significantly longer OS compared to those with wild-type MGMT (21.7 vs . 15.1 months, p=0.025). Similarly, patients with low MGMT protein expression (≤15%) exhibited significantly improved OS compared to those with high MGMT expression (27.0 vs. 15.1 months, p=0.021). The extent of resection was the strongest clinical outcome predictor. In multivariate Cox models adjusted for gender, performance status, and extent of surgery, both MGMT methylation and protein expression were found to be independent prognosticators, which was internally validated using bootstrap resampling techniques. However, no significant correlation was found between protein expression and MGMT methylation status, thus suggesting that the two assays probably assess different biological features. Conclusions: MGMT promoter methylation status and low MGMT expression were both found to be positive prognosticators in newly diagnosed glioblastoma patients treated using surgical resection and Gliadel® implants followed by Stupp9s protocol. Disclosure: Dr. Guillamo has nothing to disclose. Dr. Levallet has nothing to disclose. Dr. Dugue has nothing to disclose. Dr. Vital has nothing to disclose. Dr. Diebold has nothing to disclose. Dr. Menei has nothing to disclose. Dr. Colin has nothing to disclose. Dr. Peruzzy has nothing to disclose. Dr. Emery has nothing to disclose. Dr. Bernaudin has nothing to disclose. Dr. Chapon has nothing to disclose. Dr. Lechapt-Zalcman has nothing to disclose.