423P - O6-Methylguanine-Dna Methyltransferase (Mgmt) Cut-Off Methylation Level Determined By Pyrosequencing and Clinical Outcome in Patients with Glioblastoma Multiforme (Gbm): a Single-Institution Experience

Abstract

ABSTRACT Aim: MGMT gene is epigenetically silenced by its promoter hypermethylation in GBM. Hypermethylation is relevant predictor of response to temozolomide. Yet, there is debate around the best technique for MGMT assessment. One of the most interesting methods is pyrosequencing (PyroS) that allows defining a cut-off value for MGMT methylation Aim of our retrospective analysis was to explore if predefined levels of MGMT methylation could impact on overall survival (OS) in a cohort of GBM patients. We also analyzed the potential prognostic role of isocitrate dehydrogenase-1 (IDH1) by PyroS. Methods: Clinical and pathological data of 108 consecutive GBM patients referred to our Department between January 2008 and December 2013 were retrieved. Three groups of patients were identified: unmethylated with MGMT methylation 29% (HM). We calculated median (m) OS and compared the Kaplan Mayer survival curves across the groups through log rank test. Results: 51 cases (47.2%) were UM, 24 (22.2%) IM and 33 (30.6%) HM. The median follow-up is 38.5 months. mOS, months (95%CI) N 108 mOS, months (95%CI) Standard Stupp regimen, N 66 MGMT methylation 13.2 (8.3-15.2) 15.1 (12.8-17.4) MGMT methylation 9-29% 15.8 (9.8-30.8) 25.9 (6.93-53.5) MGMT methylation >29% 19.5 (11.5-47.1) 47 (18.5-57.6) P = 0.0002 P = 0.0001 mOS of IDH1 mutated patients (11 out of 108) was 53.5 months compared to 14.2 months in those wild type (p = 0.01). Conclusions: Our study confirms that a cut-off level of 9% in MGMT methylation has prognostic and predictive value in GBM patients treated with standard therapy. IDH1 mutation may have a prognostic role, although the small patient number does not allow drawing definitive conclusions. Disclosure: All authors have declared no conflicts of interest.