MGMT promoter methylation status as a prognostic factor for the outcome of gamma knife radiosurgery for recurrent glioblastoma

Abstract

We conducted this study to determine whether the methylation status of the O⁶-methylguanine-DNA methyltransferase (MGMT) promoter was a prognostic marker for positive outcomes of gamma knife radiosurgery (GKS) for recurrent glioblastoma (GBM). We retrospectively examined 61 patients, who underwent GKS for local recurrent GBM between 2004 and 2015; in all patients, the methylation status of the MGMT promoter was identified via methylation-specific quantitative real-time polymerase chain reaction. All patients underwent surgical resection and were diagnosed histopathologically with GBM. Prognostic factors associated with progression-free survival (PFS) and overall survival (OS) were identified in univariate and multivariate analyses. Twenty-five (41%) had a methylated MGMT promoter, and 36 (59%) had an unmethylated MGMT promoter. The median age at GKS was 58 years. The median tumor volume at GKS was 7.0 cm³, and the median marginal dose was 16 Gy. The median follow-up period after GKS was 7.5 months. The median PFS time after GKS was 8.9 months (95% CI 4.3-13.5 months) in the methylated and 4.6 months (95% CI 3.7-5.5 months) in the unmethylated group (P = 0.016). The median OS time after GKS was 14.0 months (95% CI 9.3-18.7 months) in the methylated group and 9.0 months (95% CI 6.5-11.5 months) in the unmethylated group (P = 0.026). Methylation of the MGMT promoter correlated with better PFS and OS after GKS for recurrent GBM. Prospective comparative studies are required to determine whether MGMT methylation directly affects the efficiency of GKS.

Keywords: Gamma knife; Glioblastoma; Methylation; O6-methylguanine-DNA methyltransferase; Recurrence.