Bell EH, et al. - In this correlative analysis of the NRG Oncology/RTOG 0424 trial, researchers evaluated the association of O⁶-methylgaunine-DNA-methyltransferase (MGMT) promoter methylation with survival outcomes among patients with World Health Organization grade II glioma treated with radiotherapy and temozolomide. Findings revealed MGMT promoter methylation as an independent prognostic biomarker for these patients. This was the first study to confirm the prognostic significance of MGMT promoter methylation in patients with grade II glioma treated with combined radiotherapy and temozolomide and highlights its possible prognostic value beyond IDH1/2 mutation status (wild type vs mutant).

Methods

• In order to determine MGMT promoter methylation and IDH1/2 status as well as the link between MGMT status and survival outcomes, researchers analyzed specimens collected after trial completion.
• MGMT promoter methylation status was calculated using a model derived from logistic regression (MGMT-STP27).
• They determine the association of MGMT status with survival outcomes via performing univariate and multivariable analyses using the Cox proportional hazards regression model.
• In multivariable analyses, patient pretreatment characteristics were included as covariates.
• Progression-free survival (PFS) and overall survival (OS) were assessed as main outcomes and measures.

Results

• From NRG Oncology/RTOG 0424, 129 eligible patients were identified; 75 had MGMT status available (57 methylated and 18 unmethylated).
• As opposed to oligoastrocytoma or oligodendroglioma, 13 unmethylated patients (72.2%) had astrocytoma; 23 methylated patients (40.4%) had astrocytoma.
• An unmethylated MGMT promoter was noted to be significantly associated with worse OS and PFS in univariate analyses.
• In multimarker multivariable analyses, the statistical significances remained maintained, including IDH1/2 status for both OS and PFS.