Prognostic and predictive impact of MGMT promoter methylation in grade 3 gliomas

Background: Grade 3 gliomas are aggressive primary brain tumors. Promoter methylation of methyl guanine methyl transferase (MGMT) has been associated with a favorable prognosis in patients with glioblastoma, but the impact of MGMT promoter methylation in patients with grade 3 gliomas is less clear. The purpose of the present study was to evaluate the utilization of MGMT testing in patients with Grade 3 glioma, as well its prognostic and predictive value. Methods: The National Cancer Database (NCDB) was queried (2004–2016) for patients with newly diagnosed grade 3 glioma without 1p19q codeletion. Statistics included Kaplan-Meier overall survival (OS) analysis, along with Cox proportional hazards modeling. Results: Of 20,488 total patients, 1,209 (5.0%) had MGMT testing. Of these patients, 561 (46.4%) were MGMT methylated (mMGMT), and 648 (53.6%) were MGMT unmethylated (uMGMT). mMGMT patients experienced greater median overall survival (OS) than both uMGMT patients as well as patients with no MGMT status reported (p < 0.05 for both). mMGMT was associated with improved OS for patients receiving adjuvant chemoradiation or adjuvant radiation, but not for patients receiving adjuvant chemotherapy or no adjuvant treatment. Conclusions: This is the largest study to date describing the utilization of and outcomes for mMGMT patients with grade 3 glioma. The present results demonstrate that mMGMT is a prognostic factor and possibly a predictive biomarker, and is currently under-utilized within the US. MGMT methylation status could be used to risk-stratify and select patients for treatment intensification. Importance of study: The present study is the largest of its kind to examine the prognostic and predictive impact of MGMT methylation (mMGMT) amongst patients with Grade 3 Glioma. The results suggest that mMGMT is prognostic, as amongst all patients, mMGMT was associated with improved overall survival. These results also suggest that mMGMT is predictive, as patients treated with adjuvant chemoradiation or adjuvant radiation therapy did have improved overall survival with mMGMT, though there was no difference in overall survival observes amongst patients receiving adjuvant chemotherapy or those patients receiving no adjuvant treatment. The study also found that only 5% of patients nationwide with Grade 3 Glioma are tested for MGMT.