Treatment practices and survival outcomes for IDH-wildtype glioblastoma patients according to MGMT promoter methylation status: insights from the U.S. National Cancer Database.

Abstract

Purpose: Methylation of the O⁶-methylguanine-DNA methyltransferase (MGMT) promoter is an important prognostic marker in glioblastoma (GBM); however, its implementation in clinical practice remains understudied. Here, we assessed the prevalence of MGMT methylation status among GBM patients in the United States. Additionally, we evaluated treatment practices and survival outcomes of GBM patients according to MGMT promoter methylation status.

Methods: The National Cancer Database was queried to identify all adult U.S. patients (≥ 18 years) diagnosed with IDH-wildtype GBM between 2018 and 2020. Treatment regimen was grouped into no chemotherapy and no radiotherapy, chemotherapy alone (without radiotherapy), radiotherapy alone (without chemotherapy), and chemoradiotherapy (chemotherapy and radiotherapy). Survival data were analyzed using Kaplan-Meier survival curves, log-rank tests, and multivariable Cox proportional hazard modeling.

Results: A total of 20,734 patients were included, of whom 6,404 (30.9%) had MGMT-methylated GBM, 9,065 (43.7%) had MGMT-unmethylated tumors, and 5,265 (25.4%) had unknown methylation status. The median and three-year overall survival were 12.4 months and 15.5%, respectively, for the entire cohort (16.4 months and 23.9% for MGMT-methylated patients and 11.8 months and 9.8% for MGMT-unmethylated patients, p < 0.001). Chemoradiotherapy was less commonly used for elderly (≥ 70 years, 58.5%) than non-elderly (< 70 years, 79.2%) patients. Among elderly patients, radiotherapy alone was more commonly administered than chemotherapy alone for patients with MGMT-unmethylated tumors (11.2% vs. 2.1%) and MGMT-methylated tumors (6.6% vs. 3.9%). However, chemotherapy alone was associated with a lower mortality risk (HR 0.71, 95% CI 0.51-0.99, p = 0.04) than radiotherapy alone for elderly patients with MGMT-methylated tumors, while chemotherapy alone was associated with a higher mortality risk (HR 1.63, 95% CI 1.09-2.44, p = 0.02) than radiotherapy alone for elderly patients with MGMT-unmethylated tumors. Patients who were elderly, uninsured, insured through Medicaid, lived in zip codes with lower median education levels, or received care at non-academic programs were less likely to undergo MGMT testing.

Conclusion: A high proportion of GBM patients in the United States undergo MGMT promoter testing, though significant sociodemographic disparities exist. While there was a decrease in chemoradiotherapy use with increasing age, radiotherapy alone was more commonly administered to elderly patients than chemotherapy alone irrespective of MGMT promoter methylation status.