Abstract 94: Utilization of MGMT Promoter Methylation Status to Guide Treatment in Elderly Patients With Glioblastoma

Abstract

Abstract Purpose: Glioblastoma is the most common primary malignant brain tumor in adults. In younger patients, the standard of care is chemoradiation. However, due to the increased risk of chemotherapy-associated toxicity in older patients, monotherapy is instead recommended. O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation has been found to be a prognostic indicator, with methylated MGMT (mGMT) patients having better response to chemotherapy (temozolomide) than unmethylated MGMT (uMGMT) patients. In this study, we compared the overall survival (OS) of different treatment modalities in mMGMT and uMGMT glioblastoma patients older than 60 years. Methods: Patients diagnosed with glioblastoma (ICD-O-3 histology code 9440) after the age of 60 (N = 8356) were identified in the National Cancer Database (2004-2020). Effects of MGMT methylation status and treatment modality (chemotherapy, CT; radiation therapy, RT; chemoradiation, CRT) on OS were analyzed using Kaplan-Meier curves, log-rank tests, and Cox proportional hazards modeling. Results: The average age of this sample was 70.8 ± 6.8 years, with nearly half of the sample being under the age of 70. Regardless of MGMT status, most patients received CRT (63.7% uMGMT, 65.1% mMGMT). uMGMT patients treated with CRT had better OS (14.0 months) than those receiving RT (8.2 months; p < 0.001), but there was no difference compared to those receiving CT (12.3 months; p = 0.247). A similar trend was seen in mMGMT patients (CRT: 16.9 months, RT: 9.3 months, CT: 11.8 months). However, among all patients receiving CRT, those with mMGMT survived significantly longer than their uMGMT counterparts (p < 0.001). After adjusting for all other variables, Cox regression analysis remained significant, with a decreased hazard ratio in mMGMT patients (HR = 0.631, p < 0.001). Conclusion: mMGMT patients older than 60 years of age demonstrated better survival outcomes when treated with chemoradiation. While mMGMT patients had a better response to CRT than uMGMT patients, uMGMT patients experienced improved OS with CRT than single modality treatment. Therefore, combination therapy should be considered not only in younger patients but also in older patients who otherwise have no medical contraindications. Citation Format: Tiffany Chu, Ting Wang, Peter Silberstein. Utilization of MGMT Promoter Methylation Status to Guide Treatment in Elderly Patients With Glioblastoma [abstract]. In: Proceedings of the 11th Annual Symposium on Global Cancer Research; Closing the Research-to-Implementation Gap; 2023 Apr 4-6. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(6_Suppl):Abstract nr 94.