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September 10, 2025Open Access

The role of extent of resection, chemoradiation, and MGMT promoter methylation in overall survival in a large cohort of IDH-wildtype glioblastoma

MPMegan ParkerJohns Hopkins University ACAustin CarmichaelJohns Hopkins University ASAntolin Serrano-FariasJohns Hopkins University

Key Points

Maximizing the extent of resection notably improves overall survival in glioblastoma patients.
In multivariate analysis, gross-total resection is associated with a 40% improvement in survival compared to excisional biopsy.
Chemotherapy and MGMT promoter methylation both independently enhance survival rates among individuals with glioblastoma.
The influence of gross-total resection on survival in MGMT methylated tumors receiving chemoradiation requires further research.

Abstract

OBJECTIVE Although MGMT promoter methylation, gross-total resection (GTR), and adjuvant chemoradiation therapy are known to independently improve clinical outcomes for patients with glioblastoma (GBM), their combined influence remains unclear. In the present study, the authors investigated the complementary role of these factors in GBM prognosis. METHODS The 2022 National Cancer Database was queried for individuals with histologically confirmed IDH-wildtype GBM WHO grade 4 and available MGMT promoter methylation status data. Demographic, clinical, and treatment-related variables were analyzed. Kaplan-Meier survival and multivariate Cox proportional hazards analyses were conducted, stratified by MGMT promoter methylation and chemoradiation therapy status. RESULTS A total of 27,858 patients were included in the analysis. Chemotherapy, radiation therapy, and MGMT promoter methylation status were independently associated with improved survival in the overall cohort (p < 0.001). In Kaplan-Meier analysis, MGMT promoter methylation was associated with improved overall survival for individuals who received standard chemoradiation therapy (p < 0.001) but not for individuals who did not receive chemoradiation therapy (p = 0.649). In the overall cohort, GTR was associated with a 40% improvement in overall survival relative to excisional biopsy (HR 0.633 95% CI 0.52–0.77, p < 0.001) in multivariate analysis. In patients with MGMT promoter–methylated tumors, GTR was associated with a 70% (HR 0.30 95% CI 0.12–0.71, p = 0.007) improvement in overall survival compared with excisional biopsy in those who did not receive chemoradiation therapy, but GTR did not significantly improve survival in those who received chemoradiation therapy (HR 0.97 95% CI 0.54–1.73, p = 0.912). For patients with MGMT promoter–unmethylated tumors, GTR was associated with improved overall survival for both those who received chemoradiation therapy (HR 0.48 95% CI 0.33–0.70, p < 0.001) and those who did not (HR 0.50 95% CI 0.28–0.89, p = 0.018). CONCLUSIONS In this large registry study, the authors demonstrated that maximizing the extent of resection improves overall survival, especially for individuals with MGMT unmethylated GBM or those not receiving chemoradiation therapy. However, the impact of gross-total resection requires further investigation in patients with MGMT promoter–methylated GBM who receive adjuvant therapy. These findings support future studies exploring new diagnostic techniques for preoperative evaluation of MGMT methylation to aid surgical planning.

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