October 5, 2025Open Access

P12.10.a Rethinking Treatment De-Escalation in Elderly Glioblastoma: Lessons From a Multi-Center Real World Cohort

OFOrit FurmanTel Aviv Sourasky Medical Center EFEva FalachSheba Medical Center IDIrit DvirBen-Gurion University of the Negev

Key Points

Median overall survival for chemoradiotherapy was 14 months in elderly glioblastoma patients, significantly better than TMZ or RT alone.
Survival for MGMT-methylated patients increased to 23 months with combined therapy versus 8 months on TMZ alone.
Retrospective cohort analysis of 573 elderly glioblastoma patients evaluated multiple treatment modalities across two medical centers.
Findings indicate that age should not be the sole determinant of treatment intensity, emphasizing the need for comprehensive assessments.

Abstract

Abstract BACKGROUND Glioblastoma (GBM) in elderly patients (≥65 years) is associated with increased frailty, treatment toxicity, and poor prognosis. Consequently, many elderly patients receive de-escalated treatment regimens, often guided by MGMT promoter methylation status. However, real-world data comparing outcomes across different treatment modalities remain limited. MATERIAL AND METHODS We conducted a retrospective cohort study including 573 elderly GBM patients treated between 2009 and 2023 at two tertiary medical centers in Israel. Patients were categorized according to postoperative treatment: (1) chemoradiotherapy (CRT; 60 Gy/30 fractions or 40.05 Gy/15 fractions), (2) upfront temozolomide (TMZ) alone, (3) radiotherapy (RT) alone, or (4) best supportive care. MGMT methylation status and Karnofsky Performance Status (KPS) were analyzed when available. Survival outcomes were assessed using Kaplan-Meier and Mantel-Cox tests. RESULTS Median overall survival (mOS) was significantly longer for patients treated with chemoradiotherapy (14 months) compared to TMZ alone (8 months) or RT alone (8 months). Among MGMT-methylated patients, combined therapy resulted in an mOS of 23 months, versus 8 months for TMZ alone. In TMZ-only patients, salvage treatment upon disease progression was associated with improved survival (10 vs. 5 months). TMZ-related toxicity was manageable, with grade 3/4 hematologic and non-hematologic toxicities occurring in 6% and 12% of patients, respectively. Lower KPS at diagnosis correlated with reduced treatment benefit. CONCLUSION Fit elderly patients benefit significantly from standard-of-care therapy, particularly in the presence of MGMT methylation. Age alone should not determine treatment intensity. Our findings underscore the importance of integrating clinical, molecular, and functional assessments into treatment planning, emphasizing the need for real-world validation of geriatric oncology algorithms.

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