Rethinking treatment de-escalation in elderly glioblastoma: Lessons from a multicenter real-world cohort.

Area of Science:

• Neuro-oncology
• Geriatric oncology
• Clinical trial analysis

Background:

• Elderly glioblastoma (GBM) patients face poor prognosis and high treatment toxicity.
• De-escalated regimens are common, often based on MGMT promoter methylation status.
• Real-world outcomes and molecular details of GBM treatment in the elderly are underreported.

Purpose of the Study:

• To evaluate real-world outcomes of different treatment strategies for elderly GBM patients.
• To identify factors influencing survival in this population.
• To compare the efficacy and toxicity of various post-operative treatments.

Main Methods:

• Retrospective analysis of 573 elderly GBM patients (≥65 years) treated between 2009-2023.
• Comparison of treatments: chemoradiotherapy (CRT), temozolomide (TMZ) monotherapy, radiotherapy (RT) alone, and best supportive care.
• Survival analysis using Kaplan-Meier and log-rank tests, with analysis of MGMT status and Karnofsky Performance Status (KPS).

Main Results:

• Chemoradiotherapy (CRT) showed the longest median overall survival (mOS) at 14 months, versus 8 months for TMZ/RT and 2 months for supportive care.
• Among MGMT-methylated patients, CRT mOS was 23 months vs. 8 months for TMZ.
• Higher KPS, younger age, and surgical resection predicted longer survival; TMZ toxicity was low.

Conclusions:

• Fit elderly GBM patients can benefit from standard, full-dose therapy.
• Treatment decisions should prioritize functional and clinical fitness over chronological age.
• Integrating clinical and functional factors is crucial for managing elderly GBM patients.