RADT-34. TREATMENT DE-ESCALATION IN ELDERLY GLIOBLASTOMA: WHAT WE LEARN FROM REAL-WORLD COHORTS

Abstract BACKGROUND Glioblastoma (GBM) in elderly patients (≥65 years) is associated with poor prognosis and increased treatment toxicity. As a result, many receive de-escalated treatment regimens, often guided by MGMT promoter methylation status. However, real-world outcome data across treatment strategies remain limited. METHODS We conducted a retrospective cohort study of 573 elderly GBM patients treated between 2009–2023 at two Israeli tertiary centers. Patients were categorized by post-operative treatment: (1) chemoradiotherapy (CRT; 60Gy/30 fractions or 40Gy/15 fractions) (2) temozolomide (TMZ) monotherapy, (3) radiotherapy alone (RT), or (4) best supportive care. MGMT methylation status and Karnofsky Performance Status (KPS) were analyzed where available. Survival was assessed using Kaplan-Meier and log-rank tests. RESULTS Median overall survival (mOS) was longest in the CRT group (14 months) compared to 8 months for TMZ and RT monotherapies and 2 months for best supportive care. Among MGMT-methylated patients, CRT was associated with mOS of 24 months, versus 8 months for TMZ alone. Younger age, surgical resection and higher KPS at diagnosis predicted longer survival. In the TMZ group, toxicity was low (6% hematologic, 12% non-hematologic grade 3/4 events) and survival increased with number of TMZ cycles received. Salvage therapy after progression was associated with longer overall survival (4 vs, 10 months) and extended post-progression survival (59 vsv, 131 days). CONCLUSION Fit elderly patients derive significant benefit from full standard-of-care treatment, particularly when MGMT-methylated. Age alone should not dictate treatment intensity. These real world findings support integrating clinical, molecular, and functional factors into geriatric oncology decision-making.