Abstract 7373: The dual influence of treatment and age on survival in patients with glioblastoma

Abstract Background: Glioblastoma (GBM; IDHwt) is primarily diagnosed at ≥65 years of age with a peak incidence between 70-79 years old. Increased age is a strong detrimental factor. Older patients have significantly poorer treatment outcomes for both immune-based- and standard of care (SOC)-therapies. In addition to treatment response, maladaptive age-dependent effects have been attributed to decreased physical resilience, immune system alterations, and lack of tolerance to therapies. Yet, there is insufficient research investigating age-dependent prognostic factors in electronic health record (EHR) patient data, particularly in the diverse cohort of patients that Loyola University Medical Center (LUMC) serves. Methods: Patients were identified through ICD-9/10 definitions for brain cancer and 192 IDHwt GBM patients were chart reviewed and confirmed. Demographic, co-morbid, mutational, and treatment data was compiled. Analysis of overall survival (OS) was performed using the survminer package in R 4.0.2. Data were stratified by patient age and used to construct univariate and multivariate Cox proportional-hazard models with statistical significance assessed using log-rank tests. Results: GBM patients ≥65 years old (n=103, median OS=221 days) experienced worse OS (p<0.001) compared to those<65 years of age (n=89, median OS=464 days). Older patients declined treatment more frequently (p=0.002) (OR=2.95) and had higher Charlson Comorbidity Index (CCI) scores (p<0.001). After removing patients who declined treatment (n=143), this age-influenced outcome disparity persisted (p=0.019). After further restricting to only patients who completed a full course of SOC radio-chemotherapy (n=125) (young: n=71, median OS=543 days) (old: n=54, median OS=495 days), OS differences between age groups lost significance (p=0.061). Among patients in this cohort, MGMT methylation (p=0.027) and initial tumor resection (p<0.001) was associated with increased OS. The development of neurocognitive symptoms within 6 months of diagnosis (p<0.001), higher initial CCI (p=0.019), and initial KPS under 80 (p=0.002) were independently associated with poorer OS. When accounting for initial KPS and resection status, OS differences between age groups were significant (p=0.01). Unlike the older cohort, younger patients had a significant association between increased body mass index and improved OS (p=0.017) while cachexia/significant weight loss was associated with worse OS (p=0.015). Conclusion: Though the statistical significance is missing in the completed treatment cohort, likely due to sample size, clinical trends show younger patients have better survival outcomes. The older cohort’s decreased physical resilience, as evidenced by the increased pre-existing comorbidities and higher CCI scores, could be driving their decreased participation and may suggest additional biological etiologies for the discrepancies in OS. Citation Format: James Fahey, Manon Penco, Emma Federico, Erica Power, Michael Egozi, Dayna Sloane, Isaac Ng, Kayeromi Gomez, Kristen L. Lauing, Ishan Roy, Theresa Walunas, Kevin P. Barton, Douglas E. Anderson, Anand V. Germanwala, Vikram C. Prabhu, Jigisha Thakkar, Derek A. Wainwright. The dual influence of treatment and age on survival in patients with glioblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 7373.