2581 - Impact of Radiation Therapy Fractionation on Survival Outcomes in Elderly Patients with Glioblastoma Following Surgical Resection and Adjuvant Chemotherapy

Purpose/Objective(s): Glioblastoma (GBM) is the most aggressive primary brain malignancy, with poor survival rates despite multimodal treatment. Radiation therapy (RT) remains a cornerstone of treatment; however, optimal postoperative RT regimens for elderly patients remains underexplored. This study retrospectively examines whether RT fractionation—comparing a hypofractionated regimen versus a conventional fraction schedule—affects overall survival (OS) in elderly patients with GBM.

Materials/Methods: We analyzed elderly patients (=70 years) with GBM from the National Cancer Database (2004–2018) who underwent surgical resection and received adjuvant chemotherapy. Patients were stratified by postoperative RT fractionation scheme (10–16 vs. 29–34 fractions). Kaplan-Meier survival analysis with log-rank testing was performed to compare OS between the two RT scheme groups. Cox proportional hazards modeling was used to evaluate the independent impact of RT fractionation scheme on OS, adjusting for age, sex, tumor focality (unifocal vs. multifocal), MGMT promoter methylation, and comorbidity burden as measured by the Charlson-Deyo Comorbidity Index.

Results: In 221 patients evaluated, Kaplan-Meier survival analysis demonstrated a significant improvement in median OS for patients receiving conventional RT fractionation compared to hypofractionated RT (11.5 vs. 6.34 months, log-rank p = 0.00039) and a 2.2% absolute increase in median survival rate (18.2% vs. 16.0%). Multivariate Cox regression analysis demonstrated significant survival advantage for the conventional RT fractionation cohort, with a 48.6% reduction in mortality risk (HR = 0.514, 95% CI: 0.332–0.796, p = 0.0029) after adjusting for other covariates. Additional factors negatively impacting OS included increasing age (HR = 1.05, 95% CI: 1.01–1.09, p = 0.0127), multifocal tumors (HR = 1.67, 95% CI: 1.10–2.54, p = 0.0159), and higher comorbidity burden (HR = 1.42, 95% CI: 1.14–1.79, p = 0.00223). In contrast, high MGMT promoter methylation was associated with improved OS (HR = 0.635, 95% CI: 0.463–0.870, p = 0.00471). The was no significant difference in survival by sex in this model.

Conclusion: In this retrospective study of elderly patients with GBM who underwent surgical resection and received adjuvant chemotherapy, conventional fractionation RT (29–34 fractions) was associated with a significant survival advantage compared to hypofractionation (10–16 fractions), even after adjusting for key clinical and demographic covariates. These findings suggest that a conventional fractionation scheme should be considered for select elderly patients who can tolerate a prolonged treatment course. However, given the potential implications for treatment burden and quality of life, further prospective studies are warranted to refine patient selection criteria, optimize personalized treatment strategies, and improve outcomes for elderly patients with GBM.