Background: Recurrent glioblastomas and high-grade gliomas carry a dismal prognosis and have no standard of care. Re-irradiation remains a valuable salvage therapy at recurrence, yet concern for radiation-induced toxicity and pseudoprogression continues to influence treatment decisions. Optimal modality selection, targeted therapy, and immunotherapy in the recurrent setting remain incompletely characterized. Methods: Forty patients who received re-irradiation at a single institution were retrospectively analyzed. Patient outcomes included overall survival from diagnosis (OS), overall survival from re-irradiation (OS-ReRT), and post-re-irradiation progression-free survival (PFS-ReRT). Functional status was assessed using the Karnofsky Performance Score (KPS) at initial radiation, re-irradiation, and last follow-up. Additional collected variables included systemic therapy, targeted therapy, immunotherapy, and surgical management at both initial and recurrent disease stages. Results: Tumor grade was the strongest predictor of OS and PFS-ReRT. Patients with late recurrence (≥ 12 months from the end of initial radiation) had significantly longer OS from diagnosis compared to those with early recurrence (median 82.4 vs. 15.4 months; HR 0.24, p = 0.001). KPS declined in the majority of patients over the course of disease, and fatigue emerged as the most notably increasing symptom at recurrence. No significant difference in OS-ReRT was observed between brachytherapy and other re-irradiation modalities on multivariable analysis (HR 2.02, p = 0.129). Bevacizumab (Avastin) had no significant impact on KPS change or survival outcomes. Conclusion: Re-irradiation is a safe and feasible intervention for appropriately selected recurrent glioma patients. Brachytherapy offers comparable oncological outcomes to external beam techniques with the added advantage of combining resection and radiation in a single intervention. Future studies should consider incorporating molecular re-profiling at recurrence to capture tumor evolution and guide treatment selection, alongside validated quality of life measures to better characterize the functional impact of each modality in this inherently palliative setting.
Shreeya Yarlagadda (Thu,) studied this question.