Patterns of glioblastoma recurrence and survival outcomes following initial external beam radiation therapy

Background: Glioblastoma (GBM) is an aggressive, malignant central nervous system tumor with a poor prognosis, often recurring despite standard care using a multimodal approach. This study investigates the recurrence patterns and survival outcomes in patients with GBM who underwent Gamma Knife radiosurgery (GKRS) for tumor recurrence following initial treatment with external beam radiation therapy (EBRT). Methods: A single-institution retrospective study was conducted on 41 patients with newly-diagnosed, Isocitrate Dehydrogenase (IDH)-wildtype GBM between 2020 and 2024. All patients received standard EBRT (60 Gy in 30 fractions or 5940 cGy in 33 fractions) followed by salvage GKRS for recurrence. Recurrence patterns were defined as in-field (>80% of recurrence volume), marginal (20-80% of recurrence volume), or distant (<20% of recurrence volume) based on the recurrence volume found within the 95% isodose volume from initial EBRT. Clinical, imaging, and survival data were obtained from our patient registry. Serial imaging was analyzed to obtain tumor volume data. Results: Of the 41 patients, recurrences were in-field in 35 patients (85.4%), marginal in 1 patient (2.4%), and distant in 5 patients (12.2%). Maximum ( P = 0.01) and mean ( P = 0.002) EBRT dosing was found to be significantly associated with in-field versus distant recurrence patterns. However, the recurrence pattern was not found to be significantly associated with overall survival (OS) ( P = 0.53) or recurrence-free survival ( P = 0.45). Univariate analysis identified a significant association between initial EBRT dose and OS ( P = 0.0087). Conclusion: GKRS is an effective salvage therapy for recurrent GBM, with survival outcomes independent of recurrence pattern. These findings support the use of limited radiation margins to potentially reduce radiation exposure and treatment toxicity while maintaining tumor control, reinforcing GKRS as a valuable treatment modality in recurrent GBM management.