Gamma Knife radiosurgery for primary and recurrent glioblastoma: Systematic review and meta-analysis with target- and protocol-based stratification

Stereotactic radiosurgery has been explored as monotherapy or in combination with systemic agents in newly diagnosed and recurrent Glioblastoma (GBM). Data specific to Gamma Knife radiosurgery (GKSR) remains sparse, and its role is not clearly defined in guidelines. A systematic review and meta-analysis were conducted. Pubmed, Embase, and Web of Science were searched for articles reporting median progression-free survival (PFS) and overall survival (OS) times, actuarial survival, adverse events (AREs), and radionecrosis (RN) rates following salvage or adjuvant GKSR in GBM. Subgroup analyses were performed based on target delineation and treatment protocol. A total of 33 studies encompassing 1732 patients were included. In the recurrent (rGBM) cohort (n = 1082), the pooled median PFS was 5.6 months and OS 21.4 months, with an RN of 13 %. The addition of bevacizumab was associated with an extended median PFS of 7.9 months and OS of 25.7 months, along with a reduced rate of recurrence (9 %). Expanding the treatment field did not significantly affect PFS, OS, or RN rates. In the adjuvant setting (n = 647), GKSR achieved a median PFS of 9.4 months, OS of 18.3 months, and an RN rate of 13 %. Progression-free survival outcomes were broadly comparable to those of other salvage modalities and appeared to be further enhanced when combined with bevacizumab. While current evidence remains insufficient to support its routine use, GKSR may be considered an adjunctive component within individualized, multimodal treatment strategies, particularly when the therapeutic goal is to enhance local disease control with minimal added toxicity. PROSPERO ID: CRD420251072605.