Single-fraction stereotactic radiosurgery vs. hypofractionated stereotactic radiotherapy for resected brain metastases: a systematic review and meta-analysis of comparative studies.

Postoperative stereotactic radiotherapy (SRT) is widely used after resection of limited brain metastases, but the optimal fractionation remains uncertain. Single-fraction stereotactic radiosurgery (SF-SRS) is convenient and well established, whereas hypofractionated stereotactic radiotherapy (HF-SRT) may improve dose delivery and normal tissue tolerance in larger or more complex cavities. This systematic review and meta-analysis compared these two postoperative approaches. PubMed, Scopus, and Embase were searched from inception to December 23, 2025. Original comparative studies enrolling adults treated with postoperative cavity-directed stereotactic radiotherapy were included. Risk of bias was assessed using ROBINS-I. Seven retrospective comparative studies met the inclusion criteria, representing 589 patients and 649 resection cavities. The most common primary tumor was non-small cell lung cancer followed by melanoma and breast cancer. The RT dose in the single fraction population was between 15 and 20 Gy across the studies. Also, the hypofractionated regimen consisted of 3 to 6 fractions with the total dose being anywhere from 14 to 32.5 Gy. At 6 months, local control was marginally higher with SF-SRS than HF-SRT (RR 1.05, 95% CI 1.01-1.09, p = 0.006). However, given that HF-SRT was preferentially used for larger or anatomically complex cavities, this difference likely reflects baseline imbalances rather than a true treatment effect. The 12-month local control analysis showed a non-significant trend favoring SF-SRS (RR 1.06, 95% CI 0.99-1.14, p = 0.08). Three studies were pooled for 12-month overall survival, with no significant difference between approaches (RR 1.08, 95% CI 0.82-1.41, p = 0.59). The available comparative retrospective evidence suggests that SF-SRS and HF-SRT achieve broadly similar postoperative outcomes for resected limited brain metastasis although HF-SRT cohorts included larger or deeply seated lesions. Nevertheless, SF-SRS may offer a small early local control advantage. Prospective randomized studies are needed to define the optimal postoperative strategy.