Single- and hypofractionated stereotactic radiosurgery for large (> 2 cm) brain metastases: a systematic review

Purpose Since frameless stereotactic radiosurgery (SRS) techniques have been recently introduced, hypofractionated SRS (HF-SRS) for large brain metastases (BMs) is gradually increasing. To verify the efficacy and safety of HF-SRS for large BMs, we aimed to perform a systematic review and compared them with SF-SRS. Methods We systematically searched the studies regarding SF-SRS or HF-SRS for large (> 2 cm) BM from databases including PubMed, Embase, and the Cochrane Library on July 31, 2018. Biologically effective dose with the α/β ratio of 10 (BED 10 ), 1-year local control (LC), and radiation necrosis (RN) were compared between the two groups, with the studies being weighted by the sample size. Results The 15 studies with 1049 BMs that described 1-year LC and RN were included. HF-SRS tended to be performed in larger tumors; however, higher mean BED 10 (50.1 Gy 10 versus 40.4 Gy 10 , p < 0.0001) was delivered in the HF-SRS group, which led to significantly improved 1-year LC (81.6 versus 69.0%, p < 0.0001) and 1-year overall survival (55.1 versus 47.2%, p < 0.0001) in the HF-SRS group compared to the SF-SRS group. In contrast, the incidence of radiation toxicity was significantly decreased in the HF-SRS group compared to the SF-SRS group (8.0 versus 15.6%, p < 0.0001). Conclusion HF-SRS results in better LC of large BMs while simultaneously reducing RN compared to SF-SRS. Thus, HF-SRS should be considered a priority for SF-SRS in patients with large BMs who are not suitable to undergo surgical resection.