Outcome of three-fraction gamma knife radiosurgery for brain metastases according to fractionation scheme: preliminary results

Purpose: The optimal interfraction intervals for fractionated radiosurgery has yet to be established. We investigated the outcome of fractionated gamma knife radiosurgery (FGKRS) for large brain metastases (BMs) according to different interfraction intervals. Methods: Between September 2016 and May 2018, a total of 45 patients who underwent FGKRS for BMs were enrolled in this study. They were divided into two groups (standard fractionation over 3 consecutive days with a 24-h interfraction interval versus prolonged fractionation over 4 or 5 days with an interfraction interval of at least 48-h). BMs with ≥ 2 cm in maximum diameter or ≥ 5 cm³ in volume were included in analysis. Results: Among 52 BMs treated with 3-fraction GKRS, 25 (48.1%) were treated with standard fractionation scheme, and 27 (51.9%) with prolonged fractionation scheme. The median follow-up period was 10.5 months (range 5–25). Local tumor control rates of the standard group were 88.9% at 6 months and 77.8% at 12 months, whereas those of the prolonged group were 100% at 6 and 12 months (p = 0.023, log-rank test). In multivariate analysis, fractionation scheme (hazard ratio [HR] 0.294, 95% CI 0.099–0.873; p = 0.027) and tumor volume (HR 0.200, 95% CI 0.051–0.781; p = 0.021) were revealed as the only significant factors affecting the local tumor control after 3-fraction GKRS. Conclusions: Our preliminary tumor control results suggest a promising role of 3-fraction GKRS with an interfraction interval of at least 48-h. This fractionation regimen could be an effective and safe treatment option in the management of large BMs.