Comparison of 2 stereotactic radiotherapy regimens for brain metastases: Is higher always better?

Stereotactic radiosurgery (SRS) has become a preferred treatment for brain metastases (BMs) due to its precision, minimizing neurocognitive side effects compared to whole-brain radiotherapy. However, the optimal dose-fractionation regimen for balancing local tumor control and minimizing radiation necrosis (RN) remains debated. This study compares 2 commonly used fractionated SRS regimens: 23.1Gy in 3 fractions and 27Gy in 3 fractions.

This retrospective study included 1348 BMs treated with fractionated SRS between 2014 and 2023. Treatment planning used inhomogeneous dose delivery on a TrueBeam STX linac, delivering either 23.1Gy/3 fractions or 27Gy/3 fractions to the periphery (33Gy to the isocenter). Outcomes included local relapse-free survival (LRFS), RN-free survival (RNFS) and symptomatic RN-free survival (SRNFS), analyzed using Kaplan-Meier estimates. Impact of the main clinical factors (BMs volume, histology of the primary, concomitant systemic therapies and history of radiotherapy) were analyzed using univariate and multivariate Cox regression models.

Median follow-up was 12.0 months for LRFS and 11.0 months for RNFS. The 27Gy regimen showed a non-significant improvement in LRFS (HR: 0.66, 95% CI9: 0.43-1.01) but significantly increased the risk of both RN (HR: 2.29, 95% CI: 1.60-3.26) and symptomatic RN (HR: 3.74, 95% CI: 1.93-7.26). On multivariate analysis, choice of the SRS protocol was an independent predictor of RN.

The 27Gy regimen offers modest improvements in local control but significantly increases the risk of both RN and symptomatic RN. These results emphasize the need for personalized SRS regimens and further exploration of dose optimization strategies to improve therapeutic outcomes.