Purpose: The role of stereotactic radiosurgery (SRS) alone for patients with ≥5 brain metastases is not fully understood. The objective of the study was to compare SRS-alone treatment results for 2 to 4 versus 5 to 15 tumors. Methods and Materials: This was an institutional review board–approved, retrospective cohort study using our prospectively accumulated database including 1150 patients with 2 to 4 tumors and 939 with 5 to 15 tumors who underwent Gamma Knife SRS during a 20-year period (1998-2018). The Kaplan-Meier method was used to determine post-SRS survival times, and competing risk analyses were applied to estimate cumulative incidences of the secondary endpoints. Results: The post-SRS median survival time was slightly longer in the group with 2 to 4 tumors (8.1 months) than in that with 5 to 15 tumors (7.2 months, P =.0010). Median survival time differences were statistically significant for non-small cell lung cancer, gastrointestinal tract cancer, and others but not for small cell lung cancer, breast cancer, and kidney cancer. Multivariable analysis demonstrated female sex, better Karnofsky Performance Status score, non-small cell lung cancer (vs gastrointestinal tract cancer), younger age, controlled primary cancer, and no extracerebral metastases to be significant predictors of a longer survival period in both tumor number groups. Crude and cumulative incidences of salvage whole brain radiation therapy were significantly higher in the group with 5 to 15 tumors than in that with 2 to 4 tumors, although those of other secondary endpoints were similar to or lower in the 5 to 15 tumor number group than those in the group with 2 to 4 tumors. Conclusions: We conclude that carefully selected patients with ≥5 to 15 tumors are not unfavorable candidates for SRS alone.
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