Gamma knife radiosurgery for renal cell carcinoma brain metastases across systemic therapy eras: survival, intracranial failure, and lesion-level predictors.

backgroundBrain metastases from renal cell carcinoma (RCC) are uncommon but clinically consequential. We evaluated survival, intracranial failure, lesion-level local failure, and MRI volumetric response after Gamma Knife radiosurgery (GKRS), including associations with systemic therapy exposure.

methodsWe retrospectively identified patients treated with GKRS for intracranial RCC metastases (2001-2025). Systemic therapy exposure (TKI and/or immunotherapy) was captured time-agnostically. Overall survival (OS) and patient-level intracranial treatment failure were analyzed using Kaplan-Meier/Cox models. Lesion-level treatment failure was analyzed using clustered generalized estimating equations (GEE). Six-month volumetric response was assessed using an epsilon-stabilized log volume ratio ln{(V

resultsThirty-four patients (87 lesions) were treated; 22 deaths occurred. Overall survival was numerically longer among patients who received systemic therapy compared with those who did not, although this did not reach statistical significance (log-rank p = 0.058). In a parsimonious adjusted Cox model, TKI exposure was associated with improved OS (aHR 0.191; 95% CI 0.062-0.593; p = 0.004), as was higher KPS (HR 0.37 per 10-point increase; 95% CI 0.21-0.63; p < 0.001). Ten patient-level intracranial treatment failure events occurred, without significant differences by systemic therapy exposure. At the lesion level, 15/87 lesions failed; postoperative cavities had higher failure than intact lesions (71.4% vs. 12.5%; p = 0.001) and remained associated with failure after clustered adjustment (OR 9.92; 95% CI 1.44-68.27; p = 0.020). Dmax was not correlated with 6-month log volume ratio (ρ=-0.075; p = 0.535), but poorer 6-month volumetric response was associated with subsequent lesion failure (p = 0.0023; clustered OR 2.84; 95% CI 1.16-6.96; p = 0.023).

conclusionsIn RCC brain metastases treated with GKRS, postoperative cavities showed a higher observed rate of local failure than intact lesions, although this finding should be interpreted cautiously given the small number of cavity targets. While Dmax was not associated with early volumetric change, early 6-month volumetric trajectory was associated with subsequent local failure, suggesting a pragmatic imaging marker for risk-adapted surveillance and salvage planning. Systemic therapy exposure, particularly TKIs, was associated with OS in adjusted analysis, whereas intracranial treatment failure did not differ by systemic exposure in this cohort.