Salvage Gamma Knife radiosurgery after prior non-radiation interventions for trigeminal neuralgia

Introduction Salvage Gamma Knife radiosurgery (sGKRS) is increasingly used for trigeminal neuralgia (TN) after failed microvascular decompression (MVD) or percutaneous procedures, but predictors of durable pain control are not well defined. We evaluated outcomes and predictors of pain relief following sGKRS in a single-institution cohort. Methods We retrospectively screened all patients treated with GKRS for TN at our institution (1998–2025) and identified 72 patients who received sGKRS for pain relapse after prior non-radiation interventions. Demographics, treatment plans, radiologic metrics, and pain scores were collected. Response was defined both dichotomously and continuously (change in RPPS/BNI). Multivariate logistic and linear regression identified independent predictors of dichotomous and continuous outcomes. Results Mean age was 63.3 years; 70.8% were female. Most patients received 80 Gy to the 100% isodose (median ANEZ dose: 11 Gy). sGKRS achieved a 78.1% response rate overall, rising to 81.2% in patients with prior MVD. Strikingly, a lower biologically effective dose (BED) to the trigeminal nerve — specifically BED below 2000 Gy — was the single independent predictor of response, on multivariate analysis, both overall (p=0.015) and within the prior-MVD subgroup (p=0.026). On univariate analysis, higher pre-treatment pain severity, V1 involvement, and higher body weight each correlated with better outcomes, though no factor indeoendently predicted the degree of pain improvement on multivariate analysis. Conclusions sGKRS delivers meaningful pain relief in approximately 78% of patients who have failed other interventions — including those with prior MVD. Counterintuitively, a lower BED to the trigeminal nerve, rather than a higher one, independently drives response in the salvage setting, suggesting a neuromodulatory rather than ablative mechanism. Keeping BED below 2000 Gy is the single most impactful modifiable target for treatment planning, and should reframe how salvage radiosurgery prescriptions are designed.