Longitudinal tumor response dynamics after staged gamma knife radiosurgery combined with bevacizumab in sporadic vestibular schwannoma

Background Vestibular schwannomas (VSs) are benign tumors of the eighth cranial nerve. Although Gamma Knife radiosurgery (GKRS) achieves durable tumor control, delayed regression and pseudoprogression remain clinical challenges. Staged GKRS combined with bevacizumab may alter post-radiosurgical tumor response patterns. Aim To compare longitudinal tumor response, pseudoprogression, and clinical outcomes between staged GKRS combined with bevacizumab and single-session GKRS alone in sporadic VSs. Methods We retrospectively reviewed 72 patients with sporadic VSs: 49 treated with staged GKRS plus bevacizumab and 23 with single-session GKRS alone. Longitudinal tumor volume changes were analyzed using multivariable linear mixed-effects models, while early volumetric enlargement was evaluated using Kaplan-Meier estimates and Cox proportional hazards models. Results Compared with GKRS alone, staged GKRS plus bevacizumab showed significantly different response trajectories (treatment-by-time interaction, P < 0.001), with earlier and sustained regression. Greater tumor reduction was observed from 3 to 36 months (all adjusted P < 0.05). Early volumetric enlargement (>10%) occurred in 14.3% versus 60.9% of patients (HR, 0.16; 95% CI, 0.06–0.40; P < 0.001). Pseudoprogression occurred in 4.1% versus 17.4% of patients, without statistical significance ( P = 0.078). Cystic tumor composition was independently associated with greater regression. BEV-related adverse events were mild and manageable. Conclusion Staged GKRS combined with bevacizumab was associated with earlier, more sustained tumor regression and a lower risk of early post-treatment enlargement in sporadic VSs. Larger baseline tumor volume and cystic composition were associated with greater regression. Pseudoprogression was numerically less frequent, although the difference was not statistically significant. Trial registration ChiCTR2600131856 (Chinese Clinical Trial Registry).