Long-term clinical outcomes of bevacizumab for treatment of stereotactic radiosurgery-induced radiation necrosis in patients with brain metastases

Purpose: Radiation necrosis (RN) is a potentially debilitating complication of stereotactic radiosurgery (SRS) for brain metastases (BrM). Bevacizumab, a monoclonal antibody against vascular endothelial growth factor A, is increasingly used for treating symptomatic RN. This multi-institutional retrospective study examines its longitudinal efficacy, toxicity, and steroid-sparing effect in BrM patients with SRS-induced RN over an extended follow-up. Methods: BrM patients from two Australian health networks who received bevacizumab between 2018–2023 for SRS-induced RN were identified. Patient characteristics, symptomatic and radiological responses, steroid use, and toxicities were recorded. Time-to-events and associations with outcomes were analysed with Kaplan-Meier and Cox methods. Results: 26 patients were analysed over a median follow-up of 21.2 months. The most common bevacizumab schedule was 7.5mg/kg 3-weekly for a median of 3 cycles. Symptomatic responses were detectable 1-week post-commencement, improving headache and neurological deficits in 60% and 80% of patients by 6 months. 88% had radiological improvement by a median of 7 weeks. 83% of those on steroids could cease steroids, over a median of 1 month. 19% developed recurrent, symptomatic RN 9.5–28.5 months after bevacizumab cessation. 75% of those re-treated with bevacizumab for recurrent RN gained further symptomatic improvement. Grade 2 + toxicity rate was 24% (venous thromboembolism: 12%; hypertension: 8%; intra-tumoural haemorrhage: 4%). Conclusion: Bevacizumab is an effective treatment for symptomatic, steroid-dependent SRS-induced RN but is associated with moderate rates of Grade 2–3 toxicities and recurrent, symptomatic RN after its cessation. Bevacizumab rechallenge remains useful for recurrent RN. Multi-disciplinary input and careful surveillance remain critical for its use in BrM patients.