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

Kylie Jung; Sudhir Das Sivadas; Xavier Fitzgerald; Claire Phillips; Nikki Plumridge; Lavinia Spain; Aparna D Rao; Joseph Sia

doi:10.1007/s11060-025-05121-x

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

J Neurooncol. 2025 Jun 19. doi: 10.1007/s11060-025-05121-x. Online ahead of print.

Authors

Kylie Jung^{1

2}, Sudhir Das Sivadas³, Xavier Fitzgerald⁴, Claire Phillips^{3

5}, Nikki Plumridge³, Lavinia Spain^{5

6}, Aparna D Rao^{5

6}, Joseph Sia^{3

5}

Affiliations

¹ Department of Radiation Oncology, Canberra Health Services, Canberra, Australia. kylie.jung@act.gov.au.
² The John Curtin School of Medical Research, The Australian National University, Canberra, Australia. kylie.jung@act.gov.au.
³ Department of Radiation Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia.
⁴ Department of Neurosurgery, Royal Melbourne Hospital, Melbourne, Australia.
⁵ Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Australia.
⁶ Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia.

PMID: 40536632
DOI: 10.1007/s11060-025-05121-x

Abstract

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 and 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 7.5 mg/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. 71% of those on steroids could cease steroids over a median of 1.9 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.

Keywords: Bevacizumab; Brain metastases (BrM); Radiation necrosis (RN); Recurrent radiation necrosis; Stereotactic radiosurgery (SRS); Toxicity.