Jung Kylie, Sivadas Sudhir Das, Fitzgerald Xavier, Phillips Claire, Plumridge Nikki, Spain Lavinia, Rao Aparna D, Sia Joseph
Department of Radiation Oncology, Canberra Health Services, Canberra, Australia.
The John Curtin School of Medical Research, The Australian National University, Canberra, Australia.
J Neurooncol. 2025 Jun 19. doi: 10.1007/s11060-025-05121-x.
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.
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.
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%).
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.
放射性坏死（RN）是脑转移瘤（BrM）立体定向放射外科治疗（SRS）的一种潜在致残性并发症。贝伐单抗是一种抗血管内皮生长因子A的单克隆抗体，越来越多地用于治疗有症状的RN。这项多机构回顾性研究在延长的随访期内，考察了其对接受SRS诱导的RN的BrM患者的长期疗效、毒性及激素节省效果。
确定了来自两个澳大利亚医疗网络的BrM患者，这些患者在2018年至2023年期间因SRS诱导的RN接受了贝伐单抗治疗。记录患者特征、症状和影像学反应、激素使用情况及毒性。采用Kaplan-Meier法和Cox法分析事件发生时间及与结局的关联。
对26例患者进行了分析，中位随访时间为21.2个月。最常用的贝伐单抗给药方案是每3周7.5mg/kg，中位给药3个周期。开始治疗1周后可检测到症状改善，6个月时60%的患者头痛改善，80%的患者神经功能缺损改善。88%的患者影像学改善，中位时间为7周。71%服用激素的患者在中位1.9个月后可停用激素。19%的患者在贝伐单抗停药9.5 - 28.5个月后出现复发性、有症状的RN。75%因复发性RN接受贝伐单抗再治疗的患者症状进一步改善。2级及以上毒性发生率为24%（静脉血栓栓塞：12%；高血压：8%；瘤内出血：4%）。
贝伐单抗是治疗有症状的、依赖激素的SRS诱导的RN的有效方法，但与2 - 3级毒性的中度发生率以及停药后复发性、有症状的RN相关。再次使用贝伐单抗对复发性RN仍有用。多学科参与和仔细监测对其在BrM患者中的应用仍然至关重要。
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