Berghoff Anna Sophie, Breckwoldt Michael Oliver, Riedemann Lars, Karimian-Jazi Kianush, Loew Sarah, Schlieter Franziska, Furtner Julia, Cinci Marc, Thomas Michael, Strowitzki Moritz J, Marmé Frederik, Michel Laura L, Schmidt Thomas, Jäger Dirk, Bendszus Martin, Preusser Matthias, Wick Wolfgang, Winkler Frank
Department of Medicine I, Medical University of Vienna, Vienna, Austria.
Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
Neurooncol Adv. 2020 Mar 16;2(1):vdaa038. doi: 10.1093/noajnl/vdaa038. eCollection 2020 Jan-Dec.
Salvage treatment for recurrent brain metastases (BM) of solid cancers is challenging due to the high symptomatic burden and the limited local treatment options.
Patients with recurrent BM with no option for further local therapies were retrospectively identified from BM databases. Bevacizumab-based treatment was initiated as a salvage treatment. Radiological imaging before and after bevacizumab-based treatment was reevaluated for treatment response using the Response Assessment in Neuro-Oncology (RANO) BM criteria.
Twenty-two patients (36.4% male) with recurrent BM from breast cancer (40.9%), colorectal cancer (31.8%), or lung cancer (27.3%) were identified. Previous BM-directed therapies were radiosurgery in 16/22 (72.7%) patients, whole-brain radiotherapy in 8/22 (36.4%), and neurosurgical resection in 11/22 (50.0%). Time since BM diagnosis to initiation of bevacizumab treatment was 16.5 months. Of 22 patients 14 (63.6%) received concurrent systemic therapies. Neurological symptom improvement could be achieved in 14/22 (63.6%) and stabilization in 6/22 (27.3%) patients, resulting in a clinical benefit in 20/22 (90.9%) patients. Steroids could be reduced or stopped in 15/22 (68.2%) patients. Rate of improvement on T1-weighted imaging was 15/19 (78.9%; median reduction: -26.0% ± 32.9) and 19/20 (95%; median reduction: -36.2% ± 22.2) on T2-weighted FLAIR imaging. According to RANO-BM best response was partial response in 7/19 (36.8%), stable disease in 9/19 (47.3%), and progressive disease in 3/19 (15.7%) patients. Median CNS-specific progression-free survival was 8 months and median overall survival after initiation of bevacizumab treatment was 17 months.
Bevacizumab-based treatment had clinically relevant intracranial activity in the vast majority of patients suffering from recurrent, symptomatic BM. The data supports a prospective clinical trial of bevacizumab as a salvage treatment in BM.
实体癌复发性脑转移瘤（BM）的挽救性治疗具有挑战性，因为其症状负担重且局部治疗选择有限。
从BM数据库中回顾性识别出无法进行进一步局部治疗的复发性BM患者。以贝伐单抗为基础的治疗作为挽救性治疗开始。根据神经肿瘤学疗效评估（RANO）BM标准，对以贝伐单抗为基础的治疗前后的放射影像学检查重新评估治疗反应。
确定了22例复发性BM患者（男性占36.4%），其原发癌为乳腺癌（40.9%）、结直肠癌（31.8%）或肺癌（27.3%）。之前针对BM的治疗方法包括：16/22（72.7%）例患者接受了放射外科治疗，8/22（36.4%）例接受了全脑放疗，11/22（50.0%）例接受了神经外科切除术。从BM诊断到开始贝伐单抗治疗的时间为16.5个月。22例患者中有14例（63.6%）接受了同步全身治疗。14/22（63.6%）例患者的神经症状得到改善，6/22（27.3%）例患者病情稳定，20/22（90.9%）例患者获得临床获益。15/22（68.2%）例患者的类固醇药物可减量或停用。T1加权成像的改善率为15/19（78.9%；中位缩小率：-26.0%±32.9），T2加权液体衰减反转恢复（FLAIR）成像的改善率为19/20（95%；中位缩小率：-36.2%±22.2）。根据RANO-BM标准，最佳反应为部分缓解的患者有7/19（36.8%），疾病稳定的患者有9/19（47.3%），疾病进展的患者有3/19（15.7%）。中枢神经系统特异性无进展生存期的中位数为8个月，开始贝伐单抗治疗后的总生存期中位数为17个月。
对于绝大多数患有复发性、有症状BM的患者，以贝伐单抗为基础的治疗具有临床相关的颅内活性。这些数据支持开展一项关于贝伐单抗作为BM挽救性治疗的前瞻性临床试验。
