一种基于射波刀治疗系统的放射外科新策略,随后早期使用辅助贝伐单抗治疗伴有广泛脑水肿的脑转移瘤。

A new strategy of CyberKnife treatment system based radiosurgery followed by early use of adjuvant bevacizumab treatment for brain metastasis with extensive cerebral edema.

作者信息

Wang Yang, Wang Enmin, Pan Li, Dai Jiazhong, Zhang Nan, Wang Xin, Liu Xiaoxia, Mei Guanghai, Sheng Xiaofang

机构信息

Department of Radiation Oncology, Huashan Hospital, Fudan University, Shanghai, 200235, China.

出版信息

J Neurooncol. 2014 Sep;119(2):369-76. doi: 10.1007/s11060-014-1488-0. Epub 2014 May 31.

Abstract

Bevacizumab blocks the effects of vascular endothelial growth factor in leakage-prone capillaries and has been suggested as a new treatment for cerebral radiation edema and necrosis. CyberKnife is a new, frameless stereotactic radiosurgery system. This work investigated the safety and efficacy of CyberKnife followed by early bevacizumab treatment for brain metastasis with extensive cerebral edema. The eligibility criteria of the patients selected for radiosurgery followed by early use of adjuvant bevacizumab treatment were: (1) brain tumors from metastasis with one solitary brain lesion and symptomatic extensive cerebral edema; (2) >18 years of age; (3) the patient refused surgery due to the physical conditions and the risk of surgery; (4) no contraindications for bevacizumab. (5) bevacizumab was applied for a minimum of 2 injections and a maximum of 6 injections with a 2-week interval between treatments, beginning within 2 weeks of the CyberKnife therapy; (6) Karnofsky performance status (KPS) ≥30. Tumor size and edema were monitored by magnetic resonance imaging (MRI). Dexamethasone dosage, KPS, adverse event occurrence and associated clinical outcomes were also recorded. Eight patients were accrued for this new treatment. Radiation dose ranged from 20 to 33 Gy in one to five sessions, prescribed to the 61-71 % isodose line. Bevacizumab therapy was administered 3-10 days after completion of CyberKnife treatment for a minimum of two cycles (5 mg/kg, at 2-week intervals). MRI revealed average reductions of 55.8 % (post-gadolinium) and 63.4 % (T2/FLAIR). Seven patients showed significant clinical neurological improvements. Dexamethasone was reduced in all patients, with five successfully discontinuing dexamethasone treatment 4 weeks after bevacizumab initiation. Hypertension, a bevacizumab-related adverse event, occurred in one patient. After 3-8 months, all patients studied were alive and primary brain metastases were under control, 2 developed new brain metastases and underwent salvage CyberKnife treatment. Recurrent edema and emerging radiation necrosis were not observed. CyberKnife radiosurgery followed by early use of bevacizumab is promising and appears safe for treatment of brain metastases with extensive cerebral edema.

摘要

贝伐单抗可阻断血管内皮生长因子在易渗漏毛细血管中的作用,已被提议作为治疗脑放射性水肿和坏死的一种新方法。射波刀是一种新型的无框架立体定向放射外科系统。本研究探讨了射波刀治疗后早期应用贝伐单抗治疗伴有广泛脑水肿的脑转移瘤的安全性和有效性。选择接受放射外科治疗并早期使用辅助性贝伐单抗治疗的患者的入选标准为:(1)脑转移瘤,有一个孤立性脑病灶且伴有症状性广泛脑水肿;(2)年龄>18岁;(3)患者因身体状况和手术风险拒绝手术;(4)无贝伐单抗使用禁忌证;(5)贝伐单抗至少注射2次,最多注射6次,治疗间隔为2周,在射波刀治疗后2周内开始;(6)卡氏评分(KPS)≥30。通过磁共振成像(MRI)监测肿瘤大小和水肿情况。还记录了地塞米松剂量、KPS、不良事件发生情况及相关临床结果。8例患者接受了这种新治疗。放射剂量在1至5次分割中为20至33 Gy,处方剂量为61%-71%等剂量线。在射波刀治疗完成后3至10天给予贝伐单抗治疗,至少两个周期(5 mg/kg,间隔2周)。MRI显示(钆增强后)平均缩小55.8%,(T2/FLAIR)平均缩小63.4%。7例患者临床神经功能有显著改善。所有患者地塞米松剂量均减少,5例在开始使用贝伐单抗4周后成功停用了地塞米松治疗。1例患者发生了与贝伐单抗相关的不良事件高血压。3至8个月后,所有研究患者均存活,原发性脑转移瘤得到控制,2例出现新的脑转移瘤并接受了挽救性射波刀治疗。未观察到复发性水肿和新出现的放射性坏死。射波刀放射外科治疗后早期使用贝伐单抗治疗伴有广泛脑水肿的脑转移瘤前景良好且似乎安全。

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