Safety and Feasibility of Repeated and Transient Blood-Brain Barrier Disruption by Pulsed Ultrasound in Patients with Recurrent Glioblastoma
Safety and Feasibility of Repeated and Transient Blood-Brain Barrier Disruption by Pulsed Ultrasound in Patients with Recurrent Glioblastoma
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DOI：
10.1158/1078-0432.ccr-18-3643
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发表时间：
2019-07-01
影响因子：
11.5
通讯作者：
Carpentier, Alexandre
中科院分区：
文献类型：
--
作者：
Idbaih, Ahmed;Canney, Michael;Carpentier, Alexandre
目的：血脑屏障（BBB）限制了胶质母细胞瘤（GBM）的药物治疗效果。临床前数据表明，低强度脉冲超声（LIPU）可以短暂地破坏血脑屏障，增加脑内药物concentration.Patients和方法：一个firstinman，singlearm，单中心试验（NCT 02253212）开始调查的短暂中断血脑屏障复发GBM患者。患者植入了1 MHz、11.5 mm直径的颅骨超声器械（SonoCloud 1，CarThera）。该设备每月激活，以暂时破坏血脑屏障静脉卡铂chemotherapy.Results：在2014年和2016年之间，21名患者注册的研究，并植入SonoCloud 1; 19名患者接受至少一次超声处理。在65次超声检查中，52次超声处理在T1 w MRI上可见BBB破坏。观察到的治疗相关不良事件为一过性且可管理：H1和D15时出现一过性水肿。未观察到卡铂相关的神经毒性。MRI上无BBB破坏或BBB破坏较差的患者（n = 8）的中位无进展生存期（PFS）为2.73个月，中位总生存期（OS）为8.64个月。明确BBB破坏的患者（n = 11）的中位PFS为4.11个月，中位OS为12.94 months.Conclusions：SonoCloud 1治疗耐受性良好，可能会增加全身药物治疗的有效性，如卡铂，在大脑中，而不会诱导神经毒性。
Purpose: The bloodbrain barrier (BBB) limits the efficacy of drug therapies for glioblastoma (GBM). Preclinical data indicate that lowintensity pulsed ultrasound (LIPU) can transiently disrupt the BBB and increase intracerebral drug concentrations.Patients and Methods: A firstinman, singlearm, single-center trial (NCT02253212) was initiated to investigate the transient disruption of the BBB in patients with recurrent GBM. Patients were implanted with a 1MHz, 11.5mm diameter cranial ultrasound device (SonoCloud1, CarThera). The device was activated monthly to transiently disrupt the BBB before intravenous carboplatin chemotherapy.Results: Between 2014 and 2016, 21 patients were registered for the study and implanted with the SonoCloud1; 19 patients received at least one sonication. In 65 ultrasound sessions, BBB disruption was visible on T1w MRI for 52 sonications. Treatmentrelated adverse events observed were transient and manageable: a transient edema atH1and at D15. No carboplatinrelated neurotoxicity was observed. Patients with no or poor BBB disruption (n = 8) visible on MRI had a median progressionfree survival (PFS) of 2.73 months, and a median overall survival (OS) of 8.64 months. Patients with clear BBB disruption (n = 11) had a median PFS of 4.11 months, and a median OS of 12.94 months.Conclusions: SonoCloud1 treatments were well tolerated and may increase the effectiveness of systemic drug therapies, such as carboplatin, in the brain without inducing neurotoxicity.