Park So Hee, Kim Myung Ji, Jung Hyun Ho, Chang Won Seok, Choi Hyun Seok, Rachmilevitch Itay, Zadicario Eyal, Chang Jin Woo
Department of Neurosurgery, Brain Research Institute, Yonsei University College of Medicine, Seoul, South Korea.
Department of Radiology, Yonsei University College of Medicine, Seoul, South Korea.
Front Oncol. 2020 Sep 10;10:1663. doi: 10.3389/fonc.2020.01663. eCollection 2020.
To overcome the blood-brain barrier (BBB) which interferes with the effect of chemotherapeutic agents, we performed multiple disruptions of BBB (BBBD) with magnetic resonance-guided focused ultrasound on patients with glioblastoma (GBM) during standard adjuvant temozolomide (TMZ) chemotherapy [clinical trial registration no.NCT03712293 (clinicaltrials.gov)]. We report a 1-year follow-up result of BBBD with TMZ for GBM. From September 2018 to January 2019, six patients were enrolled (four men and two women, median age: 53 years, range: 50-67 years). Of the six patients, five underwent a total of six cycles of BBBD during standard TMZ adjuvant therapy. One patient underwent three cycles of BBBD but continued with TMZ chemotherapy. The 1-year follow-up results of these six patients were reviewed. The mean follow-up duration was 15.17 ± 1.72 months. Two patients showed a recurrence of tumor at 11 and 16 months, respectively. One underwent surgery, and the other patient was restarted with TMZ chemotherapy due to the tumor location with a highly possibility of surgical complications. The survival rate up to 1 year was 100%, and the other four patients are on observation without recurrence. None of the six patients had immediate or delayed BBBD-related complications. Multiple BBBDs can be regarded as a safe procedure without long-term complications, and it seems to have some survival benefits. However, since TMZ partially crosses the BBB, a further extended study with large numbers would be needed to evaluate the benefits of BBBD resulting in an increase of TMZ concentration. This study opened a new therapeutic strategy for GBM by combining BBBD with a larger molecular agent.
为克服影响化疗药物疗效的血脑屏障（BBB），我们在标准辅助替莫唑胺（TMZ）化疗期间，对胶质母细胞瘤（GBM）患者采用磁共振引导聚焦超声多次破坏血脑屏障（BBBD）[临床试验注册号：NCT03712293（clinicaltrials.gov）]。我们报告了BBBD联合TMZ治疗GBM的1年随访结果。2018年9月至2019年1月，纳入6例患者（4例男性，2例女性，中位年龄：53岁，范围：50 - 67岁）。6例患者中，5例在标准TMZ辅助治疗期间共接受了6个周期的BBBD。1例患者接受了3个周期的BBBD，但继续TMZ化疗。对这6例患者的1年随访结果进行了回顾。平均随访时间为15.17±1.72个月。2例患者分别在11个月和16个月出现肿瘤复发。1例接受了手术，另1例因肿瘤位置手术并发症可能性高而重新开始TMZ化疗。1年生存率为100%，其他4例患者正在观察中，无复发。6例患者均未出现与BBBD相关的即刻或延迟并发症。多次BBBD可视为一种安全的操作，无长期并发症，似乎有一定的生存益处。然而，由于TMZ可部分透过血脑屏障，因此需要进一步开展大规模的扩展研究来评估BBBD提高TMZ浓度所带来的益处。本研究通过将BBBD与更大分子的药物联合，为GBM开辟了一种新的治疗策略。
