US-triggered Microbubble Destruction for Augmenting Hepatocellular Carcinoma Response to Transarterial Radioembolization: A Randomized Pilot Clinical Trial
US-triggered Microbubble Destruction for Augmenting Hepatocellular Carcinoma Response to Transarterial Radioembolization: A Randomized Pilot Clinical Trial
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DOI：
10.1148/radiol.2020202321
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发表时间：
2021-02-01
期刊：
影响因子：
19.7
通讯作者：
Shaw, Colette M.
中科院分区：
文献类型：
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作者：
Eisenbrey, John R.;Forsberg, Flemming;Shaw, Colette M.
背景：超声造影剂是充满气体的微泡（mb），可以通过外部超声局部破坏。在其他生物效应中，美国引发的MB破坏，也被称为UTMD，已被证明在临床前模型中通过对血管内皮细胞的局部损伤使实体瘤对辐射敏感。目的：评价联合us触发MB破坏和经动脉放射栓塞（TARE）治疗肝细胞癌（HCC）患者的安全性和初步疗效。材料和方法：在这项试点临床试验中，计划进行叶下去皮治疗的HCC患者被随机分为去皮治疗或去皮治疗，在去皮治疗后1-4小时，大约1周和2周，美国触发MB破坏。入学时间为2017年7月至2020年2月。通过生理监测、肝功能试验变化、不良事件和放射性药物分布来评估美国触发的MB破坏的安全性。采用改进的实体瘤反应评价标准（mRECIST）对横断面图像、到下一次治疗所需的时间、移植率和总生存率进行治疗效果评估。使用Mann-Whitney U检验比较mRECIST读数之间的差异，使用Fisher精确检验评估肿瘤反应发生率的差异，而使用log-rank （Mantel-Cox）检验比较到下一次治疗所需时间和总生存曲线的差异。结果：28名参与者（平均年龄70岁+/- 10岁[标准差]；17名男性）的安全性结果显示，在美国触发的MB破坏前后，体温（P = 0.31）、心率（P = 0.92）、舒张压（P = 0.31）或收缩压（P = 0.06）没有显著变化。TARE后1个月治疗组间肝功能检查无变化（P < 0.05）。初步疗效结果显示，同时经历了us触发的MB破坏和TARE的参与者的肿瘤反应发生率更高（15人中有14人[93%；95% CI: 68, 100] vs 10人中有5人[50%；95% CI: 19, 81]; P = 0.02）。结论：美国触发的微泡破坏和经动脉放射栓塞联合治疗在该患者群体中是可行的，具有良好的安全性，并且似乎可以改善肝细胞癌的治疗反应。(c) rsna, 2020
Background: US contrast agents are gas-filled microbubbles (MBs) that can be locally destroyed by using external US. Among other bioeffects, US-triggered MB destruction, also known as UTMD, has been shown to sensitize solid tumors to radiation in preclinical models through localized insult to the vascular endothelial cells.Purpose: To evaluate the safety and preliminary efficacy of combining US-triggered MB destruction and transarterial radioembolization (TARE) in participants with hepatocellular carcinoma (HCC).Materials and Methods: In this pilot clinical trial, participants with HCC scheduled for sublobar TARE were randomized to undergo either TARE or TARE with US-triggered MB destruction 1-4 hours and approximately 1 and 2 weeks after TARE. Enrollment took place between July 2017 and February 2020. Safety of US-triggered MB destruction was evaluated by physiologic monitoring, changes in liver function tests, adverse events, and radiopharmaceutical distribution. Treatment efficacy was evaluated by using modified Response Evaluation Criteria in Solid Tumors (mRECIST) on cross-sectional images, time to required next treatment, transplant rates, and overall survival. Differences across mRECIST reads were compared by using a Mann-Whitney U test, and the difference in prevalence of tumor response was evaluated by Fisher exact test, whereas differences in time to required next treatment and overall survival curves were compared by using a log-rank (Mantel-Cox) test.Results: Safety results from 28 participants (mean age, 70 years +/- 10 [standard deviation]; 17 men) demonstrated no significant changes in temperature (P =.31), heart rate (P =.92), diastolic pressure (P =.31), or systolic pressure (P =.06) before and after US-triggered MB destruction. No changes in liver function tests between treatment arms were observed 1 month after TARE (P > .15). Preliminary efficacy results showed a greater prevalence of tumor response (14 of 15 [93%; 95% CI: 68, 100] vs five of 10 [50%; 95% CI: 19, 81]; P =.02) in participants who underwent both US-triggered MB destruction and TARE (P =.02).Conclusion: The combination of US-triggered microbubble destruction and transarterial radioembolization is feasible with an excellent safety profile in this patient population and appears to result in improved hepatocellular carcinoma treatment response. (C) RSNA, 2020