Department of Radiology and Nuclear Medicine, St. Olav's Hospital-Trondheim University Hospital, Trondheim, Norway; Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway; Cancer Clinic, St. Olav's Hospital-Trondheim University Hospital, Trondheim, Norway.
Department of Health Research, SINTEF Digital, Trondheim, Norway; Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway.
Ultrasound Med Biol. 2023 Sep;49(9):2081-2088. doi: 10.1016/j.ultrasmedbio.2023.05.013. Epub 2023 Jun 17.
Pre-clinical trials have obtained promising results that focused ultrasound (FUS) combined with microbubbles (MBs) increases tumor uptake and the therapeutic effect of drugs. The aims of the study described here were to investigate whether FUS and MBs could improve the effect of chemotherapy in patients with liver metastases from colorectal cancer and to investigate the safety and feasibility of using FUS + MBs.
We included 17 patients with liver metastases from colorectal cancer, selected two lesions in each patient's liver and randomized the lesions for, respectively, treatment with FUS + MBs or control. After chemotherapy (FOLFIRI or FOLFOXIRI), the lesions were treated with FUS (frequency = 1.67 MHz, mechanical index = 0.5, pulse repetition frequency = 0.33 Hz, 33 oscillations, duty cycle = 0.2%-0.4% and MBs (SonoVue) for 35 min). Nine boluses of MBs were injected intravenously at 3.5 min intervals. Patients were scheduled for four cycles of treatment. Changes in the size of metastases were determined from computed tomography images.
Treatment with FUS + MBs is safe at the settings used. There was considerable variation in treatment response between lesions and mixed response between lesions receiving only chemotherapy. There is a tendency toward larger-volume reduction in lesions treated with FUS + MBs compared with control lesions, but a mixed response to chemotherapy and lesion heterogeneity make it difficult to interpret the results.
The combination of FUS and MBs is a safe, feasible and available strategy for improving the effect of chemotherapy in cancer patients. Therapeutic effect was not demonstrated in this trial. Multicenter trials with standardized protocols should be performed.
临床前试验已经取得了可喜的结果，即聚焦超声（FUS）联合微泡（MBs）可增加肿瘤摄取和药物的治疗效果。本研究旨在探讨 FUS 和 MBs 是否可以提高结直肠癌肝转移患者化疗的效果，并研究 FUS+MBs 的安全性和可行性。
我们纳入了 17 例结直肠癌肝转移患者，在每位患者的肝脏中选择两个病变，并将病变随机分为 FUS+MBs 治疗组和对照组。在化疗（FOLFIRI 或 FOLFOXIRI）后，使用 FUS（频率=1.67 MHz，机械指数=0.5，脉冲重复频率=0.33 Hz，33 个振子，占空比=0.2%-0.4%）和 MBs（SonoVue）治疗 35 分钟。每隔 3.5 分钟静脉注射 9 次 MBs。患者计划接受四个周期的治疗。通过计算机断层扫描图像确定转移灶大小的变化。
在使用的设置下，FUS+MBs 的治疗是安全的。病变之间的治疗反应存在很大差异，且仅接受化疗的病变之间存在混合反应。与对照组病变相比，接受 FUS+MBs 治疗的病变的体积减少趋势更大，但化疗和病变异质性的混合反应使得结果难以解释。
FUS 和 MBs 的联合是一种安全、可行和可用的策略，可以提高癌症患者化疗的效果。本试验未显示治疗效果。应进行具有标准化方案的多中心试验。
