METHODS: This prospective phase 1 clinical trial included patients with newly diagnosed or recurrent HN cancer (except nasopharynx malignancies) for whom locoregional radiotherapy with radical- or palliative-intent as deemed appropriate. Patients with contraindications for microbubble administration or contrast-enhanced MR were excluded. MR-coupled focussed ultrasound sonicated intravenously administered microbubbles within the MR-guided target volume. Patients receiving 5-10 and 33-35 radiation fractions were planned for 2 and 3 MRgFUS-MB treatments, respectively. Primary endpoint was toxicity per CTCAEv5.0. Secondary endpoint was tumour response at 3 months per RECIST 1.1 criteria.
RESULTS: Twelve patients were enrolled between Jun/2020 and Nov/2023, but 1 withdrew consent. Eleven patients were included in safety analysis. Median follow-up was 7 months (range, 0.3-38). Most patients had oropharyngeal cancer (55 %) and received 20-30 Gy/5-10 fractions (63 %). No systemic toxicity or MRgFUS-MB-related adverse events occurred. The most severe acute adverse events were radiation-related grade 3 toxicities in 6 patients (55 %; dermatitis in 3, mucositis in 1, dysphagia in 6). No radiation necrosis or grade 4/5 toxicities were reported. 8 patients were included in the 3-month tumour response assessment: 4 had partial response (50 %), 3 had complete response (37.5 %), and 1 had progressive disease (12.5 %).
CONCLUSIONS: MRgFUS-MB treatment was safe and associated with high rates of tumour response at 3 months.
方法:这项前瞻性1期临床试验纳入了新诊断或复发性HN癌(鼻咽恶性肿瘤除外)患者,这些患者被认为是适当的局部区域放疗,并伴有根治性或姑息性意图。排除有微泡给药或对比增强MR禁忌症的患者。MR耦合聚焦超声在MR引导的靶体积内静脉内给药的微泡。计划接受5-10和33-35次辐射的患者进行2次和3次MRgFUS-MB治疗,分别。主要终点是根据CTCAEv5.0的毒性。次要终点是根据RECIST1.1标准3个月时的肿瘤反应。
结果:在2020年6月至2023年11月之间招募了12名患者,但1名患者撤回了同意。11例患者纳入安全性分析。中位随访时间为7个月(范围,0.3-38)。大多数患者患有口咽癌(55%),并接受20-30Gy/5-10分(63%)。无全身毒性或MRgFUS-MB相关不良事件发生。最严重的急性不良事件是6例患者中与辐射相关的3级毒性(55%;3例皮炎,1例粘膜炎,6例吞咽困难)。未报告放射性坏死或4/5级毒性。8例患者被纳入3个月的肿瘤反应评估:4例部分反应(50%),3个有完全反应(37.5%),1例疾病进展(12.5%)。
结论:MRgFUS-MB治疗是安全的,并且在3个月时与高肿瘤反应率相关。