Abstract：
OBJECTIVE: Preclinical research demonstrated that the exposure of microbubbles (intravascular gas microspheres) to focussed ultrasound within the targeted tumour upregulates pro-apoptotic pathways and enhances radiation-induced tumour cell death. This study aimed to assess the safety and efficacy of magnetic resonance (MR)-guided focussed ultrasound-stimulated microbubbles (MRgFUS-MB) for head and neck cancers (HN).
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.
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.
摘要：
目的：临床前研究表明，微泡（血管内气体微球）暴露于靶向肿瘤内的聚焦超声会上调促凋亡途径并增强辐射诱导的肿瘤细胞死亡。这项研究旨在评估磁共振（MR）引导的聚焦超声刺激微泡（MRgFUS-MB）治疗头颈部癌症（HN）的安全性和有效性。
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。
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。
