Background

Unresectable solitary very early to early stage hepatocellular carcinoma is managed with ablation for curative intent. Radiation segmentectomy is a treatment option that delivers radioactive ⁹⁰yttrium (⁹⁰Y)-bound microspheres transarterially to a segment of liver. The aim of this study was to assess the safety and efficacy of radiation segmentectomy in patients with unresectable hepatocellular carcinoma deemed unfavourable for ablation.

Methods

RASER was a single-centre, single-arm study that included adults (>18 years) with solitary hepatocellular carcinoma with unfavourable location for ablation, without metastasis or macrovascular invasion. Eligibility criteria included measurable disease 3 cm or less in diameter, Child-Pugh score A–B7, an Eastern Cooperative Oncology Group score of 0, and adequate haematological and organ function. The primary endpoint was target tumour response measured by mRECIST. Patients were followed up with imaging and office visits for up to 24 months. The trial is registered with ClinicalTrials.gov (NCT03248375), and is completed.

Findings

Individuals were enrolled between Aug 3, 2016, and April 4, 2019, and the last patient follow-up occurred on March 31, 2021. Of the 44 individuals assessed for eligibility, 29 patients were included in the study. Initial target lesion complete response was observed in 24 (83%) of 29 patients, and partial response was observed in five (17%) of patients. All patients had an initial objective response and 26 (90%) individuals had a sustained complete response. Four (14%) patients had grade 3 leukopenia and two (7%) had grade 3 thrombocytopenia. There were two (7%) non-laboratory-related grade 3 adverse events (one arterial injury and one ascites). The most frequent (>10% patients) grade 1 or 2 adverse events were fatigue (nine [31%]); nausea, vomiting, or anorexia (seven [24%]); abdominal discomfort (six [21%]), leukopenia (nine [31%]), thrombocytopenia (four [14%]), increased alkaline phosphatase (four [14%]), increased alanine or aspartate aminotransferase (four [14%]), increased bilirubin (four [14%]), and decreased albumin (six [21%]). There was one death that was not treatment related.

Interpretation

Radiation segmentectomy was efficacious, with a low proportion of high-grade adverse events in patients with unresectable very early to early stage hepatocellular carcinoma with suboptimal location for ablation. These results suggest that radiation segmentectomy should be further investigated as a potential curative treatment option for well selected patients.

Funding

Boston Scientific.

中文翻译：

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放射肺段切除术治疗不可切除的极早期至早期肝细胞癌 (RASER)：一项单中心、单臂研究

背景

不可切除的孤立性极早期至早期肝细胞癌通过消融治疗达到治愈目的。放射肺段切除术是一种治疗选择，可将结合放射性⁹⁰钇 ( ⁹⁰ Y) 的微球体经动脉输送至肝段。本研究的目的是评估放射肺段切除术对被认为不利于消融的不可切除肝细胞癌患者的安全性和有效性。

方法

RASER 是一项单中心、单组研究，包括成人（>18 岁）患有孤立性肝细胞癌，其消融位置不利，没有转移或大血管浸润。资格标准包括直径为 3 cm 或更小的可测量疾病、Child-Pugh 评分 A–B7、东部肿瘤合作组评分为 0 分以及足够的血液学和器官功能。主要终点是通过 mRECIST 测量的目标肿瘤反应。对患者进行长达 24 个月的影像学检查和门诊随访。该试验已在 ClinicalTrials.gov (NCT03248375) 注册，并已完成。

发现

个人在 2016 年 8 月 3 日至 2019 年 4 月 4 日期间入组，最后一次患者随访发生在 2021 年 3 月 31 日。在评估资格的 44 名个人中，29 名患者被纳入研究。29 名患者中有 24 名 (83%) 观察到初始靶病变完全缓解，5 名 (17%) 患者观察到部分缓解。所有患者均有初始客观反应，26 人 (90%) 有持续的完全反应。四名 (14%) 患者患有 3 级白细胞减少症，两名 (7%) 患者患有 3 级血小板减少症。有两个 (7%) 非实验室相关的 3 级不良事件（一个动脉损伤和一个腹水）。最常见的（>10% 患者）1 级或 2 级不良事件是疲劳（9 [31%]）；恶心、呕吐或厌食（7 [24%]）；腹部不适（6 [21%]），白细胞减少症（9 [31%]），血小板减少症（4 [14%]）、碱性磷酸酶升高（4 [14%]）、丙氨酸或天冬氨酸氨基转移酶升高（4 [14%]）、胆红素升高（4 [14%]）和白蛋白降低（6 [21] %]). 有 1 例死亡与治疗无关。

解释

放射肺段切除术是有效的，在消融位置不理想的无法切除的极早期至早期肝细胞癌患者中，高级不良事件的比例很低。这些结果表明，对于精心挑选的患者，应进一步研究放射肺段切除术作为一种潜在的治疗选择。

资金

波士顿科学公司。