Xu Min, Xu Danxia, Dong Gang, Ren Zhigang, Zhang Wu, Aji Tuerganaili, Zhao Qiyu, Chen Xinhua, Jiang Tian'an
Department of Ultrasound Medicine, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Key Laboratory of Pulsed Power Translational Medicine of Zhejiang Province, Hangzhou, China.
Front Oncol. 2022 Jul 13;12:869316. doi: 10.3389/fonc.2022.869316. eCollection 2022.
Hepatocellular carcinoma (HCC) is a highly aggressive malignancy. Irreversible electroporation (IRE) is an ablative modality that uses high-voltage electrical pulses to permeabilize the cell membrane leading to cell necrosis. Unlike traditional thermal ablation, IRE is hardly affected by the "heat-sink" effect and can prevent damage of the adjacent vital structures. Nanosecond pulsed electric field (nsPEF) is a new IRE technique using ultra-short pulses (nanosecond duration), can not only penetrate the cell membranes, but also act on the organelles. Sufficient preclinical researches have shown that nsPEF can eliminate HCC without damaging vital organs, and elicit potent anti-tumor immune response.
This is the first clinical study to evaluate feasibility, efficacy, and safety of nsPEF for the treatment of HCC, where thermal ablation is unsuitable due to proximity to critical structures.
We will conduct an open-labeled, single-arm, prospective, multicenter, and objective performance criteria trial. One hundred and ninety-two patients with HCC, in which the tumor is located immediately (<0.5 cm) adjacent to the portal vein, hepatic veins, bile duct, gastrointestinal tract, or diaphragm, will be enrolled among 4 academic medical centers. The primary outcomes are the rate of complete ablation at 1 month and adverse events. Secondary outcomes include technical success, technique efficacy, nsPEF procedural characteristics, local tumor progression, and local progression-free survival.
The trial will be conducted according to the ethical principles of the Declaration of Helsinki and has been approved by the ethics committee of all participating centers. The results of this study will be published in peer-reviewed scientific journals and presented at relevant academic conferences.
This study is the Phase 1 clinical trial to evaluate the efficacy and safety of nsPEF in patients with HCC at high-risk locations where thermal ablation is contra-indicated. The results may expand the options and offer an alternative therapy for HCC.
ClinicalTrials.gov, identifier NCT04309747.
肝细胞癌（HCC）是一种侵袭性很强的恶性肿瘤。不可逆电穿孔（IRE）是一种消融方式，它利用高压电脉冲使细胞膜通透性增加，导致细胞坏死。与传统热消融不同，IRE几乎不受“热沉”效应影响，可防止相邻重要结构受损。纳秒级脉冲电场（nsPEF）是一种新的IRE技术，使用超短脉冲（纳秒持续时间），不仅能穿透细胞膜，还能作用于细胞器。充分的临床前研究表明，nsPEF可消除HCC且不损伤重要器官，并引发有效的抗肿瘤免疫反应。
这是第一项评估nsPEF治疗HCC的可行性、有效性和安全性的临床研究，在因肿瘤靠近关键结构而不适合热消融的情况下进行。
我们将进行一项开放标签、单臂、前瞻性、多中心且符合客观性能标准的试验。4个学术医学中心将招募192例HCC患者，其肿瘤紧邻（<0.5 cm）门静脉、肝静脉、胆管、胃肠道或膈肌。主要结局是1个月时的完全消融率和不良事件。次要结局包括技术成功、技术有效性、nsPEF操作特征、局部肿瘤进展和局部无进展生存期。
该试验将根据《赫尔辛基宣言》的伦理原则进行，并已获得所有参与中心伦理委员会的批准。本研究结果将发表在同行评审的科学期刊上，并在相关学术会议上展示。
本研究是评估nsPEF在热消融禁忌的高危部位HCC患者中的疗效和安全性的1期临床试验。结果可能会扩大治疗选择，并为HCC提供一种替代疗法。
ClinicalTrials.gov，标识符NCT04309747。
