质子束放射疗法与射频消融治疗复发性肝细胞癌：一项随机II

StephenW

Proton beam radiotherapy vs. radiofrequency ablation for recurrent hepatocellular carcinoma: A randomized phase III trial

    Tae Hyun Kim †
    Young Hwan Koh †
    Bo Hyun Kim
    Ju Hee Lee
    Boram Park
    Joong-Won Park
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Open AccessPublished:October 05, 2020DOI:https://doi.org/10.1016/j.jhep.2020.09.026

Highlights

    •
    This is the 1st phase III RCT to evaluate proton beam radiotherapy vs. radiofrequency ablation in recurrent HCC.
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    Proton beam radiotherapy was non-inferior to radiofrequency ablation in terms of local progression-free survival and safety.
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    Proton beam radiotherapy is a promising treatment option for small HCC.

Background & Aims
Proton beam radiotherapy (PBT) has recently been applied to treat hepatocellular carcinoma (HCC); however, there is no randomized controlled trial-based evidence on its safety and efficacy. We compared the outcomes of PBT and radiofrequency ablation (RFA) in patients with recurrent/residual HCC (rHCC) in a phase III non-inferiority trial.
Methods
Patients with rHCC (size <3 cm, number ≤2) were randomly assigned to receive PBT or RFA according to Child-Pugh score and tumor stage. After randomization, if the assigned treatment was technically infeasible, crossover was allowed. The primary endpoint was 2-year local progression-free survival (LPFS), with a non-inferiority margin of 15% in the per-protocol (PP) population; a complementary analysis was performed in the intention-to-treat (ITT) population (NCT01963429).
Results
The ITT population comprised 144 patients receiving either PBT (n = 72) or RFA (n = 72). Six patients switched from the PBT arm to the RFA arm and 19 patients switched from the RFA arm to the PBT arm. In the PP population, the 2-year LPFS rate with PBT (n = 80) vs. RFA (n = 56) was 94.8% vs. 83.9%, a difference of 10.9 percentage points (90% CI 1.8–20.0; p <0.001); in the ITT population, the 2-year LPFS rate with PBT vs. RFA was 92.8% vs. 83.2%, a difference of 9.6 percentage points (90% CI 0.7–18.4; p <0.001), meeting the criteria for non-inferiority. The 3- and 4-year LPFS rates for PBT were also non-inferior to those for RFA. The most common adverse events were radiation pneumonitis (32.5%) and decreased leukocyte counts (23.8%) for PBT and increased alanine aminotransferase levels (96.4%) and abdominal pain (30.4%) for RFA. No Grade 4 adverse events or mortality were noted.
Conclusions
PBT showed LPFS values that were non-inferior to those for RFA; in addition, PBT was tolerable and safe.
Clinical trial number
#NCT01963429 (ClinicalTrials.gov).
Lay summary
Radiofrequency ablation is the standard of care for patients with small hepatocellular carcinoma in whom surgery is not feasible. This study is the first phase III randomized controlled trial to evaluate the clinical outcomes of proton beam radiotherapy vs. radiofrequency ablation in patients with recurrent small HCC. Our findings show that this new technique is not inferior and can be applied safely in patients with small recurrent hepatocellular carcinoma.

StephenW

质子束放射疗法与射频消融治疗复发性肝细胞癌：一项随机III期试验

    金泰H†
    杨焕阁†
    金宝H
    李具熙
    博兰公园
    钟原公园
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开放获取发布时间：2020年10月5日DOI：https：//doi.org/10.1016/j.jhep.2020.09.026

强调

    •
    这是评估复发性肝癌中质子束放射治疗与射频消融的第一阶段RCT。
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    就局部无进展生存和安全性而言，质子束放射治疗不逊于射频消融。
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    质子束放射疗法是小型HCC的有前途的治疗选择。

背景与目标
质子束放射疗法（PBT）最近已被用于治疗肝细胞癌（HCC）。但是，尚无关于其安全性和有效性的随机对照试验证据。我们在一项III期非劣效性试验中比较了复发/残留HCC（rHCC）患者的PBT和射频消融（RFA）结果。
方法
根据Child-Pugh评分和肿瘤分期，随机分配rHCC（尺寸<3 cm，数字≤2）的患者接受PBT或RFA。随机分组后，如果指定的治疗在技术上不可行，则允许交叉。主要终点是2年局部无进展生存期（LPFS），按协议（PP）人群的非劣效性为15％；在意向治疗（ITT）人群中进行了补充分析（NCT01963429）。
结果
ITT人群包括144例接受PBT（n = 72）或RFA（n = 72）的患者。 6名患者从PBT部门转到RFA部门，19名患者从RFA部门转到PBT部门。在PP人群中，PBT（n = 80）vs RFA（n = 56）的2年LPFS率为94.8％vs. 83.9％，相差10.9个百分点（90％CI 1.8–20.0； p < 0.001）；在ITT人群中，PBT与RFA的2年LPFS率分别为92.8％和83.2％，相差9.6个百分点（90％CI 0.7-18.4； p <0.001），符合非自卑的标准。 PBT的3年和4年LPFS率也不亚于RFA。最常见的不良事件是放射性肺炎（32.5％）和PBT的白细胞计数降低（23.8％），RFA的丙氨酸转氨酶水平升高（96.4％）和腹痛（30.4％）。没有发现4级不良事件或死亡率。
结论
PBT显示的LPFS值不亚于RFA的值；此外，PBT是可以容忍和安全的。
临床试验编号
＃NCT01963429（ClinicalTrials.gov）。
放置摘要
对于不可行手术的小肝细胞癌患者，射频消融是其护理标准。这项研究是第一项随机III期随机对照试验，用于评估复发性小肝癌患者质子束放射治疗与射频消融的临床结局。我们的研究结果表明，这项新技术并不逊色，可以安全地用于患有小型复发性肝细胞癌的患者。

StephenW

https://www.journal-of-hepatolog ... 8278(20)33670-9/pdf