바로가기  >

이달의 연구자 바로가기 Click!

Abstract
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.

본 연구의 1차 목표인 2년 국소무진행생존 (local progression-free survival) Forest Plot으로서 교차치료 연구에서는 per protocol 분석이 우선이며 보조적으로 intention-to-treatment 분석도 시행하였는데 두 방법 모두에서 양성자치료가 더 우월하였다. 3년, 4년 분석에서도 비열등성 경계인 –15% 보다 충분히 적은 차이를 보여서 두 치교간의 차이가 없음을 알 수 있다.

Affiliations

Tae Hyun Kim  1 , Young Hwan Koh  2 , Bo Hyun Kim  3 , Min Ju Kim  4 , Ju Hee Lee  2 , Boram Park  5 , Joong-Won Park  6
1 Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang, Republic of Korea; Center for Proton Therapy, National Cancer Center, Goyang, Republic of Korea.
2 Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang, Republic of Korea; Department of Radiology, National Cancer Center, Goyang, Republic of Korea.
3 Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang, Republic of Korea.
4 Department of Radiology, National Cancer Center, Goyang, Republic of Korea.
5 Biostatistics Collaboration Team, Research Core Center, National Cancer Center, Goyang, Republic of Korea.
6 Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang, Republic of Korea. Electronic address: jwpark@ncc.re.kr.