울산의대 / 윤상민, 류백렬, 이소정, 임영석*
Abstract
Importance:
Patients with hepatocellular carcinoma showing macroscopic vascular invasion have a poor prognosis. Sorafenib is the sole treatment option for these patients, with unsatisfactory response and survival benefit. Combined treatment with transarterial chemoembolization (TACE) plus external beam radiotherapy (RT) has shown promising results for these patients in observational studies.
Objective:
To evaluate the efficacy and safety of TACE plus RT compared with sorafenib for patients with hepatocellular carcinoma and macroscopic vascular invasion.
Design, Setting, and Participants:
In this randomized, open-label clinical trial conducted at an academic tertiary care center between July 1, 2013, and October 31, 2016, 90 treatment-naive patients with liver-confined hepatocellular carcinoma showing macroscopic vascular invasion were randomly assigned to receive sorafenib (400 mg twice daily; 45 participants [the sorafenib group]) or TACE (every 6 weeks) plus RT (within 3 weeks after the first TACE, maximum 45 Gy with the fraction size of 2.5 to 3 Gy; 45 participants [the TACE-RT group]).
Main Outcomes and Measures:
The primary end point was the 12-week progression-free survival rate by intention-to-treat analysis. Radiologic response was assessed by independent review according to the Response Evaluation Criteria in Solid Tumors (RECIST; version 1.1). Treatment crossover was permitted after confirming disease progression.
Results:
Of the 90 patients (median age, 55 years; range, 33-82 years), 77 were men and 13 were women. All patients had portal vein invasion of hepatocellular carcinoma and Child-Pugh class A liver function. The median maximal tumor diameter was 9.7 cm. Most patients (71 [78.9%]) had multiple lesions. At week 12, the progression-free survival rate was significantly higher in the TACE-RT group than the sorafenib group (86.7% vs 34.3%; P < .001). The TACE-RT group showed a significantly higher radiologic response rate than the sorafenib group at 24 weeks (15 [33.3%] vs 1 [2.2%]; P < .001), a significantly longer median time to progression (31.0 vs 11.7 weeks; P < .001), and significantly longer overall survival (55.0 vs 43.0 weeks; P = .04). Curative surgical resection was conducted for 5 patients (11.1%) in the TACE-RT group owing to downstaging. No patients in the TACE-RT group discontinued treatment owing to hepatic decompensation.
Conclusions and Relevance:
For patients with advanced hepatocellular carcinoma showing macroscopic vascular invasion, first-line treatment with TACE plus RT was well tolerated and provided an improved progression-free survival, objective response rate, time to progression, and overall survival compared with sorafenib treatment.
Trial Registration:
clinicaltrials.gov Identifier: NCT01901692.
Author information
Yoon SM1, Ryoo BY2, Lee SJ3, Kim JH1, Shin JH3, An JH4, Lee HC4, Lim YS4.
1
Department of Radiation Oncology, Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
2
Department of Oncology, Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
3
Department of Radiology, Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
4
Department of Gastroenterology, Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
관련자료 보기
http://www.rmwebzine.re.kr/newshome/mtnmain.php?mtnkey=articleview&mkey=scatelist&mkey2=76&aid=2587
편집위원
혈관 침윤을 동반한 간암의 치료에서 방사선치료의 근거를 제시한 무작위 배정 연구
2018-06-21 10:37:46
편집위원2
진행성 간암에서 sorafenib가 유일한 치료제로 인정받고 있는데, MVI에서는 그 효과가 제한적으로, 방사선치료가 좀 더 효과적일 수 있다는 여러 연구들이 있지만 휴향적 연구들로 근거수준이 높지 않은데, 본 전향적 무작위 연구결과를 토대로 MVI에서 TACE+EBRT의 병합요법이 sorafenib 단독치료에 비해 좋은 반응율과 생존율을 보고함으로써 방사선치료의 근거수준 향상을 기대할 수 있겠다.
2018-06-21 10:43:40
편집위원3
대부분의 간암과 관련된 치료 지침에서 방사선의 역할에 대해서는 구체적인 언급이 없는 상황에서 적극적인 방사선치료의 적응증을 증명하기 위한 국내 연구의 좋은 본보기라고 할 수 있을 것이다.
2018-06-21 10:58:15