Surgery versus radiofrequency ablation for small hepatocellular carcinoma: Start of a randomized controlled trial (SURF trial)
Surgery versus radiofrequency ablation for small hepatocellular carcinoma: Start of a randomized controlled trial (SURF trial)
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手术与射频消融治疗小肝细胞癌：随机对照试验（SURF 试验）的开始
DOI：
10.1111/j.1872-034x.2010.00696.x
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发表时间：
2010
影响因子：
4.2
通讯作者：
M. Makuuchi
中科院分区：
文献类型：
--
作者：
K. Hasegawa;N. Kokudo;S. Shiina;R. Tateishi;M. Makuuchi
亲爱的编辑：“小肝细胞癌（HCC）的初始治疗，肝切除术和经皮消融术哪一种更有效？”这一直是肝病学领域最重要的问题之一。尽管最近由日本肝癌研究小组进行的两项随机对照试验（RCT）和一项前瞻性全国队列研究的结果，但它们的含义不能被接受为结论性的，因为它们都存在一些严重的问题。与此同时，日本正在进行一项多中心联合研究（缩写为手术后与射频消融后的SURF试验），以得出上述问题的有力结论。本研究受试者的主要条件是：(i)肿瘤状况（在诊断图像上表现出典型的原发性HCC，肿瘤灶数量为3个或更少，每个肿瘤灶尺寸不超过3厘米）；（ii）肝功能状况（Child-Pugh评分为7分或以下）；（iii）年龄介乎20至79岁；（iv）肝切除术或射频消融术（RFA）的适应症，由各医院决定。在日本，过去曾计划进行一些类似性质的研究，但没有一个完成。在反思前期失败的基础上，本研究在以下几个方面进行了创新。我们采用了两个共同的主要终点：总生存期和无复发生存期。在确定本试验的主要终点时，有一种观点认为，“由于有不止一种有效的治疗方法可用于复发，因此HCC初始治疗的疗效趋于降低。而且，复发本身对于直接评价治疗效果更好”，但也有观点认为“即使早期有很多复发，由于RFA比肝切除术的侵入性小，对肝功能的影响也小，复发后也容易进行治疗，生存率可能会更好。”毕竟，如果不检查总生存期，那就没有意义了”，还有一种观点认为，“复发和生存都要看”，这是争论最激烈的问题。虽然从理论上讲，从评估治疗方法的角度来看，总生存期确实是真正的终点，但为了减少样本量，缩短随访时间，增加完成的可能性，我们决定也使用无复发生存期作为主要终点。在本研究中，总共需要600例病例才能发现10%的差异，假设肝切除术和RFA后的3年无复发生存率分别为45%和35%（东京大学医院，2008）。根据同一数据库，两种治疗方式的5年总生存率约为70%。如果任何一种治疗方法的结果都落在这个数字附近，那么从统计学上证实，600例病例将足以检测到总生存率10%的差异。目前的研究旨在检测手术和RFA在总生存率和无复发生存率方面的10%差异，因此使用这两个作为主要终点是合适的。2本研究的主要目的是采用随机对照试验（RCT）形式比较和评价两种治疗方法；但考虑到可能有一些患者不希望参加RCT，计划进行平行前瞻性队列研究。对于符合RCT要求但拒绝参加RCT的患者，经其同意后进行登记，并在手术后或自行选择RFA后进行随访。预计通过本队列研究，将获得对RCT结果的解释和外推有价值的数据。我们必须强调，这项队列研究的受试者是独一无二的，因为他们是真正的手术和RFA的双重候选人，在注册前由每个研究所的外科医生和胃肠病学家确认。3 2007年1月，东京大学医院肝胆胰外科、消化内科、放射科联合编写《肝病学研究2010》；39: 851-852 doi: 10.1111/j.1872-034X.2010.00696.x
Dear Editor, “Which is more effective as an initial treatment for small hepatocellular carcinoma (HCC), hepatectomy or percutaneous ablation therapy?” This has been one of the most significant questions in the domain of hepatology. In spite of the recent results of two randomized controlled trials (RCT) and a prospective nationwide cohort study conducted by the Liver Cancer Study Group of Japan, their implications cannot be accepted as conclusive, because each of them had some severe problems. Meanwhile, a multicenter joint study (abbreviated to SURF trial after surgery vs radiofrequency ablation) is being done in Japan to reach a strong conclusion to the question cited above. The major qualifications for the subjects of this study are: (i) tumor conditions (initial HCC exhibiting typical findings on diagnostic images, tumor foci numbering three or fewer, and each measuring 3 cm or less); (ii) conditions for hepatic functions (Child–Pugh score of 7 or less); (iii) aged between 20 and 79 years; and (iv) indications for either hepatectomy or radiofrequency ablation (RFA) for the treatment which are decided at each hospital. In Japan, there were a few studies of a similar nature planned in the past but none were completed. In reflection on the earlier failures, innovations are made for the following in the current study. 1 We adopted two co-primary end-points: overall survival and recurrence-free survival. When deciding on the primary end-point in this trial, an opinion was expressed that, “Since more than one effective method of treatment is available for a recurrence, the efficacy of the initial treatment for HCC tends to diminish. Moreover, recurrences are better for directly evaluating therapeutic efficacy itself”, but there was also an opinion that “even if there are many recurrences in the early stage, because RFA is less invasive than liver resection, there is less of an impact on liver function, and treatment after recurrence can also be performed easily, the survival rate may be better. After all, if overall survival is not examined, there is no point”, as well as an opinion that, “Both recurrence and survival should be looked at”, and it was the most heatedly debated issue. While it is true that, theoretically, overall survival is the true end-point from the standpoint of evaluating treatment methods, in order to reduce the sample size, shorten the follow-up period and increase the possibility of completion, we decided to also use recurrence-free survival as a primary end-point. In the present study, a total of 600 cases are needed to find a 10% difference, assuming 3-year recurrence-free survival rates following hepatectomy and RFA of 45% and 35%, respectively (University of Tokyo Hospital, 2008). According to the same database, the 5-year overall survival rates of the two therapeutic modalities are approximately 70%. If the results of either therapeutic method are to fall around this figure, it is also statistically confirmed that 600 cases would be sufficient to detect a difference of 10% in overall survival. The current study is designed so that a 10% difference can be detected between surgery and RFA both in the overall and recurrence-free survival rates, thus it is appropriate to use these two as the primary end-points. 2 The primary purpose of this study is to compare and evaluate the two therapeutic methods by employing an RCT format; but considering that there may be a number of patients who do not wish to participate in the RCT, a parallel prospective cohort study is planned. Those patients who meet the requirements of RCT but decline to participate in the RCT will be registered upon their consent and they will be followed up after either surgery or RFA selected by themselves. It is anticipated that through this cohort study, valuable data would be obtained in interpreting and extrapolating the results of RCT. We have to emphasize that the subjects of this cohort study are unique in that they are true double candidates for surgery and RFA confirmed by both surgeons and gastroenterologists at each institute before registration. 3 In January 2007, the Departments of Hepato–Biliary– Pancreatic Surgery, Gastroenterology and Radiology of University of Tokyo Hospital jointly prepared a Hepatology Research 2010; 40: 851–852 doi: 10.1111/j.1872-034X.2010.00696.x
影响因子：
25.7
作者：
Hasegawa, Kiyoshi;Makuuchi, Masatoshi;Ikai, Iwao
通讯作者：
Ikai, Iwao