Radiation Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
Department of Human Oncology, University of Wisconsin, Madison.
JAMA Netw Open. 2024 Nov 4;7(11):e2447995. doi: 10.1001/jamanetworkopen.2024.47995.
Several locoregional therapies (LRTs) for nonmetastatic hepatocellular carcinoma (HCC) are available; however, a global comparison of the relative efficacy of each is needed.
To conduct a systematic review and direct, pairwise meta-analytic comparison of all identified randomized clinical trials evaluating the treatment of nonmetastatic HCC.
A comprehensive search of PubMed and the proceedings of the American Society of Clinical Oncology and American Society for Radiation Oncology annual meetings from January 1, 2010, to November 1, 2023, was performed.
Randomized clinical trials using a form of LRT (surgery with or without adjuvant therapy, radiofrequency ablation [RFA], microwave ablation [MWA], radiotherapy [RT], hepatic arterial infusion chemotherapy [HAIC], transarterial bland embolization [TAE], transarterial chemoembolization [TACE], or transarterial radioembolization [TARE]).
Study eligibility and data extraction were each reviewed by 2 authors independently. Random-effects meta-analyses were used to compare treatment categories.
Progression-free survival (PFS) was the primary outcome; overall survival (OS) was the secondary outcome.
Forty randomized clinical trials reporting on comparative outcomes of 11 576 total patients with localized HCC treated with LRT were included. The median follow-up was 30.0 (IQR, 18.5-40.8) months. Direct pooled comparisons between treatment classes suggested improved outcomes for surgery combined with adjuvant therapy over surgery alone (PFS: hazard ratio [HR], 0.62 [95% CI, 0.51-0.75]; P < .001; OS: HR, 0.61 [95% CI, 0.48-0.78]; P < .001), surgery over RFA (PFS: HR, 0.74 [95% CI, 0.63-0.87]; P < .001; OS: HR, 0.71 [95% CI, 0.54-0.95]; P = .02), RT over TACE (PFS: HR, 0.35 [95% CI, 0.21-0.60]; P < .001; OS: HR, 0.35 [95% CI, 0.13-0.97]; P = .04), and HAIC over TACE (PFS: HR, 0.57 [95% CI, 0.45-0.72]; P < .001; OS: HR, 0.58 [95% CI, 0.45-0.75]; P < .001). No substantial heterogeneity was noted for any pairwise comparison with the exception of RT-based regimens compared with tyrosine kinase inhibitor therapy.
The findings of this systematic review and direct, pairwise meta-analysis suggest that all LRTs are not equivalent for the treatment of localized HCC. The efficacy of LRTs appears hierarchical, with surgery-based management outcomes associated with the best treatment outcomes and embolization-based treatment options associated with the worst treatment outcomes.
有几种局部区域治疗（LRT）可用于非转移性肝细胞癌（HCC）；然而，需要对每种治疗方法的相对疗效进行全球比较。
对所有确定的评估非转移性 HCC 治疗的随机临床试验进行系统回顾和直接、两两荟萃分析比较。
从 2010 年 1 月 1 日至 2023 年 11 月 1 日，全面搜索 PubMed 和美国临床肿瘤学会和美国放射肿瘤学会年会的会议记录。
使用 LRT（手术加或不加辅助治疗、射频消融[RFA]、微波消融[MWA]、放疗[RT]、肝动脉灌注化疗[HAIC]、经动脉单纯栓塞[TAE]、经动脉化疗栓塞[TACE]或经动脉放射栓塞[TARE]）形式的随机临床试验。
两名作者独立审查了研究的资格和数据提取。使用随机效应荟萃分析比较治疗类别。
无进展生存期（PFS）是主要结局；总生存期（OS）是次要结局。
纳入了 40 项比较了 11576 例接受 LRT 局部 HCC 治疗的患者的局部 HCC 局部治疗结果的随机临床试验。中位随访时间为 30.0（IQR，18.5-40.8）个月。直接的两两比较表明，手术联合辅助治疗优于单纯手术（PFS：风险比[HR]，0.62[95%CI，0.51-0.75]；P<0.001；OS：HR，0.61[95%CI，0.48-0.78]；P<0.001）、手术优于 RFA（PFS：HR，0.74[95%CI，0.63-0.87]；P<0.001；OS：HR，0.71[95%CI，0.54-0.95]；P=0.02）、RT 优于 TACE（PFS：HR，0.35[95%CI，0.21-0.60]；P<0.001；OS：HR，0.35[95%CI，0.13-0.97]；P=0.04）和 HAIC 优于 TACE（PFS：HR，0.57[95%CI，0.45-0.72]；P<0.001；OS：HR，0.58[95%CI，0.45-0.75]；P<0.001）。除了基于 RT 的方案与酪氨酸激酶抑制剂治疗相比外，任何两两比较均未发现明显的异质性。
本系统评价和直接、两两荟萃分析的结果表明，并非所有 LRT 对局部 HCC 的治疗都是等效的。LRT 的疗效似乎呈等级性，基于手术的治疗结果与最佳治疗结果相关，而基于栓塞的治疗方案与最差的治疗结果相关。
