Research Fellow, Centre for Reviews and Dissemination, University of York, Heslington, UK.
Information Specialist, Centre for Reviews and Dissemination, University of York, Heslington, UK.
Health Technol Assess. 2023 Dec;27(29):1-172. doi: 10.3310/GK5221.
A wide range of ablative and non-surgical therapies are available for treating small hepatocellular carcinoma in patients with very early or early-stage disease and preserved liver function.
To review and compare the effectiveness of all current ablative and non-surgical therapies for patients with small hepatocellular carcinoma (≤ 3 cm).
Systematic review and network meta-analysis.
Nine databases (March 2021), two trial registries (April 2021) and reference lists of relevant systematic reviews.
Eligible studies were randomised controlled trials of ablative and non-surgical therapies, versus any comparator, for small hepatocellular carcinoma. Randomised controlled trials were quality assessed using the Cochrane Risk of Bias 2 tool and mapped. The comparative effectiveness of therapies was assessed using network meta-analysis. A threshold analysis was used to identify which comparisons were sensitive to potential changes in the evidence. Where comparisons based on randomised controlled trial evidence were not robust or no randomised controlled trials were identified, a targeted systematic review of non-randomised, prospective comparative studies provided additional data for repeat network meta-analysis and threshold analysis. The feasibility of undertaking economic modelling was explored. A workshop with patients and clinicians was held to discuss the findings and identify key priorities for future research.
Thirty-seven randomised controlled trials (with over 3700 relevant patients) were included in the review. The majority were conducted in China or Japan and most had a high risk of bias or some risk of bias concerns. The results of the network meta-analysis were uncertain for most comparisons. There was evidence that percutaneous ethanol injection is inferior to radiofrequency ablation for overall survival (hazard ratio 1.45, 95% credible interval 1.16 to 1.82), progression-free survival (hazard ratio 1.36, 95% credible interval 1.11 to 1.67), overall recurrence (relative risk 1.19, 95% credible interval 1.02 to 1.39) and local recurrence (relative risk 1.80, 95% credible interval 1.19 to 2.71). Percutaneous acid injection was also inferior to radiofrequency ablation for progression-free survival (hazard ratio 1.63, 95% credible interval 1.05 to 2.51). Threshold analysis showed that further evidence could plausibly change the result for some comparisons. Fourteen eligible non-randomised studies were identified ( ≥ 2316); twelve had a high risk of bias so were not included in updated network meta-analyses. Additional non-randomised data, made available by a clinical advisor, were also included ( = 303). There remained a high level of uncertainty in treatment rankings after the network meta-analyses were updated. However, the updated analyses suggested that microwave ablation and resection are superior to percutaneous ethanol injection and percutaneous acid injection for some outcomes. Further research on stereotactic ablative radiotherapy was recommended at the workshop, although it is only appropriate for certain patient subgroups, limiting opportunities for adequately powered trials.
Many studies were small and of poor quality. No comparative studies were found for some therapies.
The existing evidence base has limitations; the uptake of specific ablative therapies in the United Kingdom appears to be based more on technological advancements and ease of use than strong evidence of clinical effectiveness. However, there is evidence that percutaneous ethanol injection and percutaneous acid injection are inferior to radiofrequency ablation, microwave ablation and resection.
PROSPERO CRD42020221357.
This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment (HTA) programme (NIHR award ref: NIHR131224) and is published in full in ; Vol. 27, No. 29. See the NIHR Funding and Awards website for further award information.
对于早期小肝癌（肝功能正常）患者，有多种消融和非手术治疗方法可供选择。
综述并比较各种目前用于治疗小肝癌（≤3cm）的消融和非手术治疗方法的疗效。
系统评价和网络荟萃分析。
9 个数据库（2021 年 3 月）、2 个试验注册库（2021 年 4 月）和相关系统评价的参考文献列表。
纳入消融和非手术治疗小肝癌的随机对照试验，比较任何对照治疗方法。使用 Cochrane 偏倚风险 2 工具对随机对照试验进行质量评估，并进行映射。采用网络荟萃分析评估治疗的相对有效性。采用阈值分析确定哪些比较对证据的潜在变化敏感。如果基于随机对照试验证据的比较不可靠，或者没有发现随机对照试验，则对非随机、前瞻性比较研究进行有针对性的系统评价，为重复网络荟萃分析和阈值分析提供额外数据。探讨了进行经济建模的可行性。与患者和临床医生举行了一次研讨会，讨论研究结果，并确定未来研究的关键优先事项。
共纳入 37 项随机对照试验（涉及 3700 多名相关患者）。这些研究大多在中国或日本进行，且大部分存在高偏倚风险或存在一些偏倚风险。大多数比较的网络荟萃分析结果不确定。有证据表明，经皮乙醇注射在总生存率（风险比 1.45，95%可信区间 1.16-1.82）、无进展生存率（风险比 1.36，95%可信区间 1.11-1.67）、总复发率（相对风险 1.19，95%可信区间 1.02-1.39）和局部复发率（相对风险 1.80，95%可信区间 1.19-2.71）方面劣于射频消融。经皮酸注射在无进展生存率方面也劣于射频消融（风险比 1.63，95%可信区间 1.05-2.51）。阈值分析表明，进一步的证据可能合理改变某些比较的结果。确定了 14 项合格的非随机研究（≥2316 项）；其中 12 项研究存在高偏倚风险，因此未纳入更新的网络荟萃分析。临床顾问提供的额外非随机数据（=303）也包括在内。更新网络荟萃分析后，治疗排序仍存在高度不确定性。然而，更新后的分析表明，微波消融和切除术在某些结局方面优于经皮乙醇注射和经皮酸注射。在研讨会上建议进一步研究立体定向消融放射治疗，但它仅适用于某些患者亚组，限制了充分进行试验的机会。
许多研究规模较小且质量较差。一些治疗方法没有发现比较研究。
现有证据基础存在局限性；英国特定消融治疗方法的采用似乎更多地基于技术进步和易用性，而不是临床疗效的有力证据。然而，有证据表明，经皮乙醇注射和经皮酸注射劣于射频消融、微波消融和切除术。
PROSPERO CRD42020221357。
本研究由英国国家卫生与保健优化研究所（NIHR）卫生技术评估（HTA）计划资助（NIHR 拨款编号：NIHR131224），并全文发表于；第 27 卷，第 29 期。请访问 NIHR 资助和奖项网站，以获取更多的奖项信息。
