PDF(Pubmed)
Abstract：
UNASSIGNED: 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.
UNASSIGNED: To review and compare the effectiveness of all current ablative and non-surgical therapies for patients with small hepatocellular carcinoma (≤ 3 cm).
UNASSIGNED: Systematic review and network meta-analysis.
UNASSIGNED: Nine databases (March 2021), two trial registries (April 2021) and reference lists of relevant systematic reviews.
UNASSIGNED: 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.
UNASSIGNED: 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 (n ≥ 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 (n = 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.
UNASSIGNED: Many studies were small and of poor quality. No comparative studies were found for some therapies.
UNASSIGNED: 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.
UNASSIGNED: PROSPERO CRD42020221357.
UNASSIGNED: 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 Health Technology Assessment; Vol. 27, No. 29. See the NIHR Funding and Awards website for further award information.
Hepatocellular carcinoma is the most common type of primary liver cancer. There are a range of different treatments available for patients with early hepatocellular carcinoma. We looked for clinical trials in patients with small tumours (up to 3 cm) that compared different treatments. We brought together and analysed the results of these trials to see which treatments were most effective in terms of survival, progression, side effects and quality of life. Overall, the evidence has limitations; many trials had few patients and were of poor quality. Most were from China or Japan, where the common causes of liver disease and treatments available differ from those in the United Kingdom. The results of our analyses were very uncertain so we cannot be sure which treatment is the best overall. We did find that three treatments – radiofrequency ablation, microwave ablation and surgery – were generally more effective than percutaneous ethanol injection and percutaneous acid injection. There was not enough evidence to be certain which treatment was better when radiofrequency ablation was compared with laser ablation, microwave ablation, proton beam therapy or surgery. We found only poor-quality, non-randomised trials on high-intensity focused ultrasound, cryoablation and irreversible electroporation. There was very little evidence on treatments that combined radiofrequency ablation with other therapies. We found no studies that compared electrochemotherapy, histotripsy, stereotactic ablative radiotherapy or wider radiotherapy techniques with other treatments. Only two studies reported data on quality of life or patient satisfaction. We discussed the findings with patients and clinical experts. Stereotactic ablative radiotherapy was highlighted as a treatment that requires further research; however, it is only appropriate for certain subgroups of patients. Feasibility studies could inform future clinical trials by exploring issues such as whether patients are willing to take part in a trial or find the treatments acceptable.
UNASSIGNED: To review and compare the effectiveness of all current ablative and non-surgical therapies for patients with small hepatocellular carcinoma (≤ 3 cm).
UNASSIGNED: Systematic review and network meta-analysis.
UNASSIGNED: Nine databases (March 2021), two trial registries (April 2021) and reference lists of relevant systematic reviews.
UNASSIGNED: 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.
UNASSIGNED: 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 (n ≥ 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 (n = 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.
UNASSIGNED: Many studies were small and of poor quality. No comparative studies were found for some therapies.
UNASSIGNED: 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.
UNASSIGNED: PROSPERO CRD42020221357.
UNASSIGNED: 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 Health Technology Assessment; Vol. 27, No. 29. See the NIHR Funding and Awards website for further award information.
Hepatocellular carcinoma is the most common type of primary liver cancer. There are a range of different treatments available for patients with early hepatocellular carcinoma. We looked for clinical trials in patients with small tumours (up to 3 cm) that compared different treatments. We brought together and analysed the results of these trials to see which treatments were most effective in terms of survival, progression, side effects and quality of life. Overall, the evidence has limitations; many trials had few patients and were of poor quality. Most were from China or Japan, where the common causes of liver disease and treatments available differ from those in the United Kingdom. The results of our analyses were very uncertain so we cannot be sure which treatment is the best overall. We did find that three treatments – radiofrequency ablation, microwave ablation and surgery – were generally more effective than percutaneous ethanol injection and percutaneous acid injection. There was not enough evidence to be certain which treatment was better when radiofrequency ablation was compared with laser ablation, microwave ablation, proton beam therapy or surgery. We found only poor-quality, non-randomised trials on high-intensity focused ultrasound, cryoablation and irreversible electroporation. There was very little evidence on treatments that combined radiofrequency ablation with other therapies. We found no studies that compared electrochemotherapy, histotripsy, stereotactic ablative radiotherapy or wider radiotherapy techniques with other treatments. Only two studies reported data on quality of life or patient satisfaction. We discussed the findings with patients and clinical experts. Stereotactic ablative radiotherapy was highlighted as a treatment that requires further research; however, it is only appropriate for certain subgroups of patients. Feasibility studies could inform future clinical trials by exploring issues such as whether patients are willing to take part in a trial or find the treatments acceptable.
摘要：
■广泛的消融和非手术疗法可用于治疗患有非常早期或早期疾病且肝功能保留的小肝细胞癌。
■回顾和比较所有当前消融和非手术疗法对小肝细胞癌（≤3cm）患者的有效性。
■系统评价和网络荟萃分析。
■9个数据库（2021年3月），两个试验登记册(2021年4月)和相关系统综述的参考文献清单.
■符合条件的研究是消融和非手术疗法的随机对照试验，与任何比较器相比，用于小肝癌。使用Cochrane偏差风险2工具对随机对照试验进行质量评估并作图。使用网络荟萃分析评估治疗的比较有效性。使用阈值分析来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，或者没有确定随机对照试验，对非随机的有针对性的系统评价，前瞻性比较研究为重复网络荟萃分析和阈值分析提供了额外数据.探讨了进行经济模型的可行性。举行了与患者和临床医生的研讨会，以讨论研究结果并确定未来研究的重点。
■37项随机对照试验（涉及3700多名相关患者）纳入本综述。大多数是在中国或日本进行的，大多数都有很高的偏见风险或一些偏见风险。对于大多数比较，网络荟萃分析的结果是不确定的。有证据表明，经皮乙醇注射低于射频消融术的总生存期（风险比1.45，95%可信区间1.16至1.82），无进展生存期（风险比1.36，95%可信区间1.11至1.67），总体复发(相对危险度1.19,95%可信区间1.02~1.39)和局部复发(相对危险度1.80,95%可信区间1.19~2.71).对于无进展生存期，经皮注射酸也不如射频消融术（风险比1.63，95％可信区间1.05至2.51）。阈值分析表明，进一步的证据可能会改变一些比较的结果。确定了14项符合条件的非随机研究（n≥2316）；12项具有较高的偏倚风险，因此未包括在更新的网络荟萃分析中。其他非随机数据，由临床顾问提供，也包括在内（n=303）。网络荟萃分析更新后，治疗排名仍然存在高度不确定性。然而,更新后的分析显示,微波消融和切除在某些结局方面优于经皮乙醇注射和经皮酸注射.研讨会上建议对立体定向消融放射治疗进行进一步研究，虽然它只适用于某些患者亚组，限制了充分有力试验的机会。
■许多研究规模小，质量差。没有发现某些疗法的比较研究。
■现有的证据基础存在局限性；在英国，采用特定的消融疗法似乎更多地基于技术进步和易用性，而不是临床有效性的有力证据。然而,有证据表明，经皮乙醇注射和经皮酸注射不如射频消融，微波消融和切除。
■PROSPEROCRD42020221357。
■该奖项由美国国家卫生与护理研究所（NIHR）卫生技术评估（HTA）计划（NIHR奖参考：NIHR131224）资助，并在《卫生技术评估》中全文发表；卷。27号29.有关更多奖项信息，请参阅NIHR资助和奖励网站。
肝细胞癌是原发性肝癌的最常见类型。有一系列不同的治疗方法可用于早期肝细胞癌患者。我们寻找小肿瘤患者（最大3厘米）的临床试验，比较不同的治疗方法。我们汇集并分析了这些试验的结果，以了解哪些治疗在生存方面最有效，programming,副作用和生活质量。总的来说,证据有局限性;许多试验的患者较少,且质量较差.大多数来自中国或日本，肝脏疾病的常见原因和可用的治疗方法与英国不同。我们的分析结果非常不确定，因此我们无法确定哪种治疗方法总体上是最好的。我们确实发现了三种治疗方法-射频消融，微波消融和手术-通常比经皮乙醇注射和经皮酸注射更有效。没有足够的证据来确定射频消融与激光消融相比哪种治疗更好。微波消融，质子束治疗或手术。我们只发现质量差，高强度聚焦超声的非随机试验，冷冻消融和不可逆电穿孔。很少有证据表明射频消融与其他疗法相结合。我们没有发现比较电化学疗法的研究，组织切片,立体定向消融放射治疗或与其他治疗更广泛的放射治疗技术。只有两项研究报告了有关生活质量或患者满意度的数据。我们与患者和临床专家讨论了这些发现。立体定向消融放疗被强调为一种需要进一步研究的治疗方法；然而，它只适用于某些亚组患者。可行性研究可以通过探索诸如患者是否愿意参加试验或发现治疗可接受的问题来为未来的临床试验提供信息。
■回顾和比较所有当前消融和非手术疗法对小肝细胞癌（≤3cm）患者的有效性。
■系统评价和网络荟萃分析。
■9个数据库（2021年3月），两个试验登记册(2021年4月)和相关系统综述的参考文献清单.
■符合条件的研究是消融和非手术疗法的随机对照试验，与任何比较器相比，用于小肝癌。使用Cochrane偏差风险2工具对随机对照试验进行质量评估并作图。使用网络荟萃分析评估治疗的比较有效性。使用阈值分析来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，或者没有确定随机对照试验，对非随机的有针对性的系统评价，前瞻性比较研究为重复网络荟萃分析和阈值分析提供了额外数据.探讨了进行经济模型的可行性。举行了与患者和临床医生的研讨会，以讨论研究结果并确定未来研究的重点。
■37项随机对照试验（涉及3700多名相关患者）纳入本综述。大多数是在中国或日本进行的，大多数都有很高的偏见风险或一些偏见风险。对于大多数比较，网络荟萃分析的结果是不确定的。有证据表明，经皮乙醇注射低于射频消融术的总生存期（风险比1.45，95%可信区间1.16至1.82），无进展生存期（风险比1.36，95%可信区间1.11至1.67），总体复发(相对危险度1.19,95%可信区间1.02~1.39)和局部复发(相对危险度1.80,95%可信区间1.19~2.71).对于无进展生存期，经皮注射酸也不如射频消融术（风险比1.63，95％可信区间1.05至2.51）。阈值分析表明，进一步的证据可能会改变一些比较的结果。确定了14项符合条件的非随机研究（n≥2316）；12项具有较高的偏倚风险，因此未包括在更新的网络荟萃分析中。其他非随机数据，由临床顾问提供，也包括在内（n=303）。网络荟萃分析更新后，治疗排名仍然存在高度不确定性。然而,更新后的分析显示,微波消融和切除在某些结局方面优于经皮乙醇注射和经皮酸注射.研讨会上建议对立体定向消融放射治疗进行进一步研究，虽然它只适用于某些患者亚组，限制了充分有力试验的机会。
■许多研究规模小，质量差。没有发现某些疗法的比较研究。
■现有的证据基础存在局限性；在英国，采用特定的消融疗法似乎更多地基于技术进步和易用性，而不是临床有效性的有力证据。然而,有证据表明，经皮乙醇注射和经皮酸注射不如射频消融，微波消融和切除。
■PROSPEROCRD42020221357。
■该奖项由美国国家卫生与护理研究所（NIHR）卫生技术评估（HTA）计划（NIHR奖参考：NIHR131224）资助，并在《卫生技术评估》中全文发表；卷。27号29.有关更多奖项信息，请参阅NIHR资助和奖励网站。
肝细胞癌是原发性肝癌的最常见类型。有一系列不同的治疗方法可用于早期肝细胞癌患者。我们寻找小肿瘤患者（最大3厘米）的临床试验，比较不同的治疗方法。我们汇集并分析了这些试验的结果，以了解哪些治疗在生存方面最有效，programming,副作用和生活质量。总的来说,证据有局限性;许多试验的患者较少,且质量较差.大多数来自中国或日本，肝脏疾病的常见原因和可用的治疗方法与英国不同。我们的分析结果非常不确定，因此我们无法确定哪种治疗方法总体上是最好的。我们确实发现了三种治疗方法-射频消融，微波消融和手术-通常比经皮乙醇注射和经皮酸注射更有效。没有足够的证据来确定射频消融与激光消融相比哪种治疗更好。微波消融，质子束治疗或手术。我们只发现质量差，高强度聚焦超声的非随机试验，冷冻消融和不可逆电穿孔。很少有证据表明射频消融与其他疗法相结合。我们没有发现比较电化学疗法的研究，组织切片,立体定向消融放射治疗或与其他治疗更广泛的放射治疗技术。只有两项研究报告了有关生活质量或患者满意度的数据。我们与患者和临床专家讨论了这些发现。立体定向消融放疗被强调为一种需要进一步研究的治疗方法；然而，它只适用于某些亚组患者。可行性研究可以通过探索诸如患者是否愿意参加试验或发现治疗可接受的问题来为未来的临床试验提供信息。
