Southampton Health Technology Assessments Centre, University of Southampton, Southampton, UK.
Department of Radiology, University Hospital Southampton, Southampton, UK.
Health Technol Assess. 2014 Jan;18(7):vii-viii, 1-283. doi: 10.3310/hta18070.
Many deaths from cancer are caused by metastatic burden. Prognosis and survival rates vary, but survival beyond 5 years of patients with untreated metastatic disease in the liver is rare. Treatment for liver metastases has largely been surgical resection, but this is feasible in only approximately 20-30% of people. Non-surgical alternatives to treat some liver metastases can include various forms of ablative therapies and other targeted treatments.
To evaluate the clinical effectiveness and cost-effectiveness of the different ablative and minimally invasive therapies for treating liver metastases.
Electronic databases including MEDLINE, EMBASE and The Cochrane Library were searched from 1990 to September 2011. Experts were consulted and bibliographies checked.
Systematic reviews of the literature were undertaken to appraise the clinical effectiveness and cost-effectiveness of ablative therapies and minimally invasive therapies used for people with liver metastases. Studies were any prospective study with sample size greater than 100 participants. A probabilistic model was developed for the economic evaluation of the technologies where data permitted.
The evidence assessing the clinical effectiveness and cost-effectiveness of ablative and other minimally invasive therapies was limited. Nine studies of ablative therapies were included in the review; each had methodological shortcomings and few had a comparator group. One randomised controlled trial (RCT) of microwave ablation versus surgical resection was identified and showed no improvement in outcomes compared with resection. In two prospective case series studies that investigated the use of laser ablation, mean survival ranged from 41 to 58 months. One cohort study compared radiofrequency ablation with surgical resection and five case series studies also investigated the use of radiofrequency ablation. Across these studies the median survival ranged from 44 to 52 months. Seven studies of minimally invasive therapies were included in the review. Two RCTs compared chemoembolisation with chemotherapy only. Overall survival was not compared between groups and methodological shortcomings mean that conclusions are difficult to make. Two case series studies of laser ablation following chemoembolisation were also included; however, these provide little evidence of the use of these technologies in combination. Three RCTs of radioembolisation were included. Significant improvements in tumour response and time to disease progression were demonstrated; however, benefits in terms of survival were equivocal. An exploratory survival model was developed using data from the review of clinical effectiveness. The model includes separate analyses of microwave ablation compared with surgery and radiofrequency ablation compared with surgery and one of radioembolisation in conjunction with hepatic artery chemotherapy compared with hepatic artery chemotherapy alone. Microwave ablation was associated with an incremental cost-effectiveness ratio (ICER) of £3664 per quality-adjusted life-year (QALY) gained, with microwave ablation being associated with reduced cost but also with poorer outcome than surgery. Radiofrequency ablation compared with surgical resection for solitary metastases < 3 cm was associated with an ICER of -£266,767 per QALY gained, indicating that radiofrequency ablation dominates surgical resection. Radiofrequency ablation compared with surgical resection for solitary metastases ≥ 3 cm resulted in poorer outcomes at lower costs and a resultant ICER of £2538 per QALY gained. Radioembolisation plus hepatic artery chemotherapy compared with hepatic artery chemotherapy was associated with an ICER of £37,303 per QALY gained.
There is currently limited high-quality research evidence upon which to base any firm decisions regarding ablative therapies for liver metastases. Further trials should compare ablative therapies with surgery, in particular. A RCT would provide the most appropriate design for undertaking any further evaluation and should include a full economic evaluation, but the group to be randomised needs careful selection.
Funding for this study was provided by the Health Technology Assessment programme of the National Institute for Health Research.
许多癌症死亡是由转移性负担引起的。预后和生存率各不相同，但未经治疗的肝转移患者 5 年以上生存率罕见。肝转移的治疗主要是手术切除，但这在大约 20-30%的患者中是可行的。治疗一些肝转移的非手术替代方法包括各种形式的消融治疗和其他靶向治疗。
评估不同消融和微创治疗方法治疗肝转移的临床效果和成本效益。
从 1990 年到 2011 年 9 月，电子数据库包括 MEDLINE、EMBASE 和 The Cochrane Library 进行了检索。咨询了专家并检查了参考文献。
系统评价文献评估了用于治疗肝转移的消融和微创治疗的临床效果和成本效益。研究为前瞻性研究，样本量大于 100 例。在数据允许的情况下，为技术的经济评估开发了概率模型。
评估消融和其他微创治疗的临床效果和成本效益的证据有限。本综述纳入了 9 项消融治疗研究；每项研究都存在方法学上的缺陷，很少有对照组。一项随机对照试验（RCT）比较了微波消融与手术切除，结果显示与切除相比，结果没有改善。在两项前瞻性病例系列研究中，激光消融的平均生存时间为 41-58 个月。一项队列研究比较了射频消融与手术切除，五项病例系列研究也调查了射频消融的应用。在这些研究中，中位生存时间从 44 到 52 个月不等。本综述纳入了 7 项微创治疗研究。两项 RCT 比较了化疗栓塞与单纯化疗。组间未比较总生存率，且方法学上的缺陷使得结论难以得出。两项激光消融后化疗栓塞的病例系列研究也包括在内；然而，这些研究提供的联合使用这些技术的证据很少。纳入了三项放射性栓塞的 RCT。结果表明，肿瘤反应和疾病进展时间均有显著改善；然而，在生存方面的获益尚无定论。使用本临床效果评价综述中的数据，建立了一个探索性生存模型。该模型包括单独分析微波消融与手术的比较，以及射频消融与手术的比较，以及放射性栓塞联合肝动脉化疗与肝动脉化疗单独比较。与手术相比，微波消融的增量成本效益比（ICER）为每获得 1 个质量调整生命年（QALY）增加 3664 英镑，微波消融与较低的成本相关，但与较差的结果相关。与手术相比，对于直径小于 3cm 的单个转移灶，射频消融的 ICER 为-266767 英镑/QALY，表明射频消融优于手术。与手术相比，对于直径大于 3cm 的单个转移灶，射频消融的结果较差，成本较低，ICER 为 2538 英镑/QALY。与肝动脉化疗相比，放射性栓塞联合肝动脉化疗的 ICER 为 37303 英镑/QALY。
目前，基于肝转移消融治疗的任何坚定决策，仅有有限的高质量研究证据。应特别比较消融治疗与手术。随机对照试验（RCT）将为进一步评估提供最合适的设计，并应包括全面的经济评估，但需要仔细选择随机分组的对象。
本研究由英国国家卫生研究院卫生技术评估计划提供资金。
