肝动脉灌注化疗与经动脉化疗栓塞/栓塞治疗不可切除肝细胞癌疗效与安全性系统评价和Meta分析

A systematic review and Meta-analysis of hepatic arterial infusion chemotherapy versus transarterial chemoembolization/embolization for unresectable hepatocellular carcinoma

摘要:

背景与目的 肝细胞癌（HCC）是常见的恶性肿瘤之一。经动脉化疗栓塞（TACE）和经动脉栓塞（TAE）是不可切除HCC的常见治疗选择。近年来，肝动脉灌注化疗（HAIC）已用于治疗晚期HCC，并且取得了良好的治疗效果。但是，很少有研究直接将HAIC与TACE/TAE进行比较。因此，本研究旨在评估HAIC与TACE/TAE治疗不可切除HCC的疗效和安全性。方法 检索PubMed、OvidSP、Cochrane Library、Web of Science、万方数据库、中国知网及维普中文期刊数据库中截至2021年8月14日发表的有关HAIC和TACE/TAE治疗不可切除HCC的文献；提取总生存期（OS），无病生存期（PFS），客观反应率（ORR），疾病控制率（DCR）和不良事件等结局指标的相关数据，用Review Manager 5.4软件进行Meta分析。结果 最终共纳入5篇文献。Meta分析结果显示，HAIC组在OS（HR=0.39，95% CI=0.18~0.86，P= 0.02），ORR（RR=3.82，95% CI=2.41~6.04，P<0.000 01）和DCR（RR=1.52，95% CI=1.12~2.05，P=0.006）方面优于TACE/TAE组。并且，敏感度分析排除可能的异质性来源后，结果仍一致。HAIC组与TACE/TAE组之间PFS差异无统计学意义（HR=0.34，95% CI =0.11~1.04，P =0.06），但排除可能的异质性来源后，HAIC组的PFS优于TACE/TAE组（HR=0.56，95% CI=0.43~0.73，P<0.000 1）。对于任何等级的不良事件，HAIC组发生血小板减少症（RR=1.59，95% CI=1.04~2.44，P=0.03）和腹泻（RR=4.57，95% CI=2.01~10.37，P=0.003）的风险高于TACE/TAE组，而发生丙氨酸氨基转移酶升高（RR=0.57，95% CI=0.35~0.92，P=0.02）、高胆红素血症（RR=0.37，95% CI=0.26~0.53，P<0.000 01）的风险低于TACE/TAE组；对于3~4级不良事件，HAIC组发生白细胞减少症的风险高于TACE/TAE组（RR=6.32，95% CI=1.71~23.28，P=0.006）；无论是3~4级或任何等级的不良事件，HAIC组发生发热的风险低于TACE/TAE组（P<0.05）；两组的贫血、中性粒细胞减少症、低蛋白血症、腹痛、呕吐等发生情况差异均无统计学意义（均P>0.05）。结论 与TACE/TAE相比，HAIC具有更好的肿瘤反应、更长的生存期以及可接受的不良反应，是不可切除HCC患者更好的治疗选择。

Abstract:

Background and Aims Hepatocellular carcinoma (HCC) is one of the common malignant tumors. Transarterial chemoembolization (TACE) and transarterial embolization (TAE) are common treatment options for unresectable HCC. In recent years, hepatic arterial infusion chemotherapy (HAIC) has been used to treat advanced HCC and has achieved satisfactory therapeutic effects. However, few studies directly compare HAIC with TACE/TAE. Therefore, this study was conducted to evaluate the efficacy and safety of HAIC and TACE/TAE in the treatment of unresectable HCC.Methods The studies on HAIC and TACE/TAE in the treatment of unresectable HCC published as of 14 August 2021 were searched in PubMed, OvidSP, Cochrane Library, Web of Science, Wanfang Database, CNKI, and VIP Chinese Journal Database. The data relevant to the outcome variables such as overall survival (OS), disease-free survival (PFS), objective response rate (ORR), disease control rate (DCR) and adverse events were extracted, and Meta-analysis was performed using Review Manager 5.4 software.Results A total of 5 studies were finally included. Results of Meta-analysis showed that HAIC group was superior to TACE/TAE group in terms of OS (HR=0.39, 95% CI=0.18-0.86, P=0.02), ORR (RR=3.82, 95% CI=2.41-6.04, P<0.000 01) and DCR (RR=1.52, 95% CI=1.12-2.05, P=0.006). Moreover, the results were still consistent after exclusion of possible sources of heterogeneity by sensitivity analysis. There was no significant difference between HAIC group and TACE/TAE group in PFS (HR=0.34, 95% CI=0.11-1.04, P=0.06), but the PFS in HAIC group was better than that in TACE/TAE group after exclusion of possible sources of heterogeneity (HR=0.56, 95% CI=0.43-0.73, P<0.000 1). For any grade of adverse events, the risk ratios of thrombocytopenia (RR=1.59, 95% CI=1.04-2.44, P=0.03) and diarrhea (RR=4.57, 95% CI=2.01-10.37, P=0.003) were higher, while the risk ratios of elevation of alanine aminotransferase (RR=0.57, 95% CI=0.35-0.92, P=0.02) and hyperbilirubinemia (RR=0.37, 95% CI=0.26-0.53, P<0.000 01) were lower in HAIC group than those in TACE/TAE group; for grade 3-4 adverse events, the risk of leukopenia in HAIC group was higher than that in TACE/TAE group (RR=6.32, 95% CI=1.71-23.28, P=0.006); for either grade 3-4 adverse events or any grade, the risk of fever in the HAIC group was lower than that in the TACE/TAE group (P<0.05); there were no significant differences in incidence rates of anemia, neutropenia, and hypoproteinemia as well as abdominal pain and vomiting between the two groups (all P>0.05).Conclusion Compared with TACE/TAE, HAIC offers better tumor response and longer survival, and acceptable adverse reactions. So, it is a better treatment option for patients with unresectable HCC.