Optimal candidates and surrogate endpoints for HAIC versus Sorafenib in hepatocellular carcinoma: an updated systematic review and meta-analysis

医学 索拉非尼 肝细胞癌 荟萃分析 内科学 危险系数 科克伦图书馆 子群分析 肿瘤科 经导管动脉化疗栓塞 人口 胃肠病学 置信区间 外科 环境卫生
作者
Tengfei Si,Qing Shao,Wayel Jassem,Yun Ma,Nigel Heaton
出处
期刊:International Journal of Surgery [Wolters Kluwer]
标识
DOI:10.1097/js9.0000000000001889
摘要

Background and Aims: Hepatic artery infusion chemotherapy (HAIC) has been a long-standing intervention for hepatocellular carcinoma (HCC). Despite positive clinical outcomes, its inclusion in guidelines remains limited due to a lack of evidence-based support. This study aims to identify optimal target populations for HAIC and validate associations between intermediate endpoints with overall survival (OS). Methods: Following PRISMA guidelines, a comprehensive search was conducted in PubMed, Embase, Cochrane Library, and Web of Science. The primary search strategy was based on medical subject headings terms (MeSH) using “Hepatic arterial infusion chemotherapy”, “HAIC”, “Sorafenib”, “Nexavar”, “hepatocellular carcinoma”, “HCC”, “Liver cancer”, combined with free text words. Data extraction, quality assessment, and analysis were performed according to pre-registered protocol. Results: A total of 26 studies, 6456 HCC patients were included for analysis (HAIC, n=2648; Sorafenib, n=3808). Pooled outcomes revealed that Sorafenib demonstrated better OS only in patients who were refractory to trans-arterial chemoembolization (TACE) (HR=1.32,95%CI [1.01-1.73]), in other subgroups or overall HCC population HAIC consistently outperformed Sorafenib in patients’ survival. Radiologically, higher response rates in the HAIC group does not necessarily translate into survival improvement, but the hazard ratios (HRs) of 1y-OS (R 2 =0.41, P =0.0044) and 1y-progression free survival (1y-PFS) (R 2 =0.77, P =0.0002) strongly correlated with the patients OS. Meanwhile, larger tumour size (HR=1.86,95%CI [1.12-3.1, 95%), heavier tumour burden (HR=2.32, 95%CI [1.33-4.02), existence of MVI or EHS (HR=1.65,95%CI[1.36-2]; HR=1.60,95%CI[1.19-2.14]), and AFP >400 ng/mL (HR=1.52, 95%CI [1.20-1.92]) were identified as independent risk factors for OS, while HAIC treatment (HR=0.54, 95%CI[0.35-0.82]) and lower BCLC stage (HR=0.44, 95%CI[0.28-0.69]) were potential protective factors for HCC patients. Conclusion: HAIC monotherapy appears noninferior to Sorafenib in HCC treatment, with potential benefits in specific subgroups. The robust correlation between 1y-OS/1y-PFS and OS, alongside identified risk and protective factors from the present study, offers valuable insights for designing future large prospective studies in this field.
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