Si Tengfei, Shao Qing, Jassem Wayel, Ma Yun, Heaton Nigel
Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People's Republic of China.
Institute of Liver Studies, King's College Hospital NHS Foundation Trust, Denmark Hill, London, UK.
Int J Surg. 2025 Jan 1;111(1):1203-1213. doi: 10.1097/JS9.0000000000001889.
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).
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 preregistered protocol.
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 1-year-OS (R 2 =0.41, P =0.0044) and 1-year-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.
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.
肝动脉灌注化疗（HAIC）一直是肝细胞癌（HCC）的一种长期干预措施。尽管临床结果良好，但由于缺乏循证支持，其在指南中的纳入仍然有限。本研究旨在确定HAIC的最佳目标人群，并验证中间终点与总生存期（OS）之间的关联。
按照PRISMA指南，在PubMed、Embase、Cochrane图书馆和科学网进行了全面检索。主要检索策略基于医学主题词（MeSH），使用“肝动脉灌注化疗”、“HAIC”、“索拉非尼”、“多吉美”、“肝细胞癌”、“HCC”、“肝癌”，并结合自由文本词。根据预先注册的方案进行数据提取、质量评估和分析。
共纳入26项研究，6456例HCC患者进行分析（HAIC组，n = 2648；索拉非尼组，n = 3808）。汇总结果显示，索拉非尼仅在经动脉化疗栓塞（TACE）难治的患者中显示出更好的OS（HR = 1.32，95%CI[1.01 - 1.73]），在其他亚组或总体HCC人群中，HAIC在患者生存方面始终优于索拉非尼。在影像学上，HAIC组较高的缓解率不一定转化为生存改善，但1年总生存期（R² = 0.41，P = 0.0044）和1年无进展生存期（1y - PFS）（R² = 0.77，P = 0.0002）的风险比（HRs）与患者的OS密切相关。同时，较大的肿瘤大小（HR = 1.86，95%CI[1.12 - 3.1, 95%]）、较重的肿瘤负担（HR = 2.32，95%CI[1.33 - 4.02]）、存在微血管侵犯或肝外转移（HR = 1.65，95%CI[1.36 - 2]；HR = 1.60，95%CI[1.19 - 2.14]）以及甲胎蛋白>400 ng/ml（HR = 1.52，95%CI[1.20 - 1.92]）被确定为OS的独立危险因素，而HAIC治疗（HR = 0.54，95%CI[0.35 - 0.82]）和较低的BCLC分期（HR = 0.44，95%CI[0.28 - 0.69]）是HCC患者的潜在保护因素。
HAIC单药治疗在HCC治疗中似乎不劣于索拉非尼，在特定亚组中有潜在益处。本研究中1年总生存期/1年无进展生存期与总生存期之间的强相关性，以及确定的风险和保护因素，为设计该领域未来的大型前瞻性研究提供了有价值的见解。
