Su Yung-Yeh, Liu Yi-Sheng, Hsiao Chin-Fu, Hsu Chiun, Chen Li-Tzong
National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan.
Department of Oncology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
J Hepatocell Carcinoma. 2022 Jun 2;9:517-536. doi: 10.2147/JHC.S220978. eCollection 2022.
Intermediate-stage hepatocellular carcinoma (HCC) consists of heterogeneous groups of patients in terms of tumor burden and organ function reserves. Although liver-directed therapy (LDT), including trans-catheter arterial chemoembolization, radiofrequency ablation or even surgical resection, is the recommended frontline treatment modality, intrahepatic and distant failures are common. The recent advances in systemic treatment, notably the introduction of immune checkpoint inhibitor (ICI)-based therapy, have significantly improved the objective tumor response rate, quality of response and overall survival in patients with recurrent and advanced HCC. Whether the combination of systemic treatment and LDT can further improve the outcome of patients with intermediate-stage HCC is currently being extensively evaluated. In this article, the recent clinical trials incorporating different ICI-based combinations with different LDT for intermediate-stage HCC were reviewed focusing on trial design issues, including patient selection, endpoint definition, and biomarker development. The strength and caveats of different combination strategies and novel biomarker development were discussed.
中期肝细胞癌（HCC）患者在肿瘤负荷和器官功能储备方面存在异质性。尽管包括经导管动脉化疗栓塞、射频消融甚至手术切除在内的肝导向治疗（LDT）是推荐的一线治疗方式，但肝内和远处复发很常见。全身治疗的最新进展，特别是基于免疫检查点抑制剂（ICI）治疗的引入，显著提高了复发和晚期HCC患者的客观肿瘤缓解率、缓解质量和总生存期。全身治疗与LDT联合是否能进一步改善中期HCC患者的预后目前正在广泛评估中。在本文中，回顾了近期将不同基于ICI的联合方案与不同LDT用于中期HCC的临床试验，重点关注试验设计问题，包括患者选择、终点定义和生物标志物开发。讨论了不同联合策略的优势和注意事项以及新型生物标志物的开发。
