晚期肝细胞癌转化治疗的挑战与思考

卢实春

doi:10.12449/JCH240904

晚期肝细胞癌转化治疗的挑战与思考

DOI: 10.12449/JCH240904

卢实春^, ,

中国人民解放军总医院肝胆胰外科医学部，北京 100089

利益冲突声明：本文不存在任何利益冲突。

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通信作者:
卢实春， lsc620213@aliyun.com （ORCID： 0000-0003-3278-0534）

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出版历程
- 收稿日期: 2024-07-14
- 录用日期: 2024-07-28
- 出版日期: 2024-09-25

Challenges and reflections on conversion therapy for advanced hepatocellular carcinoma

Shichun LU^{,
,}

Department of Hepatopancreatobiliary Surgery，Chinese PLA General Hospital，Beijing 100089，China

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Corresponding author: LU Shichun， lsc620213@aliyun.com （ORCID： 0000-0003-3278-0534）

摘要

摘要: 近年伴随生物治疗药物不断涌现，晚期肝癌系统治疗取得了巨大进展。免疫阻断点抑制剂抗体联合抗血管生成靶向药物已成为晚期肝癌治疗的一线推荐方案并取得明确的肿瘤学获益与生存获益；免疫靶向联合局部治疗研究方案不断涌现，明确提高了客观反应率；靶免转化序贯外科治疗方案正在重塑晚期肝癌治疗格局，最终提高了根治性手术切除率与远期生存率。这场由免疫治疗±靶向治疗为基本架构引导的治疗新变局中，注定挑战不断，思考亦须随行。以免疫靶向联合转化序贯外科方案探索为例来看，任一适用方案在被广泛、成熟地应用于常规诊疗之前，均应包括药物联用方案的选择、疗效的评估、毒副反应的处理、手术标准与时机、术后辅助治疗方案、长期生存获益验证、原发与继发耐药的后线治疗方案的选择等一系列新问题与挑战。本文将择其部分要点提供一些建议与思考。
- 癌，肝细胞 /
- 免疫检查点抑制剂 /
- 血管生成抑制剂 /
- 转化治疗
Abstract: With the continuous emergence of biotherapy drugs in recent years， great progress has been made in the systemic therapy for advanced liver cancer. Immune checkpoint inhibitors combined with anti-angiogenic targeted drugs has become the first-line regimen recommended for the treatment of advanced liver cancer and has achieved clear oncology benefits and survival benefits. The regimens for immunotherapy combined with local treatment continue to emerge and have clearly improved objective response rate， and targeted and immune therapeutic regimens combined with sequential surgical treatment are reshaping the treatment pattern of advanced liver cancer and have finally improved radical surgical resection rate and long-term survival rate. Such changes in treatment guided by immunotherapy with or without targeted therapy have brought great challenges and thus require meticulous thoughts. With exploration of immune and targeted therapies combined with sequential surgical regimen as an example， there is a series of new problems and challenges before they are widely applied in routine diagnosis and treatment， including the selection of drug combination regimens， the evaluation of therapeutic efficacy， the treatment of toxic and side effects， surgical standards and timing， postoperative adjuvant treatment regimens， the validation of long-term survival benefits， and the selection of second-line treatment regimens for primary and secondary drug resistance. This article puts forward some suggestions and thoughts for several key aspects.
- Carcinoma， Hepatocellular /
- Immune Checkpoint Inhibitors /
- Angiogenesis Inhibitors /
- Conversion Therapy

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参考文献(12)

[1]	HYUN MH, LEE YS, KIM JH, et al. Hepatic resection compared to chemoembolization in intermediate- to advanced-stage hepatocellular carcinoma: A meta-analysis of high-quality studies[J]. Hepatology, 2018, 68( 3): 977- 993. DOI: 10.1002/hep.29883.
[2]	Professional Committee for Prevention and Control of Hepatobiliary and Pancreatic Diseases of Chinese Preventive Medicine Association, Chinese Society of Liver Cancer, Liver Study Group of Surgery Committee of Beijing Medical Association, et al. Chinese expert consensus on conversion therapy of immune checkpoint inhibitors combined antiangiogenic targeted drugs for advanced hepatocellular carcinoma(2021 Edition)[J]. Chin J Hepatobiliary Surg, 2021, 27( 4): 241- 251. DOI: 10.3760/cma.j.cn113884-20210415-00138. 中华预防医学会肝胆胰疾病预防与控制专业委员会, 中国抗癌协会肝癌专业委员会, 北京医学会外科学分会肝脏学组, 等. 基于免疫联合靶向方案的晚期肝细胞癌转化治疗中国专家共识(2021版)[J]. 中华肝胆外科杂志, 2021, 27( 4): 241- 251. DOI: 10.3760/cma.j.cn113884-20210415-00138.
[3]	CHEN YJ. Current state and thinking of liver cancer conversion therapy[J]. Chin J Pract Surg, 2021, 41( 3): 253- 256, 261. DOI: 10.19538/j.cjps.issn1005-2208.2021.03.03. 陈亚进. 肝癌转化治疗现状与思考[J]. 中国实用外科杂志, 2021, 41( 3): 253- 256, 261. DOI: 10.19538/j.cjps.issn1005-2208.2021.03.03.
[4]	Alliance of Liver Cancer Conversion Therapy, Committee of Liver Cancer, China Anti‐Cancer Association. Chinese expert consensus on conversion and perioperative therapy of primary liver cancer(2024 edition)[J]. Chin J Dig Surg, 2024, 23( 4): 492- 513. DOI: 10.3760/cma.j.cn115610-20240228-00135. 中国抗癌协会肝癌专业委员会转化治疗协作组. 原发性肝癌转化及围手术期治疗中国专家共识(2024版)[J]. 中华消化外科杂志, 2024, 23( 4): 492- 513. DOI: 10.3760/cma.j.cn115610-20240228-00135.
[5]	LI XR, LI JF, ZHANG WW, et al. Long-term efficacy of sequential surgery after immune combined with targeted therapy for initially unresectable hepatocellular carcinoma[J]. Chin J Hepatobiliary Surg, 2024, 30( 1): 9- 14. DOI: 10.3760/cma.j.cn113884-20231130-00147. 李雪瑞, 李俊锋, 张雯雯, 等. 免疫联合靶向序贯外科根治性手术方案治疗初始不可切除肝细胞癌的远期疗效[J]. 中华肝胆外科杂志, 2024, 30( 1): 9- 14. DOI: 10.3760/cma.j.cn113884-20231130-00147.
[6]	ZHU XD, HUANG C, SHEN YH, et al. Hepatectomy after conversion therapy using tyrosine kinase inhibitors plus anti-PD-1 antibody therapy for patients with unresectable hepatocellular carcinoma[J]. Ann Surg Oncol, 2023, 30( 5): 2782- 2790. DOI: 10.1245/s10434-022-12530-z.
[7]	CHENG AL, HSU C, CHAN SL, et al. Challenges of combination therapy with immune checkpoint inhibitors for hepatocellular carcinoma[J]. J Hepatol, 2020, 72( 2): 307- 319. DOI: 10.1016/j.jhep.2019.09.025.
[8]	ZHANG WW, TONG S, HU BY, et al. Lenvatinib plus anti-PD-1 antibodies as conversion therapy for patients with unresectable intermediate-advanced hepatocellular carcinoma: A single-arm, phase II trial[J]. J Immunother Cancer, 2023, 11( 9): e007366. DOI: 10.1136/jitc-2023-007366.
[9]	XU B, DONG SY, BAI XL, et al. Tumor radiomic features on pretreatment MRI to predict response to lenvatinib plus an anti-PD-1 antibody in advanced hepatocellular carcinoma: A multicenter study[J]. Liver Cancer, 2023, 12( 3): 262- 276. DOI: 10.1159/000528034.
[10]	LI JF, YUAN J, ZHANG WW, et al. Value of the ratio of viable tumor cells in the prognostic evaluation for patients with unresectable hepatocellular carcinoma undergoing sequential surgery after conversional therapy[J]. Chin J Hepatobiliary Surg, 2024, 30( 4): 241- 247. DOI: 10.3760/cma.j.cn113884-20240226-00056. 李俊锋, 袁静, 张雯雯, 等. 存活肿瘤细胞比例在初始不可切除肝细胞癌患者转化序贯外科治疗预后评估中的应用[J]. 中华肝胆外科杂志, 2024, 30( 4): 241- 247. DOI: 10.3760/cma.j.cn113884-20240226-00056.
[11]	RAN ZK, TANG HW, CAO YB, et al. A retrospective study of postoperative adjuvant therapy following immunotherapy combined with targeted therapy and sequential curative surgical procedures for initially unresectable hepatocellular carcinoma[J]. Chin J Surg, 2024, 62( 6): 543- 548. DOI: 10.3760/cma.j.cn112139-20240207-00068. 冉子坤, 唐浩文, 曹银彪, 等. 初始不可切除肝细胞癌免疫联合靶向序贯外科根治性手术术后辅助治疗效果分析[J]. 中华外科杂志, 2024, 62( 6): 543- 548. DOI: 10.3760/cma.j.cn112139-20240207-00068.
[12]	GAO YN, YOU MJ, FU JL, et al. Intratumoral stem-like CCR4⁺ regulatory T cells orchestrate the immunosuppressive microenvironment in HCC associated with hepatitis B[J]. J Hepatol, 2022, 76( 1): 148- 159. DOI: 10.1016/j.jhep.2021.08.029.