局部治疗联合系统治疗在肝细胞癌转化治疗中的价值

朱超凡; 王晓东

doi:10.12449/JCH240903

局部治疗联合系统治疗在肝细胞癌转化治疗中的价值

DOI: 10.12449/JCH240903

朱超凡,
王晓东^, ,

北京大学肿瘤医院暨北京市肿瘤防治研究所，介入治疗科，恶性肿瘤发病机制及转化研究教育部重点实验室，北京 100142

基金项目:

国家自然科学基金面上项目 (82172039);

北京市医院管理中心临床医学发展专项经费资助 (ZYLX202117);

北京市自然科学基金面上项目 (7212198)

利益冲突声明：本文不存在任何利益冲突。

作者贡献声明：朱超凡负责文献检索和分析及文章的撰写；王晓东负责文章的思路设计，文献深度分析及文章修改。

详细信息

通信作者:
王晓东， wangxd2003@pku.edu.cn （ORCID： 0000-0003-4727-9742）

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出版历程
- 收稿日期: 2024-07-15
- 录用日期: 2024-07-30
- 出版日期: 2024-09-25

Value of local treatment combined with systemic therapy in conversion therapy for hepatocellular carcinoma

Chaofan ZHU,
Xiaodong WANG^{,
,}

Key Laboratory of Pathogenesis and Transformation of Malignant Tumors，Ministry of Education，Department of Interventional Therapy，Peking University Cancer Hospital & Institute，Beijing 100142，China

Research funding:

General Project of National Natural Science Foundation of China (82172039);

Beijing Hospitals Authority Clinical Medicine Development of Special Funding Support (ZYLX202117);

Beijing Natural Science Foundation General Project (7212198)

More Information

Corresponding author: WANG Xiaodong， wangxd2003@pku.edu.cn （ORCID： 0000-0003-4727-9742）

摘要

摘要: 肝细胞癌是临床中最常见的恶性肿瘤之一。由于早期缺乏典型的临床表现，我国大多数患者确诊时已达中晚期，错失手术切除机会，预后较差。因此通过相关治疗手段将不可切除肝细胞癌转化为可切除肝细胞癌的探索十分必要。近年来，随着经动脉介入治疗、放射治疗技术等局部治疗的不断进步完善、新的靶向及免疫药物的临床应用，为肝细胞癌的转化治疗模式带来了新的机遇和挑战，而局部治疗联合系统治疗产生更好联合治疗作用，提高手术转化率。本文旨在对目前局部联合系统治疗在肝细胞癌转化治疗中的价值，为不可切除肝细胞癌的临床治疗提供参考。
- 癌，肝细胞 /
- 转化治疗 /
- 介入治疗 /
- 系统治疗 /
- 联合治疗
Abstract: Hepatocellular carcinoma （HCC） is one of the most common malignant tumors in clinical practice. Due to the lack of typical clinical manifestations in the early stage， most patients in China are in the advanced stage at the time of confirmed diagnosis and thus lose the opportunity for surgical resection， which leads to a poor prognosis. Therefore， it is necessary to explore related therapies for converting unresectable HCC into resectable HCC. In recent years， the improvement in local therapy such as transarterial interventional therapies and radiation therapy technology， together with the clinical application of new targeted therapies and immune checkpoint inhibitors， has brought new opportunities and challenges in the conversion therapy for advanced HCC， and local therapy combined with systemic therapy may have a good synergistic effect， improve the conversion rate of surgery. This article investigates the value of local therapy combined with systemic therapy in the conversion therapy for HCC， in order to provide a basis for the clinical treatment of unresectable HCC.
- Carcinoma， Hepatocellular /
- Conversion Therapy /
- Interventional therapy /
- Systemic therapy /
- Combination Therapy

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参考文献(35)

[1]	SUNG H, FERLAY J, SIEGEL RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2021, 71( 3): 209- 249. DOI: 10.3322/caac.21660.
[2]	ZHENG RS, CHEN R, HAN BF, et al. Cancer incidence and mortality in China, 2022[J]. Chin J Oncol, 2024, 46( 3): 221- 231. DOI: 10.3760/cma.j.cn112152-20240119-00035. 郑荣寿, 陈茹, 韩冰峰, 等. 2022年中国恶性肿瘤流行情况分析[J]. 中华肿瘤杂志, 2024, 46( 3): 221- 231. DOI: 10.3760/cma.j.cn112152-20240119-00035.
[3]	PARK JW, CHEN MS, COLOMBO M, et al. Global patterns of hepatocellular carcinoma management from diagnosis to death: The BRIDGE Study[J]. Liver Int, 2015, 35( 9): 2155- 2166. DOI: 10.1111/liv.12818.
[4]	GHOLAM PM, IYER R, JOHNSON MS. Multidisciplinary management of patients with unresectable hepatocellular carcinoma: A critical appraisal of current evidence[J]. Cancers, 2019, 11( 6): 873. DOI: 10.3390/cancers11060873.
[5]	FINN RS, IKEDA M, ZHU AX, et al. Phase Ib study of lenvatinib plus pembrolizumab in patients with unresectable hepatocellular carcinoma[J]. J Clin Oncol, 2020, 38( 26): 2960- 2970. DOI: 10.1200/JCO.20.00808.
[6]	HE MK, LIANG RB, ZHAO Y, et al. Lenvatinib, toripalimab, plus hepatic arterial infusion chemotherapy versus lenvatinib alone for advanced hepatocellular carcinoma[J]. Ther Adv Med Oncol, 2021, 13: 17588359211002720. DOI: 10.1177/17588359211002720.
[7]	KUDO M, FINN RS, QIN SK, et al. Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: A randomised phase 3 non-inferiority trial[J]. Lancet, 2018, 391( 10126): 1163- 1173. DOI: 10.1016/S0140-6736(18)30207-1.
[8]	FINN RS, QIN SK, IKEDA M, et al. Atezolizumab plus Bevacizumab in Unresectable Hepatocellular Carcinoma[J]. N Engl J Med, 2020, 382( 20): 1894- 1905. DOI: 10.1056/NEJMoa1915745.
[9]	LLOVET JM, KUDO M, MERLE P, et al. Lenvatinib plus pembrolizumab versus lenvatinib plus placebo for advanced hepatocellular carcinoma(LEAP-002): A randomised, double-blind, phase 3 trial[J]. Lancet Oncol, 2023, 24( 12): 1399- 1410. DOI: 10.1016/S1470-2045(23)00469-2.
[10]	SUN HC, ZHOU J, WANG Z, et al. Chinese expert consensus on conversion therapy for hepatocellular carcinoma(2021 edition)[J]. Hepatobiliary Surg Nutr, 2022, 11( 2): 227- 252. DOI: 10.21037/hbsn-21-328.
[11]	TANG HW, CAO YB, JIAN YP, et al. Conversion therapy with an immune checkpoint inhibitor and an antiangiogenic drug for advanced hepatocellular carcinoma: A review[J]. Biosci Trends, 2022, 16( 2): 130- 141. DOI: 10.5582/bst.2022.01019.
[12]	ARIZUMI T, UESHIMA K, IWANISHI M, et al. The overall survival of patients with hepatocellular carcinoma correlates with the newly defined time to progression after transarterial chemoembolization[J]. Liver Cancer, 2017, 6( 3): 227- 235. DOI: 10.1159/000475777.
[13]	WANG QH, XIA DD, BAI W, et al. Development of a prognostic score for recommended TACE candidates with hepatocellular carcinoma: A multicentre observational study[J]. J Hepatol, 2019, 70( 5): 893- 903. DOI: 10.1016/j.jhep.2019.01.013.
[14]	HU JG, BAO Q, CAO G, et al. Hepatic arterial infusion chemotherapy using oxaliplatin plus 5-fluorouracil versus transarterial chemoembolization/embolization for the treatment of advanced hepatocellular carcinoma with major portal vein tumor thrombosis[J]. Cardiovasc Intervent Radiol, 2020, 43( 7): 996- 1005. DOI: 10.1007/s00270-019-02406-3.
[15]	PENG ZW, FAN WZ, ZHU BW, et al. Lenvatinib combined with transarterial chemoembolization as first-line treatment for advanced hepatocellular carcinoma: A phase III, randomized clinical trial(LAUNCH)[J]. J Clin Oncol, 2023, 41( 1): 117- 127. DOI: 10.1200/JCO.22.00392.
[16]	CHEN S, WU ZQ, SHI F, et al. Lenvatinib plus TACE with or without pembrolizumab for the treatment of initially unresectable hepatocellular carcinoma harbouring PD-L1 expression: A retrospective study[J]. J Cancer Res Clin Oncol, 2022, 148( 8): 2115- 2125. DOI: 10.1007/s00432-021-03767-4.
[17]	QU WF, DING ZB, QU XD, et al. Conversion therapy for initially unresectable hepatocellular carcinoma using a combination of toripalimab, lenvatinib plus TACE: Real-world study[J]. BJS Open, 2022, 6( 5): zrac114. DOI: 10.1093/bjsopen/zrac114.
[18]	WU XK, YANG LF, CHEN YF, et al. Transcatheter arterial chemoembolisation combined with lenvatinib plus camrelizumab as conversion therapy for unresectable hepatocellular carcinoma: A single-arm, multicentre, prospective study[J]. EClinicalMedicine, 2024, 67: 102367. DOI: 10.1016/j.eclinm.2023.102367.
[19]	WU JY, ZHANG ZB, ZHOU JY, et al. Outcomes of salvage surgery for initially unresectable hepatocellular carcinoma converted by transcatheter arterial chemoembolization combined with lenvatinib plus anti-PD-1 antibodies: A multicenter retrospective study[J]. Liver Cancer, 2023, 12( 3): 229- 237. DOI: 10.1159/000528356.
[20]	LI XZ, CHEN J, WANG XB, et al. Outcomes and prognostic factors in initially unresectable hepatocellular carcinoma treated using conversion therapy with lenvatinib and TACE plus PD-1 inhibitors[J]. Front Oncol, 2023, 13: 1110689. DOI: 10.3389/fonc.2023.1110689.
[21]	OU XY, WU JY, WU JY, et al. Efficacy of lenvatinib combined with anti-PD-1 antibodies plus transcatheter arterial chemoembolization for hepatocellular carcinoma with portal vein tumor Thrombus: A retrospective, multicenter study[J]. Cancer Res Treat, 2024. DOI: 10.4143/crt.2023.1165.
[22]	LENCIONI R, KUDO M, ERINJERI J, et al. EMERALD-1: A phase 3, randomized, placebo-controlled study of transarterial chemoembolization combined with durvalumab with or without bevacizumab in participants with unresectable hepatocellular carcinoma eligible for embolization[J]. J Clin Oncol, 2024, 42( 3_suppl): LBA432. DOI: 10.1200/jco.2024.42.3_suppl.lba432.
[23]	HE MK, LI QJ, ZOU RH, et al. Sorafenib plus hepatic arterial infusion of oxaliplatin, fluorouracil, and leucovorin vs sorafenib alone for hepatocellular carcinoma with portal vein invasion: A randomized clinical trial[J]. JAMA Oncol, 2019, 5( 7): 953- 960. DOI: 10.1001/jamaoncol.2019.0250.
[24]	ZHENG KL, ZHU X, FU SJ, et al. Sorafenib plus hepatic arterial infusion chemotherapy versus sorafenib for hepatocellular carcinoma with major portal vein tumor thrombosis: A randomized trial[J]. Radiology, 2022, 303( 2): 455- 464. DOI: 10.1148/radiol.211545.
[25]	LIU DM, MU H, LIU CF, et al. Sintilimab, bevacizumab biosimilar, and HAIC for unresectable hepatocellular carcinoma conversion therapy: A prospective, single-arm phase II trial[J]. Neoplasma, 2023, 70( 6): 811- 818. DOI: 10.4149/neo_2023_230806N413.
[26]	ZHANG JL, ZHANG XH, MU H, et al. Surgical conversion for initially unresectable locally advanced hepatocellular carcinoma using a triple combination of angiogenesis inhibitors, anti-PD-1 antibodies, and hepatic arterial infusion chemotherapy: A retrospective study[J]. Front Oncol, 2021, 11: 729764. DOI: 10.3389/fonc.2021.729764.
[27]	LUO LH, XIAO YQ, ZHU GQ, et al. Hepatic arterial infusion chemotherapy combined with PD-1 inhibitors and tyrosine kinase inhibitors for unresectable hepatocellular carcinoma: A tertiary medical center experience[J]. Front Oncol, 2022, 12: 1004652. DOI: 10.3389/fonc.2022.1004652.
[28]	ZHAO WC, LIU C, WU YT, et al. Transarterial chemoembolization(TACE)-hepatic arterial infusion chemotherapy(HAIC) combined with PD-1 inhibitors plus lenvatinib as a preoperative conversion therapy for nonmetastatic advanced hepatocellular carcinoma: A single center experience[J]. Transl Cancer Res, 2024, 13( 5): 2315- 2331. DOI: 10.21037/tcr-24-93.
[29]	GABR A, RIAZ A, JOHNSON GE, et al. Correlation of Y90-absorbed radiation dose to pathological necrosis in hepatocellular carcinoma: Confirmatory multicenter analysis in 45 explants[J]. Eur J Nucl Med Mol Imaging, 2021, 48( 2): 580- 583. DOI: 10.1007/s00259-020-04976-8.
[30]	GABR A, RIAZ A, MOULI S, et al. Modified radiation lobectomy: An evolving paradigm to convert patients to liver resection candidacy[J]. Semin Intervent Radiol, 2019, 36( 4): 343- 348. DOI: 10.1055/s-0039-1696648.
[31]	RICKE J, KLÜMPEN HJ, AMTHAUER H, et al. Impact of combined selective internal radiation therapy and sorafenib on survival in advanced hepatocellular carcinoma[J]. J Hepatol, 2019, 71( 6): 1164- 1174. DOI: 10.1016/j.jhep.2019.08.006.
[32]	KAYA NA, TAI D, LIM X, et al. Multimodal molecular landscape of response to Y⁹⁰-resin microsphere radioembolization followed by nivolumab for advanced hepatocellular carcinoma[J]. J Immunother Cancer, 2023, 11( 8): e007106. DOI: 10.1136/jitc-2023-007106.
[33]	LEE YB, NAM JY, CHO EJ, et al. A phase I/IIa trial of yttrium-90 radioembolization in combination with durvalumab for locally advanced unresectable hepatocellular carcinoma[J]. Clin Cancer Res, 2023, 29( 18): 3650- 3658. DOI: 10.1158/1078-0432.CCR-23-0581.
[34]	CHIANG CL, CHIU KWH, CHAN KSK, et al. Sequential transarterial chemoembolisation and stereotactic body radiotherapy followed by immunotherapy as conversion therapy for patients with locally advanced, unresectable hepatocellular carcinoma(START-FIT): A single-arm, phase 2 trial[J]. Lancet Gastroenterol Hepatol, 2023, 8( 2): 169- 178. DOI: 10.1016/S2468-1253(22)00339-9.
[35]	LIANG XX, JIANG YH, YAO W, et al. Liver-directed moderately hypo-fractionated radiotherapy combined with pembrolizumab and bevacizumab for advanced hepatocellular carcinoma: A retrospective observational study of 23 cases[J]. Transl Cancer Res, 2024, 13( 3): 1508- 1518. DOI: 10.21037/tcr-23-1333.