中晚期肝细胞癌的局部治疗联合系统治疗研究进展

曹白露; 艾敏; 黄平; 杨永峰

doi:10.3969/j.issn.1001-5256.2023.08.031

中晚期肝细胞癌的局部治疗联合系统治疗研究进展

DOI: 10.3969/j.issn.1001-5256.2023.08.031

南京中医药大学附属南京医院(南京市第二医院)肝病科，南京 210003

基金项目:

江苏省卫健委重点科研项目 (ZD2021061)

利益冲突声明：本文不存在任何利益冲突。

作者贡献声明：曹白露负责起草文稿；艾敏负责修改文稿；黄平负责批判性审阅文稿；杨永峰负责构思与指导写作。

详细信息

通信作者:
杨永峰，yyf1979@163.com (ORCID: 0000-0002-0942-4833)

计量
- 文章访问数: 330
- HTML全文浏览量: 69
- PDF下载量: 99
- 被引次数: 0
出版历程
- 收稿日期: 2022-11-08
- 录用日期: 2022-12-12
- 出版日期: 2023-08-20

Research advances in local treatment combined with systemic therapy for advanced hepatocellular carcinoma

Department of Hepatology, Nanjing Hospital Affiliated to Nanjing University of Chinese Medicine & Nanjing Second Hospital, Nanjing 210003, China

Research funding:

Key Program of Jiangsu Commision of Health (ZD2021061)

More Information

Corresponding author: YANG Yongfeng, yyf1979@163.com (ORCID: 0000-0002-0942-4833)

摘要

摘要: 我国大部分肝细胞癌患者就诊时已处于疾病的中晚期阶段，单一治疗方案客观缓解率较低，而联合治疗明显提高了中晚期肝细胞癌患者的客观缓解率, 延长了患者的生存期。本文就近年来中晚期肝细胞癌局部治疗联合系统治疗的最新研究进展进行详细阐述。
- 癌, 肝细胞 /
- 化学栓塞, 治疗性 /
- 分子靶向治疗
Abstract: Most patients with hepatocellular carcinoma (HCC) have reached the advanced stage at the time of diagnosis in China, and a single treatment regimen tends to have a low objective response rate (ORR), while combined therapy can significantly increase the ORR of patients with advanced HCC and prolong their survival time. The article elaborates on the latest research advances in the efficacy of local treatment combined with systemic therapy for advanced HCC.
- Carcinoma, Hepatocellular /
- Chemoembolization, Therapeutic /
- Molecular Targeted Therapy

HTML全文

参考文献(35)

[1]	JEMAL A, WARD EM, JOHNSON CJ, et al. Annual report to the nation on the status of cancer, 1975-2014, featuring survival[J]. J Natl Cancer Inst, 2017, 109(9): djx030. DOI: 10.1093/jnci/djx030.
[2]	KUANG M. Advances in neoadjuvant therapy for hepatocellular carcinoma[J]. Chin J Dig Surg, 2023, 22(2): 202-208. DOI: 10.3760/cma.j.cn115610-20221203-00728. 匡铭. 肝细胞癌新辅助治疗研究进展[J]. 中华消化外科杂志, 2023, 22(2): 202-208. DOI: 10.3760/cma.j.cn115610-20221203-00728.
[3]	LIU YY. New progress of hepatocellular carcinoma treatment[J]. Chin J Dig Surg, 2022, 21(1): 15-18. DOI: 10.3760/cma.j.cn115610-20220107-00020. 刘允怡. 肝细胞癌治疗的新发展[J]. 中华消化外科杂志, 2022, 21(1): 15-18. DOI: 10.3760/cma.j.cn115610-20220107-00020.
[4]	XUE J, NI H, WANG F, et al. Advances in locoregional therapy for hepatocellular carcinoma combined with immunotherapy and targeted therapy[J]. J Interv Med, 2021, 4(3): 105-113. DOI: 10.1016/j.jimed.2021.05.002.
[5]	KUDO M, UESHIMA K, IKEDA M, et al. Randomised, multicentre prospective trial of transarterial chemoembolisation (TACE) plus sorafenib as compared with TACE alone in patients with hepatocellular carcinoma: TACTICS trial[J]. Gut, 2020, 69(8): 1492-1501. DOI: 10.1136/gutjnl-2019-318934.
[6]	LIU J, XU J, ZHANG W, et al. Safety and efficacy of drug-eluting bead transarterial chemoembolization combined with apatinib in patients with advanced hepatocellular carcinoma[J]. Acad Radiol, 2020, 27(5): 704-709. DOI: 10.1016/j.acra.2019.07.003.
[7]	PINTER M, ULBRICH G, SIEGHART W, et al. Hepatocellular carcinoma: A phase ii randomized controlled double-blind trial of transarterial chemoembolization in combination with biweekly intravenous administration of bevacizumab or a placebo[J]. Radiology, 2015, 277(3): 903-912. DOI: 10.1148/radiol.2015142140.
[8]	ZHANG H, CAO G, REN W, et al. Vascular normalization therapy with targeted localized vessel bevacizumab infusion in hepatocellular carcinoma after transarterial chemoembolization failure[J]. Ann Palliat Med, 2021, 10(8): 9149-9156. DOI: 10.21037/apm-21-2123.
[9]	MARINELLI B, KIM E, D'ALESSIO A, et al. Integrated use of PD-1 inhibition and transarterial chemoembolization for hepatocellular carcinoma: evaluation of safety and efficacy in a retrospective, propensity score-matched study[J]. J Immunother Cancer, 2022, 10(6): e004205. DOI: 10.1136/jitc-2021-004205.
[10]	MARINELLI B, KIM E, D'ALESSIO A, et al. Integrated use of PD-1 inhibition and transarterial chemoembolization for hepatocellular carcinoma: evaluation of safety and efficacy in a retrospective, propensity score-matched study[J]. J Immunother Cancer, 2022, 10(6): e004205. DOI: 10.1136/jitc-2021-004205.
[11]	PFISTER D, NÚÑEZ NG, PINYOL R, et al. NASH limits anti-tumour surveillance in immunotherapy-treated HCC[J]. Nature, 2021, 592(7854): 450-456. DOI: 10.1038/s41586-021-03362-0.
[12]	XIANG YJ, WANG K, YU HM, et al. Transarterial chemoembolization plus a PD-1 inhibitor with or without lenvatinib for intermediate-stage hepatocellular carcinoma[J]. Hepatol Res, 2022, 52(8): 721-729. DOI: 10.1111/hepr.13773.
[13]	CAO F, YANG Y, SI T, et al. The efficacy of TACE combined with lenvatinib plus sintilimab in unresectable hepatocellular carcinoma: a multicenter retrospective study[J]. Front Oncol, 2021, 11: 783480. DOI: 10.3389/fonc.2021.783480.
[14]	LI X, FU Z, CHEN X, et al. Efficacy and safety of lenvatinib combined with PD-1 inhibitors plus tace for unresectable hepatocellular carcinoma patients in china real-world[J]. Front Oncol, 2022, 12: 950266. DOI: 10.3389/fonc.2022.950266.
[15]	LLOVET JM, VOGEL A, MADOFF DC, et al. Randomized phase 3 LEAP-012 study: transarterial chemoembolization with or without lenvatinib plus pembrolizumab for intermediate-stage hepatocellular carcinoma not amenable to curative treatment[J]. Cardiovasc Intervent Radiol, 2022, 45(4): 405-412. DOI: 10.1007/s00270-021-03031-9.
[16]	CHOI JH, CHUNG WJ, BAE SH, et al. Randomized, prospective, comparative study on the effects and safety of sorafenib vs. hepatic arterial infusion chemotherapy in patients with advanced hepatocellular carcinoma with portal vein tumor thrombosis[J]. Cancer Chemother Pharmacol, 2018, 82(3): 469-478. DOI: 10.1007/s00280-018-3638-0.
[17]	HE M, LI Q, ZOU R, 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.
[18]	YAMAMOTO S, ONISHI H, TAKAKI A, et al. The early decline of α-fetoprotein and des-γ-carboxy prothrombin predicts the response of hepatic arterial infusion chemotherapy in hepatocellular carcinoma patients[J]. Gastrointest Tumors, 2020, 7(3): 83-92. DOI: 10.1159/000506941.
[19]	MEI J, LI SH, LI QJ, et al. Anti-PD-1 immunotherapy improves the efficacy of hepatic artery infusion chemotherapy in advanced hepatocellular carcinoma[J]. J Hepatocell Carcinoma, 2021, 8: 167-176. DOI: 10.2147/JHC.S298538.
[20]	YI X, FU Y, LONG Q, et al. Myosteatosis can predict unfavorable outcomes in advanced hepatocellular carcinoma patients treated with hepatic artery infusion chemotherapy and Anti-PD-1 immunotherapy[J]. Front Oncol, 2022, 12: 892192. DOI: 10.3389/fonc.2022.892192.
[21]	LIU BJ, GAO S, ZHU X, et al. Real-world study of hepatic artery infusion chemotherapy combined with anti-PD-1 immunotherapy and tyrosine kinase inhibitors for advanced hepatocellular carcinoma[J]. Immunotherapy, 2021, 13(17): 1395-1405. DOI: 10.2217/imt-2021-0192.
[22]	CHEN S, XU B, WU Z, et al. Pembrolizumab plus lenvatinib with or without hepatic arterial infusion chemotherapy in selected populations of patients with treatment-naive unresectable hepatocellular carcinoma exhibiting PD-L1 staining: a multicenter retrospective study[J]. BMC Cancer, 2021, 21(1): 1126. DOI: 10.1186/s12885-021-08858-6.
[23]	MEHTA A, OKLU R, SHETH RA. Thermal ablative therapies and immune checkpoint modulation: can locoregional approaches effect a systemic response?[J]. Gastroenterol Res Pract, 2016, 2016: 9251375. DOI: 10.1155/2016/9251375.
[24]	KAN X, JING Y, WAN QY, et al. Sorafenib combined with percutaneous radiofrequency ablation for the treatment of medium-sized hepatocellular carcinoma[J]. Eur Rev Med Pharmacol Sci, 2015, 19(2): 247-255.
[25]	BRUIX J, TAKAYAMA T, MAZZAFERRO V, et al. Adjuvant sorafenib for hepatocellular carcinoma after resection or ablation (STORM): a phase 3, randomised, double-blind, placebo-controlled trial[J]. Lancet Oncol, 2015, 16(13): 1344-1354. DOI: 10.1016/S1470-2045(15)00198-9.
[26]	DUFFY AG, ULAHANNAN SV, MAKOROVA-RUSHER O, et al. Tremelimumab in combination with ablation in patients with advanced hepatocellular carcinoma[J]. J Hepatol, 2017, 66(3): 545-551. DOI: 10.1016/j.jhep.2016.10.029.
[27]	WANG X, LIU G, CHEN S, et al. Combination therapy with PD-1 blockade and radiofrequency ablation for recurrent hepatocellular carcinoma: a propensity score matching analysis[J]. Int J Hyperthermia, 2021, 38(1): 1519-1528. DOI: 10.1080/02656736.2021.1991011.
[28]	LIU CM, HUANG BS, YEN YH, et al. Concurrent sorafenib and radiotherapy versus radiotherapy alone for locally advanced hepatocellular carcinoma: a propensity-matched analysis[J]. J Hepatocell Carcinoma, 2021, 8: 963-973. DOI: 10.2147/JHC.S323302.
[29]	FACCIORUSSO A, PAOLILLO R, TARTAGLIA N, et al. Efficacy of combined transarterial radioembolization and sorafenib in the treatment of hepatocarcinoma: A meta-analysis[J]. Dig Liver Dis, 2022, 54(3): 316-323. DOI: 10.1016/j.dld.2021.06.003.
[30]	ABULIMITI M, LI Z, WANG H, et al. Combination intensity-modulated radiotherapy and sorafenib improves outcomes in hepatocellular carcinoma with portal vein tumor thrombosis[J]. J Oncol, 2021, 2021: 9943683. DOI: 10.1155/2021/9943683.
[31]	EDELINE J, CROUZET L, CAMPILLO-GIMENEZ B, et al. Selective internal radiation therapy compared with sorafenib for hepatocellular carcinoma with portal vein thrombosis[J]. Eur J Nucl Med Mol Imaging, 2016, 43(4): 635-643. DOI: 10.1007/s00259-015-3210-7.
[32]	QASEEM Y, SALEM R. Observing durable responses and a prolonged survival tail in advanced hepatocellular carcinoma with portal vein invasion treated with Y90 radioembolization[J]. Cardiovasc Intervent Radiol, 2020, 43(9): 1423-1424. DOI: 10.1007/s00270-020-02541-2.
[33]	CHIANG CL, CHAN A, CHIU K, et al. Combined stereotactic body radiotherapy and checkpoint inhibition in unresectable hepatocellular carcinoma: a potential synergistic treatment strategy[J]. Front Oncol, 2019, 9: 1157. DOI: 10.3389/fonc.2019.01157.
[34]	ZHAN C, RUOHONIEMI D, SHANBHOGUE KP, et al. Safety of combined yttrium-90 radioembolization and immune checkpoint inhibitor immunotherapy for hepatocellular carcinoma[J]. J Vasc Interv Radiol, 2020, 31(1): 25-34. DOI: 10.1016/j.jvir.2019.05.023.
[35]	TAI D, LOKE K, GOGNA A, et al. Radioembolisation with Y90-resin microspheres followed by nivolumab for advanced hepatocellular carcinoma (CA 209-678): a single arm, single centre, phase 2 trial[J]. Lancet Gastroenterol Hepatol, 2021, 6(12): 1025-1035. DOI: 10.1016/S2468-1253(21)00305-8.