肝细胞癌转化治疗的策略及实践
DOI: 10.12449/JCH240902
利益冲突声明:本文不存在任何利益冲突。
作者贡献声明:马驰负责设计论文框架及起草;谭广负责论文修改,拟定写作思路,指导撰写并最后定稿。
-
摘要: 原发性肝癌因发病隐匿及预后较差,多数初始诊断即为不可切除。近些年,随着靶向治疗、免疫治疗及局部治疗等转化治疗方案的兴起,部分中晚期肝癌患者成功转化并行根治性手术切除,但同时也带来了诸多问题,如潜在转化人群的界定、转化方案的选择、转化后手术切除的必要性及时机、转化手术后辅助治疗的必要性及持续时间等。本文将结合笔者的自身经验,针对肝癌转化治疗中上述问题进行探讨。Abstract: Due to the insidious onset and poor prognosis of primary liver cancer, most patients are found to have unresectable primary liver cancer at initial diagnosis. In recent years, with the advent of targeted therapy, immunotherapy, and local therapy, some patients with advanced liver cancer have achieved successful conversion and undergone radical surgical resection, but at the same time, such treatment has brought many issues, such as the identification of potential population for conversion, the selection of conversion regimen, the necessity and timing of surgical resection after conversion, and the necessity and duration of adjuvant therapy after conversion surgery. This article discusses the above problems in conversion therapy for liver cancer based on the author’s own experience.
-
[1] 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. [2] VILLANUEVA A. Hepatocellular carcinoma[J]. N Engl J Med, 2019, 380( 15): 1450- 1462. DOI: 10.1056/nejmra1713263. [3] 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. [4] NAGINO M, KANAI M, MORIOKA A, et al. Portal and arterial embolization before extensive liver resection in patients with markedly poor functional reserve[J]. J Vasc Interv Radiol, 2000, 11( 8): 1063- 1068. DOI: 10.1016/s1051-0443(07)61340-2. [5] SCHWAB ME, DECKER HC, MONTO A, et al. Portal vein thrombosis after transarterial embolization for hepatocellular carcinoma[J]. JAMA Surg, 2024, 159( 3): 345- 347. DOI: 10.1001/jamasurg.2023.5909. [6] CHAN A, ZHANG WY, CHOK K, et al. ALPPS versus portal vein embolization for hepatitis-related hepatocellular carcinoma: A changing paradigm in modulation of future liver remnant before major hepatectomy[J]. Ann Surg, 2021, 273( 5): 957- 965. DOI: 10.1097/SLA.0000000000003433. [7] MATSUO K, MURAKAMI T, KAWAGUCHI D, et al. Histologic features after surgery associating liver partition and portal vein ligation for staged hepatectomy versus those after hepatectomy with portal vein embolization[J]. Surgery, 2016, 159( 5): 1289- 1298. DOI: 10.1016/j.surg.2015.12.004. [8] GUIU B, HERRERO A, PANARO F. Liver venous deprivation: A bright future for liver metastases-but what about hepatocellular carcinoma?[J]. Hepatobiliary Surg Nutr, 2021, 10( 2): 270- 272. DOI: 10.21037/hbsn-21-7. [9] CHEBARO A, BUC E, DURIN T, et al. Liver venous deprivation or associating liver partition and portal vein ligation for staged hepatectomy?: A retrospective multicentric study[J]. Ann Surg, 2021, 274( 5): 874- 880. DOI: 10.1097/SLA.0000000000005121. [10] CHAOUCH MA, MAZZOTTA A, COSTA AC DA, et al. A systematic review and meta-analysis of liver venous deprivation versus portal vein embolization before hepatectomy: Future liver volume, postoperative outcomes, and oncological safety[J]. Front Med, 2023, 10: 1334661. DOI: 10.3389/fmed.2023.1334661. [11] YANG C, ZHANG HL, ZHANG LM, et al. Evolving therapeutic landscape of advanced hepatocellular carcinoma[J]. Nat Rev Gastroenterol Hepatol, 2023, 20( 4): 203- 222. DOI: 10.1038/s41575-022-00704-9. [12] QIN SK, BI F, GU SZ, et al. Donafenib versus sorafenib in first-line treatment of unresectable or metastatic hepatocellular carcinoma: A randomized, open-label, parallel-controlled phase II-III trial[J]. J Clin Oncol, 2021, 39( 27): 3002- 3011. DOI: 10.1200/JCO.21.00163. [13] QIN SK, LI Q, GU SZ, et al. Apatinib as second-line or later therapy in patients with advanced hepatocellular carcinoma(AHELP): A multicentre, double-blind, randomised, placebo-controlled, phase 3 trial[J]. Lancet Gastroenterol Hepatol, 2021, 6( 7): 559- 568. DOI: 10.1016/S2468-1253(21)00109-6. [14] National Health Commission of the People’s Republic of China. Standard for diagnosis and treatment of primary liver cancer(2024 edition)[J]. J Clin Hepatol, 2024, 40( 5): 893- 918. DOI: 10.12449/JCH240508.中华人民共和国国家卫生健康委员会. 原发性肝癌诊疗指南(2024年版)[J]. 临床肝胆病杂志, 2024, 40( 5): 893- 918. DOI: 10.12449/JCH240508. [15] 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. [16] KUDO M, AOKI T, UESHIMA K, et al. Achievement of complete response and drug-free status by Atezolizumab plus Bevacizumab combined with or without curative conversion in patients with transarterial chemoembolization-unsuitable, intermediate-stage hepatocellular carcinoma: A multicenter proof-of-concept study[J]. Liver Cancer, 2023, 12( 4): 321- 338. DOI: 10.1159/000529574. [17] ZHU XD, HUANG C, SHEN YH, et al. Downstaging and resection of initially unresectable hepatocellular carcinoma with tyrosine kinase inhibitor and anti-PD-1 antibody combinations[J]. Liver Cancer, 2021, 10( 4): 320- 329. DOI: 10.1159/000514313. [18] GORDAN JD, KENNEDY EB, ABOU-ALFA GK, et al. Systemic therapy for advanced hepatocellular carcinoma: ASCO guideline update[J]. J Clin Oncol, 2024, 42( 15): 1830- 1850. DOI: 10.1200/JCO.23.02745. [19] TAKEDA H, NISHIJIMA N, NASU A, et al. Long-term antitumor effect of lenvatinib on unresectable hepatocellular carcinoma with portal vein invasion[J]. Hepatol Res, 2019, 49( 5): 594- 599. DOI: 10.1111/hepr.13294. [20] HIDAKA M, HARA T, SOYAMA A, et al. The outcome of conversion liver resection surgery by lenvatinib treatment: A single center experience[J]. Anticancer Res, 2022, 42( 6): 3049- 3054. DOI: 10.21873/anticanres.15791. [21] 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. [22] 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. [23] FAIVRE S, RIMASSA L, FINN RS. Molecular therapies for HCC: Looking outside the box[J]. J Hepatol, 2020, 72( 2): 342- 352. DOI: 10.1016/j.jhep.2019.09.010. [24] ZHANG B, TAO BR, LI YT, et al. Dual immune checkpoint inhibitors or combined with anti-VEGF agents in advanced, unresectable hepatocellular carcinoma[J]. Eur J Intern Med, 2023, 111: 37- 46. DOI: 10.1016/j.ejim.2022.12.025. [25] FULGENZI CAM, SCHEINER B, KOROLEWICZ J, et al. Efficacy and safety of frontline systemic therapy for advanced HCC: A network meta-analysis of landmark phase III trials[J]. JHEP Rep, 2023, 5( 5): 100702. DOI: 10.1016/j.jhepr.2023.100702. [26] CELSA C, CABIBBO G, PINATO DJ, et al. Balancing efficacy and tolerability of first-line systemic therapies for advanced hepatocellular carcinoma: A network meta-analysis[J]. Liver Cancer, 2024, 13( 2): 169- 180. DOI: 10.1159/000531744. [27] 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. [28] KUDO M, UESHIMA K, SAEKI I, et al. A phase 2, prospective, multicenter, single-arm trial of transarterial chemoembolization therapy in combination strategy with lenvatinib in patients with unresectable intermediate-stage hepatocellular carcinoma: TACTICS-L trial[J]. Liver Cancer, 2024, 13( 1): 99- 112. DOI: 10.1159/000531377. [29] 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. [30] LEE WH, BYUN HK, CHOI JS, et al. Liver-directed combined radiotherapy as a bridge to curative surgery in locally advanced hepatocellular carcinoma beyond the Milan criteria[J]. Radiother Oncol, 2020, 152: 1- 7. DOI: 10.1016/j.radonc.2020.07.046. [31] 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. [32] 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. [33] LIU JF, LI Z, ZHANG WG, et al. Comprehensive treatment of trans-arterial chemoembolization plus lenvatinib followed by camrelizumab for advanced hepatocellular carcinoma patients[J]. Front Pharmacol, 2021, 12: 709060. DOI: 10.3389/fphar.2021.709060. [34] 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. [35] MA YN, JIANG XM, LIU H, et al. Conversion therapy for initially unresectable hepatocellular carcinoma: Current status and prospects[J]. Biosci Trends, 2024, 17( 6): 415- 426. DOI: 10.5582/bst.2023.01322. [36] KE Q, XIN FL, FANG HP, et al. The significance of transarterial chemo(embolization) combined with tyrosine kinase inhibitors and immune checkpoint inhibitors for unresectable hepatocellular carcinoma in the era of systemic therapy: A systematic review[J]. Front Immunol, 2022, 13: 913464. DOI: 10.3389/fimmu.2022.913464. [37] ZHANG XY, ZHU XR, LIU C, et al. The safety and efficacy of transarterial chemoembolization(TACE)+lenvatinib+programmed cell death protein 1(PD-1) antibody of advanced unresectable hepatocellular carcinoma[J]. J Clin Oncol, 2022, 40( 4_suppl): 453. DOI: 10.1200/jco.2022.40.4_suppl.453. [38] 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
本文二维码
计量
- 文章访问数: 229
- HTML全文浏览量: 2017
- PDF下载量: 71
- 被引次数: 0