转移性肝癌的治疗现状与展望

王祥宇; 陈进宏

doi:10.12449/JCH240701

转移性肝癌的治疗现状与展望

DOI: 10.12449/JCH240701

王祥宇,
陈进宏^, ,

复旦大学附属华山医院普外科肝胆外科中心，上海 200040

基金项目:

上海市“科技创新行动计划”优秀学术带头人计划项目 (22XD1400300)

利益冲突声明：本文不存在任何利益冲突。

作者贡献声明：王祥宇负责收集数据，资料分析，撰写论文；陈进宏负责课题设计，拟定写作思路，指导撰写文章，修改论文并最后定稿。

详细信息

通信作者:
陈进宏， jinhongch@hotmail.com （ORCID： 0000-0003-0952-9990）

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出版历程
- 收稿日期: 2024-04-22
- 录用日期: 2024-05-17
- 出版日期: 2024-07-25

Treatment of metastatic liver cancer： Current status and future perspectives

Xiangyu WANG,
Jinhong CHEN^{,
,}

Center of Hepatobiliary Surgery，Department of General Surgery，Huashan Hospital，Fudan University，Shanghai 200040，China

Research funding:

Excellent Academic Leader Project of Shanghai “Science and Technology Innovation Action Plan” (22XD1400300)

More Information

Corresponding author: CHEN Jinhong， jinhongch@hotmail.com （ORCID： 0000-0003-0952-9990）

摘要

摘要: 肝脏是恶性肿瘤最常见的转移部位之一，肝转移也是转移性肿瘤的主要致死原因。转移性肝癌具有高度异质性，长期以来临床治疗进展缓慢。近年来，随着外科技术的提高、系统治疗的进步及多学科团队诊疗模式的开展，转移性肝癌的临床治疗发生了革命性的变化。本文从外科治疗、系统治疗及局部区域治疗三个方面回顾了近年来转移性肝癌临床治疗进展。以化疗、靶向与免疫治疗为基础的联合疗法仍是转移性肝癌综合治疗的基础，而外科治疗的价值也在部分寡转移患者中得到证实。另外，局部区域治疗的发展为转移性肝癌患者带来新的治疗选择。基于高级别循证医学证据及相关指南的规范化诊疗，及多学科团队指导下的个体化精准治疗，将是未来转移性肝癌临床治疗的发展方向。
- 肿瘤转移 /
- 肝 /
- 治疗学
Abstract: The liver is a common metastatic site of malignant tumors， and liver metastasis is also the leading cause of death due to metastatic tumors. Metastatic liver cancer has high heterogeneity， and there has been slow progress in the treatment of metastatic liver cancer for a long time. In recent years， the development of surgical techniques， systemic therapy， and the multidisciplinary team （MDT） diagnostic and therapeutic mode has led to revolutionary changes in the clinical management of metastatic liver cancer. The article reviews the recent progress in the treatment of metastatic liver cancer from the three aspects of surgical treatment， systemic therapy， and locoregional therapy. Combined therapy based on chemotherapy， targeted therapy， and immunotherapy remains the basic multimodality therapy for metastatic liver cancer. In addition， the development of locoregional therapy has brought new treatment options for patients with metastatic liver cancer. Standardized diagnosis and treatment based on high-level evidence-based evidence and related guidelines and individualized precise treatment under the guidance of MDT will be the future directions for the clinical management of metastatic liver cancer.
- Neoplasm Metastasis /
- Liver /
- Therapeutics

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参考文献(45)

[1]	TSILIMIGRAS DI, BRODT P, CLAVIEN PA, et al. Liver metastases[J]. Nat Rev Dis Primers, 2021, 7( 1): 27. DOI: 10.1038/s41572-021-00261-6.
[2]	HALLEMEIER CL, SHARMA N, ANKER C, et al. American Radium Society Appropriate Use Criteria for the use of liver-directed therapies for nonsurgical management of liver metastases: Systematic review and guidelines[J]. Cancer, 2023, 129( 20): 3193- 3212. DOI: 10.1002/cncr.34931.
[3]	WAGNER JS, ADSON MA, van HEERDEN JA, et al. The natural history of hepatic metastases from colorectal cancer. A comparison with resective treatment[J]. Ann Surg, 1984, 199( 5): 502- 508. DOI: 10.1097/00000658-198405000-00002.
[4]	CERVANTES A, ADAM R, ROSELLÓ S, et al. Metastatic colorectal cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up[J]. Ann Oncol, 2023, 34( 1): 10- 32. DOI: 10.1016/j.annonc.2022.10.003.
[5]	FAIRWEATHER M, SWANSON R, WANG JP, et al. Management of neuroendocrine tumor liver metastases: Long-term outcomes and prognostic factors from a large prospective database[J]. Ann Surg Oncol, 2017, 24( 8): 2319- 2325. DOI: 10.1245/s10434-017-5839-x.
[6]	KUNZ PL, REIDY-LAGUNES D, ANTHONY LB, et al. Consensus guidelines for the management and treatment of neuroendocrine tumors[J]. Pancreas, 2013, 42( 4): 557- 577. DOI: 10.1097/MPA.0b013e31828e34a4.
[7]	PAVEL M, BAUDIN E, COUVELARD A, et al. ENETS Consensus Guidelines for the management of patients with liver and other distant metastases from neuroendocrine neoplasms of foregut, midgut, hindgut, and unknown primary[J]. Neuroendocrinology, 2012, 95( 2): 157- 176. DOI: 10.1159/000335597.
[8]	GAO YH, XI HQ, SHANG L, et al. Clinical landscape and prognosis of patients with gastric cancer liver metastases: A nation-wide multicenter cohort study in China(RECORD study)[J]. Sci Bull(Beijing), 2024, 69( 3): 303- 307. DOI: 10.1016/j.scib.2023.12.024.
[9]	GRANIERI S, ALTOMARE M, BRUNO F, et al. Surgical treatment of gastric cancer liver metastases: Systematic review and meta-analysis of long-term outcomes and prognostic factors[J]. Crit Rev Oncol Hematol, 2021, 163: 103313. DOI: 10.1016/j.critrevonc.2021.103313.
[10]	MASUDA Y, YEO MHX, SYN NL, et al. Surgery for liver metastases from primary breast cancer: A reconstructed individual patient data meta-analysis[J]. Eur J Surg Oncol, 2024, 50( 1): 107277. DOI: 10.1016/j.ejso.2023.107277.
[11]	MAZZAFERRO V, SPOSITO C, COPPA J, et al. The long-term benefit of liver transplantation for hepatic metastases from neuroendocrine tumors[J]. Am J Transplant, 2016, 16( 10): 2892- 2902. DOI: 10.1111/ajt.13831.
[12]	MAZZAFERRO V, PULVIRENTI A, COPPA J. Neuroendocrine tumors metastatic to the liver: How to select patients for liver transplantation?[J]. J Hepatol, 2007, 47( 4): 460- 466. DOI: 10.1016/j.jhep.2007.07.004.
[13]	ESHMUMINOV D, STUDER DJ, LOPEZ LOPEZ V, et al. Controversy over liver transplantation or resection for neuroendocrine liver metastasis: Tumor biology cuts the deal[J]. Ann Surg, 2023, 277( 5): e1063- e1071. DOI: 10.1097/SLA.0000000000005663.
[14]	O’TOOLE D, KIANMANESH R, CAPLIN M. ENETS 2016 consensus guidelines for the management of patients with digestive neuroendocrine tumors: An update[J]. Neuroendocrinology, 2016, 103( 2): 117- 118. DOI: 10.1159/000443169.
[15]	MÜHLBACHER F, HUK I, STEININGER R, et al. Is orthotopic liver transplantation a feasible treatment for secondary cancer of the liver?[J]. Transplant Proc, 1991, 23( 1 Pt 2): 1567- 1568.
[16]	HAGNESS M, FOSS A, LINE PD, et al. Liver transplantation for nonresectable liver metastases from colorectal cancer[J]. Ann Surg, 2013, 257( 5): 800- 806. DOI: 10.1097/SLA.0b013e3182823957.
[17]	DUELAND S, GUREN TK, HAGNESS M, et al. Chemotherapy or liver transplantation for nonresectable liver metastases from colorectal cancer?[J]. Ann Surg, 2015, 261( 5): 956- 960. DOI: 10.1097/SLA.0000000000000786.
[18]	DUELAND S, FOSS A, SOLHEIM JM, et al. Survival following liver transplantation for liver-only colorectal metastases compared with hepatocellular carcinoma[J]. Br J Surg, 2018, 105( 6): 736- 742. DOI: 10.1002/bjs.10769.
[19]	DUELAND S, SYVERSVEEN T, SOLHEIM JM, et al. Survival following liver transplantation for patients with nonresectable liver-only colorectal metastases[J]. Ann Surg, 2020, 271( 2): 212- 218. DOI: 10.1097/SLA.0000000000003404.
[20]	BONNEY GK, CHEW CA, LODGE P, et al. Liver transplantation for non-resectable colorectal liver metastases: The International Hepato-Pancreato-Biliary Association consensus guidelines[J]. Lancet Gastroenterol Hepatol, 2021, 6( 11): 933- 946. DOI: 10.1016/S2468-1253(21)00219-3.
[21]	YE LC, LIU TS, REN L, et al. Randomized controlled trial of cetuximab plus chemotherapy for patients with KRAS wild-type unresectable colorectal liver-limited metastases[J]. J Clin Oncol, 2013, 31( 16): 1931- 1938. DOI: 10.1200/JCO.2012.44.8308.
[22]	TANG WT, REN L, LIU TS, et al. Bevacizumab plus mFOLFOX6 versus mFOLFOX6 alone as first-line treatment for RAS mutant unresectable colorectal liver-limited metastases: The BECOME randomized controlled trial[J]. J Clin Oncol, 2020, 38( 27): 3175- 3184. DOI: 10.1200/JCO.20.00174.
[23]	LEE JC, MEHDIZADEH S, SMITH J, et al. Regulatory T cell control of systemic immunity and immunotherapy response in liver metastasis[J]. Sci Immunol, 2020, 5( 52): eaba0759. DOI: 10.1126/sciimmunol.aba0759.
[24]	YU JL, GREEN MD, LI SS, et al. Liver metastasis restrains immunotherapy efficacy via macrophage-mediated T cell elimination[J]. Nat Med, 2021, 27( 1): 152- 164. DOI: 10.1038/s41591-020-1131-x.
[25]	TINGUELY P, DAL G, BOTTAI M, et al. Microwave ablation versus resection for colorectal cancer liver metastases-A propensity score analysis from a population-based nationwide registry[J]. Eur J Surg Oncol, 2020, 46( 3): 476- 485. DOI: 10.1016/j.ejso.2019.12.002.
[26]	van de GEEST TW, van AMERONGEN MJ, NIEROP PMH, et al. Propensity score matching demonstrates similar results for radiofrequency ablation compared to surgical resection in colorectal liver metastases[J]. Eur J Surg Oncol, 2022, 48( 6): 1368- 1374. DOI: 10.1016/j.ejso.2022.01.008.
[27]	TINGUELY P, RUITER SJS, ENGSTRAND J, et al. A prospective multicentre trial on survival after Microwave Ablation VErsus Resection for Resectable Colorectal liver metastases(MAVERRIC)[J]. Eur J Cancer, 2023, 187: 65- 76. DOI: 10.1016/j.ejca.2023.03.038.
[28]	GIANNONE F, GROLLEMUND A, FELLI E, et al. Combining radiofrequency ablation with hepatic resection for liver-only colorectal metastases: A propensity-score based analysis of long-term outcomes[J]. Ann Surg Oncol, 2023, 30( 8): 4856- 4866. DOI: 10.1245/s10434-023-13530-3.
[29]	LIU M, WANG K, WANG YY, et al. Short- and long-term outcomes of hepatectomy combined with intraoperative radiofrequency ablation for patients with multiple primarily unresectable colorectal liver metastases: A propensity matching analysis[J]. HPB(Oxford), 2021, 23( 10): 1586- 1594. DOI: 10.1016/j.hpb.2021.03.014.
[30]	RUERS T, PUNT C, VAN COEVORDEN F, et al. Radiofrequency ablation combined with systemic treatment versus systemic treatment alone in patients with non-resectable colorectal liver metastases: A randomized EORTC Intergroup phase II study(EORTC 40004)[J]. Ann Oncol, 2012, 23( 10): 2619- 2626. DOI: 10.1093/annonc/mds053.
[31]	HAO W, JUN Z, YAN L, et al. Comparison of the therapeutic efficacy between systemic chemotherapy with and without radiofrequency ablation for colorectal cancer liver metastases: A propensity score matching study[J]. Br J Radiol, 2023, 96( 1148): 20221195. DOI: 10.1259/bjr.20221195.
[32]	MEIJERINK MR, RUARUS AH, VROOMEN LGPH, et al. Irreversible electroporation to treat unresectable colorectal liver metastases(COLDFIRE-2): A phase II, two-center, single-arm clinical trial[J]. Radiology, 2021, 299( 2): 470- 480. DOI: 10.1148/radiol.2021203089.
[33]	CHMURA S, WINTER KA, ROBINSON C, et al. Evaluation of safety of stereotactic body radiotherapy for the treatment of patients with multiple metastases: Findings from the NRG-BR001 phase 1 trial[J]. JAMA Oncol, 2021, 7( 6): 845- 852. DOI: 10.1001/jamaoncol.2021.0687.
[34]	CHALKIDOU A, MACMILLAN T, GRZEDA MT, et al. Stereotactic ablative body radiotherapy in patients with oligometastatic cancers: A prospective, registry-based, single-arm, observational, evaluation study[J]. Lancet Oncol, 2021, 22( 1): 98- 106. DOI: 10.1016/S1470-2045(20)30537-4.
[35]	OLSON R, JIANG W, LIU M, et al. Treatment with stereotactic ablative radiotherapy for up to 5 oligometastases in patients with cancer: Primary toxic effect results of the nonrandomized phase 2 SABR-5 clinical trial[J]. JAMA Oncol, 2022, 8( 11): 1644- 1650. DOI: 10.1001/jamaoncol.2022.4394.
[36]	PALMA DA, OLSON R, HARROW S, et al. Stereotactic ablative radiotherapy versus standard of care palliative treatment in patients with oligometastatic cancers(SABR-COMET): A randomised, phase 2, open-label trial[J]. Lancet, 2019, 393( 10185): 2051- 2058. DOI: 10.1016/S0140-6736(18)32487-5.
[37]	HONG TS, WO JY, BORGER DR, et al. Phase II study of proton-based stereotactic body radiation therapy for liver metastases: Importance of tumor genotype[J]. J Natl Cancer Inst, 2017, 109( 9): djx031. DOI: 10.1093/jnci/djx031.
[38]	LIU Y, CHANG W, ZHOU B, et al. Conventional transarterial chemoembolization combined with systemic therapy versus systemic therapy alone as second-line treatment for unresectable colorectal liver metastases: Randomized clinical trial[J]. Br J Surg, 2021, 108( 4): 373- 379. DOI: 10.1093/bjs/znaa155.
[39]	WASAN HS, GIBBS P, SHARMA NK, et al. First-line selective internal radiotherapy plus chemotherapy versus chemotherapy alone in patients with liver metastases from colorectal cancer(FOXFIRE, SIRFLOX, and FOXFIRE-Global): A combined analysis of three multicentre, randomised, phase 3 trials[J]. Lancet Oncol, 2017, 18( 9): 1159- 1171. DOI: 10.1016/S1470-2045(17)30457-6.
[40]	HENDLISZ A, van den EYNDE M, PEETERS M, et al. Phase III trial comparing protracted intravenous fluorouracil infusion alone or with yttrium-90 resin microspheres radioembolization for liver-limited metastatic colorectal cancer refractory to standard chemotherapy[J]. J Clin Oncol, 2010, 28( 23): 3687- 3694. DOI: 10.1200/JCO.2010.28.5643.
[41]	MULCAHY MF, MAHVASH A, PRACHT M, et al. Radioembolization with chemotherapy for colorectal liver metastases: A randomized, open-label, international, multicenter, phase III trial[J]. J Clin Oncol, 2021, 39( 35): 3897- 3907. DOI: 10.1200/JCO.21.01839.
[42]	GROOT KOERKAMP B, SADOT E, KEMENY NE, et al. Perioperative hepatic arterial infusion pump chemotherapy is associated with longer survival after resection of colorectal liver metastases: A propensity score analysis[J]. J Clin Oncol, 2017, 35( 17): 1938- 1944. DOI: 10.1200/JCO.2016.71.8346.
[43]	GHOLAMI S, KEMENY NE, BOUCHER TM, et al. Adjuvant hepatic artery infusion chemotherapy is associated with improved survival regardless of KRAS mutation status in patients with resected colorectal liver metastases: A retrospective analysis of 674 patients[J]. Ann Surg, 2020, 272( 2): 352- 356. DOI: 10.1097/SLA.0000000000003248.
[44]	DʼANGELICA MI, CORREA-GALLEGO C, PATY PB, et al. Phase II trial of hepatic artery infusional and systemic chemotherapy for patients with unresectable hepatic metastases from colorectal cancer: Conversion to resection and long-term outcomes[J]. Ann Surg, 2015, 261( 2): 353- 360. DOI: 10.1097/SLA.0000000000000614.
[45]	VERHEIJ FS, KUHLMANN KFD, SILLIMAN DR, et al. Combined hepatic arterial infusion pump and systemic chemotherapy in the modern era for chemotherapy-naive patients with unresectable colorectal liver metastases[J]. Ann Surg Oncol, 2023, 30( 13): 7950- 7959. DOI: 10.1245/s10434-023-14073-3.