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ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R
Volume 39 Issue 11
Nov.  2023
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Article Contents

Neoadjuvant therapy for hepatocellular carcinoma: Current situation and prospects

DOI: 10.3969/j.issn.1001-5256.2023.11.027
Research funding:

National Natural Science Foundation of China Program (81903790);

Shandong Traditional Chinese Medicine Technology Project (Q-2023109)

More Information
  • Corresponding author: LIU Xin, tanluzhe2888@163.com (ORCID: 0000-0002-0082-9439)
  • Received Date: 2023-02-14
  • Accepted Date: 2023-02-28
  • Published Date: 2023-11-28
  • Hepatocellular carcinoma (HCC) is a major cause of cancer-related death, and surgical resection remains an important method for radical treatment, but it is urgently needed to solve the problem of high postoperative recurrence rate. Neoadjuvant therapy can reduce the high recurrence rate after surgery, and there are little benefits from neoadjuvant therapy for HCC due to a lack of effective treatment methods in the past. At present, combination therapy based on immune checkpoint inhibitors has a relatively high response rate and has thus changed the treatment landscape for patients with advanced HCC. This urges investigators to reexamine the neoadjuvant treatment strategies for HCC, and it is expected that neoadjuvant therapy can provide new opportunities, reduce the postoperative recurrence rate, and improve the survival rate after treatment. This article discusses the current status and prospects of neoadjuvant therapy for HCC and related hot topics, so as to provide more ideas for exploring neoadjuvant therapy for HCC.

     

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  • [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]
    PARK JW, CHEN M, 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.
    [3]
    KORDE LA, SOMERFIELD MR, CAREY LA, et al. Neoadjuvant chemotherapy, endocrine therapy, and targeted therapy for breast cancer: ASCO guideline[J]. J Clin Oncol, 2021, 39( 13): 1485- 1505. DOI: 10.1200/JCO.20.03399.
    [4]
    HANK T, BÜCHLER MW, NEOPTOLEMOS JP. Neoadjuvant chemotherapy in pancreatic cancer[J]. JAMA Surg, 2021, 156( 4): 397- 397. DOI: 10.1001/jamasurg.2020.6273.
    [5]
    ROSEN G, MARCOVE R C, CAPARROS B, et al. Primary osteogenic sarcoma. The rationale for preoperative chemotherapy and delayed surgery[J]. Cancer, 1979, 43( 6): 2163- 2177. DOI: 3.0.co;2-s">10.1002/1097-0142(197906)43:6<2163::aid-cncr2820430602>3.0.co;2-s.
    [6]
    FREI E 3rd. Clinical cancer research: an embattled species[J]. Cancer, 1982, 50( 10): 1979- 1992. DOI: 3.0.co;2-d">10.1002/1097-0142(19821115)50:10<1979::aid-cncr2820501002>3.0.co;2-d.
    [7]
    TRIMBLE EL, UNGERLEIDER RS, ABRAMS JA, et al. Neoadjuvant therapy in cancer treatment[J]. Cancer, 1993, 72( 11 Suppl): 3515- 3524. DOI: 10.1002/1097-0142(19931201)72:11 +<3515::aid-cncr2820721619>3. 0.co;2-a.
    [8]
    HWANG TL, CHEN MF, LEE TY, et al. Resection of hepatocellular carcinoma after transcatheter arterial embolization. Reevaluation of the advantages and disadvantages of preoperative embolization[J]. Arch Surg, 1987, 122( 7): 756- 759. DOI: 10.1001/archsurg.1987.01400190022004.
    [9]
    General Office of National Health Commission. Standard for diagnosis and treatment of primary liver cancer(2022 edition)[J]. J Clin Hepatol, 2022, 38( 2): 288- 303. DOI: 10.3969/j.issn.1001-5256.2022.02.009.

    国家卫生健康委办公厅. 原发性肝癌诊疗指南(2022年版)[J]. 临床肝胆病杂志, 2022, 38( 2): 288- 303. DOI: 10.3969/j.issn.1001-5256.2022.02.009.
    [10]
    ZHOU H, SONG T. Conversion therapy and maintenance therapy for primary hepatocellular carcinoma[J]. Biosci Trends, 2021, 15( 3): 155- 160. DOI: 10.5582/bst.2021.01091.
    [11]
    POON RT, FAN ST, NG IO, et al. Different risk factors and prognosis for early and late intrahepatic recurrence after resection of hepatocellular carcinoma[J]. Cancer, 2000, 89( 3): 500- 507.
    [12]
    TSILIMIGRAS DI, BAGANTE F, MORIS D, et al. Recurrence patterns and outcomes after resection of hepatocellular carcinoma within and beyond the barcelona clinic liver cancer criteria[J]. Ann Surg Oncol, 2020, 27( 7): 2321- 2331. DOI: 10.1245/s10434-020-08452-3.
    [13]
    ZHAO H, HUA Y, DAI T, et al. Development and validation of a novel predictive scoring model for microvascular invasion in patients with hepatocellular carcinoma[J]. Eur J Radiol, 2017, 88: 32- 40. DOI: 10.1016/j.ejrad.2016.12.030.
    [14]
    von FELDEN J, HEIM D, SCHULZE K, et al. High expression of micro RNA-135A in hepatocellular carcinoma is associated with recurrence within 12 months after resection[J]. BMC Cancer, 2017, 17( 1): 60. DOI: 10.1186/s12885-017-3053-7.
    [15]
    LIU T, TAN J, WU M, et al. High-affinity neoantigens correlate with better prognosis and trigger potent antihepatocellular carcinoma(HCC) activity by activating CD39+ CD8+ T cells[J]. Gut, 2021, 70( 10): 1965- 1977. DOI: 10.1136/gutjnl-2020-322196.
    [16]
    HARDING JJ, NANDAKUMAR S, ARMENIA J, et al. Prospective genotyping of hepatocellular carcinoma: clinical implications of next-generation sequencing for matching patients to targeted and immune therapies[J]. Clin Cancer Res, 2019, 25( 7): 2116- 2126. DOI: 10.1158/1078-0432.CCR-18-2293.
    [17]
    HORWITZ E, STEIN I, ANDREOZZI M, et al. Human and mouse VEGFA-amplified hepatocellular carcinomas are highly sensitive to sorafenib treatment[J]. Cancer Discov, 2014, 4( 6): 730- 743. DOI: 10.1158/2159-8290.CD-13-0782.
    [18]
    ZHANG Z, LIU Q, HE J, et al. The effect of preoperative transcatheter hepatic arterial chemoembolization on disease-free survival after hepatectomy for hepatocellular carcinoma[J]. Cancer, 2000, 89( 12): 2606- 2612.
    [19]
    GERUNDA GE, NERI D, MERENDA R, et al. Role of transarterial chemoembolization before liver resection for hepatocarcinoma[J]. Liver Transpl, 2000, 6( 5): 619- 626. DOI: 10.1053/jlts.2000.8312.
    [20]
    CHUA TC, LIAUW W, SAXENA A, et al. Systematic review of neoadjuvant transarterial chemoembolization for resectable hepatocellular carcinoma[J]. Liver Int, 2010, 30( 2): 166- 174. DOI: 10.1111/j.1478-3231.2009.02166.x.
    [21]
    QADAN M, FONG ZV, DELMAN AM, et al. Review of use of Y90 as a bridge to liver resection and transplantation in hepatocellular carcinoma[J]. J Gastrointest Surg, 2021, 25: 2690- 2699. DOI: 10.1007/s11605-021-05095-x.
    [22]
    SALEM R, JOHNSON GE, KIM E, et al. Yttrium‐90 radioembolization for the treatment of solitary, unresectable HCC: the LEGACY study[J]. Hepatology, 2021, 74( 5): 2342- 2352. DOI: 10.1002/hep.31819.
    [23]
    KOKABI N, CAMACHO JC, XING M, et al. Open‐label prospective study of the safety and efficacy of glass‐based yttrium 90 radioembolization for infiltrative hepatocellular carcinoma with portal vein thrombosis[J]. Cancer, 2015, 121( 13): 2164- 2174. DOI: 10.1002/cncr.29275.
    [24]
    WEI X, JIANG Y, ZHANG X, et al. Neoadjuvant three-dimensional conformal radiotherapy for resectable hepatocellular carcinoma with portal vein tumor thrombus: a randomized, open-label, multicenter controlled study[J]. J Clin Oncol, 2019, 37( 24): 2141. DOI: 10.1200/JCO.18.02184.
    [25]
    KAMIYAMA T, NAKANISHI K, YOKOO H, et al. Efficacy of preoperative radiotherapy to portal vein tumor thrombus in the main trunk or first branch in patients with hepatocellular carcinoma[J]. Int J Clin Oncol, 2007, 12( 5): 363- 368. DOI: 10.1007/s10147-007-0701-y.
    [26]
    LI Q J, HE M K, CHEN H W, et al. Hepatic arterial infusion of oxaliplatin, fluorouracil, and leucovorin versus transarterial chemoembolization for large hepatocellular carcinoma: a randomized phase Ⅲ trial[J]. J Clin Oncol, 2022, 40( 2): 150- 160. DOI: 10.1200/JCO.21.00608.
    [27]
    HE MK, LE Y, LI QJ, et al. Hepatic artery infusion chemotherapy using mFOLFOX versus transarterial chemoembolization for massive unresectable hepatocellular carcinoma: a prospective non-randomized study[J]. Chin J Cancer, 2017, 36( 1): 83. DOI: 10.1186/s40880-017-0251-2.
    [28]
    LYU N, WANG X, LI J B, et al. Arterial chemotherapy of oxaliplatin plus fluorouracil versus sorafenib in advanced hepatocellular carcinoma: a biomolecular exploratory, randomized, phase Ⅲ trial(FOHAIC-1)[J]. J Clin Oncol, 2022, 40( 5): 468- 480. DOI: 10.1200/JCO.21.01963.
    [29]
    HUANG J, HUANG W, ZHAN M, et al. Drug-eluting bead transarterial chemoembolization combined with FOLFOX-based hepatic arterial infusion chemotherapy for large or huge hepatocellular carcinoma[J]. J Hepatocell Carcinoma, 2021, 8: 1445- 1458. DOI: 10.2147/JHC.S339379.
    [30]
    BYUN HK, KIM HJ, IM YR, et al. Dose escalation by intensity modulated radiotherapy in liver-directed concurrent chemoradiotherapy for locally advanced BCLC stage C hepatocellular carcinoma[J]. Radiother Oncol, 2019, 133: 1- 8. DOI: 10.1016/j.radonc.2018.12.025.
    [31]
    BARBIER L, FUKS D, PESSAUX P, et al. Safety of liver resection for hepatocellular carcinoma after sorafenib therapy: a multicenter case-matched study[J]. Ann Surg Oncol, 2013, 20( 11): 3603- 3609. DOI: 10.1245/s10434-013-3029-z.
    [32]
    KUDO M, FINN R S, QIN S, 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.
    [33]
    TADA M, ICHIDA A, ARITA J, et al. Multicenter prospective study to evaluate the efficacy of lenvatinib to achieve conversion surgery for initially unresectable hepatocellular carcinoma: LENS-HCC trial[J]. J Clin Oncol, 2022, 40( 4): 458. DOI: 10.1200/JCO.2022.40.4_suppl.458.
    [34]
    YANG XR, SUN HC, XIE Q, et al. Chinese expert guidance on overall application of lenvatinib in hepatocellular carcinoma[J]. Chin J Dig Surg, 2023, 22( 2): 167- 180. DOI: 10.3760/cma.j.cn115610-20230201-00035.

    杨欣荣, 孙惠川, 谢青, 等. 仑伐替尼肝癌全病程应用中国专家指导意见[J]. 中华消化外科杂志, 2023, 22( 2): 167- 180. DOI: 10.3760/cma.j.cn115610-20230201-00035.
    [35]
    LIN YY, TAN CT, CHEN CW, et al. Immunomodulatory effects of current targeted therapies on hepatocellular carcinoma: implication for the future of immunotherapy[J]. Semin Liver Dis, 2018, 38( 4): 379- 388. DOI: 10.1055/s-0038-1673621.
    [36]
    LIANG J, LI L. Progress and consideration of immunotherapy strategy for hepatocellular carcinoma[J]. Chin J Dig Surg, 2021, 20( 2): 184- 190. DOI: 10.3760/cma.j.cn115610-20201228-00809.

    梁军, 李丽. 肝癌免疫治疗策略的进展与思考[J]. 中华消化外科杂志, 2021, 20( 2): 184- 190. DOI: 10.3760/cma.j.cn115610-20201228-00809.
    [37]
    HO WJ, ZHU Q, DURHAM J, et al. Neoadjuvant cabozantinib and nivolumab converts locally advanced HCC into resectable disease with enhanced antitumor immunity[J]. Nat Cancer, 2021, 2( 9): 891- 903. DOI: 10.1038/s43018-021-00234-4.
    [38]
    LIU J, BLAKE SJ, YONG MC, et al. Improved efficacy of neoadjuvant compared to adjuvant immunotherapy to eradicate metastatic disease[J]. Cancer Discov, 2016, 6( 12): 1382- 1399. DOI: 10.1158/2159-8290.CD-16-0577.
    [39]
    MARRON TU, FIEL MI, HAMON P, et al. Neoadjuvant cemiplimab for resectable hepatocellular carcinoma: a single-arm, open-label, phase 2 trial[J]. Lancet Gastroenterol Hepato, 2022, 7( 3): 219- 229. DOI: 10.1016/S2468-1253(21)00385-X.
    [40]
    KASEB AO, HASANOV E, CAO H, et al. Perioperative nivolumab monotherapy versus nivolumab plus ipilimumab in resectable hepatocellular carcinoma: a randomised, open-label, phase 2 trial[J]. Lancet Gastroenterol Hepatol, 2022, 7( 3): 208- 218. DOI: 10.1016/S2468-1253(21)00427-1.
    [41]
    RAHMA OE, HODI FS. The intersection between tumor angiogenesis and immune suppression[J]. Clin Cancer Res, 2019, 25( 18): 5449- 5457. DOI: 10.1158/1078-0432.CCR-18-1543.
    [42]
    ZHANG N, LIU XL, XU ZQ, et al. Research progress in relationship between tumor anti-angiogenesis and immunotherapy[J]. J Jilin Univ(Medicine Edition), 2021, 47( 4): 1056- 1063. DOI: 10.13481/j.1671-587X.20210434.

    张娜, 刘相良, 徐志强, 等. 肿瘤抗血管生成及其与免疫治疗关系的研究进展[J]. 吉林大学学报(医学版), 2021, 47( 4): 1056- 1063. DOI: 10.13481/j.1671-587X.20210434.
    [43]
    XIA Y, WANG P, PU L, et al. Preliminary efficacy and safety of perioperative treatment of camrelizumab combined with apatinib in resectable hepatocellular carcinoma(HCC): A prospective phase Ⅱ study[J]. J Clin Oncol, 2021, 39( 15_Suppl): 4082. DOI: 10.1200/JCO.2021.39.15_suppl.4082.
    [44]
    XU L, ZHANG Y, WANG X, et al. Transarterial infusion chemotherapy(TAI) combined with Sintilimab in locally advanced, potentially resectable hepatocellular carcinoma(HCC)[J]. J Clin Oncol, 2020, 38( 15_Suppl): e16593. DOI: 10.1200/JCO.2020.38.15_suppl.e16593.
    [45]
    LLOVET JM, VILLANUEVA A, MARRERO JA, et al. Trial design and endpoints in hepatocellular carcinoma: AASLD consensus conference[J]. Hepatology, 2021, 73: 158- 191. DOI: 10.1002/hep.31327.
    [46]
    KHAN KA, KERBEL RS. Improving immunotherapy outcomes with anti-angiogenic treatments and vice versa[J]. Nat Rev Clin Oncol, 2018, 15( 5): 310- 324. DOI: 10.1038/nrclinonc.2018.9.
    [47]
    COTTRELL TR, THOMPSON ED, FORDE PM, et al. Pathologic features of response to neoadjuvant anti-PD-1 in resected non-small-cell lung carcinoma: a proposal for quantitative immune-related pathologic response criteria(irPRC)[J]. Ann Oncol, 2018, 29( 8): 1853- 1860. DOI: 10.1093/annonc/mdy218.
    [48]
    SASAKI A, IWASHITA Y, SHIBATA K, et al. Preoperative transcatheter arterial chemoembolization reduces long-term survival rate after hepatic resection for resectable hepatocellular carcinoma[J]. Eur J Surg Oncol, 2006, 32( 7): 773- 779. DOI: 10.1016/j.ejso.2006.04.002.
    [49]
    FANG P, HU JH, CHENG ZG, et al. Efficacy and safety of bevacizumab for the treatment of advanced hepatocellular carcinoma: a systematic review of phase Ⅱ trials[J]. PLoS One, 2012, 7( 12): e49717. DOI: 10.1371/journal.pone.0049717.
    [50]
    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.
    [51]
    SUN C, LI B, LI L, et al. Effect of Huaier granules on patients with middle and advanced liver cancer[J]. J Changchun Univ Chin Med, 2022, 38( 10): 1130- 1133. DOI: 10.13463/j.cnki.cczyy.2022.10.016.

    孙川, 李宾, 李磊, 等. 槐耳颗粒治疗中晚期肝癌[J]. 长春中医药大学学报, 2022, 38( 10): 1130- 1133. DOI: 10.13463/j.cnki.cczyy.2022.10.016.
    [52]
    WANG Z, REN Z, CHEN Y, et al. Adjuvant transarterial chemoembolization for hbv-related hepatocellular carcinoma after resection: a randomized controlled studyadjuvant TACE for HCC after resection[J]. Clin Cancer Res, 2018, 24( 9): 2074- 2081. DOI: 10.1158/1078-0432.CCR-17-2899.
    [53]
    CHEN Q, SHU C, LAURENCE AD, et al. Effect of Huaier granule on recurrence after curative resection of HCC: a multicentre, randomised clinical trial[J]. Gut, 2018, 67( 11): 2006- 2016. DOI: 10.1136/gutjnl-2018-315983.
    [54]
    FENG M, TANG C, FENG W, et al. Hepatic artery-infusion chemotherapy improved survival of hepatocellular carcinoma after radical hepatectomy[J]. Onco Targets Ther, 2017, 10: 3001- 3005. DOI: 10.2147/OTT.S136806.
    [55]
    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.
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