Combination therapies plus transarterial chemoembolization in hepatocellular carcinoma: a snapshot of clinical trial progress

References

• Forner A, Reig M, Bruix J. Hepatocellular carcinoma. Lancet. 2018 Mar 31;391(10127):1301–1314.
   PubMed Web of Science ®Google Scholar
• Llovet JM, Zucman-Rossi J, Pikarsky E, et al. Hepatocellular carcinoma. Nat Rev Dis Primers. 2016 Apr;14(2):16018.
   Google Scholar
• Bellanti F, Villani R, Tamborra R, et al. Synergistic interaction of fatty acids and oxysterols impairs mitochondrial function and limits liver adaptation during nafld progression. Redox Biol. 2018 May;15:86–96.
   PubMed Web of Science ®Google Scholar
• Brown ZJ, Fu Q, Ma C, et al. Carnitine palmitoyltransferase gene upregulation by linoleic acid induces CD4(+) T cell apoptosis promoting HCC development. Cell Death Dis. 2018 May 23;9(6):620.
   PubMedGoogle Scholar
• Ma C, Kesarwala AH, Eggert T, et al. NAFLD causes selective CD4(+) T lymphocyte loss and promotes hepatocarcinogenesis. Nature. 2016 Mar 10;531(7593):253–257.
   PubMed Web of Science ®Google Scholar
• Maluccio MA, Covey AM, Porat LB, et al. Transcatheter arterial embolization with only particles for the treatment of unresectable hepatocellular carcinoma. J Vasc Interv Radiol. 2008 Jun;19(6):862–869.
   PubMed Web of Science ®Google Scholar
• Llovet JM, Real MI, Montana X, et al. Arterial embolisation or chemoembolisation versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: a randomised controlled trial. Lancet. 2002 May 18;359(9319):1734–1739.
   PubMed Web of Science ®Google Scholar
• Maluccio M, Covey AM, Gandhi R, et al. Comparison of survival rates after bland arterial embolization and ablation versus surgical resection for treating solitary hepatocellular carcinoma up to 7 cm. J Vasc Interv Radiol. 2005 Jul;16(7):955–961.
   PubMed Web of Science ®Google Scholar
• Raoul JL, Forner A, Bolondi L, et al. Updated use of TACE for hepatocellular carcinoma treatment: how and when to use it based on clinical evidence. Cancer Treat Rev. 2019 Jan;72:28–36.
   PubMed Web of Science ®Google Scholar
• Llovet JM, Ricci S, Mazzaferro V, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008 Jul 24;359(4):378–390.
   PubMed Web of Science ®Google Scholar
• Greten TF, Lai CW, Li G, et al. Targeted and immune-based therapies for hepatocellular carcinoma. Gastroenterology. 2018 Oct;1.
   Google Scholar
• Finn RS, Ryoo BY, Merle P, et al. Pembrolizumab as second-line therapy in patients with advanced hepatocellular carcinoma in keynote-240: a randomized, double-blind, phase III trial. J Clin Oncol. 2020 Jan 20;38(3):193–202.
   PubMed Web of Science ®Google Scholar
• Greten TF, Abou-Alfa GK, Cheng AL, et al. Society for immunotherapy of cancer (SITC) clinical practice guideline on immunotherapy for the treatment of hepatocellular carcinoma. J Immunother Cancer. 2021 Sep;9(9):e002794.
   PubMed Web of Science ®Google Scholar
• Finn RS, Qin S, Ikeda M, et al. Atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma. N Engl J Med. 2020 May 14;382(20):1894–1905.
   PubMed Web of Science ®Google Scholar
• Chu DZ, Hutchins L, Lang NP. Regional chemotherapy of liver metastases from colorectal carcinoma: hepatic artery or portal vein infusion? Cancer Treat Rev. 1988;15(4):243–256.
   PubMed Web of Science ®Google Scholar
• Breedis C, Young G. The blood supply of neoplasms in the liver. Am J Pathol. 1954 Sep-Oct;30(5):969–977.
   PubMed Web of Science ®Google Scholar
• Fortner JG, Beattie JEJ, Shiu MH, et al. Surgery in liver tumors. Curr Probl Surg. 1972;9(6):1–56.
   Google Scholar
• Nilsson LA. Therapeutic hepatic artery ligation in patients with secondary liver tumors. Rev Surg. 1966Sep-Oct;23(5):193–202.
   Google Scholar
• Llovet JM, De Baere T, Kulik L, et al. Locoregional therapies in the era of molecular and immune treatments for hepatocellular carcinoma. Nat Clin Pract Gastroenterol Hepatol. 2021 May;18(5):293–313.
   Google Scholar
• Huang YH, Chen CH, Chang TT, et al. The role of transcatheter arterial embolization for patients with unresectable hepatocellular carcinoma: a nationwide, multicentre study evaluated by cancer stage. Aliment Pharmacol Ther. 2005 Mar 15;21(6):687–694.
   PubMed Web of Science ®Google Scholar
• Bonomo G, Pedicini V, Monfardini L, et al. Bland embolization in patients with unresectable hepatocellular carcinoma using precise, tightly size-calibrated, anti-inflammatory microparticles: first clinical experience and one-year follow-up. Cardiovasc Intervent Radiol. 2010 Jun;33(3):552–559.
   PubMed Web of Science ®Google Scholar
• Nezami N, Vanb JMM, Konstantinidis M, et al. Lipiodol deposition and washout in primary and metastatic liver tumors after chemoembolization. Vivo. 2021 Nov-Dec;35(6):3261–3270.
   PubMed Web of Science ®Google Scholar
• Ramsey DE, Kernagis LY, Soulen MC, et al. Chemoembolization of hepatocellular carcinoma. J Vasc Interv Radiol. 2002 Sep;13(9):S211–21.
   PubMed Web of Science ®Google Scholar
• Liapi E, Geschwind JF. Intra-arterial therapies for hepatocellular carcinoma: where do we stand? Ann Surg Oncol. 2010 May;17(5):1234–1246.
   PubMed Web of Science ®Google Scholar
• Ibrahim SM, Lewandowski RJ, Sato KT, et al. Radioembolization for the treatment of unresectable hepatocellular carcinoma: a clinical review. World J Gastroenterol. 2008 Mar 21;14(11):1664–1669.
   PubMed Web of Science ®Google Scholar
• Kulik LM, Carr BI, Mulcahy MF, et al. Safety and efficacy of 90Y radiotherapy for hepatocellular carcinoma with and without portal vein thrombosis. Hepatology. 2008 Jan;47(1):71–81.
   PubMed Web of Science ®Google Scholar
• Lo CM, Ngan H, Tso WK, et al. Randomized controlled trial of transarterial lipiodol chemoembolization for unresectable hepatocellular carcinoma. Hepatology. 2002 May;35(5):1164–1171.
   PubMed Web of Science ®Google Scholar
• Llovet JM, Bruix J. Systematic review of randomized trials for unresectable hepatocellular carcinoma: chemoembolization improves survival. Hepatology. 2003 Feb;37(2):429–442.
   PubMed Web of Science ®Google Scholar
• Lammer J, Malagari K, Vogl T, et al. Prospective randomized study of doxorubicin-eluting-bead embolization in the treatment of hepatocellular carcinoma: results of the PRECISION V study. Cardiovasc Intervent Radiol. 2010 Feb;33(1):41–52.
   PubMed Web of Science ®Google Scholar
• Morse MA, Hanks BA, Suhocki P, et al. Improved time to progression for transarterial chemoembolization compared with transarterial embolization for patients with unresectable hepatocellular carcinoma. Clin Colorectal Cancer. 2012 Sep;11(3):185–190.
   PubMed Web of Science ®Google Scholar
• Brown KT, Do RK, Gonen M, et al. Randomized trial of hepatic artery embolization for hepatocellular carcinoma using doxorubicin-eluting microspheres compared with embolization with microspheres alone. J Clin Oncol. 2016 Jun 10;34(17):2046–2053.
   PubMed Web of Science ®Google Scholar
• Malagari K, Pomoni M, Kelekis A, et al. Prospective randomized comparison of chemoembolization with doxorubicin-eluting beads and bland embolization with beadblock for hepatocellular carcinoma. Cardiovasc Intervent Radiol. 2010 Jun;33(3):541–551.
   PubMed Web of Science ®Google Scholar
• Golfieri R, Giampalma E, Renzulli M, et al. Randomised controlled trial of doxorubicin-eluting beads vs conventional chemoembolisation for hepatocellular carcinoma. Br J Cancer. 2014 Jul 15;111(2):255–264.
   PubMed Web of Science ®Google Scholar
• Dhanasekaran R, Kooby DA, Staley CA, et al. Comparison of conventional transarterial chemoembolization (TACE) and chemoembolization with doxorubicin drug eluting beads (DEB) for unresectable hepatocellular carcinoma (HCC). J Surg Oncol. 2010 May 1;101(6):1234–1246.
   Web of Science ®Google Scholar
• Yang B, Liang J, Qu Z, et al. Transarterial strategies for the treatment of unresectable hepatocellular carcinoma: a systematic review. PloS One. 2020;15(2):e0227475.
   PubMed Web of Science ®Google Scholar
• Lobo L, Yakoub D, Picado O, et al. Unresectable hepatocellular carcinoma: radioembolization versus chemoembolization: a systematic review and meta-analysis. Cardiovasc Intervent Radiol. 2016 Nov;39(11):1580–1588.
   PubMed Web of Science ®Google Scholar
• Ludwig JM, Zhang D, Xing M, et al. Meta-analysis: adjusted indirect comparison of drug-eluting bead transarterial chemoembolization versus (90) Y-radioembolization for hepatocellular carcinoma. Eur Radiol. 2017 May;27(5):2031–2041.
   PubMed Web of Science ®Google Scholar
• Facciorusso A, Bellanti F, Villani R, et al. Transarterial chemoembolization vs bland embolization in hepatocellular carcinoma: a meta-analysis of randomized trials. United European Gastroenterol J. 2017 Jun;5(4):511–518.
   PubMed Web of Science ®Google Scholar
• Cucchetti A, Trevisani F, Cappelli A, et al. Cost-effectiveness of doxorubicin-eluting beads versus conventional trans-arterial chemo-embolization for hepatocellular carcinoma. Dig Liver Dis. 2016 Jul;48(7):798–805.
   PubMedGoogle Scholar
• Fateen W, Khan F, O’Neill RJ, et al. Healthcare costs of transarterial chemoembolization in the treatment of hepatocellular carcinoma. J Hepatocell Carcinoma. 2017;4:123–130.
   PubMed Web of Science ®Google Scholar
• Wilhelm SM, Adnane L, Newell P, et al. Preclinical overview of sorafenib, a multikinase inhibitor that targets both Raf and VEGF and PDGF receptor tyrosine kinase signaling. Mol Cancer Ther. 2008 Oct;7(10):3129–3140.
   PubMed Web of Science ®Google Scholar
• Xiong ZP, Yang SR, Liang ZY, et al. Association between vascular endothelial growth factor and metastasis after transcatheter arterial chemoembolization in patients with hepatocellular carcinoma. Hepatobiliary Pancreat Dis Int. 2004 Aug;3(3):386–390.
   PubMedGoogle Scholar
• Song BC, Chung YH, Kim JA, et al. Association between insulin-like growth factor-2 and metastases after transcatheter arterial chemoembolization in patients with hepatocellular carcinoma: a prospective study. Cancer. 2001 Jun 15;91(12):2386–2393.
   PubMed Web of Science ®Google Scholar
• Liu L, Chen H, Wang M, et al. Combination therapy of sorafenib and TACE for unresectable HCC: a systematic review and meta-analysis. PloS One. 2014;9(3):e91124.
   PubMed Web of Science ®Google Scholar
• Kuang J, Wan D, Wan P, et al. Efficacy of sorafenib combined with transcatheter hepatic arterial chemoembolization in treating intermediate-advanced hepatocellular carcinoma. J buon. 2021 May-Jun;26(3):868–874.
   PubMed Web of Science ®Google Scholar
• Xie Y, Tian H, Xiang B, et al. Transarterial chemoembolization plus sorafenib versus sorafenib for intermediate-advanced hepatocellular carcinoma: a meta-analysis comparing clinical outcomes. Medicine (Baltimore). 2021 Aug 20;100(33):e26958.
   PubMed Web of Science ®Google Scholar
• Facciorusso A, Paolillo R, Tartaglia N, et al. Efficacy of combined transarterial radioembolization and sorafenib in the treatment of hepatocarcinoma: a meta-analysis. Dig Liver Dis. 2021 Jun 27. doi:https://doi.org/10.1016/j.dld.2021.06.003.
   Google Scholar
• Zhao RC, Zhou J, Wei YG, et al. Cost-effectiveness analysis of transcatheter arterial chemoembolization with or without sorafenib for the treatment of unresectable hepatocellular carcinoma. Hepatobiliary Pancreat Dis Int. 2017 Oct 15;16(5):493–498.
   PubMed Web of Science ®Google Scholar
• Dai Y, Jiang H, Jiang H, et al. Optimal timing of combining sorafenib with trans-arterial chemoembolization in patients with hepatocellular carcinoma: a meta-analysis. Transl Oncol. 2021 Dec;14(12):101238.
   PubMedGoogle Scholar
• Kudo M, Finn RS, Qin S, et al. Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial. Lancet. 2018 Mar 24;391(10126):1163–1173.
   PubMed Web of Science ®Google Scholar
• Ding X, Sun W, Li W, et al. Transarterial chemoembolization plus lenvatinib versus transarterial chemoembolization plus sorafenib as first-line treatment for hepatocellular carcinoma with portal vein tumor thrombus: a prospective randomized study. Cancer. 2021 Jul 8;127(20):3782–3793.
   PubMed Web of Science ®Google Scholar
• Kudo M, Cheng AL, Park JW, et al. Orantinib versus placebo combined with transcatheter arterial chemoembolisation in patients with unresectable hepatocellular carcinoma (ORIENTAL): a randomised, double-blind, placebo-controlled, multicentre, phase 3 study. Lancet Gastroenterol Hepatol. 2018 Jan;3(1):37–46.
   PubMed Web of Science ®Google Scholar
• Kudo M, Han G, Finn RS, et al. Brivanib as adjuvant therapy to transarterial chemoembolization in patients with hepatocellular carcinoma: a randomized phase III trial. Hepatology. 2014 Nov;60(5):1697–1707.
   PubMed Web of Science ®Google Scholar
• Tian S, Quan H, Xie C, et al. YN968D1 is a novel and selective inhibitor of vascular endothelial growth factor receptor-2 tyrosine kinase with potent activity in vitro and in vivo. Cancer Sci. 2011 Jul;102(7):37–46.
   Web of Science ®Google Scholar
• Cao Y, Sun T, Guo X, et al. Sorafenib versus apatinib both combined transarterial chemoembolization for hepatocellular carcinoma with portal vein tumor thrombosis: a comparative retrospective study. Front Oncol. 2021;11:673378.
   PubMed Web of Science ®Google Scholar
• Kan X, Liang B, Zhou G, et al. Transarterial chemoembolization combined with apatinib for advanced hepatocellular carcinoma: a propensity score matching analysis. Front Oncol. 2020;10:970.
   PubMed Web of Science ®Google Scholar
• Cao Y, Ouyang T, Xiong F, et al. Efficacy of apatinib in patients with sorafenib-transarterial chemoembolization refractory hepatocellular carcinoma: a retrospective study. Hepatol Int. 2021 Aug 20;15(5):1268–1277.
   PubMed Web of Science ®Google Scholar
• Li H, Hu H, Cao G, et al. Prospective, multicenter study of apatinib combine with TACE in treating intermediate to advanced stage HCC patients: a real-world study from China. J clin oncol. 2021;39(3_suppl):282.
   Web of Science ®Google Scholar
• Pokuri VK, Tomaszewski GM, Ait-Oudhia S, et al. Efficacy, safety, and potential biomarkers of sunitinib and transarterial chemoembolization (tace) combination in advanced hepatocellular carcinoma (HCC): phase II trial. Am J Clin Oncol. 2018 Apr;41(4):332–338.
   PubMed Web of Science ®Google Scholar
• Pasche B, Wang M, Pennison M, et al. Prevention and treatment of cancer with aspirin: where do we stand? Semin Oncol. 2014 Jun;41(3):397–401.
   PubMed Web of Science ®Google Scholar
• Carrat F. Statin and aspirin for prevention of hepatocellular carcinoma: what are the levels of evidence? Clin Res Hepatol Gastroenterol. 2014 Feb;38(1):9–11.
   PubMed Web of Science ®Google Scholar
• Lee M, Chung GE, Lee JH, et al. Antiplatelet therapy and the risk of hepatocellular carcinoma in chronic hepatitis B patients on antiviral treatment. Hepatology. 2017 Nov;66(5):1556–1569.
   PubMed Web of Science ®Google Scholar
• Lee TY, Hsu YC, Tseng HC, et al. Association of daily aspirin therapy with risk of hepatocellular carcinoma in patients with chronic hepatitis B. JAMA Intern Med. 2019 May 1;179(5):633–640.
   PubMed Web of Science ®Google Scholar
• Simon TG, Duberg AS, Aleman S, et al. Association of aspirin with hepatocellular carcinoma and liver-related mortality. N Engl J Med. 2020 Mar 12;382(11):1018–1028.
   PubMed Web of Science ®Google Scholar
• Li JH, Wang Y, Xie XY, et al. Aspirin in combination with TACE in treatment of unresectable HCC: a matched-pairs analysis. Am J Cancer Res. 2016;6(9):2109–2116.
   PubMed Web of Science ®Google Scholar
• Fouad M, Abdel-Rahman O. Combination of transarterial chemoembolisation (TACE) plus antivirals for the management of hepatitis B-related hepatocellular carcinoma: a systematic review of the literature. Arab J Gastroenterol. 2015 Jun;16(2):40–45.
   PubMed Web of Science ®Google Scholar
• Fernández M, Semela D, Bruix J, et al. Angiogenesis in liver disease. J Hepatol. 2009 Mar;50(3):604–620.
   PubMed Web of Science ®Google Scholar
• Wang B, Xu H, Gao ZQ, et al. Increased expression of vascular endothelial growth factor in hepatocellular carcinoma after transcatheter arterial chemoembolization. Acta radiologica (Stockholm, Sweden: 1987). 2008 Jun;49(5):523–529.
   PubMed Web of Science ®Google Scholar
• Wu T. Cyclooxygenase-2 in hepatocellular carcinoma. Cancer Treat Rev. 2006 Feb;32(1):28–44.
   PubMed Web of Science ®Google Scholar
• Sui W, Zhang Y, Wang Z, et al. Antitumor effect of a selective COX-2 inhibitor, celecoxib, may be attributed to angiogenesis inhibition through modulating the PTEN/PI3K/Akt/HIF-1 pathway in an H₂₂ murine hepatocarcinoma model. Oncol Rep. 2014 May;31(5):2252–2260.
   PubMed Web of Science ®Google Scholar
• Yin J, Liu B, Li B, et al. The cyclooxygenase-2 inhibitor celecoxib attenuates hepatocellular carcinoma growth and c-Met expression in an orthotopic mouse model. Oncol Res. 2011;19(3):131–139.
   PubMed Web of Science ®Google Scholar
• Bassiouny AR, Zaky A, Neenaa HM. Synergistic effect of celecoxib on 5-fluorouracil-induced apoptosis in hepatocellular carcinoma patients. Ann Hepatol. 2010 Oct-Dec;9(4):410–418.
   PubMed Web of Science ®Google Scholar
• Bläker M, Schmitz M, Gocht A, et al. Differential expression of somatostatin receptor subtypes in hepatocellular carcinomas. J Hepatol. 2004 Jul;41(1):112–118.
   PubMed Web of Science ®Google Scholar
• Verhoef C, van Dekken H, Hofland LJ, et al. Somatostatin receptor in human hepatocellular carcinomas: biological, patient and tumor characteristics. Dig Surg. 2008;25(1):21–26.
   PubMed Web of Science ®Google Scholar
• Tong H, Wei B, Chen S, et al. Adjuvant celecoxib and lanreotide following transarterial chemoembolisation for unresectable hepatocellular carcinoma: a randomized pilot study. Oncotarget. 2017 Jul 18;8(29):48303–48312.
   PubMedGoogle Scholar
• Abd El Aziz MA, Facciorusso A, Nayfeh T, et al. Immune checkpoint inhibitors for unresectable hepatocellular carcinoma. Vaccines (Basel). 2020 Oct 19;8(4). DOI:https://doi.org/10.3390/vaccines8040616.
   Google Scholar
• Duffy AG, Ulahannan SV, Makorova-Rusher O, et al. Tremelimumab in combination with ablation in patients with advanced hepatocellular carcinoma. J Hepatol. 2017 Mar;66(3):545–551.
   PubMed Web of Science ®Google Scholar
• Tai WMD, Loke KSH, Gogna A, et al. A phase II open-label, single-center, nonrandomized trial of Y90-radioembolization in combination with nivolumab in Asian patients with advanced hepatocellular carcinoma: CA 209-678. J clin oncol. 2020;38(15_suppl):4590.
   Web of Science ®Google Scholar
• Guo J, Wang S, Han Y, et al. Effects of transarterial chemoembolization on the immunological function of patients with hepatocellular carcinoma. Oncol Lett. 2021 Jul;22(1):554.
   PubMed Web of Science ®Google Scholar
• He Y, Cao J, Zhao C, et al. TIM-3, a promising target for cancer immunotherapy. Onco Targets Ther. 2018;11:7005–7009.
   PubMed Web of Science ®Google Scholar
• Du W, Yang M, Turner A, et al. TIM-3 as a target for cancer immunotherapy and mechanisms of action. Int J Mol Sci. 2017 Mar 16;18(3):645.
   PubMed Web of Science ®Google Scholar
• Tampaki M, Ionas E, Hadziyannis E, et al. Association of TIM-3 with BCLC stage, serum pd-l1 detection, and response to transarterial chemoembolization in patients with hepatocellular carcinoma. Cancers (Basel). 2020 Jan 15;12(1).
   PubMed Web of Science ®Google Scholar
• Pan K, Li YQ, Wang W, et al. The efficacy of cytokine-induced killer cell infusion as an adjuvant therapy for postoperative hepatocellular carcinoma patients. Ann Surg Oncol. 2013 Dec;20(13):4305–4311.
   PubMed Web of Science ®Google Scholar
• Schmidt-Wolf IG, Lefterova P, Mehta BA, et al. Phenotypic characterization and identification of effector cells involved in tumor cell recognition of cytokine-induced killer cells. Exp Hematol. 1993 Dec;21(13):1673–1679.
   PubMed Web of Science ®Google Scholar
• Lee JH, Lee JH, Lim YS, et al. Adjuvant immunotherapy with autologous cytokine-induced killer cells for hepatocellular carcinoma. Gastroenterology. 2015 Jun;148(7):1383–91.e6.
   PubMed Web of Science ®Google Scholar
• Hui D, Qiang L, Jian W, et al. A randomized, controlled trial of postoperative adjuvant cytokine-induced killer cells immunotherapy after radical resection of hepatocellular carcinoma. Dig Liver Dis. 2009 Jan;41(1):36–41.
   PubMedGoogle Scholar
• Huang ZM, Li W, Li S, et al. Cytokine-induced killer cells in combination with transcatheter arterial chemoembolization and radiofrequency ablation for hepatocellular carcinoma patients. J Immunother. 2013 Jun;36(5):287–293.
   PubMed Web of Science ®Google Scholar
• Ji Q, Fu Y, Zhu X, et al. Effect of RFA and TACE combined with postoperative cytokine-induced killer cell immunotherapy in primary hepatocellular carcinoma. J buon. 2021 Jan-Feb;26(1):235–242.
   PubMed Web of Science ®Google Scholar
• Huang Z-M, Lai C-X, Zuo M-X, et al. Adjuvant cytokine-induced killer cells with minimally invasive therapies augmented therapeutic efficacy of unresectable hepatocellular carcinoma. J Cancer Res Ther. 2020;16(7):1603–1610.
   PubMed Web of Science ®Google Scholar
• Yamakado K, Nakatsuka A, Takaki H, et al. Early-stage hepatocellular carcinoma: radiofrequency ablation combined with chemoembolization versus hepatectomy. Radiology. 2008 Apr;247(1):260–266.
   PubMed Web of Science ®Google Scholar
• Kirikoshi H, Saito S, Yoneda M, et al. Outcome of transarterial chemoembolization monotherapy, and in combination with percutaneous ethanol injection, or radiofrequency ablation therapy for hepatocellular carcinoma. Hepatol Res. 2009 Jun;39(6):553–562.
   PubMed Web of Science ®Google Scholar
• Elnekave E, Erinjeri JP, Brown KT, et al. Long-term outcomes comparing surgery to embolization-ablation for treatment of solitary HCC<7 cm. Ann Surg Oncol. 2013 Sep;20(9):2881–2886.
   PubMed Web of Science ®Google Scholar
• Peng ZW, Zhang YJ, Chen MS, et al. Radiofrequency ablation with or without transcatheter arterial chemoembolization in the treatment of hepatocellular carcinoma: a prospective randomized trial. J Clin Oncol. 2013 Feb 1;31(4):426–432.
   PubMed Web of Science ®Google Scholar
• Shibata T, Isoda H, Hirokawa Y, et al. Small hepatocellular carcinoma: is radiofrequency ablation combined with transcatheter arterial chemoembolization more effective than radiofrequency ablation alone for treatment? Radiology. 2009 Sep;252(3):905–913.
   PubMed Web of Science ®Google Scholar
• Kim JH, Won HJ, Shin YM, et al. Medium-sized (3.1-5.0 cm) hepatocellular carcinoma: transarterial chemoembolization plus radiofrequency ablation versus radiofrequency ablation alone. Ann Surg Oncol. 2011 Jun;18(6):1624–1629.
   PubMed Web of Science ®Google Scholar
• Peng ZW, Zhang YJ, Liang HH, et al. Recurrent hepatocellular carcinoma treated with sequential transcatheter arterial chemoembolization and RF ablation versus RF ablation alone: a prospective randomized trial. Radiology. 2012 Feb;262(2):689–700.
   PubMed Web of Science ®Google Scholar
• Sheta E, El-Kalla F, El-Gharib M, et al. Comparison of single-session transarterial chemoembolization combined with microwave ablation or radiofrequency ablation in the treatment of hepatocellular carcinoma: a randomized-controlled study. Eur J Gastroenterol Hepatol. 2016 Oct;28(10):1198–1203.
   PubMed Web of Science ®Google Scholar
• Liu J, Zhang W, Lu H, et al. Drug-eluting bead trans-arterial chemoembolization combined with microwave ablation therapy vs. microwave ablation alone for early stage hepatocellular carcinoma: a preliminary investigation of clinical value. J Cancer Res Clin Oncol. 2021 Aug 17. doi:https://doi.org/10.1007/s00432-021-03760-x.
   Google Scholar
• Yuan-Dong S, Hao Z, Hui-Rong X, et al. Combination therapy: meta-analysis of the effects of TACE and cryoablation on hepatocellular carcinoma. Medicine (Baltimore). 2019 Dec;98(49):e18030.
   PubMed Web of Science ®Google Scholar
• Wang W, Shi J, Xie WF. Transarterial chemoembolization in combination with percutaneous ablation therapy in unresectable hepatocellular carcinoma: a meta-analysis. Liver Int. 2010 May;30(5):741–749.
   PubMed Web of Science ®Google Scholar
• Koda M, Murawaki Y, Mitsuda A, et al. Combination therapy with transcatheter arterial chemoembolization and percutaneous ethanol injection compared with percutaneous ethanol injection alone for patients with small hepatocellular carcinoma: a randomized control study. Cancer. 2001 Sep 15;92(6):1516–1524.
   PubMed Web of Science ®Google Scholar
• Becker G, Soezgen T, Olschewski M, et al. Combined TACE and PEI for palliative treatment of unresectable hepatocellular carcinoma. World J Gastroenterol. 2005 Oct 21;11(39):6104–6109.
   PubMed Web of Science ®Google Scholar
• Huo YR, Eslick GD. Transcatheter arterial chemoembolization plus radiotherapy compared with chemoembolization alone for hepatocellular carcinoma: a systematic review and meta-analysis. JAMA Oncol. 2015 Sep;1(6):756–765.
   PubMed Web of Science ®Google Scholar
• Abdel-Rahman O, Elsayed Z. External beam radiotherapy for unresectable hepatocellular carcinoma. Cochrane Database Syst Rev. 2017 Mar 7;3(3):Cd011314.
   PubMedGoogle Scholar
• Yoon SM, Ryoo BY, Lee SJ, et al. Efficacy and safety of transarterial chemoembolization plus external beam radiotherapy vs sorafenib in hepatocellular carcinoma with macroscopic vascular invasion: a randomized clinical trial. JAMA Oncol. 2018 May 1;4(5):661–669.
   PubMed Web of Science ®Google Scholar
• Hamada M, Ueshima E, Ishihara T, et al. The feasibility of transcatheter arterial chemoembolization following radiation therapy for hepatocellular carcinoma. Acta Radiol Open. 2021 Jul;10(7):20584601211034965.
   Web of Science ®Google Scholar
• Huang Y, Zhang Z, Liao W, et al. Combination of sorafenib, camrelizumab, transcatheter arterial chemoembolization, and stereotactic body radiation therapy as a novel downstaging strategy in advanced hepatocellular carcinoma with portal vein tumor thrombus: a case series study. Front Oncol. 2021;11:650394.
   PubMed Web of Science ®Google Scholar
• Katsanos K, Kitrou P, Spiliopoulos S, et al. Comparative effectiveness of different transarterial embolization therapies alone or in combination with local ablative or adjuvant systemic treatments for unresectable hepatocellular carcinoma: a network meta-analysis of randomized controlled trials. PloS One. 2017;12(9):e0184597.
   PubMed Web of Science ®Google Scholar
• Daly JM, Kemeny N, Oderman P, et al. Long-term hepatic arterial infusion chemotherapy: anatomic considerations, operative technique, and treatment morbidity. Arch Surg. 1984;119(8):936–941.
   PubMedGoogle Scholar
• Kemeny N, Daly J, Oderman P, et al. Hepatic artery pump infusion: toxicity and results in patients with metastatic colorectal carcinoma. J Clin Oncol. 1984 Jun;2(6):595–600.
   PubMed Web of Science ®Google Scholar
• Liu BJ, Gao S, Zhu X, et al. Combination therapy of chemoembolization and hepatic arterial infusion chemotherapy in hepatocellular carcinoma with portal vein tumor thrombosis compared with chemoembolization alone: a propensity score-matched analysis. Biomed Res Int. 2021;2021:6670367.
   PubMed Web of Science ®Google Scholar
• Izumi R, Shimizu K, Iyobe T, et al. Postoperative adjuvant hepatic arterial infusion of lipiodol containing anticancer drugs in patients with hepatocellular carcinoma. Hepatology. 1994 Aug;20(2):295–301.
   PubMed Web of Science ®Google Scholar
• Li JQ, Zhang YQ, Zhang WZ, et al. Randomized study of chemoembolization as an adjuvant therapy for primary liver carcinoma after hepatectomy. J Cancer Res Clin Oncol. 1995;121(6):364–366.
   PubMed Web of Science ®Google Scholar
• Liu C, Sun L, Xu J, et al. Clinical efficacy of postoperative adjuvant transcatheter arterial chemoembolization on hepatocellular carcinoma. World J Surg Oncol. 2016 Apr;14(1):100.
   PubMedGoogle Scholar
• Li C, Wen TF, Yan LN, et al. Liver resection versus liver resection plus TACE for patients with hepatocellular carcinoma beyond milan criteria. J Surg Res. 2017 Mar;209 8–16.
   PubMed Web of Science ®Google Scholar
• Qi YP, Zhong JH, Liang ZY, et al. Adjuvant transarterial chemoembolization for patients with hepatocellular carcinoma involving microvascular invasion. Am J Surg. 2019 Apr;217(4):739–744.
   PubMed Web of Science ®Google Scholar
• Chen ZH, Zhang XP, Zhou TF, et al. Adjuvant transarterial chemoembolization improves survival outcomes in hepatocellular carcinoma with microvascular invasion: a systematic review and meta-analysis. Eur J Surg Oncol. 2019 Nov;45(11):2188–2196.
   PubMed Web of Science ®Google Scholar
• Shen A, Liu M, Zheng D, et al. Adjuvant transarterial chemoembolization after curative hepatectomy for hepatocellular carcinoma with microvascular invasion: a systematic review and meta-analysis. Clin Res Hepatol Gastroenterol. 2020 Apr;44(2):142–154.
   PubMed Web of Science ®Google Scholar
• Chen W, Ma T, Zhang J, et al. A systematic review and meta-analysis of adjuvant transarterial chemoembolization after curative resection for patients with hepatocellular carcinoma. HPB. 2020 Jun;22(6):795–808.
   PubMed Web of Science ®Google Scholar
• Kudo M, Imanaka K, Chida N, et al. Phase III study of sorafenib after transarterial chemoembolisation in Japanese and Korean patients with unresectable hepatocellular carcinoma. Eur J Cancer. 2011 Sep;47(14):2117–2127.
   PubMed Web of Science ®Google Scholar
• Lencioni R, Llovet JM, Han G, et al. Sorafenib or placebo plus TACE with doxorubicin-eluting beads for intermediate stage HCC: the SPACE trial. J Hepatol. 2016 May;64(5):1090–1098.
   PubMed Web of Science ®Google Scholar
• Meyer T, Fox R, Ma YT, et al. Sorafenib in combination with transarterial chemoembolisation in patients with unresectable hepatocellular carcinoma (TACE 2): a randomised placebo-controlled, double-blind, phase 3 trial. Lancet Gastroenterol Hepatol. 2017 Aug;2(8):565–575.
   PubMed Web of Science ®Google Scholar
• Park JW, Kim YJ, Kim DY, et al. Sorafenib with or without concurrent transarterial chemoembolization in patients with advanced hepatocellular carcinoma: the phase III STAH trial. J Hepatol. 2019 Apr;70(4):684–691.
   PubMed Web of Science ®Google Scholar
• 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. Gut. 2020 Aug;69(8):1492–1501.
   PubMed Web of Science ®Google Scholar
• 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. Lancet Oncol. 2015 Oct;16(13):1344–1354.
   PubMed Web of Science ®Google Scholar
• Tran E, Turcotte S, Gros A, et al. Cancer immunotherapy based on mutation-specific CD4+ T cells in a patient with epithelial cancer. Science (New York, NY). 2014 May 9;344(6184):641–645.
   Google Scholar