Kudo M, Izumi N, Kubo S, Kokudo N, Sakamoto M, Shiina S, et al. Report of the 20th nationwide follow-up survey of primary liver cancer in Japan. Hepatol Res. 2020;50(1):15–46.

Article  PubMed  PubMed Central  Google Scholar 

Lu J, Zhang XP, Zhong BY, Lau WY, Madoff DC, Davidson JC, et al. Management of patients with hepatocellular carcinoma and portal vein tumour thrombosis: comparing east and west. Lancet Gastroenterol Hepatol. 2019;4(9):721–30.

Article  PubMed  Google Scholar 

Cheng S, Chen M, Cai J, Sun J, Guo R, Bi X, et al. Chinese expert consensus on multidisciplinary diagnosis and treatment of hepatocellular carcinoma with portal vein tumor thrombus. Liver Cancer. 2020;9(1):28–40.

Article  PubMed  Google Scholar 

Zhang XP, Gao YZ, Chen ZH, Chen MS, Li LQ, Wen TF, et al. An eastern hepatobiliary surgery hospital/portal vein tumor thrombus scoring system as an aid to decision making on hepatectomy for hepatocellular carcinoma patients with portal vein tumor thrombus: a multicenter study. Hepatology. 2019;69(5):2076–90.

Article  PubMed  Google Scholar 

Reig M, Forner A, Rimola J, Ferrer-Fàbrega J, Burrel M, Garcia-Criado Á, et al. BCLC strategy for prognosis prediction and treatment recommendation: the 2022 update. J Hepatol. 2022;76(3):681–93.

Article  PubMed  Google Scholar 

Bruix J, Raoul JL, Sherman M, Mazzaferro V, Bolondi L, Craxi A, et al. Efficacy and safety of sorafenib in patients with advanced hepatocellular carcinoma: subanalyses of a phase III trial. J Hepatol. 2012;57(4):821–9.

Article  CAS  PubMed  Google Scholar 

Zheng K, Zhu X, Fu S, Cao G, Li WQ, Xu L, et al. Sorafenib plus hepatic arterial infusion chemotherapy versus sorafenib for hepatocellular carcinoma with major portal vein tumor thrombosis: a randomized trial. Radiology. 2022;303(2):455–64.

Article  PubMed  Google Scholar 

He M, Li Q, Zou R, Shen J, Fang W, Tan G, et al. Sorafenib plus hepatic arterial infusion of oxaliplatin, fluorouracil, and leucovorin versus sorafenib alone for hepatocellular carcinoma with portal vein invasion: a randomized clinical trial. JAMA Oncol. 2019;5(7):953–60.

Article  PubMed  PubMed Central  Google Scholar 

El-Khoueiry AB, Sangro B, Yau T, Crocenzi TS, Kudo M, Hsu C, et al. Nivolumab in patients with advanced hepatocellular carcinoma (CheckMate 040): an open-label, non-comparative, phase 1/2 dose escalation and expansion trial. Lancet. 2017;389(10088):2492–502.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Finn RS, Ryoo BY, Merle P, Kudo M, Bouattour M, Lim HY, et al. Pembrolizumab as second­line therapy in patients with advanced hepatocellular carcinoma in KEYNOTE­240: a randomized, double­blind, phase III trial. J Clin Oncol. 2020;38(3):193–202.

Article  CAS  PubMed  Google Scholar 

Qin S, Ren Z, Meng Z, Chen Z, Chai X, Xiong J, et al. Camrelizumab in patients with previously treated advanced hepatocellular carcinoma: a multicentre, open-label, parallel-group, randomised, phase 2 trial. Lancet Oncol. 2020;21(4):571–80.

Article  CAS  PubMed  Google Scholar 

Finn RS, Qin S, Ikeda M, Galle PR, Ducreux M, Kim TY, et al. Atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma. New Engl J Med. 2020;382(20):1894–905.

Article  CAS  PubMed  Google Scholar 

Breder VV, Vogel A, Merle P, et al. IMbrave150: exploratory efficacy and safety results of hepatocellular carcinoma (HCC) patients (pts) with main trunk and/or contralateral portal vein invasion (Vp4) treated with atezolizumab (atezo) + bevacizumab (bev) versus sorafenib (sor) in a global Ph III study. J Clin Oncol. 2021;39(suppl 15):4073.

Article  Google Scholar 

Ren Z, Xu J, Bai Y, Xu A, Cang S, Du C, et al. Sintilimab plus a bevacizumab biosimilar (IBI305) versus sorafenib in unresectable hepatocellular carcinoma (ORIENT-32): a randomised, open-label, phase 2–3 study. Lancet Oncol. 2021;22(7):977–90.

Article  CAS  PubMed  Google Scholar 

Xu J, Shen J, Gu S, Zhang Y, Wu L, Wu J, et al. Camrelizumab in combination with apatinib in patients with advanced hepatocellular carcinoma (RESCUE): a nonrandomized, open-label phase II trial. Clin Cancer Res. 2021;27(4):1003–11.

Article  CAS  PubMed  Google Scholar 

Finn RS, Ikeda M, Zhu AX, Sung MW, Baron AD, Kudo M, et al. Phase Ib study of lenvatinib plus pembrolizumab in patients with unresectable hepatocellular carcinoma. J Clin Oncol. 2020;38(26):2960–70.

Article  PubMed  PubMed Central  Google Scholar 

Farid K, Elalfy H, Abo El-Khair SM, Elgamal H, Besheer T, Elmokadem A, et al. Prognostic value of vascular endothelial growth factor in both conventional and drug eluting beads transarterial chemoembolization for treatment of unresectable hepatocellular carcinoma in HCV patients. Expert Rev Gastroenterol Hepatol. 2020;14(12):1203–14.

Article  CAS  PubMed  Google Scholar 

Takaki H, Hirata Y, Ueshima E, Kodama H, Matsumoto S, Wada R, et al. Hepatic artery embolization enhances expression of programmed cell death 1 ligand 1 in an orthotopic rat hepatocellular carcinoma model in vivo and in vitro experimentation. J Vasc Interv Radiol. 2020;31(9):1475-1482 e2.

Article  PubMed  Google Scholar 

Llovet JM, De Baere T, Kulik L, Haber PK, Greten TF, Meyer T, et al. Locoregional therapies in the era of molecular and immune treatments for hepatocellular carcinoma. Nat Rev Gastroenterol Hepatol. 2021;18(5):293–313.

Article  CAS  PubMed  Google Scholar 

Pinato DJ, Murray SM, Forner A, Kaneko T, Fessas P, Toniutto P, et al. Trans-arterial chemoembolization as a loco-regional inducer of immunogenic cell death in hepatocellular carcinoma: implications for immunotherapy. J Immunother Cancer. 2021;9(9):e003311. https://doi.org/10.1136/jitc-2021-003311.

Article  PubMed  PubMed Central  Google Scholar 

Ochoa de Olza M, Navarro Rodrigo B, Zimmermann S, Coukos G. Turning up the heat on non-immunoreactive tumours: opportunities for clinical development. Lancet Oncol. 2020;21(9):e419–30.

Article  CAS  PubMed  Google Scholar 

Zhou J, Sun H, Wang Z, Cong W, Zeng M, Zhou W, et al. Guidelines for the diagnosis and treatment of primary liver cancer. Liver Cancer. 2023;12(5):405–44.

Article  PubMed  PubMed Central  Google Scholar 

Kudo M, Kawamura Y, Hasegawa K, Tateishi R, Kariyama K, Shiina S, et al. Management of hepatocellular carcinoma in Japan: JSH consensus statements and recommendations 2021 update. Liver Cancer. 2021;10(3):181–223.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Llovet JM, Lencioni R. mRECIST for HCC: performance and novel refinements. J Hepatol. 2020;72(2):288–306.

Article  PubMed  Google Scholar 

US Department of Health and Human Services, National Institutes of Health, National Cancer Institute. Common terminology criteria for adverse events (CTCAE) common terminology criteria for adverse events (CTCAE) version 5. Published: Nov 27, 2017.

Halpern EF. Behind the numbers: inverse probability weighting. Radiology. 2014;271(3):625–8.

Article  PubMed  Google Scholar 

Yuan Y, He W, Yang Z, Qiu J, Huang Z, Shi Y, et al. TACE-HAIC combined with targeted therapy and immunotherapy versus TACE alone for hepatocellular carcinoma with portal vein tumour thrombus: a propensity score matching study. Int J Surg. 2023;109(5):1222–30.

Article  PubMed  PubMed Central  Google Scholar 

Zhu K, Chen J, Lai L, Meng X, Zhou B, Huang W, et al. Hepatocellular carcinoma with portal vein tumor thrombus: treatment with transarterial chemoembolization combined with sorafenib-a retrospective controlled study. Radiology. 2014;272(1):284–93.

Article  PubMed  Google Scholar 

Wu JY, Yin ZY, Bai YN, Chen YF, Zhou SQ, Wang SJ, et al. Lenvatinib combined with anti-PD-1 antibodies plus transcatheter arterial chemoembolization for unresectable hepatocellular carcinoma: a multicenter retrospective study. J Hepatocell Carcinoma. 2021;5(8):1233–40.

Article  Google Scholar 

Zhang JX, Chen YX, Zhou CG, Liu J, Liu S, Shi HB, et al. Efficacy and safety of the combination of transarterial chemoembolization with camrelizumab plus apatinib for advanced hepatocellular carcinoma: a retrospective study of 38 patients from a single center. Can J Gastroenterol Hepatol. 2022;9(2022):7982118. https://doi.org/10.1155/2022/7982118.

Article  Google Scholar 

Huang JT, Zhong BY, Jiang N, Li WC, Zhang S, Yin Y, et al. Transarterial chemoembolization combined with immune checkpoint inhibitors plus tyrosine kinase inhibitors versus immune checkpoint inhibitors plus tyrosine kinase inhibitors for advanced hepatocellular carcinoma. J Hepatocell Carcinoma. 2022;9:1217–28.

Article  PubMed  PubMed Central  Google Scholar 

Li X, Wang Y, Ye X, Liang P. Locoregional combined with systemic therapies for advanced hepatocellular carcinoma: an inevitable trend of rapid development. Front Mol Biosci. 2021;8:635243. https://doi.org/10.3389/fmolb.2021.635243.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Akyildiz A, Guven DC, Ozluk AA, Ismayilov R, Mutlu E, Unal OU, et al. The safety and efficacy of first-line atezolizumab plus bevacizumab in patients with unresectable hepatocellular carcinoma: a multicenter real-world study from Turkey. Medicine. 2023;102(45):e35950.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Wang Q, Xia D, Bai W, Wang E, Sun J, Huang M, et al. Development of a prognostic score for recommended TACE candidates with hepatocellular carcinoma: a multicentre observational study. J Hepatol. 2019;70(5):893–903.

Article  PubMed  Google Scholar 

Cheng S, Hu G, Jin Z, Wang Z, Xue H. CT-based radiomics nomogram for prediction of survival after transarterial chemoembolization with drug-eluting beads in patients with hepatocellular carcinoma and portal vein tumor thrombus. Eur Radiol. 2023. https://doi.org/10.1007/s00330-023-09830-7.

Article  PubMed  PubMed Central  Google Scholar