Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024;74(3):229–63.

Article  PubMed  Google Scholar 

Koo JE, Kim JH, Lim YS, Park SJ, Won HJ, Sung KB, et al. Combination of transarterial chemoembolization and three-dimensional conformal radiotherapy for hepatocellular carcinoma with inferior vena cava tumor thrombus. Int J Radiat Oncol Biol Phys. 2010;78(1):180–7.

Article  PubMed  Google Scholar 

Wang Y, Yuan L, Ge RL, Sun Y, Wei G. Survival benefit of surgical treatment for hepatocellular carcinoma with inferior vena cava/right atrium tumor thrombus: results of a retrospective cohort study. Ann Surg Oncol. 2013;20(3):914–22.

Article  PubMed  Google Scholar 

Kokudo T, Hasegawa K, Yamamoto S, Shindoh J, Takemura N, Aoki T, et al. Surgical treatment of hepatocellular carcinoma associated with hepatic vein tumor thrombosis. J Hepatol. 2014;61(3):583–8.

Article  PubMed  Google Scholar 

Eskens FA, van Erpecum KJ, de Jong KP, van Delden OM, Klumpen HJ, Verhoef C, et al. Hepatocellular carcinoma: dutch guideline for surveillance, diagnosis and therapy. Neth J Med. 2014;72(6):299–304.

PubMed  CAS  Google Scholar 

Kudo M, Finn RS, Qin S, Han KH, Ikeda K, Piscaglia F, et al. Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial. Lancet. 2018;391(10126):1163–73.

Article  PubMed  CAS  Google Scholar 

Cheng AL, Guan Z, Chen Z, Tsao CJ, Qin S, Kim JS, et al. Efficacy and safety of sorafenib in patients with advanced hepatocellular carcinoma according to baseline status: subset analyses of the phase III Sorafenib Asia-Pacific trial. Eur J Cancer. 2012;48(10):1452–65.

Article  PubMed  CAS  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 

Vogel A, Siegler GM, Siebler J, Lindig U, Schultheiß M, Müller T et al. (2022) IMMUNIB trial (AIO-HEP-0218/ass): A single-arm, phase II study evaluating safety and efficacy of immunotherapy nivolumab in combination with lenvatinib in advanced-stage hepatocellular carcinoma (HCC). 40(16_suppl):4107–4107

Kudo M, Ikeda M, Motomura K, Okusaka T, Kato N, Dutcus CE et al. (2020) A phase Ib study of lenvatinib (LEN) plus nivolumab (NIV) in patients (pts) with unresectable hepatocellular carcinoma (uHCC): Study 117. 38(4_suppl):513–513

Park JW, Chen M, Colombo M, Roberts LR, Schwartz M, Chen PJ, et al. Global patterns of hepatocellular carcinoma management from diagnosis to death: the BRIDGE Study. Liver Int. 2015;35(9):2155–66.

Article  PubMed  PubMed Central  Google Scholar 

Chu HH, Chun SY, Kim JH, Kim PH, Il Gwon D, Ko HK, et al. A prediction model for overall survival after transarterial chemoembolization for hepatocellular carcinoma invading the hepatic vein or inferior vena cava. Eur Radiol. 2021;31(6):4232–42.

Article  PubMed  Google Scholar 

Alrashidi I, Chu HH, Kim JH, Shim JH, Yoon SM, Kim PH, et al. Combined chemoembolization and radiotherapy versus chemoembolization alone for hepatocellular carcinoma invading the hepatic vein or inferior vena cava. Cardiovasc Intervent Radiol. 2021;44(7):1060–9.

Article  PubMed  Google Scholar 

Chern MC, Chuang VP, Cheng T, Lin ZH, Lin YM. Transcatheter arterial chemoembolization for advanced hepatocellular carcinoma with inferior vena cava and right atrial tumors. Cardiovasc Intervent Radiol. 2008;31(4):735–44.

Article  PubMed  CAS  Google Scholar 

Lee IJ, Chung JW, Kim HC, Yin YH, So YH, Jeon UB, et al. Extrahepatic collateral artery supply to the tumor thrombi of hepatocellular carcinoma invading inferior vena cava: the prevalence and determinant factors. J Vasc Interv Radiol. 2009;20(1):22–9.

Article  PubMed  Google Scholar 

Kim YJ, Lee HG, Park JM, Lim YS, Chung MH, Sung MS, et al. Polyvinyl alcohol embolization adjuvant to oily chemoembolization in advanced hepatocellular carcinoma with arterioportal shunts. Korean J Radiol. 2007;8(4):311–9.

Article  PubMed  PubMed Central  Google Scholar 

Heimbach JK, Kulik LM, Finn RS, Sirlin CB, Abecassis MM, Roberts LR, et al. AASLD guidelines for the treatment of hepatocellular carcinoma. Hepatology. 2018;67(1):358–80.

Article  PubMed  Google Scholar 

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 

Kokudo T, Hasegawa K, Matsuyama Y, Takayama T, Izumi N, Kadoya M, et al. Liver resection for hepatocellular carcinoma associated with hepatic vein invasion: a Japanese nationwide survey. Hepatology. 2017;66(2):510–7.

Article  PubMed  CAS  Google Scholar 

Komatsu S, Kido M, Asari S, Toyama H, Ajiki T, Demizu Y, et al. Particle radiotherapy, a novel external radiation therapy, versus liver resection for hepatocellular carcinoma accompanied with inferior vena cava tumor thrombus: a matched-pair analysis. Surgery. 2017;162(6):1241–9.

Article  PubMed  Google Scholar 

Rim CH, Kim CY, Yang DS, Yoon WS. External beam radiation therapy to hepatocellular carcinoma involving inferior vena cava and/or right atrium: a meta-analysis and systemic review. Radiother Oncol. 2018;129(1):123–9.

Article  PubMed  Google Scholar 

Duan F, Yu W, Wang Y, Liu FY, Song P, Wang ZJ, et al. Trans-arterial chemoembolization and external beam radiation therapy for treatment of hepatocellular carcinoma with a tumor thrombus in the inferior vena cava and right atrium. Cancer Imaging. 2015;15(1):7.

Article  PubMed  PubMed Central  Google Scholar 

Ning S, Li X, Ma X, Liu J, Chang X (2023) Efficacy of TACE Combined with Lenvatinib Plus Sintilimab for Hepatocellular Carcinoma with Tumor Thrombus in the Inferior Vena Cava and/or Right Atrium. J Hepatocell Carcinoma. 101511–1525

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  PubMed  CAS  Google Scholar 

Tischfield DJ, Gurevich A, Johnson O, Gatmaytan I, Nadolski GJ, Soulen MC, et al. Transarterial embolization modulates the immune response within target and nontarget hepatocellular carcinomas in a rat model. Radiology. 2022;303(1):215–25.

Article  PubMed  Google Scholar 

Fu Z, Li X, Zhong J, Chen X, Cao K, Ding N, et al. Lenvatinib in combination with transarterial chemoembolization for treatment of unresectable hepatocellular carcinoma (uHCC): a retrospective controlled study. Hepatol Int. 2021;15(3):663–75.

Article  PubMed  Google Scholar 

Matsuki M, Hoshi T, Yamamoto Y, Ikemori-Kawada M, Minoshima Y, Funahashi Y, et al. Lenvatinib inhibits angiogenesis and tumor fibroblast growth factor signaling pathways in human hepatocellular carcinoma models. Cancer Med. 2018;7(6):2641–53.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Chan SL, Sangro B, Kudo M, Erinjeri JP, Qin S, Ren Z et al. (2024) Safety analysis by treatment periods from EMERALD-1: A phase 3, randomized, placebo-controlled study of transarterial chemoembolization with durvalumab with/without bevacizumab in participants with embolization-eligible unresectable hepatocellular carcinoma. 42:4122–4122

Li S, Wu J, Wu J, Fu Y, Zeng Z, Li Y, et al. Prediction of early treatment response to the combination therapy of TACE plus lenvatinib and anti-PD-1 antibody immunotherapy for unresectable hepatocellular carcinoma: Multicenter retrospective study. Front Immunol. 2023;14:141109771.

Google Scholar 

Zhou T, Wang X, Cao Y, Yang L, Wang Z, Ma A, et al. Cost-effectiveness analysis of sintilimab plus bevacizumab biosimilar compared with lenvatinib as the first-line treatment of unresectable or metastatic hepatocellular carcinoma. BMC Health Serv Res. 2022;22(1):1367.

Article  PubMed  PubMed Central  Google Scholar 

Zhang L, Sun J, Wang K, Zhao H, Zhang X, Ren Z. First- and second-line treatments for patients with advanced hepatocellular carcinoma in China: a systematic review. Curr Oncol. 2022;29(10):7305–26.

Article  PubMed  PubMed Central  Google Scholar 

Wang M, Sun L, Han X, Ren J, Li H, Wang W, et al. The addition of camrelizumab is effective and safe among unresectable hepatocellular carcinoma patients who progress after drug-eluting bead transarterial chemoembolization plus apatinib therapy. Clin Res Hepatol Gastroenterol. 2022;47(1):102060.

Article  PubMed  Google Scholar