To compare the efficacy and safety of hepatic arterial infusion chemotherapy (HAIC) to transarterial chemoembolization/embolization (TACE/TAE) for the treatment of advanced hepatocellular carcinoma (HCC) with major portal vein tumor thrombosis (PVTT).
Materials and Methods
Forty-six patients with advanced HCC with major PVTT who underwent HAIC or TACE/TAE between April 2013 and April 2017 were included. In the HAIC group (n = 22), oxaliplatin (35–40 mg/m2 for 2 h) and 5-fluorouracil (600–800 mg/m2 for 22 h) on days 1–3 every 4 weeks were administered for a maximum of six serial courses. In the TACE/TAE group (n = 24), an emulsion of epirubicin (40–60 mg) and lipiodol was administered followed by particles (cTACE), or particles alone embolization (TAE). Overall survival (OS), tumor response according to mRECIST, progression-free survival (PFS), and adverse events were investigated.
Median OS was 20.8 months in the HAIC group versus 4.0 months in the TACE/TAE group (P < 0.001; hazard ratio [HR], 0.17). The HAIC group showed higher tumor response rates than the TACE/TAE group (59.1% [13/22] vs. 22.7% [5/22]; P = 0.014) and a longer median PFS (9.6 vs. 1.5 months; P < 0.001; HR, 0.09). The Child–Pugh class (P = 0.007) and treatment method (P = 0.002) were independent risk factors of survival. The most frequent grade 3 or worse treatment-related adverse events were liver dysfunction (2 [9.1%] vs. 5 [20.8%]), hematological abnormalities (1 [4.5%] vs. 2 [8.3%]), and fever (1 [4.5%] vs. 4 [16.7%]). One treatment-related death due to acute liver failure occurred 3 days after TACE treatment.
HAIC may significantly improve OS and provide better tumor control with mild side effects and preserved liver function in patients with advanced HCC with major PVTT compared to TACE/TAE treatment.
This is a preview of subscription content, log in to check access.
Buy single article
Instant access to the full article PDF.
Price includes VAT for USA
Subscribe to journal
Immediate online access to all issues from 2019. Subscription will auto renew annually.
This is the net price. Taxes to be calculated in checkout.
Hepatic arterial infusion chemotherapy
Portal vein tumor thrombosis
Llovet JM, Bustamante J, Castells A, et al. Natural history of untreated nonsurgical hepatocellular carcinoma: rationale for the design and evaluation of therapeutic trials. Hepatology. 1999;29:62–7.
Yu SJ, Kim YJ. Effective treatment strategies other than sorafenib for the patients with advanced hepatocellular carcinoma invading portal vein. World J Hepatol. 2015;7:1553–61.
Kudo M, Izumi N, Kokudo N, et al. Management of hepatocellular carcinoma in Japan: consensus-based clinical practice guidelines proposed by the Japan Society of Hepatology (JSH) 2010 updated version. Dig Dis. 2011;29:339–64.
Jeong SW, Jang JY, Shim KY, et al. Practical effect of sorafenib monotherapy on advanced hepatocellular carcinoma and portal vein tumor thrombosis. Gut Liver. 2013;7:696–703.
Choi JH, Chung WJ, Bae SH, et al. Randomized, prospective, comparative study on the effects and safety of sorafenib versus hepatic arterial infusion chemotherapy in patients with advanced hepatocellular carcinoma with portal vein tumor thrombosis. Cancer Chemother Pharmacol. 2018;82:469–78.
Kokudo T, Hasegawa K, Matsuyama Y, et al. Survival benefit of liver resection for hepatocellular carcinoma associated with portal vein invasion. J Hepatol. 2016;65:938–43.
Lv WF, Liu KC, Lu D, et al. Transarterial chemoembolization for hepatocellular carcinoma combined with portal vein tumor thrombosis. Cancer Manag Res. 2018;10:4719–26.
Cho YY, Lee M, Kim HC, et al. Radioembolization is a safe and effective treatment for hepatocellular carcinoma with portal vein thrombosis: a propensity score analysis. PLoS ONE. 2016;11:e0154986.
Liang H, Cui P, Guo Q, et al. Prognostic factors of hepatocellular carcinoma patients with portal vein tumor thrombosis treated with transcatheter arterial chemoembolization. Asia Pac J Clin Oncol. 2017;13:e331–41.
Sun J, Shi J, Huang B, et al. The degree of hepatic arterial blood supply of portal vein tumor thrombus in patients with hepatocellular carcinoma and its impact on overall survival after transarterial chemoembolization. Oncotarget. 2017;8:79816–24.
Obi S, Sato S, Kawai T. Current status of hepatic arterial infusion chemotherapy. Liver cancer. 2015;4:188–99.
Del Freo A, Fiorentini G, Sanguinetti F, et al. Hepatic arterial chemotherapy with oxaliplatin, folinic acid and 5-fluorouracil in pre-treated patients with liver metastases from colorectal cancer. In Vivo (Athens, Greece). 2006;20:743–6.
Wang X, Hu J, Cao G, et al. Phase II study of hepatic arterial infusion chemotherapy with oxaliplatin and 5-fluorouracil for advanced perihilar cholangiocarcinoma. Radiology. 2017;283:580–9.
Lyu N, Lin Y, Kong Y, et al. FOXAI: a phase II trial evaluating the efficacy and safety of hepatic arterial infusion of oxaliplatin plus fluorouracil/leucovorin for advanced hepatocellular carcinoma. Gut. 2018;67:395–6.
He MK, Zou RH, Li QJ, et al. Phase II study of sorafenib combined with concurrent hepatic arterial infusion of oxaliplatin, 5-fluorouracil and leucovorin for unresectable hepatocellular carcinoma with major portal vein thrombosis. Cardiovasc Intervent Radiol. 2018;41:734–43.
Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45:228–47.
Ando E, Tanaka M, Yamashita F, et al. Hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma with portal vein tumor thrombosis: analysis of 48 cases. Cancer. 2002;95:588–95.
Hu J, Zhu X, Wang X, Cao G, Wang X, Yang R. Evaluation of percutaneous unilateral trans-femoral implantation of side-hole port-catheter system with coil only fixed-catheter-tip for hepatic arterial infusion chemotherapy. Cancer Imaging. 2019;19:15.
Hildebrandt B, Pech M, Nicolaou A, et al. Interventionally implanted port catheter systems for hepatic arterial infusion of chemotherapy in patients with colorectal liver metastases: a phase II-study and historical comparison with the surgical approach. BMC Cancer. 2007;7:69.
Tsimberidou AM, Fu S, Ng C, et al. A phase 1 study of hepatic arterial infusion of oxaliplatin in combination with systemic 5-fluorouracil, leucovorin, and bevacizumab in patients with advanced solid tumors metastatic to the liver. Cancer. 2010;116:4086–94.
Qin B, Tanaka R, Shibata Y, et al. In-vitro schedule-dependent interaction between oxaliplatin and 5-fluorouracil in human gastric cancer cell lines. Anticancer Drugs. 2006;17:445–53.
Wang J-C, Xia A-L, Xu Y, Lu X-J. Comprehensive treatments for hepatocellular carcinoma with portal vein tumor thrombosis. J Cell Physiol. 2019;234:1062–70.
Kim PH, Choi SH, Kim JH, Park SH. Comparison of radioembolization and sorafenib for the treatment of hepatocellular carcinoma with portal vein tumor thrombosis: a systematic review and meta-analysis of safety and efficacy. Korean J Radiol. 2019;20:385–98.
Zhang L, Hu B, Li W, et al. 125I irradiation stent for hepatocellular carcinoma with main portal vein tumor thrombosis: a systematic review. Cardiovasc Interv Radiol. 2020;43:196–203.
Lee JM, Jang BK, Lee YJ, et al. Survival outcomes of hepatic resection compared with transarterial chemoembolization or sorafenib for hepatocellular carcinoma with portal vein tumor thrombosis. Clin Mol Hepatol. 2016;22:160–7.
Zhu K, Chen J, Lai L, et al. Hepatocellular carcinoma with portal vein tumor thrombus: treatment with transarterial chemoembolization combined with sorafenib—a retrospective controlled study. Radiology. 2014;272:284–93.
Georgiades CS, Hong K, D’Angelo M, Geschwind JF. Safety and efficacy of transarterial chemoembolization in patients with unresectable hepatocellular carcinoma and portal vein thrombosis. J Vasc Interv Radiol JVIR. 2005;16:1653–9.
Mazzaferro V, Sposito C, Bhoori S, et al. Yttrium-90 radioembolization for intermediate-advanced hepatocellular carcinoma: a phase 2 study. Hepatology. 2013;57:1826–37.
Edeline J, Crouzet L, Campillo-Gimenez B, et al. Selective internal radiation therapy compared with sorafenib for hepatocellular carcinoma with portal vein thrombosis. Eur J Nucl Med Mol Imaging. 2016;43:635–43.
Golfieri R, Mosconi C, Cappelli A, et al. Efficacy of radioembolization according to tumor morphology and portal vein thrombosis in intermediate-advanced hepatocellular carcinoma. Future Oncol (London, England). 2015;11:3133–42.
Theysohn JM, Ertle J, Muller S, et al. Hepatic volume changes after lobar selective internal radiation therapy (SIRT) of hepatocellular carcinoma. Clin Radiol. 2014;69:172–8.
Kudo M, Matsui O, Izumi N, et al. JSH consensus-based clinical practice guidelines for the management of hepatocellular carcinoma: 2014 update by the Liver Cancer Study Group of Japan. Liver Cancer. 2014;3:458–68.
Lin CC, Hung CF, Chen WT, Lin SM. Hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma with portal vein thrombosis: impact of early response to 4 weeks of treatment. Liver cancer. 2015;4:228–40.
Nouso K, Miyahara K, Uchida D, et al. Effect of hepatic arterial infusion chemotherapy of 5-fluorouracil and cisplatin for advanced hepatocellular carcinoma in the Nationwide Survey of Primary Liver Cancer in Japan. Br J Cancer. 2013;109:1904–7.
Kelland L. The resurgence of platinum-based cancer chemotherapy. Nat Rev Cancer. 2007;7:573–84.
Melichar B, Ferko A, Krajina A, et al. Hepatic arterial infusion of oxaliplatin, 5-fluorouracil and leucovorin in patients with liver metastases from colorectal carcinoma. J BUON. 2012;17:677–83.
Karanicolas PJ, Metrakos P, Chan K, et al. Hepatic arterial infusion pump chemotherapy in the management of colorectal liver metastases: expert consensus statement. Curr Oncol (Toronto, Ont). 2014;21:e129–36.
Luo J, Guo RP, Lai EC, et al. Transarterial chemoembolization for unresectable hepatocellular carcinoma with portal vein tumor thrombosis: a prospective comparative study. Ann Surg Oncol. 2011;18:413–20.
Nakazawa T, Hidaka H, Shibuya A, et al. Overall survival in response to sorafenib versus radiotherapy in unresectable hepatocellular carcinoma with major portal vein tumor thrombosis: propensity score analysis. BMC Gastroenterol. 2014;14:84.
This project was supported by National Science Foundation of China (No. 81471759). We would like to thank Accdon for its linguistic assistance during the preparation of this manuscript. We thank LetPub (www.letpub.com) for its linguistic assistance during the preparation of this manuscript.
Conflict of interest
The authors declare that they have no conflict of interest.
Ethical Approval Statement
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. For this retrospective study, formal consent is not required.
Informed Consent Statement
Informed consent was obtained from all individual participants included in the study.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Jungang Hu and Quan Bao are co-first author.
About this article
Cite this article
Hu, J., Bao, Q., Cao, G. et al. Hepatic Arterial Infusion Chemotherapy Using Oxaliplatin Plus 5-Fluorouracil Versus Transarterial Chemoembolization/Embolization for the Treatment of Advanced Hepatocellular Carcinoma with Major Portal Vein Tumor Thrombosis. Cardiovasc Intervent Radiol 43, 996–1005 (2020). https://doi.org/10.1007/s00270-019-02406-3
- Hepatic arterial infusion chemotherapy
- Hepatocellular carcinoma
- Portal vein tumor thrombosis
- Transarterial chemoembolization