Sorafenib is not recommended for advanced hepatocellular carcinoma (HCC) patients with Vp4 (portal invasion at the main trunk) by the Japan Society of Hepatology (JSH) due to a risk of hepatic failure. This study aimed to elucidate the safety and efficacy of sorafenib monotherapy on HCC with macro-vascular invasion (MVI). A total of 415 consecutive advanced HCC patients received sorafenib in our hospital. Patients with only MVI and sorafenib monotherapy were retrospectively enrolled. We enrolled 113 (27.2%) patients, including 56 (49.5%) Vp3 (portal invasion at the first branch) and 57 (50.5%) Vp4. Their median intervals of follow-up and sorafenib-use were 7.8 months and 2.7 months respectively. Using sorafenib, more Vp4 had hepatic decompensation (HD) (37% VS 18.2%, p = 0.028) than Vp3 patients. The multivariate analysis showed Vp4 (Odds ratio: 2.91; 95% CI: 1.02–8.3, p = 0.041) and baseline alpha-fetoprotein (AFP) ≥ 200 ng/ml were associated with HD. Dividing our patients into four subgroups as Vp3 + AFP < 200 ng/ml, Vp3 + AFP ≥ 200 ng/ml, Vp4 + AFP < 200 ng/ml and Vp4 + AFP ≥ 200 ng/ml, the proportions of HD were 16.7%, 19.4%, 16.7% and 55.2% respectively (p = 0.002). The overall survival rates were distributed with a significant decreasing trend as 10.2 ± 4.4 months, 6.5 ± 1.0 months, 6.0 ± 1.3 months and 2.5 ± 0.5 months (p = 0.001). We found only Vp4 plus AFP ≥ 200 ng/ml could induce more HD and a poorer prognosis than Vp3 patients. Hence, in Vp4 patients with higher AFP, sorafenib should not be the first-line treatment due to its limited survival benefit.
This is a preview of subscription content, log in to check access.
We appreciated Miss Chih-Yun Lin and the Biostatistics Center, Kaohsiung Chang Gung Memorial Hospital for the excellent statistical analysis.
Compliance with ethical standards
All procedures performed in studies involving human participants were in accordance with the ethical standards of the Institutional Review Board of Kaohsiung Chang Gung Memorial Hospital and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Written informed consent was obtained from all individual participants included in the present study.
Conflict of interest
Prof. Sheng-Nan Lu received a grant from Chang Gung Memorial Hospital (CMRPG:8B1413). The remaining authors have no conflict of interest.
This study was supported by a grant from Chang Gung Memorial Hospital (CMRPG:8B1413) to Prof. Sheng-Nan Lu.
Lozano R, Naghavi M, Foreman K et al (2012) Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the global burden of disease study 2010. Lancet 380:2015–2028CrossRefGoogle Scholar
Kuo YH1, Lu SN, Chen CL, et al. Hepatocellular carcinoma surveillance and appropriate treatment options improve survival for patients with liver cirrhosis. Eur J Cancer. 2010;46(4):744–751.Google Scholar
Llovet JM, Ricci S, Mazzaferro V et al (2008) Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 359:378–390CrossRefPubMedGoogle Scholar
Cheng AL, Kang YK, Chen Z et al (2009) Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial. Lancet Oncol 10:25–34CrossRefPubMedGoogle Scholar
European Association for the Study of the Liver1 (2012) European Organisation for Research and Treatment of Cancer EASL-EORTC clinical practice guidelines: management of hepatocellular carci- noma. J Hepatol 56:908–943CrossRefGoogle Scholar
Omata M, Lesmana LA, Tateishi R et al (2010) Asian Pacific Association for the Study of the liver consensus recommendations on hepatocellular carcinoma. Hepatol Int 4:439–474CrossRefPubMedPubMedCentralGoogle Scholar
Kane RC, Farrell AT, Madabushi R et al (2009) Sorafenib for the treatment of unresectable hepatocellular carcinoma. Oncologist 14:95–100CrossRefPubMedGoogle Scholar
Lee IC, Chen YT, Chao Y et al (2015) Determinants of survival after sorafenib failure in patients with BCLC-C hepatocellular carcinoma in real-world practice. Medicine (Baltimore) 94(14):e688CrossRefGoogle Scholar
Nishikawa H, Takeda H, Tsuchiya K et al (2014) Sorafenib therapy for BCLC stage B/C hepatocellular carcinoma; clinical outcome and safety in aged patients: a multicenter study in Japan. J Cancer 5:499–509CrossRefPubMedPubMedCentralGoogle Scholar
Lee WJ, Lee JL, Chang SE et al (2009) Cutaneous adverse effects in patients treated with the multitargeted kinase inhibitors sorafenib and sunitinib. Br J Dermatol 161:1045–1051CrossRefPubMedGoogle Scholar
Ogasawara S, Kanai F, Obi S et al (2011) Safety and tolerance of sorafenib in Japanese patients with advanced he- patocellular carcinoma. Hepatol Int 5:850–856CrossRefPubMedGoogle Scholar
Shen A, Tang C, Wang Y et al (2013) A systematic review of sorafenib in Child-Pugh a patients with unresectable hepatocellular carcinoma. J Clin Gastroenterol 47(10):871–880CrossRefPubMedGoogle Scholar
Yamakado K, Tanaka N, Nakatsuka A, Matsumura K, Takase K (1999) Clinical efficacy of portal vein stent placement in patients with hepatocellular carcinoma invading the main portal vein. J Hepatol 30:660–668CrossRefPubMedGoogle Scholar
Kudo M, Matsui O, Izumi N et al (2014) JSH consensus-based clinical practice guidelines for the Management of Hepatocellular Carcinoma: 2014 update by the liver cancer study Group of Japan. Liver Cancer 3(3–4):458–468CrossRefPubMedPubMedCentralGoogle Scholar
Lencioni R, Llovet JM (2010) Modified RECIST (mRECIST) assessment for hepatocellular carcinoma. Semin Liver Dis 30:52–60CrossRefPubMedGoogle Scholar
Lens S, Rincón D, García-Retortillo M et al (2015) Association between severe portal hypertension and risk of liver decompensation in patients with hepatitis C, regardless of response to antiviral therapy. Clin Gastroenterol Hepatol 13:1846–1853CrossRefPubMedGoogle Scholar
Perumalswami PV, Patel N, Bichoupan K et al (2016) High baseline bilirubin and low albumin predict liver decompensation and serious adverse events in HCV-infected patients treated with sofosbuvir-containing regimens. J Viral Hepat 23:667–676CrossRefPubMedGoogle Scholar
Ban D, Shimada K, Yamamoto Y et al (2009) Efficacy of a hepatectomy and a tumor thrombectomy for hepatocellular carcinoma with tumor thrombus extending to the main portal vein. J Gastrointest Surg 13:1921–1928CrossRefPubMedGoogle Scholar
Hidaka H, Nakazawa T, Kaneko T et al (2012) Portal hemodynamic effects of sorafenib in patients with advanced hepatocellular carcinoma: a prospective cohort study. J Gastroenterol 47:1030–1035CrossRefPubMedGoogle Scholar
Raoul JL, Bruix J, Greten TF et al (2012) Relationship between baseline hepatic status and outcome, and effect of sorafenib on liver function: SHARP trial subanalyses. J Hepatol 56:1080–1088CrossRefPubMedGoogle Scholar
Iavarone M, Cabibbo G, Biolato M et al (2015) Predictors of survival of patients with advanced hepatocellular carcinoma who permanently discontinued sorafenib. Hepatology 62(3):784–791CrossRefPubMedGoogle Scholar
Iavarone M, Cabibbo G, Piscaglia F et al (2011) Field-practice study of sorafenib therapy for hepatocellular carcinoma: a prospective multi- center study in Italy. Hepatology 54:2055–2063CrossRefPubMedGoogle Scholar