A Systematic Review Of Hepatic Arterial Infusion Chemotherapy Versus Sorafenib In Patients With Hepatocellular Carcinoma With Portal Vein Tumor Thrombosis

Objective: Portal vein tumor thrombosis(PVTT)is one of the main complications of hepatocellular carcinoma(HCC),which occurs in about40% of first-diagnosited patients.PVTT is an important marker of HCC with poor prognosis.If only choose optimal supportive treatment,the patients' median overall survival(mOS)is only 2-12 months.The American Association for the Study of Liver Diseases(AASLD),Asian-Pacific Association for the Study of the Liver(APASL)and European Association for the Study of the Liver(EASL)guidelines recommended sorafenib as the only first-line treatment strategy for HCC with PVTT patients,but the result is still not very satisfactory for the mOS extended only about three months.Before the development of molecular targeted drug therapies based on evidence from randomized controlled trials,in east asian regions like Japan or Korea,the hepatic arterial infusion chemotherapy(HAIC)was widely used in advanced HCC which with vascular invasion or metastasis of intrahepatic lesions in clinical for its exact efficacy.Several recent studies have shown that HAIC is better than sorafenib in the treatment of HCC with PVTT.But for the relevant of these studies are small,the evidence level is limited.Sorafenib is still the only first-line treatment strategy for advanced HCC.Our Meta-analysis systematically evaluates theefficacy and safety of hepatic artery infusion chemotherapy verses sorafenib in the treatment of HCC patients with PVTT,aims for attentions at the choice of treatment strategies in HCC with PVTT.Methods: Searched online in Embase and MEDLINE for all literatures about HAIC comparing with sorafenib in treatment of HCC with PVTT.The first endpoints were overall survival(OS),the secondary endpoints were progression-free survival(PFS),disease control rate(DCR)and adverse effects.Made inclusion and exclusion criterias,screening the literature according to the flow figure,extracted the data from the studies,used Stata 13.0 software and selected the DerSimonian and Laird random effect model for merge analysis,discussed whether if there are heterogeneities and the reason of heterogeneities.The Begg's and Egger's test were used to detect whether there was publication bias in included studies and discussed the reason.Our study strictly followed the requirements of the PRISMA Statements.Results: We finally found 6 eligible studies,including 417 patients.Among these patients,225 were in the HAIC group and 192 were in the sorafenib group.Our meta-analysis showed that,for OS,the HAIC was superior to sorafenib(hazard ratio(HR): 0.50,95% CI(0.38,0.66),P <0.001),DFS got the same clusion(HR: 0.47,95% CI: 0.31-0.73,P=0.001),independently different of the scopes and quality of these studies.Our meta-analysis also demonstrated that HAIC is superior than sorafenib in terms of disease control rate(DCR).Subgroup analysis showed that for the III or the IV types of PVTT,HAIC has more advantages(OS(HR: 0.29,P<0.001))and(HR: 0.39,P=0.001).HAIC causes more 3-4 grades of neutropenia(RR: 10.71),anemia(RR: 7.55),leukopenia(RR: 10.38),and thrombocytopenia(RR: 13.09),but less 3-4 grades of AST elevation(RR:0.21),diarrhea(RR: 0.14),and hand or foot syndromes(HFS).Conclusion: Hepatic arterial infusion chemotherapy has more advantages than sorafenib in OS?PFS and DCR when treating patients of III-IV types hepatocellular carcinoma with portal vein tumor thrombosis.Meanwhile,hepatic arterial infusion chemotherapy causes more bone marrow suppression,while sorafenib causes more diarrhea and hand-foot syndrome.