SITS Combination Therapy In Advanced Hepatocellular Carcinoma With Portal Vein Tumor Thrombus

Background: Portal vein tumor thrombus(PVTT)is one of the most severe complications of hepatocellular carcinoma(HCC).Most HCC patients are in advanced stage at the time of diagnosis,losing the opportunity of surgical resection and having a poor prognosis.In recent years,with the continuous emergence and development of targeted therapy and immunotherapeutic drugs for hepatocellular carcinoma,as well as the progress of locoregional therapy such as transcatheter arterial chemoembolization,radiotherapy and hepatic arterial infusion chemotherapy,the combination of different treatment methods has been studied as a combined treatment scheme for advanced HCC with PVTT,which has significantly improved the prognosis of advanced HCC with PVTT.Some combination therapies can achieve the successful downstaging of advanced hepatocellular carcinoma and transform the initial unresectable hepatocellular carcinoma into resectable hepatocellular carcinoma.Some patients with advanced HCC with PVTT underwent surgical resection after successful conversion,thereby improving the prognosis and achieving long-term survival.Aim: This retrospective study aims to compare the effectiveness of a combination therapy(SITS group)of sorafenib,immune checkpoint inhibitor(ICI),transcatheter arterial chemoembolization(TACE),and stereotactic body radiation therapy(SBRT)with a combination therapy(ST group)of sorafenib and TACE in treating and downstaging advanced hepatocellular carcinoma with portal vein tumor thrombus,and to evaluate the downstaging conversion efficacy and safety profile of SITS combination therapy.Methods: This retrospective comparative study included patients having advanced HCC with PVTT,who received one of the two combination therapies from January 2014 to August 2021 in Xiangya Hospital,Central South University.The successful conversion rate,treatment responses,progression-free survival(PFS),overall survival(OS),disease control rate(DCR),and safety profile were evaluated.Results: A total of 62 patients were finally included and analyzed in this study.The objective response rate was significantly higher in the SITS group than the ST group(53.3% vs.25.0%,P=0.036),however no significant difference was shown in DCR(P=0.067).Survival analysis showed a better PFS(P=0.015)and OS(P=0.013)of patients in the SITS group with the median PFS time as 10.4 months,and the median OS time as 13.8 months.10(33.3%)patients experienced successful downstaging conversion and received surgery in the SITS group,while none in the ST group.The prognosis of the surgery subgroup was significantly better than the non-surgery subgroup regardless of PFS(P<0.001)and OS(P=0.003).Although a significant higher incidence of adverse events was shown in the SITS group(76.7% vs.46.9%,P=0.020)with two severe adverse events observed,the safety profile of the SITS combination therapy was acceptable.Conclusion: The SITS combination therapy is associated with better effectiveness than the ST combination therapy in advanced HCC with PVTT,and has the potential to become a clinical feasible downstaging conversion strategy with acceptable safety profile.