Clinical Study Of Stereotactic Body Radiotherapy Combined With Lenvatinib For Advanced Hepatocellular Carcinoma

ObjectiveAdvanced hepatocellular carcinoma(HCC),especially for patients with portal vein tumor thrombosis(PVTT),has a poor prognosis and there is still a lack of effective treatment options.Treatment options for advanced HCC include local treatment(such as radiation therapy and interventional therapy)and systemic treatment(such as targeted drug therapy and immunotherapy).However,the current efficacy of monotherapy is still limited,and the combination of local and systemic therapy is one of the main strategies to prolong the survival of advanced HCC patients,especially in patients with PVTT.However,how to combine to achieve better efficacy deserves further investigation.The purpose of this study is to observe the clinical efficacy and safety of stereotactic radiotherapy(SBRT)in combined with lenvatinib for the treatment of advanced HCC,and to provide an evidence-based basis for optimizing the treatment strategy.Methods(1)Comparison of SBRT with and without lenvatinib for Advanced HCC:Retrospective analysis of 144 patients with advanced HCC,106 patients were treated with SBRT(SBRT group)and 38 patients were treated with SBRT combined with lenvatinib(SBRT+LEN group).Propensity score matching(PSM)analysis was used to balance the baseline characteristics between the two groups of patients.Overall survival(OS),progression-free survival(PFS),intrahepatic PFS(IHPFS),and objective response rate(ORR)were compared between the two groups,and the safety of the two groups was evaluated.(2)Comparison of lenvatinib with or without SBRT for HCC with PVTT only:Retrospective analysis of 114 patients with advanced HCC with PVTT only,37 patients were treated with lenvatinib in combination with SBRT(SBRT+LEN group)and 77 patients were treated with lenvatinib alone(LEN group).OS,PFS,IHPFS and ORR were compared between the two groups,and treatment-related adverse events were analyzed in both groups to assess safety.Results(1)After PSM,the baseline characteristics was well balanced between the two groups of patients.Median OS,PFS and IHPFS were significantly prolonged in the SBRT+LEN group compared with the SBRT group(median OS:16.8 vs.11.0 months,P=0.043;median PFS:9.1 vs.3.7 months,P<0.001;median IHPFS:9.5 vs.4.2 months,P=0.004).In addition,ORR was higher in the SBRT+LEN group(P=0.007),and patients who achieved objective response had better survival.In terms of treatmentrelated adverse events,the incidence of hypertension was higher in the SBRT combined with lenvatinib group than in the SBRT group,but both treatment modalities were well tolerated by patients in both groups.(2)The baseline characteristics were well balanced between the two groups of patients.Median OS,PFS and IHPFS were significantly longer in the SBRT+LEN group compared with the LEN group(median OS:19.3 months vs 11.2 months,p<0.001;median PFS:10.3 vs 5.3 months,p<0.001;median IHPFS:10.7 vs 5.3 months,p<0.001).A higher ORR was observed in the SBRT+LEN group(p<0.001)and patients who achieved objective remission had a better survival.Median OS,PFS and IHPFS were also significantly longer in the combination therapy group than in the LEN group in the subgroup analysis of PVTT type(Vp1-2 subgroup and Vp3-4 subgroup).In addition,there were no significant differences in treatment-related adverse events between the two groups,and both were well tolerated.ConclusionOur study shows that SBRT combined with lenvatinib is a safe and effective treatment for patients with advanced HCC compared to SBRT or lenvatinib alone,and HCC patients with different types of PVTT all can benefit from the combined therapy.In addition,subgroup analysis of the different treatment modalities all showed that patients who achieved objective remission had better survival.