| Objective:Hepatocellular carcinoma(HCC)with portal vein tumor thrombus has poor prognosis and short survival.The aim of this study is to evaluate the efficacy and safety of tyrosine kinase inhibitor(TKI)combined with transcatheter arterial chemoembolization(TACE)+ radiotherapy(RT)for HCC with portal vein tumor thrombus.Methods:This study retrospectively analyzed HCC patients with portal vein tumor thrombus who received TACE + RT with or without TKI at the First Bethune Hospital of Jilin University from September 2013 to September 2021.The primary end points were overall survival(OS)and progression-free survival(PFS),and the secondary end points were objective response rate(ORR),disease control rate(DCR),and incidence of treatment-related adverse reactions.Prognostic factors were assessed using the COX proportional hazards model.Results:A total of 81 patients were included in the study.Among them,39 patients were treated with TKI combined with TACE + RT(TKI + TACE + RT group,n = 39),and42 patients were treated with TACE + RT(TACE + RT group,n = 42).In TKI +TACE + RT group,the median OS(17.9 months vs 10.3 months,95%CI,10.308 ～17.672,P = 0.008)and median PFS(10.2 months vs 8.0 months,95%CI 6.720 ～10.280,P = 0.041)were significantly higher than in TACE + RT group.In addition,the TKI + TACE + RT group had a higher ORR(33.3% vs 26.2%)and DCR(79.5%vs 76.2%)compared to the TACE + RT group.In patients with type I/II tumor thrombus,the median OS was 19.4 months in the TKI + TACE + RT group,which was significantly higher than 8.2 months in the TACE + RT group(95%CI 10.342 ～18.258,P < 0.001).Median PFS was also significantly higher in the TKI + TACE +RT group compared with the TACE + RT group(10.3 months vs 8.0 months,95%CI6.611 ～ 10.389,P = 0.006).Furthermore,the median OS and PFS in TACE + RT concurrent TKI group were 18.4 months and 10.7 months,respectively,slightly higher than the 15.3 months(95%CI 12.342 ～ 23.458,P = 0.933)and 8.5 months(95%CI8.212 ～ 12.188,P = 0.356)in TACE + RT sequential TKI group.Median OS(19.4months vs 11.3 months,95%CI 12.342 ～ 23.458,P = 0.202)and median PFS(10.2months vs 8.5 months,95%CI 8.212 ～ 12.188,P = 0.812)in TACE + RT + Lenvatinib group were slightly higher than those treated with TACE + RT + sorafenib,but did not reach statistical significance.Multivariate analysis confirmed that whether combined with TKI treatment(HR 0.466,95%CI 0.259 ～ 0.838,P = 0.011),radiotherapy models(HR 0.425,95%CI 0.215 ～ 0.838,P = 0.014),viral infection(HR 3.544,95%CI 1.030 ～ 12.194,P = 0.045),and Child-Pugh classification(HR 2.212,95%CI1.206 ～ 4.059,P = 0.010)were independent prognostic factors for OS.Whether combined with TKI treatment(HR 0.578,95%CI 0.342 ～ 0.977,P = 0.040)was an independent prognostic factor for PFS.The incidence of adverse reactions was similar in the TKI + TACE + RT group and TACE + RT group.The most common adverse reactions were myelosuppression,hepatic impairment,fatigue,diarrhea,nausea,and vomiting.The incidence of grade 3 and higher hematologic toxicity,including leukopenia,thrombocytopenia,and anemia was 7.7%,10.3%,and 0.0%,respectively.Grade 3 or higher hepatic impairment,including AST increased,ALT increased,bilirubin increased was 7.7%,2.6%,and 5.1%,respectively. |
