| Background and ObjectiveAt present,whether transarterial chemoembolization(TACE)plus sorafenib can be more clinically meaningful than TACE alone for patients with Barcelona Clinic Liver Cancer(BCLC)-B stage hepatocellular carcinoma(HCC)has not been conclusive.The purpose of this study was to compare the efficacy and safety of TACE plus sorafenib and TACE alone in treatment of patients with BCLC-B stage HCC and analyze the prognostic factors of these patients.Materials and MethodsThis study is a prospective,multicenter,compared study.Patients with BCLC-B stage HCC were included in combination treatment group and TACE group at a ratio of 1:2.Combination treatment group patients began taking sorafenib 3-7 days before its first TACE(with an initial dose of 400mg bid).There was no standard treatment plan after tumor progression of all patients.Progress free survival(PFS)was used as the primary endpoint.Overall suivival(OS),objective response rate(ORR),disease control rate(DCR),the rate of lipiodol deposition>50%,macrovascular invasion(MVI)or extrahepatic spread(EHS)rate,time interval of TACE,liver function index and(Alpha-fetoprotein)AFP value after 1-2 months of treatment were secondary endpoints.The safety parameters of two groups were summarized in a table.Results?From June 2016 to June 2018,249 patients were included,including 79 patients in combination treatment group and 170 patients in TACE group.PFS of combination treatment group was significantly higher than that of TACE group(7.2 vs 4.8 months,?2=6.626,P=0.010).The 3,6 and 12-month PFS rate in combination treatment group was 78.2%,56.8%,and 28.5%respectively,and the 3,6 and 12-month PFS rate in TACE group was 69.0%,39.1%,and 15.5%respectively.Subgroup analysis showed that PFS in combination treatment group was significantly higher than that in TACE group when the AFP value was>400 ng/ml(6.1 months vs 3.4 months,?2=4.094,P=0.043).? Median OS of combination treatment group and TACE group was 14.1 months and 13.9 months respectively,and the difference was not statistically significant(?2=1.195,P=0.274).According to the mRECIST evaluation criteria for solid tumors,ORR of combination treatment group and TACE group was 43.0%and 28.8%respectively(?2=4.904,P=0.027).DCR of combination treatment group and TACE group was 69.6%and 66.5%respectively.The MVI or EHS rates of combination treatment group was significantly lower than that of TACE group(8.9%vs 41.2%,?2=26.368,P<0.001).The rate of lipiodol deposition>50%of combination treatment group was significantly higher than that of TACE group(79.7%vs 58.2%,?2=9.681,P=0.002).The total bilirubin of the combination treatment group and TACE group was(26.56 ±19.90)umol/1 and(18.98±13.24)umol/1 respectively after 1-2 months of treatment,and the difference was statistically significant(t=2.441,P=0.017).?Univariate analysis showed that prealbumin,AFP value,maximum tumor diameter,lipiodol deposition>50%rate,recurrence after surgical resection,and TACE combined with sorafenib treatment were risk factors for PFS.Multivariate Cox proportional hazard regression model analysis showed that AFP value,maximum tumor diameter,lipiodol deposition>50%rate,and TACE combined with sorafenib treatment were independent risk factors for PFS.?There were 1(1.3%)cases grade 4 fatigue and 40 cases grade 3 adverse events in the combination treatment group,of which 9(11.4%)cases were fatigue,9(11.4%)cases were abdominal pain,8(10.1%)cases patients had diarrhea,and 1(1.3%)cases had nausea and vomiting,7(8.9%)cases had hand-foot syndrome,3(3.8%)cases had rash or pruritus,1(1.3%)cases had hair loss,and 2(2.5%)cases had hypertension.Adverse events in TACE gruop were all TACE-related.Grade 3 adverse events included 15(8.8%)cases of abdominal pain and 2(1.2%)cases of nausea and vomiting.The rests were adverse events of grade 1-2.Conclusions?Compared with TACE alone,combined with sorafenib treatment can significantly prolong the PFS of patients with BCLC-B stage HCC,especially when the AFP value is>400 ng/ml;?Compared with TACE alone,combined with sorafenib therapy can significantly increase the patient's ORR,reduce the MVI or EHS rates,and increase the patient's lipiodol deposition>50%rate of patients with BCLC-B stage HCC;? AFP value,maximum tumor diameter,lipiodol deposition>50%,and TACE combined with sorafenib treatment are independent risk factors of PFS for patients with BCLC-B stage HCC;?Compared with TACE alone,combined sorafenib treatment can significantly increase total bilirubin in patients with BCLC-B stage HCC,suggesting that combined treatment may increase liver toxicity.Adverse events are mostly grade 1 and 2,suggesting that TACE combined with sorafenib treatment is generally feasible and safe. |
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