Adjuvant Transarterial Chemoembolization After Radical Resection Contributed To The Outcomes Of Hepatocellular Carcinoma Patients With High-risk Factors

Objective:Hepatocellular carcinoma(HCC)is a serious harm to human globally,and the situation is particularly severe in our country,the current surgical resection is still the most important treatment of HCC.However,even for patients who underwent radical resection have a high risk of recurrence and mortality,and 70%of patients undergoing hepatocellular resection will eventually relapse within 5 years,so the researchers hope that adjuvant therapy will be used to improve the prognosis after radical surgery We aim to investigate the effects of different times of postoperative adjuvant transarterial chemoembolization(TACE)on survival and recurrence in hepatocellular carcinoma(HCC)patients with different risk factors after radical resection.Materials and Methods:Three hundred and twenty HCC patients underwent radical resection between January 2010 and January 2014 in Qilu hospital,Shandong University were divided into 4 groups according to the frequency of postoperative adjuvant TACE.The patients’ characteristics including sex,age,serum total bilirubin.alanine aminotransferase,aspartate aminotransferase,glutamyl transpeptidase,alkaline phosphatase,serum albumin levels,hepatitis B surface antigen,cirrhosis,Child-pugh classification,serum alpha Protein level,tumor size,number of tumors,degree of tumor cell differentiation,microvascular invasion,and postoperative adjuvant TACE were screened.The factors influencing the recurrence and survival of patients with hepatocellular carcinoma after radical resection were analyzed by multivariate analysis.The factors such as the number of postoperative TACE,tumor size and Edmondson classification were screened.Patients were further stratified into subgroups(tumor diameter≤5 cm or>5 cm)with low or high risk factors for recurrence or death.A low risk factor for recurrence or death was defined as Edmondson grade Ⅰ/Ⅱ without microvascular invasion(MiVI),while a high risk factor was defined as Edmondson grade Ⅲ/Ⅳ or with microvascular invasion.Survival data and recurrence rates were compared using the Kaplan-Meier method.Uni-and mul-tivariate analyses were based on the Cox proportional analysis.Results:The characteristics in four groups of patients concluding sex,age,serum total bilirubin,alanine aminotransferase,aspartate aminotransferase,glutamyl transpeptidase,alkaline phosphatase,serum albumin levels,hepatitis B surface antigen,cirrhosis,Child-pugh,the level of serum alpha-fetoprotein,tumor size,tumor number,tumor cell differentiation,and microvascular invasion were comparable(P>0.05).Compared to those received no TACE,patients underwent 2(log-rank,χ2=9.054,P=0.003)or 3(log-rank,χ2=4.228,P=0.04)TACE showed delayed recurrence.Patients received 2 or 3 TACE showed extended overall survival(OS)compared with the other patients.For the subgroup analysis,several factors were entered into the Cox regression analysis to screen the factors that may affect the recurrence and survival,including times of adjuvant TACE,liver cirrhosis,AFP level(<400 or>400),tumor size(≤5 or>5),tumor number(1/2),Edmondson grade(Ⅰ-Ⅳ),and MiVI.Multivariate analysis showed four factors,including times of adjuvant TACE(HR=0.797,95%CI:0.707-0.897,P<0.001).tumor size(HR=0.649,95%,CI:0.484-0.871,P=0.004).Edmondson grade(Edmondson grade:HR=0.563,95%,CI:0.423-0.750,P<0.001),and MiVI(HR=0.240,95%,CI:0.155-0.373,P<0.001),were the risk factors for the recurrence.Meanwhile,these factors were also the risk factor of decreased survival duration(times of adjuvant TACE:HR=0.523,95%CI:0.411-0.666,P<0.001;tumor size:HR=0.434.95%,CI:0.261-0.719,P=0.001;Edmondson grade:HR=0.317,95%,CI:0.193-0.521.P<0.001;MiVI:HR=0.137,95%,CI:0.072-0.259,P<0.001).Then a stratified analysis was performed based on the tumor diameter to identify the effects on the recurrence or death.A low risk factor for recurrence or death was defined as Edmondson grade Ⅰ/Ⅱ without microvascular invasion(MiVI),while a high risk factor was defined as Edmondson grade Ⅲ/Ⅳ or with microvascular invasion.The number of patients with a tumor diameter of<5 cm in the low-risk subgroup was 66,24,24,29,respectively.Meanwhile,in patients with tumor diameter of<5 cm in the high-risk subgroup,the number was 32,12,11,10,respectively.In tumor diameter>5 cm low-risk subgroup,the number was 26,14,7,11,and in tumor diameter>5 cm high-risk subgroup,the number was 22,10,9,13,respectively.No statistical differences were found between all the disease-free survival(DFS)and OS in low-risk subgroups.In the patients of the high-risk subgroup with a tumor diameter of<5,those received 2 TACE showed delayed recurrence compared with those received no TACE,and TACE(twice or thrice)can improve OS.For those of the high-risk subgroup with a tumor diameter of>5,TACE(twice or thrice)can delay recurrence and improve OS.Conclusion:Adjuvant TACE(twice or thrice)after radical resection is beneficial for HCC patients with poor differentiation and MiVI,especially for those with a tumor diameter of>5 cm.