| Backgroud and aimsTumor burden heavily impacts the prognosis of patients with intermediate-stage hepatocellular carcinoma(HCC)undergoing transarterial chemoembolization(TACE).However,there are no robust criteria to stratify the patients according to tumor characteristics.We aimed to establish a method based on the largest tumor size(Ts)and number(Tn)to accurately predict prognosis.Alpha-fetoprotein(AFP)response has been indentified it could predict the prognosis of patients with unresectable hepatocellular carcinoma treated with TACE.However,the definition of AFP response remained controversial,thus,the aim of this study is to define the AFP response.Methods1.Between January 2010 and December 2014,1515 treatment-na?ve patients with intermediate-stage HCC and well-preserved liver function who underwent TACE were recruited from 24 tertiary Chinese centers,which were randomly designated either training(12 centers,N=820)or validation cohort(12 centers,N=695).The indicative criteria were developed by Cox and spline function analyses,and subsequently validated.Furthermore,discriminations among the cohorts were evaluated and compared with currently available approaches.2.According to inclusion and exclusion criteria,we retrospectively enrolled consecutive patients with HCC from January 2010 to December 2014 at Xijing hospital of digestive diseases.The factors included AFP were collected at baseline and 4 to 6 weeks after TACE.The receiver operating characteristic(ROC)curve was used to determine the best cut-off value of AFP changes for predicting prognosis.The AFP response was defined as the AFP decrease rate greater than the cutoff point.The others were the AFP non-response.The Kaplan-Meier method was used to calculate overall survival and survival rates,and univariate and multivariate Cox regression analysis were used for prognostic analysis.Results 1.Tn and Ts were identified as independent predictors in the training cohort and different subsets of the entire cohort(p<0.001);Then,we set a Tn of two and a Ts of seven centimeters,defined as “two-and-seven criteria”,which revealed three substages with different prognoses as follows: B-1(Tn≤2 and Ts≤7 cm),B-2(Tn≤2 and Ts>7 cm or Tn>2 and Ts≤7 cm but exceeding the Milan criteria),and B-3(Tn>2 and Ts>7 cm);when transitioning to the sequential substages,the hazard ratio(HR)elevated twofold(HR 2.0,P<0.001),which were confirmed in the validation cohort.Compared with up-to-seven and 4-and-7 criteria,our method provided best discrimination across both cohorts as well as various subsets of the entire cohort.2.We finally enrolled 116 patients with HCC.The median tumor size was 7.5 centimeter.Most patients(96.6%)were Child-Pugh A.A level of 16% was chosen as the best cut-off value to define AFP response.The median overall survival in AFP response group was significant longer than AFP non-response group(26.6 vs 7.0 months,p<0.001),and consistently in the sub-group analysis.Multivariate analysis showed age,tumor size,ECOG score,AFP response were the dependent risk factors of survival.Conclusions 1.The two-and-seven criteria offer an objective,evidence-based method to readily discriminate patients with intermediate-stage HCC receiving TACE in that it may allow for better treatment-decision making and reasonable prognostic prediction,as well as for adequate considerations of trial design.2.AFP response could could provide a simple,reproducible,objective,and adjuvant method to predict the prognosis of patients with intermediate-stage HCC treated with TACE... |
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