| 【Background and aims】Barcelona Clinic Liver Cancer(BCLC)staging system is nowadays the most widely recognized clinical staging system for hepatocellular carcinoma(HCC)around the world.According to BCLC,transarterial chemoembolization(TACE)is the only recommended treatment for intermediate stage(BCLC-B)HCC.The treatment outcome of TACE has been confirmed in two randomized controlled trails previously.However,in actual clinical practice,patients receiving TACE exceed the range of BCLC-B due to the huge heterogeneity of patients with unresectable HCC.In converse,there is currently few relevant researches provide strong evidence on the efficacy of TACE in patients beyond the guideline recommendation range.Under this circumstance,some particular prognostic score models for TACE treatment have been proposed in succession on the basis of BCLC.Liver function is an important factor affecting the prognosis of liver cancer.From multiple prognostic models,the Child-Pugh score is an important indicator for evaluating liver function.In recent years,another study has proposed albumin-bilirubin(ALBI)score as a new index for evaluating liver function.At the same time,ALBI scores have shown its superiority in subsequent verification studies.Clear clarification on the applicability of the two scores in patients receiving TACE treatment will have guidance value for the development of further prognostic models.Therefore,our center has carried out a retrospective study(Research 1)to evaluate the survival prediction and discriminating ability of Child-Pugh score and ALBI score in real-world HCC patients receiving TACE treatment.The prognosis scores developed for the first time TACE treatment outcome are HAP(Hepatoma Arterial-embolization Prognostic)scoring system and its modified versions mHAP score,mHAP2 score and mHAP3 score,as well as Six-and-twelve Criteria(6&12).The scores which suitable for the prognosis of multiple times TACE treatments are ART(assessment for re-treatment with TACE),ABCR(alpha-fetoprotein,BCLC,Child-Pugh and Response)and STATE(Selection for Tr Ansarterial chemoembolization Tr Eatment).Because the above scores are targeted at different target groups in the development process,there is no persuasive comparative research of their true prediction capabilities.Therefore,according to the actual situation of the real-world TACE treatment population in China,our center has conducted a multi-center retrospective study(Research 2)to evaluate the prognostic ability of each score to explore its applicability for clinical decision-making.Recently,based on the ideal BCLC-B population,a TACE prognosis score 6&12 Criteria was published by our center,revealing the relationship between tumor burden and survival.Patients with unresectable HCC but without macrovascular invasion(MVI)and extrahepatic spread(EHS)were classified as advanced HCC by BCLC system once they were valued as Eastern Cooperative Oncology Group(ECOG)score 1.In some previous studies,these patients were included in the scope of TACE treatment.However,it is unknown whether these patients are suitable for TACE treatment and whether there is a further risk stratification.Therefore,our center cooperated with nation-wide external centers to conduct a retrospective study(Research 3)of verifying and modifying the 6 & 12 Criteria in advanced stage patients with exclusive ECOG 1.【Methods】1.Patients with unresectable HCC who underwent TACE treatment from January 2010 to June 2016 in our center and a number of external cooperation centers were retrospectively collected,then,the survival follow-up was performed in patients who met the eligibility criteria.The total population was screened and grouped according to the inclusion criteria of three studies.2.Clinical events data,imaging data and laboratory examination data before TACE and fourth week after TACE were collected.Same information was collected every eight weeks thereafter.3.In Research 1,univariate and Cox multivariate analysis were used to find predictors of overall survival time among the population;after using the Child-Pugh score and ALBI score and grade to stratify the population,Kaplan-Meier survival curve and log-rank test were used to perform survival analysis;Survival prediction abilities of the adjusted Cox multivariate analysis regression models were compared by hazard ratio(HR);timedependent area under time-dependent receiving operator characteristic curve(AUROC)curve,concordance index(C index),likelihood ratio Chi-square(LR X~2)statistics,and Rsquare(R2)value were used to compare discrimination ability of three predictors;KaplanMeier survival curve and log-rank test were used to verify the hierarchical ability of ChildPugh scores in a subgroup of ALBI grades,and to verify the hierarchical ability of ALBI grades in a subgroup of Child-Pugh scores.4.In Research 2,Kaplan-Meier survival curve and log-rank test were used to describe and compare the overall survival rate under stratification of each score;Cox proportional hazard regression model was used to calculate risk rate of each score;comparisons of survival prediction abilities at different time points were described by time-dependent AUROC curves;Spearman test and Kappa value were used to evaluate the consistency between prediction models and the first postoperative imaging response;the C index and likelihood ratio(LR)were used to evaluate the predictive value of each score for overall survival time;Kaplan-Meier survival curve and log-rank test were used to describe and compare the risk stratification ability of the combined use of scores.5.In Research 3,univariate analysis was used to disclose statistically significant variables,and then three Cox’s multivariate regression analysis models were used to incorporate different variables to find predictors;different HR value of the factors determines its weighting coefficients,and the linear predictors(LP)of the three models are calculated after grouping and adding each variable with its own weight;using the AUROC curve,the C index,LR X~2,and R2 to compare the prediction and description capabilities of the three models with the 6 & 12 model respectively;Kaplan-Meier survival curve and logrank test were used to describe the population’s overall survival rate under the Child-Pugh level,ALBI level,and AFP value stratification,and compare the overall survival rate and median survival time between subgroups under the 6 & 12 risk stratification;a contour plot was used to describe the linear relationship between tumor burden and time survival rate,and a Nomogram was applied to represent specific numerical relationship between the tumor burden and its 1-year,2-year,3-year survival rate.【Results】1.In Research 1,among the unresectable HCC patients in good liver function without MVI and EHS receiving TACE from a single center:1)Through univariate and multivariate analysis,it was found that ECOG score,maximum tumor size,portal vein tumor thrombosis(PVTT)and ALBI grade were independent predictors,while Child-Pugh score was not.2)Child-Pugh score,ALBI score,and ALBI grade could stratify patients,and median survival time was statistically different between groups.At the same time,in the adjusted regression model,all three showed effective predictive abilities.3)With the extension of the survival time after TACE,the predictive value of ChildPugh score gradually decreased,and the ALBI score and ALBI grade maintained a relatively stable predictive value.The ALBI score had the best discrimination ability.4)The ALBI level could further subdivide the Child-Pugh 5-point subgroup,but not the Child-Pugh 6-point subgroup;the Child-Pugh score could further subdivide the ALBI 1 subgroup,but not the ALBI 2 Subgroups;2.In Research 2,among the unresectable HCC patients in good liver function with ECOG 0 or 1 but without MVI and EHS receiving TACE from multiple centers:1)In the comparison of the various scores applicable to the first TACE,the 6 & 12 Criteria showed the best correlation and consistency with the image response.2)In comparing the individual scores applicable to the first TACE,the mHAP3 score had the best ability to predict overall survival time.3)In the comparison of scores applicable to the multiple TACE sessions,the predictive ability of ABCR score was much better than ART score.4)The mHAP3 score was used in combination with the ABCR score to select "applicable patients" for TACE.Compared with "non-applicable patients",the median survival time was significantly improved.3.In Research 3,among the BCLC-C stage HCC patients with ECOG 0 or 1 and without MVI and EHS receiving TACE from multiple centers:1)Child-Pugh grade,ALBI grade,and AFP value stratification could stratify the overall survival time of the population,and the median survival time was statistically different.2)According to univariate and multivariate analysis,it was found that the largest tumor size,tumor number,AFP grade and total bilirubin were independent predictors,while Child-Pugh grade and ALBI grade were not.3)The maximum tumor size and the number of tumors were independent predictors.The sum of the two values was linearly related to the overall survival time.4)In the comparison of the LP of 6 & 12 model and other three models established with relevant predictors,it was found that the 6 & 12 model with the largest tumor size plus the number of tumors as the LP showed better predictive ability and discrimination ability,and was the most convenient tool for clinical use.5)Taking the LP values 6 and 12 as the cutoff points,this model could stratify patients into three strata,and has a good ability of discrimination.While its Nomogram has the ability to predict survival individually.【Conclusions】 1.In Research 1:1)The ALBI system had a better survival predictive value than the Child-Pugh score in patients undergoing TACE treatment who had good liver function without MVI and EHS.2)The ALBI score could further stratify the Child-Pugh 5 patients.3)The ALBI score obtained more accurate prognostic ability.2.In Research 2:1)In patients undergoing TACE treatment with unresectable HCC,no MVI or EHS,ECOG of 0 or 1,and good liver function,the 6 & 12 Criteria could predict postoperative imaging response.2)mHAP3 for first TACE should be used in combination with ABCR for multiple TACE sessions to determine whether patients should receive TACE treatment.3.In Research 3:1)TACE treatment was safe and effective in BCLC-C stage HCC patients with ECOG 1 alone.2)The 6 & 12 Criteria could predict individual survival in these patients through tumor burden and be used as an easy-to-use clinical prognosis tool. |
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