Validation of the six-and-twelve criteria among patients with hepatocellular carcinoma and performance score 1 receiving transarterial chemoembolization

BACKGROUND Transarterial chemoembolization(TACE)is recommended for patients with intermediate hepatocellular carcinoma(HCC)according to treatment guidelines.However,a large number of patients with advanced HCC also receive TACE in clinical practice,especially for those with liver-confined HCC and Eastern Cooperative Oncology Group score(ECOG)1.In view of previous studies,such patients have different prognoses from advanced HCC patients with macrovascular invasion or extrahepatic spread;therefore,patients with ECOG 1 alone might be classified into the intermediate stage and benefit from TACE treatment,but a study particularly focusing on such patients and exploring the effectiveness of TACE therapy is lacking.AIM To investigate treatment outcomes of TACE in HCC patients with ECOG 1 alone and propose a specific prognostic model.METHODS Patients from 24 Chinese tertiary hospitals were selected in this nationwide multicenter observational study from January 2010 to May 2016.Overall survival(OS)was estimated using Kaplan–Meier curves and compared by the log-rank test.Multivariate Cox regression was used to develop the potential prognostic models.The discriminatory ability of the models was compared and validated in various patient subgroups.The individual survival prediction for six-and-twelve(6&12)criteria,defined as the algebraic sum of tumor size(cm)and tumor number,was illustrated by contour plot of 3-year survival probability and nomogram.RESULTS A total of 792 eligible patients were included.During follow-up,median OS reached 18.9 mo[95%confidence interval(CI):16.9-21.0].Three independent multivariate analyses demonstrated that tumor size,tumor number,α-fetoprotein level,albumin–bilirubin grade and total bilirubin were prognostic factors of OS(P<0.05).The previously proposed 6&12 criteria was comparable or even better than currently proposed with the highest predictive ability.In addition,the 6&12 criteria was correlated with OS in various subgroups of patients.The patients were stratified into three strata with score≤6,>6 but≤12,and>12 with different median OS of 39.8 mo(95%CI:23.9-55.7),21.1 mo(95%CI:18.4-23.8)and 9.8 mo(95%CI:8.3-11.3),respectively(P<0.001).CONCLUSION TACE is effective for advanced HCC patients with ECOG 1 alone,and the 6&12 criteria may help with clinical decision-making.

Validation and evaluation of clinical prediction systems for first and repeated transarterial chemoembolization in unresectable hepatocellular carcinoma: A Chinese multicenter retrospective study

BACKGROUND The treatment outcome of transarterial chemoembolization(TACE)in unresectable hepatocellular carcinoma(HCC)varies greatly due to the clinical heterogeneity of the patients.Therefore,several prognostic systems have been proposed for risk stratification and candidate identification for first TACE and repeated TACE(re-TACE).AIM To investigate the correlations between prognostic systems and radiological response,compare the predictive abilities,and integrate them in sequence for outcome prediction.METHODS This nationwide multicenter retrospective cohort consisted of 1107 unresectable HCC patients in 15 Chinese tertiary hospitals from January 2010 to May 2016.The Hepatoma Arterial-embolization Prognostic(HAP)score system and its modified versions(mHAP,mHAP2 and mHAP3),as well as the six-and-twelve criteria were compared in terms of their correlations with radiological response and overall survival(OS)prediction for first TACE.The same analyses were conducted in 912 patients receiving re-TACE to evaluate the ART(assessment for re-treatment with TACE)and ABCR(alpha-fetoprotein,Barcelona Clinic Liver Cancer,Child-Pugh and Response)systems for post re-TACE survival(PRTS).RESULTS All the prognostic systems were correlated with radiological response achieved by first TACE,and the six-and-twelve criteria exhibited the highest correlation(Spearman R=0.39,P=0.026)and consistency(Kappa=0.14,P=0.019),with optimal performance by area under the receiver operating characteristic curve of 0.71[95%confidence interval(CI):0.68-0.74].With regard to the prediction of OS,the mHAP3 system identified patients with a favorable outcome with the highest concordance(C)-index of 0.60(95%CI:0.57-0.62)and the best area under the receiver operating characteristic curve at any time point during follow-up;whereas,PRTS was well-predicted by the ABCR system with a C-index of 0.61(95%CI:0.59-0.63),rather than ART.Finally,combining the mHAP3 and ABCR systems identified candidates suitable for TACE with an improved median PRTS of 36.6 mo,compared with non-candidates with a median PRTS of 20.0 mo(logrank test P<0.001).CONCLUSION Radiological response to TACE is closely associated with tumor burden,but superior prognostic prediction could be achieved with the combination of mHAP3 and ABCR in patients with unresectable liver-confined HCC.