Multicentric Validation And Prognostic Prediction Of Transarterial Chemoembolization Monotherapy Or Combined With Sorafenib For Hepatocellular Carcinoma

Part ?: Multicentric Assessment of the Hong Kong Liver Cancer Staging System in Chinese Patients following Transarterial Chemoembolization as Initial TreatmentBackground & Aims Recently,the hepatitis B–based Hong Kong Liver Cancer(HKLC)staging system was reported to guide treatment options.We aimed to validate the performance of the HKLC compared with the Barcelona Clinic Liver Cancer(BCLC)staging system in Chinese hepatocellular carcinoma(HCC)patients treated with conventional transarterial chemoembolization(c TACE)as initial treatment.Materials & Methods This retrospective study included patients with HCC who underwent c TACE between January 2008 and December 2016 at three Chinese institutions.All of the patients were calculated HCC stage using 5-substage HKLC(HKLC-5),9-substage HKLC(HKLC-9),and the BCLC system.Based on overall survival(OS),these three staging systems' performance on treatment outcome prediction were compared using C statistic,Akaike information criterion(AIC),area under the receiver operating characteristic curve(AUC),linear trend chi-square,likelihood ratio chi-square,and calibration plots respectively.Results 715 patients with mean age of 58 years old were included.Of them,591(82.7%)were men.The median OS was 10.1 months.Compared with the BCLC system,the HKLC system,especially HKLC-9 showed better performance on survival prediction(HKLC-9: C=0.689,AIC=6646.162;HKLC-5: C=0.683,AIC=6662.663;BCLC: C=0.680,AIC=6654.146),homogeneity(likelihood ratio chi-square: HKLC-9=232.38,HKLC-5=215.87,and BCLC=224.39,p <0.001)and calibration(R2: HKLC-9=0.923,HKLC-5=0.916,and BCLC=0.914).HKLC-9 outperformed on AUC at 6,12,and 24 months' survival prediction than HKLC-5 and BCLC.BCLC showed better performance on monotonicity(linear trend chisquare: HKLC-9=121.641,HKLC-5=117.389,and BCLC=125.752;p <0.001).Conclusions Combining survival prediction,discrimination,and calibration,the HKLC,especially HKLC-9 system performed better for Chinese patients treated with c TACE than theBCLC system.Part ?: Nomogram and Artificial Neural Network for Prognostic Performance on the Albumin-Bilirubin Grade for HCC undergoing TACEBackground & Aims The albumin-bilirubin(ALBI)grade is a newly raised objective liver function assessment tool as well as an emerging alternative of the Child-Turcotte-Pugh(CTP)grade in hepatocellular carcinoma(HCC).We aimed to construct ALBI and CTP grades based nomograms as well as develop an artificial neural network(ANN)to compare the prognostic performance of these two grades.Materials & Methods This multicentric retrospective study included all patients with HCC who underwent TACE monotherapy as initial treatment between January 2008 and December 2016 at four institutions.In the training cohort,independent risk factors associated with overall survival(OS)were identified by univariate and multivariate Cox proportional hazards analyses.The prognostic nomograms and ANN were then established in the training cohort and validated in the two validation cohorts.Results Totally,838 patients(548,115,and 175 in the training cohort and validation cohorts 1 and 2,respectively)were included.The median OS was 10.4,15.7,and 9.2 months in the training cohort and validation cohorts 1 and 2,respectively.In the training cohort,independent risk factors were identified as: higher Eastern Cooperative Oncology Group(ECOG)grade,portal vein tumor thrombosis(PVTT),extrahepatic spread(exclude PVTT),higher ALBI/CTP grade,a-fetoprotein level greater than 200 ng/m L,multiple tumors,and tumor size larger than 5 cm.The ALBI and CTP grades based nomograms were then established separately,and showed comparable prognostic performance when assessed externally in two independent validation cohorts(C-index in validation cohort 1: 0.823 vs.0.802,P =0.417;in validation cohort 2: 0.716 vs.0.729,P =0.793).ANN showed that ALBI grade had higher importance on survival prediction than CTP grade.Conclusions The ALBI grade outperforms the CTP grade on survival prediction for HCC patients who undergo TACE.Considering the easy application,the ALBI grade should be regarded as an alternative to CTP grade.Part ?: Early Sorafenib-related Biomarkers for Combination Treatment with Transarterial Chemoembolization and Sorafenib in Patients with Hepatocellular CarcinomaBackground & aims Transarterial chemoembolization(TACE)plus sorafenib is widely used in hepatocellular carcinoma(HCC)patients.However,the treatment outcome is diverse.We aim to identify early sorafenib-related biomarkers for the predictions of the therapeutic response in HCC patients treated with TACE plus sorafenib and establish an effective prognostic nomogram for these patients.Materials & Methods This retrospective study included all HCC patients receiving TACE plus sorafenib therapy between January 2010 and December 2013 in two institutions.Based on the overall survival(OS),early biomarkers were identified by univariate and multivariate analyses;then,a prognostic nomogram was established and internally validated using the concordance(c)statistic.Results There were 97 patients included in this study,and the median OS was 25.7 months.After the univariate and multivariate analyses,the onset of sorafenib-induced hypertension and/or dermatologic adverse events(AEs)(? grade 2)within the first month of sorafenib initiation were demonstrated as independent predictors of OS.The median OS of patients with either of the two independent risk factors was 32.2 months,which was significantly longer than for those patients without such AEs(19.8 months;P=0.005).Survival analyses showed that the earlier the AEs(sorafenib-related dermatologic AEs or hypertension)occurred,the better the outcome of the combination therapy.A prognostic nomogram was established and showed high accuracy of the nomogram with the c statistic of 0.73.Conclusions The early onset of hypertension and/or sorafenib-related dermatologic AEs are early biomarkers for the clinical prognosis of HCC patients treated with TACE plus sorafenib.Part ?: Stratification and Prognosis for Advanced-Stage Hepatocellular Carcinoma Treated with TACE Monotherapy or TACE Plus SorafenibBackground & Aims There is a potential that some of the advanced-stage hepatocellular carcinoma(HCC)will benefit from transarterial chemoembolization(TACE)monotherapy.We aim to establish a prediction model to determine who will benefit from TACE monotherapy compared with TACE plus sorafenib for advanced-stage HCC.Materials & Methods This multicentric retrospective study included all patients with HCC who underwent TACE monotherapy as initial treatment between January 2010 and December 2014 at three institutions.In the training cohort,independent risk factors associated with overall survival(OS)were identified by univariate and multivariate Cox proportional hazards analyses.The prognostic model as well as the nomogram were then established in the training cohort and validated in the validation cohort.Results A total of 169(115 in training cohort and 54 in validation cohort)patients were included.In the training cohort,77 underwent TACE monotherapy(TACE group),and the remaining 38 received TACE plus sorafenib(combination group).The prognostic prediction(PP)model was established based on the following three independent risk factors associated with OS for patients in the TACE group: portal vein tumor thrombus(PVTT)(0 if no,5 if branch,6 if main),number of HCC nodules(0 if 1,4 if 2-3,5.5 if >3),and Child-Pugh(CP)stage(0 if A,4 if B).Patients were divided into two groups by PP score of <5.25 and >5.25 in survival benefit(13.9 vs.6.5 months;P <0.001).A nomogram for TACE group was created.These two prediction models received high accuracy when validated in validation cohort.Conclusions Advanced-stage HCC patients with PP score <5.25 may benefit most from TACE monotherapy.