Recommendations for the use of chemoembolization in patients with hepatocellular carcinoma: Usefulness of scoring system?

Several hepatocellular carcinoma(HCC) staging systems have been established, and a variety of countryspecific treatment strategies are also proposed. The barcelona- clinic liver cancer(BCLC) system is the most widely used in Europe. The Hong Kong liverCancer is a new prognostic staging system; it might become the reference system in Asia. Transarterial chemoembolization(TACE) is the most widely used treatment for HCC worldwide; but it showed a benefit only for intermediate stage HCC(BCLC B), and there is still no consensus concerning treatment methods and treatment strategies. In view of the highly diverse nature of HCC and practices, a scoring system designed to assist with decision making before the first TACE is performed or prior to repeating the procedure would be highly useful.

Usefulness of staging systems and prognostic scores for hepatocellular carcinoma treatments

Therapeutic management of hepatocellular carcinoma(HCC) is quite complex owing to the underlying cirrhosis and portal vein hypertension. Different scores or classification systems based on liver function and tumoral stages have been published in the recent years. If none of them is currently "universally" recognized, the Barcelona Clinic Liver Cancer(BCLC) staging system has become the reference classification system in Western countries. Based on a robust treatment algorithm associated with stage stratification, it relies on a high level of evidence. However, BCLC stage B and C HCC include a broad spectrum of tumors but are only matched with a single therapeutic option. Some experts have thus suggested to extend the indications for surgery or for transarterial chemoembolization. In clinical practice, many patients are already treated beyond the scope of recommendations. Additional alternative prognostic scores that could be applied to any therapeutic modality have been recently proposed. They could represent complementary tools to the BCLC staging system and improve the stratification of HCC patients enrolled in clinical trials, as illustrated by the NIACE score. Prospective studies are needed to compare these scores and refine their role in the decision making process.

Barcelona clinic liver cancer nomogram and others staging/scoring systems in a French hepatocellular carcinoma cohort

AIM To compare the performances of the Barcelona clinic liver cancer(BCLC) nomogram and others systems(BCLC, HKLC, CLIP, NIACE) for survival prediction in a large hepatocellular carcinoma(HCC) French cohort.METHODS Data were collected retrospectively from 01/2007 to 12/2013 in five French centers. Newly diagnosed HCC patients were analyzed. The discriminatory ability, homogeneity ability, prognostic stratification ability Akaike information criterion(AIC) and C-index were compared among scoring systems. RESULTS The cohort included 1102 patients, mostly men, median age 68 [60-74] years with cirrhosis(81%), child-Pugh A(73%), alcohol-related(41%), HCV-related(27%). HCC were multinodular(59%) and vascular invasion was present in 41% of cases. At time of HCC diagnosis BCLC stages were A(17%), B(16%), C(60%) and D(7%). First line HCC treatment was curative in 23.5%, palliative in 59.5%, BSC in 17% of our population. Median OS was 10.8 mo [4.9-28.0]. Each system distinguished different survival prognosis groups(P < 0.0001). The nomogram had the highest discriminatory ability, the highest C-index value. NIACE score had the lowest AIC value. The nomogram distinguished sixteen different prognosis groups. By classifying unifocal large HCC into tumor burden 1, the nomogram was less powerful. CONCLUSION In this French cohort, the BCLC nomogram and the NIACE score provided the best prognostic information, but the NIACE could even help treatment strategies.

Expected outcomes and patients’selection before chemoembolization—“Six-and-Twelve or Pre-TACE-Predict”scores may help clinicians:Real-life French cohorts results

BACKGROUND Careful selection of hepatocellular carcinoma(HCC)patients prior to chemoembolization treatment is a daily reality,and is even more necessary with new available therapeutic options in HCC.To propose two new models to better stratify patients and maximize clinical benefit:“6 and 12”and“pre/post-TACE-predict”(TACE,transarterial chemoembolization).METHODS We evaluated and compared their performance in predicting overall survival with other systems{Barcelona Clinic Liver Cancer(BCLC),Albumin-Bilirubin(ALBI)and NIACE[Number of tumor(s),Infiltrative HCC,alpha-fetoprotein,Child-Pugh(CP),and performance status]}in two HCC French cohorts of different stages enrolled between 2010 and 2018.RESULTS The cohorts included 324 patients classified as BCLC stages A/B(cohort 1)and 137 patients classified as BCLC stages B/C(cohort 2).The majority of the patients had cirrhosis with preserved liver function.“Pre-TACE-predict”and“6 and 12”models identified three distinct categories of patients exhibiting different prognosis in cohort 1.However,their prognostic value was no better than the BCLC system or NIACE score.Liver function based on CP and ALBI grades significantly impacted patient survival.Conversely,the“post-TACE-predict”model had a higher predictive value than other models.The stratification ability as well as predictive performance of these new models in an intermediate/advanced stage population was less efficient(cohort 2).CONCLUSION The newly proposed“Pre-TACE-predict”and“6 and 12”models offer an interesting stratification into three categories in a recommended TACE population,as they identify poor candidates,those with partial control and durable response.The models'contribution was reduced in a population with advanced stage HCCs.

Second-line therapy for advanced hepatocellular carcinoma with regorafenib or cabozantinib:Multicenter French clinical experience in real-life after matching

BACKGROUND Starting a second-line systemic treatment for hepatocellular carcinoma(HCC)is a common situation.The only therapeutic options in France are two broadspectrum tyrosine kinase inhibitors(TKIs),regorafenib(REG)and cabozantinib(CBZ),but no comparative real-life studies are available.AIM To evaluate the progression-free survival(PFS)of patients treated with REG or CBZ,we investigated the disease control rate(DCR),overall survival(OS),and safety of both drugs.To identify the variables associated with disease progression over time.METHODS A retrospective multicenter study was performed on the clinical data of patients attending one of three referral centers(Avignon,Marseille,and Nice)between January 2017 and March 2021 using propensity score matching.PFS and OS were assessed using the Kaplan-Meier method.Multivariate analysis(MA)of progression risk factors over time was performed in matched-pair groups.RESULTS Fifty-eight patients 68(62-74)years old with HCC,Barcelona clinic liver cancer(BCLC)B/C(86%),Child-Pugh(CP)-A/B(24%)received REG for 3.4(1.4-10.5)mo as second-line therapy.Twentyeight patients 68(60-73)years,BCLC B/C(75%),CP-A/B(25%)received CBZ for 3.7(1.8-4.9)mo after first-line treatment with sorafenib[3(2-4)(CBZ)vs 4(2.9-11.8)mo(REG),P=0.0226].Twenty percent of patients received third-line therapy.After matching,PFS and DCR were not significantly different after a median follow-up of 6.2(2.7-11.7)mo(REG)vs 5.2(4-7.2)mo(CBZ),P=0.6925.There was no difference in grade 3/4 toxicities,dose reductions,or interruptions.The OS of CP-A patients was 8.3(5.2-24.8)vs 4.9(1.6-11.7)mo(CP-B),P=0.0468.The MA of risk factors for progression over time identified C-reactive protein(CRP)>10 mg/L,neutrophil-to-lymphocyte ratio(NLR)>3,and aspartate aminotransferase(AST)>45 IU as predictive factors.CONCLUSION This multicenter indirect comparative study found no significant difference in PFS between REG and CBZ as second-line therapy for advanced HCC.Elevated levels of inflammatory markers(CRP and NLR)and AST were associated with non-control of TKIs over time.A 2-mo online progression risk calculation is proposed.

Intrahepatic Cholangiocarcinoma and Hepatocellular Carcinoma:Real-life Data on Liver Disease,Treatment and Prognosis

Background and Aims:Hepatocellular carcinoma(HCC)and intrahepatic cholangiocarcinoma(iCCA)have common features and differences.This real-life study investigated their characteristics,treatment modalities,and prognoses.Methods:This retrospective comparative study was performed in 1,075 patients seen at one tertiary center between January 2008 and December 2020.Overall survival(OS)was estimated by the Kaplan-Meier method.Subclassification of iCCAs after histological and radiological review,and molecular profiling was performed.Results:HCCs patients were more likely to have early-stage disease than iCCA patients.iCCA patients were more likely to be female,especially those patients without cirrhosis(43%vs.17%).Cirrhosis was prominent among HCC patients(89%vs.34%),but no difference in underlying liver disease among cirrhotic patients was found.OS of HCC patients was 18.4(95%CI:6.4,48.3)months,that of iCCA patients was 7.0(95%CI:3.4,20.1)months.OS of Barcelona Clinic Liver Cancer C HCC patients was 7.8(95%CI:4.3,14.2)months,that of advanced/metastatic iCCA patients was 8.5(95%CI:5.7,12.3)months.In patients treated with sorafenib,OS was longer in HCC patients who received subsequent tyrosine kinase inhibitor therapies.No significant OS difference was found between iCCA patients with and without cirrhosis or according to histological subtype.A targetable molecular alteration was detected in 50%of the iCCA patients.Conclusions:In this French series,cirrhosis was common in iCCA,which showed etiological factors comparable to those of HCC,implying a distinct oncogenic pathway.Both entities had a dismal prognosis at advanced stages.However,systemic therapies sequencing in HCC and molecular profiling in iCCA offer new insights.