BCLC-B Hepatocellular Carcinoma Patients Research Articles

Postoperative outcomes and recurrence patterns of intermediate-stage hepatocellular carcinoma dictated by the sum of tumor size and number

The selection criteria for Barcelona Clinic Liver Cancer (BCLC) intermediate-stage hepatocellular carcinoma (HCC) patients who would truly benefit from liver resection (LR) remain undefined. To identify BCLC-B HCC patients more suitable for LR. We included patients undergoing curative LR for BCLC stage A or B multi-nodular HCC (MNHCC) and stratified BCLC-B patients by the sum of tumor size and number (N + S). Overall survival (OS), recurrence-free survival (RFS), recur-rence-to-death survival (RTDS), recurrence patterns, and treatments after recurrence in BCLC-B patients in each subgroup were compared with those in BCLC-A patients. In total, 143 patients who underwent curative LR for MNHCC with BCLC-A (n = 25) or BCLC-B (n = 118) were retrospectively analyzed. According to the N + S, patients with BCLC-B HCC were divided into two subgroups: BCLC-B1 (N + S ≤ 10, n = 83) and BCLC-B2 (N + S > 10, n = 35). Compared with BCLC-B2 patients, those with BCLC-B1 had a better OS (5-year OS rate: 67.4% vs 33.6%; P < 0.001), which was comparable to that in BCLC-A patients (5-year OS rate: 67.4% vs 74.1%; P = 0.250), and a better RFS (median RFS: 19 mo vs 7 mo; P < 0.001), which was worse than that in BCLC-A patients (median RFS: 19 mo vs 48 mo; P = 0.022). Further analysis of patients who developed recurrence showed that both BCLC-B1 and BCLC-A patients had better RTDS (median RTDS: Not reached vs 49 mo; P = 0.599), while the RTDS in BCLC-B2 patients was worse (median RTDS: 16 mo vs not reached, P < 0.001; 16 mo vs 49 mo, P = 0.042). The recurrence patterns were similar between BCLC-B1 and BCLC-A patients, but BCLC-B2 patients had a shorter recurrence time and a higher proportion of patients had recurrence with macrovascular invasion and/or extrahepatic metastasis, both of which were independent risk factors for RTDS. BCLC-B HCC patients undergoing hepatectomy with N + S ≤ 10 had mild recurrence patterns and excellent OS similar to those in BCLC-A MNHCC patients, and LR should be considered in these patients.

A simple CD4+ T cells to FIB-4 ratio for evaluating prognosis of BCLC-B hepatocellular carcinoma: a retrospective cohort study

IntroductionImmunotherapy has become a new therapy for advanced hepatocellular carcinoma (HCC); however, its treatment results are considerably different. CD4+ T cells (CD4+) are the key to immunotherapy, but patients with HCC that have low CD4+ are rarely observed for clinical evidence. Hepatitis B virus-related HCC is often accompanied by cirrhosis and portal hypertension; therefore, CD4+ tend to be relatively low in number. TACE is the standard treatment for Barcelona Clinic Liver Cancer (BCLC)-B HCC, which may further reduce the number of CD4 + .MethodsThis retrospective cohort study further reduced CD4+ by including patients with human immunodeficiency virus (HIV) to observe the relationship between CD4+ and Chronic hepatitis B virus (CHB) induced HCC. A total of 170 BCLC-B HCC patients (42 HIV+) were included. Univariate and multivariate analyses, and artificial neural networks (ANNs) were used to evaluate the independent risk factors for the two-year survival.ResultsThe statistical analysis of the two-year survival rate showed that the main factors influencing survival were liver function and immune indices, including CD4+, platelet, alanine aminotransferase, aspartate aminotransferase, aspartate aminotransferase-to-platelet ratio index, and fibrosis-4 (FIB-4) (P < 0.05). Compared with that in other indices, in logistic and ANN multivariate analysis, CD4 + -to-FIB-4 ratio (CD4+/FIB-4) had the highest importance with 0.716 C-statistic and 145.93 cut-off value. In terms of overall survival rate, HIV infection was not a risk factor (P = 0.589); however, CD4+/FIB-4 ≤ 145.93 significantly affected patient prognosis (P = 0.002).ConclusionHIV infection does not affect the prognosis of BCLC-B HCC, but CD4+ have a significant predictive value. CD4+ played a vital role in HCC and this deserves the attention from physicians. Further, the CD4+/FIB-4 is a clinically valuable effective prognostic indicator for these patients.

Effect of Transarterial Chemoembolization on ALBI Grade in Intermediate-Stage Hepatocellular Carcinoma: Criteria for Unsuitable Cases Selection.

Simple SummaryBCLC-B HCC encompasses heterogeneous populations with varied tumor burden and liver reserve resulting in diverse clinical outcomes to TACE. Liver function deterioration would happen after TACE in patients with high tumor burden. Here, we found that the risk of post-TACE acute ALBI-grade migration was 24.3% and chronic ALBI-grade migration was 16% for BCLC-B HCC patients; HBV infection, up-to-seven criteria, and up-to-eleven criteria were factors of acute ALBI-grade migration, whereas bilobar tumor involvement had high risk of chronic ALBI migration once acute ALBI-grade migration developed after TACE. Overall, up-to-eleven criteria consistently associated with acute and chronic ALBI-grade migration, suggesting that up-to-eleven is an appropriate parameter to select TACE-unsuitable HCC patients who are at risk of liver function deterioration. In addition, patients with ALBI-grade migration in acute or chronic phases had significantly poorer PFS than patients without ALBI-grade migration.Transarterial chemoembolization (TACE) is the standard of care for intermediate stage hepatocellular carcinoma (HCC). We aimed to identify unsuitable cases who were at risk of ALBI-grade migration by TACE. Consecutive 531 BCLC-B HCC patients undergoing TACE were reviewed, and factors associated with ALBI-grade migration were analyzed. There were 129 (24.3%) patients experienced acute ALBI-grade migration after TACE, and 85 (65.9%) out of the 129 patients had chronic ALBI-grade migration. Incidences of acute ALBI-grade migration were 13.9%, 29.0% for patients within or beyond up-to-7 criteria (p < 0.001) and 20.0%, 36.2% for patients within or beyond up-to-11 criteria (p < 0.001), respectively. HBV infection, tumor size plus tumor number criteria were risk factors associated with acute ALBI-grade migration. Bilobar tumor involvement was the risk factor of chronic ALBI-grade migration in patients with acute ALBI-grade migration. Up-to-eleven (p = 0.007) performed better than up-to-seven (p = 0.146) to differentiate risk of dynamic ALBI score changes. Moreover, ALBI-grade migration to grade 3 has adverse effect on survival. In conclusion, tumor burden beyond up-to-eleven was associated with ALBI-grade migration after TACE, indicating that up-to-eleven can select TACE-unsuitable HCC patients who are at risk of liver function deterioration.

Outcome of TACE treatment in HIV infected patients with hepatocellular carcinoma

The surgical treatment and transcatheter arterial chemoembolization (TACE) rate of human immunodeficiency virus (HIV)-infected hepatocellular carcinoma (HCC) patients is relatively low in West China. For various reasons, most patients do not receive timely surgical treatment. Upon transfer to an infectious disease centralized hospital, they were already classified in the Barcelona Clinic Liver Cancer (BCLC)-B stage. A total of 2249 BCLC-B HCC patients were analyzed. The eligible population was divided into three groups for analysis of survival and prognostic factors; These were 21 HIV infected (HIV+) HCC patients treated with TACE (TACE+), 1293 non-HIV-infected (HIV−) HCC patients treated with TACE, and 150 HIV− HCC patients who only receive medication (TACE−) as a second control group. After 1:2 matching, 1- and 2-year survival of HIV+ TACE+ and HIV− TACE+ groups was 64.3% and 76.5% (P = 0.453) and 45.5% vs. 50.0% (P = 0.790) respectively. We also compared one and two-year survival between HIV+ TACE+ and HIV− TACE−. One-year overall survival was 64.3% vs. 45.7% (P = 0.097) and 2-year survival was 45.5% vs. 7.1% (P = 0.004). Multivariate analysis showed that the most important prognostic factors for survival were serum alpha-fetoprotein (AFP) and Child–Pugh score and tumor size, while HIV status had no significant effect on prognosis statistically. CD4 levels below 200 may increase the risk of opportunistic infection after surgery, but after anti-infection and systematic supportive therapy, it has no effect on survival. HIV+ patients should have the same treatment opportunities as HIV− patients. If the patient's immune status permits, we suggest that early TACE treatment should be administered to BCLC-B HCC patients, regardless of HIV infection.

A Five-Gene Signature for Recurrence Prediction of Hepatocellular Carcinoma Patients.

Background Hepatocellular carcinoma (HCC) is one of the most aggressive malignancies with poor prognosis. There are many selectable treatments with good prognosis in Barcelona Clinic Liver Cancer- (BCLC-) 0, A, and B HCC patients, but the most crucial factor affecting survival is the high recurrence rate after treatments. Therefore, it is of great significance to predict the recurrence of BCLC-0, BCLC-A, and BCLC-B HCC patients. Aim To develop a gene signature to enhance the prediction of recurrence among HCC patients. Materials and Methods The RNA expression data and clinical data of HCC patients were obtained from the Gene Expression Omnibus (GEO) database. Univariate Cox regression analysis and least absolute shrinkage and selection operator (LASSO) regression analysis were conducted to screen primarily prognostic biomarkers in GSE14520. Multivariate Cox regression analysis was introduced to verify the prognostic role of these genes. Ultimately, 5 genes were demonstrated to be related with the recurrence of HCC patients and a gene signature was established. GSE76427 was adopted to further verify the accuracy of gene signature. Subsequently, a nomogram based on gene signature was performed to predict recurrence. Gene functional enrichment analysis was conducted to investigate the potential biological processes and pathways. Results We identified a five-gene signature which performs a powerful predictive ability in HCC patients. In the training set of GSE14520, area under the curve (AUC) for the five-gene predictive signature of 1, 2, and 3 years were 0.813, 0.786, and 0.766. Then, the relative operating characteristic (ROC) curves of five-gene predictive signature were verified in the GSE14520 validation set, the whole GSE14520, and GSE76427, showed good performance. A nomogram comprising the five-gene signature was built so as to show a good accuracy for predicting recurrence-free survival of HCC patients. Conclusion The novel five-gene signature showed potential feasibility of recurrence prediction for early-stage HCC.

Prediction of Prognosis of Intermediate-Stage HCC Patients: Validation of the Tumor Marker Score in a Nationwide Database in Japan

Background/Aim: Adequate assessment of transcatheter arterial chemoembolization (TACE)-refractory status has become more important for switching treatment in intermediate-stage (BCLC-B) hepatocellular carcinoma (HCC) patients treated with TACE. The usefulness of a previously proposed tumor marker score for predicting prognosis of BCLC-B HCC patients treated with TACE was investigated. Methods: Using a nationwide database, we examined the records of 1,306 naïve BCLC-B HCC with Child-Pugh A who were treated from 2001 to 2007, after excluding those with missing data (hepatic function or tumor markers) or cases with a single large tumor. Alpha-fetoprotein (AFP) ≥100 ng/mL, fucosylated AFP (AFP-L3) ≥10%, and des-gamma-carboxy prothrombin ≥100 mAU/mL were markers used to define positive cases. The number of positive tumor markers was used as a prognostic score, and its predictive value was evaluated in a retrospective manner. Results: Median survival time became shorter along with increased score (0, 1, ≥2 = 4.8, 3.8, 3.2 years, respectively; p < 0.01). Tumor marker score (≥2; hazard ratio [HR] 1.675, 95% confidence interval [CI] 1.372–2.044, p < 0.001), serum levels of albumin (≥3.5 g/dL; HR 0.726, 95% CI 0.528–0.997, p = 0.048), and up-to-7 criteria (HR 1.673, 95% CI 1.400–2.000, p < 0.001) were significant prognostic factors for death in the Cox hazard multivariate analysis. Conclusion: Tumor marker score had a useful predictive prognostic value in BCLC-B HCC treated with TACE. Especially in patients with a tumor marker score of 2 or greater, a poor therapeutic response should be expected, and appropriate judgement of TACE-refractory status is necessary.

BCLC-B hepatocellular carcinoma treatment or when should the systemic therapy be started

Choice of the optimal therapy for BCLC-B hepatocellular carcinoma (HCC) is a significant clinical problem. Transarterial chemoembolisation (TACE) is considered to be the method of choice as this approach is reported to produce a direct effect and to have a significant survival rate. However, TACE is not always applicable and produce a survival benefit due to the clinical heterogeneity of BCLC-B HCC. The article includes different approaches for BCLC-B HCC patients, TACE prediction and refractory criteria as well as the results obtained. The necessity of timely sorafenib systemic therapy in BCLC-B and in advanced HCC after TACE is discussed. Practical application of regorafenib as the second line in HCC systemic treatment is discussed.

Improved survival with double platinum therapy transcatheter arterial infusion using cisplatin and transcatheter arterial chemoembolization using miriplatin for BCLC-B hepatocellular carcinoma.

Transcatheter arterial chemoembolization (TACE) is the standard therapy for Barcelona Clinic Liver Cancer (BCLC) classification intermediate stage B hepatocellular carcinoma (HCC). However, other transcatheter methods, such as transcatheter arterial infusion (TAI), also play an important role in the treatment of advanced HCC. Although it has been reported that TAI with a high concentration of a fine-powder formulation of cisplatin (DDP-H) reduced intrahepatic recurrence and improved survival, the combined use of TAI with DDP-H and TACE has not yet been investigated. The aim of this study was to evaluate which TACE chemotherapeutic agent in combination with DDP-H TAI contributes more to improved survival in BCLC-B HCC. Survival was analyzed in 55 patients who underwent DDP-H TAI and TACE for BCLC-B HCC. The patients were classified into two groups; Epirubicin was used as the TACE agent in 29 patients, whereas miriplatin was used in 26 patients. The cumulative survival rates at 1 and 2 years were 66.4 and 36.0% in the epirubicin and 95.8 and 61.30% in the miriplatin group, respectively. Survival time was significantly prolonged in the miriplatin group compared with that in the epirubicin group. Multivariate analysis identified Child-Pugh classification and up-to-seven criteria as factors affecting survival. In addition, the selection of miriplatin as the TACE chemoagent was the treatment factor that most significantly affected survival. Thus, double-platinum therapy with DDP-H TAI and miriplatin TACE may be a useful treatment strategy for improving survival in BCLC-B HCC patients.