Drug-eluting bead transarterial chemoembolization followed by apatinib is effective and safe in treating hepatocellular carcinoma patients with BCLC stage C

BackgroundThe present study aimed to evaluate the efficacy and safety of drug-eluting beads transarterial chemoembolization (DEB-TACE) followed by apatinib in treating hepatocellular carcinoma (HCC) patients with Barcelona Clinic Liver Cancer (BCLC) stage C.MethodsTotally, 110 HCC patients with BCLC stage C treated with DEB-TACE followed by apatinib were consecutively enrolled. Treatment response (including complete response rate (CR), objective response rate (ORR) and disease control rate (DCR)), survival data (progression-free survival (PFS), overall survival (OS)), and adverse events were documented during the follow-up.ResultsCR, ORR and DCR were 25.5%, 77.2% and 79.1% at 3 months, then were 29.1%, 59.1% and 71.0% at 6 months, respectively. Regarding survival, median PFS (95%CI) was 6.3 (5.0-7.7) months, meanwhile 1-year and 2-year PFS were 19.8% and 3.3%, respectively; median OS (95%CI) was 16.9 (10.2-23.7) months, then 1-year, 2-year and 3-year OS were 66.5%, 34.7% and 14.2%, respectively. Further subgroup analysis indicated that nodule size, Child-Pugh stage, Eastern Cooperative Oncology Group performance status score and level of portal vein invasion were negatively correlated with PFS or OS, which were further validated by univariate and multivariate Cox's regression analysis. Most adverse events by DEB-TACE and apatinib treatment were mild and well-tolerable.ConclusionDEB-TACE followed by apatinib is effective and safe in treating BCLC stage C HCC patients, indicating its role as an acceptable option in HCC management.     

Chemotherapy for transarterial chemoembolization in patients with unresectable hepatocellular carcinoma

AIM: To compare the efficacy of different chemotherapeutic agents during conventional transarterial chemoembolization (cTACE) in the treatment of unresectable hepatocellular carcinoma (HCC).METHODS: A retrospective review was undertaken of patients with unresectable HCC undergoing cTACE from May 2003 to November 2011. A total of 107 patients were treated with at least one cTACE session. Irinotecan (CPT-11) was used as a chemotherapeutic agent in 24 patients, gemcitabine (GEM) in 24 and doxorubicin in 59.RESULTS: The time to progression and overall survival rates were significantly superior in patients treated with CPT-11 compared with the GEM or doxorubicin treated groups (11.4, 8.2, 9.5 mo, P = 0.02 and 21.7, 12.7, 14.5 mo, P = 0.004, respectively). Subgroup analysis showed that for intermediate-stage HCC, CPT-11 resulted in a significantly longer time to progression and overall survival compared with the GEM or doxorubicin treated groups (P = 0.022; P = 0.003, respectively). There were no significant differences in adverse events among the three groups (P > 0.05).CONCLUSION: For patients treated with cTACE, the chemotherapeutic agent CPT-11 was significantly associated with improved overall survival and delayed tumor progression compared with GEM or doxorubicin. There were no significant differences in clinical adverse events between the three agents. CPT-11 thus appears to be a promising agent when combined with cTACE for the treatment of HCC.     

Renal failure in patients with hepatocellular carcinoma and ascites undergoing transarterial chemoembolization

Background: Ascites is often present in patients with hepatocellular carcinoma (HCC) with cirrhosis. Advanced cirrhosis may predispose to renal dysfunction. Acute renal failure (ARF) may occur after transarterial chemoembolization (TACE) for HCC because of radiocontrast agents. This study aimed to investigate the incidence and risk factors of ARF and prognostic predictors in HCC patients with ascites undergoing TACE. Methods: A total of 591 HCC patients receiving TACE were enrolled. Results: In a mean follow‐up duration of 19±17 months, 239 (40.4%) patients undergoing TACE died. Ascites, which was present in 91 (15.4%) patients at entry, independently predicted a poor prognosis in the Cox proportional hazard model [risk ratio (RR): 1.71, P=0.002]. Of these, 11 (12.6%) of 87 patients with complete follow‐up developed ARF after TACE. Serum albumin level <3.3 g/dl (odds ratio: 7.3, P=0.009) was the only independent risk factor associated with ARF in the logistic regression analysis. ARF (RR: 2.17, P=0.036), α‐fetoprotein >400 ng/ml (RR: 1.84, P=0.04), multiple tumours (RR: 2.11, P=0.013), tumour size ≥5 cm (RR: 2.32, P=0.006) and serum sodium level <139 mmol/L (RR: 2.4, P=0.005) were independent poor prognostic predictors for HCC patients with ascites receiving TACE. Conclusions: Pre‐existing ascites is associated with increased mortality in HCC patients receiving TACE. In HCC patients with ascites, hypoalbuminaemia is associated with the occurrence of post‐TACE ARF. Post‐TACE ARF is a poor prognostic predictor in this subset of HCC patients.     

Transcatheter arterial chemoembolization (TACE) in treatment of hepatocellular carcinoma

BACKGROUND/AIMS: Substantial differences about the efficacy of transcatheter arterial chemoembolization for the treatment of hepatocellular carcinoma are reported in literature. This probably depends on the fact that in each single study, different patient selection criteria, type of epidemiological approach, end points adopted and kind of technical approach were used. This study aims to evaluate the efficacy of segmental transcatheter arterial chemoembolization in amelioring patient survival and to determine which patients might really benefit from this treatment. METHODOLOGY: To achieve our goals 193 consecutive patients (110 treated and 83 untreated) were studied. They were selected in the same period of time and matched as far as their demographic and clinical characteristics. RESULTS: Our results demonstrate that both in treated and control patients, Child class, alpha-fetoprotein and tumor diameter significantly influenced survival, resulting important prognostic factors. Transcatheter arterial chemoembolization significantly ameliorated survival in treated patients compared to controls (p < 0.0001). CONCLUSIONS: Transcatheter arterial chemoembolization significantly ameliorates survival in patients with hepatocellular carcinoma. However, the presence of large tumors producing high alpha-fetoprotein levels in patients with advanced Child class should discourage treatment.     

Lipiodolized transarterial chemoembolization in hepatocellular carcinoma patients after curative resection

Purpose

To explore the effect of lipiodolized transarterial chemoembolization (lip-TACE) in hepatocellular carcinoma (HCC) patients at different risk of recurrence after curative resection.

Methods

One thousand nine hundred and twenty-four consecutive HCC patients who underwent curative resection were retrospectively analyzed. Patients who underwent resection only were classified into control group, while those received adjuvant lip-TACE were classified into intervention group. Patients were further stratified into 4 groups, that is, tumor ≤5 cm with low or high risk factors, as well as tumor >5 cm with low or high risk factors for recurrence. Tumor number and microscopic tumor thrombus were defined as risk factors for recurrence. The effect of adjuvant lip-TACE on early (<2 year) or late (≥2 year) recurrence was evaluated.

Results

There was no significant difference in recurrence curve between intervention group and control group in each stratum. Adjuvant lip-TACE showed an overall survival benefit in patients with tumor >5 cm and presenting high risk factors, mainly for those with time to recurrence (TTR) <2 years after operation. For them, the median survival was 17 months in the intervention group and 11 months in the control group (P = 0.010). For patients who were confirmed to be recurrence-free at 2 years after operation, it had the negative effect for survival (HR = 1.75, P = 0.004).

Conclusion

Adjuvant lip-TACE had no preventive effect on recurrence, but may be of benefit to detect early recurrence.     

Evaluation of the relationship between hepatocellular carcinoma location and transarterial chemoembolization efficacy

AIM To evaluate the relationship between the location of hepatocellular carcinoma(HCC) and the efficacy of transarterial chemoembolization(TACE).METHODS We evaluated 115 patients(127 nodules), excluding recurrent nodules, treated with TACE between January 2011 and June 2014. TACE efficacy was evaluated according to m RECIST. The HCC location coefficient was calculated as the distance from the central portal portion to the HCC center(mm)/liver diameter(mm) on multiplanar reconstruction images rendered(MPR) to visualize bifurcation of the right and left branches of the portal vein and HCC center. The HCC location coefficient was compared between complete response(CR) and non-CR groups in Child-Pugh grade A and B patients.RESULTS The median location coefficient of HCC among all nodules, the right lobe, and the medial segment was significantly higher in the CR group than in the non-CR group in the Child-Pugh grade A patients(0.82 vs 0.62, P 0.001; 0.71 vs 0.59, P 0.01; 0.81 vs 0.49, P 0.05, respectively). However, there was no significant difference in the median location coefficient of the HCC in the lateral segment between in the CR and in the non-CR groups(0.67 vs 0.65, P 0.05). On the other hand, in the Child-Pugh grade B patients, the HCC median location coefficient in each lobe and segment was not significantly different between in the CR and in the non-CR groups.CONCLUSION Improved TACE efficacy may be obtained for HCC in the peripheral zone of the right lobe and the medial segment in Child-Pugh grade A patients.     

Transarterial chemoembolization (TACE) plus apatinib vs. TACE alone for hepatocellular carcinoma

ObjectiveTransarterial chemoembolization (TACE) is a common therapy for hepatocellular carcinoma (HCC), while TACE-induced tumor angiogenesis would increase progression and metastasis risk. Besides, apatinib possesses the capability of inhibiting tumor angiogenesis. Thus, this study aimed to explore the efficacy and safety of TACE plus apatinib compared to TACE alone in HCC patients.MethodsNinety-six intermediate-advanced HCC patients were retrospectively enrolled and classified into TACE plus apatinib group (N = 45) and TACE group (N = 51) based on the treatment.ResultsObjective response rate (68.9% vs. 47.1%) was increased in TACE plus apatinib group than in TACE group (P = 0.031). However, no difference was found in disease-control rate between groups (95.6% vs. 86.3%) (P = 0.167). Progression-free survival (PFS) (median PFS (95% confidence interval (CI)): 20.0 (13.2–26.8) vs. 14.0 (8.3–19.7) months) was enhanced in TACE plus apatinib group compared with TACE group (P = 0.030), while no difference was found in overall survival between groups (P = 0.060). Additionally, multivariate Cox's analysis presented that TACE plus apatinib (vs. TACE alone) independently associated with prolonged PFS (P = 0.043, hazard ratio = 0.617). Regarding safety profile, no difference in liver function indexes (albumin, total bilirubin, alanine aminotransferase and aspartate aminotransferase) was found after treatment between two groups; meanwhile, only the incidence of hand-foot skin reaction (24.4% vs. 7.8%) was higher in TACE plus apatinib group compared to TACE group (P = 0.025), while no difference was found in other adverse events between two groups (all P > 0.05).ConclusionTACE plus apatinib illustrates a superior efficacy with tolerable safety than TACE alone in intermediate-advanced HCC patients.     

Preresection transarterial chemoembolization for hepatocellular carcinoma: An experience with 23 patients

Purpose

The routine use of transarterial chemoembolization (TACE) prior to resection for hepatocellular carcinoma (HCC) is not recommended, although its use in the transplant setting is gaining popularity. In the absence of other effective neoadjuvant or adjuvant treatment options, TACE may benefit selected patients. The aim was to evaluate the feasibility and outcomes of preoperative TACE for selected patients with HCC.

Methods

From November 2010 to October 2012, 23 patients of HCC were selected by a multidisciplinary team to undergo TACE prior to resection.

Results

TACE was successful in all patients with no intraprocedural complications. TACE reduced the mean maximum tumor diameter from 9.2 to 8.2 cm and increased the mean future liver remnant (FLR) from 37.7 % to 49.1 %. Nineteen resections were completed with negative margins, of which only three patients (15.8 %) had cirrhosis. Two patients (10.5 %) experienced postoperative bile leaks and six patients (31.5 %) developed postoperative liver failure, two (10.5 %) of which succumbed to grade C liver failure. From the date of surgery, the median follow up time was 17.1 months. Four patients (17 %) did not undergo curative resection due to disease progression in three patients and severe TACE toxicity in one patient. None of the resected patients developed disease recurrence and the overall survival was 21 months.

Conclusion

Encouraging outcomes in terms of disease recurrence and overall survival need to be balanced with the risk of surgical drop out and perioperative complications when selecting patients for TACE prior to resection.     

Analysis of aggressiveness factors in hepatocellular carcinoma patients undergoing transarterial chemoembolization

AIM To investigate novel predictors of survival in hepatocellular carcinoma(HCC) patients following transarterial chemoembolization(TACE).METHODS One hundred sixty seven patients with un-resectable HCC were retrospectively analyzed to identify factors that might contribute to their HCC biology and aggressiveness. We correlated routine laboratory results(total bilirubin, AST, ALKP, GGTP, albumin etc.) to maximum tumor diameter, number of tumor nodules, portal vein thrombosis and blood alpha-fetoprotein levels. These 4 parameters were previously combined to form an aggressiveness index(AgI). We used The Wilcoxon ranksum(Mann-Whitney), to test the correlation between the AgI categories and liver function parameters. The Cox proportional hazards model was applied to evaluate the categories of AgI associated with overall survival. RESULTS The AgI was strongly correlated with survival in this novel patient population. Three year survival probability for AgI or 4 was 42.4% vs 61.8%; P 0.0863 respectively. Several factors independently correlated with AgI using univariate multiple logistic regression of AgI with 8 laboratory parameters. Lower albumin levels had an OR of 2.56(95%CI: 1.120-5.863 P 0.026), elevated Alkaline phosphatase and gamma glutamyl transpeptidase(GGTP) had ORs of 1.01(95%CI: 1.003-1.026, P 0.017) and 0.99(95%CI: 0.99-1.00, P 0.053) respectively. In a Cox proportional hazard model combining mortality for AgI score and liver function parameters, only GGTP levels and the AgI were independently associated with survival. An AgI 4 had HR for mortality of 2.18(95%CI: 1.108-4.310, P 0.024). GGTP's single unit change had a HR for mortality of 1.003(95%CI: 1.001-1.006, P 0.016). These were considered in the final multivariate model with the total cohort. An AgI 4 had a HR for mortality of 2.26(95%CI: 1.184-4.327, P 0.016). GGTP had a HR of 1.003(95%CI: 1.001-1.004, P 0.001).CONCLUSION Our study validates the AgI in a new population with un-resectable HCC patients undergoing TACE. The analysis establishes a correlation between GGTP and the AgI.     

Selecting a prognostic renal surrogate for patients with hepatocellular carcinoma undergoing transarterial chemoembolization

Background and Aim: Renal insufficiency (RI) often coexists with hepatocellular carcinoma (HCC) and predicts a poor outcome in patients receiving transarterial chemoembolization (TACE). The modification of diet in renal disease (MDRD) and chronic kidney disease epidemiology collaboration (CKD‐EPI) equations are used to provide estimated glomerular filtration rate (eGFR). This study aimed to determine a prognsotic renal surrogate for outcome prediction in HCC patients receiving TACE. Methods: A total of 684 patients with HCC undergoing TACE were retrospectively analyzed. The prognostic ability between the MDRD and CKD‐EPI equation was compared by the Akaike information criterion (AIC). Results: Patients were categorized by eGFR into > 60, 30–60 and < 30 mL/min per 1.73 m² (equivalent to CKD stages 1–2, 3, and 4–5, respectively) groups. The eGFR generated by the MDRD equation had a better predictive accuracy by having a lower AIC score (3234.5) compared to the CKD‐EPI equation (3236.7). The adjusted risk ratio for patients with eGFR 30–60 mL/min per 1.73 m² by the MDRD was 1.313 (P = 0.041) compared with patients with eGFR > 60 mL/min per 1.73 m² in the multivariate Cox model. The eGFR defined by the MDRD equation consistently had better prognostic ability when patients were stratified by the Child‐Turcotte‐Pugh score of 5 and > 5 and Cancer of the Liver Italian Program score 0 to 1 and > 1. Conclusions: The eGFR according the MDRD equation may provide better prognostic accuracy than the CKD‐EPI equation independent of liver functional reserve and tumor staging, and is a more feasible renal surrogate for outcome prediction in CKD stage 1–3 HCC patients receiving TACE.