The radiological prognostic factors of transcatheter arterial chemoembolization to hepatocellular carcinoma.

Transcatheter arterial chemoembolization (TACE) is the recommended treatment modality for intermediate stage hepatocellular carcinoma (HCC). The aim of this study was to determine the HCC radiological characteristics associated with prognosis of patients with intermediate stage HCC receiving TACE. Patients with HCC BCLC stage B from January 2005 to December 2009 were collected. According to mRECIST criteria, patients with complete response and partial response were assigned to the objective response (OR) group, while those with stable disease and progressive disease were assigned to the nonobjective response (non-OR) group. Among a total of 128 enrolled patients, there were 66 (51.6%) and 62 (48.4%) patients in the OR group and non-OR group, respectively. The clinical parameters in the two groups were similar, although HCC size was smaller in the OR group. Logistic analysis found combined radiological characteristics including complete lipiodol retention, tumor feeding artery blockage, and no residual tumor blush were significant correlated with achievement of OR (odds ratio 2.46, 95% CI 1.08-5.61, P = .032). However, no radiological characteristics had significant strength to predict overall survival. Patients with OR after TACE had significantly longer survival time than those with non-OR. Combined characteristics of complete lipiodol retention, tumor feeding artery blockage, and no residual tumor blush had a positive impact on OR in TACE. In patients receiving TACE, those who achieved OR had a better overall survival.

The correlation with tumor radiological characteristics and prognosis of patients with early-stage hepatocellular carcinoma receiving transcatheter arterial chemoembolization.

ABSTRACT: Transcatheter arterial chemoembolization (TACE) is a standard treatment modality for intermediate stage hepatocellular carcinoma (HCC). The aim of this study was to determine the tumor radiological characteristics associated with prognosis of patients with early-staged HCC receiving TACE.Patients with BCLC stage A HCC were enrolled at Taichung Veterans General Hospital from January 2005 to December 2009. According to mRECIST criteria, patients with or without complete response (CR) were assigned to either the CR group or the non-CR group. Clinical and radiological characteristics were compared between the two groups.In 40 enrolled patients, 24 (60%) were in the CR group, and 16 (40%) in the non-CR group. Clinical parameters were similar between the 2 groups. Radiological characteristics including complete lipidol retention and the absence of residual tumor blush were significantly correlated with achievement of CR in the patients with small-sized HCC. Patients with CR after TACE had a significantly longer overall survival than those without (31.29 vs 22.63 months, P = .021).Complete lipidol retention and the absence of residual tumor blush were correlated with the radiological complete tumor response of these patients with small-sized early-stage HCC receiving TACE.

Impact of Glutathione and Vitamin B-6 in Cirrhosis Patients: A Randomized Controlled Trial and Follow-Up Study.

Vitamin B-6 and glutathione (GSH) are antioxidant nutrients, and inadequate vitamin B-6 may indirectly limit glutathione synthesis and further affect the antioxidant capacities. Since liver cirrhosis is often associated with increased oxidative stress and decreased antioxidant capacities, we conducted a double-blind randomized controlled trial to assess the antioxidative effect of vitamin B-6, GSH, or vitamin B-6/GSH combined supplementation in cirrhotic patients. We followed patients after the end of supplementation to evaluate the association of vitamin B-6 and GSH with disease severity. In total, 61 liver cirrhosis patients were randomly assigned to placebo, vitamin B-6 (50 mg pyridoxine/d), GSH (500 mg/d), or B-6 + GSH groups for 12 weeks. After the end of supplementation, the condition of patient's disease severity was followed until the end of the study. Neither vitamin B-6 nor GSH supplementation had significant effects on indicators of oxidative stress and antioxidant capacities. The median follow-up time was 984 d, and 21 patients were lost to follow-up. High levels of GSH, a high GSH/oxidized GSH ratio, and high GSH-St activity at baseline (Week 0) had a significant effect on low Child-Turcotte-Pugh scores at Week 0, the end of supplementation (Week 12), and the end of follow-up in all patients after adjusting for potential confounders. Although the decreased GSH and its related enzyme activity were associated with the severity of liver cirrhosis, vitamin B-6 and GSH supplementation had no significant effect on reducing oxidative stress and increasing antioxidant capacities.

The therapeutic benefits of combined sorafenib and transarterial chemoembolization for advanced hepatocellular carcinoma.

OBJECTIVE: Systemic therapy, such as sorafenib, has been used clinically to treat patients with advanced stage or Barcelona Clinic Liver Cancer staging system (BCLC) stage C hepatocellular carcinoma (HCC). The aim of the study was to evaluate the therapeutic benefit of combined sorafenib and transarterial chemoembolization (TACE) in this group of patients. METHODS: Data on patients with HCC at BCLC stage C from August 2012 to September 2017 were collected. Patients who were given sorafenib alone were classified as the monotherapy group and those taking sorafenib and TACE were classed as the combined therapy group. RESULTS: A total of 118 patients were enrolled. There were 65 and 53 patients in the monotherapy and the combined therapy group, respectively. The groups' general characteristics were similar. Compared with the monotherapy group the combined therapy group experienced prolonged time-to-progression (TTP) (mean 6.42 mo vs 3.63 mo, P = 0.003) and overall survival (OS) (mean 11.21 mo vs 5.98 mo, P = 0.001). A subgroup analysis found that patients with macroscopic vascular invasion (MVI) also had prolonged TTP and OS in the combined therapy group than the monotherapy group (mean TTP, 7.93 mo vs 3.43 mo, P = 0.007; mean OS, 13.41 mo vs 5.50 mo, P = 0.001), however, these significant differences did not exist for those with extrahepatic spread (EHS). CONCLUSION: Combined sorafenib and TACE therapy has significant better outcomes than sorafenib alone in patients with stage C HCC, particularly those with MVI.

Sorafenib treatment on Chinese patients with advanced hepatocellular carcinoma: A study on prognostic factors of the viral and tumor status.

Sorafenib is of proven efficacy in treating patients of hepatocellular carcinoma (HCC). Our study was aimed to determine the factors influence the sorafenib efficacy.We evaluated data of HCC patients receiving sorafenib from June 2012 to October 2016. All HCC cases were of the Barcelona Clinic Liver Cancer (BCLC) classification stage C. The exclusion criteria: those of BCLC classification stage A or B, with the absence or co-infection of hepatitis B (HBV) and hepatitis C (HCV). The presence of HBV, HCV, macoscopic vascular invasion (MVI) or extrahepatic spread (EHS) was recorded for each patient. Time-to-progression (TTP) and overall survival (OS) were analyzed.Among a total of 90 HCC patients, 48 (53.3%) had HBV infection, 42 (46.7%) had HCV infection, 51 (56.7%) had MVI, and 39 (43.3%) had EHS. Patients with HCV infection showed better TTP and OS than those with HBV infection. Patients with EHS had a longer TTP and OS than those with MVI. For patients with HBV infection, those with EHS had a longer TTP (mean 4.60 vs 2.64 months, P = .002) and OS (mean 6.65 vs 4.53 months, P = .045) compared to those with MVI. Among those with MVI, patients with HBV infection had a poorer TTP (mean 2.64 vs 4.74 months, P = .019) and shorter OS (mean 4.53 vs 7.00 months, P = .059) compared to those with HCV infection.HCC patients with HCV infection or with the presence of EHS showed better sorafenib efficacy.

Transcatheter arterial chemoembolization after stopping sorafenib therapy for advanced hepatocellular carcinoma.

Targeted therapy is currently the standard treatment for advanced hepatocellular carcinoma (HCC), but an effective treatment after the discontinuation of sorafenib therapy remains uncertain. We aim to investigate the survival benefits of transcatheter arterial chemoembolization (TACE) after stopping sorafenib therapy. We retrospectively analyzed all patients with advanced HCC, who had received palliative TACE after terminating sorafenib therapy, from January 2008 to June 2016. Patients who were in the terminal stage (Child-Pugh class C or performance status 3-4), who received a liver transplantation, or who had received any HCC treatment other than TACE, were excluded. Finally, 28 patients were recruited as the TACE group, and were randomly matched 1:1 by age, gender, Child-Pugh class, extrahepatic metastasis, and portal vein thrombosis with 28 controls who only received supportive care. For avoiding any immortal time bias, the index date of outcome follow-up was also matched. Cumulative incidences of, and hazard ratios (HRs) for, patient mortality were analyzed. The baseline demographic data between the TACE group and the control group were similar, but the 1-year overall survival rate in the TACE group was significantly higher than that of the control group (41.2%, 95% confidence interval [CI]: 19.4-63.0% vs. 24.5%, 95% CI: 6.3-42.7%; p < 0.01). In multivariate analysis, after adjusting for alpha-fetoprotein > 400ng/mL, Child-Pugh class B, and tumor extension > 50% of liver volume, TACE was independently associated with a decreased mortality risk(HR 0.19, 95% CI: 0.08-0.42). In addition, tumor extension > 50% of the liver was another independent prognostic factor associated with an increased mortality risk (HR 2.99, 95% CI: 1.31-6.82). Multivariate stratified analyses verified the association of TACE with a decreased mortality rate in each patient subgroup (all HR < 1.0). By controlling intrahepatic tumor growth, TACE may be a treatment option for use in improving patient survival in advanced HCC, after the termination of sorafenib therapy.

The combination of transcatheter arterial chemoembolization and sorafenib is well tolerated and effective in Asian patients with hepatocellular carcinoma: final results of the START trial.

This phase II, investigator-initiated, prospective single-arm multinational study (ClinicalTrials.gov registration NCT00990860) evaluated sorafenib in combination with doxorubicin-based transarterial chemoembolization (TACE) in patients with intermediate-stage, unresectable hepatocellular carcinoma (HCC). Patients with histologically or clinically diagnosed HCC received TACE with interrupted dosing of sorafenib (sorafenib discontinued for 3 days before and 4-7 days after TACE). TACE/sorafenib cycles were repeated every 6-8 weeks. Primary and secondary objectives were, respectively: to evaluate the safety and tolerability of TACE combined with sorafenib, and also their efficacy. The full analysis set comprised 192 patients (mean age 56.1 years). Most were male (87.0%), Eastern Cooperative Oncology Group (ECOG) score 0 (81.8%), Child-Pugh A (91.8%) and Barcelona Clinic Liver Cancer (BCLC) stage B (81.5%); 81.2% had chronic hepatitis B. Combined TACE/sorafenib was well tolerated, with only 8.1% of patients discontinuing owing to adverse events (AEs). The most common grade ≥3 AEs were palmar-plantar erythrodysesthesia syndrome (15.1%) and decreased platelet count (10.9%). Serious AEs (SAEs) occurred in 52 patients during the study; however, only four were considered related to sorafenib. A mean of 2.7 TACE cycles were administered and 52.6% of patients achieved complete response in target lesions; 16.8% achieved partial response, and 5.8% had progression of disease as their best response, evaluated by modified RECIST. Median progression-free survival and time to progression were 384 and 415 days, respectively, and the estimated 3-year overall survival was 86.1%. This study suggests that the combination of TACE and sorafenib is well tolerated and efficacious; the interrupted sorafenib dosing schedule may have contributed to a considerably lower AE profile than observed in other combination trials.

Interim analysis of START: Study in Asia of the combination of TACE (transcatheter arterial chemoembolization) with sorafenib in patients with hepatocellular carcinoma trial.

Transarterial chemoembolization (TACE) represents a first-line noncurative therapy for hepatocellular carcinoma (HCC). Sorafenib, a multikinase inhibitor, has been shown to be effective and safe monotherapy in patients with advanced HCC and the current study reports the interim results of a prospective Phase II, open label, trial investigating the safety and efficacy of the combination of sorafenib and conventional TACE in patients from the Asia-Pacific region with intermediate HCC. Patients with histologically or clinically diagnosed HCC were treated with conventional TACE followed by sorafenib 4 to 7 days later. TACE was performed by selective transarterial chemotherapy in the vessels feeding the tumor with an emulsion of lipiodol (5-20 ml) and doxorubicin (30-60 mg) followed by embolization with absorbable particles (gel foam). TACE/sorafenib cycles were repeated every 6-8 weeks. Primary objectives were to evaluate the safety and tolerability, in addition to the efficacy of TACE combined with sorafenib for HCC. A total of 147 patients were included in the intention-to-treat analysis and received at least one dose of sorafenib. Gastrointestinal AEs were reported by 62.6% of patients while 57.8% reported skin AEs although most were mild to moderate. The mean number of cycles undertaken was 2.1 and 63.3% of patients achieved either partial response or stable disease. Clinically, the disease control rate was 91.2% while the overall response rate was calculated as 52.4%. Our study shows that concurrent sorafenib and TACE therapy is safe and effective with no unexpected side effects.