International and multicenter real-world study of sorafenib-treated patients with hepatocellular carcinoma under dialysis.

BACKGROUND & AIMS: Information on safety and efficacy of systemic treatment in patients with hepatocellular carcinoma (HCC) under dialysis are limited due to patient exclusion from clinical trials. Thus, we aimed to evaluate the rate, prevalence, tolerability, and outcome of sorafenib in this population. METHODS: We report a multicenter study comprising patients from Latin America and Europe. Patients treated with sorafenib were enrolled; demographics, dose modifications, adverse events (AEs), treatment duration, and outcome of patients undergoing dialysis were recorded. RESULTS: As of March 2018, 6156 HCC patients were treated in 44 centres and 22 patients were concomitantly under dialysis (0.36%). The median age was 65.5 years, 40.9% had hepatitis C, 75% had Child-Pugh A, and 85% were Barcelona Clinic Liver Cancer-C. The median time to first dose modification, treatment duration and overall survival rate were 2.4 months (interquartile ranges [IQR], 0.8-3.8), 10.8 months (IQR, 4.5-16.9), and 17.5 months (95% CI, 7.2-24.5), respectively. Seventeen patients required at least 1 dose modification. The main causes of first dose modification were asthenia/worsening of Eastern Cooperative Oncology Group-Performance Status and diarrhoea. At the time of death or last follow-up, four patients were still on treatment and 18 had discontinued sorafenib: 14 were due to tumour progression, 2 were sorafenib-related, and 2 were non-sorafenib-related AE. CONCLUSIONS: The outcomes observed in this cohort seem comparable to those in the non-dialysis population. Thus, to the best of our knowledge, this is the largest and most informative dataset regarding systemic treatment outcomes in HCC patients undergoing dialysis.

Real-life glecaprevir/pibrentasvir in a large cohort of patients with hepatitis C virus infection: The MISTRAL study.

BACKGROUND AND AIMS: It is paramount to identify predictors of treatment failure with direct antiviral agents in 'field-practice' patients, including people who inject drugs (PWID). Data on the efficacy of glecaprevir/pibrentasvir (GLE/PIB) in a field-practice scenario are scant. The multicentre MISTRAL study enrolled 1177 patients, including PWID, to assess real-life efficacy and safety of GLE/PIB and to identify the predictive factors for this treatment. METHODS: This was a prospective, longitudinal study. The outcome variable was the rate of sustained virological response (SVR) at week 12. RESULTS: A total of 123 patients (10%) were infected from hepatitis C virus (HCV) 3. METAVIR fibrosis score was F4 in 104 subjects (9%); 118 patients (10%) were PWID. Overall, 1163/1177 (99%) patients achieved SVR. The baseline clinical factors discriminating between treatment success and treatment failure were age at treatment (P = 0.031) and creatinine level (P = 0.034). SVR rates were not influenced by gender, substance abuse, previous treatment, treatment duration, fibrosis or chronic kidney disease stage. Compared with non-substance users, the 118 PWID exhibited a significantly different genotype pattern distribution (χ2  < 0.001). A total of 40/118 (33.9%) of substance users were HCV3 compared to 83/1056 (7.9%) non-substance users. Only 6 patients (0.5%) reported a serious adverse event. CONCLUSIONS: The MISTRAL study provides evidence of GLE/PIB efficacy in a field-practice scenario in a highly epidemic HCV area in southern Italy; it unveiled significant differences in genotype distribution among the most underserved and difficult-to-treat patient subgroups including PWID.

Decrease in total lesion glycolysis and survival after yttrium-90-radioembolization in poorly differentiated hepatocellular carcinoma with portal vein tumour thrombosis.

PURPOSE: This study aims to evaluate the prognostic role of the decrease in total lesion glycolysis (TLG) assessed by fluorine-18-fluorodeoxyglucose (F-FDG) PET-computed tomography (CT) 1 month after yttrium-90-radioembolization (Y-RE) in patients affected by hepatocellular carcinoma (HCC) with portal vein tumour thrombosis (PVTT). PATIENTS AND METHODS: Twenty-one patients with histologically proven poorly differentiated HCC and evidence of PVTT at the enhanced multislice CT underwent Y-RE. All patients underwent an F-FDG PET-CT scan at baseline and 1 month after the loco-regional therapy. The variation in TLG (ΔTLG) between the two studies was calculated. Patients were divided in two groups (group 1: 1 month ΔTLG >50%, group 2: ΔTLG <50%). Statistical analysis was carried out to assess the prognostic role of TLG in overall survival (OS). RESULTS: On the 21 patients enrolled, all presented a decrease in TLG after the administration of Y-microspheres. The OS was 11.5±1.2 months. Nine out of 21 (42.9%) patients showed ΔTLG more than 50% with a mean OS of 16.8±1.3 months, whereas the remaining 12 (57.1%) patients had ΔTLG less than 50% with a mean OS of 7.5±0.5 months. Statistical analysis showed ΔTLG to be a significant (P<0.001) predictor of survival. None of the other examined variables including age, Child-Pugh classification, previously performed therapies, the presence of extrahepatic metastases, α-fetoprotein and bilirubin levels had a significant prognostic impact on patients' outcome. CONCLUSION: Decrease in TLG measured by F-FDG PET-CT is correlated with a trend towards a longer median survival in patients affected by HCC and PVTT who have undergone Y-RE.

Circulating SCCA-IgM complex is a useful biomarker to predict the outcome of therapy in hepatocellular carcinoma patients.

INTRODUCTION: Hepatocellular carcinoma (HCC) develops in about 3-4% of cirrhotic patients every year. The squamous cell carcinoma antigen (SCCA) has been found elevated in liver cancer specimens by immunohistochemistry, and detected in complex with IgM (SCCA-IgM) in the serum of patients with HCC. The aim of this study was to evaluate the ability of serological SCCA-IgM levels to predict the efficacy of HCC therapy. MATERIALS AND METHODS: From April 2012 to April 2014, 131 patients with a new diagnosis of HCC were enrolled. The HCC diagnosis was made according to the EASL guidelines. The patients were staged and treated according to the BCLC Staging System: BCLC stages A and B were treated with locoregional therapy, and BCLC stage C was treated with Sorafenib. Response to therapy was evaluated according to the mRECIST criteria. Serum SCCA-IgM levels were determined by a commercially available ELISA kit at basal time (T0) and after one month of treatment (T1). RESULTS: At baseline and one month into therapy, SCCA-IgM levels were significantly lower (p value <.05) in patients who responded to therapy compared to those who did not respond (median SCCA-IgM level [25th + 75th percentile] at T0:115.1 AU/mL [50.0 + 174.4] vs. 149.1 AU/mL [111.3 + 198.8]; median SCCA-IgM level [25th + 75th percentile] at T1: 113.4 AU/mL [50.0 + 194.2] vs. 170.6 AU/mL [111.7 + 344.2]). CONCLUSION: Our study suggests that the SCCA-IgM determination could be helpful in predicting the response to therapy in patients with HCC.