Hepatocellular carcinoma: French Intergroup Clinical Practice Guidelines for diagnosis, treatment and follow-up (SNFGE, FFCD, GERCOR, UNICANCER, SFCD, SFED, SFRO, AFEF, SIAD, SFR/FRI).

Introduction: This document is a summary of the French Intergroup guidelines regarding the management of hepatocellular carcinoma (HCC) published in March 2019.

Method: It is a collaborative work under the auspices of most of the French medical societies involved in the management of HCC. It is based on the previous guidelines published in 2017.

Geographical Disparities of Outcomes of Hepatocellular Carcinoma in France: The Heavier Burden of Alcohol Compared to Hepatitis C.

Background: Data on alcohol-related HCC are limited.

Aims: Our aim was to describe the incidence, management, and prognosis of alcohol compared to Hepatitis C (HCV)-related HCC at a national level.

Methods: Incident cases of HCC were identified in French healthcare databases between 2009 and 2012 and analyzed retrospectively.

Idarubicin-loaded Beads for Chemoembolization of Hepatocellular Carcinoma: The IDASPHERE II Single-Arm Phase II Trial.

Background A prior in vitro study showed that idarubicin was the most cytotoxic agent for hepatocellular carcinoma (HCC) cell lines. Idarubicin-loaded beads for transarterial chemoembolization (TACE) were previously evaluated for the appropriate dose in a phase I dose-escalation study. Purpose To evaluate objective response rate (ORR), safety, and survival after TACE by using idarubicin-loaded beads for unresectable HCC.

Early decrease in serum amphiregulin or vascular endothelial growth factor levels predicts sorafenib efficacy in hepatocellular carcinoma.

Sorafenib is the standard of care for the treatment of advanced hepatocellular carcinoma (HCC). However, identifying secreted biomarkers that predict sorafenib efficacy in all HCC patients remains challenging. It was recently reported that sorafenib interferes with protein homeostasis and inhibits global translation in tumour cells.

[Care pathway of patients with hepatocellular carcinoma in France: State of play in 2017].

Hepatocellular carcinoma is a major public health problem with one of the highest overall mortality compared to other cancers. The median overall survival in France in a hospital population with hepatocellular carcinoma is 9.4 months.

Alpha-foetoprotein (AFP): A multi-purpose marker in hepatocellular carcinoma.

Alpha-foetoprotein (AFP), one of the first protein tumour markers discovered, is widely used today in clinical practice. Its application for the screening and diagnosis of hepatocellular carcinoma (HCC), the most frequent form of primary liver tumour, is a matter of extensive debate. In addition to the studies focused on the role of the AFP in the diagnosis of HCC, in recent years AFP has been used to guide the therapeutic choice in HCC and monitor the treatment.

Geographical variations in incidence, management and survival of hepatocellular carcinoma in a Western country.

Background & Aims: Information on the incidence, management, and prognosis of hepatocellular carcinoma (HCC) is derived from population samples, regional data, or registries. Comprehensive national evaluations within a given country are lacking. This study aimed to investigate regional variations in HCC care within France.

Metallothionein-1 as a biomarker of altered redox metabolism in hepatocellular carcinoma cells exposed to sorafenib.

Background: Sorafenib, a kinase inhibitor active against various solid tumours, induces oxidative stress and ferroptosis, a new form of oxidative necrosis, in some cancer cells. Clinically-applicable biomarkers that reflect the impact of sorafenib on the redox metabolism of cancer cells are lacking.

Methods: We used gene expression microarrays, real-time PCR, immunoblot, protein-specific ELISA, and gene reporter constructs encoding the enzyme luciferase to study the response of a panel of cancer cells to sorafenib.

Alpha-fetoprotein is a biomarker of unfolded protein response and altered proteostasis in hepatocellular carcinoma cells exposed to sorafenib.

Sorafenib is the treatment of reference for advanced hepatocellular carcinoma (HCC). A decrease in the serum levels of Alpha-fetoprotein (AFP) is reported to be the biological parameter that is best associated with disease control by sorafenib. In order to provide a biological rationale for the variations of AFP, we analyzed the various steps of AFP production in human HCC cell lines exposed to sorafenib.

Biomarkers of apoptosis and necrosis in patients with hepatocellular carcinoma treated with sorafenib.

Background/aim: Sorafenib is the medical reference for treatment of hepatocellular carcinoma (HCC). Multiple forms of cytotoxicity are induced by sorafenib in HCC cells in vitro but it is unclear what extent of apoptosis and necrosis is induced in HCC patients receiving sorafenib.

Patients And Methods: The M30 and M65 biomarkers, which reflect the release of cytokeratin-18 and its apoptotic cleavage fragments, were measured in patients with HCC (n=36) and matched patients with cirrhosis (n=47).

Optimal cut points for quality of life questionnaire-core 30 (QLQ-C30) scales: utility for clinical trials and updates of prognostic systems in advanced hepatocellular carcinoma.

Background: Health-related quality of life (QoL) has been validated as a prognostic factor for cancer patients; however, to be used in routine practice, QoL scores must be dichotomized. Cutoff points are usually based on arbitrary percentile values. We aimed to identify optimal cutoff points for six QoL scales and to quantify their added utility in the performance of four prognostic classifications in patients with hepatocellular carcinoma (HCC).

The retinoblastoma (Rb) protein regulates ferroptosis induced by sorafenib in human hepatocellular carcinoma cells.

Sorafenib is the treatment of reference for advanced hepatocellular carcinoma (HCC), the most frequent form of primary liver tumour. The loss of function of the retinoblastoma (Rb) protein is an important event during liver carcinogenesis, but it is unclear whether the Rb status modulates the response of HCC cells to sorafenib. Here, we examined this question in HCC cells with reduced levels of Rb achieved through stable RNA interference.

[Should cases of hepatocellular carcinoma be discussed by non-specialized multidisciplinary team meetings?].

The treatment of hepatocellular carcinoma (HCC) is difficult due to the underlying cirrhosis which has its own influence on therapeutic issues. An inquiry was performed in centres with specialized multidisciplinary team meetings dedicated to HCC (HCC-MTM) or in centres with non-specialized (digestive oncology or general oncology) multidisciplinary team meetings (NS-MTM). The number of cases of HCCs taken in charge yearly was significantly higher in HCC-MTM than in NS-MTM (p=0,0014).

New biological perspectives for the improvement of the efficacy of sorafenib in hepatocellular carcinoma.

Sorafenib, an orally-available kinase inhibitor, is the only medical treatment with a proven efficacy against Hepatocellular Carcinoma (HCC). Although the overall clinical efficacy of sorafenib is modest, recent experimental results have uncovered new potential strategies that may increase its clinical benefits. The potential implication of Receptor Tyrosine Kinases (RTKs), such as the Epidermal Growth Factor Receptor (EGFR), in the development of resistance to sorafenib highlights the importance of the RAF kinase pathway.

Heterogeneous sensitivity of hepatocellular carcinoma to sorafenib revealed by the short-term culture of tumor fragments.

Background/aim: Sorafenib is currently the only medical treatment with proven efficacy against hepatocellular carcinoma (HCC). HCC cell lines display heterogeneous sensitivity to sorafenib, but little is known about the sensitivity of clinical tumors. We aimed to examine this aspect.

The added value of quality of life (QoL) for prognosis of overall survival in patients with palliative hepatocellular carcinoma.

Background & Aims: Several prognostic classifications (PCs) have been developed for use in palliative care in patients with hepatocellular carcinoma (HCC). We have recently suggested that CLIP combined with WHO PS has the greatest discriminative power. We evaluated the prognostic value of quality of life (QoL) data and whether the latter could improve classification of palliative HCC patients.

EGFR activation is a potential determinant of primary resistance of hepatocellular carcinoma cells to sorafenib.

Sorafenib is currently the medical treatment of reference for hepatocellular carcinoma (HCC), but it is not known whether sorafenib is equally active in all HCC. Here, our aim was to explore intrinsic differences in the response of HCC cells to sorafenib, to identify potential mechanisms leading to primary resistance to this treatment. We analyzed a panel of six human HCC cell lines and compared the activity of the main oncogenic kinase cascades, their clonogenic potential, proliferation and apoptosis upon exposure to sorafenib.

Development and validation of a new prognostic score of death for patients with hepatocellular carcinoma in palliative setting.

Background & Aims: Patients with hepatocellular carcinoma (HCC) in a palliative setting have a poor prognosis despite recent therapeutic progress. Several prognostic scores, such as the BCLC and the CLIP, have been shown to be useful in helping select treatment options ranging from transplantation to palliative care. However, the discriminatory ability of these scores is inadequate in palliative settings, which concern about 70% of HCC patients.

BAD, a proapoptotic member of the BCL2 family, is a potential therapeutic target in hepatocellular carcinoma.

Proteins of the BCL2 family are key regulators of apoptosis. Their expression levels are frequently altered in cancers, enabling tumor cells to survive. To gain insight into the pathogenesis of hepatocellular carcinoma (HCC), we performed a comprehensive survey of the expression of the members of the BCL2 family in samples obtained from surgically resected HCCs.

Somatostatin receptor scintigraphy screening in advanced hepatocarcinoma: A multi-center French study.

Background: Somatostatin receptor scintigraphy (SRS) has been reported for receptor (SSTR) screening in advanced hepatocarcinoma (aHC) prior to somatostatin analogue treatment.

Aims: To evaluate SSTR screening with SRS in aHC patients.

Results: Seventy aHC patients (63 men) aged 65 +/- 11 y were included, with alcohol, viral or other causes cirrhosis in 35 (50%), 23 (33%), 12 (17%) cases respectively.

Marked iron overload related to ribavirin and iron sulfate treatment in a patient with active viral C cirrhosis.

Increased ferritin levels are common in the course of chronic hepatitis C, regardless of antiviral therapy. Usually, this increase in ferritin levels has minimal clinical and biological impact, and drops after therapy discontinuation. We report here on a dramatic increase in ferritin levels in a cirrhotic patient with hepatitis C treated by ribavirin monotherapy and oral iron sulphate, and discuss the possible mechanisms of this deleterious effect.

Treatment of advanced hepatocellular carcinoma with long-acting octreotide: a phase III multicentre, randomised, double blind placebo-controlled study.

Background: A previous study reported a significant survival benefit for octreotide compared with no treatment in patients with advanced hepatocellular carcinoma (HCC). This was investigated further in this multicentre study.

Patients And Methods: Two hundred and seventy two patients with HCC who were ineligible for curative treatments or had relapsed following potentially curative therapies were randomised to receive long-acting octreotide, 30 mg as an intramuscular injection once every 4 weeks for up to 2 years, or placebo.