Hepatocarcinoma

Biotherapies are biological (extracted from an organism or living tissue) or biotechnological drugs used in the treatment of multiple conditions, such as autoimmune inflammatory diseases, cancers, and hematologic diseases. In recent years, these biotherapies have notably emerged in the treatment of cancers and hematologic disorders. As such, most patients with cancers or hematologic diseases will likely receive a biotherapy as part of their care pathway. These biotherapies are associated with various side effects, including hypersensitivity or allergic reactions, which are often poorly characterized in clinical trials. These reactions manifest as symptoms without specific dermatologic or allergologic semiology (such as itching, erythema, shortness of breath, sometimes digestive issues, or discomfort, and in some cases, an anaphylactic reaction). Unlike other treatments, such as antibiotics and neuromuscular blockers, there are currently no guidelines on the concentrations to use in skin tests for biotherapies. We propose conducting prospective clinical research to scientifically establish the concentrations to be used when investigating hypersensitivity to a biotherapy, in line with best practice recommendations for drug skin testing.

The main objectives of this research project concern the identification of microRNAs circulating and of serum metabolites predictive of treatment response in patients with early stage hepatocellular carcinoma undergoing locoregional treatment with thermoablation. In addition, the molecular mechanisms involved in reprogramming will be identified metabolic via bioinformatics analysis and pretreatment liver biopsy analysis and analysis of screening on patient-derived primary lines for personalized therapy.

This is a national, observational, retrospective, cross-sectional, non-profit study focused on patients with HCC. The study aims to characterize the expression and function of novel noncoding regulatory transcripts, including those containing TEsin the microenvironment of liver tumors, with emphasis on their role in T cell dysfunction.

The aim of this observational study is to predict the short- and long-term development of acute severe disease events, de novo hepatocarcinoma (HCC) and mortality in patients with advanced chronic liver disease using the M10S20 (Liver stiffness and Model for End-Stage Liver Disease Score \[MELD\] combined) and PLEASE (Platelet, Etiology, Age, Sex und Elastography) scores, as well as the validation of the cost-effectiveness of the algorithm. Patients in this study are randomly divided into two groups: * Control group: patients are examined according to the current clinical standard protocol (biannual follow-up). * Stratified surveillance program: * High-risk patients will receive an appointment for a hospital visit every 3 months. * Low-risk patients could receive an appointment in one year. When necessary, if decompensation develops or HCC occurs, patients could be followed-up more frequently.

This is a prospective, single-center, phase II study，to evaluate the efficacy and safety of icariin soft capsules combined with TACE as adjuvant therapy in hepatocellular carcinoma (HCC) patients at high risk of recurrence after resection.

This trial was designed to investigate the safety, response rates and survival outcomes of patients with advanced solid tumors by trans-artery/intra-tumor infusion of PD1/PDL1 antibody and/or CTLA4 antibody ipilimumab plus chemotherapeutic drug and to compare their differences.

Hepatic (hepatocellular carcinoma (HCC)) and pancreatic (pancreatic adenocarcinoma (ADKP); pancreatic neuroendocrine tumors (TNEP)) primary tumors are the most common malignant tumors of the hepato-bilio-pancreatic system and represent a major public health issue. At present, the management of these tumors is based on recommendations based on the existence of rudimentary prognostic and theranostics markers that do not sufficiently accurately reflect the heterogeneity of tumor biology. It therefore seems essential to identify new and more relevant markers in order to optimize the care of these patients in daily practice. Metabolic reprogramming is now recognized as an essential feature of cancer cells, allowing them to fuel and maintain their proliferation and tumor growth. Such metabolic reprogramming requires modification of several energy pathways, the most commonly recognized being the transition from energy metabolism based on oxidative phosphorylation to energy metabolism based on glycolysis, even under aerobic conditions (Warburg effect). In this context, the investigators hypothesized that the consumption of nutrients by the tumor cell differs significantly from that of the normal cell in order to support its increased energy needs, and that this important and specific metabolic reprogramming would be correlated with the histo-prognostic and theranostics factors of these tumors. Preliminary analyses on surgical resection parts conducted by the various partners in 2019 made it possible to characterize the metabolic signatures of a series of HCC and ADKP resected using the Metafora biosystems technology platform. These signatures reflect a metabolic program characteristic of these tumors, which reveal strong specificities. Similarly, a candidate signature correlating with the presence of vascular microscopic invasion has been identified in HCC, and the level of activation of glycolysis and glutaminolysis by certain ADKP cells also appears as a trait of interest vis-à-vis the aggressiveness of this cancer. Thus, the current project will aim to confirm the feasibility of identifying specific prognostic and theranostics metabolic signatures early, on biopsy samples and / or circulating blood cells.

1. Explore the impact of postoperative administration of multi-kinase inhibitors (including sorafenib, lenvatinib, and regorafenib) in conjunction with bevacizumab on post-transplant recurrence, overall survival, and drug safety in liver transplant recipients at high risk of recurrence in hepatocellular carcinoma. 2. The primary objective of this study is to evaluate the efficacy of multi-kinase inhibitors in combination with bevacizumab as adjuvant therapy in liver transplant recipients with hepatocellular carcinoma who present high-risk factors for recurrence, based on the one-year recurrence-free survival rate (1-year RFS rate). 3. The secondary objectives of this study are to assess the effectiveness and safety of multi-kinase inhibitors in combination with bevacizumab as adjuvant therapy in liver transplant recipients with hepatocellular carcinoma who present high-risk factors for recurrence, based on the following parameters: Recurrence-free survival (RFS) duration, Overall survival (OS), Two-year and three-year RFS rates, Graft survival, Quality of life evaluation (QoL), Incidence of adverse events and serious adverse events.

The implementation of liquid biopsy in clinical practice has been favored by the rapid development of genome sequencing techniques designed to analyze mutations in ctDNA. Among these, the Next generation sequencing (NGS) is a technique that consists in sequencing several genomes in a short time span, collecting information about a wider range of genomic alterations, using small quantities of genetic material. It is used to identify potential circulating dynamic biomarkers of treatment sensitivity or resistance in a real word multi-pathology evaluation. In this way, defining the mutational status of clinical relevance genes in real world, as a predictive biomarker to identify those patients most likely to benefit from target therapy, offers the potential to optimize access to further therapies. The aim of this study is to evaluate the real-world prevalence of clinically useful mutations in patients who are receiving therapy for advanced and locally advanced solid tumor through liquid biopsy.