Digestive Cancer

Targeted therapy drug monitoring in digestive oncology: Dosage of plasma levels of various multikinase inhibitors (MKI) in patients treated for advanced digestive cancer (gastrointestinal stromal tumor (GIST), metastatic colorectal cancer (mCRC), hepatocellular carcinoma (HCC), gastroenteropancreatic neuroendocrine tumor (gepNET), or pancreatic neuroendocrine tumor (pNET)), with the aim of determine the optimal dose adapted for each patient, in the future.

The goal of this clinical trial is to establish guidelines for fluoropyrimidine dose reduction according to uracilemia in patients with DPD deficiency in the treatment of digestive cancers. The main question it aims to answer is: \- Which reduction dose of fluoropyrimidine is needed for patient with DPD deficiency? Participants will: * Take the treatment with the reduction of dose stated by the protocol * Visit the clinic once every 2-3 weeks for checkups and tests for collection of adverse events

The aim of this study is to establish and optimize the target-specific PET/CT imaging method, and its physiological and pathological distribution characteristics, on the basis of which the diagnostic efficacy of the above imaging agents in digestive system malignant tumors will be evaluated.

Circulating tumor DNA (ctDNA) offers the possibility of accessing the tumor genome from circulating blood through a simple blood test. It is currently used for diagnostic, prognostic and predictive purposes of response or resistance to oncological treatments. These advances in ctDNA have been made possible by major developments in molecular biology techniques in recent years, as the detection of ctDNA requires very sensitive techniques such as Next Generation Sequencing (NGS). CtDNA overcomes this problem of very limiting tumor heterogeneity during a solid biopsy. All of these applications make circulating DNA an increasingly essential tool in the management of cancer patients. The studies are currently in most cases on small numbers and are retrospective. In addition, exosomes are also a biomarker of the future that can also be detected in the bloodstream . Exosomes are nanovesicles 50 to 200 nm in diameter released into the extracellular environment via the endosomal pathway by fusion with the plasma membrane. They are very informative since they transport tumor genetic material in the form of DNA, mRNA and miRNA, but also adhesion proteins, immunostimulatory molecules and cytoskeleton, enzymes and Heats shock proteins ( HSP). The aim of the ADIGYN study is to set up a large prospective cohort to assess the diagnostic, prognostic and predictive impact of ctDNA and exosomes in digestive and gynecological / breast cancers. From the circulating DNA, we characterize the ActDNA on the molecular level thanks to the study of different point mutations usually used but also of new described mutations having a therapeutic impact and the search for other genetic alterations having an impact on the therapeutic strategy (such as microsatellite instability) or the study of exosomes and their composition. To assess resistance to oncological treatments, ctDNA will be analyzed at the start of treatment, during treatment, during progression and / or relapse and also during monitoring or treatment break

Nutritional status represents a crucial issue in the management of cancer patients, as between 40% and 60% of them suffer from malnutrition at the time of diagnosis. This condition worsens morbidity, increases treatment-related adverse effects, infections, and hospitalizations, and can lead to death in 10% to 20% of cases, independently of tumor progression. Anticancer treatments often exacerbate malnutrition due to their side effects, such as loss of appetite or taste alterations. Although international guidelines (ESPEN, ESMO, ASCO) recommend a multimodal nutritional intervention combining nutritional support and physical activity. The effectiveness of these approaches varies among patients. This variability can be explained by several factors, including individual differences in dietary intake response, metabolic status, and digestive tolerance to treatments. The intestinal and oral microbiota appear to be key cofactors in regulating these various parameters, influencing appetite, host metabolism, and intestinal absorption. Alterations in the microbiota-particularly a decrease in bacterial diversity and an increase in Candida albicans-have been associated with appetite loss and taste perception disorders, especially in patients with digestive cancers. Therefore, the intestinal microbiota constitutes a potential therapeutic and diagnostic target to improve nutritional strategies in oncology. Interventions targeting the microbiota (such as probiotic supplementation or fecal microbiota transplantation) have already demonstrated an impact on nutritional parameters in preclinical models of malnourished cancer-bearing mice; however, clinical data remain scarce and limited. The ONCONUTRIBIOTA-cohort study aims to characterize and investigate the oral and intestinal microbiota of patients initiating chemotherapy for digestive cancer, in relation to their nutritional status clinical characteristics and food preferences, in order to identify potential biomarkers or therapeutic targets to optimize their nutritional management. Patients will be followed during two of their routine care visits: on the day of the first chemotherapy treatment and at the end of the first cycle of chemotherapy. During these visits, stool and saliva samples will be collected, completed by additional assessments including global quality of life and nutritional quality of life questionnaires, olfactory and gustatory tests, and measurements of parameters used to determine the presence of malnutrition, general health status and oncological evaluation.

The study is designed to investigate the effect of a multicomponent prehabilitation pathway on early and long-term outcomes in elderly patients with frailty recovering from surgery for digestive cancer.

NEONEC is a single-phase, phase II study evaluating the efficacy of the 12-month neoadjuvant chemotherapy in patients with locally differentiated digestive NEC. The recommended chemotherapy is based on the current reference combination of platinum (cisplatin or carboplatin) and etoposide (VP16). For anorectal locations, radiochemotherapy is proposed to avoid the morbidity of conventional surgery. The objective of the study is to improve relapse-free survival (RFS) in NEC patients treated with neoadjuvant chemotherapy followed by surgery or chemoradiotherapy. In parallel, we will perform a prospective cohort study with patients whose diagnosis is made during surgery, who have not received neoadjuvant treatment, and who are offered an adjuvant treatment of the same type (combination of platinum and platinum salts and etoposide).

A psychoneurological symptom cluster is increasingly documented in oncology. It is composed of cancer-related fatigue, sleep difficulties, pain, emotional distress, and cognitive difficulties. These symptoms are linked by strong but complex relationships, and reinforce each other, negatively impacting patients' quality of life and survival. The configuration of this cluster (i.e., the relationships between the symptoms) seems different according to the cancer diagnosis or moment in the cancer journey. It has however been very little studied. Network analysis is an innovative method that allows a deeper understanding of the interactions between these symptoms. It also allows to compare patterns of clustering between distinct populations or measurement times. Finally, it allows to determine one core symptom in a cluster (i.e., the one with the strongest associations with the other symptoms), which could represent a target of choice for interventions aiming to improve the whole symptom cluster. This innovative project has then two main goals. First, the investigators will assess the evolution of the psychoneurological symptom cluster in two populations of patients with cancer: women with breast cancer, and patients with digestive cancer, over two years. Second, the investigators will test the feasibility and preliminary benefits of a new mind-body group intervention specifically designed to address the core symptom of the cluster, determined with network analysis in each population. As suggested by many authors, the proposed intervention will be based on the common-sense model of self-regulation developed by Leventhal and focus on cognitive-behavioral, self-care and mind-body (i.e., hypnosis) empowering strategies. The aim is to assess the satisfaction of the participants regarding the intervention, as well as its impact on the symptoms involved in the cluster.

The BCB is a tool: * for research in analytical and public health epidemiology, biological research and for the development of data useful for clinical research and therapeutic trials; * to help scientists understand and explain phenomena ranging from the interaction of molecules to the whole metabolism of the organism in normal and pathological situations; * to identify potential strategies for prevention, diagnosis, management and analysis of cancer subtypes. The creation of a broad clinical and biological prospective base dedicated to different types of cancer is essential for the development of such projects.

20 participants are expected to be enrolled for this open，Single-armed clinical trial to evaluate the safety and efficacy of the recombinant herpes simplex virus Ⅰ, R130 in patients with advanced solid tumors.