BRAF + EGFR +/- MEK inhibitors after immune checkpoint inhibitors in BRAF V600E mutated and deficient mismatch repair or microsatellite instability high metastatic colorectal cancer.

Background: Immune checkpoint inhibitors (ICIs) are the guideline endorsed first choice for patients with deficient mismatch repair or microsatellite instability high (dMMR/MSI-H) mCRC, however a significant proportion experience primary or secondary resistance. BRAF V600E mutated (BRAFm) and dMMR/MSI-H mCRC can be treated with BRAF + EGFR inhibitors but specific data on the efficacy after progression to ICIs are missing.

Methods: We collected consecutive patients with BRAFm dMMR/MSI-H mCRC treated from 2017 to 2024 with a combination of BRAFi+EGFRi+/-MEKi, after disease progression on ICIs.

A multicenter study evaluating efficacy of immune checkpoint inhibitors in advanced non-colorectal digestive cancers with microsatellite instability.

Background: One randomized phase III trial comparing chemotherapy (CT) with immune checkpoint inhibitors (ICI) has demonstrated significant efficacy of ICI in deficient DNA mismatch repair system/microsatellite instability-high (dMMR/MSI-H) metastatic colorectal cancer. However, few studies have compared ICI with CT in other advanced dMMR/MSI-H digestive tumors.

Methods: In this multicenter study, we included patients with advanced dMMR/MSI-H non-colorectal digestive tumors treated with chemotherapy and/or ICIs.

Primary resistance to immunotherapy in patients with a dMMR/MSI metastatic gastrointestinal cancer: who is at risk? An AGEO real-world study.

Background: The outstanding efficacy of immunotherapy in metastatic dMMR/MSI gastro-intestinal (GI) cancers has led to a rapid increase in the number of patients treated. However, 20-30% of patients experience primary resistance to immune checkpoint inhibitors (ICIPR) and need better characterization.

Methods: This AGEO real-world study retrospectively analyzed the efficacy and safety of ICIs and identified clinical variables associated with ICIPR in patients with metastatic dMMR/MSI GI cancers treated with immunotherapy between 2015 and 2022.

Features of colorectal adenomas among young patients with Lynch syndrome according to path_MMR: Results from the PRED-IdF registry.

Background: Lynch syndrome (LS) is the most frequent inherited colorectal cancer syndrome.

Aim: To assess the burden of adenoma in LS patients under 50 years-old followed in the PRED-IdF network.

Methods: From January 2010 to January 2019, all patients under 50 years of age with a confirmed LS germline mutation were included.

Primary Colorectal Tumor Displays Differential Genomic Expression Profiles Associated with Hepatic and Peritoneal Metastases.

Background: Despite improvements in characterization of CRC heterogeneity, appropriate risk stratification tools are still lacking in clinical practice. This study aimed to elucidate the primary tumor transcriptomic signatures associated with distinct metastatic routes.

Methods: Primary tumor specimens obtained from CRC patients with either isolated LM (CRC-Liver) or PM (CRC-Peritoneum) were analyzed by transcriptomic mRNA sequencing, gene set enrichment analyses (GSEA) and immunohistochemistry.

Lynch syndrome: influence of additional susceptibility variants on cancer risk.

Some patients with Lynch syndrome (LS) have extreme phenotypes, i.e. cancer before the recommended screening age, or cancer for which there are no screening guidelines.

Next-Generation Sequencing Targeted Panel in Routine Care for Metastatic Colon Cancers.

In digestive oncology, the clinical impact of targeted next-generation sequencing (NGS) in routine practice should be addressed. In this work, we studied the impact of a 22-gene NGS amplicon-based panel with Ion Torrent Proton Sequencing, prospectively performed in routine practice. We analyzed the results of extended molecular testing, beyond and in metastatic colorectal cancer (mCRC) patients in a single-center, retrospective, observational study of consecutive mCRC patients followed up at the Georges Pompidou European Hospital between January 2016 and December 2018.

Complement C1s and C4d as Prognostic Biomarkers in Renal Cancer: Emergence of Noncanonical Functions of C1s.

The complement system plays a complex role in cancer. In clear cell renal cell carcinoma (ccRCC), local production of complement proteins drives tumor progression, but the mechanisms by which they do this are poorly understood. We found that complement activation, as reflected by high plasma C4d or as C4d deposits at the tumor site, was associated with poor prognosis in two cohorts of patients with ccRCC.

Chemotherapy use in end-of-life digestive cancer patients: a retrospective AGEO observational study.

Background: The use of chemotherapy (CT) near the end-of-life (EOL) is an important issue in oncology since it could degrade quality of life. CT near EOL is still poorly studied, with no dedicated study in gastrointestinal (GI) cancer patients.

Aim: To analyze in GI cancer patients the factors associated with the use of CT within 3- and 1-month before patients' death.

Feasibility of high-throughput sequencing in clinical routine cancer care: lessons from the cancer pilot project of the France Genomic Medicine 2025 plan.

Background: Whole exome sequencing and RNA sequencing (WES/RNASeq) should now be implemented in the clinical practice in order to increase access to optimal care for cancer patients. Providing results to Tumour Boards in a relevant time frame-that is, compatible with the clinical pathway-is crucial. Assessing the feasibility of this implementation in the French care system is the primary objective of the Multipli study, as one of the four pilot projects of the national France Genomic Medicine 2025 (FGM 2025) plan.

Reasons for chemotherapy discontinuation and end-of-life in patients with gastrointestinal cancer: A multicenter prospective AGEO study.

Background: Previous research on chemotherapy discontinuation has mainly focused on predictive factors and outcomes. Few data are available on the reasons for chemotherapy discontinuation. The main objective was to identify the reasons for chemotherapy discontinuation in patients with gastrointestinal cancer.

[Hereditary breast and ovarian cancer syndrome: Diagnosis and therapeutic implications].

Patients who carry the BReast Cancer 1 or 2 (BRCA) gene mutations have an underlying hereditary predisposition for breast and ovarian cancers. These deleterious genetic mutations are the most common ones implicated in hereditary breast and ovarian cancers. Oncogenetic counselling plays a key role in identifying patient for BRCA testing and for mutation identification.

Can we classify ampullary tumours better? Clinical, pathological and molecular features. Results of an AGEO study.

Background: Ampullary adenocarcinoma (AA) originates from either intestinal (INT) or pancreaticobiliary (PB) epithelium. Different prognostic factors of recurrence have been identified in previous studies.

Methods: In 91 AA patients of the AGEO retrospective multicentre cohort, we evaluated the centrally reviewed morphological classification, panel markers of Ang et al.

[Lynch syndrome: What is new?].

Lynch syndrome is a genetic condition defined by a germline mutation of an MMR (MisMatch Repair) gene leading to a defective DNA MMR system. Therefore, it is characterized by the predisposition to a spectrum of cancers, primarily colorectal cancer (CRC) and endometrial cancer (EC). Lynch syndrome-related CRC accounts for 3% of all CRC.

Impact of an optimized colonoscopic screening program for patients with Lynch syndrome: 6-year results of a specialized French network.

Background: Despite colonoscopic screening, colorectal cancer (CRC) remains frequent in patients with Lynch syndrome (LS). The objective of this study was to evaluate the impact of an optimized colorectal screening program within a French dedicated network.

Methods: All LS patients followed at our institution were consecutively included in the Prédisposition au Cancer Colorectal-Ile de France (PRED-IdF) network.

Role of circulating tumor DNA in the management of patients with colorectal cancer.

Colorectal cancer is a major health burden with a prognosis that has been improved with the progresses in diagnosis and the advance of chemotherapy and personalized medicine. However, because of intra-tumor heterogeneity, clonal evolution and selection, tumors often develop resistance to treatments. "Liquid biopsy" is a minimally invasive method, based on analysis of tumor-specific material in peripheral blood samples of patients.

Association of Prognostic Value of Primary Tumor Location in Stage III Colon Cancer With RAS and BRAF Mutational Status.

Importance: We know of no data on the prognostic value of primary tumor location (PTL) according to BRAF, RAS, and microsatellite instability (MSI) status in patients who have undergone resection for colon cancer (CC) and have been treated with current standard adjuvant chemotherapy.

Objective: To determine the prognostic and predictive value of PTL according to BRAF, RAS, and MSI status in patients with stage III CC receiving adjuvant treatment with FOLFOX (folinic acid [leucovorin calcium], fluorouracil, and oxaliplatin) with or without cetuximab.

Design, Setting, And Participants: This post hoc analysis included patients with available tumor blocks of resected stage III colon adenocarcinoma who participated in the Pan-European Trials in Alimentary Tract Cancer (PETACC)-8 phase 3 randomized trial.

Early Evaluation of Circulating Tumor DNA as Marker of Therapeutic Efficacy in Metastatic Colorectal Cancer Patients (PLACOL Study).

Markers of chemotherapy efficacy in metastatic colorectal cancer (mCRC) are essential for optimization of treatment strategies. We evaluated the applicability of early changes in circulating tumor DNA (ctDNA) as a marker of therapeutic efficacy. This prospective study enrolled consecutive patients with mCRC receiving a first- or second-line chemotherapy.

A Study of Hypermethylated Circulating Tumor DNA as a Universal Colorectal Cancer Biomarker.

Background: Circulating tumor DNA (ctDNA) has emerged as a good candidate for tracking tumor dynamics in different cancer types, potentially avoiding repeated tumor biopsies. Many different genes can be mutated within a tumor, complicating procedures for tumor monitoring, even with highly sensitive next-generation sequencing (NGS) strategies. Droplet-based digital PCR (dPCR) is a highly sensitive and quantitative procedure, allowing detection of very low amounts of circulating tumor genetic material, but can be limited in the total number of target loci monitored.