Deep learning on histological slides accurately predicts Consensus Molecular Subtypes and spatial heterogeneity in colon cancer.

Colon cancer (CC) is the third most prevalent cancer type. It is highly heterogeneous, particularly in terms of molecular profiles, which have both prognostic and predictive impacts on the treatment efficacy. However, CC treatment in adjuvant situations is currently guided solely by T and N staging.

Circulating tumor DNA driving anti-EGFR rechallenge therapy in metastatic colorectal cancer: the RASINTRO prospective multicenter study.

Background: In RAS wild-type (WT) metastatic colorectal cancer (mCRC), preliminary data have suggested that circulating tumor DNA (ctDNA) may select patients for anti-EGFR rechallenge therapy.

Methods: RASINTRO is a prospective nonrandomized study evaluating anti-EGFR rechallenge strategy in third and later line treatment in RAS/BRAF WT mCRC. Liquid biopsies for ctDNA analysis were collected before the first (C1) and second (C2) cycle of anti-EGFR rechallenge therapy.

First-line PD-1 +/- CTLA-4 blockade in patients with deficient mismatch repair and/or microsatellite instability-high metastatic colorectal cancer.

Background: Patients with deficient mismatch repair (dMMR) and/or microsatellite instability-high (MSI-H) metastatic colorectal cancer (mCRC) show marked sensitivity to immune checkpoint inhibitors (ICIs). Dual PD-1/CTLA-4 blockade with nivolumab and ipilimumab showed superior progression-free survival (PFS) over chemotherapy and anti-PD-1 monotherapy, but data on treatment-naïve patients is not available yet.

Methods: This international multicenter study included patients with dMMR/MSI-H mCRC receiving either chemotherapy with or without biologics, or anti-PD-1 monotherapy, or dual PD-1/CTLA-4 blockade as a first-line treatment.

Health-related quality of life in patients with KRAS-mutated chemorefractory metastatic colorectal cancer treated with sotorasib plus panitumumab or standard of care (CodeBreaK 300): results from a phase 3, randomised clinical trial.

Background: In the phase 3 CodeBreaK 300 study, sotorasib (KRAS inhibitor) plus panitumumab (EGFR inhibitor) significantly prolonged progression-free survival versus investigator's choice of trifluridine-tipiracil or regorafenib (standard of care) in patients with KRAS-mutated chemorefractory metastatic colorectal cancer. This analysis evaluated patient-reported outcomes (PROs) as secondary and exploratory endpoints.

Methods: In this open-label, randomised clinical trial, adult (aged ≥18 years) patients from 67 centres in 13 countries in Asia, Australia, Europe, and North America with KRAS-mutated chemorefractory metastatic colorectal cancer (as assessed by central molecular testing of tumour biopsy specimens) who were KRAS inhibitor-naive, had progressed to recurrence after previous therapy with fluoropyrimidine, oxaliplatin, and irinotecan, with measurable disease according to the Response Evaluation Criteria in Solid Tumors version 1.

FedECA: federated external control arms for causal inference with time-to-event data in distributed settings.

External control arms can inform early clinical development of experimental drugs and provide efficacy evidence for regulatory approval. However, accessing sufficient real-world or historical clinical trials data is challenging. Indeed, regulations protecting patients' rights by strictly controlling data processing make pooling data from multiple sources in a central server often difficult.

Real-world efficacy of immune checkpoint inhibitors in microsatellite unstable/mismatch repair-deficient biliary tract cancer: An AGEO study.

Background: Immune checkpoint inhibitors (ICIs) significantly improve survival in patients with mismatch repair-deficient (dMMR) or microsatellite instability-high (MSI) tumors. In 2022, ICIs were approved as first-line treatment with chemotherapy for advanced biliary tract cancers (BTCs). MSI/dMMR BTC represents a rare subtype, and its response to ICIs remains poorly understood.

Impact of trifluridine/tipiracil plus bevacizumab on tumor shrinkage and depth of response in refractory metastatic colorectal cancer: analysis of the SUNLIGHT trial.

Objectives: This post hoc analysis of the SUNLIGHT trial sought to assess the response to treatment with trifluridine/tipiracil (FTD/TPI) + bevacizumab and FTD/TPI in patients with refractory metastatic colorectal cancer using tumor shrinkage (TS), early TS (ETS), duration of TS (DTS) and depth of response (DpR) as response-related parameters.

Methods: TS was defined as any decrease from baseline of the sum of the longest diameter of target lesions. TS at first assessment was specified as ETS.

Prognostic impact of the BRAF V600E mutation in patients with MSI-high metastatic colorectal cancer treated with immune checkpoint inhibitors.

Introduction: The prognostic impact of the BRAF V600E mutation in patients with deficient mismatch repair (dMMR)/microsatellite instability (MSI) metastatic colorectal cancer (mCRC) treated with immune checkpoint inhibitors (ICI) is poorly understood.

Material And Methods: This retrospective international study included patients with dMMR/MSI mCRC treated with ICI all lines between 2014 and 2023, and available BRAF mutation status.

Results: Of 909 patients included, 345 (38 %) had BRAF V600E dMMR/MSI mCRC.

Impact of concomitant medication on recurrence, survival and tolerability of chemotherapy in early colon cancer patients - A post-hoc analysis of the PETACC 8 trial.

Background: Only few information is available about the impact of concomitant medication (CM) and comorbidities on the outcome of cancer patients and the tolerability of chemotherapy.

Methods: Patients of the phase III randomized trial PETACC8 had resection with curative intent of a stage III colon cancer (CC) and were treated with standard adjuvant fluoropyrimidine and oxaliplatin + /- cetuximab over 6 months. Information on CM intake has been gathered by study visits at inclusion as well as during chemotherapy.

ctDNA Detection in Cancer: A Comprehensive Overview of Current Detection Methods and Prospects.

The analysis of circulating tumor DNA (ctDNA) has emerged as a major minimally invasive biomarker in oncology. Numerous methods exist for ctDNA detection and should be selected based on the specific oncological context. PCR-based methods are often preferred for their sensitivity and cost-effectiveness; however, they are limited to a narrower range of genes.

Early ctDNA and Survival in Metastatic Colorectal Cancer Treated With Immune Checkpoint Inhibitors: A Secondary Analysis of the SAMCO-PRODIGE 54 Randomized Clinical Trial.

Importance: Immune checkpoint inhibitors (ICIs) have dramatically transformed the therapeutic landscape of deficient mismatch repair/microsatellite unstable-high (dMMR/MSI-H) metastatic colorectal cancer (mCRC); however, ICI use is challenged by primary resistance and timing of discontinuation. Whether circulating tumor DNA (ctDNA) may be predictive of progression-free survival (PFS) and overall survival (OS) in this treatment context remains unknown.

Objective: To assess the prognostic and predictive role of ctDNA, detected by tumor-specific methylation markers, in patients with dMMR/MSI-H mCRC treated with ICIs.

Predictive and prognostic factors of efficacy of third-line chemotherapy in patients with unresectable pancreatic cancer: a cohort-based study.

Background: Advanced pancreatic ductal adenocarcinoma (aPDAC) has a poor prognosis with median overall survival (OS) of about 12 months. It is therefore important to explore factors that predict the efficacy of third-line chemotherapy (L3) to identify patients who may benefit from this controversial treatment.

Methods: We conducted a multicenter retrospective cohort-based study of 202 French patients treated for aPDAC who received at least three treatment lines from January 2011 to March 2022.

Incidence of catheter-related infection in cancer patients receiving parenteral nutrition: A retrospective cohort study of French administrative claims data.

Data confirming parenteral nutrition (PN) as an independent risk factor for catheter-related infection (CRI) are scarce and not recent. This study aims to estimate the effect of PN on CRI in cancer patients after catheter placement. A retrospective cohort analysis of the French National Health Data System was conducted.

Circulating tumor DNA: A new tool to predict recurrence and guide treatment of colorectal cancer.

Circulating tumor DNA (ctDNA) has emerged as a promising biomarker with diverse applications across different stages of colorectal cancer management. One of its primary roles is as a prognostic biomarker for detecting post-surgical molecular residual disease and predicting recurrence risk. Compared to traditional biomarkers and tissue biopsies, ctDNA provides a minimally invasive, dynamic, and comprehensive representation of tumor burden and molecular heterogeneity.

Overcoming barriers to advanced biomolecular technologies that inform treatment of solid tumors: a roadmap to access.

The advent of advanced biomolecular technologies for detecting molecular and genomic signatures of individual tumors has transformed oncology care, introducing proven methodologies that can inform treatment with matched targeted therapies and predict response at the individual patient level. However, access to these technologies has been hampered by multiple barriers, most notably price and obtainability. Other barriers include lack of knowledge of available technologies, concerns about value, and outdated infrastructures that impede critical operations within the clinic or laboratory.

Advances and challenges in targeted therapies for HER2-amplified colorectal cancer.

Colorectal cancer is the third most common cancer in terms of incidence rate in adults and the second most common cause of cancer-related death in Europe. Despite an increase in overall survival throughout the years, the prognosis of metastatic colorectal cancer remains poor. Until recently, its treatment was based on the use of standard chemotherapy combined with, anti-epidermal growth factor receptor (for RAS wild-type tumors) or anti-vascular endothelial growth factor, or immunotherapy for tumors with mismatch repair deficiency.

TFOX versus FOLFOX in first-line treatment of patients with advanced HER2-negative gastric or gastro-oesophageal junction adenocarcinoma (PRODIGE 51- FFCD-GASTFOX): an open-label, multicentre, randomised, phase 3 trial.

Background: Perioperative FLOT (fluorouracil, oxaliplatin, and docetaxel) triplet chemotherapy is the standard of care for localised and resectable gastric and gastro-oesophageal junction adenocarcinoma. We aimed to compare a modified FLOT regimen (also known as TFOX) with FOLFOX as first-line treatment for patients with HER2-negative advanced gastric and gastro-oesophageal junction adenocarcinoma.

Methods: PRODIGE 51-FFCD-GASTFOX is an open-label, multicentre, randomised, phase 3 trial conducted at 96 medical centres in France.

Neoadjuvant FOLF(IRIN)OX Chemotherapy for Resectable Pancreatic Adenocarcinoma: A Multicenter Randomized Noncomparative Phase II Trial (PANACHE01 FRENCH08 PRODIGE48 study).

Purpose: Despite limited RCTs, neoadjuvant chemotherapy (NAC) shows promise for resectable pancreatic adenocarcinoma (rPAC). Few prospective results are available on completing the full therapeutic sequence and oncologic outcomes with NAC.

Methods: The PANACHE01-PRODIGE48 phase II trial randomly assigned 153 patients with rPAC (2:2:1) to four cycles of NAC (modified leucovorin, fluorouracil, irinotecan, and oxaliplatin [mFOLFIRINOX], arm 1; leucovorin, fluorouracil, and oxaliplatin [FOLFOX], arm 2) or up-front surgery (control) across 28 French centers (February 2017-July 2020).

Epidemiology, pathogenesis, biology and evolving management of MSI-H/dMMR cancers.

Deficiency in DNA mismatch repair (dMMR) is a common pathway of carcinogenesis across different tumour types and confers a characteristic microsatellite instability-high (MSI-H) molecular phenotype. The prevalence of the MSI-H/dMMR phenotype is highest in endometrial and colorectal cancers, and this phenotype is associated with a distinct tumour biology, prognosis and responsiveness to various anticancer treatments. In a minority of patients, MSI-H/dMMR cancers result from an inherited pathogenic variant in the context of Lynch syndrome, which has important implications for familial genetic screening.