LIBELULE: a randomized phase III study to evaluate the clinical relevance of early liquid biopsy in patients with suspicious metastatic lung cancer.

Purpose: Genomic profiling is a major component for first-line treatment decisions in patients with non-small cell lung cancer (NSCLC) and the timeliness of biomarker testing is essential to improve time to treatment initiation (TTI) or avoid inappropriate treatment.

Patients And Methods: The phase III LIBELULE trial (NCT03721120) included patients with radiological suspicion of advanced lung cancer. They were randomized (1:1), the control arm receiving diagnostic procedures according to each center's practice and the liquid biopsy arm with additional testing performed at the first visit using the InVisionFirst®-Lung assay.

Correction: What went right during the COVID crisis: The capabilities of local actors and lasting innovations in oncology care and research.

[This corrects the article DOI: 10.1371/journal.pgph.

Targeting ERK-MYD88 interaction leads to ERK dysregulation and immunogenic cancer cell death.

The quest for targeted therapies is critical in the battle against cancer. The RAS/MAP kinase pathway is frequently implicated in neoplasia, with ERK playing a crucial role as the most distal kinase in the RAS signaling cascade. Our previous research demonstrated that the interaction between ERK and MYD88, an adaptor protein in innate immunity, is crucial for RAS-dependent transformation and cancer cell survival.

An Integrated Cancer Prevention Strategy: the Viewpoint of the Leon Berard Comprehensive Cancer Center Lyon, France.

This article describes some of the key prevention services in the Leon Berard Comprehensive Cancer Center (CLB) Lyon, France, which are based on clinical prevention services, outreach activities, and collaboration with professional and territorial health communities. In addition, research is embedded at all stages of the prevention continuum, from understanding cancer causes through to the implementation of prevention interventions during and after cancer. Health promotion activities in the community and dedicated outpatient primary cancer prevention services for individuals at increased risk have been implemented.

Added value of whole-exome and RNA sequencing in advanced and refractory cancer patients with no molecular-based treatment recommendation based on a 90-gene panel.

Introduction: The objective was to determine the added value of comprehensive molecular profile by whole-exome and RNA sequencing (WES/RNA-Seq) in advanced and refractory cancer patients who had no molecular-based treatment recommendation (MBTR) based on a more limited targeted gene panel (TGP) plus array-based comparative genomic hybridization (aCGH).

Materials And Methods: In this retrospective analysis, we selected 50 patients previously included in the PROFILER trial (NCT01774409) for which no MBT could be recommended based on a targeted 90-gene panel and aCGH. For each patient, the frozen tumor sample mirroring the FFPE sample used for TGP/aCGH analysis were processed for WES and RNA-Seq.

Survival of bronchopulmonary cancers according to radon exposure.

Introduction: Residential exposure is estimated to be responsible for nearly 10% of lung cancers in 2015 in France, making it the second leading cause, after tobacco. The Auvergne-Rhône-Alpes region, in the southwest of France, is particularly affected by this exposure as 30% of the population lives in areas with medium or high radon potential. This study aimed to investigate the impact of radon exposure on the survival of lung cancer patients.

Uncovering immune checkpoint heterogeneity in oral squamous cell carcinoma using single cell RNA-sequencing data highlights three subgroups of patients with distinct immune phenotypes.

Objectives: In head and neck squamous cell carcinoma (HNSCC), PD-1/PD-L1 inhibitors remain inefficient in most patients, which points to the need for better characterization of immune checkpoint (ICP) molecule expression.

Material And Methods: We evaluated the expression of 22 ICP ligands (ICPL) in 2,176 malignant cells from 10 patients in a public single-cell RNA-sequencing dataset and in two cohorts of HNSCC patients for which gene expression data are available.

Results: Based on ICPL expression, malignant cells formed three distinct clusters characterized either by a strong expression of ICPL together with an immune phenotype linked to IFN-γ response (cluster 1) or by a weak ICPL expression and little response to IFN-γ (clusters 2 and 3).

GIInger predicts homologous recombination deficiency and patient response to PARPi treatment from shallow genomic profiles.

Homologous recombination deficiency (HRD) is a predictive biomarker for poly(ADP-ribose) polymerase 1 inhibitor (PARPi) sensitivity. Routine HRD testing relies on identifying BRCA mutations, but additional HRD-positive patients can be identified by measuring genomic instability (GI), a consequence of HRD. However, the cost and complexity of available solutions hamper GI testing.

RSK3 switches cell fate: from stress-induced senescence to malignant progression.

Background: TGFβ induces several cell phenotypes including senescence, a stable cell cycle arrest accompanied by a secretory program, and epithelial-mesenchymal transition (EMT) in normal epithelial cells. During carcinogenesis cells lose the ability to undergo senescence in response to TGFβ but they maintain an EMT, which can contribute to tumor progression. Our aim was to identify mechanisms promoting TGFβ-induced senescence escape.

A Radiomics Approach to Identify Immunologically Active Tumor in Patients with Head and Neck Squamous Cell Carcinomas.

Background: We recently developed a gene-expression-based HOT score to identify the hot/cold phenotype of head and neck squamous cell carcinomas (HNSCCs), which is associated with the response to immunotherapy. Our goal was to determine whether radiomic profiling from computed tomography (CT) scans can distinguish hot and cold HNSCC.

Method: We included 113 patients from The Cancer Genome Atlas (TCGA) and 20 patients from the Groupe Hospitalier Pitié-Salpêtrière (GHPS) with HNSCC, all with available pre-treatment CT scans.

Spatial Transcriptomics Reveal Pitfalls and Opportunities for the Detection of Rare High-Plasticity Breast Cancer Subtypes.

Breast cancer is one of the most prominent types of cancers, in which therapeutic resistance is a major clinical concern. Specific subtypes, such as claudin-low and metaplastic breast carcinoma (MpBC), have been associated with high nongenetic plasticity, which can facilitate resistance. The similarities and differences between these orthogonal subtypes, identified by molecular and histopathological analyses, respectively, remain insufficiently characterized.

An Early Neoplasia Index (ENI10), Based on Molecular Identity of CD10 Cells and Associated Stemness Biomarkers, is a Predictor of Patient Outcome in Many Cancers.

Unlabelled: An accurate estimate of patient survival at diagnosis is critical to plan efficient therapeutic options. A simple and multiapplication tool is needed to move forward the precision medicine era. Taking advantage of the broad and high CD10 expression in stem and cancers cells, we evaluated the molecular identity of aggressive cancer cells.

Radiomics combined with transcriptomics to predict response to immunotherapy from patients treated with PD-1/PD-L1 inhibitors for advanced NSCLC.

Introduction: In this study, we aim to build radiomics and multiomics models based on transcriptomics and radiomics to predict the response from patients treated with the PD-L1 inhibitor.

Materials And Methods: One hundred and ninety-five patients treated with PD-1/PD-L1 inhibitors were included. For all patients, 342 radiomic features were extracted from pretreatment computed tomography scans.

Dissecting the Origin of Heterogeneity in Uterine and Ovarian Carcinosarcomas.

Unlabelled: Gynecologic carcinosarcomas (CS) are biphasic neoplasms composed of carcinomatous (C) and sarcomatous (S) malignant components. Because of their rarity and histologic complexity, genetic and functional studies on CS are scarce and the mechanisms of initiation and development remain largely unknown. Whole-genome analysis of the C and S components reveals shared genomic alterations, thus emphasizing the clonal evolution of CS.

Occupational asbestos exposure and survival among lung cancer patients.

Objective: This study investigated the association between occupational asbestos exposure (OAE) and survival in patients with histologically confirmed lung cancer (LC).

Methods: This monocentric study was conducted in the Comprehensive Cancer Centre Léon Bérard, Lyon, France. A systematic screening has been in place since 2014 for occupational exposure to carcinogens using a self-assessment questionnaire sent to all patients newly diagnosed with histologically confirmed LC identified through the multidisciplinary LC board from 2014 to 2019.

Intestinal Epithelial Cells Adapt to Chronic Inflammation through Partial Genetic Reprogramming.

Reactive oxygen species (ROS) are considered to be the main drivers of inflammatory bowel disease. We investigated whether this permanent insult compels intestinal stem cells to develop strategies to dampen the deleterious effects of ROS. As an adverse effect, this adaptation process may increase their tolerance to oncogenic insults and facilitate their neoplastic transformation.

Reliability of gene-expression profiling from tumor biopsy for refining neoadjuvant strategies in patients with head and neck squamous cell carcinoma.

While recent clinical trials evaluating neoadjuvant immune checkpoint inhibitors showed promising results in a subset of patients with head and neck squamous cell carcinomas (HNSCC), there is a need for the identification of robust biomarkers in tumor biopsies to improve patient selection. This context suggests unravelling transcriptomic heterogeneity between untreated paired samples from same patient with HNSCC. Based on previous studies and the analysis of publicly available gene expression profiles of paired tumor biopsies and surgical resection specimens, we discuss the reliability of tumor biopsy to capture the overall activation of targetable biological pathways in patients with HNSCC.

Immunologically active phenotype by gene expression profiling is associated with clinical benefit from PD-1/PD-L1 inhibitors in real-world head and neck and lung cancer patients.

Introduction: Identification of tumours harbouring an overall active immune phenotype may help for selecting patients with advanced head and neck squamous cell carcinomas (HNSCC) and non-small cell lung cancer (NSCLC) who may benefit from immunotherapies. Our objective was to develop a reliable and stable scoring system to identify those immunologically active tumours.

Methods: Using gene expression profiles of 421 HNSCC, we developed a score to identify immunologically active tumours.

Biomarkers of radioresistance in head and neck squamous cell carcinomas.

Purpose: Head and neck squamous cell carcinoma (HNSCC) is a major cause of morbidity and mortality. Although HNSCC is mainly caused by tobacco and alcohol consumption, infection by Human Papilloma Virus (HPV) has been also associated with the increasing incidence of oropharyngeal squamous cell carcinomas (OPSCC) during the past decades. HPV-positive HNSCC is characterized by a higher radiosensitivity compared to HPV-negative tumor.

Epithelial-to-mesenchymal transition promotes immune escape by inducing CD70 in non-small cell lung cancer.

Introduction: Epithelial-to-mesenchymal transition (EMT) is associated with tumor aggressiveness, drug resistance, and poor survival in non-small cell lung cancer (NSCLC) and other cancers. The identification of immune-checkpoint ligands (ICPLs) associated with NSCLCs that display a mesenchymal phenotype (mNSCLC) could help to define subgroups of patients who may benefit from treatment strategies using immunotherapy.

Methods: We evaluated ICPL expression in silico in 130 NSCLC cell lines.

Teaching how to break bad news in Oncology: In-class vs. virtual peer role-plays.

Background: We report two different peer role-play training courses for breaking bad news (BBN) in Oncology, the classic "in-class" model and the "virtual" peer role-play (VPRP) model developed during the SARS-CoV-2 pandemic.

Methods: Each session included 20-25 4th year medical students supervised by two practitioners experienced in oncology. After an ice breaking activity to exchange with students on means to promote hope to patients when BBN, peer role-plays started.