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Background: Pulmonary nodules are a common incidental finding on chest Computed Tomography scans (CT), most of the time outside of lung cancer screening (LCS). We aimed to evaluate the number of incidental pulmonary nodules (IPN) found in 1 year in our hospital, as well as the follow-up (FUP) rate and the clinical and radiological features associated with FUP., Methods: We trained a Natural Language Processing (NLP) tool to identify the transcripts mentioning the presence of a pulmonary nodule, among a large population of patients from a French hospital. We extracted nodule characteristics using keyword analysis. NLP algorithm accuracy was determined through manual reading from a sample of our population. Electronic health database and medical record analysis by clinician allowed us to obtain information about FUP and cancer diagnoses., Results: In this retrospective observational study, we analyzed 101,703 transcripts corresponding to the entire CTs performed in 2020. We identified 1,991 (2 %) patients with an IPN. NLP accuracy for nodule detection in CT reports was 99 %. Only 41 % received a FUP between January 2020 and December 2021. Patient age, nodule size, and the mention of the nodule in the impression part were positively associated with FUP, while nodules diagnosed in the context of COVID-19 were less followed. 36 (2 %) lung cancers were subsequently diagnosed, with 16 (45 %) at a non-metastatic stage., Conclusions: We identified a high prevalence of IPN with a low FUP rate, encouraging the implementation of IPN management program. We also highlighted the potential of NLP for database analysis in clinical research., Competing Interests: Declaration of interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background: First-line standard-of-care for unresectable, pleural mesothelioma (PM) changed with the phase 3 CheckMate 743 study results, showing that nivolumab plus ipilimumab (Nivo + Ipi) significantly extended overall survival (OS) versus platinum + pemetrexed chemotherapy for PM (median OS 18.1 versus 14.1 months; hazard ratio: 0.74; p = 0.002). Efficacy and safety data in real-world (rw) settings are needed to confirm these results., Methods: This French multicenter, retrospective cohort study was undertaken to assess the outcomes of treatment-naïve PM patients given Nivo + Ipi via an early-access program (EAP). The primary objective was investigator-assessed real world -progression-free survival (PFS). The secondary objectives were the combination's -overall survival (OS) and safety., Results: From 1 April 2021 to 15 Feb 2022, the analysis included 201 of the 305 EAP-enrolled patients treated in 63 centers (79.6 % men; median age: 75 years; 91.8 % Eastern Cooperative Oncology Group performance status (ECOG-PS) 0/1; 74.5 % epithelioid histology). With median (95 % CI) follow-up for all patients of 18.4 (17.7-19.2) months, -PFS and OS were 6.3 (5.3-7.5) and 18.9 (17.6-not reached (NR)) months, with 1-year OS at 66.4 % (60.1-73.3 %). Median OS and 1-year survival rates were 21.0 (18.7-NR) and 70.8 % (63.9 %-780.6 %), and 14.1 (10.9-21.0) months and 54.9 % (42.8 %-70.4 %) for epithelioid and non-epithelioid PM subgroups, respectively. PFS was equal between the two subgroups. Grade 3-4 adverse events occurred in 23.3 % of patients and three deaths were treatment-related., Conclusions: For this unselected PM population, efficacy and safety outcomes compared favorably with CheckMate 743 trial results., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: In COVID-19 patients, older age (sixty or older), comorbidities, and frailty are associated with a higher risk for mortality and invasive mechanical ventilation (IMV) failure. It therefore seems appropriate to suggest limitations of care to older and vulnerable patients with severe COVID-19 pneumonia and a poor expected outcome, who would not benefit from invasive treatment. HFNO (high flow nasal oxygen) is a non-invasive respiratory support device already used in de novo acute respiratory failure. The main objective of this study was to evaluate the survival of patients treated with HFNO outside the ICU (intensive care unit) for a severe COVID-19 pneumonia, otherwise presenting limitations of care making them non-eligible for IMV. Secondary objectives were the description of our cohort and the identification of prognostic factors for HFNO failure., Methods: We conducted a retrospective cohort study. We included all patients with limitations of care making them non-eligible for IMV and treated with HFNO for a severe COVID-19 pneumonia, hospitalized in a COVID-19 unit of the pulmonology department of Lyon Sud University Hospital, France, from March 2020 to March 2021. Primary outcome was the description of the vital status at day-30 after HFNO initiation, using the WHO (World Health Organization) 7-points ordinal scale., Results: Fifty-six patients were included. Median age was 83 years [76.3-87.0], mean duration for HFNO was 7.5 days, 53% had a CFS score (Clinical Frailty Scale) >4. At day-30, 73% of patients were deceased, one patient (2%) was undergoing HFNO, 9% of patients were discharged from hospital. HFNO failure occurred in 66% of patients. Clinical signs of respiratory failure before HFNO initiation (respiratory rate >30/min, retractions, and abdominal paradoxical breathing pattern) were associated with mortality (p = 0.001)., Conclusions: We suggest that HFNO is an option in non-ICU skilled units for older and frail patients with a severe COVID-19 pneumonia, otherwise non-suitable for intensive care and mechanical ventilation. Observation of clinical signs of respiratory failure before HFNO initiation was associated with mortality., Competing Interests: Declaration of Competing Interest None, (Copyright © 2023. Published by Elsevier Masson SAS.)

The molecular profiling of circulating tumor DNA (ctDNA) is a helpful tool not only in cancer treatment, but also in the early detection of relapse. However, the clinical interpretation of a ctDNA negative result remains challenging. The characterization of circulating nucleosomes (carrying cell-free DNA) and associated epigenetic modifications (playing a key role in the tumorigenesis of different cancers) may provide useful information for patient management, by supporting the contributive value of ctDNA molecular profiling. Significantly elevated concentrations of H3K27Me3 nucleosomes were found in plasmas at the diagnosis, and during the follow-up, of NSCLC patients, compared to healthy donors ( p -value < 0.0001). By combining the H3K27Me3 level and the ctDNA molecular profile, we found that 25.5% of the patients had H3K27Me3 levels above the cut off, and no somatic alteration was detected at diagnosis. This strongly supports the presence of non-mutated ctDNA in the corresponding plasma. During the patient follow-up, a high H3K27Me3-nucleosome level was found in 15.1% of the sample, despite no somatic mutations being detected, allowing the identification of disease progression from 43.1% to 58.2% over molecular profiling alone. Measuring H3K27Me3-nucleosome levels in combination with ctDNA molecular profiling may improve confidence in the negative molecular result for cfDNA in lung cancer at diagnosis, and may also be a promising biomarker for molecular residual disease (MRD) monitoring, during and/or after treatment.

Introduction: Implementation of Lung cancer screening (LCS) programs is challenging. The ILYAD study objectives is to evaluate communication methods to improve participation rate among the Lyon University Hospital employees. In this first part of the study, we aimed to determinate the number of eligible individuals among our population of employees., Method: In November 2020, we conducted a questionnaire based cross sectional survey among the Lyon University Hospital employees (N = 26,954). We evaluated the PLCO m2012 risk prediction model and the eligibility criteria recommended by French guidelines. We assessed the proportion of eligible individuals among the responders and calculated the total eligible individuals in our hospital., Results: Overall, 4,526 questionnaires were available for analysis. 16.0% were current smokers, and 28.2% were former smokers. Among the 50-75yo ever-smoker employees, 27% were eligible according to the French guidelines, 2.7% of all eversmokers according to a PLCO m2012 score ≥ 1.51%, and thus, 3.8% of the surveyed population were eligible to the combined criteria. The factors associated with higher eligibility among 50-75yo ever-smokers were educational level, feeling symptoms related to tobacco smoking, personal history of COPD and family history of lung cancer. Using the French guidelines criteria only, we estimated the total number of eligible individuals in the hospital at 838., Conclusion: In this study, we determined a theoretical number of eligible employees to LCS in our institution and the factors associated to eligibility. Secondly, we will propose LCS to all eligible employees of Lyon University Hospital with incremented information actions., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022. Published by Elsevier Masson SAS.)

Introduction: Progressive advanced non-small cell lung cancer (NSCLC) accounts for about 80-85% of all lung cancers. Approximately 10-50% of patients with NSCLC harbor targetable activating mutations, such as in-frame deletions in Exon 19 (Ex19del) of EGFR . Currently, for patients with advanced NSCLC, testing for sensitizing mutations in EGFR is mandatory prior to the administration of tyrosine kinase inhibitors., Patients and Methods: Plasma was collected from patients with NSCLC. We carried out targeted NGS using the Plasma-SeqSensei™ SOLID CANCER IVD kit on cfDNA (circulating free DNA). Clinical concordance for plasma detection of known oncogenic drivers was reported. In a subset of cases, validation was carried out using an orthogonal OncoBEAM TM EGFR V2 assay, as well as with our custom validated NGS assay. Somatic alterations were filtered, removing somatic mutations attributable to clonal hematopoiesis for our custom validated NGS assay., Results: In the plasma samples, driver targetable mutations were studied, with a mutant allele frequency (MAF) ranging from 0.00% (negative detection) to 82.25%, using the targeted next-generation sequencing Plasma-SeqSensei™ SOLID CANCER IVD Kit. In comparison with the OncoBEAM TM EGFR V2 kit, the EGFR concordance is 89.16% (based on the common genomic regions). The sensitivity and specificity rates based on the genomic regions ( EGFR exons 18, 19, 20, and 21) were 84.62% and 94.67%. Furthermore, the observed clinical genomic discordances were present in 25% of the samples: 5% in those linked to the lower of coverage of the OncoBEAM TM EGFR V2 kit, 7% in those induced by the sensitivity limit on the EGFR with the Plasma-SeqSensei™ SOLID CANCER IVD Kit, and 13% in the samples linked to the larger KRAS , PIK3CA , BRAF coverage of the Plasma-SeqSensei™ SOLID CANCER IVD kit. Most of these somatic alterations were cross validated in our orthogonal custom validated NGS assay, used in the routine management of patients. The concordance is 82.19% in the common genomic regions ( EGFR exons 18, 19, 20, 21; KRAS exons 2, 3, 4; BRAF exons 11, 15; and PIK3CA exons 10, 21). The sensitivity and specificity rates were 89.38% and 76.12%, respectively. The 32% of genomic discordances were composed of 5% caused by the limit of coverage of the Plasma-SeqSensei™ SOLID CANCER IVD kit, 11% induced by the sensitivity limit of our custom validated NGS assay, and 16% linked to the additional oncodriver analysis, which is only covered by our custom validated NGS assay., Conclusions: The Plasma-SeqSensei™ SOLID CANCER IVD kit resulted in de novo detection of targetable oncogenic drivers and resistance alterations, with a high sensitivity and accuracy for low and high cfDNA inputs. Thus, this assay is a sensitive, robust, and accurate test.

Patient-Derived Xenografts (PDXs) in the Chorioallantoic Membrane (CAM) are a representative model for studying human tumors. Circulating Tumor Cells (CTCs) are involved in cancer dissemination and treatment resistance mechanisms. To facilitate research and deep analysis of these few cells, significant efforts were made to expand them. We evaluated here whether the isolation of fresh CTCs from patients with metastatic cancers could provide a reliable tumor model after a CAM xenograft. We enrolled 35 patients, with breast, prostate, or lung metastatic cancers. We performed microfluidic-based CTC enrichment. After 48-72 h of culture, the CTCs were engrafted onto the CAM of embryonated chicken eggs at day 9 of embryonic development (EDD9). The tumors were resected 9 days after engraftment and histopathological, immunochemical, and genomic analyses were performed. We obtained in ovo tumors for 61% of the patients. Dedifferentiated small tumors with spindle-shaped cells were observed. The epithelial-to-mesenchymal transition of CTCs could explain this phenotype. Beyond the feasibility of NGS in this model, we have highlighted a genomic concordance between the in ovo tumor and the original patient's tumor for constitutional polymorphism and somatic alteration in one patient. Alu DNA sequences were detected in the chicken embryo's distant organs, supporting the idea of dedifferentiated cells with aggressive behavior. To our knowledge, we performed the first chicken CAM CTC-derived xenografts with NGS analysis and evidence of CTC dissemination in the chicken embryo.

Backgrounds: Malignant pleural mesothelioma (MPM) is a cancer with poor prognosis. Second-line and onward therapy has many options, including immune-checkpoint inhibitors with demonstrated efficacy: 10−25% objective response rate (ORR) and 40−70% disease-control rate (DCR) in clinical trials on selected patients. This study evaluated real-life 2L+ nivolumab efficacy in MPM patients and looked for factors predictive of response. Methods: This retrospective study included (September 2017−July 2021) all MPM patients managed in 11 French centers. Results: The 109 enrolled patients’ characteristics were: median age: 69 years; 67.9% men; 82.6% epithelioid subtype. Strictly, second-line nivolumab was given to 51.4%. Median PFS and OS were 3.8 (3.2−5.9) and 12.8 (9.2−16.4) months. ORR was 17/109 (15.6%); 34/109 patients had a stabilized disease (DCR 46.8%). Univariable analysis identified several parameters as significantly (p < 0.05) prognostic of OS [HR (95% CI)]: biphasic subtype: 3.3 (1.52−7.0), intermediate Lung Immune Prognostic Index score: 0.46 (0.22−0.99), progression on the line preceding nivolumab: 2.1 (1.11−3.9) and age > 70 years: 2.5 (1.5−4.0). Multivariable analyses retained only biphasic subtype: 3.57 (1.08−11.8) and albumin < 25 g/L: 10.28 (1.5−70.7) as significant and independent predictors. Conclusions: Second-line and onward nivolumab is effective against MPM in real life but with less effectiveness in >70 years. Ancillary studies are needed to identify the predictive factors.

Competing Interests: All authors declare no competing interests.

Introduction: Smoking prevalence in the overall population in France was 27% in 2017. There are few data about smoking prevalence in hospital workers. The aim of this study was to assess prevalence of current smoking in student and staff populations at Lyon University Hospital. Secondary objectives were to identify main variables associated with current smoking and willingness to quit., Methods: We designed a single center, cross-sectional survey, using printed questionnaires. During one day, all registered staff and students were surveyed. We used optical reading to extract information from questionnaires. We performed univariate and multivariate analysis adjusted on most relevant factors., Results: We analyzed 9712 questionnaires. The participating rates were high: 40.6% in the student cohort and 51.5% in the staff cohort. The proportion of current cigarette users was 26% in students and 25% in staff. In multivariate analysis, current smoking was significantly associated with: younger age, male sex, occupation type (e.g. logistical staff, and paramedical students), overnight work, and e-cigarette use. Among smokers, 53% reported a willingness to quit. In multivariate analysis, number of quit attempts, and feeling symptoms from tobacco were associated with willingness to quit., Conclusions: Current smoking is less frequent in our cohorts of hospital staff and students than in the general French population. However, there are deep disparities in current smoking prevalence underlining a heterogeneous population. Among smokers, the majority reported a willingness to quit and some predictive factors may help to target this audience., Competing Interests: The authors have each completed and submitted an ICMJE form for disclosure of potential conflicts of interest. The authors declare that they have no competing interests, financial or otherwise, related to the current work. B. Rolland reports grants from Abbvie, Gilead, and Camurus, consulting fees from Abbvie, Gilead, Camurus, Pileje, Accord Health, Indivior, and Zentiva, honorary payments from Abbvie, Gilead, Recordati, Ethypharm, HAC Pharma, and Shire, and other payment from Camurus, outside the submitted work. M. Darrason reports honorary payment from Bristol Meyers Squibb, CCA congress colloquia, outside the submitted work., (© 2021 Sébastien Couraud.)

Background and Objectives: The use of ultra-sensitive diagnostic tests to detect clinically actionable somatic alterations within the gene encoding the epidermal growth factor receptor (EGFR) within circulating cell-free DNA is an important first step in determining the eligibility of patients with non-small cell lung cancer to receive tyrosine kinase inhibitors., Methods: We present the clinical validation (accuracy, sensitivity, and specificity) of a highly sensitive OncoBEAM TM EGFR V2 test, which we compare to a custom next-generation sequencing assay, for the treatment of patients with non-small cell lung cancer with EGFR tyrosine kinase inhibitor therapies. The OncoBEAM TM digital-polymerase chain reaction method detects 36 different EGFR alterations in circulating cell-free DNA, whereas the next-generation sequencing assay covers major solid tumor oncodrivers. Of the 540 samples analyzed with the OncoBEAM TM EGFR V2 test, 42.4% of patients had undergone molecular testing at diagnosis (N = 229/540) and 57.7% of patients during disease progression (N = 311/540)., Results: The sensitivity and specificity were measured for this BEAMing assay. The number of mutant beads and mutant allelic fraction were measured for each EGFR alteration and the level of detection was established at 0.1% for a median of 2861 genome equivalent (GE) in each reaction using HD780 horizon control DNA, as well as by an internal quality reference standard. Approximately 10%, 27%, and 63% of the 540 samples contained < 1500 GE, a range of 1500-3000 GE, and > 3000 GE, which corresponded to a maximal assay sensitivity of 2.0%, 0.5-0.1%, and 0.1-0.05% mutant allelic fraction, respectively. In a routine hospital setting, 11.4% of non-small cell lung cancer tumors were positive at diagnosis for EGFR alterations, while 43.7% samples harbored EGFR mutations at progression, among which 40.3% expressed EGFR resistance mutations after first-line tyrosine kinase inhibitor treatment with first- and second-generation drugs., Conclusions: The OncoBEAM TM EGFR V2 is a sensitive, robust, and accurate assay that delivers reproducible results. Next-generation sequencing and BEAMing technologies act complementarily in the routine molecular screening. We show that using a next-generation sequencing assay, despite its lower sensitivity, enables the identification of rare EGFR alterations or resistance mechanisms (mutation, deletion, insertion, and copy number variation) to orient first- and second-line treatments.

How to implement lung cancer screening ? In this review, we will focus on practical approaches to lung cancer screening in France and worldwide. In France, these modalities are determined by recommendations, currently in edition. However, main outcomes recommended for screening are reported here., Competing Interests: S. Couraud déclare des liens ponctuels avec Amgen, AstraZeneca, Bayer, BMS, Boehringer Ingelheim, Chugai, Edimark, Ellipses, Laidet, Lilly, MSD, Novartis, Pfizer, Santor, Roche, Sysmex Innostics, Takeda, Vitalaire. E. Grolleau déclare n’avoir aucun lien d’intérêts.