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Supplemental Figure S1. Sample inclusion flow chart. Supplemental Figure S2. Boxplot of circulating free DNA concentration in plasma (in ng/microl) regarding M stage (up), and number of metastatic sites (down) in all samples (n=106). Y axis is in logarithmic scale. Supplemental Table S1. Processes used in the different participating labs for tumor DNA extraction, storage, shipment, and biomarker analysis. Supplemental Table S2. Primers used for amplicon sequencing by IonTorrent next-generation sequencing Supplemental Table S3. Multiplex reaction conditions. Supplemental Table S4. NGS mutation screening results in the 68 paired samples Supplemental Table S5. IonTorrent NGS test results in cfDNA, for each individual amplicon and overall, taking tDNA as a reference and restricted to stage IV samples (n=50). Supplemental Table S6. NGS test results in tDNA and cfDNA for all amplicons concomitantly using the ITVC strategy (5A), or the in-house strategy (5B); and corresponding calculated sensitivity for all matched samples analyzed by NGS (n=68)

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 OncoBEAMTM 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 OncoBEAMTM 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 OncoBEAMTM 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.

PURPOSE The ability of next-generation sequencing (NGS) assays to interrogate thousands of genomic loci has revolutionized genetic testing. However, translation to the clinic is impeded by false-negative results that pose a risk to patients. In response, regulatory bodies are calling for reliability measures to be reported alongside NGS results. Existing methods to estimate reliability do not account for sample- and position-specific variability, which can be significant. Here, we report an approach that computes reliability metrics for every genomic position and sample interrogated by an NGS assay. METHODS Our approach predicts the limit of detection (LOD), the lowest reliably detectable variant fraction, by taking technical factors into account. We initially explored how LOD is affected by input material amount, library conversion rate, sequencing coverage, and sequencing error rate. This revealed that LOD depends heavily on genomic context and sample properties. Using these insights, we developed a computational approach to predict LOD on the basis of a biophysical model of the NGS workflow. We focused on targeted assays for cell-free DNA, but, in principle, this approach applies to any NGS assay. RESULTS We validated our approach by showing that it accurately predicts LOD and distinguishes reliable from unreliable results when screening 580 lung cancer samples for actionable mutations. Compared with a standard variant calling workflow, our approach avoided most false negatives and improved interassay concordance from 94% to 99%. CONCLUSION Our approach, which we name LAVA (LOD-aware variant analysis), reports the LOD for every position and sample interrogated by an NGS assay. This enables reliable results to be identified and improves the transparency and safety of genetic tests.

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.

Circulating cell-free DNA (cfDNA) has the potential to be a specific biomarker for the therapeutic management of lung cancer patients. Here, a new sequencing error-reduction method based on molecular amplification pools (MAPs) was utilized to analyze cfDNA in lung cancer patients. We determined the accuracy of MAPs plasma sequencing with respect to droplet digital polymerase chain reaction assays (ddPCR), and tested whether actionable mutation discovery is improved by next-generation sequencing (NGS) in a clinical setting. This study reports data from 356 lung cancer patients receiving plasma testing as part of routine clinical management. Sequencing of cfDNA via MAPs had a sensitivity of 98.5% and specificity 98.9%. The ddPCR assay was used as the reference, since it is an established, accurate assay that can be performed contemporaneously on the same plasma sample. MAPs sequencing detected somatic variants in 261 of 356 samples (73%). Non-actionable clonal hematopoiesis-associated variants were identified via sequencing in 21% of samples. The accuracy of this cfDNA sequencing approach was similar to that of ddPCR assays in a clinical setting, down to an allele frequency of 0.1%. Due to broader coverage and high sensitivity for insertions and deletions, sequencing via MAPs afforded important detection of additional actionable mutations.

Following the American National Lung Screening Trial results in 2011 a consortium of French experts met to edit a statement. Recent results of other randomized trials gave the opportunity for our group to meet again in order to edit updated guidelines. After literature review, we provide here a new update on lung cancer screening in France. Notably, in accordance with all international guidelines, the experts renew their recommendation in favor of individual screening for lung cancer in France as per the conditions laid out in this document. In addition, the experts recommend the very rapid organization and funding of prospective studies, which, if conclusive, will enable the deployment of lung cancer screening organized at the national level.

Introduction: Treatment options of lung cancer (LC) comprise radiotherapy, and/or combined treatment approaches, including chemotherapy, immunotherapy and targeted therapies based on the tumoral molecular profile. Following curative-intent first-line therapies, clinical surveillance involves serial CT imaging. However, such surveillance can detect only macroscopic disease recurrence and is frequently inconclusive. NGS has been utilized to help identify and monitor treatment plans. Nucleosomes, complexes of DNA and histones proteins, are released during cell death into blood circulation. Trimethylation of lysine 27 on histone H3 (H3K27Me3), catalyzed by enhancer of zeste homolog 2 (EZH2), is a crucial epigenetic process in tumorigenesis. We investigated if H3K27Me3-nucleosome concentration could be a biomarker for molecular residual disease (MRD). Patients and Methods: Plasmas were retrospectively collected from patients with advanced LC during treatment (CIRCAN’s cohort, n= 200) and from healthy donors (n=100). We carried out standard targeted NGS on paired plasmas. Samples were divided in two sub-groups based on genetical results: ctDNA negative (n=120) or positive (n=80) for presence of somatic alterations. Concentration of circulating H3K27Me3-nucleosome was measured using chemiluminescent Nu.Q® immunoassay (Belgian Volition SRL, Belgium). Results: Significantly elevated concentrations of H3K27Me3-nucleosomes were found in LC plasmas during the follow-up of patients compared to healthy donors (median 14.9 ng/ml vs 6.15 ng/ml, respectively, p Conclusions: High levels of Nu.Q® H3K27Me3 could allow physicians to detect MRD in LC patients following treatment with curative intent. This could be achieved by monitoring testing of patients at defined intervals of treatment and recovery, alongside imaging, to incorporate analyses of evolving molecular landscapes during treatment. In this setting, the H3K27Me3-nucleosome quantification, to complete the molecular exploration of cfDNA is highly encouraging, especially in advanced NSCLC, where re-tissue biopsies are impractical, expensive, and may cause undue harm. H3K27Me3-nucleosome quantification may also be useful in patient identification for specific treatments such as EZH2 inhibitor, but this requires investigation. Citation Format: Emmanuel Grolleau, Julie Candiracci, Arnaud Gauthier, Gaelle Lescuyer, David Barthelemy, Christine Haon, Florence Geiguer, Margaux Raffin, Nathalie Hardat, Julie Balandier, Rémi Rabeuf, Anne-Sophie Wozny, Guillaume Rommelaere, Claire Rodriguez-Lafrasse, Fabien Subtil, Sébastien Couraud, Marielle Herzog, Lea Payen-Gay. Circulating H3K27 nucleosomes to monitor lung cancer patients during treatment, a universal biomarker quantifying the molecular residual disease (MRD) in plasma samples [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2163.

Background: Noninvasive genotyping using plasma cell-free DNA (cfDNA) has the potential to obviate the need for some invasive biopsies in cancer patients. We sought to validate an ultra-deep plasma Next-Generation Sequencing (NGS) assay for patients with Non-Small-Cell Lung Cancers (NSCLC) for detecting Minimal Residual Disease (MRD) following curative-intent NSCLC treatment or EGFR detection at an early stage. Patients and Methods: We carried out targeted NGS using the Plasma-SeqSensei™ Solid Cancer IVD Kit on cfDNA extracted from plasma. Somatic alterations were filtered, removing somatic mutations attributable to clonal hematopoiesis. Sensitivity and specificity for plasma detection of known oncogenic drivers were calculated. In a subset of cases, validation was carried out using an orthogonal OncoBEAMTM EGFR V2 assay, as well as with a custom-validated NGS assay. Results: In comparison with the OncoBEAMTM EGFR V2 kit, we observed a 75% concordance with the Plasma-SeqSensei™ Solid Cancer IVD Kit. The 25% genomic discordances were respectively observed in 5%, 7% and 13% linked to the limit of coverage of the OncoBEAMTM EGFR V2 kit, the limit of EGFR sensitivity of the Plasma-SeqSensei™ Solid Cancer IVD Kit and the larger KRAS, PIK3CA, BRAF coverage of the Plasma-SeqSensei™ Solid Cancer IVD Kit. In comparison with the custom-validated NGS assay, we observed a 68% concordance with the Plasma-SeqSensei™ Solid Cancer IVD Kit. The 32% genomic discordances were respectively observed in 5%, 11% and 16% linked to the limit of coverage of the Plasma-SeqSensei™ Solid Cancer IVD Kit, the limit of covered sensitivity of the custom-validated NGS assay and the additional oncodrivers analysis only covered by the custom-validated NGS assay. Benefitting from the higher coverage from targetable BRAF, KRAS, PIK3CA targetable alterations, the plasma targeted NGS Plasma-SeqSensei™ Solid Cancer IVD Kit showed 13% additional discordances with the Plasma OncoBEAMTM EGFR V2 kit. Most of these additional somatic alterations were cross-validated in our orthogonal custom-validated NGS assay, used in the routine management of patients. The custom-validated NGS assay sensitivity is determined for MAF at 1%, explaining the limit of sensitivity with the Plasma-SeqSensei™ Solid Cancer IVD Kit. Conclusions: Plasma-SeqSensei™ Solid Cancer IVD Kit resulted in de novo detection of targetable oncogenic drivers and resistance mechanisms in patients with NSCLC, including when tissue biopsies were inadequate for genotyping with high sensitivity and accuracy for low and high cfDNA inputs. Citation Format: David Barthelemy, Emmanuel Grolleau, Gaelle Lescuyer, Florence Geiguer, Arnaud Gauthier, Julie Balandier, Margaux Raffin, Claire Bardel, Bruno Bouyssounouse, Claire Rodriguez-Lafrasse, Sébastien Couraud, Anne-Sophie Wozny, Lea Payen-Gay. Paired comparison of routine molecular screening of patient samples with advanced non-small cell lung cancer in circulating cell-free DNA using OncoBEAMTM EGFR V2, targeted next-generation sequencing Plasma-SeqSensei™ Solid Cancer IVD Kit and custom-validated NGS assay. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6691.

Background Lung cancer in women is on the rise, with a higher proportion occurring in lifelong never-smokers. Lung cancer in never-smokers (LCINS) exhibits a high frequency of driver oncogene alterations. In this study, we aimed to investigate whether exposure to reproductive factors in women with LCINS may modulate the molecular pattern. Methods All newly diagnosed LCINSs were included in a prospective, observational study (IFCT-1002 BioCAST). Each patient responded to a questionnaire including reproductive factors. Biomarker test results were also collected. Results Two hundred and sixty women were included in this analysis, and 166 alterations were characterized. EGFR mutation frequency proved greater among patients with late menarche (74% in age > 14 vs. 40% and 41% for 12–14 and ≤ 12 years, respectively; P = 0.020) and tended to decrease with increasingly late age at menopause. In multivariate analysis, EGFR mutation frequency increased by 23% per increment of 1 year of age at menarche (P = 0.048), and by 9% for each year at age at first birth (P = 0.035). ALK alteration frequency was greater in women with high parity (50% in ≥ 5 vs. 12% and 7% for 1–4 and nulliparity, respectively; P = 0.021). Conclusion In a cohort of women LCINSs, female hormonal factors appear to impact molecular pattern.

Background In previous studies, patient-reported outcomes (PROs) have been shown to improve survival in cancer patients. The aim of the present study was to assess symptoms potentially related to adverse events experienced by cancer outpatients treated by oral anticancer agents (OAAs) using PROs. Methods Between September 2018 and May 2019, outpatients starting OAAs were included in a 12-week follow-up to assess 15 symptoms listed in the National Cancer Institute PRO Common Terminology Criteria for Adverse Events, using a 5-point scale of severity or frequency. Patients were requested to alert a referral nurse or pharmacist when they self-assessed high-level (level 3 or 4) symptoms. Results 407 questionnaires were completed by 63 patients in which 2333 symptoms were reported. Almost three-quarters (74.6%) reported at least one high-level symptom. The symptoms that were most commonly experienced were fatigue (>9 in 10 patients; 13.2% of symptoms declared), various psychological disorders (>9 in 10 patients; 28.6% of symptoms declared) and general pain (>8 in 10 patients; 9.4% of symptoms declared). Conclusion PROs are appropriate to detect potential adverse events in cancer outpatients treated by OAAs. This study is the first step for integrating the patient’s perspective in a digital e-health device in routine oncology care.

Contains fulltext : 215810.pdf (Publisher’s version ) (Closed access) BACKGROUND: Anti-PD1/PD-L1 directed immune checkpoint inhibitors (ICI) are widely used to treat patients with advanced non-small-cell lung cancer (NSCLC). The activity of ICI across NSCLC harboring oncogenic alterations is poorly characterized. The aim of our study was to address the efficacy of ICI in the context of oncogenic addiction. PATIENTS AND METHODS: We conducted a retrospective study for patients receiving ICI monotherapy for advanced NSCLC with at least one oncogenic driver alteration. Anonymized data were evaluated for clinicopathologic characteristics and outcomes for ICI therapy: best response (RECIST 1.1), progression-free survival (PFS), and overall survival (OS) from ICI initiation. The primary end point was PFS under ICI. Secondary end points were best response (RECIST 1.1) and OS from ICI initiation. RESULTS: We studied 551 patients treated in 24 centers from 10 countries. The molecular alterations involved KRAS (n = 271), EGFR (n = 125), BRAF (n = 43), MET (n = 36), HER2 (n = 29), ALK (n = 23), RET (n = 16), ROS1 (n = 7), and multiple drivers (n = 1). Median age was 60 years, gender ratio was 1 : 1, never/former/current smokers were 28%/51%/21%, respectively, and the majority of tumors were adenocarcinoma. The objective response rate by driver alteration was: KRAS = 26%, BRAF = 24%, ROS1 = 17%, MET = 16%, EGFR = 12%, HER2 = 7%, RET = 6%, and ALK = 0%. In the entire cohort, median PFS was 2.8 months, OS 13.3 months, and the best response rate 19%. In a subgroup analysis, median PFS (in months) was 2.1 for EGFR, 3.2 for KRAS, 2.5 for ALK, 3.1 for BRAF, 2.5 for HER2, 2.1 for RET, and 3.4 for MET. In certain subgroups, PFS was positively associated with PD-L1 expression (KRAS, EGFR) and with smoking status (BRAF, HER2). CONCLUSIONS: : ICI induced regression in some tumors with actionable driver alterations, but clinical activity was lower compared with the KRAS group and the lack of response in the ALK group was notable. Patients with actionable tumor alterations should receive targeted therapies and chemotherapy before considering immunotherapy as a single agent.

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.

Resume Cette revue a pour objectif d’orienter le clinicien dans l’interpretation des nodules thoraciques decouverts au scanner thoracique. Deux situations sont traitees de maniere distincte: la decouverte fortuite d’un nodule sur une imagerie, et la decouverte au cours d’un examen de depistage. Il s’agit en effet de situations distinctes en terme de population, d’intention de l’imagerie initiale et donc de recommandations. Pour chaque situation, trois lesions semeiologiques sont abordees: les nodules solides, les nodules mixtes et les nodules en verre depoli.

Summary Even though tobacco-induced sleep disturbances (TISDs) have been reported in previous studies, the present article is the first meta-analysis quantitatively assessing the impact of tobacco on sleep parameters. We conducted a systematic review and meta-analysis of the studies comparing objective (i.e. polysomnography and actigraphy) and/or subjective sleep parameters in chronic tobacco smokers without comorbidities versus healthy controls. Studies were retrieved using PubMed, PsycINFO, and Web of Science. Differences are expressed as standardized mean deviations (SMD) and their 95% confidence intervals (95%CI). Fourteen studies were finally included into the review, among which ten were suitable for meta-analysis. Compared to healthy controls, chronic tobacco users displayed increased N1 percentage (SMD = 0.65, 95%CI: 0.22 to 1.07), N2 percentage (SMD = 1.45, 95%CI: 0.26 to 2.63), wake time after sleep onset (SMD = 6.37, 95%CI: 2.48 to 10.26), and decreased slow-wave sleep (SMD = −2.00, 95%CI: −3.30 to −0.70). Objective TISDs preferentially occurred during the first part of the night. Regarding subjective parameters, only the Pittsburgh Sleep Quality Index (PSQI) total score could be analyzed, with no significant between-groups difference (SMD = 0.53, 95%CI: −0.18 to 1.23). Smoking status should be carefully assessed in sleep medicine, while TISDs should be regularly explored in chronic tobacco users.

Resistance of Aspergillus fumigatus to triazoles has been reported increasingly in Europe. As few data are available from Southern France, the objectives of this study were to assess the burden of A. fumigatus isolates with azole resistance from clinical specimens in Lyon, and explore the resistance mechanisms involved. In this retrospective cross-sectional study, 221 consecutive A. fumigatus isolates from respiratory samples were identified from an 8-month period from 195 patients attending the Pulmonary Medicine Departments of Lyon University Hospitals. Morphological identification was confirmed by sequence analysis of the β-tubulin gene. All samples were tested for susceptibilities to itraconazole, voriconazole, posaconazole and isavuconazole using concentration gradient strips, and the results were confirmed using the EUCAST broth microdilution method. Resistance mechanisms were investigated by sequencing the cyp51A gene and its promoter, and by expression analysis of cyp51 and genes encoding several efflux transporters. Four isolates exhibited azole resistance. Three isolates presented with polymorphisms in an intronic region of cyp51A, and one isolate had F46Y, M172V and E427K polymorphisms. No mutations were identified in the cyp51A promoter, but significant induction of cyp51A and cyp51B gene expression was observed for all four and three isolates, respectively. Significant induction of atrF and cdr1B gene expression was observed for two and three isolates, respectively. No significant induction of MDR1/2/3/4, MFS56 and M85 gene expression was observed. To conclude, the observed prevalence of azole resistance was 2.1%. Significant induction of expression of the cyp51 genes and two genes encoding efflux transporters was evidenced, underlying the diversity of resistance mechanisms to be explored.

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.Quelle mise en pratique du dépistage des cancers du poumon ? L’objectif de cet article est de faire le point sur les modalités pratiques du dépistage du cancer bronchique en France et dans le monde. En France, les modalités pratiques sont fixées par des recommandations de pratique, en cours de publication, dont les principales conclusions sont rapportées.

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 OncoBEAMTM 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 OncoBEAMTM 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 OncoBEAMTM 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 OncoBEAMTM 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. Supplementary Information The online version contains supplementary material available at 10.1007/s40291-021-00515-9.

OBJECTIVE To assess awareness of bladder cancer (BCa) in France. METHODS The French nationwide observational survey EDIFICE 6 was conducted online (26 June-28 July 2017) in 12,046 individuals (age, 18-69 years). The present analysis focuses on laypersons' knowledge of the severity and frequency of BCa, signs and symptoms, associated risk factors and screening tests. Quantitative data were expressed as means and standard deviation, and categorical data as percentages. RESULTS Analyses were conducted on 11,313 questionnaires. Among the top five acknowledged risk factors for BCa, tobacco was ranked as having the second lowest impact (5.9/10 [2.5]). Only 28% of the study population were aware that active tobacco smoking is a major risk factor for BCa (rating ≥8/10); 61% of the study population was unaware of the existence of any signs or symptoms of BCa, and 69% was not able to cite any of the most widely used diagnostic tests. CONCLUSIONS We found that the French population has a poor knowledge of BCa risk factors, early signs and diagnostic tests. Effective prevention of BCa requires dissemination of clear information and prevention messages to the lay population, focusing particularly on tobacco consumption and early signs of the disease.

El cancer broncopulmonar es un buen candidato para la deteccion sistematica en fumadores y exfumadores debido a la frecuencia de esta enfermedad, curable en los estadios precoces, y a los resultados del estudio National Lung Screening Trial (NLST). Este estudio ha demostrado, en mas de 53.000 grandes fumadores o exfumadores, que la deteccion anual mediante tomografia computarizada (TC) de baja dosis disminuye en el 20% la mortalidad especifica por cancer broncopulmonar y en el 6,7% la mortalidad general. Sin embargo, se han descrito varios inconvenientes potenciales de esta deteccion mediante TC: frecuencia de falsos positivos y atencion medica a estos, radiacion relacionada con la TC, riesgo relacionado con el sobrediagnostico, influencia sobre el tabaquismo, alteracion de la calidad de vida, ansiedad y coste. En general, estos obstaculos siguen siendo manejables y la mayoria de las publicaciones recientes concluyen en una relacion beneficio/riesgo favorable a la deteccion por TC, de modo que en la actualidad las sociedades cientificas de Norteamerica recomiendan de rutina esta deteccion. En Francia, un grupo de expertos tambien se ha pronunciado de manera favorable, recomendando esta deteccion a los fumadores o exfumadores de 55-75 anos que han fumado como minimo 30 paquetes/anos. Sin embargo, la Haute Autorite de Sante (HAS) ha considerado que la implementacion de esta deteccion en Francia seria prematura.

Few studies have looked at lung cancer in prisoners, despite this population is possibly at increased risk of malignancy. In a previous study, we found an early onset of lung cancer in prisoners. Thus, the present CARCAN study was aimed at assessing the epidemiological characteristics, management, prognosis, and incidence of lung cancer in prisoners compared to a sample of non-prisoner patients. We performed a multi-center observational case–control study. Cases were prisoners diagnosed with lung cancer from 2005 to 2013. Controls were non-prisoner lung cancer patients selected from hospital databases and randomly matched to cases (targeted case–control ratio: 1:3). Incidence rates in both groups were calculated using national statistics. Seventy-two cases and 170 controls met inclusion criteria. Cases were mainly men (99%). Mean age at diagnosis was 52.9 (± 11.0) in cases and 64.3 (± 10.1) in controls (p

Context Residents in respiratory medicine are often confronted with breaking bad news to patients. In communication skill training, a recurring question is whether to use standardized or peer-played patients for simulation Methods In this prospective single-center crossover study in pulmonology residents, a range of scenarios were performed during training sessions using standardized or peer-played patients. The aim was to assess whether patient type did alter the quality of the role-play. The residents completed post-scenario questionnaires about the role-play of each scenario, but also pre- and post-session questionnaires about their perception of the effectiveness of both modalities, and pre- and post-testing questionnaires about the psychological impact of the training. Results Collectively, 4 scenarios were performed 52 times and evaluated 208 times by 52 residents. The use of standardized patients appeared to improve the quality of the patient role (8.8 ± 1.0 vs. 8.3 ± 1.1; p = 0.001) and the general quality of role-play (8.8 ± 1.0 vs. 8.2 ± 0.9; p = 0.008), without affecting the quality of the physician role played by the resident. There were no significant differences between standardized and peer-played patients regarding learning interest or psychological impact. Regardless of the modality, the training sessions did appear to significantly affect the residents' evaluations of their ability to break bad news to patients (5.7 ± 1.1 vs. 7.4 ± 1.1; p Conclusion Our results did not point to a superiority of either of these modalities for learning how to break bad news. Both may be used, depending on the local resources.

// Jessica Garcia 1, 2, 3, 4, ** , Eric Dusserre 1, 3, 4, ** , Valerie Cheynet 3, 5 , Pierre Paul Bringuier 6 , Karen Brengle-Pesce 3, 5 , Anne-Sophie Wozny 1, 7 , Claire Rodriguez-Lafrasse 1, 3, 4, 7 , Gilles Freyer 4, 8, 9 , Marie Brevet 4, 6, 9 , Lea Payen 1, 2, 3, 4, 7, * and Sebastien Couraud 4, 9, 10, * 1 Laboratoire de Biochimie et Biologie Moleculaire, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, 69310, Pierre Benite, France 2 Centre de Recherche en Cancerologie de Lyon, INSERM 1052, CNRS 5286, Universite Claude Bernard Lyon 1, Lyon, 69003, France 3 Laboratoire Commun de Recherche Hospices Civils de Lyon – BioMerieux, Centre Hospitalier Lyon Sud, 69310, Pierre Benite, France 4 Institut de Cancerologie des Hospices Civils de Lyon, CIRculating CANcer Program (CIRCAN), 69002 Lyon, France 5 Medical Diagnostic Discovery Department, BioMerieux, 69290 Craponne, France 6 Service d’Anatomie et de Cytologie Pathologiques, Groupement Hospitalier Est, Hospices Civils de Lyon, 69500, Bron, France 7 Faculte de Pharmacie de Lyon (IPSB), Universite de Lyon1, Lyon, 69008, France 8 Service d’Oncologie Medicale, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, Lyon, 69003, France 9 EMR 3738 Ciblage Therapeutique en Oncologie, Faculte de Medecine Lyon Sud, Universite Lyon 1, 69600, Oullins, France 10 Service de Pneumologie Aigue Specialisee et Cancerologie Thoracique, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, Lyon, 69003, France * Authors share co-senior authorship ** Authors share co-first authorshop Correspondence to: Lea Payen, email: lea.payen-gay@chu-lyon.fr Keywords: lung cancer, EGFR mutation, circulating-free DNA, liquid biopsy, digital PCR Received: December 22, 2016 Accepted: June 26, 2017 Published: September 21, 2017 ABSTRACT Non invasive somatic detection assays are suitable for repetitive tumor characterization or for detecting the appearance of somatic resistance during lung cancer. Molecular diagnosis based on circulating free DNA (cfDNA) offers the opportunity to track the genomic evolution of the tumor, and was chosen to assess the molecular profile of several EGFR alterations, including deletions in exon 19 (delEX19), the L858R substitution on exon 21 and the EGFR resistance mutation T790M on exon 20. Our study aimed at determining optimal pre-analytical conditions and EGFR mutation detection assays for analyzing cfDNA using the picoliter-droplet digital polymerase chain reaction (ddPCR) assay. Within the framework of the CIRCAN project set-up at the Lyon University Hospital, plasma samples were collected to establish a pre-analytical and analytical workflow of cfDNA analysis. We evaluated all of the steps from blood sampling to mutation detection output, including shipping conditions (4H versus 24H in EDTA tubes), the reproducibility of cfDNA extraction, the specificity/sensitivity of ddPCR (using external controls), and the comparison of different PCR assays for the detection of the three most important EGFR hotspots, which highlighted the increased sensitivity of our in-house primers/probes. Hence, we have described a new protocol facilitating the molecular detection of somatic mutations in cancer patients from liquid biopsies, improving their diagnosis and introducing a less traumatic monitoring system during tumor progression.

Resume L’etude NLST a demontre chez plus de 53 000 grands fumeurs ou anciens grands fumeurs que le depistage annuel par scanner faiblement dose diminue de 20 % la mortalite specifique par cancer bronchopulmonaire et de 6,7 % la mortalite globale. Neanmoins, plusieurs inconvenients potentiels de ce depistage par scanner ont ete regulierement mis en avant, tels que le risque de surdiagnostic, l’irradiation liee aux scanners, et surtout le nombre eleve de faux positifs pouvant generer des examens invasifs et potentiellement dangereux, alterer la qualite de vie et l’anxiete et majorer les couts. Tous ces obstacles theoriques a l’implantation du depistage ont ete abordes dans de nombreuses publications recentes qui concluent pour la plupart a un rapport benefice/risque favorable au scanner. La plupart des societes savantes americaines recommandent de fait ce depistage. En France, un groupe d’experts s’est egalement prononce favorablement en recommandant ce depistage aux fumeurs ou anciens fumeurs de 55 a 75 ans ayant fume au minimum 30 paquets/annees. Ce groupe suggerait egalement la realisation d’etudes cliniques pour preciser et adapter la mise en œuvre de ce depistage aux contraintes et particularites francaises. La Haute Autorite de sante a toutefois juge que la mise en place de ce depistage en France etait prematuree.

Introduction Le College des pneumologues des hopitaux generaux (CPHG) va mener, 10 ans apres l’etude ESCAP-2011-CPHG, l’etude ESCAP-2020-CPHG, nouvelle etude longitudinale prospective en vie reelle sur le cancer bronchique primitif (CBP) pris en charge dans les centres hospitaliers generaux (CH) et constituee a partir de la cohorte principale KBP-2020-CPHG. L’objectif principal d’ESCAP-2020-CPHG est de decrire la strategie therapeutique mise en œuvre durant les trois premieres annees qui suivent le diagnostic de CBP. Les objectifs secondaires sont de mener des evaluations pharmaco-economiques et pharmaco-epidemiologiques ainsi que d’evaluer l’impact des nouvelles therapeutiques sur la prise en charge et la survie des patients pris en charge en CH. Methodes Cette etude ancillaire de cohorte prospective, observationnelle, nationale, multicentrique, avec un suivi longitudinal n’affectant pas la prise en charge des patients, porte sur les patients et les centres de l’etude KBP-2020-CPHG ayant accepte de participer a l’etude ancillaire. Les investigateurs volontaires recueilleront de facon exhaustive et prospective reguliere tous les traitements mis en place dans les 3 annees qui suivent le diagnostic du CBP des patients de KBP-2020-CPHG sur un e-CRF. L’analyse d’ESCAP-2020-CPHG sera essentiellement descriptive. Cette description sera faite avec les methodes classiques et bayesiennes. Des analyses complementaires (regression logistique, de Poisson, lineaire ou Beta) seront utilisees pour les criteres de jugement secondaires, avec comparaisons entre sous-groupes. Les analyses seront realisees a l’aide des logiciels R, avec tous les packages requis, et JAGS. Resultats L’etude ESCAP-2020-CPHG decrira de maniere precise tous les traitements realises (locaux, locaux-regionaux, systemiques), quelles qu’en soient les modalites, pendant les 3 ans qui suivent le diagnostic de CBP avec leurs durees, les motifs d’initiation et d’arret des traitements ainsi que les effets des traitements sur la survie. 6000 patients sont attendus dans cette cohorte ; en 2011, 3943 patients avaient ete inclus. Conclusion L’etude ESCAP-2020-CPHG permettra d’evaluer la prise en charge du CBP en CH et de mesurer les progres realises en 10 ans avec l’apport des nouvelles therapeutiques. L’impact de l’acces aux soins sur les differentes modalites therapeutiques et sur la survie sera egalement evalue grâce a cette etude.

International audience; Circulating tumor cells (CTCs) derived from the primary tumor are shed into the bloodstream or lymphatic system. These rare cells (1-10 cells per mL of blood) warrant a poor prognosis and are correlated with shorter overall survival in several cancers (e.g., breast, prostate and colorectal). Currently, the anti-EpCAM-coated magnetic bead-based CTC capturing system is the gold standard test approved by the U.S. Food and Drug Administration (FDA) for enumerating CTCs in the bloodstream. This test is based on the use of magnetic beads coated with anti-EpCAM markers, which specifically target epithelial cancer cells. Many studies have illustrated that EpCAM is not the optimal marker for CTC detection. Indeed, CTCs are a heterogeneous subpopulation of cancer cells and are able to undergo an epithelial-to-mesenchymal transition (EMT) associated with metastatic proliferation and invasion. These CTCs are able to reduce the expression of cell surface epithelial marker EpCAM, while increasing mesenchymal markers such as vimentin. To address this technical hurdle, other isolation methods based on physical properties of CTCs have been developed. Microfluidic technologies enable a label-free approach to CTC enrichment from whole blood samples. The spiral microfluidic technology uses the inertial and Dean drag forces with continuous flow in curved channels generated within a spiral microfluidic chip. The cells are separated based on the differences in size and plasticity between normal blood cells and tumoral cells. This protocol details the different steps to characterize the programmed death-ligand 1 (PD-L1) expression of CTCs, combining a spiral microfluidic device with customizable immunofluorescence (IF) marker set.

BACKGROUND: Phase 3 clinical data has shown higher proportions of patients with objective response, longer response duration, and longer overall survival with nivolumab versus docetaxel in patients with previously treated advanced non-small-cell lung cancer (NSCLC). We aimed to evaluate the long-term benefit of nivolumab and the effect of response and disease control on subsequent survival. METHODS: We pooled data from four clinical studies of nivolumab in patients with previously treated NSCLC (CheckMate 017, 057, 063, and 003) to evaluate survival outcomes. Trials of nivolumab in the second-line or later setting with at least 4 years follow-up were included. Comparisons of nivolumab versus docetaxel included all randomised patients from the phase 3 CheckMate 017 and 057 studies. We did landmark analyses by response status at 6 months to determine post-landmark survival outcomes. We excluded patients who did not have a radiographic tumour assessment at 6 months. Safety analyses included all patients who received at least one dose of nivolumab. FINDINGS: Across all four studies, 4-year overall survival with nivolumab was 14% (95% CI 11–17) for all patients (n=664), 19% (15–24) for those with at least 1% PD-L1 expression, and 11% (7–16) for those with less than 1% PD-L1 expression. In CheckMate 017 and 057, 4-year overall survival was 14% (95% CI 11–18) in patients treated with nivolumab, compared with 5% (3–7) in patients treated with docetaxel. Survival subsequent to response at 6 months on nivolumab or docetaxel was longer than after progressive disease at 6 months, with hazard ratios for overall survival of 0·18 (95% 0·12–0·27) for nivolumab and 0·43 (0·29–0·65) for docetaxel; for stable disease versus progressive disease, hazard ratios were 0·52 (0·37–0·71) for nivolumab and 0·80 (0·61–1·04) for docetaxel. Long-term data did not show any new safety signals. INTERPRETATION: Patients with advanced NSCLC treated with nivolumab achieved a greater duration of response compared with patients treated with docetaxel, which was associated with a long-term survival advantage. FUNDING: Bristol-Myers Squibb.

Resume La majorite des Cancers Bronchiques Non a Petites Cellules sont diagnostiques a un stade metastatique et ne peuvent beneficier que d’une chimiotherapie, les alterations oncogeniques traitables en premiere ligne par des therapeutiques ciblees, ne sont presentes que dans moins de 20 % de ces cancers non epidermoides. Si les progres sont moindres que pour les therapeutiques ciblees, la strategie de chimiotherapie a beneficie de plusieurs avancees au benefice des patients. La mise a disposition du pemetrexed et du bevacizumab, pour les CBNPC non epidermoides a permis la de la mise en place de la strategie de maintenance qui a demontre son efficacite en termes de survie sans progression et de survie globale. Cette strategie a permis aussi la reduction du nombre des cycles de chimiotherapie d’induction, permettant ainsi une moindre toxicite. Dans les CBNPC non epidermoides, les strategies de « maintenance continuation » par monotherapie, par doublet pemetrexed et bevacizumab ou switch maintenance, seront definies au debut de la prise en charge et affinees suivant les toxicites et la reponse aux quatre premiers cycles de chimiotherapie. Dans les CBNPC epidermoides, la strategie de stop-and-go est preconisee.

Resume Introduction Le depistage du cancer bronchique par scanner thoracique faible dose annuel permet une reduction de mortalite. Une enquete menee en Rhone-Alpes pointait le besoin de formation des medecins sur le depistage. Les tests de concordance de script (TCS) sont une modalite d’evaluation du raisonnement clinique en situation d’incertitude, mais n’ont jamais ete utilises en France pour l’evaluation de connaissance en formation continue. Methode Un questionnaire comprenant 5 questions a choix multiples (QCM) et deux scenarios de TCS a ete envoye par courriel a tous les medecins et internes inscrits sur les listes de diffusion de la Societe de pneumologie de langue francaise (SPLF) et de l’association des jeunes pneumologues (AJPO2). Resultats Au total, 190 reponses ont ete analysees. Soixante-dix pour cent consideraient que reduire la mortalite etait le meilleur critere d’efficacite et 75 % que le scanner sans injection etait le meilleur examen de depistage. Quarante-cinq pour cent connaissaient les criteres d’eligibilite recommandes et 62 % la frequence de realisation des scanners. La participation a des reunions de concertation pluridisciplinaires, le fait d’avoir une qualification en oncologie thoracique etaient des variables significativement associees a un meilleur score aux QCM et aux TCS. Les scores obtenus aux QCM et aux TCS etaient correles (Rho de Spearman 0,339 ; p Conclusion Les TCS sont realisables a grande echelle par voie electronique et semblent pertinents. Les connaissances des pneumologues sur le depistage et sa pratique restent imparfaites.

In 2011, the investigators of the National Lung Cancer Screening Trial reported significant decreases in lung cancer mortality (20 %) and overall mortality (6.7 %) in a selected high-risk population screened by annual low-dose computed tomography. In so doing, they relaunched the debate on lung cancer screening. In this review, we report on what has changed in this field since the publication of the NLST. We analyze results from ongoing or recent randomized trials, present data on screening optimization (such as population selection or nodule management), and discuss the practical aspects of screening, including economics considerations.

Resume Introduction L’echo-endoscopie bronchique (EEB) est une technique recente pour le diagnostic et la classification ganglionnaire des cancers bronchiques. Elle a aussi montre son interet dans le diagnostic des adenomegalies mediastino-hilaires d’etiologies autres. Cette etude rapporte les trois premieres annees d’experience de notre centre en termes d’usage pratique de l’echo-endoscopie bronchique comme nouvel outil diagnostique dans ce domaine. Methodes Etude retrospective des cas consecutifs de patients ayant beneficie d’une echo-endoscopie bronchique de novembre 2008 a juin 2011 au centre hospitalier Lyon-Sud (CHLS). Resultats Sur les 65 echo-endoscopies bronchiques, une anesthesie generale a ete pratiquee dans 89 % des cas, avec une bonne tolerance dans 81 % des cas. Dans 77 % des cas, l’EEB a permis d’etablir le diagnostic permettant d’eviter la mediastinoscopie dans 60,5 % des cas. Les valeurs respectives de la sensibilite, specificite, valeurs predictives positives (VPP) et negatives (VPN) etaient de 74 %, 100 %, 100 % et 48 %. Conclusions Ces donnees, reflet de l’experience d’une equipe debutante, illustrent les resultats obtenus dans la pratique courante en termes d’etiologie diagnostique. L’EEB semble ainsi promise a un bel avenir mais necessite le developpement de centres dedies permettant la formation de pneumologues et d’anatomopathologistes specialises dans ce domaine.

Resume Introduction Le traitement des cancers broncho-pulmonaires (CBP) repose parfois sur des therapies ciblees orales. La croyance des patients envers ces medicaments – un parametre pouvant influencer l’observance – n’a jamais ete evaluee en oncologie thoracique. Methode Il s’agit d’une etude prospective monocentrique non interventionnelle. Les criteres d’inclusion etaient : patients atteints de CBP, necessitant un traitement par therapie ciblee orale en seconde ligne ou plus. L’objectif principal etait d’evaluer la croyance des patients envers le traitement antineoplasique specifiquement (CS) et en general (CG) selon le questionnaire BMQ (Believes about Medicines Questionnaire). L’observance declaree etait mesuree par le test de Morisky. Chaque patient inclus beneficiait aussi d’un entretien semi-directif avec une psychologue. Resultats Quinze patients ont ete inclus : 12 sous erlotinib et 3 sous crizotinib. Le score moyen (± ecart-type) au BMQ etait de 54/85 (± 6) globalement, 34/50 (± 5) pour la croyance specifique, et 19/35 (± 3) pour la croyance generale envers les medicaments. En entretien semi-directif, 47 % croient en l’efficacite du traitement, 93 % rapportent une inquietude par rapport a celui-ci, 80 % considerent la consultation medicale satisfaisante mais 40 % ressentent un besoin d’information complementaire. Le score moyen au questionnaire Morisky etait de 3/4 (±2) et 53 % rapportaient avoir oublie au moins une fois de prendre leur traitement. Aucune correlation n’a ete retrouvee entre croyance et observance. Conclusion La croyance des patients envers les ITK est relativement bonne mais l’observance est modeste dans cette etude pilote. L’entretien pointe le besoin de suivi et d’informations complementaires.

Resume Introduction Le diabete est une maladie metabolique systemique pouvant toucher plusieurs organes. Une des complications moins connues du diabete est l’alteration de la fonction respiratoire. L’objectif de cette etude est de comparer la fonction respiratoire chez des patients diabetiques et des patients obeses non diabetiques et de mettre en evidence des facteurs predictifs de l’alteration de la permeabilite alveolo-capillaire. Population et methode Nous avons inclus de maniere retrospective l’ensemble des patients hospitalises en endocrinologie ayant beneficie d’une exploration fonctionnelle respiratoire du 1 er juillet 2013 au 31 decembre 2013. L’ensemble des dossiers medicaux ont ete revus et les patients ont ete categorises en 2 groupes : patients diabetiques et patients obeses non diabetiques. Resultat Nous avons inclus 89 patients, 62 diabetiques et 27 non diabetiques. Dans le groupe diabetique, il existe une diminution significative de la capacite vitale forcee (CVF), du volume expiratoire maximal par seconde (VEMS), du debit expiratoire moyen, du volume residuel expiratoire, de la capacite pulmonaire totale (CPT) et de la capacite pulmonaire de diffusion du monoxyde de carbone (DLCO). Une DLCO abaissee est significativement associee a l’existence d’une neuropathie diabetique, d’une macroangiopathie au doppler des troncs supra-aortiques, d’une alteration de la fonction renale et d’une insulinotherapie. Conclusion La fonction respiratoire est alteree au cours du diabete, avec une diminution significative de la CVF, du VEMS, de la CPT et de la DLCO.

Free circulating DNA (cfDNA) has been known for several decades. These small DNA fragments are released into the circulation from nucleated cells through necrosis, apoptosis and/or active secretion. These genomic fragments are mainly constitutional (nucleated blood cell DNA), but in patients with cancer, a fraction comes from tumor cells. Although poorly known in the field of thoracic oncology, quantitative and qualitative analysis of the cDNA is nevertheless of great interest. Total cfDNA concentration appears to be an independent prognostic factor in lung cancer. Although changes in total cfDNA concentration is not informative to assess the effectiveness of chemotherapy, following-up the fraction of mutated genes such as EGFR during therapy with tyrosine kinase inhibitors appears to be particularly promising for the early detection of disease progression. The use of cfDNA as liquid biopsy is also very promising for the non-invasive somatic molecular profile either at baseline either for sampling at follow-up. Thus, cfDNA is a very promising tool in thoracic oncology and its translation into practice should be developed quickly.

Introduction BRAF (v-Raf murine sarcoma viral oncogene homolog B) mutations are identified in approximately 2% of non-small cell lung cancer (NSCLC). Because of the rarity of those mutations, associated clinical features and prognostic significance have not been thoroughly described so far. Methods Here we took advantage of the French National Cancer Institute Program of systematic molecular profiling of metastatic lung cancer, to collect clinical characteristics and analyze the outcome of consecutive patients with NSCLC harboring BRAF mutations at the Lyon University Hospital laboratory between February 2012 and October 2014. Especially, we compared those variables with that of patients with EGFR-, BRAF-, KRAS-, HER2-, PIK3CA- wild-type NSCLCs. Results Among 2690 patients with genotyped NSCLC during the study period, BRAF mutations were identified in 80 (3%) cases, consisting of V600E substitution in 42 (53%) cases; non-V600E mutation were observed in 38 (48%) cases. Concurrent mutations were not observed in case of BRAF V600 mutation, and were identified in 5 patients with BRAF non-V600E mutations, in all cases consisting of KRAS mutations. Non-V600E mutations were more likely to be observed in smokers, as compared V600E mutations. There was no significant difference in age, histologic type, performance status, and stage at diagnosis between cases of V600E and non-V600E mutations. Overall survival did not significantly differ in BRAF wild-type, V600E, and non-V600E patients. Conclusion This one of the largest series of patients with BRAF mutant NSCLC. Our clinical data suggest that BRAF mutations define specific subsets of patients with NSCLC; while their oncogenic nature is yet to be established in lung cancer, especially for non-V600E mutations, the value of BRAF mutations to predict the efficacy of targeted agents remains unclear.

Resume Plusieurs essais randomises demontrent desormais qu’une strategie de depistage par scanner thoracique faiblement dose sans injection de produit de contraste, diminue la mortalite par cancer broncho-pulmonaire. En France et en Europe, plusieurs societes savantes se sont prononcees pour la realisation de ce depistage chez des individus eligibles. Les criteres d’eligibilite retenus sont : âge entre 50 et 75 ans, fumeur a plus de 10 cigarettes par jour depuis plus de 30 ans ou plus de 15 cigarettes pendant 25 ans, actif ou sevre depuis moins de 10 ans (option : sevrage de moins de 15 ans et tabagisme superieur a 30 ans). Les biomarqueurs, notamment sanguins, sont une piste prometteuse. De meme, l’optimisation de la selection de la population eligible pour ameliorer les performances globales du depistage est une thematique majeure de recherche. © 2020 SPLF. Publie par Elsevier Masson SAS. Tous droits reserves.

Background To assess skill enhancement and maintenance by virtual-reality simulation of laparoscopic salpingectomy in gynecologic surgery fellows. Skill acquisition by virtual-reality surgical simulation is an active field of research and technological development. Salpingectomy is one of the first gynecologic surgery techniques taught to fellows that requires accompanied learning. Methods A single-center prospective study was performed in the University of Lyon, France, including 26 junior fellows (≤ 3 semesters’ internship) performing laparoscopic salpingectomy exercises on a LapSim® virtual reality simulator. Salpingectomy was performed and timed on 3 trials in session 1 and 3 trials in session 2, at a 3-month interval. Analysis was based on students’ subjective assessments and a senior surgeon’s objective assessment of skill. Progress between the 2 sessions was assessed on McNemar test and Wilcoxon test for matched series. Results 26 junior specialist trainees performed all trials. Most performed anterograde salpingectomy, both in session 1 (69 %) and session 2 (86 %). Mean procedure time was significantly shorter in session 2: 6.10 min versus 7.82 min (p = 0.0003). There was a significant decrease in blood loss between the first trial in session 1 and the last trial in session 2: 167 ml versus 70.3 ml (p = 0.02). Subjective assessment showed a significant decrease in anxiety and significant increase in perceived efficacy, eye-hand coordination and ergonomics. Efficacy, performance quality and speed of execution as assessed by the senior surgeon all improved significantly from trial to trial, while hesitation significantly decreased. Conclusions The study showed that junior trainees improved their surgical skills on a short laparoscopic exercise using a virtual reality simulator. Virtual reality simulation is useful in the early learning curve, accelerating the acquisition of reflexes. Maintaining skill requires simulation sessions at shorter intervals.

Introduction Le College des pneumologues des hopitaux generaux (CPHG) va mener, 20 ans apres l’etude KBP-2000-CPHG et dix ans apres l’etude KBP-2010-CPHG, une nouvelle etude epidemiologique en vie reelle sur le cancer bronchique primitif (CBP) pris en charge dans les centres hospitaliers generaux (CH). L’objectif principal est d’evaluer la mortalite a 1 an et jusqu’a 5 ans apres le diagnostic chez les patients ayant un CBP. Methodes Cette etude de cohorte prospective, observationnelle, nationale, multicentrique, porte sur tous les nouveaux cas de CBP diagnostiques histologiquement ou cytologiquement entre le 1er janvier et le 31 decembre 2020. L’analyse de KBP-2020-CPHG comportera une analyse de la survie globale et sans progression et d’une analyse du temps jusqu’a echec du traitement d’induction. Les resultats de KBP-2020-CPHG seront compares aux etudes KBP-2010 et KBP-2000 a l’aide des modeles bayesiens et du modele de Cox classique. Ceux-ci permettront d’estimer la survie a 1 an, 2 ans, et 5 ans, ainsi que la mediane de survie. Une analyse intermediaire sera realisee sur les donnees de KBP-2020-CPHG disponibles 3 ans apres le debut du recueil des donnees. Les analyses seront realisees a l’aide des logiciels R, avec tous les packages requis, et JAGS. Resultats L’etude KBP-2020-CPHG collectera les donnees suivantes : la survie globale a 1 et 5 ans, la survie sans progression, les donnees concernant le patient (sexe, âge, commune de naissance, taille, pourcentage de perte de poids, tabagisme, cannabis, Performance status ou score ECOG, score de precarite, statut vital), les donnees concernant la pathologie (mode de decouverte et date de premier contact specialise, methode diagnostique, classification anatomopathologique, recherche d’anomalies moleculaires, statut PDL-1, charge mutationnelle, metastase et stade tumoral initial), la strategie therapeutique de 1ere intention reellement mise en place jusqu’a progression. Les 10 000 patients attendus dans cette cohorte seront compares aux 5667 patients inclus en 2000 et aux 7051 patients de la cohorte 2010. Conclusion L’etude KBP-2020-CPHG permettra de recueillir des donnees de vie reelle sur le CBP et son evolution en 10 et 20 ans avec un « effet barometre » sur la population prise en charge dans les CH en France. L’acces aux soins sur le territoire national et son impact sur la prise en charge et la survie des patients seront egalement evalues grâce a cette etude.