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1. Respiratory recovery trajectories after severe-to-critical COVID-19: a 1-year prospective multicentre study

Author

Frédéric Schlemmer, Simon Valentin, Laurent Boyer, Anne Guillaumot, François Chabot, Clairelyne Dupin, Pierre Le Guen, Gwenael Lorillon, Anne Bergeron, Damien Basille, Julia Delomez, Claire Andrejak, Valentine Bonnefoy, Hélène Goussault, Jean-Baptiste Assié, Pascaline Choinier, Anne-Marie Ruppert, Jacques Cadranel, Maria Chiara Mennitti, Mehdi Roumila, Charlotte Colin, Sven Günther, Olivier Sanchez, Thomas Gille, Lucile Sésé, Yurdagul Uzunhan, Morgane Faure, Maxime Patout, Capucine Morelot-Panzini, Pierantonio Laveneziana, Maeva Zysman, Elodie Blanchard, Chantal Raherison-Semjen, Violaine Giraud, Etienne Giroux-Leprieur, Stéfanie Habib, Nicolas Roche, Anh Tuan Dinh-Xuan, Islem Sifaoui, Pierre-Yves Brillet, Camille Jung, Emmanuelle Boutin, Richard Layese, Florence Canoui-Poitrine, Bernard Maitre, Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre d'études et de recherche sur les services de santé et la qualité de vie (CEReSS), Aix Marseille Université (AMU), Département Universitaire de Psychiatrie - [Hôpital Sainte Marguerite - APHM] (Hôpitaux Sud), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpitaux Universitaires de Genève (HUG), CHU Amiens-Picardie, Agents infectieux, résistance et chimiothérapie - UR UPJV 4294 (AGIR ), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, Université de Picardie Jules Verne (UPJV), Service de Pneumologie [CHI Créteil], CHI Créteil, Clinical Epidemiology and Ageing : Geriatrie Soins Primaires et Santé Publique (CEpiA), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Centre Hospitalier de Versailles André Mignot (CHV), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Hôpital Avicenne [AP-HP], Hypoxie et Poumon : pneumopathologies fibrosantes, modulations ventilatoires et circulatoires (H&P), UFR SMBH-Université Sorbonne Paris Nord, CHU Pitié-Salpêtrière [AP-HP], Neurophysiologie Respiratoire Expérimentale et Clinique (UMRS 1158), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Centre de recherche Cardio-Thoracique de Bordeaux [Bordeaux] (CRCTB), Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier de Basse-Terre [Guadeloupe], Hôpital Ambroise Paré [AP-HP], Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Service de physiologie et explorations fonctionelles [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Service de radiologie [Avicenne], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Sorbonne Paris Nord, Centre Hospitalier Intercommunal de Créteil (CHIC), IMRB - CEPIA/'Clinical Epidemiology And Ageing : Geriatrics, Primary Care and Public Health' [Créteil] (U955 Inserm - UPEC), and Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)

Subjects
Pulmonary and Respiratory Medicine, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

BackgroundSurvivors of severe-to-critical coronavirus disease 2019 (COVID-19) may have functional impairment, radiological sequelae and persistent symptoms requiring prolonged follow-up. This pragmatic study aimed to describe their clinical follow-up and determine their respiratory recovery trajectories, and the factors that could influence them and their health-related quality of life.MethodsAdults hospitalised for severe-to-critical COVID-19 were evaluated at 3 months and up to 12 months post-hospital discharge in this prospective, multicentre, cohort study.ResultsAmong 485 enrolled participants, 293 (60%) were reassessed at 6 months and 163 (35%) at 12 months; 89 (51%) and 47 (27%) of the 173 participants initially managed with standard oxygen were reassessed at 6 and 12 months, respectively. At 3 months, 34%, 70% and 56% of the participants had a restrictive lung defect, impaired diffusing capacity of the lung for carbon monoxide (DLCO) and significant radiological sequelae, respectively. During extended follow-up, bothDLCOand forced vital capacity percentage predicted increased by means of +4 points at 6 months and +6 points at 12 months. Sex, body mass index, chronic respiratory disease, immunosuppression, pneumonia extent or corticosteroid use during acute COVID-19 and prolonged invasive mechanical ventilation (IMV) were associated withDLCOat 3 months, but not its trajectory thereafter. Among 475 (98%) patients with at least one chest computed tomography scan during follow-up, 196 (41%) had significant sequelae on their last images.ConclusionsAlthough pulmonary function and radiological abnormalities improved up to 1 year post-acute COVID-19, high percentages of severe-to-critical disease survivors, including a notable proportion of those managed with standard oxygen, had significant lung sequelae and residual symptoms justifying prolonged follow-up.

Published
2023

2. Outcomes of Patients With Advanced NSCLC From the Intergroupe Francophone de Cancérologie Thoracique Biomarkers France Study by KRAS Mutation Subtypes

Author

Fabrice Barlesi, H. Janicot, Pierre-Jean Souquet, Didier Debieuvre, Michel Poudenx, Virginie Westeel, Julien Mazieres, Michèle Beau-Faller, M. Wislez, Isabelle Monnet, Fabienne Escande, Pierre-Paul Bringuier, L'Houcine Ouafik, Pascal Foucher, Alexandra Langlais, Isabelle Rouquette, Jean-Philippe Merlio, Antoinette Lemoine, Anne-Marie Ruppert, Franck Morin, Charles Ricordel, Groupe de recherche clinique Biomarqueurs Théranostiques des Cancers Bronchiques Non à Petites Cellules (GRC 4 - Theranoscan), Sorbonne Université (SU), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire de Biochimie et Biologie Moléculaire [Strasbourg] (HUS), Les Hôpitaux Universitaires de Strasbourg (HUS), Univ Strasbourg, INSERM, IRFAC, UMR S1113, F-67200 Strasbourg, France, Groupe hospitalier de la région de Mulhouse Sud-Alsace (GHRMSA), Institut de neurophysiopathologie (INP), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Transfert d'Oncologie Biologique [Hôpital Nord - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital Nord [CHU - APHM], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service Pneumologie-Allergologie [CHU Toulouse], Pôle Clinique des Voies respiratoires [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Groupement Hospitalier Lyon-Est (GHE), Hospices Civils de Lyon (HCL), Centre Hospitalier Intercommunal de Créteil (CHIC), Laboratoire de Biochimie et Biologie Moléculaire [CHRU Lille] (Pôle de Biologie Pathologie Génétique), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Oncogenesis, Stress, Signaling (OSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Rennes (CHU Rennes), INSERM U1053, Université Bordeaux, Bordeaux, France., Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Clermont-Ferrand, INSERM UMR S1193, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Intergroupe Francophone de Cancérologie Thoracique [Paris] (IFCT), Intergroupe Francophone de Cancérologie thoracique, Service de pneumologie [Centre Hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Service d'oncologie multidisciplinaire innovations thérapeutiques [Hôpital Nord - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital Nord [CHU - APHM], Service de pneumologie [CHU Cochin], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), AstraZeneca, Roche, 2011-038, Institut National Du Cancer, France, Novartis, France, Ouafik, L'Houcine, Theranoscan [CHU Tenon] (GRC 4), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service de Pneumologie = Pneumologie - Oncologie Thoracique - Maladies Pulmonaires Rares [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), École pratique des hautes études (EPHE), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Unité pneumologie et oncologie thoracique [CHU Tenon], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Nord [CHU - APHM]-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de pneumologie [CHU Toulouse], Groupement hospitalier lyon Est (Hospices Civils de Lyon), INSERM U1242, Université Rennes 1, and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP)

Subjects
Pulmonary and Respiratory Medicine, Oncology, medicine.medical_specialty, endocrine system diseases, [SDV.CAN]Life Sciences [q-bio]/Cancer, medicine.disease_cause, NSCLC, lcsh:RC254-282, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Non-small cell lung cancer, Internal medicine, medicine, Overall survival, Non–small cell lung cancer, Stage (cooking), neoplasms, 030304 developmental biology, 0303 health sciences, Mutation, Transition (genetics), business.industry, KRAS mutation, medicine.disease, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Prognosis, Confidence interval, digestive system diseases, 3. Good health, respiratory tract diseases, 030220 oncology & carcinogenesis, Adenocarcinoma, Original Article, KRAS, business, Kras mutation
Abstract

Introduction KRAS mutations are detected in 20% to 30% of NSCLC. However, KRAS mutation subtypes may differently influence the outcome of patients with advanced NSCLC. Methods In the Biomarkers France study, 4894 KRAS mutations (26.2%) were detected in 4634 patients from the 17,664 enrolled patients with NSCLC. Survival and treatment data on noncurative stage III to IV NSCLC were available for 901 patients. First- and second-line treatment effects on progression-free survival and overall survival were analyzed according to the KRAS mutations subtype. Results Over 95% of patients with KRAS mutation were smokers or former smokers who were white (99.5%), presenting with adenocarcinoma (82.5%). The most common KRAS mutation subtype was G12C (374 patients; 41.5%), followed by G12V (168; 18.6%), G12D (131; 14.5%), G12A (62; 6.9%), G13C (45; 5.0%), G13D (31; 3.4%), and others (10; 1%). Approximately 21% of patients had transition mutation and 68.2% had a transversion mutation. G12D and transition mutations were predominant in never-smokers. The median overall survival for patients with KRAS-mutated NSCLC was 8.1 months (95% confidence interval [CI]: 7.5–9.5), without any differences according to the different KRAS subtypes mutations. The median progression-free survival was 4.6 months (95% CI: 4.2–5.1) for first-line treatment and 4.8 months (95% CI: 4.3–6.8) for second-line treatment, without any differences according to the different KRAS subtypes mutations. Conclusions KRAS mutation subtypes influenced neither treatment responses nor outcomes. The KRAS G12C mutation was detected in 41.5% of patients, who are now eligible for potent and specific G12C inhibitors.

Published
2020

3. Detection of secondary causes of spontaneous pneumothorax: Comparison between computed tomography and chest X-ray

Author

Anne-Marie Ruppert, A. Khallil, M. Giot, J. Assouad, Jacques Cadranel, Valérie Gounant, D. Sroussi, Theranoscan [CHU Tenon] (GRC 4), CHU Tenon [AP-HP], and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)

Subjects
Adult, Male, Tuberculosis, Adolescent, Concordance, [SDV]Life Sciences [q-bio], Computed tomography, 030218 nuclear medicine & medical imaging, Young Adult, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, Radiology, Nuclear Medicine and imaging, In patient, Prospective cohort study, Lung cancer, Aged, Retrospective Studies, Aged, 80 and over, Radiological and Ultrasound Technology, medicine.diagnostic_test, business.industry, Pneumothorax, General Medicine, Middle Aged, medicine.disease, 3. Good health, 030220 oncology & carcinogenesis, Lymphangioleiomyomatosis, Female, Radiography, Thoracic, Tomography, X-Ray Computed, Nuclear medicine, business
Abstract

Purpose The aim of this study was to compare the effectiveness of chest X-ray to that of thoracic computed tomography (CT) for the detection of the causes of secondary spontaneous pneumothorax (SP). Methods A prospective cohort of patients with SP was studied. All chest X-ray and CT examinations of the patients were reviewed retrospectively by an expert radiologist blinded to clinical data. The concordance between the CT examination and chest X-ray was assessed using the Cohen Kappa coefficient (κ), based on a bootstrap resampling method. Results A total of 105 patients with SP were included. There were 78 men and 27 women, with a mean age of 34.5 years ± 14.2 (SD) (range: 16–87 years). Of these, 44/105 (41%) patients had primary SP and 61/105 (59%) had secondary SP due to emphysema (47/61; 77%), tuberculosis (3/61, 5%), lymphangioleiomyomatosis (3/61; 5%), lung cancer (2/61, 3%) or other causes (6/61; 10%). Apart from pneumothorax, CT showed abnormal findings in 85/105 (81%) patients and chest X-ray in 29/105 (28%). Clinically relevant abnormalities were detected on 62/105 (59%) CT examinations. The concordance between chest X-ray and CT was fair for detecting emphysema (κ = 0.39; 95% CI: 0.2420–0.55), moderate for a mass or nodule (κ = 0.60; 95% CI: 0.28–0.90), fair for alveolar opacities (κ = 0.39; 95% CI: −0.02–1.00), and slight for interstitial syndrome (κ = 0.20; 95% CI: −0.02–0.85). Conclusion Chest X-ray is not sufficient for detecting the cause of secondary SP. As the detection of the cause of secondary SP may alter the therapeutic approach and long-term follow-up in patients with SP, the usefulness of a systematic CT examination should be assessed in a prospective trial.

Published
2020

4. Calpain 1 in bronchoalveolar lavage fluid is associated with poor prognosis in lepidic predominant pulmonary adenocarcinoma

Author

Marie Wislez, Nathalie Rabbe, Joëlle Perez, Martine Antoine, T. Vieira, Jacques Cadranel, Anne-Marie Ruppert, Laurent Baud, Michael Duruisseaux, Theranoscan, Sorbonne Université (SU), Service de pneumologie et réanimation [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Tenon [APHP], Departement Hospitalo- Universitaire - Inflammation, Immunopathologie, Biothérapie [Paris] (DHU - I2B), CHU Pitié-Salpêtrière [APHP]-Sorbonne Université (SU), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Cochin [AP-HP], Service d’Anatomie et cytologie pathologiques [CHU Tenon], Theranoscan [CHU Tenon] (GRC 4), CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Pneumologie - Oncologie Thoracique - Maladies Pulmonaires Rares [CHU Tenon], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Trousseau [APHP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)

Subjects
0301 basic medicine, Male, Cancer Research, Lung Neoplasms, Polymorphonuclear neutrophils, Neutrophils, [SDV.CAN]Life Sciences [q-bio]/Cancer, Adenocarcinoma, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Proinflammatory cytokine, Flow cytometry, 03 medical and health sciences, 0302 clinical medicine, Cell Line, Tumor, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], medicine, Extracellular, Humans, Radiology, Nuclear Medicine and imaging, Aged, Inflammation, medicine.diagnostic_test, biology, Chemistry, Calpain, Toll like receptor 2, Hematology, General Medicine, Prognosis, Toll-Like Receptor 2, 3. Good health, Neoplasm Proteins, TLR2, 030104 developmental biology, Bronchoalveolar lavage, Oncology, Cell culture, Tumor progression, 030220 oncology & carcinogenesis, biology.protein, Cancer research, Disease Progression, Female, Lung cancer, Bronchoalveolar Lavage Fluid
Abstract

International audience; Calpain 1 is a proinflammatory calcium-activated cysteine protease, which can be partly externalized. Extracellular calpains limit inflammatory processes and promote tissue repair, through cell proliferation and migration. Toll like receptor (TLR) 2 has been identified as a target of extracellular calpains in lymphocytes. The aim was to investigate the externalization of calpain 1 and the release of soluble TLR2 during tumor progression of pulmonary lepidic predominant adenocarcinoma (LPA). Extracellular calpain 1, soluble fragment of TLR2 and cytokines were analyzed by ELISA in bronchoalveolar lavage fluid (BALF) supernatants from patients with LPA (n = 68). Source of calpain was analyzed by immunohistochemistry and soluble TLR2 by flow cytometry on polymorphonuclear neutrophils (PMN) and human lung cancer cell lines. Extracellular calpain 1, secreted by tumor cells, was associated to tumor progression, neutrophilic inflammation, with a poor prognostic factor on survival (P = 0.003). TLR2 was expressed on PMN and tumor cells and decreased after calpain exposure. Soluble fragment of TLR2 in BALF supernatants was correlated to the extracellular calpain 1 concentration (r = 0.624; P < 0.001), and its high level was associated with tumor progression and a pro-inflammatory environment. Extracellular calpain 1 secreted by tumor cells, could participate in inflammatory microenvironment and tumor progression through TLR2 in LPA.

Published
2019

5. Place des traitements complémentaires pour les cancers bronchiques non à petites cellules opérables non N2

Author

Marie Wislez, Jalal Assouad, Armelle Lavolé, Anne-Marie Ruppert, Jacques Cadranel, Service de Pneumologie - Oncologie Thoracique - Maladies Pulmonaires Rares [CHU Tenon], CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Theranoscan, Université Pierre et Marie Curie - Paris 6 (UPMC), Service de chirurgie thoracique [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)

Subjects
Oncology, Cancer Research, medicine.medical_specialty, Cancer bronchique non à petites cellules, medicine.medical_treatment, [SDV.CAN]Life Sciences [q-bio]/Cancer, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Chimiothérapie adjuvante, medicine, Chemotherapy, Radiology, Nuclear Medicine and imaging, 030212 general & internal medicine, Stage (cooking), Lung cancer, Pathological, Neoadjuvant therapy, Radiothérapie, Radiotherapy, business.industry, Neo-adjuvant chemotherapy, Hematology, General Medicine, Perioperative, Immunotherapy, medicine.disease, Chimiothérapie néo-adjuvante, respiratory tract diseases, 3. Good health, Adjuvant chemotherapy, Radiation therapy, 030220 oncology & carcinogenesis, Non small cell lung cancer, business, Chimiothérapie
Abstract

International audience; Platinum-based perioperative chemotherapy is actually the standard of care in stage II–IIIa non-small cell lung cancer (NSCLC). A benefit may also be seen in stage IB NSCLC with tumors of more than 4 cm of diameter. Perioperative chemotherapy improves 5-year survival of 4 to 15%. This benefit is mainly proved by postoperative chemotherapy trials. Nevertheless, preoperative chemotherapy has advantages: a better tolerance, an estimation of tumor chemosensibility, without an increased postoperative morbimortality. However, pTNM and pathological tumor analyses are modified. Indications of postoperative radiotherapy are limited. In early stage NSCLC (stage I-II), radiotherapy worsens survival. Radiotherapy is routinely achieved in NSCLC with parietal tumor invasion and incomplete tumor resection. Indications of immunotherapy and targeted therapies in case of oncogenic addiction remain to be established in resected NSCLC. Several biomarkers are studied to better describe the indications of perioperative chemotherapy: recognize groups of patients with a worse prognosis and distinguish chemosensibility of the tumor.; Une chimiothérapie à base de platine administrée en périopératoire a démontré un bénéfice sur la survie dans le traitement des cancers bronchiques non à petites cellules (CBNPC) de stades II, IIIA et peut être IB (tumeur de plus de 4 cm de diamètre). Ce gain de survie varie entre 4 et 15 % selon les études. Le niveau de preuve est plus élevé pour la chimiothérapie adjuvante que néo-adjuvante. La chimiothérapie néo-adjuvante présente cependant certains avantages : une meilleure adhésion au traitement et une évaluation de la chimiosensibilité de la tumeur. Néanmoins, l’analyse précise anatomopathologique et le pTNM sont modifiés. La place de la radiothérapie postopératoire est restreinte. Dans les stades précoces (stades I-II), elle est délétère sur la survie. Elle est réalisée en routine en cas d’atteinte pariétale avec résection incomplète. La place de l’immunothérapie ou des thérapies ciblées en situation d’addiction oncogéniques reste à déterminer dans les CBNPC réséqués. Plusieurs marqueurs biologiques sont étudiés pour mieux définir les indications à un traitement médical périopératoire afin de déterminer les groupes de patients ayant un pronostic péjoratif et identifier les patients ayant une tumeur chimiosensible.

Published
2016

6. Role of the Sonic Hedgehog pathway in thoracic cancers

Author

E. Giroux Leprieur, Marie Wislez, Nathalie Rabbe, Anne-Marie Ruppert, Jacques Cadranel, T. Vieira, N. Rozensztajn, Martine Antoine, CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de pneumologie et oncologie thoracique, Groupe hospitalier Ambroise Paré, Theranoscan, Université Pierre et Marie Curie - Paris 6 (UPMC), Service de Pneumologie - Oncologie Thoracique - Maladies Pulmonaires Rares [CHU Tenon], and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)

Subjects
Pulmonary and Respiratory Medicine, Mesothelioma, animal structures, biology, business.industry, Cancer bronchique non à petites cellules, Mésothéliome, Cancer bronchique à petites cellules, [SDV.CAN]Life Sciences [q-bio]/Cancer, Lung pathology, Molecular biology, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, 3. Good health, Non-small cell lung carcinoma, Sonic Hedgehog, embryonic structures, biology.protein, Medicine, Small cell lung carcinoma, Sonic hedgehog, Chimiorésistance, business, Chemoresistance
Abstract

International audience; Introduction : Sonic Hedgehog (Shh) pathway is physiologically activated during embryogenesis and development. It plays a role in idiopathic lung fibrosis and is also activated in several solid cancers.State of the art : Shh pathway is reactivated in thoracic cancers, as small cell lung carcinoma, non-small cell lung carcinoma and malignant pleural mesothelioma. Shh pathway is associated with cancer stem cells and seems to have a crucial role in tumor proliferation, aggressiveness and chemoresistance in these cancers. This review describes the activation mode of Shh pathway in thoracic cancers and its role in small cell lung carcinoma, non-small cell lung carcinoma and malignant pleural mesothelioma, using in vitro and in vivo models. Notably, data from literature show that inhibition of Shh pathway has an antitumor action and sensitizes to chemotherapy.Perspectives : These results incite to develop targeted therapies against Shh pathway in the treatment of thoracic cancers.; Introduction : La voie de signalisation Sonic Hedgehog (Shh) est une voie physiologiquement activée durant l’embryogenèse et le développement. Elle jouerait un rôle dans la fibrose pulmonaire idiopathique et est aussi réactivée dans plusieurs cancers solides.État des connaissances : La voie Shh est réactivée dans les cancers thoraciques, comme le cancer bronchique à petites cellules, le cancer bronchique non à petites cellules et le mésothéliome pleural malin. Cette voie est intimement liée aux cellules souches cancéreuses et semble jouer un rôle important dans la prolifération tumorale, l’agressivité et la chimiorésistance de ces cancers. Cette revue décrit le mode d’activation de la voie Shh dans les cancers thoraciques et son rôle dans les formes à petites cellules, non à petites cellules et les mésothéliomes malins, à partir de modèles in vitro et in vivo. Les données de la littérature montrent que l’inhibition de la voie Shh a une action antitumorale et permet une sensibilisation à la chimiothérapie.Perspectives : Ces résultats incitent à développer des thérapies ciblant la voie Shh dans la prise en charge thérapeutique des cancers thoraciques.

Published
2015

7. Factors associated with early progression of non-small-cell lung cancer treated by epidermal growth factor receptor tyrosine-kinase inhibitors

Author

Jacques Cadranel, Roger Lacave, Marie Wislez, Michael Duruisseaux, Martine Antoine, T. Vieira, Anne-Marie Ruppert, Nathalie Rabbe, Etienne Giroux Leprieur, N. Rozensztajn, Armelle Lavolé, Service de Pneumologie - Oncologie Thoracique - Maladies Pulmonaires Rares [CHU Tenon], CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Theranoscan, Université Pierre et Marie Curie - Paris 6 (UPMC), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'anatomie pathologique [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)

Subjects
Male, Oncology, Cancer Research, Pathology, erlotinib, Carcinogenesis, gefitinib, Metastasis, Epidermal growth factor receptor tyrosine-kinase inhibitors, 0302 clinical medicine, Carcinoma, Non-Small-Cell Lung, 030212 general & internal medicine, Epidermal growth factor receptor, Original Research, Aged, 80 and over, biology, Middle Aged, Prognosis, 3. Good health, ErbB Receptors, 030220 oncology & carcinogenesis, Disease Progression, Female, Erlotinib, medicine.drug, medicine.medical_specialty, [SDV.CAN]Life Sciences [q-bio]/Cancer, Erlotinib Hydrochloride, 03 medical and health sciences, Gefitinib, Internal medicine, medicine, Carcinoma, Humans, Radiology, Nuclear Medicine and imaging, Lung cancer, Protein Kinase Inhibitors, Aged, Performance status, business.industry, medicine.disease, respiratory tract diseases, non-small-cell lung cancer, Mutation, Quinazolines, biology.protein, progressive disease, business, Progressive disease
Abstract

International audience; Epidermal growth factor receptor tyrosine-kinase inhibitors (EGFR-TKI) are a therapeutic option as second-line therapy in non-small-cell lung carcinoma (NSCLC), regardless of the EGFR gene status. Identifying patients with early progression during EGFR-TKI treatment will help clinicians to choose the best regimen, TKI or chemotherapy. From a prospective database, all patients treated with gefitinib or erlotinib between 2001 and 2010 were retrospectively reviewed. Patients were classified into two groups according to their tumor response by RECIST after 45 days of treatment, progressive disease (PD) or controlled disease (CD). Two hundred and sixty-eight patients were treated with EGFR-TKI, among whom 239 were classified as PD (n = 75) and CD (n = 164). Median overall survival was 77 days (95% CI 61–109) for PD and 385 days (95% CI 267–481) for CD. Patients with PD were of younger age (P = 0.004) and more frequently current smokers (P = 0.001) had more frequently a performance status ≥2 (P = 0.012), a weight loss ≥10% (P = 0.025), a shorter time since diagnosis (P < 0.0001), a pathological classification as non-otherwise-specified NSCLC (P = 0.01), and the presence of abdominal metasta-ses (P = 0.008). In multivariate analysis, abdominal metastases were the only factor associated with early progression (odds ratio (OR) 2.17, 95% CI [1.12– 4.19]; P = 0.021). Wild-type EGFR versus mutated EGFR was associated with early progression. The presence of abdominal metastasis was independently associated with early progression in metastatic NSCLC receiving EGFR-TKI.

Published
2014

8. Detection of K-Ras mutations in tumour samples of patients with non-small cell lung cancer using PNA-mediated PCR clamping

Author

Thomas Lavaux, Michèle Legrain, Eric Guérin, Michèle Beau-Faller, Gilbert Massard, Marie Pierre Gaub, Elisabeth Quoix, Agnès Neuville, Jean-Marie Wihlm, Anne-Claire Voegeli, Anne-Marie Ruppert, Pierre Oudet, Laboratoire de Biochimie et de Biologie Moléculaire, CHU Strasbourg-Hôpital de Hautepierre [Strasbourg], Institut de génétique et biologie moléculaire et cellulaire (IGBMC), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Louis Pasteur - Strasbourg I, Service de pneumologie, CHU Strasbourg-Hopital Civil, Laboratoire de Pathologie, Service de Chirurgie Thoracique, CHU Strasbourg-Nouvel Hôpital Civil, Peney, Maité, and Université Louis Pasteur - Strasbourg I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Male, Peptide Nucleic Acids, Cancer Research, Pathology, Lung Neoplasms, K-Ras mutations, medicine.disease_cause, Polymerase Chain Reaction, law.invention, MESH: Nucleic Acid Hybridization, 0302 clinical medicine, law, Carcinoma, Non-Small-Cell Lung, Mutation frequency, Polymerase chain reaction, MESH: Aged, 0303 health sciences, Mutation, MESH: Middle Aged, Nucleic Acid Hybridization, Middle Aged, 3. Good health, ErbB Receptors, Real-time polymerase chain reaction, Oncology, 030220 oncology & carcinogenesis, Adenocarcinoma, Female, MESH: ras Proteins, medicine.medical_specialty, MESH: Mutation, [SDV.CAN]Life Sciences [q-bio]/Cancer, MESH: Receptor, Epidermal Growth Factor, Biology, Sensitivity and Specificity, Proto-Oncogene Proteins p21(ras), MESH: Peptide Nucleic Acids, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, Proto-Oncogene Proteins, medicine, Humans, Lung cancer, Molecular Diagnostics, non-small cell lung cancer, 030304 developmental biology, Aged, COLD-PCR, MESH: Humans, Cancer, MESH: Polymerase Chain Reaction, medicine.disease, sensitivity, MESH: Sensitivity and Specificity, MESH: Male, MESH: Lung Neoplasms, MESH: Proto-Oncogene Proteins, MESH: Genes, ras, Genes, ras, Cancer research, ras Proteins, real-time PCR, MESH: Female, PNA, MESH: Carcinoma, Non-Small-Cell Lung
Abstract

International audience; Non-small cell lung cancers (NSCLC), in particular adenocarcinoma, are often mixed with normal cells. Therefore, low sensitivity of direct sequencing used for K-Ras mutation analysis could be inadequate in some cases. Our study focused on the possibility to increase the detection of K-Ras mutations in cases of low tumour cellularity. Besides direct sequencing, we used wild-type hybridisation probes and peptide-nucleic-acid (PNA)-mediated PCR clamping to detect mutations at codons 12 and 13, in 114 routine consecutive NSCLC frozen surgical tumours untreated by targeted drugs. The sensitivity of the analysis without or with PNA was 10 and 1% of tumour DNA, respectively. Direct sequencing revealed K-Ras mutations in 11 out of 114 tumours (10%). Using PNA-mediated PCR clamping, 10 additional cases of K-Ras mutations were detected (21 out of 114, 18%, P

Published
2009

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