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162 results on '"Université de Lille-UNICANCER-Université de Lille-UNICANCER"'

1. Evaluation of an ultrasound bladder scanner in supine and standing position

Author: David Pasquier, Florence Le Tinier, F. Crop, Pauline Comte, Xavier Mirabel, Centre de Recherche en Informatique, Signal et Automatique de Lille - UMR 9189 [CRIStAL], Physique médicale, Service de radiothérapie / curiethérapie, Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER-Université de Lille-UNICANCER-Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER-Université de Lille-UNICANCER, Centre de Recherche en Informatique, Signal et Automatique de Lille - UMR 9189 (CRIStAL), Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS), and Université de Lille-UNICANCER
Subjects: Male, Scanner, Supine position, [SDV]Life Sciences [q-bio], Urinary Bladder, Position (vector), Technical Note, Supine Position, Humans, Medicine, BladderScan, Radiology, Nuclear Medicine and imaging, Instrumentation, radiotherapy, Ultrasonography, Reproducibility, Radiation, business.industry, Reproducibility of Results, Repeated measures design, BVI 9400, Repeatability, Standing Position, Bladder volume, Technical Notes, Nuclear medicine, business, Bladder ultrasound, bladder filling, Radiotherapy, Image-Guided
Abstract: Purpose This study examined the performance of a bladder volume measuring device, the BladderScan (BS) BVI9400. The use of the BS offers the possibility of assessing the bladder volume before positioning the patient and performing the daily image‐guided radiotherapy procedure. Patients often cannot lie down before entering the treatment vault. Therefore, the BS was also assessed in a standing position. Methods The repeatability precision was first evaluated, which is the variability of immediate repeated measures of the BS with same operator and subject. This was followed by the reproducibility precision of the BS in which the operator and subjects differ. Finally, the trueness was evaluated in terms of fixed and proportional bias of the results by applying weighted least‐squares fitting. Note that 53 and 85 patient measurements were carried out in supine and standing position, respectively, each consisting of three repeated BS measurements. These were compared with the computed tomography (CT)‐delineated bladder volume. Results Repeatability was dependent on measurement value (heteroscedasticity) with σ repeatability (BS) = ±15 cm3 ± 10%. However, the total agreement between BS and CT was low with the 95% limits of agreement (LOAs) exceeding ±200 cm3 due to poor patient reproducibility and presence of fixed and proportional bias. Only in the best case of male patients in the supine position, three BS measurements, and correction for the fixed and proportional bias, 95% LOAs of [–147, +114] cm3 were obtained between CT and BS. Conclusion The agreement of the BVI9400 BS with CT was found to be too low for radiotherapy applications.
Published: 2021

2. Quelle démarche d’éducation thérapeutique (ETP) pour les adolescents et jeunes adultes atteints de cancer ? Expérience du groupe ETP de « Go-AJA »

Author: Leila Gofti-Laroche, Marielle Retailleau, Nathalie Gaspar, Nadège Corradini, Hélène Sudour-Bonnange, Françoise Rédini, Anne Le Rhun, Loïc Dagorne, Dispositif AJA en cancérologie [Lyon], Centre Léon Bérard [Lyon]-Institut d'hématologie et d'oncologie pédiatrique [CHU - HCL] (IHOPe), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), programme Spécifique de Prise en charge Interdisciplinaire Adolescents et Jeunes Adultes (SPIAJA), Département de cancérologie de l'enfant et de l'adolescent [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Département d'Oncologie Pédiatrique [CHU Nantes], Hôpital Mère-Enfant, CHU de Nantes, Physiopathologie des Adaptations Nutritionnelles (PhAN), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), équip'AJA [Lille] (Centre Oscar-Lambret), Unité d'oncologie pédiatrique [Centre Oscar Lambret, Lille], Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université Lille Nord de France (COMUE)-UNICANCER-Université Lille Nord de France (COMUE)-UNICANCER-Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université Lille Nord de France (COMUE)-UNICANCER-Université Lille Nord de France (COMUE)-UNICANCER, CHU Grenoble, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, équipe AJA Arc Alpin [CHU Grenoble Alpes], Centre Hospitalier Universitaire Grenoble Alpes (CHU Grenoble Alpes)-hôpital couple-enfant [CHU Grenoble Alpes], unité d'éducation thérapeutique [CHU Nantes] (Département de santé publique), Centre hospitalier universitaire de Nantes (CHU Nantes)-Hôpital Saint-Jacques [CHU Nantes], maurice, sandrine, Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN), Université de Lille-UNICANCER-Université de Lille-UNICANCER-Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER-Université de Lille-UNICANCER, and Centre Hospitalier Universitaire [Grenoble] (CHU)-hôpital couple-enfant [CHU Grenoble Alpes]
Subjects: Cancer Research, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, Patient care team, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, [SDV.CAN]Life Sciences [q-bio]/Cancer, Hematology, General Medicine, Therapeutic education, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.PED] Life Sciences [q-bio]/Human health and pathology/Pediatrics, Oncology, [SDV.CAN] Life Sciences [q-bio]/Cancer, 030220 oncology & carcinogenesis, Self care, Radiology, Nuclear Medicine and imaging, 030212 general & internal medicine, Psychology, Humanities, ComputingMilieux_MISCELLANEOUS, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Resume Introduction L’allongement de la survie des patients et l’evolution des relations soignants–patients contribuent au developpement de l’education therapeutique du patient (ETP) en onco-hematologie, necessaire notamment pour les patients adolescents et jeunes adultes (AJA) ayant une moindre observance et des difficultes organisationnelles dans leurs parcours de soins. La societe savante « Go-AJA » a structure un groupe de travail assurant la promotion et la structuration d’une demarche d’ETP adaptee aux AJA atteints de cancer. Materiel et methodes Ce groupe de travail national a pu federer des equipes multidisciplinaires formees et engagees dans des actions educatives aupres des AJA et s’est reuni periodiquement entre 2012 et 2015. Resultats Un referentiel de competence a ete construit et adapte a la population des AJA atteints de cancer. Des outils ont ete valides afin d’aider dans les 4 etapes classiques de l’ETP : le diagnostic educatif, l’alliance therapeutique, la mise en œuvre, et l’evaluation. Les competences d’auto-soins ont ete renforcees grâce a des ateliers individuels et/ou collectifs et le developpement des competences d’adaptation a ete integre a ce programme, afin d’ameliorer la coordination et le vecu des therapies. Discussion et conclusion Quels que soient les structures et lieux de soins, l’ETP doit s’integrer dans la prise en charge des AJA en onco-hematologie afin d’ameliorer leur implication et leur vecu de la maladie. Cette premiere experience nationale merite d’etre poursuivie et confortee par des etudes evaluant plus precisement l’impact de tels programmes d’ETP integres au parcours de soins de ces patients AJA atteints de cancer.
Published: 2016

3. Surface imaging, laser positioning or volumetric imaging for breast cancer with nodal involvement treated by helical TomoTherapy

Author: Frederik Crop, Lena Bequet, Amandine Baczkiewic, Emeline Steux, Mathilde Lacour, Laurence Muszynski, Julie Doré, Clement Florence, Eric Lartigau, David Pasquier, Jacqueline Bouillon, Anne Gadroy, Méthodes et Outils pour la Conception Intégrée de Systèmes (MOCIS), Centre de Recherche en Informatique, Signal et Automatique de Lille - UMR 9189 (CRIStAL), Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Physique médicale, Service de radiothérapie / curiethérapie, Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université Lille Nord de France (COMUE)-UNICANCER-Université Lille Nord de France (COMUE)-UNICANCER-Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université Lille Nord de France (COMUE)-UNICANCER-Université Lille Nord de France (COMUE)-UNICANCER, Université Lille Nord de France (COMUE)-UNICANCER, Université de Lille-UNICANCER-Université de Lille-UNICANCER-Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER-Université de Lille-UNICANCER, and Université de Lille-UNICANCER
Subjects: Volumetric imaging, Positioning system, medicine.medical_treatment, Movement, [SDV]Life Sciences [q-bio], tomotherapy, Breast Neoplasms, [SDV.CAN]Life Sciences [q-bio]/Cancer, Tomotherapy, Standard deviation, Patient Positioning, 030218 nuclear medicine & medical imaging, law.invention, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, breast cancer, law, Image Processing, Computer-Assisted, Medicine, Humans, Radiation Oncology Physics, Radiology, Nuclear Medicine and imaging, Instrumentation, radiotherapy, ComputingMilieux_MISCELLANEOUS, Nodal involvement, Radiation, business.industry, Lasers, Radiotherapy Planning, Computer-Assisted, Radiotherapy Dosage, image‐guided radiotherapy, medicine.disease, Laser, 3. Good health, 030220 oncology & carcinogenesis, Lymphatic Metastasis, Female, Tomography, Lymph Nodes, Radiotherapy, Conformal, business, Nuclear medicine, Tomography, Spiral Computed
Abstract: A surface imaging system, Catalyst (C‐Rad), was compared with laser‐based positioning and daily mega voltage computed tomography (MVCT) setup for breast patients with nodal involvement treated by helical TomoTherapy. Catalyst‐based positioning performed better than laser‐based positioning. The respective modalities resulted in a standard deviation (SD), 68% confidence interval (CI) of positioning of left–right, craniocaudal, anterior–posterior, roll: 2.4 mm, 2.7 mm, 2.4 mm, 0.9° for Catalyst positioning, and 6.1 mm, 3.8 mm, 4.9 mm, 1.1° for laser‐based positioning, respectively. MVCT‐based precision is a combination of the interoperator variability for MVCT fusion and the patient movement during the time it takes for MVCT and fusion. The MVCT fusion interoperator variability for breast patients was evaluated at one SD left–right, craniocaudal, ant–post, roll as: 1.4 mm, 1.8 mm, 1.3 mm, 1.0°. There was no statistically significant difference between the automatic MVCT registration result and the manual adjustment; the automatic fusion results were within the 95% CI of the mean result of 10 users, except for one specific case where the patient was positioned with large yaw. We found that users add variability to the roll correction as the automatic registration was more consistent. The patient position uncertainty confidence interval was evaluated as 1.9 mm, 2.2 mm, 1.6 mm, 0.9° after 4 min, and 2.3 mm, 2.8 mm, 2.2 mm, 1° after 10 min. The combination of this patient movement with MVCT fusion interoperator variability results in total standard deviations of patient position when treatment starts 4 or 10 min after initial positioning of, respectively: 2.3 mm, 2.8 mm, 2.0 mm, 1.3° and 2.7 mm, 3.3 mm, 2.6 mm, 1.4°. Surface based positioning arrives at the same precision when taking into account the time required for MVCT imaging and fusion. These results can be used on a patient‐per‐patient basis to decide which positioning system performs the best after the first 5 fractions and when daily MVCT can be omitted. Ideally, real‐time monitoring is required to reduce important intrafraction movement. PACS number(s): 87.53.Jw, 87.53.Kn, 87.56.Da, 87.63.L‐, 81.70.Tx
Published: 2016

4. Technical efficiency and complementarity of agroecological innovations in French West Indies banana production

Author: Jean-Joseph Minviel, M’Hand Fares, Jean-Marc Blazy, Alban Thomas, Unité Mixte de Recherche sur les Herbivores - UMR 1213 (UMRH), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université Clermont Auvergne (UCA), Systèmes d'élevage méditerranéens et tropicaux (UMR SELMET), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Agro Montpellier, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Agrosystèmes tropicaux (ASTRO), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Paris-Saclay Applied Economics (UMR PSAE), AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Observatoire des Programmes Communautaires de Développement Rural (US ODR), Département de Sénologie, Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER-Université de Lille-UNICANCER, and Systèmes d'Elevage Méditerranéens et Tropicaux - Laboratoire de Recherche sur le Développement de l'Elevage (SELMET-LRDE)
Subjects: Economics and Econometrics, farm performance, agroecological innovations, [QFIN]Quantitative Finance [q-fin], [SDV]Life Sciences [q-bio], [SDE]Environmental Sciences, Conditional efficiency, complementarity, [SHS]Humanities and Social Sciences
Abstract: International audience; In context of global challenges facing agriculture, our article addresses the extent to which the synergistic nature of agroecological innovations may reconcile environmental and technical efficiency of farms. We develop an empirical model, namely conditional efficiency framework, which explicitly accounts for context-dependent drivers like synergy and complementarity of innovations. Using a sample of 567 banana farms in the French West Indies, our estimates confirm the complementarity effect since the joint adoption of agroecological innovations increases the technical efficiency scores much more than other drivers and each of the innovations taken in isolation. We also show that advice and extension services as well as human capital variables are key adoption levers for public policy since they reduce the variability of production and thus the risk associated with the joint adoption of the agroecological innovations.
Published: 2022

5. The subjective experience of young women with non-metastatic breast cancer: the Young Women with Breast Cancer Inventory

Author: Anne Congard, Pascal Antoine, A. Lesur, Laurence Vanlemmens, Véronique Christophe, Emmanuelle Fournier, Christelle Duprez, Site de Recherche Intégrée en Cancérologie (SIRIC-ONCOLille), Université de Lille, Sciences et Technologies-Université de Lille, Sciences Humaines et Sociales-Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER-Université de Lille-UNICANCER-Cancéropole Nord-Ouest-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Laboratoire Sciences Cognitives et Sciences Affectives - UMR 9193 (SCALab), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Psychologie de la Connaissance, du Langage et de l'Émotion (PsyCLÉ), Aix Marseille Université (AMU), Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), UNICANCER, Département de Sénologie, Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER-Université de Lille-UNICANCER, Université Lille Nord de France (COMUE)-UNICANCER-Université Lille Nord de France (COMUE)-UNICANCER-Cancéropole Nord-Ouest-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Sciences Cognitives et Sciences Affectives (SCALab) - UMR 9193 (SCALab), and Université Lille Nord de France (COMUE)-UNICANCER-Université Lille Nord de France (COMUE)-UNICANCER
Subjects: Psychometrics, [SDV]Life Sciences [q-bio], Subjective experience, NEEDS, RECOMMENDATIONS, 0302 clinical medicine, Breast cancer, Quality of life, QUALITY-OF-LIFE, Surveys and Questionnaires, Activities of Daily Living, Adaptation, Psychological, 030212 general & internal medicine, Young adult, PSYCHOLOGICAL DISTRESS, SURVIVORS, General Medicine, 3. Good health, 030220 oncology & carcinogenesis, Female, Psychology, Attitude to Health, Clinical psychology, Adult, PARTNERS, Sexual Behavior, Concurrent validity, Breast Neoplasms, [SDV.CAN]Life Sciences [q-bio]/Cancer, ADJUSTMENT, PATIENT, Negative affectivity, 03 medical and health sciences, Young Adult, Cronbach's alpha, medicine, Body Image, Humans, Research, Public Health, Environmental and Occupational Health, Cancer, Reproducibility of Results, medicine.disease, ONCOLOGY, QUESTIONNAIRES, Health psychology, Socioeconomic Factors, Self Report, Young women
Abstract: International audience; Background: The subjective experience of young women with breast cancer has some particular features linked to the impact of the disease and its treatment on their age-related issues (e.g. desire for a child, couple relationship, career management). Despite these specific concerns, no questionnaire currently targets the young breast cancer patient's quality of life, subjective experience or common problems when facing cancer. This study presents the psychometric validation of an inventory that aimed to measure the impact of breast cancer on the quality of life of young women (
Published: 2015

6. Luminescence et OSL dans une préforme de silice sol-gel dopée Cu+ sous différentes conditions d’irradiation

Author: Capoen, Bruno, El Hamzaoui, Hicham, Bouwmans, Géraud, Ouerdane, Youcef, Boukenter, Aziz, Girard, Sylvain, Marcandella, Claude, Olivier, Duhamel, Crop, Frederik, Sarrazin, Thierry, Bouazaoui, Mohamed, Laboratoire de Physique des Lasers, Atomes et Molécules - UMR 8523 (PhLAM), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Laboratoire Hubert Curien (LHC), Institut d'Optique Graduate School (IOGS)-Université Jean Monnet - Saint-Étienne (UJM)-Centre National de la Recherche Scientifique (CNRS), DAM Île-de-France (DAM/DIF), Direction des Applications Militaires (DAM), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Physique médicale, Service de radiothérapie / curiethérapie, Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER-Université de Lille-UNICANCER-Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER-Université de Lille-UNICANCER, Capoen, Bruno, Laboratoire Hubert Curien [Saint Etienne] (LHC), Institut d'Optique Graduate School (IOGS)-Université Jean Monnet [Saint-Étienne] (UJM)-Centre National de la Recherche Scientifique (CNRS), Université Lille Nord de France (COMUE)-UNICANCER-Université Lille Nord de France (COMUE)-UNICANCER-Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), and Université Lille Nord de France (COMUE)-UNICANCER-Université Lille Nord de France (COMUE)-UNICANCER
Subjects: [PHYS.PHYS.PHYS-OPTICS] Physics [physics]/Physics [physics]/Optics [physics.optics], [PHYS.PHYS.PHYS-OPTICS]Physics [physics]/Physics [physics]/Optics [physics.optics], ComputingMilieux_MISCELLANEOUS
Abstract: National audience
Published: 2014

7. NALCN-mediated sodium influx confers metastatic prostate cancer cell invasiveness

Author: Folcher, Antoine, Gordienko, Dmitri, Iamshanova, Oksana, Bokhobza, Alexandre, Shapovalov, George, Kannancheri-Puthooru, Dheeraj, Mariot, Pascal, Allart, Laurent, Desruelles, Emilie, Spriet, Corentin, Diez, Raquel, Oullier, Thibauld, Marionneau-Lambot, Séverine, Brisson, Lucie, Geraci, Sandra, Impheng, Hathaichanok, Lehen'Kyi, V'Yacheslav, Haustrate, Aurélien, Mihalache, Adriana, Gosset, Pierre, Chadet, Stéphanie, Retif, Stéphanie, Laube, Maryline, Sobilo, Julien, Lerondel, Stéphanie, Villari, Giulia, Serini, Guido, Pla, Alessandra Fiorio, Roger, Sébastien, Fromont-Hankard, Gaelle, Djamgoz, Mustafa, Clezardin, Philippe, Monteil, Arnaud, Prevarskaya, Natalia, Laboratoire de Physiologie Cellulaire : Canaux ioniques, inflammation et cancer - U 1003 (PHYCELL), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Site de Recherche Intégrée en Cancérologie (SIRIC-ONCOLille), Université de Lille, Sciences et Technologies-Université de Lille, Sciences Humaines et Sociales-Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER-Université de Lille-UNICANCER-Cancéropole Nord-Ouest-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Universidad de Extremadura - University of Extremadura (UEX), Cancéropôle du Grand Ouest, Université de Nantes (UN), Nutrition, croissance et cancer (U 1069) (N2C), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiopathologie, diagnostic et traitements des maladies osseuses / Pathophysiology, Diagnosis & Treatments of Bone Diseases (LYOS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Naresuan University, Université catholique de Lille (UCL), EA4245 - Transplantation, Immunologie, Inflammation [Tours] (T2i), Université de Tours (UT), Transgenèse et archivage d'animaux modèles (TAAM), Centre National de la Recherche Scientifique (CNRS), French National Infrastructure for Mouse Phenogenomics (PHENOMIN), Centre d'Imagerie du Petit Animal (CIPA), Université d'Orléans (UO), Università degli studi di Torino = University of Turin (UNITO), Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Imperial College London, Cyprus International University, Institut de Génomique Fonctionnelle (IGF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), LabEx Ion Channels Science and Therapeutics [France], and ANR-11-LABX-0015,ICST,Canaux ioniques d'intérêt thérapeutique(2011)
Subjects: Sodium leak channel, calcium oscillations, invasion, oncochannelopathy, vesicle secretion, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology
Abstract: International audience; There is growing evidence that ion channels are critically involved in cancer cell invasiveness and metastasis. However, the molecular mechanisms of ion signaling promoting cancer behavior are poorly understood and the complexity of the underlying remodeling during metastasis remains to be explored. Here, using a variety of in vitro and in vivo techniques, we show that metastatic prostate cancer cells acquire a specific Na+ /Ca2+ signature required for persistent invasion. We identify the Na+ leak channel, NALCN, which is overexpressed in metastatic prostate cancer, as a major initiator and regulator of Ca2+ oscillations required for invadopodia formation. Indeed, NALCN-mediated Na+ influx into cancer cells maintains intracellular Ca2+ oscillations via a specific chain of ion transport proteins including plasmalemmal and mitochondrial Na+ /Ca2+ exchangers, SERCA and store-operated channels. This signaling cascade promotes activity of the NACLN-colocalized proto-oncogene Src kinase, actin remodeling and secretion of proteolytic enzymes, thus increasing cancer cell invasive potential and metastatic lesions in vivo. Overall, our findings provide new insights into an ion signaling pathway specific for metastatic cells where NALCN acts as persistent invasion controller.
Published: 2023

8. Sol-gel derived ionic copper-doped glasses and microstructured optical fibers: a potential radiation dosimeter

Author: Capoen, Bruno, El Hamzaoui, Hicham, Bigot, Laurent, Bouwmans, Géraud, Ouerdane, Youcef, Boukenter, Aziz, Girard, Sylvain, Chadeyron, Geneviève, Mahiou, Rachid, Crop, Frederik, Thierry, Sarrazin, Bouazaoui, Mohamed, Laboratoire de Physique des Lasers, Atomes et Molécules - UMR 8523 (PhLAM), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Laboratoire Hubert Curien (LHC), Institut d'Optique Graduate School (IOGS)-Université Jean Monnet - Saint-Étienne (UJM)-Centre National de la Recherche Scientifique (CNRS), MI, Institut de Chimie de Clermont-Ferrand (ICCF), Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-SIGMA Clermont (SIGMA Clermont)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-SIGMA Clermont (SIGMA Clermont)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Matériaux Inorganiques (MI), Physique médicale, Service de radiothérapie / curiethérapie, Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER-Université de Lille-UNICANCER-Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER-Université de Lille-UNICANCER, Laboratoire Hubert Curien [Saint Etienne] (LHC), Institut d'Optique Graduate School (IOGS)-Université Jean Monnet [Saint-Étienne] (UJM)-Centre National de la Recherche Scientifique (CNRS), Université Lille Nord de France (COMUE)-UNICANCER-Université Lille Nord de France (COMUE)-UNICANCER-Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université Lille Nord de France (COMUE)-UNICANCER-Université Lille Nord de France (COMUE)-UNICANCER, and Capoen, Bruno
Subjects: [PHYS.PHYS.PHYS-OPTICS] Physics [physics]/Physics [physics]/Optics [physics.optics], [PHYS.PHYS.PHYS-OPTICS]Physics [physics]/Physics [physics]/Optics [physics.optics], ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2014

9. Comprehensive Genome Profiling in Patients With Metastatic Non-Small Cell Lung Cancer: The Precision Medicine Phase II Randomized SAFIR02-Lung Trial

Author: Boyault, Sandrine, Attignon, Valery, Soubeyran, Isabelle, Morel, Alain, Tran-Dien, Alicia, Jacquet, Alexandra, Dall'Olio, Filippo Gustavo, Jimenez, Marta, Soria, Jean-Charles, Besse, Benjamin, Barlesi, Fabrice, Tomasini, Pascale, Karimi, Maryam, Michiels, Stefan, Raimbourg, Judith, Daniel, Catherine, Janicot, Henri, Madroszyk, Anne, Audigier-Valette, Clarisse, Quoix, Elisabeth, Mazieres, Julien, Moro-Sibilot, Denis, Dansin, Eric, Molinier, Olivier, Morel, Hugues, Pichon, Eric, Cortot, Alexis, Otto, Josiane, Chomy, Francois, Souquet, Pierre-Jean, Cloarec, Nicolas, Giroux-Leprieur, Etienne, Bieche, Ivan, Lacroix, Ludovic, Fondation Synergie Lyon Cancer [Lyon], Centre Léon Bérard [Lyon], Institut Bergonié [Bordeaux], UNICANCER, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Centre de Recherche en Cancérologie et Immunologie Intégrée Nantes-Angers (CRCI2NA ), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), Prédicteurs moléculaires et nouvelles cibles en oncologie (PMNCO), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Centre d'Investigation Clinique en Biotherapie des cancers (CIC 1428 , CBT 507 ), Institut Gustave Roussy (IGR)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Multidisciplinary Oncology and Therapeutic Innovations Unit, Hôpital Nord [CHU - APHM], Tarbiat Modares University [Tehran], Service de biostatistique et d'épidémiologie (SBE), Direction de la recherche clinique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Oncostat (U1018 (Équipe 2)), Institut Gustave Roussy (IGR)-Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Institut Curie [Paris], Service de Pneumologie [CHU Clermont-Ferrand], Pôle RHEUNNIRS [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Centre Hospitalier Intercommunal Toulon-La Seyne sur Mer - Hôpital Sainte-Musse, CHU Strasbourg, Service de pneumologie [Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), CHU de Grenoble-Alpes, Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER, Centre Hospitalier Le Mans (CH Le Mans), Intergroupe Francophone de Cancérologie Thoracique [Paris] (IFCT), Intergroupe Francophone de Cancérologie thoracique, Centre Hospitalier Régional d'Orléans (CHRO), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Site de Recherche Intégrée en Cancérologie (SIRIC-ONCOLille), Université de Lille, Sciences et Technologies-Université de Lille, Sciences Humaines et Sociales-Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER-Université de Lille-UNICANCER-Cancéropole Nord-Ouest-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Université Côte d'Azur (UCA), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Centre Hospitalier Henri Duffaut (Avignon), Biomarqueurs et essais cliniques en Cancérologie et Onco-Hématologie (BECCOH), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Saclay, and Département de biologie et pathologie médicales [Gustave Roussy]
Subjects: ErbB Receptors, Lung Neoplasms, Carcinoma, Non-Small-Cell Lung, [SDV]Life Sciences [q-bio], Antineoplastic Combined Chemotherapy Protocols, Mutation, Humans, Receptor Protein-Tyrosine Kinases, Precision Medicine, B7-H1 Antigen
Abstract: International audience; Purpose: Targeted therapies (TT) and immune checkpoint blockers (ICB) have revolutionized the approach to non-small cell lung cancer (NSCLC) treatment in the era of precision medicine. Their impact as switch maintenance therapy based on molecular characterization is unknown.Patients and Methods: SAFIR02-Lung was an open-label, randomized, phase II trial, involving 33 centers in France. We investigated eight TT (substudy-1) and one ICB (substudy-2), compared with standard-of-care as a maintenance strategy in patients with advanced EGFR, ALK wild-type (wt) NSCLC without progression after first-line chemotherapy, based on high-throughput genome analysis. The primary outcome was progression-free survival (PFS).Results: Among the 175 patients randomized in substudy-1, 116 received TT (selumetinib, vistusertib, capivasertib, AZD4547, AZD8931, vandetanib, olaparib, savolitinib) and 59 standard-of-care. Median PFS was 2.7 months [95% confidence interval (CI), 1.6-2.9] with TT versus 2.7 months (1.6-4.1) with standard-of-care (HR, 0.97; 95% CI, 0.7-1.36; P = 0.87). There were no significant differences in PFS within any molecular subgroup. In substudy-2, 183 patients were randomized, 121 received durvalumab and 62 standard-of-care. Median PFS was 3.0 months (2.3-4.4) with durvalumab versus 3.0 months (2.0-5.1) with standard-of-care (HR, 0.86; 95% CI, 0.62-1.20; P = 0.38). Preplanned subgroup analysis showed an enhanced benefit with durvalumab in patients with PD-L1 tumor proportion score (TPS) >= 1%, (n = 29; HR, 0.29; 95% CI, 0.11-0.75) as compared with PD-L1 < 1% (n = 31; HR, 0.71; 95% CI, 0.31-1.60; P-interaction = 0.036). Conclusions: Molecular profiling can feasibly be implemented to guide treatment choice for the maintenance strategy in EGFR/ALK wt NSCLC; in this study it did not lead to substantial treatment benefits beyond durvalumab for PD-L1 >= 1 patients.
Published: 2022

10. Traitement du cancer de la prostate localisé à l’apex par curiethérapie ou ultrasons focalisés

Author: G. Fiard, S. Crouzet, P. Graff-Cailleaud, Service d'urologie [CHU Grenoble], Centre Hospitalier Universitaire [Grenoble] (CHU), Service de radiothérapie / curiethérapie, Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER-Université de Lille-UNICANCER, and Université Lille Nord de France (COMUE)-UNICANCER-Université Lille Nord de France (COMUE)-UNICANCER
Subjects: 03 medical and health sciences, 0302 clinical medicine, 030220 oncology & carcinogenesis, Urology, [SDV]Life Sciences [q-bio], 030218 nuclear medicine & medical imaging
Abstract: Resume Nous rapportons le cas d’un patient de 64 ans presentant un cancer de la prostate de bon pronostic localise au niveau de l’apex, visible en IRM, pour lequel la possibilite d’un traitement par curietherapie exclusive ou ultrasons focalisee est discutee. Les indications, resultats et limites des deux techniques sont presentes.
Published: 2020

11. Semaphorin7A regulates neuroglial plasticity in the adult hypothalamic median eminence

Author: Parkash, J, Messina, A, Langlet, F, Cimino, I, Loyens, A, Mazur, D, Gallet, S, Balland, E, Malone, SA, Pralong, F, Cagnoni, G, Schellino, R, De Marchis, S, Mazzone, M, Pasterkamp, RJ, Tamagnone, L, Prevot, V, Giacobini, P, Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U1172 Inserm - U837 (JPArc), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Lille Nord de France (COMUE)-Université de Lille, Institut de médecine predictive et de recherche thérapeutique (IMPRT), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université Lille Nord de France (COMUE)-UNICANCER-Université Lille Nord de France (COMUE)-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Faculty of Biology and Medicine [Lausanne, Switzerland], Université de Lausanne (UNIL), Candiolo Cancer Institute [Candiolo, Italie], Università degli studi di Torino (UNITO), Vesalius Research Center [Louvain, Belgique], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Brain Centre Rudolf Magnus [Utrecht], University Medical Center [Utrecht], Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 (JPArc), Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Université de Lille-UNICANCER-Université de Lille-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Université de Lausanne = University of Lausanne (UNIL), Università degli studi di Torino = University of Turin (UNITO), and Prevot, Vincent
Subjects: endocrine system, Chemistry(all), Ovariectomy, Blotting, Western, Fluorescent Antibody Technique, Enzyme-Linked Immunosorbent Assay, PLEXINC1, Semaphorins, Physics and Astronomy(all), Real-Time Polymerase Chain Reaction, Article, ACTIN, AXON GUIDANCE, Rats, Sprague-Dawley, Mice, Antigens, CD, Image Processing, Computer-Assisted, Journal Article, Animals, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Progesterone, SEMAPHORIN 7A, GENE-EXPRESSION, Analysis of Variance, Science & Technology, Neuronal Plasticity, RECEPTOR, Estradiol, Biochemistry, Genetics and Molecular Biology(all), Research Support, Non-U.S. Gov't, Median Eminence, TGF-BETA, Flow Cytometry, Immunohistochemistry, GNRH NEURONS, Rats, Multidisciplinary Sciences, ESTROUS-CYCLE, HORMONE NERVE-TERMINALS, GONADOTROPIN, GnRH, Science & Technology - Other Topics, RAT, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Settore BIO/17 - ISTOLOGIA, Neuroglia
Abstract: Reproductive competence in mammals depends on the projection of gonadotropin-releasing hormone (GnRH) neurons to the hypothalamic median eminence (ME) and the timely release of GnRH into the hypothalamic–pituitary–gonadal axis. In adult rodents, GnRH neurons and the specialized glial cells named tanycytes periodically undergo cytoskeletal plasticity. However, the mechanisms that regulate this plasticity are still largely unknown. We demonstrate that Semaphorin7A, expressed by tanycytes, plays a dual role, inducing the retraction of GnRH terminals and promoting their ensheathment by tanycytic end feet via the receptors PlexinC1 and Itgb1, respectively. Moreover, Semaphorin7A expression is regulated during the oestrous cycle by the fluctuating levels of gonadal steroids. Genetic invalidation of Semaphorin7A receptors in mice induces neuronal and glial rearrangements in the ME and abolishes normal oestrous cyclicity and fertility. These results show a role for Semaphorin7A signalling in mediating periodic neuroglial remodelling in the adult ME during the ovarian cycle., Reproduction in mammals is dependent on the function of specific neurons that secrete gonadotropin-releasing hormone (GnRH) and project their axons to the median eminence (ME) of the hypothalamus. Here the authors show that Semaphorin7A signaling plays a role in mediating the plasticity of GnRH axon terminals and tanycytes in the ME.
Published: 2020

12. The Role of a Proprotein Convertase Inhibitor in Reactivation of Tumor-Associated Macrophages and Inhibition of Glioma Growth

Author: Rose, Mélanie, Duhamel, Marie, Aboulouard, Soulaimane, Kobeissy, Firas, Le Rhun, Emilie, Desmons, Annie, Tierny, Dominique, Fournier, Isabelle, Rodet, Franck, SALZET, Michel, Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U 1192 (PRISM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Site de Recherche Intégrée en Cancérologie (SIRIC-ONCOLille), Université de Lille, Sciences et Technologies-Université de Lille, Sciences Humaines et Sociales-Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER-Université de Lille-UNICANCER-Cancéropole Nord-Ouest-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Department of Psychiatry [Gainesville, FL, USA] (McKnight Brain Institute), University of Florida [Gainesville] (UF), SALZET, Michel, Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Université Lille Nord de France (COMUE)-UNICANCER-Université Lille Nord de France (COMUE)-UNICANCER-Cancéropole Nord-Ouest-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), INSERM, Université de Lille, Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U1192, Oncovet, and McKnight Brain Institute [Gainesville] [UF|MBI]
Subjects: glioma, immunotherapy, macrophages, mass spectrometry-based proteomic, proprotein convertases, temozolomide, [SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio], lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, lcsh:RC254-282, Article
Abstract: Tumors are characterized by the presence of malignant and non-malignant cells, such as immune cells including macrophages, which are preponderant. Macrophages impact the efficacy of chemotherapy and may lead to drug resistance. In this context and based on our previous work, we investigated the ability to reactivate macrophages by using a proprotein convertases inhibitor. Proprotein convertases process immature proteins into functional proteins, with several of them having a role in immune cell activation and tumorigenesis. Macrophages were treated with a peptidomimetic inhibitor targeting furin, PC1/3, PC4, PACE4, and PC5/6. Their anti-glioma activity was analyzed by mass spectrometry-based proteomics and viability assays in 2D and 3D in vitro cultures. Comparison with temozolomide, the drug used for glioma therapy, established that the inhibitor was more efficient for the reduction of cancer cell density. The inhibitor was also able to reactivate macrophages through the secretion of several immune factors with antitumor properties. Moreover, two proteins considered as good glioma patient survival indicators were also identified in 3D cultures treated with the inhibitor. Finally, we established that the proprotein convertases inhibitor has a dual role as an anti-glioma drug and anti-tumoral macrophage reactivation drug. This strategy could be used together with chemotherapy to increase therapy efficacy in glioma., Graphical Abstract, Despite significant advances in cancer treatment, resistance to applied therapy remains a major problem. Salzet and colleagues established that inhibition of proprotein convertases exerts a dual activity at the same time by its anti-tumoral effect on glioma cells and by its ability to switch macrophages to an anti-tumoral phenotype.
Published: 2020

13. Lorlatinib for advanced ALK and ROS1+non-small cell lung cancer (NSCLC): Efficacy and treatment sequences in the IFCT-1803 LORLATU expanded access program (EAP) cohort

Author: Julien Mazieres, Bertrand Mennecier, Jacques Cadranel, Hélène Doubre, Renaud Descourt, Pascale Dubray-Longeras, P. Missy, Denis Moro-Sibilot, Sophie Schneider, Franck Morin, Virginie Westeel, Benjamin Besse, Michael Duruisseaux, J. Otto, Simon Baldacci, Nicolas Girard, Sigolene Galland-Girodet, Virginie Avrillon, Charles Ricordel, Isabelle Monnet, Site de Recherche Intégrée en Cancérologie (SIRIC-ONCOLille), Université de Lille, Sciences et Technologies-Université de Lille, Sciences Humaines et Sociales-Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université Lille Nord de France (COMUE)-UNICANCER-Université Lille Nord de France (COMUE)-UNICANCER-Cancéropole Nord-Ouest-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Léon Bérard [Lyon], Prédicteurs moléculaires et nouvelles cibles en oncologie (PMNCO), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Institut Gustave Roussy (IGR), 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), Sorbonne Université (SU), Sorbonne Université - Faculté de médecine Pitié Salpétrière, 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)-Sorbonne Université (SU), CHU Pontchaillou [Rennes], Chemistry, Oncogenesis, Stress and Signaling (COSS), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Pneumologie [CHI Créteil], CHI Créteil, Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), Université Côte d'Azur (UCA)-UNICANCER, Intergroupe Francophone de Cancérologie Thoracique [Paris] (IFCT), Intergroupe Francophone de Cancérologie thoracique, Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Institut Curie [Paris], IFCT, Pharmaceutical/Biotech Company, Université de Lille-UNICANCER-Université de Lille-UNICANCER-Cancéropole Nord-Ouest-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université - Faculté de médecine [CHU Pitié Salpétrière], Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), UNICANCER-Université Côte d'Azur (UCA), 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), and Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)
Subjects: Cancer Research, medicine.drug_class, business.industry, non-small cell lung cancer (NSCLC), [SDV.CAN]Life Sciences [q-bio]/Cancer, medicine.disease, Lorlatinib, Tyrosine-kinase inhibitor, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, Oncology, Refractory, 030220 oncology & carcinogenesis, Expanded access, Cohort, Cancer research, medicine, ROS1, business, ComputingMilieux_MISCELLANEOUS, 030215 immunology
Abstract: 9615 Background: Lorlatinib, a third-generation tyrosine kinase inhibitor targeting ALK and ROS1, has been made available in France starting October 2015 through an EAP for advanced, refractory, ALK+ NSCLC after the failure of chemotherapy and TKIs. Besides the landmark, multi-cohort phase II trial that assessed lorlatinib in ALK+ NSCLC, real-life evidence regarding the efficacy and safety, as well as treatment sequences including lorlatinib, is lacking. Methods: We report the cohort of consecutive patients with advanced, refractory, ALK or ROS1+ NSCLC enrolled in the French EAP of lorlatinib from October 2015 to October 2019. Data were collected from medical records by French Cooperative Thoracic Intergroup (IFCT) research study assistants on site. Primary endpoint was progression-free survival. Results: 200 patients were included: 143 (71.5%) ALK+, 57 (28.5%) ROS1+, 87 (44%) men, 127 (66%) never-smokers, and 167 (85%) stage IV disease. Mean age was 59 years. At the time of initiation of lorlatinib, 146 (74%) patients had Central Nervous System (CNS) disease (78 % for ALK+, 63% for ROS1+), 131 (76%) were PS 0/1. Lorlatinib was delivered as 2nd/3rd/4th/5th+ line in 3%/17%/27%/53%of ALK+ patients and in 30%/30%/16%/24%of ROS1+ patients, respectively. 150 (75%), 185 (93%), 138 (69%), and 80 (40%) patients had received prior chemotherapy, crizotinib, 2nd generation TKIs, and brain radiotherapy, respectively. Median PFS and OS from the initiation of lorlatinib were 11.8 (95% CI 7.3-14.6) months and NR (95% CI 18.6-NR) months, respectively for ALK+ patients and 7.6 (95% CI 6.2-10.2) months and 20.9 (95% CI 10.0-NR) months, respectively for ROS1+ patients. ORR and DCR were 46.2% (95% CI 37.6-54.7) and 86.2% (95% CI 80.2-92.1), respectively for ALK+ patients and 47.1% (95% CI 33.4-60.8) and 88.2% (95% CI 79.4-97.1), respectively for ROS1+ patients. CNS ORR was 41.7% (95% CI 33.3-50.1) and 37.7% (95% CI 24.7-50.8), respectively. With a median follow-up of 15.6 (95% CI 14.0-17.6) months, progression under lorlatinib treatment was observed in 71 (50%) ALK+ patients and 35 (61%) ROS1+ patients, and CNS progression in 24 (34%) and 8 (23%) patients, respectively. The safety profile of lorlatinib was consistent with published data. Conclusions: These real-life results confirmed lorlatinib as a major treatment option for patients with advanced refractory ALK or ROS1+ NSCLC.
Published: 2020

14. Skipping Nonsense to Maintain Function: The Paradigm of BRCA2 Exon 12

Author: Romy L. S. Mesman, Marine Guillaud-Bataille, Mélanie Léoné, Capucine Delnatte, Aurélie Drouet, Alexandra Martins, Hélène Tubeuf, Laëtitia Meulemans, Omar Soukarieh, Pascaline Gaildrat, Violaine Bourdon, Nadia Boutry-Kryza, Sophie Krieger, Myriam Bronner, Fabienne Calléja, Johanna Sokolowska, Maud Privat, Dominique Stoppa-Lyonnet, Harry Vrieling, Maaike P.G. Vreeswijk, Françoise Révillion, Sandrine M. Caputo, Claude Houdayer, Sarab Lizard, Charlotte Grout, Françoise Bonnet-Dorion, Lisa Golmard, Virginie Caux-Moncoutier, Paul Vilquin, Virginie Guibert, Thierry Frebourg, Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Center for Human and Clinical Genetics, Leiden University Medical Center (LUMC), Service de Génétique Oncologique, Institut Curie [Paris], Université Paris sciences et lettres (PSL), Institut Gustave Roussy (IGR), Unité Mixte de Génétique Constitutionnelle des Cancers Fréquents, Centre Léon Bérard [Lyon]-Hospices Civils de Lyon (HCL), Hospices Civils de Lyon (HCL), Service de Génétique [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Laboratoire d'Oncologie Moléculaire Humaine, Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université Lille Nord de France (COMUE)-UNICANCER-Université Lille Nord de France (COMUE)-UNICANCER, Service de génétique médicale - Unité de génétique clinique [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Validation et identification de nouvelles cibles en oncologie (VINCO), Institut Bergonié [Bordeaux], UNICANCER-UNICANCER-Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Service d'Oncologie Génétique, de Prévention et Dépistage, Service de Biopathologie [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER, Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de génétique et biologie des cancers (U830), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de génétique [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Universiteit Leiden-Universiteit Leiden, Université de Lille-UNICANCER-Université de Lille-UNICANCER, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), UNICANCER-Université Lille Nord de France (COMUE)-UNICANCER-Université Lille Nord de France (COMUE), Centre hospitalier universitaire de Nantes (CHU Nantes), Imagerie Moléculaire et Stratégies Théranostiques - Clermont Auvergne (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Service de biochimie [CHU Trousseau], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Trousseau [APHP]
Subjects: 0301 basic medicine, Genetics, Cancer Research, media_common.quotation_subject, Nonsense, Alternative splicing, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Biology, 3. Good health, 03 medical and health sciences, Exon, 030104 developmental biology, 0302 clinical medicine, Oncology, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, 030220 oncology & carcinogenesis, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], RNA splicing, splice, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Allele, Gene, media_common, Minigene
Abstract: Germline nonsense and canonical splice site variants identified in disease-causing genes are generally considered as loss-of-function (LoF) alleles and classified as pathogenic. However, a fraction of such variants could maintain function through their impact on RNA splicing. To test this hypothesis, we used the alternatively spliced BRCA2 exon 12 (E12) as a model system because its in-frame skipping leads to a potentially functional protein. All E12 variants corresponding to putative LoF variants or predicted to alter splicing (n = 40) were selected from human variation databases and characterized for their impact on splicing in minigene assays and, when available, in patient lymphoblastoid cell lines. Moreover, a selection of variants was analyzed in a mouse embryonic stem cell–based functional assay. Using these complementary approaches, we demonstrate that a subset of variants, including nonsense variants, induced in-frame E12 skipping through the modification of splice sites or regulatory elements and, consequently, led to an internally deleted but partially functional protein. These data provide evidence, for the first time in a cancer-predisposition gene, that certain presumed null variants can retain function due to their impact on splicing. Further studies are required to estimate cancer risk associated with these hypomorphic variants. More generally, our findings highlight the need to exercise caution in the interpretation of putative LoF variants susceptible to induce in-frame splicing modifications. Significance: This study presents evidence that certain presumed loss-of-function variants in a cancer predisposition gene can retain function due to their direct impact on RNA splicing.
Published: 2020

15. Pooled overall survival and safety data from the pivotal phase II studies (NP28673 and NP28761) of alectinib in ALK-positive non-small-cell lung cancer

Author: Walter Bordogna, Sanjay Popat, Bogdana Balas, Emmanuel Mitry, Luigi De Petris, Fabrice Barlesi, Alice T. Shaw, Ramaswamy Govindan, James Chih-Hsin Yang, Dong Wan Kim, Shirish M. Gadgeel, Barbara Muller, Anne-Marie C. Dingemans, Peter N. Morcos, Jin Seok Ahn, Eric Dansin, Lucio Crinò, Sai-Hong Ignatius Ou, Hervé Lena, RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, Pulmonologie, MUMC+: MA Med Staf Spec Longziekten (9), Assistance Publique - Hôpitaux de Marseille (APHM), Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Department of Microbiology, Chang Won National University, Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht], Département de Cancérologie Générale [Lille], Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER-Université de Lille-UNICANCER, Institut Curie [Paris], Savoirs dans l'espace anglophone : représentations, culture, histoire (SEARCH), Université de Strasbourg (UNISTRA), Roche, Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), Signalisation et Réponses aux Agents Infectieux et Chimiques (SeRAIC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-IFR140, UNICANCER-Université Lille Nord de France (COMUE)-UNICANCER-Université Lille Nord de France (COMUE), and Université Lille Nord de France (COMUE)-UNICANCER-Université Lille Nord de France (COMUE)-UNICANCER
Subjects: 0301 basic medicine, Alectinib, Oncology, Male, Cancer Research, Lung Neoplasms, ALK+, [SDV]Life Sciences [q-bio], Peripheral edema, NSCLC, 0302 clinical medicine, alk, Piperidines, Carcinoma, Non-Small-Cell Lung, Anaplastic Lymphoma Kinase, education.field_of_study, Prognosis, 3. Good health, Survival Rate, 030220 oncology & carcinogenesis, Female, medicine.symptom, medicine.drug, Pulmonary and Respiratory Medicine, safety, medicine.medical_specialty, Nausea, overall survival, Population, Carbazoles, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Pooled analysis, 03 medical and health sciences, Internal medicine, medicine, Humans, Lung cancer, education, Adverse effect, Protein Kinase Inhibitors, Aged, crizotinib, Crizotinib, business.industry, medicine.disease, Confidence interval, 030104 developmental biology, business, Follow-Up Studies
Abstract: International audience; Objectives - A pooled analysis of two open-label phase II studies of alectinib (NP28673 [NCT01801111] and NP28761 [NCT01871805]) demonstrated clinical activity in patients with advanced, anaplastic lymphoma kinase-positive (ALK+) non-small-cell lung cancer (NSCLC) previously treated with crizotinib. Longer-term and final pooled analyses of overall survival (OS) and safety data from the two studies are presented here. Patients and methods - The pooled population totaled 225 patients (NP28673: n = 138, NP28761: n = 87) who received 600 mg oral alectinib twice daily until disease progression, death, or withdrawal. OS was defined as the time from date of first treatment to date of death, regardless of cause. OS was estimated using Kaplan-Meier methodology, with 95% confidence intervals (CIs) determined using the Brookmeyer-Crowley method. Safety was assessed through adverse event (AE) reporting. Results - Baseline characteristics were generally comparable between the studies. At final data cutoff (October 27, 2017 [NP28673], October 12, 2017 [NP28761]; median pooled follow-up time, ∼21 months), 53.3% of patients had died, 39.1% were alive and in follow-up, and 7.6% had withdrawn consent or were lost to follow-up. Alectinib demonstrated a median OS of 29.1 months (95% CI 21.3-39.0). No new or unexpected safety findings were observed. The most common all-grade AEs included constipation (39.1%), fatigue (35.1%), peripheral edema (28.4%), myalgia (26.2%), and nausea (24.0%). Conclusion - Updated results from this pooled analysis further demonstrate that alectinib has robust clinical activity and a manageable safety profile in patients with advanced, ALK+ NSCLC pretreated with crizotinib.
Published: 2020

16. Aggressiveness potential of spontaneous canine mucosal melanoma can dictate distinct cancer stem cell compartment behaviors in regard to their initial size and expansion abilities

Author: Zacharie Segaoula, Dominique Tierny, Bruno Quesnel, Yasmine Touil, Sylvie Galiègue-Zouitina, Xavier Thuru, Unité de Pharmacologie Chimique et Génétique (UPCG - UMR_S 640/UMR 8151), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Institut des sciences du Médicament -Toxicologie - Chimie - Environnement (IFR71), Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Institut de Chimie du CNRS (INC), Lille Neurosciences & Cognition - U 1172 (LilNCog (ex-JPARC)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 (CANTHER), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Site de Recherche Intégrée en Cancérologie (SIRIC-ONCOLille), Université de Lille, Sciences et Technologies-Université de Lille, Sciences Humaines et Sociales-Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université Lille Nord de France (COMUE)-UNICANCER-Université Lille Nord de France (COMUE)-UNICANCER-Cancéropole Nord-Ouest-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut des sciences du Médicament -Toxicologie - Chimie - Environnement (IFR71), Institut de Recherche pour le Développement (IRD)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Lille Neurosciences & Cognition - U 1172 (LilNCog), and Université de Lille-UNICANCER-Université de Lille-UNICANCER-Cancéropole Nord-Ouest-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)
Subjects: 0301 basic medicine, Time Factors, comparative oncology, Carcinogenesis, [SDV]Life Sciences [q-bio], Cell, Mice, Nude, Mice, SCID, Biology, Phosphatidylinositol 3-Kinases, 03 medical and health sciences, Dogs, 0302 clinical medicine, Original Research Reports, stem cells, Cancer stem cell, Cell Line, Tumor, Spheroids, Cellular, melanoma, Biomarkers, Tumor, medicine, Canine Melanoma, Animals, Neoplasm Invasiveness, neoplasms, PI3K/AKT/mTOR pathway, ComputingMilieux_MISCELLANEOUS, Cell Proliferation, Cell Size, Mucous Membrane, Melanoma, Cell Cycle, Mucosal melanoma, Cell Biology, Hematology, medicine.disease, 3. Good health, 030104 developmental biology, medicine.anatomical_structure, Cutaneous melanoma, Neoplastic Stem Cells, Cancer research, ATP-Binding Cassette Transporters, Stem cell, Proto-Oncogene Proteins c-akt, 030217 neurology & neurosurgery, Signal Transduction, Developmental Biology
Abstract: Mucosal melanoma represents one of the most highly metastatic and aggressive subtypes of melanoma. The biology of mucosal melanoma is poorly documented, and the lack of experimental models makes it difficult to design and test new therapies. Dogs are frequently affected by melanomas of the oral cavity, making spontaneous canine melanoma a potentially predictable model for their human counterpart. We recently established and characterized two new canine mucosal melanoma cell lines named OCR_OCMM1 and OCR_OCMM2. Here, we identified quiescent cancer stem cell (CSC) subpopulations in both canine cell lines that displayed similarities to human quiescent CSCs: canine melanoma CSCs had the ability to self-renew, produced nonstem cell (SC) progeny, and formed melanospheres that recapitulated the phenotypic profile of the parental tumor. These CSCs also formed melanoma in immunodeficient mice, and the inhibition of PI3K/AKT signaling expanded the CSC pool. A subset of non-CSCs transitioned to become CSCs. OCR_OCMM1 and OCR_OCMM2 displayed different CSC compartment behaviors in regard to their initial size and expansion abilities. Collectively, this study showed that the OCR_OCMM1 and OCR_OCMM2 canine melanoma cell lines are powerful cellular tools to study melanoma SCs, not only for mucosal but also for the more common human cutaneous melanoma.
Published: 2020

17. Fine-scale geographical distribution and ecological risk factors for Crohn's disease in France (2007-2014)

Author: Michaël Genin, Grégoire Ficheur, Florent Occelli, Luc Dauchet, Cécile Vignal, Hélène Sarter, Mathilde Body-Malapel, Corinne Gower-Rousseau, Guillaume Savoye, Benjamin Pariente, Jonathan Giovannelli, Mathurin Fumery, Santé publique : épidémiologie et qualité des soins-EA 2694 (CERIM), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Unité de Méthodologie et Biostatistique [Centre Oscar Lambret, Lille], Centre Oscar Lambret [Lille], Registre EPIMAD, CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Amiens-Picardie-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service d'Hépato Gastroenterologie [CHU Amiens-Picardie], CHU Amiens-Picardie, Impact de l'environnement chimique sur la santé humaine (IMPECS), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille, Service d'Hépato-Gastroentérologie [Rouen], Hôpital Charles Nicolle [Rouen]-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Nutrition, inflammation et dysfonctionnement de l'axe intestin-cerveau (ADEN), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute for Research and Innovation in Biomedicine (IRIB), UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Normandie Université (NU)-Normandie Université (NU), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement (Inserm U1167 - RID-AGE - Institut Pasteur), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service d'Epidémiologie et de Santé Publique [Lille], Lille Inflammation Research International Center (LIRIC), Normandie Université (NU)-Normandie Université (NU)-Hôpital Charles Nicolle [Rouen]-CHU Rouen, Evaluation des technologies de santé et des pratiques médicales - ULR 2694 (METRICS), Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université Lille Nord de France (COMUE)-UNICANCER-Université Lille Nord de France (COMUE)-UNICANCER, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Amiens-Picardie, Impact de l'environnement chimique sur la santé humaine - ULR 4483 (IMPECS), Service d'Hépato-Gastroentérologie [CHU Rouen], Normandie Université (NU)-Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 (RID-AGE), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Institute for Translational Research in Inflammation - U 1286 (INFINITE (Ex-Liric)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Lille, Inserm, Université de Lille, Evaluation des technologies de santé et des pratiques médicales - ULR 2694 [METRICS], Impact de l'environnement chimique sur la santé humaine - ULR 4483 [IMPECS], Université de Rouen Normandie [UNIROUEN], Lille Inflammation Research International Center - U 995 [LIRIC], Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 [RID-AGE], Université de Lille-UNICANCER-Université de Lille-UNICANCER, Hôpital Charles Nicolle [Rouen], Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, and Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Adult, Male, Adolescent, Databases, Factual, Urban Population, Social Determinants of Health, Disease, Environment, Spatial distribution, History, 21st Century, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Crohn Disease, Risk Factors, Urbanization, Prevalence, Humans, Medicine, Pharmacology (medical), 030212 general & internal medicine, Child, Aged, Aged, 80 and over, Geography, Hepatology, business.industry, Infant, Newborn, Gastroenterology, Infant, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Middle Aged, Patient Discharge, Confidence interval, 3. Good health, Spatial heterogeneity, Ascendant, Social deprivation, Socioeconomic Factors, Child, Preschool, Relative risk, Female, 030211 gastroenterology & hepatology, France, business, Demography
Abstract: BACKGROUND: Geographical variations in Crohn's disease (CD) suggest that the environment has a role in the pathogenesis of this condition. OBJECTIVE: To describe the spatial distribution and the clustering of CD cases in France, and to assess the relationship between the prevalence of CD and environmental risk factors. METHODS: We identified all patients with CD included in the French hospital discharge database from 2007 to 2014. Age- and gender-smoothed standardised prevalence ratios over this period were computed for 5610 spatial units. An ecological regression analysis was used to assess the relationship between the risk of CD and ecological variables (health care, latitude, socio-economic deprivation, urbanisation, proportion of agricultural surfaces and density of industries). Local spatial clusters of high-CD prevalence were searched for using elliptic spatial scan statistics and characterised in a hierarchical ascendant classification based on the same ecological variables. RESULTS: About 129 089 patients with CD were identified, yielding a crude prevalence of 203 per 100 000 inhabitants. The overall spatial heterogeneity was statistically significant (P
Published: 2020

18. Single-arm phase II trial to evaluate efficacy and tolerance of regorafenib monotherapy in patients over 70 with previously treated metastatic colorectal adenocarcinoma FFCD 1404 - REGOLD

Author: Gaetan Des Guetz, Thomas Aparicio, Denis Smith, Bruno Valenza, Nathalie Baize, Côme Lepage, Catherine Delbaldo, Denis Père Verge, Olivier Romano, Frédéric Pamoukdjian, Emmanuelle Norguet Monnereau, Anthony Dohan, Claire Falandry, L. Cany, Ariane Darut-Jouve, Christine Le Foll, Pascal Artru, Yves Rinaldi, Carole Monterymard, E. Maillard, Meher Ben Abdelghani, Faiza Khemissa Akouz, Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Clinique Drévon, Service de hépato-gastro-entérologie - cancérologie digestive [CH de Perpignan], Centre Hospitalier Saint Jean de Perpignan, Fédération Francophone de la Cancérologie Digestive, FFCD, Service Biostatistiques et Informatique Médicale (CHU de Dijon) (DIM), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Clinique Jean-Mermoz, Hôpital privé Jean Mermoz, Polyclinique Francheville, Site de Recherche Intégrée en Cancérologie (SIRIC-ONCOLille), Université de Lille, Sciences et Technologies-Université de Lille, Sciences Humaines et Sociales-Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université Lille Nord de France (COMUE)-UNICANCER-Université Lille Nord de France (COMUE)-UNICANCER-Cancéropole Nord-Ouest-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Groupe Hospitalier Diaconesses Croix Saint-Simon, Laboratoire de Biologie Moléculaire de la Cellule (LBMC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), CRLCC Paul Strauss, IRCER - Axe 1 : procédés céramiques (IRCER-AXE1), Institut de Recherche sur les CERamiques (IRCER), Institut des Procédés Appliqués aux Matériaux (IPAM), Université de Limoges (UNILIM)-Université de Limoges (UNILIM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut des Procédés Appliqués aux Matériaux (IPAM), Université de Limoges (UNILIM)-Université de Limoges (UNILIM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Service de gastro-entérologie (Hôpital Européen de Marseille), Hôpital Européen [Fondation Ambroise Paré - Marseille], Service d'Oncologie médicale [CHU Limoges], CHU Limoges, Service d'hépato-gastroentérologie et cancérologie digestive (CHU de Dijon), Institut de Cancérologie de Bourgogne, Hôpital privé Jean Mermoz [Lyon], Clinique Francheville [Périgueux], Université de Lille-UNICANCER-Université de Lille-UNICANCER-Cancéropole Nord-Ouest-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Hospitalier Intercommunal Fréjus - St Raphaël (CHI Fréjus - St Raphaël), Grand Hôpital de l'Est Francilien (GHEF), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Hôpital de la Timone [CHU - APHM] (TIMONE), CHU Bordeaux [Bordeaux], Hôpital Européen de Marseille (HEM), Service de Gastro entérologie [Hôpital Paris Saint-Joseph], Hôpital Paris Saint-Joseph, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Centre Hospitalier Annecy-Genevois [Saint-Julien-en-Genevois], Hôpital Cochin [AP-HP], Hôpital Dupuytren [CHU Limoges], Hôpital Avicenne [AP-HP], Equipe EPICAD (LNC - U1231), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Agro Dijon, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Agro Dijon, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), CCSD, Accord Elsevier, École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: medicine.medical_specialty, Colorectal cancer, Pyridines, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Adenocarcinoma, Gastroenterology, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Quality of life, Regorafenib, Internal medicine, medicine, Clinical endpoint, Humans, 030212 general & internal medicine, Adverse effect, Chemotherapy, business.industry, Phenylurea Compounds, medicine.disease, 3. Good health, [SDV] Life Sciences [q-bio], Diarrhea, Oncology, chemistry, 030220 oncology & carcinogenesis, Toxicity, Quality of Life, Geriatrics and Gerontology, medicine.symptom, business, Colorectal Neoplasms
Abstract: International audience; BACKGROUND: Regorafenib significantly increases overall survival (OS) in patients with metastatic colorectal cancer previously treated but gives toxicities. OBJECTIVES: to assess the efficacy and safety of regorafenib at it's approved dose in the older population. PATIENTS AND METHODS: This multicenter single-arm phase II enrolled patients ≥70 years old after the failure of fluoropyrimidine-based chemotherapy, anti-VEGF, and anti-EGFR treatment. The primary endpoint was disease control rate (DCR) 2 months after initiation of regorafenib (160 mg/day, 3 weeks on/1 week off). RESULTS: Forty-three patients were enrolled, with a median age of 77 years. The 2 months DCR was 31.4% in the 35 evaluable patients. For the 42 patients that received at least one dose of regorafenib, median progression-free survival and OS were 2.2 and 7.5 months. The median time to autonomy degradation and quality of life degradation was 3.1 and 3.2 months, respectively. A grade 3-4 treatment-related adverse events was observed in 35/42 patients, notably: fatigue (45.2%), hand-foot skin reaction (19.0%), hypertension (21.4%), and diarrhea (7.1%). There is a trend to achieve DCR in patients ≤80 years and a trend to discontinue the study due to toxicity in patients with ECOG ≥1, over 80 years and with impaired baseline autonomy. CONCLUSION: Treatment with regorafenib in pretreated patients ≥70 years is feasible and demonstrate similar efficacy that was observed in previous studies in young patients. Fatigue is the most frequent severe adverse event. However, caution should be taken for older patients with ECOG ≥1, over 80 years, and with impaired baseline autonomy.
Published: 2020

19. Novel diagnostic tool for prediction of variant spliceogenicity derived from a set of 395 combined in silico/in vitro studies: an international collaborative effort

Author: Gérald Le Gac, Alexandra Martins, Pascaline Gaildrat, Florence Coulet, Françoise Revillon, Antoine Rousselin, Sandrine M. Caputo, Marine Guillaud-Bataille, Chandran Ka, Mélanie Léoné, Nadia Boutry-Kryza, Virginie Caux-Moncoutier, Claude Férec, Capucine Delnatte, Danielle Muller, Grégoire Davy, Amanda B. Spurdle, Maria Rossing, Raphaël Leman, Yann Fichou, Michael T. Parsons, Barbara Wappenschmidt, Violaine Bourdon, Joanna Sokolowska, Nicolas Sevenet, Claude Houdayer, M.-P. Audrézet, Brigitte Bressac-de Paillerets, Françoise Bonnet-Dorion, Sylvie Mazoyer, Gaia Castelain, Sophie Krieger, Laurent Castera, Etienne Rouleau, Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Génétique, génomique fonctionnelle et biotechnologies (UMR 1078) (GGB), EFS-Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Unité de génétique et biologie des cancers (U830), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5), Université Sorbonne Paris Cité (USPC), Institut Curie [Paris], Unité Mixte de Génétique Constitutionnelle des Cancers Fréquents, Centre Léon Bérard [Lyon]-Hospices Civils de Lyon (HCL), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Validation et identification de nouvelles cibles en oncologie (VINCO), Institut Bergonié [Bordeaux], UNICANCER-UNICANCER-Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Génétique (Biologie pathologie), Département de biologie et pathologie médicales [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), University Hospital of Cologne [Cologne], IT University of Copenhagen (ITU), Centre Paul Strauss, CRLCC Paul Strauss, Laboratoire d'oncogénétique moléculaire, Unite d'Oncogenese Virale, Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER-Université de Lille-UNICANCER, QIMR Berghofer Medical Research Institute, Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Service de Génétique Clinique [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Génétique épidémiologique et moléculaire des pathologies cardiovasculaires, Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR14-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Génétique médicale [CHU Pitié-Salpêtrière], 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)-Sorbonne Université (SU), Centre hospitalier universitaire de Nantes (CHU Nantes), Etablissement Français du Sang Bretagne, EFS, Laboratoire de Génétique Moléculaire et d'Histocompatibilité [Brest], Hôpital Morvan [Brest]-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), COMBE, Isabelle, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), UNICANCER, Paris-Centre de Recherche Cardiovasculaire (PARCC - UMR-S U970), 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)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), IT University of Copenhagen, Institut Gustave Roussy (IGR), Service d'Oncologie Génétique, de Prévention et Dépistage, Laboratoire d'Oncologie Moléculaire Humaine, Université Lille Nord de France (COMUE)-UNICANCER-Université Lille Nord de France (COMUE)-UNICANCER, CHU Pontchaillou [Rennes], Université de Caen Normandie - UFR Santé (UNICAEN Santé), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Centre René Gauducheau, and CRLCC René Gauducheau
Subjects: 0301 basic medicine, International Cooperation, RNA Splicing, In silico, Spice, Breast Neoplasms, Computational biology, Biology, Sensitivity and Specificity, Set (abstract data type), 03 medical and health sciences, Exon, 0302 clinical medicine, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Genetics, Consensus sequence, RNA and RNA-protein complexes, Humans, Computer Simulation, 030304 developmental biology, BRCA2 Protein, Ovarian Neoplasms, Internet, 0303 health sciences, [SDV.BIBS] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], BRCA1 Protein, Intron, Computational Biology, Genetic Variation, Reproducibility of Results, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], In vitro, 030104 developmental biology, 030220 oncology & carcinogenesis, RNA splicing, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Female, RNA Splice Sites, RNA characterisation and manipulation, Corrigendum, Computational Methods, Optimal decision
Abstract: Variant interpretation is the key issue in molecular diagnosis. Spliceogenic variants exemplify this issue as each nucleotide variant can be deleterious via disruption or creation of splice site consensus sequences. Consequently, reliable in silico prediction of variant spliceogenicity would be a major improvement. Thanks to an international effort, a set of 395 variants studied at the mRNA level and occurring in 5′ and 3′ consensus regions (defined as the 11 and 14 bases surrounding the exon/intron junction, respectively) was collected for 11 different genes, including BRCA1, BRCA2, CFTR and RHD, and used to train and validate a new prediction protocol named Splicing Prediction in Consensus Elements (SPiCE). SPiCE combines in silico predictions from SpliceSiteFinder-like and MaxEntScan and uses logistic regression to define optimal decision thresholds. It revealed an unprecedented sensitivity and specificity of 99.5 and 95.2%, respectively, and the impact on splicing was correctly predicted for 98.8% of variants. We therefore propose SPiCE as the new tool for predicting variant spliceogenicity. It could be easily implemented in any diagnostic laboratory as a routine decision making tool to help geneticists to face the deluge of variants in the next-generation sequencing era. SPiCE is accessible at (https://sourceforge.net/projects/spicev2-1/).
Published: 2018

20. Discrepancy Between Clinical and Pathologic Nodal Status of Esophageal Cancer and Impact on Prognosis and Therapeutic Strategy

Author: Alain Duhamel, Christophe Mariette, Bernard Meunier, Gil Lebreton, Denis Collet, Arnaud Pasquer, Cécile Brigand, Hélène Behal, Sheraz R. Markar, Jérémie Thereaux, Caroline Gronnier, Florence Renaud, Johan Gagnière, Guillaume Piessen, Imperial College London, Hôpital Claude Huriez [Lille], CHU Lille, Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 (JPArc), Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Site de Recherche Intégrée en Cancérologie (SIRIC-ONCOLille), Université de Lille, Sciences et Technologies-Université de Lille, Sciences Humaines et Sociales-Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER-Université de Lille-UNICANCER-Cancéropole Nord-Ouest-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital de la Cavale Blanche - CHRU Brest (CHU - BREST ), CHU Clermont-Ferrand, CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Hôpital de Hautepierre [Strasbourg], Service de pathologie [CHU Lille], CHU Pontchaillou [Rennes], Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Herrada, Anthony, Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U1172 Inserm - U837 (JPArc), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Lille Nord de France (COMUE)-Université de Lille, Université Lille Nord de France (COMUE)-UNICANCER-Université Lille Nord de France (COMUE)-UNICANCER-Cancéropole Nord-Ouest-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Inserm, Université de Lille, Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer (JPArc) - U1172, Centre Hospitalier Régional Universitaire [Lille] [CHRU Lille], Evaluation des technologies de santé et des pratiques médicales - ULR 2694 [METRICS], Centre Hospitalier Régional Universitaire de Brest [CHRU Brest], and Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 [JPArc]
Subjects: Male, Pathology, Esophageal Neoplasms, [SDV.MHEP.CHI] Life Sciences [q-bio]/Human health and pathology/Surgery, medicine.medical_treatment, Aucun, Gastroenterology, 0302 clinical medicine, Risk Factors, Surgical oncology, Medicine, 10. No inequality, Neoadjuvant therapy, Hazard ratio, Middle Aged, Esophageal cancer, 3. Good health, Survival Rate, Oncology, 030220 oncology & carcinogenesis, Resection margin, Adenocarcinoma, Female, 030211 gastroenterology & hepatology, medicine.medical_specialty, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.MHEP.CHI]Life Sciences [q-bio]/Human health and pathology/Surgery, Sciences du Vivant [q-bio]/Médecine humaine et pathologie, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, Humans, Survival rate, Neoplasm Staging, Retrospective Studies, Gastrointestinal Oncology, business.industry, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, medicine.disease, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, T-stage, Surgery, Lymph Nodes, business, Follow-Up Studies
Abstract: International audience; BACKGROUND: The impact of discrepancies between clinical (c) and pathologic (p) stages of esophageal cancer remains a poorly understood issue. This study aimed to compare the prognosis of patient groups treated by primary surgery including clinical N0/pathologic N0 (cN0pN0), clinical N0/pathologic N+ (cN0pN+), clinical N+/pathologic N0 (cN+pN0), and clinical N+/pathologic N+ (cN+pN+).METHODS: Data were collected from 30 European centers during the years 2000 to 2010. Among 2944 recruited patients, 1554 patients receiving primary surgery met the inclusion criteria including 613 cN0pN0, 403 cN0pN+, 220 cN+pN0, and 318 cN+pN+ patients. Analyses with adjustment of the propensity score were used to compensate for differences in baseline characteristics.RESULTS: Clinical T stages 3 and 4 were increased in cN+pN+ (73.0%), cN0pN+ (49.6%), and cN+pN0 (51.8%) compared with cN0pN0 (32.8%). Compared with cN0pN0, cN+pN+ and cN0pN+ showed an increase in the proportion of adenocarcinoma histologic subtype, poor tumor differentiation, pathologic T3 and T4 stages, and R1/2 resection margin. Adjusted 5-year overall survival (hazard ratio [HR] 3.12; 95% confidence interval [CI] 2.57-3.78; P
Published: 2017

21. French updated recommendations in Stage I to III melanoma treatment and management

Author: Nathalie Lassau, Bernard Guillot, Thomas Jouary, Elif Hindié, Alain Dupuy, R. Vanwijck, Sophie Dalac, M.G. Denis, Jean-François Emile, S. Piperno Neumann, X. Mirabel, S. De Raucourt, A. De La Fouchardiere, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Pathogénèse et contrôle des infections chroniques (PCCI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre Hospitalier Universitaire de Montpellier (CHU Montpellier ), Service de Dermatologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre hospitalier universitaire de Nantes (CHU Nantes), Service de Dermatologie [Rennes] = Dermatology [Rennes], CHU Pontchaillou [Rennes], Service de pathologie [CHU Ambroise Paré], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Ambroise Paré [AP-HP], Centre Léon Bérard [Lyon], Service de médecine nucléaire [Bordeaux], CHU de Bordeaux Pellegrin [Bordeaux], CH Pau, Institut Gustave Roussy (IGR), Service de radiothérapie / curiethérapie, Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université Lille Nord de France (COMUE)-UNICANCER-Université Lille Nord de France (COMUE)-UNICANCER, Institut Curie [Paris], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), and Université de Lille-UNICANCER-Université de Lille-UNICANCER
Subjects: medicine.medical_specialty, Skin Neoplasms, Routine ultrasound, Genotype, medicine.medical_treatment, Sentinel lymph node, MEDLINE, Dermoscopy, Dermatology, Stage ii, 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, medicine, Adjuvant therapy, Stage (cooking), Melanoma, Neoplasm Staging, Sentinel Lymph Node Biopsy, business.industry, General surgery, Margins of Excision, medicine.disease, 3. Good health, Surgery, Radiation therapy, Infectious Diseases, Chemotherapy, Adjuvant, Population Surveillance, 030220 oncology & carcinogenesis, Radiotherapy, Adjuvant, France, business, [SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology
Abstract: International audience; As knowledge continues to develop, regular updates are necessary concerning recommendations for practice. The recommendations for the management of melanoma stages I to III were drawn up in 2005. At the request of the Société Française de Dermatologie, they have now been updated using the methodology for recommendations proposed by the Haute Autorité de Santé in France. In practice, the principal recommendations are as follows: for staging, it is recommended that the 7th edition of AJCC be used. The maximum excision margins have been reduced to 2 cm. Regarding adjuvant therapy, the place of interferon has been reduced and no validated emerging medication has yet been identified. Radiotherapy may be considered for patients in Stage III at high risk of relapse. The sentinel lymph node technique remains an option. Initial examination includes routine ultrasound as of Stage II, with other examinations being optional in stages IIC and III. A shorter strict follow-up period (3 years) is recommended for patients, but with greater emphasis on imaging.
Published: 2017

22. Patients atteints d’un cancer gastrique localisé MSI/dMMR, pas de chimiothérapie mais une immunothérapie périopératoire : l’essai de phase II GERCOR NEONIPIGA vient d’être ouvert au recrutement

Author: Cohen, Romain, Pudlarz, Thomas, Garcia-Larnicol, Marie-Line, Vernerey, Dewi, Dray, Xavier, Clavel, Léa, Jary, Marine, Piessen, Guillaume, Zaanan, Aziz, Aparicio, Thomas, Louvet, Christophe, Tournigand, Christophe, Chibaudel, Benoist, Tougeron, David, Guimbaud, Rosine, Benouna, Jaafar, Adenis, Antoine, Sokol, Harry, Borg, Christophe, Duval, Alex, Svrcek, Magali, André, Thierry, Service d'Oncologie Médicale [CHU Saint -Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), Cooperator Multidisciplinary Oncology Group (GERCOR), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Claude Huriez [Lille], CHU Lille, 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), Université Sorbonne Paris Cité (USPC), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Mutualiste de Montsouris (IMM), Service d'Oncologie médicale [CHU Henri Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Henri Mondor, Centre hospitalier universitaire de Poitiers (CHU Poitiers), CHU Toulouse [Toulouse], Centre hospitalier universitaire de Nantes (CHU Nantes), Institut du Cancer de Montpellier (ICM), Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], 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 Gastroentérologie et nutrition [CHU Saint-Antoine], Site de Recherche Intégrée en Cancérologie (SIRIC-ONCOLille), Université de Lille, Sciences et Technologies-Université de Lille, Sciences Humaines et Sociales-Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université Lille Nord de France (COMUE)-UNICANCER-Université Lille Nord de France (COMUE)-UNICANCER-Cancéropole Nord-Ouest-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Instabilité des microsatellites et cancers [CHU Saint-Antoine], 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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Service de Pathologie [CHU Saint-Antoine], 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), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Henri Mondor [Créteil], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Université de Lille-UNICANCER-Université de Lille-UNICANCER-Cancéropole Nord-Ouest-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Instabilité des microsatellites et cancers [CRSA], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)
Subjects: [SDV]Life Sciences [q-bio], Patient Selection, Adenocarcinoma, DNA Mismatch Repair, Ipilimumab, Disease-Free Survival, Neoadjuvant Therapy, Perioperative Care, Instabilité des microsatellites, Lynch syndrome, Antineoplastic Agents, Immunological, Clinical Trials, Phase II as Topic, Nivolumab, Phenotype, Treatment Outcome, Chemotherapy, Adjuvant, Stomach Neoplasms, Humans, Multicenter Studies as Topic, Cancer de l’estomac, Microsatellite Instability, Gastric cancer, Syndrome de Lynch
Abstract: International audience; IntroductionPerioperative chemotherapy is the standard strategy for localized gastric cancers. Nevertheless, this strategy seems to be inefficient, if not deleterious, for patients with tumors harboring microsatellite instability (MSI) and/or mismatch repair deficiency (dMMR), a tumor phenotype predictive for the efficacy of immune checkpoint inhibitors (ICKi).AimThe GERCOR NEONIPIGA single-arm phase II study (NCT04006262; EUDRACT 2018-004712-22) aims at evaluating the efficacy of a peri-operative strategy with nivolumab and ipilimumab in neoadjuvant setting, then nivolumab alone after surgery for patients with resectable MSI/dMMR gastric cancer.Material and methodsMain inclusion criteria are: gastric and oesogastric junction adenocarcinoma (GOA), T2-T4, all N stage and M0, MSI/dMMR. Patients will be treated with nivolumab 240 mg Q2 W, 6 infusions, and ipilimumab 1 mg/kg Q6 W, 2 infusions in neoadjuvant setting. Following surgery, patients with TRG 1-2-3 (Mandard tumor regression grade), acceptable tolerance of neoadjuvant treatment and postoperative ECOG performance status 0–1, will be treated with adjuvant nivolumab 480 mg Q4 W, 9 infusions.ResultsThe primary endpoint is pathological complete response rate (pCR-R). Based on a Fleming design, with α = 5% and β = 20%, 27 patients have to be evaluated (H0 = 5%; H1 = 20%). Secondary endpoints include disease-free survival, overall survival and safety.ConclusionThis study is planned to include 32 patients to evaluate the pCR-R with the combination of nivolumab and ipilimumab in neoadjuvant setting for MSI/dMMR localized GOA. The MSI/MMR status should be systematically assessed on diagnostic biopsies of all GOA. If it meets its primary endpoint, the GERCOR NEONIPIGA study might mark a turning point in the management of localized MSI/dMMR GOA patients.; IntroductionLa chimiothérapie périopératoire est la stratégie de référence pour les cancers gastriques (CG) localisés, mais semble inefficace voire délétère pour les patients avec un cancer MSI/dMMR (microsatellites instables/MMR-déficient), biomarqueur prédictif de l’efficacité de l’immunothérapie.ObjectifL’essai de phase 2 mono-bras GERCOR NEONIPIGA (NCT04006262; EUDRACT 2018-004712-22) évalue l’efficacité du nivolumab plus ipilimumab en néo-adjuvant puis nivolumab seul en adjuvant pour les CG ou de la jonction œsogastrique (JOG) MSI/dMMR résécables.Matériel et méthodesLes principaux critères d’inclusion sont : CG/JOG, T2-4 tout N M0, MSI/dMMR. Les patients sont traités en néo-adjuvant par nivolumab 240 mg Q2 W, 6 perfusions, et ipilimumab 1 mg/kg Q6 W, deux injections. Les patients avec un degré de régression tumorale 1-3 selon Mandard, une tolérance acceptable du traitement néo-adjuvant et un indice de performance postopératoire ECOG 0-1 recevront neuf perfusions mensuelles de nivolumab 480 mg en adjuvant.RésultatsL’objectif principal est le taux de réponse complète pathologique (pCR). Selon un design de Fleming avec α = 5 % et β = 20 %, 27 patients évaluables sont à analyser (H0 = 5 % ; H1 = 20 %). Les critères secondaires de jugement sont la survie sans maladie, la survie globale et le profil de tolérance.ConclusionIl est prévu d’inclure 32 patients pour évaluer le taux de pCR pour les CG/JOG MSI/dMMR traités par nivolumab et ipilimumab néo-adjuvant. Le statut MSI/MMR doit être systématiquement analysé sur les biopsies diagnostiques de tout CG/JOG. L’étude NEONIPIGA pourrait marquer un tournant dans la prise en charge des CG/JOG MSI/dMMR si elle atteint son objectif principal.
Published: 2019

23. Relevance of Detection of Mechanisms of Resistance to ALK Inhibitors in ALK-Rearranged NSCLC in Routine Practice

Author: Marie Christine Copin, Philippe Jamme, Radj Gervais, Valérie Grégoire, Nathalie Rabbe, Nicolas Richard, Simon Baldacci, Alexis B. Cortot, Fabienne Escande, Maeva Kyheng, Marie Wislez, Eric Dansin, Zoulika Kherrouche, C. Descarpentries, Mécanismes de tumorigenèse et thérapies ciblées, Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Pôle de Biologie Pathologie Génétique [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université Lille Nord de France (COMUE)-UNICANCER, CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Génétique [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Biologie, génétique et thérapies ostéoarticulaires et respiratoires (BIOTARGEN), Normandie Université (NU)-Normandie Université (NU), Mécanismes de la Tumorigénèse et Thérapies Ciblées - UMR 8161 (M3T), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), 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), Site de Recherche Intégrée en Cancérologie (SIRIC-ONCOLille), Université de Lille, Sciences et Technologies-Université de Lille, Sciences Humaines et Sociales-Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université Lille Nord de France (COMUE)-UNICANCER-Université Lille Nord de France (COMUE)-UNICANCER-Cancéropole Nord-Ouest-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Université de Lille-UNICANCER, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Université de Lille-UNICANCER-Université de Lille-UNICANCER-Cancéropole Nord-Ouest-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)
Subjects: 0301 basic medicine, Oncology, Male, Cancer Research, Lung Neoplasms, Resistance, Disease, Routine practice, medicine.disease_cause, Anaplastic lymphoma kinase, 0302 clinical medicine, Carcinoma, Non-Small-Cell Lung, hemic and lymphatic diseases, Antineoplastic Combined Chemotherapy Protocols, Medicine, Gene Rearrangement, Real-world evidence, Mutation, Middle Aged, 3. Good health, 030220 oncology & carcinogenesis, Female, Tyrosine kinase, Pulmonary and Respiratory Medicine, Adult, medicine.medical_specialty, Adolescent, [SDV.CAN]Life Sciences [q-bio]/Cancer, 03 medical and health sciences, Young Adult, Crizotinib, Internal medicine, Humans, Clinical significance, In patient, Lung cancer, Protein Kinase Inhibitors, Aged, Neoplasm Staging, Retrospective Studies, business.industry, medicine.disease, Lung neoplasm, respiratory tract diseases, 030104 developmental biology, Drug Resistance, Neoplasm, business
Abstract: Background Anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) have shown efficacy in the treatment of ALK-rearranged non–small-cell lung cancer (NSCLC), but the disease eventually progresses in all patients. In many cases, resistance to ALK TKIs arises through ALK mutations. Although clinical and biological data suggest variations in TKI efficacy according to the mechanism of resistance, ALK mutations are still rarely investigated in routine practice. Materials and Methods We performed a retrospective multicentric study with an aim to determine the frequency and clinical relevance of ALK alterations detected using targeted next-generation sequencing in patients with advanced ALK-rearranged NSCLC after progression during an ALK TKI treatment. Data on clinical, pathological, and molecular characteristics and patient outcomes were collected. Results We identified 23 patients with advanced ALK-rearranged NSCLC who, between January 2012 and May 2017, had undergone at least 1 repeat biopsy at progression during an ALK TKI treatment. A resistance mechanism was identified in 9 of the 23 patients (39%). The anomalies involved included 9 ALK mutations in 8 patients and one ALK amplification. The ALK mutation rate was 15% after failure of a first ALK TKI and 33% after failure of 2 ALK TKI treatments. Five of 7 patients who received a different ALK TKI after detection of an ALK mutation achieved an objective response. All of the patients who received a TKI presumed to act on the detected ALK mutant achieved disease control. Conclusion Targeted next-generation sequencing is suitable for detecting ALK resistance mutations in ALK-rearranged NSCLC patients in routine practice. It might help select the best treatment at the time of disease progression during treatment with an ALK TKI.
Published: 2019

24. L'expression de s-SHIP identifie une population de cellules souches cancéreuses chez la souris

Author: Tian, Lu, Truong, Marie-José, Lagadec, Chann, Adriaenssens, Eric, Bouchaert, Emmanuel, Bauderlique-Le Roy, Hélène, Figeac, Martin, Le Bourhis, Xuefen, Bourette, Roland, Stanford School of Medicine [Stanford], Stanford Medicine, Stanford University-Stanford University, Signalisation des Facteurs de Croissance Dans Le Cancer du Sein . Proteomique Fonctionnelle, Université de Lille, Sciences et Technologies-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de biologie de Lille - IBL (IBLI), Université de Lille, Sciences et Technologies-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique (CNRS), Site de Recherche Intégrée en Cancérologie (SIRIC-ONCOLille), Université de Lille, Sciences et Technologies-Université de Lille, Sciences Humaines et Sociales-Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER-Université de Lille-UNICANCER-Cancéropole Nord-Ouest-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Plateforme de génomique fonctionnelle et structurelle [Lille], Institut pour la recherche sur le cancer de Lille [Lille] (IRCL)-Université de Lille, Droit et Santé, Signalisation des facteurs de croissance dans le cancer du sein. Protéomique fonctionnelle, Institut National de la Santé et de la Recherche Médicale (INSERM), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Centre National de la Recherche Scientifique (CNRS)-Université de Lille, Droit et Santé, and Université Lille Nord de France (COMUE)-UNICANCER-Université Lille Nord de France (COMUE)-UNICANCER-Cancéropole Nord-Ouest-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)
Subjects: [SDV.CAN]Life Sciences [q-bio]/Cancer, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2019

25. Preclinical septic shock research: why we need an animal ICU

Author: Antoine Guillon, Sebastien Preau, Jérôme Aboab, Eric Azabou, Boris Jung, Stein Silva, Julien Textoris, Fabrice Uhel, Dominique Vodovar, Lara Zafrani, Nicolas de Prost, Peter Radermacher, Translational Research Committee of the French Intensive Care Society (Société de Réanimation de Langue Française), Laboratoire de Physico -& Toxico Chimie des systèmes naturels (LPTC), Université Sciences et Technologies - Bordeaux 1-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Institut de médecine predictive et de recherche thérapeutique (IMPRT), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER-Université de Lille-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut Mondor de recherche biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital Raymond Poincaré [AP-HP], Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service d’Anesthésie Réanimation, Unité Mixte bioMérieux-HCL, Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Microenvironnement et cancer (MiCa), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Variabilité de réponse aux Psychotropes (VariaPsy - U1144), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Réanimation Médicale, Hôpital Saint Louis, Paris, France, Service de réanimation médicale, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Sektion Anästhesiologische Pathophysiologie und Verfahrensentwicklung, Universitätsklinikum Ulm - University Hospital of Ulm, GRK 2003, Deutsche Forschungsgemeinschaft, Université Sciences et Technologies - Bordeaux 1 (UB)-Centre National de la Recherche Scientifique (CNRS), Pôle Anesthésie Réanimation [CHU de Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), MORNET, Dominique, Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Université Lille Nord de France (COMUE)-UNICANCER-Université Lille Nord de France (COMUE)-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-CRLCC Oscar Lambret-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), AP-HP Hôpital Raymond Poincaré [Garches], Optimisation Thérapeutique en Neuropsychopharmacologie (VariaPsy - U1144), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5), and Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)
Subjects: medicine.medical_specialty, [SDV]Life Sciences [q-bio], Context (language use), Review, Disease, Critical Care and Intensive Care Medicine, Sepsis, 03 medical and health sciences, Preclinical research, 0302 clinical medicine, Small animal, Anesthesiology, Septic shock, medicine, Intensive care medicine, ComputingMilieux_MISCELLANEOUS, business.industry, lcsh:Medical emergencies. Critical care. Intensive care. First aid, 030208 emergency & critical care medicine, lcsh:RC86-88.9, medicine.disease, Medical research, 3. Good health, Animal models, [SDV] Life Sciences [q-bio], 030228 respiratory system, business
Abstract: Animal experiments are widely used in preclinical medical research with the goal of disease modeling and exploration of novel therapeutic approaches. In the context of sepsis and septic shock, the translation into clinical practice has been disappointing. Classical animal models of septic shock usually involve one-sex-one-age animal models, mostly in mice or rats, contrasting with the heterogeneous population of septic shock patients. Many other factors limit the reliability of preclinical models and may contribute to preclinical research failure in critical care, including the host specificity of several pathogens, the fact that laboratory animals are raised in pathogen-free facilities and that organ support techniques are either absent or minimal. Advanced animal models have been developed with the aim of improving the clinical translatability of experimental findings. So-called animal ICUs refer to the preclinical investigation of adult or even aged animals of either sex, using—in case of rats and mice—miniaturized equipment allowing for reproducing an ICU environment at a small animal scale and integrating chronic comorbidities to more closely reflect the clinical conditions studied. Strength and limitations of preclinical animal models designed to decipher the mechanisms involved in septic cardiomyopathy are discussed. This article reviews the current status and the challenges of setting up an animal ICU.
Published: 2019

26. Cancer du sein et exosomes tumoraux circulants dans les troubles cognitifs associés au cancer : Etude preuve de concept

Author: Castel, Hélène, Parment, Renaud, Dubois, Martine, Desrues, Laurence, Delhem, N., Morales, O, Joly, Florence, Morin, Fabrice, Gandolfo, Pierrick, Différenciation et communication neuronale et neuroendocrine (DC2N), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Plateforme Cancer et Cognition, CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Ligue Nationale Contre le Cancer (LNCC)-Cancéropole Nord-Ouest, Site de Recherche Intégrée en Cancérologie (SIRIC-ONCOLille), Université de Lille, Sciences et Technologies-Université de Lille, Sciences Humaines et Sociales-Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER-Université de Lille-UNICANCER-Cancéropole Nord-Ouest-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), CASTEL, Hélène, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Cancéropole Nord-Ouest-Ligue Nationale Contre le Cancer (LNCC), Université Lille Nord de France (COMUE)-UNICANCER-Université Lille Nord de France (COMUE)-UNICANCER-Cancéropole Nord-Ouest-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), and UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)
Subjects: [SDV] Life Sciences [q-bio], TheoryofComputation_MISCELLANEOUS, [SDV.CAN] Life Sciences [q-bio]/Cancer, [SDV]Life Sciences [q-bio], ComputingMilieux_COMPUTERSANDEDUCATION, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, GeneralLiterature_MISCELLANEOUS, ComputingMilieux_MISCELLANEOUS
Abstract: Invited lecture; National audience
Published: 2019

27. Incorporating individual historical controls and aggregate treatment effect estimates into a Bayesian survival trial: a simulation study

Author: Lisa V. Hampson, Marie-Cécile Le Deley, Caroline Brard, Nathalie Gaspar, Gwénaël Le Teuff, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de biostatistique et d'épidémiologie (SBE), Direction de la recherche clinique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Statistical Methodology [Bâle, Suisse], Novartis Pharma AG, Département de cancérologie de l'enfant et de l'adolescent [Gustave Roussy], Institut Gustave Roussy (IGR), Unité de Méthodologie et de Biostatistique [Lille] (UMB), Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER-Université de Lille-UNICANCER, We acknowledge for the design, analysis, interpretation of the simulation study, and for the writing of the manuscript, funding from – PhD grant from doctoral school of public health, Paris-Sud, Paris-Saclay – Lisa Hampson’s contribution to the paper was partly funded by the UK Medical Research Council (grant MR/M013510/1) and was completed while she was an employee of Lancaster University – Ligue contre le cancer, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Université Lille Nord de France (COMUE)-UNICANCER-Université Lille Nord de France (COMUE)-UNICANCER, and Bodescot, Myriam
Subjects: Simulation study, Epidemiology, Computer science, Bayesian probability, Health Informatics, [SDV.CAN]Life Sciences [q-bio]/Cancer, Power prior, law.invention, 03 medical and health sciences, 0302 clinical medicine, Adjuvants, Immunologic, [SDV.CAN] Life Sciences [q-bio]/Cancer, Randomized controlled trial, law, Statistics, Prior probability, Humans, Computer Simulation, 030212 general & internal medicine, Set (psychology), Baseline (configuration management), Bayesian randomised survival trial, Randomized Controlled Trials as Topic, Weibull distribution, Osteosarcoma, lcsh:R5-920, Phosphatidylethanolamines, 030503 health policy & services, Aggregate (data warehouse), Bayes Theorem, Variance (accounting), Models, Theoretical, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, Control Groups, Mixture prior, 3. Good health, [SDV.SP] Life Sciences [q-bio]/Pharmaceutical sciences, Research Design, Sample Size, Individual control data, 0305 other medical science, lcsh:Medicine (General), Aggregate treatment effect, Acetylmuramyl-Alanyl-Isoglutamine, Rare disease, Algorithms, Research Article
Abstract: Background Performing well-powered randomised controlled trials (RCTs) of new treatments for rare diseases is often infeasible. However, with the increasing availability of historical data, incorporating existing information into trials with small sample sizes is appealing in order to increase the power. Bayesian approaches enable one to incorporate historical data into a trial’s analysis through a prior distribution. Methods Motivated by a RCT intended to evaluate the impact on event-free survival of mifamurtide in patients with osteosarcoma, we performed a simulation study to evaluate the impact on trial operating characteristics of incorporating historical individual control data and aggregate treatment effect estimates. We used power priors derived from historical individual control data for baseline parameters of Weibull and piecewise exponential models, while we used a mixture prior to summarise aggregate information obtained on the relative treatment effect. The impact of prior-data conflicts, both with respect to the parameters and survival models, was evaluated for a set of pre-specified weights assigned to the historical information in the prior distributions. Results The operating characteristics varied according to the weights assigned to each source of historical information, the variance of the informative and vague component of the mixture prior and the level of commensurability between the historical and new data. When historical and new controls follow different survival distributions, we did not observe any advantage of choosing a piecewise exponential model compared to a Weibull model for the new trial analysis. However, we think that it remains appealing given the uncertainty that will often surround the shape of the survival distribution of the new data. Conclusion In the setting of Sarcome-13 trial, and other similar studies in rare diseases, the gains in power and accuracy made possible by incorporating different types of historical information commensurate with the new trial data have to be balanced against the risk of biased estimates and a possible loss in power if data are not commensurate. The weights allocated to the historical data have to be carefully chosen based on this trade-off. Further simulation studies investigating methods for incorporating historical data are required to generalise the findings. Electronic supplementary material The online version of this article (10.1186/s12874-019-0714-z) contains supplementary material, which is available to authorized users.
Published: 2019

28. Large scale multifactorial likelihood quantitative analysis of BRCA1 and BRCA2 variants: An ENIGMA resource to support clinical variant classification

Author: Luigi Mori, Sara González, Elia Grau, Dieter Niederacher, Alexandra C. Kölbl, Ares Solanes, Cassandra B. Nichols, Marine Guillaud-Bataille, Ulrike Schoenwiese, Katherine L. Nathanson, Alfons Meindl, Ellen Honisch, Hans Ehrencrona, Ute Enders, Anke Waha, Trinidad Caldés, Inge Søkilde Pedersen, Ana Blanco, Emma Tudini, Conxi Lázaro, Paolo Radice, Torben A Kruse, María Concepción Alonso-Cerezo, Chantal Farra, Shan Wang-Gohrke, Wilko Weichert, Heli Nevanlinna, Setareh Moghadasi, Bernd Auber, Carla Bruzzone, Aliana Guerrieri-Gonzaga, Sabine Grill, Raymonda Varon, Nicolas Derive, Ana Vega, Nicolai Maass, Åke Borg, Cora M. Aalfs, Nadia Naldi, Silvia Iglesias, Kai Ren Ong, Encarna B. Gomez Garcia, Karl Hackmann, Emma R. Woodward, Norbert Arnold, David E. Goldgar, Bernard Peissel, Karolin Bucksch, Berardino Porfirio, Françoise Révillion, Angel Izquierdo, Isabell Witzel, Sebastian Wagner, Silke Zachariae, Elisa Alducci, Mads Thomassen, Jesús del Valle, Valentina Zampiga, Kerstin Rhiem, Lidia Moserle, Edenir Inêz Palmero, Maaike P.G. Vreeswijk, Christoph Mundhenke, Laura Papi, Alejandro Moles-Fernández, Paula Rofes, Ulrike Faust, Andrea Gehrig, Sandrine M. Caputo, Logan C. Walker, Fiona Lalloo, Ute Felbor, Joan Brunet, Henriette Roed Nielsen, Sean V. Tavtigian, Beatrice Bortesi, Thomas Hansen, Maria Grazia Tibiletti, Estela Carrasco, Lisa Wiesmüller, Viviana Gismondi, Sophie Krieger, Pedro Pérez-Segura, Esther Pohl-Rescigno, Emanuela Lucci-Cordisco, Barbara Wappenschmidt, Rui Manuel Reis, Gabriele Lorenzo Capone, Ileana Carnevali, Christi J. van Asperen, KCon Fab Investigators, Jochen Seggewiß, Rhiannon J. Walters, Irmgard Debatin, Susan M. Domchek, Marco Montagna, Francesca Gensini, Kristiina Aittomäki, Véronique Dutrannoy, Arcangela De Nicolo, Giulia Cagnoli, Elisa J. Cops, Henrique de Campos Reis Galvão, Giulia Cini, Barbara Riboli, Eva Tornero, Paul A. James, Judith Balmaña, Anne-Marie Gerdes, Heide Hellebrand, Miriam Fine, Mathias Stiller, Aldo Germani, Diana Eccles, Britta Blümcke, Dominique Stoppa-Lyonnet, Elena Leinert, Alexandra Lewis, Daniela Rivera, Verena Hübbel, Fergus J. Couch, Gunnar Schmidt, Katharina Keupp, Bernhard H. F. Weber, Tilman Heinrich, Mariarosaria Calvello, Michael Dean, Udo Jeschke, Vanessa Lattimore, Linda A.M. Janssen, Siranoush Manoukian, Eva Gross, Kelly J. Sullivan, Doris Steinemann, Susanne Ledig, Alessandra Viel, Christoph Engel, Ana Sánchez de Abajo, Nina Ditsch, Sandra Bonache, Maria A. Caligo, Katharina Pfeifer, Thomas Haaf, Christian Sutter, Eric Hahnen, Laura Matricardi, Marc Tischkowitz, Alex Teulé, Katherine M. Tucker, Jutta Giesecke, Silvia Tognazzo, Gemma Montalban, Carolina Gómez, Anders Kvist, Joanna Lim, Alison H. Trainer, Rachel Susman, Judit Horvath, Amanda B. Spurdle, Mirjam Larsen, Therese Törngren, Mónica Salinas, Nicholas Pachter, Rachel Austin, Nicola K. Poplawski, C Zeder-Göß, Juliane Ramser, Julia Ritter, Anne Sophie Vesper, Paola Concolino, D. Gareth Evans, Clemens R. Müller, Matilde Navarro, Sara Torres-Esquius, Claus R. Bartram, Laura Cortesi, Jacopo Azzollini, Marion Harris, Edward M. Clarke, Marion Kiechle, Lídia Feliubadaló, Almuth Caliebe, Karen N. Herold, Charlotte Kvist Lautrup, Anne S. Quante, Gardenia Vargas-Parra, Michael T. Parsons, Pietro Cavalli, Hongyan Li, Rodrigo Augusto Depieri Michelli, Irene Feroce, Achim Wöckel, Kerstin Wieland, Silke Kaulfuß, Soo Hwang Teo, Angela Velasco, Capucine Delnatte, Marta Pineda, Marion van Mackelenbergh, Eva Montes, Angela Toss, Rita K. Schmutzler, William D. Foulkes, Alvaro N.A. Monteiro, Jan Hauke, Monica Marabelli, Miguel de la Hoya, Sara Gutiérrez-Enríquez, Esther Darder, Simona Agata, Amanda E. Toland, Bernardo Bonanni, Liliana Varesco, Orland Diez, Andreas Rump, Virginie Caux-Moncoutier, Gaetana Gambino, Markus Loeffler, Claude Houdayer, Elena Barbieri, Adrià López-Fernández, et. al., Universidade do Minho, QIMR Berghofer Medical Research Institute, Chinese Academy of Geological Sciences [Beijing] (CAGS), Ministry of Land and Resources (MLR), Department of Gynaecology and Obstetrics, University Hospital of Cologne [Cologne]-Centre of Familial Breast and Ovarian Cancer-Centre for Integrated Oncology (CIO), Programa de Càncer Hereditari, Unitat de Diagnòstic Molecular, Laboratori de Recerca Translacional, Institut Català d'Oncologia-IDIBELL, Department of Clinical Genetics, Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA)-University of Amsterdam [Amsterdam] (UvA), Helsinki University Central Hospital, University Hospital of Schleswig-Holstein-Christian-Albrechts-Universität zu Kiel (CAU), Università degli Studi di Milano [Milano] (UNIMI), Medical Oncology Department, Vall d'Hebron University Hospital [Barcelona], Institute of Human Genetics, Universität Heidelberg [Heidelberg], Fundación Pública Galega de Medicina Xenómica-SERGAS & Grupo de Medicina Xenómica-USC, CIBER-ER, Division of Cancer Prevention and Genetics, Department of Oncology, Clinical Sciences, Lund University [Lund]-Skåne University Hospital, Genetic Counseling and Hereditary Cancer Programme, Catalan Institute of Oncology, Molecular Oncology Laboratory, Hospital Clínico San Carlos, Institut Curie [Paris], Programa de Consell Genètic en Càncer, Institut Català d'Oncologia, Girona-IdIBGi, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos [Madrid, Spain] (IdISSC), Centre René Gauducheau, CRLCC René Gauducheau, Institut de biochimie et génétique cellulaires (IBGC), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Oncogenetics Laboratory, Vall d'Hebron Institute of Oncology (VHIO), Ludwig-Maximilians-Universität München (LMU), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Genetics, University of Southampton, Departament of Genetics and Pathology, Uppsala University-Rudbeck Laboratory, Department of Genomic Medicine, University of Manchester [Manchester], Department of Medical Genetics, Julius-Maximilians-Universität Würzburg [Wurtzbourg, Allemagne] (JMU)-Centre of Familial Breast and Ovarian Cancer, Obstetrics and Gynaecology, Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), Institüt für Humangenetik [Würzburg], Julius-Maximilians-Universität Würzburg [Wurtzbourg, Allemagne] (JMU), Heinrich Heine Universität Düsseldorf = Heinrich Heine University [Düsseldorf], Institute of Chemistry [Budapest], Faculty of Sciences [Budapest], Eötvös Loránd University (ELTE)-Eötvös Loránd University (ELTE), Service de Biochimie et de Biologie Moléculaire [CHU Trousseau], 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), I. Frauenklinik, Klinikum der Ludwig-Maximilians-Universitaet, Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Biochemistry, Pharmacology and Genetics, Odense University Hospital, Department of Oncology, Lund University [Lund]-Clinical Sciences, Genetic Medicine, Manchester Academic Health Sciences Centre-Central Manchester University Hospitals, Institute for Medical Informatics, Department of Gynecology and Obstetrics, University Medical Center Schleswig-Holstein, Unit of Medical Genetics, Fondazione IRCCS Istituto Nazionale Tumouri (INT), Immunology and Molecular Oncology Unit, Istituto Oncologico Veneto IOV - IRCCS, University Medical Center Kiel, Department of Obstetrics and Gynecology, University Hospital Düsseldorf-Heinrich Heine Universität Düsseldorf = Heinrich Heine University [Düsseldorf], Medical Genetics Unit, Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), Department of Biochemistry, Section of Molecular Diagnostics, Laboratoire d'Oncologie Moléculaire Humaine, Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université Lille Nord de France (COMUE)-UNICANCER-Université Lille Nord de France (COMUE)-UNICANCER, Institute of Cell and Molecular Pathology, Medizinische Hochschule Hannover (MHH), University of California [Santa Cruz] (UCSC), University of California, Heidelberg University Hospital [Heidelberg], International Agency for Cancer Research (IACR), Programa de Consejo Genético en Cáncer, Instituto Catalán de Oncología-IDIBELL, L'Hospitalet, Programa de Diagnòstic Molecular de Càncer Hereditari, Laboratori de Recerca Translacional, Institut Català d'Oncologia-IDIBELL, Hospital Duran i Reynals, Hospitalet de Llobregat, Unit of Hereditary Cancers, Istituto Nazionale per la Ricerca sul Cancro, CIBER de Enfermedades Raras (CIBERER), Unit of Experimental Oncology 1, Centro di Riferimento Oncologico, University of Otago [Dunedin, Nouvelle-Zélande], Institute of Pathology, Department of Gynecology, Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), King‘s College London, Molecular Diagnostic Unit, IDIBELL-Catalan Institute of Oncology, Unit of Molecular Bases of Genetic Risk and Genetic Testing, Fondazione IRCCS Istituto Nazionale Tumouri (INT)-Fondazione Istituto FIRC di Oncologia Molecolare, Institute for Medical Informatics, Statistics and Epidemiology [Leipzig] (IMISE), Universität Leipzig [Leipzig], Division of Molecular Gynaeco-Oncology, Department of Gynaecology and Obstetrics, Clinical Center University of Cologne, Medicum, Research Programs Unit, Genome-Scale Biology (GSB) Research Program, Kristiina Aittomäki / Principal Investigator, HUSLAB, Department of Medical and Clinical Genetics, HUS Gynecology and Obstetrics, University Management, University of Helsinki, Università degli Studi di Milano = University of Milan (UNIMI), Universität Heidelberg [Heidelberg] = Heidelberg University, Department of Genetics and Pathology, Uppsala University, Julius-Maximilians-Universität Würzburg (JMU)-Centre of Familial Breast and Ovarian Cancer, Julius-Maximilians-Universität Würzburg (JMU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Università degli Studi di Firenze = University of Florence (UniFI), Université de Lille-UNICANCER-Université de Lille-UNICANCER, University of California [Santa Cruz] (UC Santa Cruz), University of California (UC), Universität Leipzig, University of Cologne, RS: GROW - R4 - Reproductive and Perinatal Medicine, MUMC+: DA KG Polikliniek (9), and Klinische Genetica
Subjects: Male, Multifactorial Inheritance, BRCA1, BRCA2, classification, clinical, multifactorial, quantitative, uncertain significance, variant, Alternative Splicing, BRCA1 Protein, BRCA2 Protein, Computational Biology, Early Detection of Cancer, Female, Genetic Predisposition to Disease, Humans, Likelihood Functions, Neoplasms, Mutation, Missense, Medicina Básica [Ciências Médicas], Settore MED/03 - GENETICA MEDICA, GUIDELINES, Genetic analysis, CLINGEN, SEQUENCE VARIANTS, Missense mutation, FUNCTIONAL ASSAYS, Genetics (clinical), BRCA1, BRCA2, quantitative, clinical, classification, multifactorial, variant, uncertain significance, 0303 health sciences, education.field_of_study, 030305 genetics & heredity, 1184 Genetics, developmental biology, physiology, SPLICING ANALYSIS, OVARIAN, BRCA2 Protein/genetics, 3. Good health, ddc, Mutation (genetic algorithm), Ciências Médicas::Medicina Básica, Medical genetics, Special Articles, medicine.medical_specialty, Posterior probability, Population, Computational biology, Biology, INTEGRATED EVALUATION, 03 medical and health sciences, Special Article, medicine, Genetics, BREAST-CANCER, Genetic variability, ddc:610, education, 030304 developmental biology, Tumors, Science & Technology, Proteins, Computational Biology/methods, RISKS, Mutation, BRCA1 Protein/genetics, 3111 Biomedicine, Missense, Proteïnes, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Genètica, Neoplasms/diagnosis
Abstract: The multifactorial likelihood analysis method has demonstrated utility for quantitative assessment of variant pathogenicity for multiple cancer syndrome genes. Independent data types currently incorporated in the model for assessing BRCA1 and BRCA2 variants include clinically calibrated prior probability of pathogenicity based on variant location and bioinformatic prediction of variant effect, co-segregation, family cancer history profile, co-occurrence with a pathogenic variant in the same gene, breast tumor pathology, and case-control information. Research and clinical data for multifactorial likelihood analysis were collated for 1,395 BRCA1/2 predominantly intronic and missense variants, enabling classification based on posterior probability of pathogenicity for 734 variants: 447 variants were classified as (likely) benign, and 94 as (likely) pathogenic; and 248 classifications were new or considerably altered relative to ClinVar submissions. Classifications were compared with information not yet included in the likelihood model, and evidence strengths aligned to those recommended for ACMG/AMP classification codes. Altered mRNA splicing or function relative to known nonpathogenic variant controls were moderately to strongly predictive of variant pathogenicity. Variant absence in population datasets provided supporting evidence for variant pathogenicity. These findings have direct relevance for BRCA1 and BRCA2 variant evaluation, and justify the need for gene-specific calibration of evidence types used for variant classification., Ohio State University Comprehensive Cancer Center Barretos Cancer Hospital. Grant Number: FINEP ‐ CT‐INFRA (02/2010) Breast Cancer Foundation of New Zealand Canadian Institutes of Health Research. Grant Number: PSR‐SIIRI‐701 Cancer Research UK. Grant Numbers: C8197/A16565, C5047/A8384, C1281/A12014, C12292/A11174, C1287/A10710, C1287/A10118, C1287/A16563, C5047/A10692, C5047/A15007 Department of Defence, USA. Grant Number: W81XWH‐10‐1‐0341 Helsinki University Hospital Research fund Scientific Foundation Asociación Española Contra el Cáncer Leiden University Medical Centre. Grant Number: Grant 30.925 Generalitat de Catalunya. Grant Numbers: PERIS_MedPerCan, URDCat, 2017SGR1282, 2017SGR496 Royal Society of New Zealand Cancer Council Victoria Netherlands Organization for Scientific Research (NWO). Grant Number: Grant 017.008.022 Breast Cancer Research Foundation Cancer Foundation of Western Australia EU H2020. Grant Number: 634935 Fundación Mutua Madrileña Seventh Framework Programme. Grant Numbers: 634935, 223175, 633784 Cancer Council South Australia Government of Galicia. Grant Number: Consolidation and structuring program: IN607B Cancer Council Tasmania Italian Association of Cancer Research. Grant Number: 15547 Queensland Cancer Fund AstraZeneca National Institute of Health (USA). Grant Numbers: 1U19 CA148065‐01, CA128978, CA192393, 1U19 CA148537, P50 CA1162091, CA116167, 1U19 CA148112 Newcastle University Dutch Cancer Society KWF. Grant Numbers: KWF/Pink Ribbon‐11704, UL2012‐5649 National Institute for Health Research. Grant Number: Manchester Biomedical Research centre (IS‐BRC‐1215 National Council of Technological and Scientific Development (CNPq) Instituto de Salud Carlos III. Grant Numbers: FIS PI15/00355, FIS PI13/01711, CIBERONC, FIS PI16/01218, PI16/00563 French National Institute of Cancer National Breast Cancer Foundation National Health and Medical Research Council. Grant Numbers: ID1061778, ID1104808 Carlos III National Health Centro de Investigación Biomédica en Red de Enferemdades Raras. Grant Number: ACCI 2016: ER17P1AC7112/2018 Cancer Council NSW Deutsche Krebshilfe. Grant Numbers: (#110837, #70111850 Fondazione Pisa. Grant Number: Grant “Clinical characterization of BRCA 1/2 Mis
Published: 2019

29. Radiomics : principles and radiotherapy applications

Author: Hortense A. Kirisli, Juliette Thariat, David Gibon, Pierre Vera, V. Grégoire, Isabelle Gardin, David Pasquier, Equipe Quantification en Imagerie Fonctionnelle (QuantIF-LITIS), Laboratoire d'Informatique, de Traitement de l'Information et des Systèmes (LITIS), Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Université Le Havre Normandie (ULH), Normandie Université (NU)-Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Normandie Université (NU), Service de médecine nucléaire [Rouen], CRLCC Haute Normandie-Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Aquilab, Service de radiothérapie / curiethérapie, Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université Lille Nord de France (COMUE)-UNICANCER-Université Lille Nord de France (COMUE)-UNICANCER, Université Le Havre Normandie (ULH), Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Université Le Havre Normandie (ULH), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA), Centre de Recherche en Informatique, Signal et Automatique de Lille - UMR 9189 (CRIStAL), Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Université de Lille-UNICANCER, Université Lille Nord de France (COMUE)-UNICANCER, and Université de Lille-UNICANCER-Université de Lille-UNICANCER
Subjects: Diagnostic Imaging, 0301 basic medicine, medicine.medical_specialty, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Medical Oncology, 03 medical and health sciences, 0302 clinical medicine, Radiomics, Neoplasms, Image Interpretation, Computer-Assisted, medicine, Humans, Medical physics, Modality (human–computer interaction), Radiotherapy, business.industry, Patient survival, Hematology, Method of analysis, Chemoradiotherapy, Response to treatment, 3. Good health, Radiation therapy, Identification (information), 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, Medical imaging, business
Abstract: International audience; Radiomics is defined as the extraction of a large quantity of quantitative image features. The different radiomic indexes that have been proposed in the literature are described as well as the various factors that have an impact on the robustness of these indexes. We will see that several hundred quantitative features can be extracted per lesion and imaging modality. The ever-growing number of features studied raises the question of the statistical method of analysis used.This review addresses the research supporting the clinical use of radiomics in oncology in the staging of disease, discrimination between healthy and pathological tissues, the identification of genetic features, the prediction of patient survival, the response to treatment, the recurrence after radiotherapy and chemoradiotherapy and the side effects.Based on the existing literature, it remains difficult to identify features that should be used for current clinical practice.
Published: 2019

30. Isolated ipsilateral local recurrence of breast cancer: predictive factors and prognostic impact

Author: Eric Lambaudie, Pierre-Emmanuel Colombo, Gilles Houvenaeghel, Christine Tunon de Lara, Monique Cohen, Anne-Sophie Azuar, Emile Daraï, Roman Rouzier, Jean-Marc Classe, Marie-Pierre Chauvet, Pierre Gimbergues, Alexandre de Nonneville, Anthony Gonçalves, Chafika Mazouni, Fabien Reyal, Charles Coutant, Aubert Agostini, Nicolas Chopin, Alejandra Martinez, Xavier Muracciole, Centre de Recherche en Cancérologie de Marseille (CRCM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Institut Curie [Paris], Institut Gustave Roussy (IGR), Centre Léon Bérard [Lyon], Institut Claudius Regaud, Gynécologie-obstétrique et médecine de la reproduction - Maternité [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), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), Département de Sénologie, Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université Lille Nord de France (COMUE)-UNICANCER-Université Lille Nord de France (COMUE)-UNICANCER, Hopital de Grasse, Hôpital René HUGUENIN (Saint-Cloud), Institut Bergonié [Bordeaux], Hôpital de la Timone [CHU - APHM] (TIMONE), Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Université de Lille-UNICANCER-Université de Lille-UNICANCER
Subjects: Adult, 0301 basic medicine, Oncology, Cancer Research, medicine.medical_specialty, Multivariate analysis, Survival, Breast Neoplasms, [SDV.CAN]Life Sciences [q-bio]/Cancer, Mastectomy, Segmental, Disease-Free Survival, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, Risk Factors, Internal medicine, medicine, Local recurrence, Humans, Endocrine system, Initial treatment, Aged, Retrospective Studies, business.industry, Systemic chemotherapy, Endocrine therapy, Cancer, Chemoradiotherapy, Middle Aged, medicine.disease, Prognosis, 3. Good health, Ipsilateral, 030104 developmental biology, Receptors, Estrogen, 030220 oncology & carcinogenesis, Multivariate Analysis, Cohort, Female, Neoplasm Recurrence, Local, business
Abstract: International audience; BACKGROUND:Tumour features associated with isolated invasive breast cancer (BC) ipsilateral local recurrence (ILR) after breast conservative treatment (BCT) and consequences on overall survival (OS) are still debated. Our objective was to investigate these points.METHODS:Patients were retrospectively identified from a cohort of patients who underwent BCT for invasive BC in 16 cancer centres. End-points were ILR rate and OS. The impact of ILR on OS was assessed by multivariate analysis (MVA) for all patients and according to endocrine receptors (ERs) and grade or tumour subtypes.RESULTS:Of 15,570 patients, ILR rate was 3.1%. Cumulative ILR rates differed according to ERs/grade (ERs+/Grade2: HR 1.42, p = 0.010; ERs+/Grade3: HR 1.41, p = 0.067; ERs-: HR 2.14, p
Published: 2019

31. French Recommendations for Osteoporosis Prevention and Treatment in Patients with Prostate Cancer Treated by Androgen Deprivation

Author: Pierre Mongiat Artus, Catherine Cormier, Philippe Beuzeboc, Françoise Debiais, Christophe Hennequin, Julien Paccou, Marie-Hélène Vieillard, Cyrille B. Confavreux, Eric Lespessailles, Didier Mayeur, Jacques Bonneterre, Jean-Michel Hannoun-Levi, Karine Briot, Bernard Cortet, Rose-Marie Javier, Béatrice Bouvard, Service de rhumatologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Marrow Adiposity & Bone Lab - Adiposité Médullaire et Os - ULR 4490 (MABLab (ex-pmoi)), Université du Littoral Côte d'Opale (ULCO)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Department of Medical Oncology, Institut Curie [Paris], Département de Sénologie, Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université Lille Nord de France (COMUE)-UNICANCER-Université Lille Nord de France (COMUE)-UNICANCER, Groupe d'Études Remodelage Osseux et bioMatériaux (GEROM), Université d'Angers (UA), Physiopathologie, diagnostic et traitements des maladies osseuses / Pathophysiology, Diagnosis & Treatments of Bone Diseases (LYOS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de rhumatologie[Lille], Hôpital Roger Salengro [Lille]-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), Université Côte d'Azur (UCA)-UNICANCER, Conservatoire botanique national de Franche-Comté, Les Hôpitaux Universitaires de Strasbourg (HUS), Centre Hospitalier Régional d'Orléans (CHRO), Institut mediterranéen des sciences de l'information et de la communication (IMSIC), Aix Marseille Université (AMU)-Université de Toulon (UTLN), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Université de Lille-UNICANCER-Université de Lille-UNICANCER, UNICANCER-Université Côte d'Azur (UCA), Imagerie Multimodale Multiéchelle et Modélisation du Tissu Osseux et articulaire (I3MTO), and Université d'Orléans (UO)
Subjects: Male, medicine.medical_specialty, Prévention, Bone disease, [SDV]Life Sciences [q-bio], Osteoporosis, 030232 urology & nephrology, Androgen deprivation therapy, Risk Assessment, Medication prescription, Gonadotropin-Releasing Hormone, 03 medical and health sciences, Prostate cancer, 0302 clinical medicine, Rheumatology, Bone Density, Risk Factors, Internal medicine, medicine, Humans, Dementia, Bone Resorption, LHRH agonists, bisphosphonates, Prostatectomy, 2. Zero hunger, Diphosphonates, business.industry, Prostatic Neoplasms, Androgen Antagonists, medicine.disease, osteoporosis, 3. Good health, Denosumab, 030220 oncology & carcinogenesis, recommendations, France, business, Orchiectomy, Body mass index, Osteoporotic Fractures, Surgical orchiectomy, medicine.drug, Bone loss Fracture
Abstract: International audience; Androgen-deprivation therapy (ADT) in patients with prostate cancer can be achieved surgically or chemically, notably by prescribing LHRH analogs. Major bone loss occurs rapidly in both cases, due to the decrease in testosterone levels, and can increase the fracture risk. The objective of developing these recommendations was to achieve a practical consensus among various scientific societies, based on a literature review, about osteoporosis prevention and treatment in patients on ADT. The following scientific societies contributed to the work: Société Française de Rhumatologie (SFR), Groupe de Recherche et d’Information sur les Ostéoporoses (GRIO), Groupe Européen d’Etudes des Métastases Osseuses (GEMO), Association Francophone pour les SOins de Support (AFSOS), Association Française d’Urologie (AFU), Société Française de Radiothérapie Oncologique (SFRO). Medication prescription and reimbursement modalities in France were taken into account. The recommendations state that a fracture-risk evaluation and interventions targeting risk factors for fractures should be provided to all patients on ADT. Those patients with a history of severe osteoporotic fracture and/or a T-score
Published: 2019

32. Isolation and characterization of two canine melanoma cell lines: new models for comparative oncology

Author: Zacharie Segaoula, Aline Primot, Benoit Hedan, Dominique Tierny, Frédéric Leprêtre, Catherine André, François Serres, Emmanuel Bouchaert, Sylvie Galiègue-Zouitina, Xavier Thuru, Kevin Minier, Bruno Quesnel, Laurent Marescaux, Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 (JPArc), Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Site de Recherche Intégrée en Cancérologie (SIRIC-ONCOLille), Université de Lille, Sciences et Technologies-Université de Lille, Sciences Humaines et Sociales-Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER-Université de Lille-UNICANCER-Cancéropole Nord-Ouest-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Lille, Sciences et Technologies, OCR SAS, French governmental association for industrial research, ANRT, Institut pour la Recherche sur le Cancer de Lille (IRCL), Jonchère, Laurent, Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U1172 Inserm - U837 (JPArc), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Lille Nord de France (COMUE)-Université de Lille, Université Lille Nord de France (COMUE)-UNICANCER-Université Lille Nord de France (COMUE)-UNICANCER-Cancéropole Nord-Ouest-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)
Subjects: 0301 basic medicine, Oncology, Cancer Research, [SDV.BIO]Life Sciences [q-bio]/Biotechnology, Skin Neoplasms, Preclinical models, Metastasis, 0403 veterinary science, Mice, Surgical oncology, Dog, Tumor Cells, Cultured, Medicine, Melanoma, Cancer, Mucosal melanoma, 04 agricultural and veterinary sciences, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, 3. Good health, Immunohistochemistry, Cell lines, Female, Mouth Neoplasms, Sample collection, Research Article, medicine.medical_specialty, 040301 veterinary sciences, Mice, Nude, [SDV.CAN]Life Sciences [q-bio]/Cancer, Antineoplastic Agents, Malignancy, lcsh:RC254-282, 03 medical and health sciences, Dogs, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, Cell Line, Tumor, Genetics, Canine Melanoma, Animals, Humans, Comparative oncology, Dose-Response Relationship, Drug, business.industry, medicine.disease, Xenograft Model Antitumor Assays, [SDV.BIO] Life Sciences [q-bio]/Biotechnology, 030104 developmental biology, business
Abstract: Background Metastatic melanoma is one of the most aggressive forms of cancer in humans. Among its types, mucosal melanomas represent one of the most highly metastatic and aggressive forms, with a very poor prognosis. Because they are rare in Caucasian individuals, unlike cutaneous melanomas, there has been fewer epidemiological, clinical and genetic evaluation of mucosal melanomas. Moreover, the lack of predictive models fully reproducing the pathogenesis and molecular alterations of mucosal melanoma makes its treatment challenging. Interestingly, dogs are frequently affected by melanomas of the oral cavity that are characterized, as their human counterparts, by focal infiltration, recurrence, and metastasis to regional lymph nodes, lungs and other organs. In dogs, some particular breeds are at high risk, suggesting a specific genetic background and strong genetic drivers. Altogether, the striking homologies in clinical presentation, histopathological features, and overall biology between human and canine mucosal melanomas make dogs invaluable natural models with which to investigate tumor development, including tumor ætiology, and develop tailored treatments. Methods We developed and characterized two canine oral melanoma cell lines from tumors isolated from dog patients with distinct clinical profiles; with and without lung metastases. The cells were characterized using immunohistochemistry, pharmacology and genetic studies. Results We have developed and immunohistochemically, genetically, and pharmacologically characterized. Two cell lines (Ocr_OCMM1X & Ocr_OCMM2X) were produced through mouse xenografts originating from two clinically contrasting melanomas of the oral cavity. Their exhaustive characterization showed two distinct biological and genetic profiles that are potentially linked to the stage of malignancy at the time of diagnosis and sample collection of each melanoma case. These cell lines thus constitute relevant tools with which to perform genetic and drug screening analyses for a better understanding of mucosal melanomas in dogs and humans. Conclusions The aim of this study was to establish and characterize xenograft-derived canine melanoma cell lines with different morphologies, genetic features and pharmacological sensitivities that constitute good predictive models for comparative oncology. These cell lines are relevant tools to advance the use of canine mucosal melanomas as natural models for the benefit of both veterinary and human medicine. Electronic supplementary material The online version of this article (10.1186/s12885-018-5114-y) contains supplementary material, which is available to authorized users.
Published: 2018

33. Prognostic and predictive factors for angiosarcoma patients receiving paclitaxel once weekly plus or minus bevacizumab: an ancillary study derived from a randomized clinical trial

Author: Thomas Ryckewaert, Axel Le Cesne, Yves Toiron, Olivier Mir, Luc Camoin, Emmanuelle Tresch-Bruneel, François Bertucci, Isabelle Ray-Coquard, Emmanuelle Bompas, Nicolas Penel, Marie-Cécile Le Deley, Antoine Italiano, Jean-Yves Blay, Loïc Lebellec, Anthony Gonçalves, Ecole de Médecine [CHRU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Département d’Oncologie Médicale [IPC, Marseille], Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Direction de la recherche et de l'innovation [Lille] (Centre Oscar Lambret), Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER-Université de Lille-UNICANCER, Département d'Oncologie Médicale [Lyon] ( Centre Léon Bérard), Centre Léon Bérard [Lyon], Sarcome, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Département d'oncologie médicale [ICO, Saint Herblain], Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER-UNICANCER, Département d'oncologie médicale, Institut Bergonié [Bordeaux], Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Université Paris-Sud - Paris 11 (UP11), Service de biostatistique et d'épidémiologie (SBE), Direction de la recherche clinique [Gustave Roussy], This work was supported by the French National Cancer Institute (INCa) [PHRC 2010] and ROCHE [grant number 0906-EPPA153667-G]., Bodescot, Myriam, Université Lille Nord de France (COMUE)-UNICANCER-Université Lille Nord de France (COMUE)-UNICANCER, CHU Lille, Université de Lille, METRICS : Evaluation des technologies de santé et des pratiques médicales - ULR 2694, Centre Hospitalier Régional Universitaire [Lille] [CHRU Lille], Department of Medical Oncology [Lyon], Institut Gustave Roussy [IGR], CRLCC René Gauducheau, Centre René Gauducheau, Service d'Oncologie Médicale [Centre hospitalier Lyon Sud - HCL], Evaluation des technologies de santé et des pratiques médicales - ULR 2694 [METRICS], Université Paris-Sud - Paris 11 [UP11], and Université Paris-Saclay
Subjects: 0301 basic medicine, Oncology, Vascular Endothelial Growth Factor A, Cancer Research, Multivariate analysis, Weekly paclitaxel, law.invention, chemistry.chemical_compound, 0302 clinical medicine, Randomized controlled trial, law, Surgical oncology, Angiosarcoma, Aged, 80 and over, Univariate analysis, Middle Aged, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Prognosis, 3. Good health, Bevacizumab, Paclitaxel, 030220 oncology & carcinogenesis, Female, medicine.drug, Research Article, Adult, medicine.medical_specialty, Hemangiosarcoma, [SDV.CAN]Life Sciences [q-bio]/Cancer, lcsh:RC254-282, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, Genetics, medicine, Biomarkers, Tumor, Humans, Aged, Placenta Growth Factor, Proportional hazards model, business.industry, Radiation-induced angiosarcoma, Antineoplastic Agents, Phytogenic, 030104 developmental biology, chemistry, Biomarkers, business
Abstract: Background We report here a correlation analysis conducted along with a phase II trial assessing bevacizumab in combination with weekly paclitaxel. Methods Circulating pro/anti-angiogenic factors were assessed on day 1 (D1) and day 8 (D8). The prognostic value for progression-free survival (PFS) was evaluated using a Cox model with biomarkers as continuous variables. Results Among the 51 patients enrolled and treated in this trial, biomarker analysis was performed for 42: 18 in Arm A (single-agent) and 24 in Arm B (combination). With a median follow-up of 46 months, PFS was 5.5 versus 5.7 months, respectively (p = 0.75). According to univariate analysis, factors associated with a poor PFS were as follows: visceral angiosarcoma, de novo angiosarcoma, and high PlGF and low VEGF-C baseline values. In multivariate analysis, de novo angiosarcoma (HR = 2.5; p = 0.024) and baseline VEGF-C value (HR = 0.7; p = 0.003) were significant prognostic factors. We observed a significant increase in circulating PlGF (
Published: 2018

34. Salvage Surgery for Esophageal Cancer: How to Improve Outcomes?

Author: Denis Collet, Christophe Mariette, Jérémie Thereaux, Caroline Gronnier, Bernard Meunier, Charlotte Cohen, Fregat, Guillaume Piessen, Williams Tessier, Johan Gagnière, Florence Renaud, Arnaud Pasquer, Centre Hospitalier Universitaire de Nice (CHU Nice), Hôpital Claude Huriez [Lille], CHU Lille, Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 (JPArc), Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Service de pathologie [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Hôpital de la Cavale Blanche - CHRU Brest (CHU - BREST ), CHU Clermont-Ferrand, CHU Pontchaillou [Rennes], Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Site de Recherche Intégrée en Cancérologie (SIRIC-ONCOLille), Université de Lille, Sciences et Technologies-Université de Lille, Sciences Humaines et Sociales-Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER-Université de Lille-UNICANCER-Cancéropole Nord-Ouest-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université de Montpellier (UM), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U1172 Inserm - U837 (JPArc), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Lille Nord de France (COMUE)-Université de Lille, and Université Lille Nord de France (COMUE)-UNICANCER-Université Lille Nord de France (COMUE)-UNICANCER-Cancéropole Nord-Ouest-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)
Subjects: Adult, Male, medicine.medical_specialty, Neoplasm, Residual, Esophageal Neoplasms, Anastomotic Leak, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.MHEP.CHI]Life Sciences [q-bio]/Human health and pathology/Surgery, Anastomosis, 03 medical and health sciences, 0302 clinical medicine, Humans, Medicine, Hospital Mortality, Stage (cooking), Survival rate, Aged, Neoplasm Staging, Retrospective Studies, Aged, 80 and over, Salvage Therapy, business.industry, Standard treatment, Radiotherapy Dosage, Retrospective cohort study, Chemoradiotherapy, Middle Aged, Esophageal cancer, medicine.disease, 3. Good health, Surgery, Esophagectomy, Survival Rate, Treatment Outcome, Oncology, 030220 oncology & carcinogenesis, Cohort, Carcinoma, Squamous Cell, Female, 030211 gastroenterology & hepatology, Neoplasm Recurrence, Local, business
Abstract: International audience; BACKGROUND:Locoregional recurrence rates after definitive chemoradiotherapy (dCRT) for locally advanced esophageal cancer (EC) are high. Salvage surgery (SALV) is considered the best treatment option in case of persistent or recurrent disease for operable patients, but SALV has been associated with increased morbidity and mortality. The aim of this study is to identify factors linked to outcomes after SALV to better select candidates and to optimize perioperative care.STUDY DESIGN:We retrospectively analyzed data from 308 consecutive SALV patients from a large multicenter European cohort. Univariate and multivariate analyses were performed to identify factors associated with in-hospital postoperative morbidity, anastomotic leakage (AL), and overall survival (OS).RESULTS:The in-hospital postoperative mortality and morbidity rates were 8.4 and 34.7%, respectively. Squamous cell histology (p = 0.040) and radiation dose ≥ 55 Gy (p = 0.047) were independently associated with major morbidity. The AL rate was 12.7%, and cervical anastomosis was independently associated with AL (p = 0.002). OS at 5 years was 34.0%. Radiation dose ≥ 55 Gy (p = 0.003), occurrence of postoperative complications (p = 0.006), ypTNM stage 3 (p = 0.019), and positive surgical margins (p < 0.001) were linked to poor prognosis.CONCLUSIONS:SALV is a valuable option for patients with persistent or recurrent disease after dCRT and offers long-term survival. Factors such as radiation dose and anastomosis location identified here will help to optimize outcomes after SALV, which may be considered a standard treatment in the EC therapeutic armamentarium.
Published: 2018

35. In Reply to El Majjaoui et al

Author: David Pasquier, Service de radiothérapie / curiethérapie, Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université Lille Nord de France (COMUE)-UNICANCER-Université Lille Nord de France (COMUE)-UNICANCER, Centre de Recherche en Informatique, Signal et Automatique de Lille - UMR 9189 (CRIStAL), Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS), and Université de Lille-UNICANCER-Université de Lille-UNICANCER
Subjects: Cancer Research, Radiation, Oncology, business.industry, [SDV]Life Sciences [q-bio], Medicine, Radiology, Nuclear Medicine and imaging, [SDV.CAN]Life Sciences [q-bio]/Cancer, business, Humanities, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2018

36. Diffusion weighted MRI as an early predictor of tumor response to hypofractionated stereotactic boost for prostate cancer

Author: Abderraouf Hadj Henni, Eric Lartigau, Olivier Colot, Nick Reynaert, Alexandre Escande, Emmanuelle Tresch, Nacim Betrouni, David Pasquier, Service de radiothérapie / curiethérapie, Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER-Université de Lille-UNICANCER, Laboratoire Pluridisciplinaire de Recherche en Ingénierie des Systèmes, Mécanique et Energétique (PRISME), Université d'Orléans (UO)-Ecole Nationale Supérieure d'Ingénieurs de Bourges (ENSI Bourges), Université de Lille-UNICANCER, LAGIS-SI, Laboratoire d'Automatique, Génie Informatique et Signal (LAGIS), Université de Lille, Sciences et Technologies-Centrale Lille-Centre National de la Recherche Scientifique (CNRS)-Université de Lille, Sciences et Technologies-Centrale Lille-Centre National de la Recherche Scientifique (CNRS), ImaBiotech, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Université Lille Nord de France (COMUE)-UNICANCER-Université Lille Nord de France (COMUE)-UNICANCER, Ecole Nationale Supérieure d'Ingénieurs de Bourges (ENSI Bourges)-Université d'Orléans (UO), Université Lille Nord de France (COMUE)-UNICANCER, Pasquier, David, Centre de Recherche en Informatique, Signal et Automatique de Lille - UMR 9189 (CRIStAL), and Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, medicine.medical_treatment, [SDV]Life Sciences [q-bio], lcsh:Medicine, [SDV.CAN]Life Sciences [q-bio]/Cancer, Tumor response, Article, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, Prostate cancer, 0302 clinical medicine, Imaging, Three-Dimensional, [SDV.CAN] Life Sciences [q-bio]/Cancer, Medicine, Humans, In patient, External beam radiotherapy, lcsh:Science, ComputingMilieux_MISCELLANEOUS, Aged, Multidisciplinary, business.industry, lcsh:R, Prostate, Prostatic Neoplasms, Middle Aged, Prostate-Specific Antigen, medicine.disease, [SDV] Life Sciences [q-bio], Prostate-specific antigen, Diffusion Magnetic Resonance Imaging, 030220 oncology & carcinogenesis, Biomarker (medicine), lcsh:Q, Radiation Dose Hypofractionation, Intermediate risk, business, Nuclear medicine, [SPI.SIGNAL]Engineering Sciences [physics]/Signal and Image processing, Diffusion MRI
Abstract: We evaluated the feasibility of using the kinetic of diffusion-weighted MRI (DWI) and the normalized apparent coefficient diffusion (ADC) map value as an early biomarker in patients treated by external beam radiotherapy (EBRT). Twelve patients were included within the frame of a multicenter phase II trial and treated for intermediate risk prostate cancer (PCa). Multiparametric MRI was performed before treatment (M0) and every 6 months until M24. Association between nADC and PSA or PSA kinetic was evaluated using the test of nullity of the Spearman correlation coefficient. The median rates of PSA at the time of diagnosis, two years and four years after EBRT were 9.29 ng/ml (range from 5.26 to 17.67), 0.68 ng/ml (0.07–2.7), 0.47 ng/ml (0.09–1.39), respectively. Median nADC increased from 1.14 × 10−3 mm2/s to 1.59 × 10−3 mm2/s between M0 and M24. Only one patient presented a decrease of nADC (1.35 × 10−3 mm2/s and 1.11 × 10−3 mm2/s at M0 and M12 respectively). The increase in nADC at M6 was correlated with PSA decrease at M18, M24 and M30 (p
Published: 2018

37. c-MET Overexpression as a Poor Predictor of MET Amplifications or Exon 14 Mutations in Lung Sarcomatoid Carcinomas

Author: Nicolas Girard, Alexis B. Cortot, Denis Moro-Sibilot, Antoinette Lemoine, Raphaël Saffroy, Sylvie Lantuejoul, Xavier Mignard, Isabelle Rouquette, Nathalie Rabbe, Anne-Marie Ruppert, Julie Vasseur, Marie Wislez, Julien Mazieres, Jacques Cadranel, Vincent Fallet, Françoise Thivolet-Béjui, Martine Antoine, Sorbonne Université (SU), 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), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Theranoscan, Université Pierre et Marie Curie - Paris 6 (UPMC), Service d’Anatomie et cytologie pathologiques [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), Hôpital Paul Brousse, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse, Hospices Civils de Lyon (HCL), Hôpital Louis Pradel [CHU - HCL], CHU Grenoble, Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Léon Bérard [Lyon], Site de Recherche Intégrée en Cancérologie (SIRIC-ONCOLille), Université de Lille, Sciences et Technologies-Université de Lille, Sciences Humaines et Sociales-Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université Lille Nord de France (COMUE)-UNICANCER-Université Lille Nord de France (COMUE)-UNICANCER-Cancéropole Nord-Ouest-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Groupe de recherche clinique Biomarqueurs Théranostiques des Cancers Bronchiques Non à Petites Cellules (GRC 4 - Theranoscan), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), 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), Université de Lille-UNICANCER-Université de Lille-UNICANCER-Cancéropole Nord-Ouest-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: 0301 basic medicine, Oncology, Male, Lung Neoplasms, [SDV]Life Sciences [q-bio], MET Exon 14 Mutation, Cohort Studies, chemistry.chemical_compound, Exon, 0302 clinical medicine, Carcinoma, Non-Small-Cell Lung, Medicine, Copy-number variation, In Situ Hybridization, Fluorescence, Chromosome 7 (human), Aged, 80 and over, biology, medicine.diagnostic_test, Carcinoma, Giant Cell, Sarcoma, Exons, Middle Aged, Proto-Oncogene Proteins c-met, Prognosis, Immunohistochemistry, 3. Good health, 030220 oncology & carcinogenesis, MET, Female, Antibody, Pulmonary and Respiratory Medicine, Adult, medicine.medical_specialty, C-Met, Amplification, 03 medical and health sciences, Internal medicine, Biomarkers, Tumor, Humans, Aged, Lung sarcomatoid carcinoma, business.industry, Gene Amplification, 030104 developmental biology, chemistry, Mutation, biology.protein, Exon 14 mutations, business, Fluorescence in situ hybridization, Follow-Up Studies
Abstract: Introduction MNNG HOS transforming gene (MET) abnormalities such as amplification and exon 14 mutations may be responsive to targeted therapies. They are prevalent in lung sarcomatoid carcinomas (LSCs) and must be diagnosed as efficiently as possible. Hypothetically, c-MET overexpression by immunohistochemistry (IHC) may prove effective as a screening test for MET abnormalities. Methods Tissue samples were obtained from consecutive patients with a resected LSC in four oncologic centers. IHC was performed using the SP44 antibody (Ventana, Tucson, Arizona) and evaluated using the MetMab score and H-score. Fluorescence in situ hybridization was applied with the dual color probe set from Zytovision (Clinisciences, Nanterre, France). True MET amplification was diagnosed when MET gene copy number was 5 or greater and the ratio between MET gene copy number and chromosome 7 number was greater than 2. All MET exon 14 alterations including those affecting splice sites occurring within splice donor and acceptor sites were detected in the routine molecular testing on genetic platforms. Results A total of 81 LSCs were included. Fourteen (17%) exhibited positive IHC using the MetMab score and 15 (18.5%) using the H-score. MET amplification was detected in six tumors (8.5%) and MET exon 14 mutation in five (6%). A weak positive correlation between IHC and fluorescence in situ hybridization was found (r = 0.27, p = 0.0001). IHC sensitivity for MET amplification was 50%, with a specificity of 83%, positive predictive value of 21.4%, and negative predictive value of 94.7%. IHC sensitivity for MET exon 14 mutations was 20%, with a specificity of 83%, positive predictive value of 7%, and negative predictive value of 94%. Conclusion IHC is not a relevant screening tool for MET abnormalities in LSC.
Published: 2018

38. Impact of Trabectedin Interruption and Subsequent Rechallenge on Progression in Patients With Advanced Soft Tissue Sarcoma

Author: Kotecki, Nuria, Le Cesne, Axel, Tresch-Bruneel, Emmanuelle, Ray-Coquard, Isabelle, Chevreau, Christine, Bertucci, François, Bogart, Emilie, Mir, Olivier, Pautier, Patricia, Decoupigny, Emilie, Clisant, Stéphanie, Blay, Jean-Yves, Penel, Nicolas, Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 (JPArc), Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Sarcome, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Direction de la recherche et de l'innovation [Lille] (Centre Oscar Lambret), Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER-Université de Lille-UNICANCER, Département d'Oncologie Médicale [Lyon] ( Centre Léon Bérard), Centre Léon Bérard [Lyon], 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), Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Lille-UNICANCER, Service d'Oncologie Médicale [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Ecole de Médecine [CHRU Lille], and Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)
Subjects: [SDV.CAN]Life Sciences [q-bio]/Cancer, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2018

39. Clinicopathological description of 43 oncocytic adrenocortical tumors: importance of Ki-67 in histoprognostic evaluation

Author: Delphine Vezzosi, Abir Al Ghuzlan, Delphine Drui, Matthieu Wargny, Sébastien Aubert, Sarra Smati, Olivier Chabre, Laurence Amar, Claire Briet, François Pattou, Rossella Libé, Martine Patey, Bertrand Cariou, Frédérique Tissier, Karine Renaudin, Nathalie Sturm, Jérôme Bertherat, Magalie Haissaguerre, Peggy Pierre, Mathilde Sibony, Jean Christophe Lifante, Claudine Berthozat, Emmanuelle Leteurtre, Christine Do Cao, Eric Baudin, Eric Mirallié, Service de Pathologie [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), Département de biologie et pathologie médicales [Gustave Roussy], Institut Gustave Roussy (IGR), Service de pathologie [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U1172 Inserm - U837 (JPArc), Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Site de Recherche Intégrée en Cancérologie (SIRIC-ONCOLille), Université de Lille, Sciences et Technologies-Université de Lille, Sciences Humaines et Sociales-Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université Lille Nord de France (COMUE)-UNICANCER-Université Lille Nord de France (COMUE)-UNICANCER-Cancéropole Nord-Ouest-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Laboratoire d’anatomie et cytologie pathologique, Hôpital Robert Debré, CHU de Reims, 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), Département de Gastroentérologie et hépatologie, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-Hôpital Michallon, Centre Hospitalier Universitaire Grenoble Alpes (CHU Grenoble Alpes), Université Paris-Sorbonne (UP4), Service d'HYPERVASC [CHU HEGP), 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)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Service d'Endocrinologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre de Référence pour les Maladies Rares, Université Grenoble Alpes - UFR Médecine (UGA UFRM), Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Service d'endocrinologie-diabétologie-nutrition [CHU Grenoble-Alpes], Service d’endocrinologie, diabétologie et maladies métaboliques [CHRU LIlle], Département d'endocrinologie - Bordeaux 2, Université Bordeaux Segalen - Bordeaux 2, Service d'Endocrinologie (TOURS - Endocrino), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'Endocrinologie (TOULOUSE - Endocrino), CHU Toulouse [Toulouse], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Service de Chirurgie Générale et Endocrinienne [Lyon], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Health Service and Performance Research (HESPER), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Service de chirurgie générale et endocrinienne, Hôpital Claude Huriez [Lille], CHU Lille-CHU Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de Chirurgie Digestive et Endocrinienne [Nantes], Médecine nucléaire, Département d'imagerie médicale [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5), Service d'Endocrinologie [Nantes], Unité de recherche de l'institut du thorax (ITX-lab), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 (JPArc), Université de Lille-UNICANCER-Université de Lille-UNICANCER-Cancéropole Nord-Ouest-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Universitaire [Grenoble] (CHU), MitoVasc - Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), Service Endocrinologie, maladies métaboliques et nutrition [CHU Toulouse], Pôle Cardiovasculaire et Métabolique [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Lille Nord de France (COMUE)-Université de Lille
Subjects: 0301 basic medicine, Oncology, Adult, Male, medicine.medical_specialty, Pathology, Proliferation index, Adenoma, [SDV]Life Sciences [q-bio], Malignancy, Pathology and Forensic Medicine, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Carcinoma, Biomarkers, Tumor, Adenoma, Oxyphilic, Humans, Stage (cooking), Retrospective Studies, biology, business.industry, Retrospective cohort study, Middle Aged, medicine.disease, Prognosis, Adrenal Cortex Neoplasms, 3. Good health, 030104 developmental biology, Ki-67 Antigen, 030220 oncology & carcinogenesis, Ki-67, Cohort, biology.protein, Female, business
Abstract: International audience; Oncocytic adrenocortical tumors are a rare subtype of adrenal tumors with challenging diagnosis and histoprognostic assessment. It is usually believed that oncocytic adrenocortical tumors have a more indolent clinical behavior than conventional adrenocortical tumors. As the Weiss score overestimates the malignancy of oncocytic adrenocortical tumors owing to intrinsic parameters, alternative scores have been proposed. The Lin-Weiss-Bisceglia score is currently recommended. We performed a large nationwide multicenter retrospective clinicopathologic study of oncocytic adrenocortical tumors. Among the 43 patients in our cohort, 40 patients were alive without disease, 2 patients died of their disease and 1 patient was alive with relapse after a median follow-up of 38 months (20-59). Our data revealed that over 50% of the oncocytic adrenocortical tumor cases were diagnosed as carcinoma whatever the classification systems used, including the Lin-Weiss-Bisceglia score. The exception is the Helsinki score, which incorporates the Ki-67 proliferation index and was the most specific prognostic score for oncocytic adrenocortical tumor malignancy without showing a loss in sensitivity. A comparison of malignant oncocytic adrenocortical tumors with conventional adrenocortical carcinomas matched for age, sex, ENS@T stage and surgical resection status showed significant better overall survival of malignant oncocytic adrenocortical tumors.
Published: 2018

40. Induction of fetal hemoglobin synthesis by CRISPR/Cas9-mediated editing of the human beta-globin locus

Author: Giulia Pavani, Wassim El Nemer, Oriana Romano, Chiara Antoniani, Ante Sven Lundberg, Yukio Nakamura, Vasco Meneghini, Sara El Hoss, Fulvio Mavilio, Annarita Miccio, Annalisa Lattanzi, Thomas J. Cradick, Mario Amendola, Marina Cavazzana, Ryo Kurita, Tristan Felix, Matthew H. Porteus, Elisa Magrin, Leslie Weber, Approches génétiques intégrées et nouvelles thérapies pour les maladies rares (INTEGRARE), Université d'Évry-Val-d'Essonne (UEVE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Généthon-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), Human Lymphohematopoiesis Laboratory (Equipe Inserm U1163), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Site de Recherche Intégrée en Cancérologie (SIRIC-ONCOLille), Université de Lille, Sciences et Technologies-Université de Lille, Sciences Humaines et Sociales-Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université Lille Nord de France (COMUE)-UNICANCER-Université Lille Nord de France (COMUE)-UNICANCER-Cancéropole Nord-Ouest-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), European Synchrotron Radiation Facility (ESRF), INSERM U665, affiliation inconnue, Généthon, École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université d'Évry-Val-d'Essonne (UEVE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Généthon, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Université de Lille-UNICANCER-Université de Lille-UNICANCER-Cancéropole Nord-Ouest-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), and ANR-16-CE18-0004,GETH,L'Édition Génomique comme outil Thérapeutique contre les ß-Hémoglobinopathies(2016)
Subjects: 0301 basic medicine, Cell Line, Hematopoietic Stem Cells, Humans, beta-Globins, Anemia, Sickle Cell, CRISPR-Cas Systems, Fetal Hemoglobin, Gene Editing, Genetic Loci, congenital, hereditary, and neonatal diseases and abnormalities, Hereditary persistence of fetal hemoglobin, [SDV]Life Sciences [q-bio], Immunology, Biology, Biochemistry, 03 medical and health sciences, Human β-globin locus, hemic and lymphatic diseases, Fetal hemoglobin, medicine, CRISPR, Globin, Epigenetics, Genetics, Cas9, Anemia, Cell Biology, Hematology, medicine.disease, Chromatin, Sickle Cell, 030104 developmental biology, BLOOD Commentary
Abstract: International audience; Naturally occurring, large deletions in the beta-globin locus result in hereditary persistence of fetal hemoglobin, a condition that mitigates the clinical severity of sickle cell disease (SCD) and beta-thalassemia. We designed a clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated protein 9 (Cas9) (CRISPR/Cas9) strategy to disrupt a 13.6-kb genomic region encompassing the delta- and beta-globin genes and a putative gamma-delta intergenic fetal hemoglobin (HbF) silencer. Disruption of just the putative HbF silencer results in a mild increase in gamma-globin expression, whereas deletion or inversion of a 13.6-kb region causes a robust reactivation of HbF synthesis in adult erythroblasts that is associated with epigenetic modifications and changes in chromatin contacts within the beta-globin locus. In primary SCD patient-derived hematopoietic stem/progenitor cells, targeting the 13.6-kb region results in a high proportion of gamma-globin expression in erythroblasts, increased HbF synthesis, and amelioration of the sickling cell phenotype. Overall, this study provides clues for a potential CRISPR/Cas9 genome editing approach to the therapy of beta-hemoglobinopathies.
Published: 2018

41. Hypofractionated stereotactic boost in intermediate risk prostate carcinoma: Preliminary results of a multicenter phase II trial (CKNO-PRO)

Author: David Pasquier, Philippe Nickers, Didier Peiffert, Philippe Maingon, Pascal Pommier, Thomas Lacornerie, Geoffrey Martinage, Emmanuelle Tresch, Eric Lartigau, Amir Abdollahi, Service de radiothérapie / curiethérapie, Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER-Université de Lille-UNICANCER, Centre de Recherche en Informatique, Signal et Automatique de Lille - UMR 9189 (CRIStAL), Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), UNICANCER, Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), Centre Léon Bérard [Lyon], Université de Lille-UNICANCER, Pasquier, David, Université Lille Nord de France (COMUE)-UNICANCER-Université Lille Nord de France (COMUE)-UNICANCER, and Université Lille Nord de France (COMUE)-UNICANCER
Subjects: [SDV] Life Sciences [q-bio], [SDV.CAN] Life Sciences [q-bio]/Cancer, [SDV]Life Sciences [q-bio], [SDV.CAN]Life Sciences [q-bio]/Cancer, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2017

42. Results of methotrexate-etoposide-ifosfamide based regimen (M-EI) in osteosarcoma patients included in the French OS2006/sarcome-09 study

Author: Cécile Verite-Goulard, Nadir Cheurfa, Laurence Brugières, Sophie Piperno-Neumann, Laure Saumet, Nathalie Gaspar, Nadège Corradini, Perrine Marec-Berard, Hervé Brisse, Marie-Cécile Le Deley, Françoise Rédini, Claudine Schmitt, Gsf-Geto (Groupe Sarcome Français), Jessy Delaye, Hélène Pacquement, Emmanuelle Bompas, Marie-Pierre Castex, Jean-Claude Gentet, Bob-Valéry Occean, Natacha Entz-Werle, Cyril Lervat, Eric Mascard, Marie-Dominique Tabone, Corine Bouvier, Sfce, Antoine Italiano, Département de cancérologie de l'enfant et de l'adolescent [Gustave Roussy], Institut Gustave Roussy (IGR), Service de biostatistique et d'épidémiologie (SBE), Direction de la recherche clinique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Département d'oncologie pédiatrique [Institut Curie, Paris], Institut Curie [Paris], Département d'oncologie médicale [Saint Herblain], Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER-UNICANCER, Département de pathologie [CHU La Timone, Marseille], Hôpital de la Timone [CHU - APHM] (TIMONE), Service de l'Imagerie [Institut Curie, Paris], Paris-Sciences-et-Lettres Research University [Paris], Département d'oncologie pédiatrique [CHU Toulouse], CHU Toulouse [Toulouse], Département d'Oncologie Pédiatrique [CHU Nantes], Hôpital Mère-Enfant, CHU de Nantes, UNICANCER [Paris], Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Département d'Oncologie Pédiatrique [CHU Hautepierre, Strasbourg], Hôpital de Hautepierre [Strasbourg], Pédiatrie et oncologie pédiatrique [Hôpital de la Timone - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Département d'oncologie médicale, Institut Bergonié [Bordeaux], Unité d'oncologie pédiatrique [Centre Oscar Lambret, Lille], Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université Lille Nord de France (COMUE)-UNICANCER-Université Lille Nord de France (COMUE)-UNICANCER, Département d'oncologie pédiatrique [Centre Léon Bérard, Lyon], Centre Léon Bérard [Lyon], Service de chirurgie orthopédique et traumatologie pédiatrique [CHU Necker ], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Physiopathologie des Adaptations Nutritionnelles (PhAN), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Département d'oncologie pédiatrique [Hôpital A. de Villeneuve, Montpellier], Hôpital Arnaud de Villeneuve [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service d'Hématologie et d'Oncologie Pédiatrique [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Département d'oncologie pédiatrique [CHU Bordeaux], Hôpital des Enfants - Groupe hospitalier Pellegrin - CHU de Bordeaux, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Lille Nord de France (COMUE)-UNICANCER, Département d'Oncologie Médicale [Institut Curie, Paris], French National Cancer Institute (INCa) (INCA RC004 and PHRC-K13-041), NOVARTIS, Chugai, Ligue Nationale contre le Cancer, Fédération Enfants et Santé, Société Française des Cancers et Leucémies de l’Enfant., the SFCE (Société Française des Cancers de l’Enfant et l’adolescent), GSF-GETO (Groupe Sarcome Français), the UNICANCER sarcoma group., Sercice Hématologie, immunologie et oncologie pédiatrique [CHU Toulouse], Pôle Enfants [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Lille-UNICANCER-Université de Lille-UNICANCER, Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN), Université de Lille-UNICANCER, and maurice, sandrine
Subjects: Male, 0301 basic medicine, Cancer Research, medicine.medical_treatment, Kaplan-Meier Estimate, Zoledronic Acid, 0302 clinical medicine, Antineoplastic Combined Chemotherapy Protocols, Medicine, Young adult, Child, Etoposide, [SDV.MHEP.RSOA] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Osteosarcoma, Ifosfamide, Diphosphonates, Imidazoles, Combined Modality Therapy, 3. Good health, Oncology, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Child, Preschool, 030220 oncology & carcinogenesis, Female, France, medicine.drug, Adult, medicine.medical_specialty, Neutropenia, Adolescent, Bone Neoplasms, [SDV.CAN]Life Sciences [q-bio]/Cancer, Young Adult, 03 medical and health sciences, [SDV.MHEP.PED] Life Sciences [q-bio]/Human health and pathology/Pediatrics, [SDV.CAN] Life Sciences [q-bio]/Cancer, Humans, Chemotherapy, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, business.industry, medicine.disease, Surgery, Regimen, 030104 developmental biology, Methotrexate, Doxorubicin, Cisplatin, business
Abstract: Background In most countries, reference chemotherapy for osteosarcoma is MAP regimen (M = high-dose methotrexate, AP = doxorubicin-cisplatinum). In France, the standard preoperative chemotherapy for children/adolescents combines M and etoposide-ifosfamide (EI), based on the OS94-trial. We report the safety and efficacy results of patients ≤25 years treated with preoperative M-EI regimen enroled in the French OS2006-study, between 2007 and 2014. Methods Treatment comprised preoperative chemotherapy with the 7 M-courses and 2 EI-courses, then surgery and postoperative chemotherapy assigned by risk's groups: standard-risk (good histological response without metastases) received 12 M-courses, 3 EI-courses; high-risk (poor histologic response, initial metastases or unresectable primary) received 5 M-courses alternated with 5 AP-courses. 253 patients were randomised to receive (n = 128) or not (n = 125) zoledronate. Results 409/522 patients enroled in the OS2006 study who received preoperative M-EI were analysed. Median age was 14.3 years (4.7–24.5), with 55 patients aged 18–25 years. Primary tumour location was limb in 383 patients (94%) and 85 (21%) presented metastases. Median chemotherapy duration was 37.4 weeks. 381 (96%) patients underwent surgery, 258 patients (65%) had a good histologic response. 187/324 patients (58%) with localised disease did not receive doxorubicin nor cisplatinum. Toxicity was evaluated in the randomised study: most patients experienced ≥1 severe toxicity (grade IV haematological or grade III/IV extra-haematological). Median follow-up was 4.8 years, and 168 patients had events. Five-year event-free survival was 56% (95% CI, 51–62%) and overall survival 71% (66–76%). Conclusion M-EI regimen/strategy was feasible for patient aged ≤25 years with survival rates are comparable to those obtained with MAP regimen.
Published: 2017

43. Longitudinal serum metabolomics evaluation of trastuzumab and everolimus combination as pre-operative treatment for HER-2 positive breast cancer patients

Author: Maria Rios, Marta Jimenez, Jacques Bonneterre, Bénédicte Elena-Herrmann, Olivier Tredan, Elodie Jobard, Véronique Diéras, Celine Mahier Ait-Oukhatar, Monica Arnedos, Thomas Bachelot, Jean-Louis Merlin, Arnaud M. Vigneron, Mario Campone, ISA NMR Methods for Metabolism - Methodes RMN en métabolomique (2014-2018), Institut des Sciences Analytiques (ISA), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Department of Medical Oncology [Lyon], Centre Léon Bérard [Lyon], Oncogénèse et progression tumorale, Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Pathologie mammaire, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Département d’Oncologie Médicale [Vandoeuvre Les Nancy], Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), UNICANCER-UNICANCER, Département de Sénologie, Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER-Université de Lille-UNICANCER, Institut Curie [Paris], UNICANCER, Centre de Recherche en Automatique de Nancy (CRAN), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Financial support from the IR-RMN-THC Fr3050 CNRS for conducting the research is gratefully acknowledged., Université Lille Nord de France (COMUE)-UNICANCER-Université Lille Nord de France (COMUE)-UNICANCER, and Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL)
Subjects: 0301 basic medicine, Oncology, medicine.medical_specialty, mTOR inhibitor, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, 03 medical and health sciences, Breast cancer, Trastuzumab, [CHIM.ANAL]Chemical Sciences/Analytical chemistry, Internal medicine, Medicine, In patient, Protein translation, skin and connective tissue diseases, Preoperative treatment, Everolimus, business.industry, HER-2 positive breast cancer, medicine.disease, Serum samples, Discovery and development of mTOR inhibitors, metabolomics, targeted therapies, 3. Good health, Surgery, nuclear magnetic resonance, 030104 developmental biology, business, medicine.drug, Research Paper
Abstract: // Elodie Jobard 1, 2 , Olivier Tredan 2 , Thomas Bachelot 2 , Arnaud M. Vigneron 3 , Celine Mahier Ait-Oukhatar 4 , Monica Arnedos 5 , Maria Rios 6 , Jacques Bonneterre 7 , Veronique Dieras 8 , Marta Jimenez 4 , Jean-Louis Merlin 9, 10 , Mario Campone 11 and Benedicte Elena-Herrmann 1 1 Universite de Lyon, Institut des Sciences Analytiques, UMR 5280, CNRS, Universite Lyon 1, ENS de Lyon, Villeurbanne, France 2 Universite de Lyon, Centre Leon Berard, Departement d’oncologie medicale, Lyon, France 3 Universite de Lyon, Centre de Cancerologie de Lyon, UMR Inserm 1052 CNRS 5286, Centre Leon Berard, Lyon, France 4 R&D Unicancer, UNICANCER, Paris, France 5 Department of Medicine, Gustave Roussy, Villejuif, France 6 Department of Medical Oncology, Centre Alexis Vautrin, Vandoeuvre-les-Nancy, France 7 Department of Medical Oncology, Centre Oscar Lambret, Lille, France 8 Department of Medical Oncology, Institut Curie, Paris, France 9 CNRS UMR7039 CRAN, Universite de Lorraine, Vandoeuvre-les-Nancy, France 10 Department of Biopathology Unit, Institut de Cancerologie de Lorraine, Vandoeuvre-Les-Nancy, France 11 Institut de Cancerologie de l’Ouest, Centre Rene Gauducheau, Saint-Herblain, France Correspondence to: Benedicte Elena-Herrmann, email: benedicte.elena@ens-lyon.fr Olivier Tredan, email: olivier.tredan@lyon.unicancer.fr Keywords: HER-2 positive breast cancer, metabolomics, nuclear magnetic resonance, targeted therapies, mTOR inhibitor Received: April 04, 2017 Accepted: May 23, 2017 Published: June 28, 2017 ABSTRACT The mammalian target of rapamycin complex 1 (mTORC1) is an attractive target for HER-2 positive breast cancer therapy because of its key role in protein translation regulation, cell growth and metabolism. We present here a metabolomic investigation exploring the impact of mTOR inhibition on serum metabolic profiles from patients with non-metastatic breast cancer overexpressing HER-2. Baseline, treatment-related and post-treatment serum samples were analyzed for 79 patients participating in the French clinical trial RADHER, in which randomized patients with HER-2 positive breast cancer received either trastuzumab alone (arm T) or a trastuzumab and everolimus combination (arm T+E). Longitudinal series of NMR serum metabolic profiles were exploited to investigate treatment effects on the patients metabolism over time, in both group. Trastuzumab and everolimus combination induces faster changes in patients metabolism than trastuzumab alone, visible after only one week of treatment as well as a residual effect detectable up to three weeks after ending the treatment. These metabolic fingerprints highlight the involvement of several metabolic pathways reflecting a systemic effect, particularly on the liver and visceral fat. Comparison of serum metabolic profiles between the two arms shows that everolimus, an mTORC1 inhibitor, is responsible for host metabolism modifications observed in arm T+E. In HER-2 positive breast cancer, our metabolomic approach confirms a fast and persistent host metabolism modification caused by mTOR inhibition.
Published: 2017

44. 773TiPPRODIGE 51 - GASTFOX: Phase III randomised trial evaluating FOLFOX with or without DOCETAXEL (TFOX) as 1st line chemotherapy for locally advanced or metastatic oesophago-gastric adenocarcinoma

Author: Zaanan, A., Samalin, E., Louvet, C., Montérymard, C., Khemissa, F., Bouche, O., Louafi, S., Ghiringhelli, F., Bernard, P., Chibaudel, B., Artru, P., Molin, Y., Baba-Hamed, N., Romano, O., Aparicio, T., Michel, P., Rougier, P., Tougeron, D., Manfredi, S., Taieb, J., Service de gastroenterologie [CHU Georges Pompidou], Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Européen Georges Pompidou [APHP] ( HEGP ), UNICANCER - Institut régional du Cancer [Montpellier] ( ICM ), CRLCC Val d'Aurelle - Paul Lamarque, Institut Mutualiste de Montsouris ( IMM ), Fédération Francophone de la Cancérologie Digestive, FFCD, Service Biostatistiques et Informatique Médicale (CHU de Dijon) ( DIM ), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Service de hépato-gastro-entérologie - cancérologie digestive [CH de Perpignan], Centre Hospitalier Saint Jean de Perpignan, Hôpital Robert Debré, Service d'Hépato-gastroentérologie, 51092 Reims, France, affiliation inconnue, Service d'oncologie [Hôpital Sud Francilien, Corbeil Essonnes], Hôpital Sud Francilien Corbeil-Essonnes, Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc ( CRLCC - CGFL ), Service d'oncologie [Hôpital privé Toulon Hyères : Sainte Marguerite], Hôpital privé Toulon Hyères : Sainte Marguerite, Service d'oncologie [Institut Hospitalier Franco-Britannique : Levallois-Perret], Institut hospitalier Franco-Britannique [Levallois-Perret], Clinique Jean-Mermoz, Hôpital privé Jean Mermoz, Clinique de la Sauvegarde [Lyon], Site de Recherche Intégrée en Cancérologie ( SIRIC-ONCOLille ), Université de Lille, Sciences et Technologies-Université de Lille, Sciences Humaines et Sociales-CRLCC Oscar Lambret-Cancéropole Nord-Ouest-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Service de Gastro-entérologie [Avicenne], Université Paris 13 ( UP13 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Avicenne, Service d'hépato-gastro-entérologie [Hôpital Saint-Louis], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Centre hospitalier universitaire de Nantes ( CHU Nantes ), Service d’hépato-gastro-entérologie et assistance nutritive [CHU de Poitiers], CHU de Poitiers, Service d'hépato-gastroentérologie et cancérologie digestive (CHU de Dijon), Lipides - Nutrition - Cancer [Dijon - U1231] ( LNC ), Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service de gastroenterologie [CHU HEGP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-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)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), UNICANCER - Institut régional du Cancer Montpellier Val d'Aurelle (ICM), Institut Mutualiste de Montsouris (IMM), Service Biostatistiques et Informatique Médicale (CHU de Dijon) (DIM), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, Site de Recherche Intégrée en Cancérologie (SIRIC-ONCOLille), Université de Lille, Sciences et Technologies-Université de Lille, Sciences Humaines et Sociales-Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER-Université de Lille-UNICANCER-Cancéropole Nord-Ouest-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Université Lille Nord de France (COMUE)-UNICANCER-Université Lille Nord de France (COMUE)-UNICANCER-Cancéropole Nord-Ouest-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), and Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: EudraCT 2016-002331-16 NCT03006432, [SDV.CAN]Life Sciences [q-bio]/Cancer, [ SDV.CAN ] Life Sciences [q-bio]/Cancer
Abstract: IF 11.855; International audience
Published: 2017

45. Immune-checkpoint inhibitors associated with interstitial lung disease in cancer patients

Author: Amélie Lusque, Eric Dansin, Sébastien Couraud, Judith Raimbourg, Myriam Delaunay, Martin Früh, Nicolas Girard, Julie Milia, Stéphane Dalle, David Planchard, Nicolas Meyer, Samia Collot, G. Prévot, Florian Guisier, Marion Campana, Clarisse Audigier-Valette, Jean-David Fumet, Oliver Gautschi, Anne-cecile Metivier, Pascale Tomasini, Valérie Gounant, Maurice Pérol, Jean-Marie Michot, Julien Mazieres, M. Jaffro, Jacques Cadranel, Denis Moro-Sibilot, Marie-Thérèse Leccia, Service de pneumologie [Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Service de Pneumologie = Pneumologie - Oncologie Thoracique - Maladies Pulmonaires Rares [CHU Tenon], CHU Tenon [AP-HP], 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), Université Pierre et Marie Curie - Paris 6 (UPMC), Cellule Biostatistique [IUCT Oncopole, Toulouse] (Bureau des Essais Cliniques), Institut Claudius Regaud-Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), 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)-Université Toulouse III - Paul Sabatier (UT3), 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), Service Dermatologie [CHU Toulouse], Pôle Clinique des Voies respiratoires [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Service d’oncologie thoracique et essais précoces [CHU Bichat], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Département d'oncologie thoracique [CHU Grenoble], Centre Hospitalier Universitaire [Grenoble] (CHU), Département d'hématologie [Gustave Roussy], Institut Gustave Roussy (IGR), Département d’Innovation Thérapeutique et essais précoces [Gustave Roussy] (DITEP), Département d'oncologie médicale [Saint Herblain], Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER-UNICANCER, Apoptosis and Tumor Progression (CRCINA-ÉQUIPE 9), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), 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 de pneumologie, oncologie thoracique et soins intensifs respiratoires [Rouen], Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Equipe Quantification en Imagerie Fonctionnelle (QuantIF-LITIS), Laboratoire d'Informatique, de Traitement de l'Information et des Systèmes (LITIS), Université Le Havre Normandie (ULH), Normandie Université (NU)-Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Université Le Havre Normandie (ULH), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA), Service de Pneumologie [Suresne], Hôpital Foch [Suresnes], Service d'oncologie multidisciplinaire innovations thérapeutiques [Hôpital Nord - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital Nord [CHU - APHM], Département de Cancérologie Générale [Lille], Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER-Université de Lille-UNICANCER, Département de Cancérologie Médicale [Lyon], Centre Léon Bérard : Centre Régional de Lutte Contre le Cancer Lyon Rhône-Alpes, Service de Pneumologie [CHRU Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Medical Oncology Department [Luzern, Switzerland], Lucerne Cantonal Hospital [Luzern, Switzerland], Medical Oncology Department [St Gallen, Switzerland], Kantonsspital St Gallen [Switzerland], Département d'oncologie médicale [Centre Georges-François Leclerc], Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), Service de Pneumonologie [Toulon], Hôpital Saint Musse [Toulon], Service de Pneumologie Aiguë Spécialisée et Cancérologie Thoracique [HCL Lyon], Hospices Civils de Lyon (HCL), Ciblage thérapeutique en Oncologie (EA3738), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Service de Dermatologie [HCL, Lyon], Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Dermatologie [CHU de Grenoble site Nord], CHU de Grenoble site Nord, Service de radiologie, Bernardo, Elizabeth, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), 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)-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), Centre Léon Bérard [Lyon], CHU Toulouse [Toulouse]-Hôpital Larrey [Toulouse], CHU Toulouse [Toulouse], 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 Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de Dermatologie [IUCT Oncopole, Toulouse], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Hôpital Charles Nicolle [Rouen]-CHU Rouen, Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Université Le Havre Normandie (ULH), Université Lille Nord de France (COMUE)-UNICANCER-Université Lille Nord de France (COMUE)-UNICANCER, Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Pulmonary and Respiratory Medicine, Adult, Male, medicine.medical_specialty, Programmed Cell Death 1 Receptor, [SDV.CAN]Life Sciences [q-bio]/Cancer, Kaplan-Meier Estimate, Severity of Illness Index, 03 medical and health sciences, Young Adult, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Risk Factors, Internal medicine, Neoplasms, Severity of illness, medicine, Humans, Risk factor, Adverse effect, Lung cancer, Lung, Aged, Retrospective Studies, Aged, 80 and over, business.industry, Interstitial lung disease, Cancer, Retrospective cohort study, Middle Aged, medicine.disease, respiratory tract diseases, 3. Good health, Surgery, 030228 respiratory system, 030220 oncology & carcinogenesis, Female, France, Immunotherapy, business, Lung Diseases, Interstitial, Tomography, X-Ray Computed, Hypersensitivity pneumonitis, Switzerland
Abstract: International audience; Immunotherapy is becoming a standard of care for many cancers. Immune-checkpoint inhibitors (ICI) can generate immune-related adverse events. Interstitial lung disease (ILD) has been identified as a rare but potentially severe event.Between December 2015 and April 2016, we conducted a retrospective study in centres experienced in ICI use. We report the main features of ICI-ILD with a focus on clinical presentation, radiological patterns and therapeutic strategies.We identified 64 (3.5%) out of 1826 cancer patients with ICI-ILD. Patients mainly received programmed cell death-1 inhibitors. ILD usually occurred in males, and former or current smokers, with a median age of 59 years. We observed 65.6% grade 2/3 severity, 9.4% grade 4 severity and 9.4% fatal ILD. The median (range) time from initiation of immunotherapy to ILD was 2.3 (0.2-27.4) months. Onset tended to occur earlier in lung cancer versus melanoma: median 2.1 and 5.2 months, respectively (p=0.02). Ground-glass opacities (81.3%) were the predominant lesions, followed by consolidations (53.1%). Organising pneumonia (23.4%) and hypersensitivity pneumonitis (15.6%) were the most common patterns. Overall survival at 6 months was 58.1% (95% CI 37.7-73.8%).ICI-ILD often occurs early and displays suggestive radiological features. As there is no clearly identified risk factor, oncologists need to diagnose and adequately treat this adverse event.
Published: 2017

46. Impact of emotional competence on supportive care needs, anxiety and depression symptoms of cancer patients: a multiple mediation model

Author: Anne-Sophie Baudry, Véronique Christophe, M. Mahieuxe, Sophie Lelorain, Site de Recherche Intégrée en Cancérologie (SIRIC-ONCOLille), Université de Lille, Sciences et Technologies-Université de Lille, Sciences Humaines et Sociales-Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université Lille Nord de France (COMUE)-UNICANCER-Université Lille Nord de France (COMUE)-UNICANCER-Cancéropole Nord-Ouest-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Sciences Cognitives et Sciences Affectives (SCALab) - UMR 9193 (SCALab), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Université de Lille-UNICANCER-Université de Lille-UNICANCER-Cancéropole Nord-Ouest-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), and Laboratoire Sciences Cognitives et Sciences Affectives - UMR 9193 (SCALab)
Subjects: Adult, Mediation (statistics), medicine.medical_specialty, Emotions, Psychological intervention, Anxiety, Hospital Anxiety and Depression Scale, Emotional competence, 03 medical and health sciences, Social support, [SCCO]Cognitive science, 0302 clinical medicine, Neoplasms, Surveys and Questionnaires, medicine, Humans, Psychiatry, Aged, Aged, 80 and over, 030504 nursing, Depression, Negotiating, business.industry, Emotional intelligence, Social Support, Middle Aged, 3. Good health, Cross-Sectional Studies, Oncology, 030220 oncology & carcinogenesis, Female, medicine.symptom, 0305 other medical science, business, Psychosocial, Needs Assessment
Abstract: PURPOSE: The aim of this study was to test the effect of intrapersonal and interpersonal emotional competence on cancer patients' supportive care needs, as mediated by anxiety and depression symptoms. METHODS: Cross-sectional design: 137 cancer patients (42% breast or ovarian cancer, 58% gastrointestinal cancer) in 4 French hospitals completed the Profile of Emotional Competence (PEC), the Hospital Anxiety and Depression Scale (HADS), and the Supportive Care Needs Survey Short Form (SCNS-SF). Bootstrap methods with PROCESS Macro were used to test multiple mediation models. RESULTS: Emotional competence presented a direct or indirect beneficial effect on the satisfaction of supportive care needs, anxiety and depression symptoms. As expected, anxiety and depression symptoms had also strong positive correlations with unmet needs. All multiple mediation models were significant, except for physical needs: intrapersonal and interpersonal emotional competence impacted anxiety and depression symptoms, which in turn impacted psychological, sexual, care/support, and information needs. CONCLUSIONS: These innovative results show the important effect of patients' emotional competence on their supportive care need satisfaction, as mediated by anxiety and depression. Consequently, patients with high emotional competence may require less psychosocial input from medical clinicians. Thus, emotional competence may be integrated into health models and psychosocial interventions to improve patient adjustment. Further investigation is, however, needed to know which are the most beneficial specific emotional competences and at what point of the cancer pathway.
Published: 2017

47. Evaluation of non-supervised MALDI mass spectrometry imaging combined with microproteomics for glioma grade III classification

Author: Isabelle Fournier, Marie Duhamel, Fabienne Escande, Maxence Wisztorski, Firas Kobeissy, Fahed Zairi, Jean-Pascal Gimeno, Claude-Alain Maurage, Nicolas Reyns, Michel Salzet, Emilie Le Rhun, Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U 1192 (PRISM), Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université Lille Nord de France (COMUE)-UNICANCER, Site de Recherche Intégrée en Cancérologie (SIRIC-ONCOLille), Université de Lille, Sciences et Technologies-Université de Lille, Sciences Humaines et Sociales-Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université Lille Nord de France (COMUE)-UNICANCER-Université Lille Nord de France (COMUE)-UNICANCER-Cancéropole Nord-Ouest-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), American University of Beirut [Beyrouth] (AUB), University of Florida [Gainesville] (UF), SALZET, Michel, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Université de Lille-UNICANCER, and Université de Lille-UNICANCER-Université de Lille-UNICANCER-Cancéropole Nord-Ouest-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)
Subjects: Adult, Male, Proteomics, 0301 basic medicine, MALDI imaging, Proteome, Biopsy, Neurogenesis, [SDV]Life Sciences [q-bio], Biophysics, Microproteomics, Computational biology, Bioinformatics, Biochemistry, Anaplastic glioma, Mass spectrometry imaging, Analytical Chemistry, Young Adult, 03 medical and health sciences, Molecular classification, Neoplasms, Glioma, medicine, Humans, Molecular Biology, Aged, Neoplasm Staging, Inflammation, WHO classification, Matrix-assisted laser desorption/ionization mass spectrometry imaging, Enzymatic digestion, Brain Neoplasms, Chemistry, Proteins, Middle Aged, medicine.disease, 3. Good health, [SDV] Life Sciences [q-bio], Label-free quantification, 030104 developmental biology, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Female, Trypsin Digestion, Peptides
Abstract: International audience; An integrated diagnosis using molecular features is recommended in the 2016 World Health Organization (WHO) classification. Our aim was to explore non-targeted molecular classification using MALDI mass spectrometry imaging (MALDI MSI) associated to microproteomics in order to classify anaplastic glioma by integration of clinical data. We used fresh-frozen tissue sections to perform MALDI MSI of proteins based on their digestion peptides after in-situ trypsin digestion of the tissue sections and matrix deposition by micro-spraying. The generated 70μm spatial resolution image datasets were further processed by individual or global segmentation in order to cluster the tissues according to their molecular protein signature. The clustering gives 3 main distinct groups. Within the tissues the ROIs (regions of interest) defined by these groups were used for microproteomics by micro-extraction of the tryptic peptides after on-tissue enzymatic digestion. More than 2500 proteins including 22 alternative proteins (AltProt) are identified by the Shotgun microproteomics. Statistical analysis on the basis of the label free quantification of the proteins shows a similar classification to the MALDI MSI segmentation into 3 groups. Functional analysis performed on each group reveals sub-networks related to neoplasia for group 1, glioma with inflammation for group 2 and neurogenesis for group 3. This demonstrates the interest on these new non-targeted large molecular data combining both MALDI MSI and microproteomics data, for tumor classification. This analysis provides new insights into grade III glioma organization. This specific information could allow a more accurate classification of the biopsies according to the prognosis and the identification of potential new targeted therapeutic options. This article is part of a Special Issue entitled: MALDI Imaging, edited by Dr. Corinna Henkel and Prof. Peter Hoffmann.
Published: 2017

48. Regosarc: regorafenib versus placebo in doxorubicin-refractory soft-tissue sarcoma-a quality-adjusted time without symptoms of progression or toxicity analysis

Author: Berry, V. (Vincent), Basson, L. (Laurent), Bogart, E. (Emilie), Mir, O. (Olivier), Blay, J-Y. (Jean-Yves), Italiano, A. (Antoine), Bertucci, F. (François), Chevreau, C. (Christine), Clisant-Delaine, S. (Stephanie), Liegl-Atzwanger, B. (Bernadette), Tresch-Bruneel, E. (Emmanuelle), Wallet, J. (Jennifer), Taieb, S. (Sophie), Decoupigny, E. (Emilie), Le Cesne, A. (Axel), Brodowicz, T. (Thomas), Penel, N. (Nicolas), Site de Recherche Intégrée en Cancérologie (SIRIC-ONCOLille), Université de Lille, Sciences et Technologies-Université de Lille, Sciences Humaines et Sociales-Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER-Université de Lille-UNICANCER-Cancéropole Nord-Ouest-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER, Institut Gustave Roussy (IGR), Centre Léon Bérard [Lyon], Institut Bergonié [Bordeaux], UNICANCER, Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Institut Claudius Regaud, Karl-Franzens-Universität Graz, University of Vienna [Vienna], Evaluation des technologies de santé et des pratiques médicales - ULR 2694 (METRICS), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Université Lille Nord de France (COMUE)-UNICANCER-Université Lille Nord de France (COMUE)-UNICANCER-Cancéropole Nord-Ouest-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Université Lille Nord de France (COMUE)-UNICANCER, Karl-Franzens-Universität [Graz, Autriche], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille, CHU Lille, Université de Lille, Site de Recherche Intégrée en Cancérologie [SIRIC-ONCOLille], METRICS : Evaluation des technologies de santé et des pratiques médicales - ULR 2694, Institut Gustave Roussy [IGR], and Evaluation des technologies de santé et des pratiques médicales - ULR 2694 [METRICS]
Subjects: [SDV]Life Sciences [q-bio], Mesh:Diarrhea/chemically induced, Mesh:Alopecia/chemically induced, Mesh:Phenylurea Compounds/therapeutic use, Mesh:Aged, Mesh:Synovial/drug therapy, Mesh:Treatment Outcome, Mesh:Anorexia/chemically induced, Mesh:Quality of Life, Mesh:Proportional Hazards Models, Mesh:Severity of Illness Index, Mesh:Female, quality-adjusted survival, Mesh:Fecal Incontinence/chemically induced, Mesh:Male, Mesh:Sarcoma, Mesh:Middle Aged, quality-adjusted time without symptoms of progression or toxicity (Q-TWiST), Mesh:Asthenia/chemically induced, Mesh:Liposarcoma/drug therapy, metastatic soft-tissue sarcoma, placebo, regorafenib, Mesh:Mucositis/chemically induced, Mesh:Hospitalization, Mesh:Sarcoma/drug therapy, Mesh:Hand-Foot Syndrome/etiology, Mesh:Pyridines/therapeutic use, Mesh:Antineoplastic Agents/therapeutic use, Mesh:Leiomyosarcoma/drug therapy, Mesh:Humans, Mesh:Hypertension/chemically induced, Mesh:Double-Blind Method
Abstract: International audience; BACKGROUND: In a placebo-controlled, randomized phase 2 trial (ClinicalTrials.gov identifier NCT01900743), regorafenib improved progression-free survival (PFS) for patients with doxorubicin-pretreated advanced nonadipocytic sarcoma. A quality-adjusted time without symptoms of progression or toxicity (Q-TWiST) post hoc exploratory analysis was applied to provide an integrated measure of its clinical benefit.METHODS: In the base-case analysis, each patient's overall survival (OS) was partitioned into 3 mutually exclusive health states: the time with a grade 3 or 4 adverse event (TOX), the time without symptoms of disease or grade 3 or 4 toxicity from treatment, and the time after tumor progression or relapse. The time spent in each state was weighted with a health-state utility associated with that state and was summed to calculate the Q-TWiST. The stability of the base-case analysis was explored with several sensitivity analyses.RESULTS: In nonadipocytic sarcoma, the PFS was (4.0 months [2.6-5.5 months] with regorafenib vs 1.0 month [0.9-1.8 months] with a placebo; hazard ratio, 0.36 [0.25-0.53]; P < .0001); the OS was 13.4 months (8.6-17.3 months) with regorafenib and 9.0 months (6.8-12.5 months) with a placebo (hazard ratio, 0.67 [0.44-1.02]). With the classic definition of TOX (including all grade 3 and 4 clinical adverse events), the Q-TWiSTs were 8.0 months (7.0-9.0 months) with regorafenib and 5.7 months (4.9-6.4 months) with a placebo (P
Published: 2017

49. Retroviral Scanning: Mapping MLV Integration Sites to Define Cell-specific Regulatory Regions

Author: Valentina Poletti, Clelia Peano, Ingrid Cifola, Fulvio Mavilio, Oriana Romano, Gianluca De Bellis, Marco Severgnini, Annarita Miccio, Site de Recherche Intégrée en Cancérologie (SIRIC-ONCOLille), Université de Lille, Sciences et Technologies-Université de Lille, Sciences Humaines et Sociales-Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université Lille Nord de France (COMUE)-UNICANCER-Université Lille Nord de France (COMUE)-UNICANCER-Cancéropole Nord-Ouest-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Pierantoni-Morgagni Hospital, Partenaires INRAE, Approches génétiques intégrées et nouvelles thérapies pour les maladies rares (INTEGRARE), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université d'Évry-Val-d'Essonne (UEVE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Généthon, Université de Lille-UNICANCER-Université de Lille-UNICANCER-Cancéropole Nord-Ouest-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), and École Pratique des Hautes Études (EPHE)
Subjects: Virus Integration, General Chemical Engineering, [SDV]Life Sciences [q-bio], Population, Integration sites, Virus-host interaction, MLV, Computational biology, Regulatory Sequences, Nucleic Acid, Biology, Genome, General Biochemistry, Genetics and Molecular Biology, Epigenetic regulation, Retroviral scanning, Genetics, Humans, Cell identity, Cis-regulatory elements, Issue 123, Massive sequencing, Moloney leukemia virus, Enhancer, education, education.field_of_study, General Immunology and Microbiology, General Neuroscience, LM-PCR, retroviral vectors, Amplicon, integration sites, Restriction enzyme, genomic DNA, Retroviridae, Regulatory sequence, NGS
Abstract: International audience; Moloney murine leukemia (MLV) virus-based retroviral vectors integrate predominantly in acetylated enhancers and promoters. For this reason, mLV integration sites can be used as functional markers of active regulatory elements. Here, we present a retroviral scanning tool, which allows the genome-wide identification of cell-specific enhancers and promoters. Briefly, the target cell population is transduced with an mLV-derived vector and genomic DNA is digested with a frequently cutting restriction enzyme. After ligation of genomic fragments with a compatible DNA linker, linker-mediated polymerase chain reaction (LM-PCR) allows the amplification of the virus-host genome junctions. Massive sequencing of the amplicons is used to define the mLV integration profile genome-wide. Finally, clusters of recurrent integrations are defined to identify cell-specific regulatory regions, responsible for the activation of cell-type specific transcriptional programs. The retroviral scanning tool allows the genome-wide identification of cell-specific promoters and enhancers in prospectively isolated target cell populations. Notably, retroviral scanning represents an instrumental technique for the retrospective identification of rare populations (e.g. somatic stem cells) that lack robust markers for prospective isolation.
Published: 2017

50. Factors related to pregnancy and birth and the risk of childhood brain tumours: The ESTELLE and ESCALE studies (SFCE, France)

Author: Jean Michon, Jacqueline Clavel, Cécile Faure-Conter, Isabelle Pellier, Paula Rios, Claire Freycon, Léa Guerrini-Rousseau, Pierre Leblond, Anne-Isabelle Bertozzi, Stéphanie Puget, Helen D. Bailey, Stéphane Ducassou, Brigitte Lacour, Laurent Orsi, Equipe 7 : EPICEA - Epidémiologie des cancers de l'enfant et de l'adolescent (CRESS - U1153), Université Paris Descartes - Paris 5 (UPD5)-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Registre National des Cancers de l'Enfant - National Registry of Childhood Cancers [Villejuif & CHU Nancy] (RNCE), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de cancérologie de l'enfant et de l'adolescent [Gustave Roussy], Institut Gustave Roussy (IGR), Unité d’Hémato-Immuno-Oncologie pédiatrique [CHU Toulouse] (Pôle Pédiatrique), CHU Toulouse [Toulouse], Unité d'oncologie pédiatrique [Centre Oscar Lambret, Lille], Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université Lille Nord de France (COMUE)-UNICANCER-Université Lille Nord de France (COMUE)-UNICANCER, Institut d'hématologie et d'oncologie pédiatrique [CHU - HCL] (IHOPe), Hospices Civils de Lyon (HCL), Innate Immunity and Immunotherapy (CRCINA-ÉQUIPE 7), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Service d'Immunologie Hématologie et Oncologie pédiatriques [CHU Angers], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Clinique Universitaire de Pédiatrie [CHU Grenoble-Alpes], Hôpital Sud, CHU de Grenoble-Hôpital Couple Enfant de Grenoble, Département de Pédiatrie Adolescents et Jeunes Adultes [Institut Curie], Institut Curie [Paris], Service de neurochirurgie pédiatrique [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Descartes - Paris 5 (UPD5), Université Sorbonne Paris Cité (USPC), Service d’Onco-Hématologie Pédiatrique [Hôpital Pellegrin, Bordeaux], Hôpital Pellegrin - Bordeaux, The authors would also like to thank all of the Société Française de lutte contre les Cancers de l’Enfant et de l’Adolescent (SFCE) principal investigators., Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Sorbonne Paris Cité (USPC), Centre Oscar Lambret [Lille], Innate immunity and Immunotherapy (CRCINA - Département INCIT - Equipe 7), Centre de recherche de Cancérologie et d'Immunologie / Nantes - Angers (CRCINA), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Sercice Hématologie, immunologie et oncologie pédiatrique [CHU Toulouse], Pôle Enfants [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Lille-UNICANCER-Université de Lille-UNICANCER, Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Bernardo, Elizabeth
Subjects: Adult, Male, Cancer Research, medicine.medical_specialty, Pediatrics, Adolescent, Birth weight, case-control study, Population, Breastfeeding, Mothers, [SDV.CAN]Life Sciences [q-bio]/Cancer, Body Mass Index, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Pregnancy, Risk Factors, medicine, Birth Weight, Humans, 030212 general & internal medicine, education, 2. Zero hunger, fertility, education.field_of_study, child, Brain Neoplasms, Obstetrics, business.industry, Case-control study, Odds ratio, medicine.disease, 3. Good health, Breast Feeding, Logistic Models, Oncology, Case-Control Studies, 030220 oncology & carcinogenesis, brain tumors, Female, France, business, Body mass index, Breast feeding, folic acid supplementation, fetal growth
Abstract: International audience; Little is known of the causes of childhood brain tumors (CBT). The aims of this study were to investigate whether extremes of birth weight were associated with increased risk of CBT and whether maternal preconceptional folic acid supplementation or breastfeeding reduced the risk. In addition, other maternal characteristics and birth related factors were also investigated. We pooled data from two French national population-based case-control studies with similar designs conducted in 2003–2004 and 2010–2011. The mothers of 510 CBT cases (directly recruited from the national childhood cancer register) and 3,102 controls aged under 15 years, frequency matched by age and gender did a telephone interview, which focussed on demographic and perinatal characteristics, and maternal life style habits and reproductive history. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using unconditional logistic regression, adjusted for age, sex, study of origin and relevant confounders. No association was found between CBT and birth weight or fetal growth. The use of preconceptional folic acid supplementation was rare (5.3% in cases and 7.8% in controls) and the OR was 0.8 (95% CI 0.5, 1.4). There was no association with breastfeeding, even prolonged (six months or more; OR 1.0, 95% CI 0.8, 1.4). Neither was there any association between CBT and other investigated factors (maternal body mass index, gestational weight gain, congenital abnormality, maternal reproductive history or use of fertility treatments. Although large, this study was underpowered for subtype analyses. Pooling data with other population-based studies may provide further insight into findings by CBT subtypes.
Published: 2017

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