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1. Effectiveness and safety of dupilumab for the treatment of severe asthma in a real‐life French multi‐centre adult cohort

Author: Laurent Guilleminault, Lise Rosencher, A. Proust, Arnaud Bourdin, Clairelyne Dupin, S. Fry, Drifa Belhadi, Cécile Chenivesse, Patrick Berger, Frédéric de Blay, Alain Didier, Anne‐Sophie Gamez, Camille Couffignal, Philippe Bonniaud, Gilles Garcia, Camille Taillé, Pierre-Olivier Girodet, Chantal Raherison, Christophe Leroyer, Geneviève Le Bourdellès, Guillaume Mahay, MORNET, Dominique, Physiopathologie et Epidémiologie des Maladies Respiratoires (PHERE (UMR_S_1152 / U1152)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Département d'épidémiologie, biostatistique et recherche clinique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre de Physiopathologie Toulouse Purpan (CPTP), 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)-Centre National de la Recherche Scientifique (CNRS), Centre de recherche Cardio-Thoracique de Bordeaux [Bordeaux] (CRCTB), Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Strasbourg, 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, Département de Médecine Interne et Pneumologie [Brest] (DMIP - Brest), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Université européenne de Bretagne - European University of Brittany (UEB), CHU Rouen, Normandie Université (NU), Université de Bordeaux (UB), Centre d'Investigation Clinique - Epidemiologie Clinique / Essais Cliniques Bordeaux, Institut National de la Santé et de la Recherche Médicale (INSERM), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de pneumologie [Hôpital Foch], Hôpital Foch [Suresnes], Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Paris-Sud - Paris 11 (UP11), Université Paris-Saclay, Hôpital Bicêtre, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), 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), Service Pneumologie et allergologie pédiatrique [CHU Toulouse], Pôle Enfants [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Centre d'Investigation Clinique – Épidémiologie Clinique [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], 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), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Service de pneumologie et allergologie pédiatrique [CHU Toulouse]
Subjects: Male, 0301 basic medicine, Hypereosinophilia, Severity of Illness Index, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, 0302 clinical medicine, Prednisone, Interquartile range, Immunology and Allergy, [SDV.IMM.ALL]Life Sciences [q-bio]/Immunology/Allergology, oral steroid, MESH: Antibodies, Monoclonal, Humanized / adverse effects, MESH: Middle Aged, EPICENE, MESH: Follow-Up Studies, Middle Aged, Dupilumab, 3. Good health, Cohort, Female, France, [SDV.IMM.IMM] Life Sciences [q-bio]/Immunology/Immunotherapy, medicine.symptom, [SDV.IMM.ALL] Life Sciences [q-bio]/Immunology/Allergology, Cohort study, medicine.drug, Adult, medicine.medical_specialty, Immunology, Antibodies, Monoclonal, Humanized, 03 medical and health sciences, T2 inflammation, MESH: Severity of Illness Index, Internal medicine, side‐effect, medicine, Humans, MESH: Asthma / physiopathology, hypereosinophilia, MESH: Antibodies, Monoclonal, Humanized / administration & dosage, Retrospective Studies, Asthma, MESH: Humans, business.industry, MESH: Adult, MESH: Retrospective Studies, Retrospective cohort study, MESH: Asthma / drug therapy, [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy, asthma, medicine.disease, MESH: Male, MESH: France, 030104 developmental biology, 030228 respiratory system, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, MESH: Asthma / blood, business, MESH: Female, Follow-Up Studies
Abstract: International audience; Background: Dupilumab is a monoclonal anti‐IL‐4Rα antibody developed for the treatment of severe asthma (SA). An early access programme for dupilumab was opened in France in SA patients experiencing unacceptable steroids side‐effects and/or life‐threatening exacerbations.Objective: To assess changes in asthma control between baseline and 12 months of treatment.Methods: Multi‐centre (n = 13) retrospective real‐life cohort study. This study is registered on ClinicalTrials.gov (NCT04022447).Results: Overall, 64 patients with SA (median age 51, interquartile range [44‐61]; 53% females) received dupilumab as add‐on therapy to maximal standard of care; and 76% were on oral daily steroids at baseline. After 12 months, median asthma control test score improved from 14 [7‐16] to 22 [17‐24] (P < .001); median forced expiratory volume in 1 seconds increased from 58% [47‐75] to 68% [58‐88] (P = .001); and daily prednisone dose was reduced from 20 [10‐30] to 5 [0‐7] mg/d (P < .001). Annual exacerbations decreased from 4 [2‐7] to 1 [0‐2] (P < .001). Hypereosinophilia ≥1500/mm3 was observed at least once during follow‐up in 16 patients (25%), persisting after 6 months in 8 (14%) of them. Increase in blood eosinophil count did not modify the clinical response during the study period. Injection‐site reaction was the most common side effect (14%). Three deaths were observed, none related to treatment by investigators.Conclusion & clinical relevance: In this first real‐life cohort study of predominantly steroid‐dependent SA, dupilumab significantly improved asthma control and lung function and reduced oral steroids use and exacerbations rate. Despite limitations due to the retrospective study, these results are consistent with controlled trials efficacy data. Further studies are required to assess the clinical significance and long‐term prognosis of sustained dupilumab‐induced hypereosinophilia.
Published: 2020

2. A subset of epithelioid and spindle cell rhabdomyosarcomas is associated with TFCP2 fusions and common ALK upregulation

Author: Benjamin Bonhomme, Cleofe Romagosa, Gaëlle Pierron, Anne Moreau, Jean Michel Coindre, Arjen H.G. Cleven, Irma Ramos-Oliver, François Le Loarer, Sophie Le Guellec, Corinne Bouvier, Sébastien Salas, Anne Gomez-Brouchet, Virginie Audard, Marie Pierre Castex, Frédérique Larousserie, Anand Sherwood, Anne-Marie Cleton-Jansen, Dilara C. Savci-Heijink, Camille Laurent, Franck Tirode, Judith V.M.G. Bovée, Daniel Pissaloux, Jessica Baud, Antoine Giraud, Herman M. Kroon, Institut Bergonié [Bordeaux], UNICANCER, Université de Bordeaux (UB), Actions for OnCogenesis understanding and Target Identification in ONcology (ACTION), UNICANCER-UNICANCER-Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Leiden University Medical Center (LUMC), Département de pathologie [CHU La Timone, Marseille], Hôpital de la Timone [CHU - APHM] (TIMONE), Département d'oncologie pédiatrique [CHU Toulouse], CHU Toulouse [Toulouse], Vall d'Hebron University Hospital [Barcelona], Service de Pathologie [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Service d’Oncologie Médicale [Hôpital de la Timone - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), 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), Service de Pathologie [AP-HP Hôpital Cochin], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre d'Investigation Clinique - Epidemiologie Clinique / Essais Cliniques Bordeaux, Institut National de la Santé et de la Recherche Médicale (INSERM), Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA), Centre Léon Bérard [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-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de Biologie des Tumeurs, Institut Curie [Paris], Department of Conservative Dentistry and Endodontics [CSI College of Dental Sciences, Madurai, India], 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 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 de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and TIRODE, Franck
Subjects: Male, 0301 basic medicine, Pathology, [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Fusion gene, 0302 clinical medicine, CDKN2A, Rhabdomyosarcoma, Anaplastic Lymphoma Kinase, Prospective Studies, Child, Exome, Aged, 80 and over, medicine.diagnostic_test, Epithelioid Cells, Soft tissue, Middle Aged, Prognosis, Immunohistochemistry, Up-Regulation, 3. Good health, DNA-Binding Proteins, Phenotype, Molecular Diagnostic Techniques, 030220 oncology & carcinogenesis, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Female, Sarcoma, Gene Fusion, Adult, medicine.medical_specialty, Adolescent, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, Pathology and Forensic Medicine, Young Adult, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Biomarkers, Tumor, medicine, Humans, Genetic Predisposition to Disease, Craniofacial, Retrospective Studies, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, medicine.disease, 030104 developmental biology, Transcription Factors, Fluorescence in situ hybridization
Abstract: International audience; Rhabdomyosarcomas with TFCP2 fusions represent an emerging subtype of tumors, initially discovered by RNA-sequencing. We report herein the clinicopathological, transcriptional, and genomic features of a series of 14 cases. Cases were retrospectively and prospectively recruited and studied by immunohistochemistry (MYF4, MYOD1, S100, AE1/E3, ALK), fluorescence in situ hybridization with TFCP2 break-apart probe (n = 10/14), array-comparative genomic hybridization (Agilent), whole RNA-sequencing (Truseq Exome, Illumina), or anchored multiplex PCR-based targeted next-generation sequencing (Archer® FusionPlex® Sarcoma kit). Patient's age ranged between 11 and 86 years, including 5 pediatric cases. Tumors were located in the bone (n = 12/14) and soft tissue (n = 2/14). Most bone tumors invaded surrounding soft tissue. Craniofacial bones were over-represented (n = 8/12). Median survival was 8 months and five patients are currently alive with a median follow-up of 20 months. Most tumors displayed a mixed spindle cell and epithelioid pattern with frequent vesicular nuclei. All tumors expressed keratins and showed a rhabdomyogenic phenotype (defined as expression of MYF4 and/or MYOD1). ALK was overexpressed in all but three cases without underlying ALK fusion on break-apart FISH (n = 5) nor next-generation sequencing (n = 14). ALK upregulation was frequently associated with an internal deletion at genomic level. TFCP2 was fused in 5' either to EWSR1 (n = 6) or FUS (n = 8). EWSR1 was involved in both soft tissue cases. FISH with TFCP2 break-apart probe was positive in all tested cases (n = 8), including one case with unbalanced signal. On array-CGH, all tested tumors displayed complex genetic profiles with genomic indexes ranging from 13 to 107.55 and recurrent CDKN2A deletions. FET-TFCP2 rhabdomyosarcomas clustered together and distinctly from other rhabdomyosarcomas subgroups. Altogether, our data confirm and expand the spectrum of the new family of FET-TFCP2 rhabdomyosarcomas, which are associated with a predilection for the craniofacial bones, an aggressive course, and recurrent pathological features. Their association with ALK overexpression might represent a therapeutic vulnerability.
Published: 2020

3. Pazopanib or methotrexate–vinblastine combination chemotherapy in adult patients with progressive desmoid tumours (DESMOPAZ): a non-comparative, randomised, open-label, multicentre, phase 2 study

Author: Céleste Lebbé, Isabelle Ray-Coquard, Todd Hembrough, Jean-Yves Blay, Nicolas Penel, Maud Toulmonde, Fabiola Cecchi, Antoine Italiano, Carlo Lucchesi, Axel Le Cesne, Nicolas Isambert, Sophie Piperno-Neumann, François Le Loarer, Emmanuelle Bompas, Michèle Kind, Patrick Soulié, Christine Chevreau, Marina Pulido, Thierry André, François Bertucci, Stephen Sweet, Carine Bellera, Esma Saada, Amandine Crombé, Institut Bergonié [Bordeaux], UNICANCER, CIC Bordeaux, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Léon Bérard [Lyon], Centre de Recherche Saint-Antoine (UMRS893), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département d'oncologie médicale [Centre Georges-François Leclerc], Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER, Institut Claudius Regaud, Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université Lille Nord de France (COMUE)-UNICANCER, Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), Institute of Developmental Biology and Cancer (IBDC), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), 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), Immunologie, dermatologie, oncologie, Oncodermatologie, immunologie et cellules souches cutanées (IDO (U976 / UMR_S 976)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR), Service Oncologie Médicale [Angers], Département d'Oncologie Médicale [Institut Curie, Paris], Institut Curie [Paris], Oxford PharmaGenesis Ltd, Research Evaluation Unit, Oxford, United Kingdom of Great Britain and Northern Ireland., Centre d'Investigation Clinique - Epidemiologie Clinique / Essais Cliniques Bordeaux, Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Oncologie Médicale, CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), 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), Université de Lille-UNICANCER, Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Nantomics, and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: 0301 basic medicine, Adult, Male, medicine.medical_specialty, Indazoles, Adolescent, Drug-Related Side Effects and Adverse Reactions, [SDV]Life Sciences [q-bio], [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Vinblastine, Pazopanib, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Clinical endpoint, Humans, Progression-free survival, Aged, Sulfonamides, business.industry, Combination chemotherapy, Middle Aged, medicine.disease, Chemotherapy regimen, Progression-Free Survival, 3. Good health, body regions, Regimen, Fibromatosis, Aggressive, 030104 developmental biology, Methotrexate, Pyrimidines, Treatment Outcome, Oncology, Response Evaluation Criteria in Solid Tumors, 030220 oncology & carcinogenesis, Female, business, Progressive disease, medicine.drug
Abstract: Summary Background Desmoid tumours are locally aggressive tumours associated with substantial morbidity. No systemic treatments are approved for this disease, with methotrexate–vinblastine the only chemotherapy regimen assessed in a clinical trial setting to date. VEGF overexpression is a common feature in aggressive desmoid tumours. Pazopanib is an oral antiangiogenic agent targeting VEGF receptors 1, 2, and 3, platelet-derived growth factor receptor-like protein (PDGFR) α and β, and c-KIT tyrosine kinases. We aimed to assess antitumour activity and safety of targeted therapy or combination chemotherapy in progressive desmoid tumours. Methods DESMOPAZ was a non-comparative, randomised, open-label, phase 2 trial conducted at 12 centres from the French Sarcoma Group. We enrolled adults (≥18 years) with progressive desmoid tumours, normal organ function and centrally documented progressive disease according to Response Evaluation Criteria in Solid Tumors version 1.1 based on two imaging assessments obtained within less than a 6-month interval. Participants were randomly assigned (2:1) to oral pazopanib 800 mg per day for up to 1 year or to an intravenous regimen combining vinblastine (5 mg/m2 per dose) and methotrexate (30 mg/m2 per dose), administered weekly for 6 months and then every other week for 6 months. Randomisation was stratified according to inclusion centre and tumour location. The primary endpoint was the proportion of patients who had not progressed at 6 months in the first 43 patients who had received one complete or two incomplete cycles of pazopanib. This endpoint was also assessed as a prespecified exploratory endpoint in all patients who had received one complete or two incomplete cycles of methotrexate–vinblastane. Safety analyses were done for all patients who received at least one dose of allocated treatment. This trial was registered with ClinicalTrials.gov , number NCT01876082 . Findings From Dec 4, 2012, to Aug 18, 2017, 72 patients were enrolled and randomly assigned (n=48 in the pazopanib group; n=24 in the methotrexate–vinblastine group). Median follow-up was 23·4 months (IQR 17·1–25·5). 46 patients in the pazopanib group and 20 patients in the methotrexate–vinblastine group were assessable for activity. In the first 43 patients assessable for the primary endpoint in the pazopanib group, the proportion of patients who had not progressed at 6 months was 83·7% (95% CI 69·3–93·2). The proportion of patients treated with methotrexate–vinblastine who had not progressed at 6 months was 45·0% (95% CI 23·1–68·5). The most common grade 3 or 4 adverse events in the pazopanib group were hypertension (n=10, 21%) and diarrhoea (n=7, 15%) and in the methotrexate–vinblastine group were neutropenia (n=10, 45%) and liver transaminitis (n=4, 18%). 11 patients (23%) had at least one serious adverse event related to study treatment in the pazopanib group, as did and six patients (27%) in the methotrexate–vinblastine group. Interpretation Pazopanib has clinical activity in patients with progressive desmoid tumours and could be a valid treatment option in this rare and disabling disease. Funding GlaxoSmithKline and Novartis.
Published: 2019

4. Randomized clinical trial of sacral nerve stimulation for refractory constipation

Author: F Zerbib, L Siproudhis, P-A Lehur, C Germain, F Mion, A-M Leroi, B Coffin, A Le Sidaner, V Vitton, C Bouyssou-Cellier, G Chene, M Simon, Q Denost, P Lepicard, G Meurette, V Wyart, C Kubis, S Roman, H Damon, X Barth, V Bridoux, G Gourcerol, B Castel, C Gorbatchef, Anne Le Sidaner, M Mathonnet, N Lesavre, P Orsoni, C Brochard, V Desfourneaux, CIC Bordeaux, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Foie, métabolismes et cancer, 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 ), CHU Pontchaillou [Rennes], Institut des Maladies de l'Appareil Digestif, Université de Nantes (UN), CIC CHU Lyon (inserm), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Rouen, Normandie Université (NU), Université Paris Diderot - Paris 7 (UPD7), CHU Limoges, Centre de recherche en neurobiologie - neurophysiologie de Marseille (CRN2M), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), This study was funded by a grant from the French Ministry of Health (PHRC 2011) and promoted by Bordeaux University Hospital (Délégation à la Recherche Clinique, Centre Hospitalier Universitaire de Bordeaux)., CHU Bordeaux [Bordeaux], CHU Rennes - Service gastroentérologie, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre d'Investigation Clinique - Epidemiologie Clinique / Essais Cliniques Bordeaux, Institut National de la Santé et de la Recherche Médicale (INSERM), Hospices Civils de Lyon (HCL), Service de physiologie digestive, urinaire, respiratoire et de l'exercice [CHU Rouen], Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Hôpital Charles Nicolle [Rouen], 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), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), CHU Marseille, Enjalbert, Alain, and 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 )
Subjects: Adult, Male, medicine.medical_specialty, Constipation, Adolescent, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Lumbosacral Plexus, Electric Stimulation Therapy, Stimulation, law.invention, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Hematoma, Double-Blind Method, Randomized controlled trial, Refractory, law, medicine, Humans, ComputingMilieux_MISCELLANEOUS, Aged, Cross-Over Studies, business.industry, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Middle Aged, medicine.disease, Crossover study, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Surgery, Lumbosacral plexus, Implantable Neurostimulators, Treatment Outcome, 030220 oncology & carcinogenesis, Anesthesia, Defecation, Female, 030211 gastroenterology & hepatology, medicine.symptom, business, Follow-Up Studies
Abstract: Background Open studies have reported favourable results for sacral nerve stimulation in the treatment of refractory constipation. Here, its efficacy was assessed in a double-blind crossover RCT. Methods Patients with at least two of the following criteria were included: fewer than three bowel movements per week; straining to evacuate on more than 25 per cent of attempts; or sensation of incomplete evacuation on more than 25 per cent of occasions. Response to therapy was defined as at least three bowel movements per week and/or more than 50 per cent improvement in symptoms. Responders to an initial 3-week peripheral nerve evaluation were offered permanent implantation of a pulse generator and were assigned randomly in a crossover design to two 8-week intervals of active or sham stimulation. At the end of the two trial periods, the patients received active stimulation until the final evaluation at 1 year. Results Thirty-six patients (34 women; mean(s.d.) age 45(14) years) underwent peripheral nerve evaluation. Twenty responded and received a permanent stimulator. A positive response was observed in 12 of 20 and 11 of 20 patients after active and sham stimulation periods respectively (P = 0·746). Pain related to the device occurred in five patients and wound infection or haematoma in three, leading to definitive removal of the pulse generator in two patients. At 1 year, 11 of the 20 patients with an implanted device continued to respond. Stimulation had no significant effect on colonic transit time. Conclusion These results do not support the recommendation of permanent implantation of a pulse generator in patients with refractory constipation who initially responded to temporary nerve stimulation. Registration number: NCT01629303 (http://www.clinicaltrials.gov).
Published: 2016

5. Time trends of overall survival among metastatic breast cancer patients in the real-life ESME cohort

Author: Laurence Vanlemmens, Marc Debled, Christian Cailliot, Elisa Gobbini, Thomas Bachelot, Monia Ezzalfani, Christelle Jouannaud, Suzette Delaloge, Magali Lacroix-Triki, Anne Patsouris, Thierry Petit, Simone Mathoulin-Pélissier, Veronique Lorgis, William Jacot, Marie Ange Mouret-Reynier, Mathieu Robain, C. Lefeuvre-Plesse, Florence Dalenc, Audrey Lardy Cleaud, Etienne Brain, Christelle Levy, David Pérol, C. Courtinard, Véronique Diéras, Marianne Leheurteur, Lionel Uwer, Anthony Gonçalves, Jean Marc Ferrero, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR), Cancer et génome: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, Institut Curie [Paris]-MINES ParisTech - École nationale supérieure des mines de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute Curie, Centre Léon Bérard [Lyon], Institut Curie [Saint-Cloud], Service d'Oncologie Médicale, CRLCC Haute Normandie-Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), CRLC Val d'Aurelle-Paul Lamarque, CRLCC Val d'Aurelle - Paul Lamarque, 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), 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), École nationale supérieure d'architecture de Toulouse (ENSA Toulouse), Centre de Recherches en Cancérologie de Toulouse (CRCT), 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)-Centre National de la Recherche Scientifique (CNRS), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Service d'Oncologie médicale [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), 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), Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université Lille Nord de France (COMUE)-UNICANCER, Department of Medical Oncology, CRLCC Eugène Marquis (CRLCC), Centre d'Investigation Clinique - Epidemiologie Clinique / Essais Cliniques Bordeaux, Institut National de la Santé et de la Recherche Médicale (INSERM), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), CRLCC Jean Godinot, Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), Département de biologie et pathologie médicales [Gustave Roussy], Cancer et génôme: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, MINES ParisTech - École nationale supérieure des mines de Paris-Institut Curie-Institut National de la Santé et de la Recherche Médicale (INSERM), CRLCC Haute Normandie-CRLCC Henri Becquerel, CRLCC Val d'Aurelle - Paul Lamarque-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Imagerie Moléculaire et Stratégies Théranostiques - Clermont Auvergne (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA), Institut de cancérologie de l'Ouest - Paul Papin (ICO - Paul Papin), Service d'oncologie Médicale, Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Hôpital Jean Minjoz, Center Oscar Lambret, CRLCC Oscar Lambret, Institut de Cancérologie de Lorraine - Alexis Vautrin (ICL), Mines Paris - PSL (École nationale supérieure des mines de Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Curie - Saint Cloud (ICSC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Université de Lille-UNICANCER
Subjects: Adult, Cancer Research, medicine.medical_specialty, Multivariate analysis, Time Factors, Receptor, ErbB-2, [SDV.CAN]Life Sciences [q-bio]/Cancer, Breast Neoplasms, Triple Negative Breast Neoplasms, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Cancer Survivors, Risk Factors, HER2, Internal medicine, polycyclic compounds, Overall survival, Biomarkers, Tumor, Medicine, Humans, 030212 general & internal medicine, Neoplasm Metastasis, skin and connective tissue diseases, Aged, Retrospective Studies, Subtypes, Aged, 80 and over, business.industry, Time trends, Hazard ratio, Middle Aged, Metastatic breast cancer, medicine.disease, Confidence interval, 3. Good health, Treatment Outcome, Oncology, Receptors, Estrogen, 030220 oncology & carcinogenesis, Cohort, Observational study, Female, France, business, Receptors, Progesterone
Abstract: Real-life analysis of overall survival (OS) trends among metastatic breast cancer (MBC) patients may help define medical needs and evaluate the impact of public health investments. The present study aimed to evaluate the independent impact of the year of MBC diagnosis on OS in the Epidemio-Strategy-Medical-Economical (ESME)-MBC cohort.ESME-MBC (NCT03275311) is a French, national, multicentre, observational cohort including 16,702 consecutive newly diagnosed MBC patients (01 January 2008-31 December 2014). Of 16,680 eligible patients, 15,085 had full immunohistochemistry data, allowing classification as hormone receptor-positive and HER2-negative (HR+/HER2-, N = 9907), HER2-positive (HER2+, N = 2861) or triple-negative (HR-/HER2-, N = 2317) subcohorts. Multivariate analyses of OS were conducted among the full ESME cohort and subcohorts.Median OS of the whole cohort was 37.22 months (95% confidence interval [CI], 36.3-38.04). Year of diagnosis was an independent predictor of OS (hazard ratio 0.98 [95% CI, 0.97-1.00], P = .01) together with age, subtype, disease-free interval, visceral metastases and number of organs involved. Median OS of HR+/HER2-, HER2+ and HR-/HER2- subcohorts was, respectively, 42.12 (95% CI, 40.90-43.10), 44.91 (95% CI, 42.51-47.90) and 14.52 (95% CI, 13.70-15.24) months. Year of diagnosis was a strong independent predictor of OS in HER2+ subcohort (hazard ratio 0.91 [95% CI, 0.88-0.94], P .001), but not in HR+/HER2- nor HR-/HER2- subcohorts (hazard ratio 1.00 [95% CI, 0.98-1.01], P = .80 and 1.00 [95% CI, 0.97-1.02], P = .90, respectively).The OS of MBC patients has slightly improved over the past decade. However, this effect is confined to HER2+ cases, highlighting the need of new strategies in the other subtypes.
Published: 2018

6. Effect of Zr content on friction and wear behavior of Cr‐Zr‐N coating system

Author: Alain Iost, Mamoun Fellah, Hamid Djebaili, Corinne Nouveau, Agung Purnama, Alex Montagne, Linda Aissani, Mohammed Abdul Samad, Administrateur Ensam, Compte De Service, Université Badji Mokhtar Annaba (UBMA), Universite Abbes Laghrour [Khenchela], Université Mohammed Seddik Benyahia [Jijel] | University of Jijel (UMSBJ), King Fahd University of Petroleum and Minerals (KFUPM), Centre d'Investigation Clinique - Epidemiologie Clinique / Essais Cliniques Bordeaux, Institut National de la Santé et de la Recherche Médicale (INSERM), Mechanics surfaces and materials processing (MSMP), Arts et Métiers Sciences et Technologies, HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), Laboratoire Bourguignon des Matériaux et Procédés (LABOMAP), Université Badji Mokhtar - Annaba [Annaba] (UBMA), Badji Mokhtar-Annaba University, Université Jijel, and HESAM Université (HESAM)-HESAM Université (HESAM)
Subjects: wear, Materials science, [SPI] Engineering Sciences [physics], friction, 02 engineering and technology, Surface finish, Sciences de l'ingénieur, 01 natural sciences, CrZrN, [SPI]Engineering Sciences [physics], Coating system, 0103 physical sciences, Materials Chemistry, tribological behavior, Thin film, Composite material, 010302 applied physics, Marketing, Metallurgy, Tribology, 021001 nanoscience & nanotechnology, Condensed Matter Physics, Wear resistance, PVD, Physical vapor deposition, Ceramics and Composites, Crystallite, 0210 nano-technology, Tribometer
Abstract: International audience; Nanostructured Cr‐Zr‐N thin film with different Zr content (0 to 48.8 at.%) was deposited, using an RF magnetron‐sputtering technique. The structural evolution and morphological changes were performed. The tribological performances were evaluated, using a ball‐on‐disk type Oscillating tribometer. The tests were carried out under normal loads of 2, 4 and 6 N, respectively, with an alumina ball (Al2O3) as a counter face. The results showed that the crystallite size of the Cr‐Zr‐N system was reduced to 10.8 nm at 31.8 at.% Zr content. Morphological studies of the films showed that the roughness continuously decreased with increasing Zr content, exhibiting a value of 11.2 nm at 31.8 at.% Zr. The wear rate tends to decrease with the increasing of Zr content to reach a lowest value of 1.95 × 10‐2 μm3.N.μm‐1 at 31.8 at.% Zr. The wear rate and friction coefficient were lower in the samples with 31.8 at.% Zr content. The improved friction and wear resistance were attributed to the grain refinement strengthening mechanism at 31.8 at.% of Zr.
Published: 2018

7. Guidelines for time-to-event end-point definitions in trials for pancreatic cancer. Results of the DATECAN initiative (Definition for the Assessment of Time-to-event End-points in CANcer trials)

Author: Manfred B. Lutz, Roberto Labianca, Patrick Pessaux, Bert A. Bonsing, Benoist Chibaudel, David Malka, Claudio Bassi, Sophie Gourgou-Bourgade, Geertjan van Tienhoven, Pascal Hammel, Carine Bellera, Laeticia Dahan, Jean-Luc Van Laethem, Daniela Aust, Emmanuel Chamorey, Jean Robert Delpero, Josep Tabernero, Adelaide Dousseau, Teresa Macarulla, Franck Bonnetain, Julien Taieb, Karin Haustermans, Laurence Collette, Thomas Aparicio, François Lacaine, John P. Neoptolemos, Simone Mathoulin-Pélissier, Bengt Glimelius, Thierry Conroy, Paula Ghaneh, Alain Sauvanet, Erich Gerber, Christos Dervenis, Aurélien Latouche, Murielle Mauer, Michel Ducreux, Valérie Jooste, Virginie Berger, Jocelyn Gal, Alain Hendlisz, Aimery de Gramont, Emmanuel Mitry, Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (UR 3181) (CEF2P / CARCINO), 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), UNICANCER, Leiden University Medical Center (LUMC), Maladies chroniques, santé perçue, et processus d'adaptation (APEMAC), Université Paris Descartes - Paris 5 (UPD5)-Université de Lorraine (UL), Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), Université Victor Segalen - Bordeaux 2, CHU Bordeaux [Bordeaux], Uppsala Universitet [Uppsala], University Hospitals Leuven [Leuven], CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Service de Gastro-entérologie [Avicenne], Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Carl Gustav Carus University (DRESDEN - CGCU), Technische Universität Dresden = Dresden University of Technology (TU Dresden), G.B. Rossi Hospital, Verona University, Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Service d'Oncologie Médicale [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Cooperator Multidisciplinary Oncology Group (GERCOR), Service d'oncologie digestive et hépato-gastro-entérologie [Hôpital de la Timone - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Agia Olga Hospital [Athènes] (Konstantopoulio ), Oncologie digestive, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Institut für Radioonkologie, Royal Liverpool University Hospital, University of Liverpool-Royal Liverpool and Broadgreen University Hospital NHS Trust, Service de Gastroentérologie [Hôpital Beaujon], Hôpital Beaujon [AP-HP], Institut Jules Bordet [Bruxelles], Registre Bourguignon des Cancers Digestifs, Lipides - Nutrition - Cancer (U866) (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-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-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-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), 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-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), Azienda Ospedaleria Ospedali Riuniti di Bergamo, 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), CaritasKlinikum Saarbrücken, Vall d'Hebron University Hospital [Barcelona], European Organisation for Research and Treatment of Cancer [Bruxelles] (EORTC), European Cancer Organisation [Bruxelles] (ECCO), Institut Curie [Paris], CRLCC René Huguenin, L'Institut hospitalo-universitaire de Strasbourg (IHU Strasbourg), Institut National de Recherche en Informatique et en Automatique (Inria)-l'Institut de Recherche contre les Cancers de l'Appareil Digestif (IRCAD)-Les Hôpitaux Universitaires de Strasbourg (HUS)-La Fédération des Crédits Mutuels Centre Est (FCMCE)-L'Association pour la Recherche contre le Cancer (ARC)-La société Karl STORZ, Service d’Hépatologie [Hôpital Beaujon], 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), Academisch Medisch Centrum bij, Universiteit van Amsterdam (UvA), Institut de recherche en cancérologie de Montpellier (IRCM - U896 Inserm - UM1), Université Montpellier 1 (UM1)-CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre d'Investigation Clinique - Epidemiologie Clinique / Essais Cliniques Bordeaux, Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Bergonié [Bordeaux], Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC ( CEF2P / CARCINO ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Université Bourgogne Franche-Comté ( UBFC ) -Université de Franche-Comté ( UFC ), Maladies chroniques, santé perçue, et processus d'adaptation. Approches épidémiologiques et psychologiques. ( APEMAC - EA 4360 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Université de Lorraine ( UL ), Institut de Cancérologie de Lorraine - Alexis Vautrin ( ICL ), CHU Tenon [APHP], Hôpital Erasme (Bruxelles), Université Paris 13 ( UP13 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Avicenne, Carl Gustav Carus University ( DRESDEN - CGCU ), Technische Universität Dresden ( TUD ), Institut de cancérologie de l'Ouest - Nantes ( ICO Nantes ), CRLCC Paul Papin-CRLCC René Gauducheau, CRLCC Antoine Lacassagne, Service d'Oncologie Médicale [CHU Saint -Antoine], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Saint-Antoine [APHP], Cooperator Multidisciplinary Oncology Group ( GERCOR ), Assistance Publique - Hôpitaux de Marseille ( APHM ) - Hôpital de la Timone [CHU - APHM] ( TIMONE ), Institut Paoli Calmettes, Agia Olga Hospital [Athènes] ( Konstantopoulio ), Institut Gustave Roussy ( IGR ) -Institut Gustave Roussy ( IGR ), Hôpital Beaujon, Institut Jules Bordet, Lipides - Nutrition - Cancer (U866) ( 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-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ) -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-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ) -Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), 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-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ), 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)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale ( INSERM ), European Organisation for Research and Treatment of Cancer [Bruxelles] ( EORTC ), European Cancer Organisation [Bruxelles] ( ECCO ), Institut Curie, L'Institut hospitalo-universitaire de Strasbourg ( IHU Strasbourg ), Institut National de Recherche en Informatique et en Automatique ( Inria ) -l'Institut de Recherche contre les Cancers de l'Appareil Digestif (IRCAD)-Les Hôpitaux Universitaires de Strasbourg (HUS)-La Fédération des Crédits Mutuels Centre Est (FCMCE)-L'Association pour la Recherche contre le Cancer (ARC)-La société Karl STORZ, Service de gastroenterologie [CHU Georges Pompidou], Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Européen Georges Pompidou [APHP] ( HEGP ), Universiteit van Amsterdam ( UvA ), Institut de recherche en cancérologie de Montpellier ( IRCM ), Université Montpellier 1 ( UM1 ) -CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Montpellier ( UM ), Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut Bergonié - CRLCC Bordeaux, Universiteit Leiden, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Università degli studi di Verona = University of Verona (UNIVR), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (EA 3181) (CEF2P / CARCINO), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bourgogne (UB)-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-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)-Université de Bourgogne (UB)-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bourgogne (UB)-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, 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), and CRLCC Val d'Aurelle - Paul Lamarque-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 1 (UM1)
Subjects: Oncology, Cancer Research, Pathology, Delphi Technique, MESH : Randomized Controlled Trials as Topic, MESH: Delphi Technique, MESH : Consensus, law.invention, Clinical trials, 0302 clinical medicine, Pancreatic cancer, Time to event end-point, Consensus, Guidelines, Methodology, Clinical trials, Randomized controlled trial, law, 030212 general & internal medicine, Time to event end-point, Randomized Controlled Trials as Topic, Event (probability theory), MESH: Endpoint Determination, [ SDV.SPEE ] Life Sciences [q-bio]/Santé publique et épidémiologie, 16. Peace & justice, 3. Good health, 030220 oncology & carcinogenesis, MESH : Disease-Free Survival, MESH : Endpoint Determination, MESH: Pancreatic Neoplasms, medicine.medical_specialty, Consensus, Endpoint Determination, Guidelines, Disease-Free Survival, 03 medical and health sciences, Internal medicine, Pancreatic cancer, medicine, Overall survival, Humans, MESH: Consensus, Distributed File System, neoplasms, MESH: Humans, End point, business.industry, MESH : Humans, Methodology, Cancer, medicine.disease, Pancreatic Neoplasms, Clinical trial, MESH: Randomized Controlled Trials as Topic, MESH : Delphi Technique, MESH: Disease-Free Survival, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, MESH : Pancreatic Neoplasms
Abstract: International audience; BACKGROUND:Using potential surrogate end-points for overall survival (OS) such as Disease-Free- (DFS) or Progression-Free Survival (PFS) is increasingly common in randomised controlled trials (RCTs). However, end-points are too often imprecisely defined which largely contributes to a lack of homogeneity across trials, hampering comparison between them. The aim of the DATECAN (Definition for the Assessment of Time-to-event End-points in CANcer trials)-Pancreas project is to provide guidelines for standardised definition of time-to-event end-points in RCTs for pancreatic cancer.METHODS:Time-to-event end-points currently used were identified from a literature review of pancreatic RCT trials (2006-2009). Academic research groups were contacted for participation in order to select clinicians and methodologists to participate in the pilot and scoring groups (>30 experts). A consensus was built after 2 rounds of the modified Delphi formal consensus approach with the Rand scoring methodology (range: 1-9).RESULTS:For pancreatic cancer, 14 time to event end-points and 25 distinct event types applied to two settings (detectable disease and/or no detectable disease) were considered relevant and included in the questionnaire sent to 52 selected experts. Thirty experts answered both scoring rounds. A total of 204 events distributed over the 14 end-points were scored. After the first round, consensus was reached for 25 items; after the second consensus was reached for 156 items; and after the face-to-face meeting for 203 items.CONCLUSION:The formal consensus approach reached the elaboration of guidelines for standardised definitions of time-to-event end-points allowing cross-comparison of RCTs in pancreatic cancer.
Published: 2014

8. Effects of Maternal Supplementation With Omega-3 Precursors on Human Milk Composition

Author: Jean-Charles Picaud, Virginie Rigourd, Fabienne Nacka, Claude Billeaud, Paul Perez, Gilles Cambonie, Rémi Sitta, Evelyne Mazurier, Wafae Belcadi, Rachel Buffin, Leslie Couëdelo, Delphine Lamireau, Carole Vaysse, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Bordeaux [Bordeaux], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL), Université de Bordeaux (UB), Centre d'Investigation Clinique - Epidemiologie Clinique / Essais Cliniques Bordeaux, Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Pellegrin, and CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin
Subjects: Adult, 0301 basic medicine, Rapeseed, Breastfeeding, Mothers, [SDV.MHEP.GEO]Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, Washout period, 03 medical and health sciences, Fatty Acids, Omega-3, Humans, Lactation, Medicine, Food science, Milk Banks, Maternal Behavior, ComputingMilieux_MISCELLANEOUS, 2. Zero hunger, chemistry.chemical_classification, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, 030109 nutrition & dietetics, Milk, Human, business.industry, alpha-Linolenic Acid, Obstetrics and Gynecology, Fatty acid, Feeding Behavior, Breast Feeding, chemistry, Dietary Supplements, Female, Composition (visual arts), France, business, Polyunsaturated fatty acid, Olive oil
Abstract: Background:Long-chain polyunsaturated fatty acids (LC-PUFAs) are important for newborn neurosensory development. Supplementation of breastfeeding mothers’ diets with omega-3 PUFAs, such as alpha-linolenic acid (ALA), may increase their concentration in human milk.Research aim:This study aimed to assess human milk composition after 15-day supplementation regimens containing either omega-3 PUFAs or olive oil, which does not provide ALA.Methods:A multicenter factorial randomized trial was conducted with four groups of breastfeeding women, with each group containing 19 to 22 women. After a 15-day ALA washout period, three groups received supplementation with omega-3 precursors for 15 days: an enriched margarine (M), a rapeseed oil (R), and a margarine and rapeseed oil (MR). The fourth was unexposed to omega-3 precursors (olive oil control diet, O). After 15 days, blind determination of human milk fatty acid (FA) composition was assessed by gas chromatography, and the FA composition was compared among groups using variance analyses.Results:Alpha-linolenic acid content, expressed as the mean (standard deviation) total human milk FA percentage, was significantly higher after diet supplementation with omega-3 PUFAs, with values of 2.2% (0.7%) (MR), 1.3% (0.5%) (R), 1.1% (0.4%) (M), and 0.8% (0.3%) (O at D30) ( p < .003 for each comparison). The lowest LA–ALA ratio (5.5) was found in the MR group ( p < .001). Docosahexaenoic acid and trans FA concentrations did not differ among groups.Conclusion:In lactating women, omega-3 supplementation via the combination of enriched margarine and rapeseed oil increased the ALA content of human milk and generated the most favorable LA–ALA ratio for LC-PUFA synthesis.
Published: 2017

9. Group and individual cognitive therapies in Alzheimer's disease: the ETNA3 randomized trial

Author: Sandrine Andrieu, Chantal Girtanner, Jacques Touchon, Muriel Rainfray, Fati Nourhashemi, Jocelyne De Rotrou, Béatrice Desgranges, Céline Meillon, Anne-Sophie Grandoulier, Bruno Dubois, Benoît Lavallart, Marie-Eve Joel, Hélène Amieva, Jean-François Dartigues, Florence Pasquier, P. Robert, Claudine Berr, Geneviève Chêne, Epidémiologie et Biostatistique [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Nice (CHU Nice), CHU Bordeaux [Bordeaux], Centre d'Investigation Clinique - Epidemiologie Clinique / Essais Cliniques Bordeaux, Institut National de la Santé et de la Recherche Médicale (INSERM), AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Epidémiologie et analyses en santé publique : risques, maladies chroniques et handicaps (LEASP), 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, Neuropsychiatrie : recherche épidémiologique et clinique (PSNREC), Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Neuropsychologie et imagerie de la mémoire humaine (NIMH), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière (CRICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Saint-Etienne, Laboratoire d'Economie et de Gestion des Organisations de Santé (Legos), Université Paris Dauphine-PSL, Laboratoire d'Economie de Dauphine (LEDa), Direction Générale de la Santé (DGS), Ministère de la santé, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Normandie Université (NU)-Normandie Université (NU)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)
Subjects: Male, medicine.medical_treatment, Kaplan-Meier Estimate, law.invention, cognitive training, 0302 clinical medicine, Randomized controlled trial, law, Adaptation, Psychological, 030212 general & internal medicine, Aged, 80 and over, reminiscence, [SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, Depression, [SDV.MHEP.GEG]Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, individualized cognitive rehabilitation, Cognitive training, 3. Good health, Psychiatry and Mental health, Clinical Psychology, Treatment Outcome, Caregivers, Psychotherapy, Group, Female, France, Alzheimer's disease, medicine.medical_specialty, non-drug therapies, 03 medical and health sciences, Reminiscence therapy, Quality of life (healthcare), Alzheimer Disease, Memory, medicine, Humans, Dementia, Cognitive Dysfunction, Cognitive rehabilitation therapy, Psychiatry, Aged, Proportional Hazards Models, Psychiatric Status Rating Scales, Cognitive Behavioral Therapy, business.industry, medicine.disease, Logistic Models, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Quality of Life, Cognitive therapy, Physical therapy, Alzheimer, Geriatrics and Gerontology, business, Gerontology, 030217 neurology & neurosurgery, dementia
Abstract: Background:Although non-drug interventions are widely used in patients with Alzheimer's disease, few large scale randomized trials involving a long-term intervention and several cognitive-oriented approaches have been carried out. ETNA3 trial compares the effect of cognitive training, reminiscence therapy, and an individualized cognitive rehabilitation program in Alzheimer's disease to usual care.Methods:This is a multicenter (40 French clinical sites) randomized, parallel-group trial, with a two-year follow-up comparing groups receiving standardized programs of cognitive training (group sessions), reminiscence therapy (group sessions), individualized cognitive rehabilitation program (individual sessions), and usual care (reference group). Six hundred fifty-three outpatients with Alzheimer's disease were recruited. The primary efficacy outcome was the rate of survival without moderately severe to severe dementia at two years. Secondary outcomes were cognitive impairment, functional disability, behavioral disturbance, apathy, quality of life, depression, caregiver's burden, and resource utilization.Results:No impact on the primary efficacy measure was evidenced. For the two group interventions (i.e. cognitive training and reminiscence), none of the secondary outcomes differed from usual care. The larger effect was seen with individualized cognitive rehabilitation in which significantly lower functional disability and a six-month delay in institutionalization at two years were evidenced.Conclusions:These findings challenge current management practices of Alzheimer's patients. While cognitive-oriented group therapies have gained popularity, this trial does not show improvement for the patients. The individualized cognitive rehabilitation intervention provided clinically significant results. Individual interventions should be considered to delay institutionalization in Alzheimer's disease.
Published: 2016

10. One-Year Mortality in Older Patients with Cancer: Development and External Validation of an MNA-Based Prognostic Score

Author: Carine Bellera, Simone Mathoulin-Pélissier, Adélaïde Doussau, Muriel Rainfray, Pierre Soubeyran, Jessica Durrieu, Isabelle Bourdel-Marchasson, Christelle Blanc-Bisson, Christine Germain, Mariane Fonck, Abou Diallo, Centre de Gériatrie, CHU Bordeaux [Bordeaux]-Groupe Hospitalier Sud, Institut de Santé Publique, d'Epidémiologie et de Développement (ISPED), Université Bordeaux Segalen - Bordeaux 2, Centre d'Investigation Clinique - Epidemiologie Clinique / Essais Cliniques Bordeaux, Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Régional de lutte contre le Cancer du Sud-Ouest, Institut Bergonié [Bordeaux], UNICANCER-UNICANCER, Plateforme de génétique moléculaire des cancers d'Aquitaine, CHU Bordeaux [Bordeaux], Epidémiologie et Biostatistique [Bordeaux], and Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Male, Gerontology, Cachexia, Multivariate analysis, Physiology, [SDV]Life Sciences [q-bio], Cancer Treatment, lcsh:Medicine, law.invention, Cohort Studies, Hematologic Cancers and Related Disorders, White Blood Cells, 0302 clinical medicine, Randomized controlled trial, Animal Cells, Weight loss, law, Neoplasms, Medicine and Health Sciences, Prospective Studies, Lymphocytes, 030212 general & internal medicine, lcsh:Science, Prospective cohort study, Aged, 80 and over, 2. Zero hunger, Multidisciplinary, Pharmaceutics, Mortality rate, Hematology, Prognosis, 3. Good health, Oncology, Physiological Parameters, 030220 oncology & carcinogenesis, Cancer Therapy, Female, Lymphomas, France, Cellular Types, medicine.symptom, Research Article, Cohort study, medicine.medical_specialty, Death Rates, Immune Cells, Immunology, Nutritional Status, 03 medical and health sciences, Drug Therapy, Population Metrics, Diagnostic Medicine, Internal medicine, Weight Loss, medicine, Humans, Chemotherapy, Geriatric Assessment, Aged, Demography, Nutrition, Blood Cells, Population Biology, business.industry, lcsh:R, Malnutrition, Body Weight, Biology and Life Sciences, Cancers and Neoplasms, Cancer, Cell Biology, medicine.disease, Logistic Models, Nutrition Assessment, Multivariate Analysis, People and Places, lcsh:Q, business
Abstract: PURPOSE:The MNA (Mini Nutritional Assessment) is known as a prognosis factor in older population. We analyzed the prognostic value for one-year mortality of MNA items in older patients with cancer treated with chemotherapy as the basis of a simplified prognostic score. METHODS:The prospective derivation cohort included 606 patients older than 70 years with an indication of chemotherapy for cancers. The endpoint to predict was one-year mortality. The 18 items of the Full MNA, age, gender, weight loss, cancer origin, TNM, performance status and lymphocyte count were considered to construct the prognostic model. MNA items were analyzed with a backward step-by-step multivariate logistic regression and other items were added in a forward step-by-step regression. External validation was performed on an independent cohort of 229 patients. RESULTS:At one year 266 deaths had occurred. Decreased dietary intake (p = 0.0002), decreased protein-rich food intake (p = 0.025), 3 or more prescribed drugs (p = 0.023), calf circumference
Published: 2016

11. A new approach to integrate toxicity grade and repeated treatment cycles in the analysis and reporting of phase I dose-finding trials

Author: Adélaïde Doussau, Rodolphe Thiébaut, M.C. Le Deley, Elisa Rizzo, C. Le Tourneau, Pierre Fumoleau, B Geoerger, Xavier Paoletti, Simone Mathoulin-Pélissier, Patrick Schöffski, Anne Floquet, Epidémiologie et Biostatistique [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Bordeaux (UB), Statistics In System biology and Translational Medicine (SISTM), Inria Bordeaux - Sud-Ouest, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)- Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Vectorologie et transfert de gènes (VTG / UMR8121), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Centre National de la Recherche Scientifique (CNRS), Department of General Medical Oncology [Leuven], University Hospitals Leuven [Leuven], Institut Bergonié [Bordeaux], UNICANCER, Epidémiologie des cancers : Radiocarcinogénèse et effets iatrogènes des traitements, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de santé publique, Institut Gustave Roussy (IGR), Centre d'Investigation Clinique - Epidemiologie Clinique / Essais Cliniques Bordeaux, Institut National de la Santé et de la Recherche Médicale (INSERM), European Organisation for Research and Treatment of Cancer [Bruxelles] (EORTC), European Cancer Organisation [Bruxelles] (ECCO), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), Cancer et génome: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, MINES ParisTech - École nationale supérieure des mines de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), and Mines Paris - PSL (École nationale supérieure des mines de Paris)
Subjects: Oncology, Male, medicine.medical_specialty, Cyclophosphamide, Maximum Tolerated Dose, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Antineoplastic Agents, Pharmacology, Dose finding, Repeated treatment, Internal medicine, Neoplasms, medicine, Humans, Models, Statistical, Clinical Trials, Phase I as Topic, business.industry, Cumulative distribution function, Hematology, Toxicity Grade, 3. Good health, Radiation therapy, Toxicity, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Female, Erlotinib, business, medicine.drug
Abstract: In phase I trials, severe and moderate toxicities occurring after the first cycle of treatment are important sources of information. Model-based approach can be used to evaluate per cycle probability of moderate or severe toxicity and cumulative probability of severe toxicity over time. It increases precision of estimates, and it enables investigating increased probability of toxicity over time. Background Safety assessment beyond the dose-limiting toxicity evaluation period provides relevant information to define the recommended phase II dose (RP2D) of a new treatment. We retrospectively analyzed three phase I trials to illustrate two indicators: per-cycle probability of graded toxicity and cumulative probability of severe toxicity over the treatment period. Patients and methods Data were collected from two continual reassessment method (CRM) trials (T1: aviscumine in solid tumors with short time on treatment; T2: erlotinib + radiotherapy in brainstem gliomas with longer time on treatment) and one 3 + 3 design (T3: liposomal doxorubicin + cyclophosphamide combination in ovarian carcinoma). The probability of severe and moderate or severe toxicity per cycle was estimated at each dose level with mixed proportional odds model. The cumulative probability of severe toxicity was also estimated with the time-to-event CRM. Results Eighty-three patients were included in the three trials; 94, 96 and 72 treatment cycles were administered, in T1, T2 and T3, respectively. Moderate toxicities were at least twice as frequent as severe toxicities. An increased probability of toxicity over time was detected in T3 [P = 0.04; per-cycle probability of severe toxicity: 27% (cycle 1) to 59% (cycle 6) at the RP2D]. At the RP2D, 37% of patients experienced at least one severe toxicity over the first six cycles in T2, and 78% in T3. Conclusions Dedicated methods can be used to analyze toxicities from all cycles of treatment. They do not delay accrual and should be integrated in the analysis and reporting of phase I dose-finding trials.
Published: 2014

12. Dose-finding design using mixed-effect proportional odds model for longitudinal graded toxicity data in phase I oncology clinical trials

Author: Adélaïde Doussau, Rodolphe Thiébaut, Xavier Paoletti, Centre d'Investigation Clinique - Epidemiologie Clinique / Essais Cliniques Bordeaux, Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Santé Publique, d'Epidémiologie et de Développement (ISPED), Université Bordeaux Segalen - Bordeaux 2, Epidémiologie et Biostatistique [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Statistics In System biology and Translational Medicine (SISTM), Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Inria Bordeaux - Sud-Ouest, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Service de Biostatistiques, Institut Curie [Paris], Cancer et génome: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, Mines Paris - PSL (École nationale supérieure des mines de Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), and MINES ParisTech - École nationale supérieure des mines de Paris
Subjects: Adult, Statistics and Probability, Oncology, medicine.medical_specialty, Maximum Tolerated Dose, longitudinal, Epidemiology, Ordinal Scale, Phase (waves), Antineoplastic Agents, 01 natural sciences, proportional odds, 010104 statistics & probability, 03 medical and health sciences, Dose finding, 0302 clinical medicine, Neoplasms, Internal medicine, Humans, Medicine, Computer Simulation, Longitudinal Studies, 0101 mathematics, Adverse effect, Toxins, Biological, Proportional odds, Likelihood Functions, Models, Statistical, Clinical Trials, Phase I as Topic, business.industry, dose finding, ordinal, 3. Good health, Ribosome Inactivating Proteins, Type 2, Clinical trial, 030220 oncology & carcinogenesis, Toxicity, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Plant Preparations, Ordered logit, business, continual reassessment method
Abstract: International audience; Phase I oncology clinical trials are designed to identify the optimal dose that will be recommended for phase II trials. This dose is typically defined as the dose associated with a certain probability of severe toxicity during the first cycle of treatment, although toxicity is repeatedly measured over cycles on an ordinal scale. We propose a new adaptive dose-finding design using longitudinal measurements of ordinal toxic adverse events, with proportional odds mixed-effect models. Likelihood-based inference is implemented. The optimal dose is then the dose producing a target rate of severe toxicity per cycle. This model can also be used to identify cumulative or late toxicities. The performances of this approach were compared with those of the continual reassessment method in a simulation study. Operating characteristics were evaluated in terms of correct identification of the target dose, distribution of the doses allocated and power to detect trends in the risk of toxicities over time. This approach was also used to reanalyse data from a phase I oncology trial. Use of a proportional odds mixed-effect model appears to be feasible in phase I dose-finding trials, increases the ability of selecting the correct dose and provides a tool to detect cumulative effects.
Published: 2013

13. Shared random-effect models for the joint analysis of longitudinal and time-to-event data: application to the prediction of prostate cancer recurrence

Author: Sène, Mbéry, Bellera, Carine, Proust-Lima, Cecile, Epidémiologie et Biostatistique [Bordeaux], Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Université Bordeaux Segalen - Bordeaux 2, Centre d'Investigation Clinique - Epidemiologie Clinique / Essais Cliniques Bordeaux, Institut National de la Santé et de la Recherche Médicale (INSERM), Département de recherche clinique et d'information médicale, Institut Bergonié [Bordeaux], UNICANCER-UNICANCER, This work was supported by the French National Institute of Cancer INCa [grant PREDYC number 2010-059], Proust-Lima, Cecile, and Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Prognos- tic cross-entropy, Joint models, Prostate cancer, [SDV.BIBS] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Shared random-effect models, Predictive accuracy, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], Dynamic predictions, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], [INFO.INFO-BI] Computer Science [cs]/Bioinformatics [q-bio.QM]
Abstract: In the last decade, joint modeling research has expanded very rapidly in bio- statistics and medical research. This type of models enables the simultaneous study of a longitudinal marker and a correlated time-to-event. Among them, the shared random-effect models that define a mixed model for the longitudinal marker and a survival model for the time-to-event including characteristics of the mixed model as covariates received the main interest. Indeed, they extend naturally the survival model with time-dependent covariates and offer a flexible framework to explore the link between a longitudinal biomarker and a risk of event. The objective of this paper is to briefly review the shared random-effect model methodology and detail its implementation and evaluation through a real example from the study of prostate cancer progression after a radiation therapy. In particular, different specifications of the dependency between the longitudinal biomarker, the prostate-specific antigen (PSA), and the risk of clinical recurrence are investigated to better understand the link between the PSA dynamics and the risk of clinical recurrence. These different joint models are compared in terms of goodness-of-fit and adequation to the joint model assumptions but also in terms of predictive accuracy using the expected prognostic cross-entropy. Indeed, in addition to better understand the link between the PSA dynamics and the risk of clinical recurrence, the perspective in prostate cancer studies is to provide dynamic prognostic tools of clinical recurrence based on the biomarker history.
Published: 2013

14. Phase III randomized equivalence trial of early breast cancer treatments with or without axillary clearance in post-menopausal patients Results after 5 years of follow-up

Author: A, Avril, G, Le Bouëdec, G, Lorimier, J M, Classe, C, Tunon-de-Lara, S, Giard, G, MacGrogan, M, Debled, S, Mathoulin-Pélissier, L, Mauriac, Isabelle, de Mascarel, Département de chirurgie, Institut Bergonié [Bordeaux], UNICANCER-UNICANCER, Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER, Centre Paul Papin, CRLCC Paul Papin, Centre René Gauducheau, CRLCC René Gauducheau, Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université Lille Nord de France (COMUE)-UNICANCER, Département de pathologie, Département d'oncologie médicale, Centre d'Investigation Clinique - Epidemiologie Clinique / Essais Cliniques Bordeaux, Institut National de la Santé et de la Recherche Médicale (INSERM), Peer, Hal, and Université de Lille-UNICANCER
Subjects: Oncology, medicine.medical_treatment, Kaplan-Meier Estimate, Mastectomy, Segmental, law.invention, 0302 clinical medicine, Randomized controlled trial, law, axillary lymph nodes, Clinical endpoint, Medicine, 030212 general & internal medicine, Aged, 80 and over, Carcinoma, Ductal, Breast, axillary dissection, General Medicine, Middle Aged, 3. Good health, Postmenopause, Survival Rate, medicine.anatomical_structure, Equivalence Trial, Chemotherapy, Adjuvant, 030220 oncology & carcinogenesis, Lymphatic Metastasis, Early Termination of Clinical Trials, Female, Mastectomy, axillary clearance, medicine.medical_specialty, Axillary lymph nodes, Antineoplastic Agents, Hormonal, Breast Neoplasms, Disease-Free Survival, 03 medical and health sciences, Breast cancer, Mastectomy, Modified Radical, Internal medicine, Humans, early breast cancer, Survival rate, Aged, Neoplasm Staging, business.industry, medicine.disease, Radiation therapy, Carcinoma, Lobular, Tamoxifen, breast cancer surgery, Axilla, Lymph Node Excision, Surgery, Radiotherapy, Adjuvant, Lymph Nodes, Neoplasm Recurrence, Local, business, Follow-Up Studies
Abstract: Background Axillary lymph node clearance (ALNC) improves locoregional control and provides prognostic information for early breast cancer treatment, but effects on survival are controversial. This multicentre, randomized pragmatic equivalence trial compares outcomes for post-menopausal early invasive breast cancer patients after locoregional treatment with ALNC and adjuvant therapies to outcomes after locoregional treatment without ALNC and adjuvant therapies. Methods From 1995–2005, women aged ≥50 years with early breast cancer (tumor ≤ 10 mm) and clinically-negative axillary nodes were randomized to receive treatment with ALNC (Ax) or without (no-Ax). Adjuvant therapies were prescribed according to hormonal receptor status and individual histological results. The primary endpoint was overall survival (OS); secondary endpoints were event-free survival (EFS) and functional outcomes. The trial was terminated due to lack of equivalence and low accrual after first interim analyses. Trial registration: NCT00210236. Results Of 625 patients, 297 no-Ax and 310 Ax patients were maintained for final per-protocol analyses. OS and EFS at five years were not equivalent (Ax vs. no-Ax: 98% vs. 94% and 96% vs. 90% respectively). Recurrence was higher for no-Ax, particularly in the first five years after surgery. Axillary nodes were positive for 14% Ax patients but only 2% no-Ax patients experienced axillary node recurrence. Functional impairments were greater after ALNC. Conclusion Our results fail to demonstrate equivalence of outcomes when ALNC is omitted from post-menopausal early breast cancer patient treatment. However the low locoregional recurrence rates warrant further examination over a longer duration, in particular to consider whether these would impact on survival.
Published: 2011

15. High-dose chemotherapy consolidation for chemosensitive advanced soft tissue sarcoma patients: an open-label, randomized controlled trial

Author: Bui-Nguyen, B., Ray-Coquard, Isabelle, Chevreau, C., Penel, N., Bay, J. O., Coindre, J. M., Cupissol, D., Italiano, A., Bonichon, F., Lotz, J. P., Thyss, A., Jimenez, M., Mathoulin-Pélissier, S., Blay, J. Y., Renseigné, Non, Institut Bergogné, Department of Medical Oncology, Centre Léon Bérard [Lyon], Institut Claudius Regaud, CRLCC Institut Claudius Regaud, Centre Régional de Lutte Contre le Cancer Oscar Lambret, Centre Jean Perrin, CRLCC Jean Perrin, Institut bergogné, Centre Val d'Aurelle-Paul Lamarque, Plateforme de génétique moléculaire des cancers d'Aquitaine, Institut Bergonié - CRLCC Bordeaux, Service d'oncologie Médicale, Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Hôpital Jean Minjoz, Centre Antoine Lacassagne, CRLCC Antoine Lacassagne, Unité Matériaux et Transformations - UMR 8207 (UMET), Centre National de la Recherche Scientifique (CNRS)-Université de Lille-Ecole Nationale Supérieure de Chimie de Lille (ENSCL)-Institut National de la Recherche Agronomique (INRA), Centre d'Investigation Clinique - Epidemiologie Clinique / Essais Cliniques Bordeaux, Institut National de la Santé et de la Recherche Médicale (INSERM), Eq 11, Centre Léon Bérard [Lyon]-Centre de Recherche en Cancérologie de Lyon (CRCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre Léon Bérard [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), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université Lille Nord de France (COMUE)-UNICANCER, Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER, Institut Bergonié [Bordeaux], UNICANCER-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), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Institut de Chimie du CNRS (INC)-Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Lille-Ecole Nationale Supérieure de Chimie de Lille (ENSCL), Centre Léon Bérard [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-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Lille-UNICANCER, Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Supérieure de Chimie de Lille (ENSCL)-Institut de Chimie du CNRS (INC)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), and Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL)
Subjects: Male, MESH: Combined Modality Therapy, MESH: Consolidation Chemotherapy, MESH: Peripheral Blood Stem Cell Transplantation, Kaplan-Meier Estimate, Carboplatin, chemistry.chemical_compound, 0302 clinical medicine, MESH: Mesna, MESH: Carboplatin, Antineoplastic Combined Chemotherapy Protocols, Etoposide, Mesna, MESH: Etoposide, MESH: Aged, Ifosfamide, MESH: Middle Aged, Soft tissue sarcoma, Sarcoma, Hematology, Middle Aged, Chemotherapy regimen, Combined Modality Therapy, 3. Good health, Dacarbazine, MESH: Antineoplastic Combined Chemotherapy Protocols, Oncology, MESH: Young Adult, 030220 oncology & carcinogenesis, Female, medicine.drug, Adult, medicine.medical_specialty, Adolescent, [SDV.CAN]Life Sciences [q-bio]/Cancer, MESH: Dacarbazine, Disease-Free Survival, 03 medical and health sciences, MESH: Doxorubicin, Young Adult, medicine, Humans, Progression-free survival, MESH: Ifosfamide, MESH: Kaplan-Meier Estimate, Aged, MESH: Adolescent, Peripheral Blood Stem Cell Transplantation, MESH: Humans, business.industry, MESH: Adult, medicine.disease, MESH: Male, Surgery, Consolidation Chemotherapy, chemistry, Doxorubicin, MESH: Sarcoma, MESH: Disease-Free Survival, business, MESH: Female, 030215 immunology
Abstract: International audience; BACKGROUND: Metastatic soft tissue sarcoma (STS) prognosis remains poor and few cytotoxic agents offer proven efficacy. This randomized open phase III study examines whether high-dose (HD) chemotherapy with peripheral blood stem cells (PBSCs) could improve overall survival (OS) of chemosensitive patients. PATIENTS AND METHODS: Advanced STS patients aged 18-65 years received four courses of standard mesna, adryamycin, ifosfamide and dacarbazine (MAID) treatment. Chemotherapy-responding patients and patients with at least stable disease amenable to complete surgical resection were randomized to receive standard dose (SD) with two successive MAID cycles or HD treatments of one MAID then MICE intensification: mesna (3.6 g/m(2), day 1-5), ifosfamide (2.5 g/m(2), day 1-4), carboplatin [area under the curve (AUC) 5/day 2-4] and etoposide (300 mg/m(2), day 1-4) with PBSC reinjection at day 7. RESULTS: From 2000 to 2008, 207 patients received four cycles of MAID and 87 assessable patients were randomly assigned to receive the following: 46 SD, 41 HD, with 45 and 38 maintained for analyses after secondary centralized histological review. Futility analyses led to study closure in November 2008. Three-year OS was 49.4% for the SD group versus 32.7% for HD arm, hazard ratio= 1.26, 95% confidence interval 0.70-2.29; progression-free survival was 32.4% and 14.0%, respectively. HD treatment led to higher grades 3-4 toxicity. CONCLUSION: This study failed to show an OS advantage for advanced STS patients treated with dose-intensified chemotherapy with PBSC.
Published: 2011

16. Breast cancer care compared with clinical Guidelines: an observational study in France

Author: Marie, Lebeau, Simone, Mathoulin-Pélissier, Carine, Bellera, Christine, Tunon-de-Lara, Alain, Daban, Francis, Lipinski, Dominique, Jaubert, Pierre, Ingrand, Virginie, Migeot, A, Veret, BMC, Ed., Service de Radiothérapie [Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Réseau de Cancérologie d'Aquitaine, Département de recherche clinique et d'information médicale, Institut Bergonié [Bordeaux], UNICANCER-UNICANCER, Centre d'Investigation Clinique - Epidemiologie Clinique / Essais Cliniques Bordeaux, Institut National de la Santé et de la Recherche Médicale (INSERM), Département de chirurgie, Réseau de Cancérologie de Poitou-Charentes, Centre Oncoradiothérapie de la Côte Basque, the REPERES group, and Institut Bergonié - CRLCC Bordeaux
Subjects: MESH: Decision Making, Pediatrics, MESH: Logistic Models, Logistic regression, MESH: Aged, 80 and over, Surveys and Questionnaires, Epidemiology, Odds Ratio, MESH: Quality of Health Care, Young adult, Practice Patterns, Physicians', Aged, 80 and over, MESH: Aged, MESH: Middle Aged, Medical record, lcsh:Public aspects of medicine, MESH: Neoplasm Staging, Middle Aged, MESH: Patient Compliance, MESH: Young Adult, MESH: Guideline Adherence, Female, France, Guideline Adherence, Research Article, Adult, medicine.medical_specialty, Decision Making, Breast Neoplasms, MESH: Multivariate Analysis, MESH: Social Class, Young Adult, Breast cancer, Internal medicine, medicine, Humans, MESH: Physician's Practice Patterns, Aged, Neoplasm Staging, Quality of Health Care, MESH: Humans, business.industry, Public health, MESH: Questionnaires, Public Health, Environmental and Occupational Health, lcsh:RA1-1270, MESH: Adult, Odds ratio, medicine.disease, MESH: Odds Ratio, MESH: France, Logistic Models, Social Class, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Multivariate Analysis, Patient Compliance, Observational study, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, MESH: Female, MESH: Breast Neoplasms
Abstract: Background Great variability in breast cancer (BC) treatment practices according to patient, tumour or organisation of care characteristics has been reported but the relation between these factors is not well known. In two French regions, we measured compliance with Clinical Practice Guidelines for non-metastatic BC care management and identified factors associated with non-compliance at clinical and organisational levels. Methods Eligible patients had invasive unilateral BC without distant metastases and at least two contacts with one of the two regional healthcare systems (2003-2004) in the first year after diagnosis. Medical data were collected from patient medical records in all public and private hospitals (99 hospitals). The care process was defined by 20 criteria: clinical decisions for treatment and therapeutic procedures. Each criterion was classified according to level of compliance ("Compliant", "Justifiable" and "Not Compliant") and factors of non-compliance were identified (mixed effect logistic regression). Results 926 women were included. Non-compliance with clinical decisions for treatment was associated with older patient age (OR 2.1; 95%CI: 1.3-3.6) and region (OR 3.0; 95%CI: 1.2-7.4). Non-compliance with clinical decisions for radiotherapy was associated with lymph node involvement or the presence of peritumoural vascular invasion (OR 1.5; 95%CI: 1.01-2.3) and non-compliance with overall treatment (clinical decisions for treatment + therapeutic procedures) was associated with the presence of positive lymph nodes (OR 2.0; 95%CI: 1.2-3.3), grade III versus grade I (OR 2.9; 95%CI: 1.4-6.2), and one region of care versus another (OR 3.5; 95%CI: 1.7-7.1). Finally, heterogeneity of compliance in overall treatment sequence was identified between local cancer units (p < 0.05). Conclusion This study provides interesting insights into factors of non-compliance in non-metastatic BC management and could lead to quality care improvements.
Published: 2011

17. Pseudomonas aeruginosa acquisition on an intensive care unit: relationship between antibiotic selective pressure and patients' environment

Author: Van Tran, Frédéric Vargas, Adélaïde Doussau, Hélène Boulestreau, Alexandre Boyer, Anne Gaëlle Venier, Rodolphe Thiébault, Gilles Hilbert, Cécile Bébéar, Didier Gruson, Anne Marie Rogues, Service de Réanimation Médicale, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Pharmacoepidemiologie et évaluation de l'impact des produits de santé sur les populations, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Bordeaux Segalen - Bordeaux 2-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), Centre d'Investigation Clinique - Epidemiologie Clinique / Essais Cliniques Bordeaux, Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Santé Publique, d'Epidémiologie et de Développement (ISPED), Université Bordeaux Segalen - Bordeaux 2, Epidémiologie et Biostatistique [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Hygiène Hospitalière, Service de Bactériologie, BMC, Ed., Université Bordeaux Segalen - Bordeaux 2-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Université Bordeaux Segalen - Bordeaux 2
Subjects: Adult, Male, medicine.medical_specialty, medicine.drug_class, Antibiotics, Urine, Critical Care and Intensive Care Medicine, medicine.disease_cause, law.invention, 03 medical and health sciences, 0302 clinical medicine, law, Internal medicine, Throat, medicine, Humans, Pseudomonas Infections, 030212 general & internal medicine, Prospective Studies, Prospective cohort study, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, Aged, 0303 health sciences, Cross Infection, 030306 microbiology, business.industry, Pseudomonas aeruginosa, Research, Odds ratio, Middle Aged, Intensive care unit, 3. Good health, Surgery, Anti-Bacterial Agents, Intensive Care Units, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, medicine.anatomical_structure, Sputum, Female, medicine.symptom, business, Water Microbiology
Abstract: Introduction The purpose of this study was to investigate the relationship among Pseudomonas aeruginosa acquisition on the intensive care unit (ICU), environmental contamination and antibiotic selective pressure against P. aeruginosa. Methods An open, prospective cohort study was carried out in a 16-bed medical ICU where P. aeruginosa was endemic. Over a six-month period, all patients without P. aeruginosa on admission and with a length of stay >72 h were included. Throat, nasal, rectal, sputum and urine samples were taken on admission and at weekly intervals and screened for P. aeruginosa. All antibiotic treatments were recorded daily. Environmental analysis included weekly tap water specimen culture and the presence of other patients colonized with P. aeruginosa. Results A total of 126 patients were included, comprising 1,345 patient-days. Antibiotics were given to 106 patients (antibiotic selective pressure for P. aeruginosa in 39). P. aeruginosa was acquired by 20 patients (16%) and was isolated from 164/536 environmental samples (31%). Two conditions were independently associated with P. aeruginosa acquisition by multivariate analysis: (i) patients receiving ≥3 days of antibiotic selective pressure together with at least one colonized patient on the same ward on the previous day (odds ratio (OR) = 10.3 ((% confidence interval (CI): 1.8 to 57.4); P = 0.01); and (ii) presence of an invasive device (OR = 7.7 (95% CI: 2.3 to 25.7); P = 0.001). Conclusions Specific interaction between both patient colonization pressure and selective antibiotic pressure is the most relevant factor for P. aeruginosa acquisition on an ICU. This suggests that combined efforts are needed against both factors to decrease colonization with P. aeruginosa.
Published: 2010

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17 results on '"Centre d'Investigation Clinique - Epidemiologie Clinique / Essais Cliniques Bordeaux"'

1. Effectiveness and safety of dupilumab for the treatment of severe asthma in a real‐life French multi‐centre adult cohort

2. A subset of epithelioid and spindle cell rhabdomyosarcomas is associated with TFCP2 fusions and common ALK upregulation

3. Pazopanib or methotrexate–vinblastine combination chemotherapy in adult patients with progressive desmoid tumours (DESMOPAZ): a non-comparative, randomised, open-label, multicentre, phase 2 study

4. Randomized clinical trial of sacral nerve stimulation for refractory constipation

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6. Effect of Zr content on friction and wear behavior of Cr‐Zr‐N coating system

7. Guidelines for time-to-event end-point definitions in trials for pancreatic cancer. Results of the DATECAN initiative (Definition for the Assessment of Time-to-event End-points in CANcer trials)

8. Effects of Maternal Supplementation With Omega-3 Precursors on Human Milk Composition

9. Group and individual cognitive therapies in Alzheimer's disease: the ETNA3 randomized trial

10. One-Year Mortality in Older Patients with Cancer: Development and External Validation of an MNA-Based Prognostic Score

11. A new approach to integrate toxicity grade and repeated treatment cycles in the analysis and reporting of phase I dose-finding trials

12. Dose-finding design using mixed-effect proportional odds model for longitudinal graded toxicity data in phase I oncology clinical trials

13. Shared random-effect models for the joint analysis of longitudinal and time-to-event data: application to the prediction of prostate cancer recurrence

14. Phase III randomized equivalence trial of early breast cancer treatments with or without axillary clearance in post-menopausal patients Results after 5 years of follow-up

15. High-dose chemotherapy consolidation for chemosensitive advanced soft tissue sarcoma patients: an open-label, randomized controlled trial

16. Breast cancer care compared with clinical Guidelines: an observational study in France

17. Pseudomonas aeruginosa acquisition on an intensive care unit: relationship between antibiotic selective pressure and patients' environment

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