Author: "Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology ( MCMCC )" - Searchworks@Jio Institute Digital Library Search Results

Your search keyword '"Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology ( MCMCC )"' showing total 32 results

Start Over Author "Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology ( MCMCC )"

32 results on '"Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology ( MCMCC )"'

1. Management of acute mesenteric ischaemia: Results of a worldwide survey

Author: Benjamin Hess, Martin Cahenzli, Alastair Forbes, Rosa Burgos, Federico Coccolini, Olivier Corcos, Mette Holst, Øivind Irtun, Stanislaw Klek, Loris Pironi, Henrik Højgaard Rasmussen, Mireille J. Serlie, Ronan Thibault, Simon Gabe, Annika Reintam Blaser, Emrah Akin, Syed Muhammad Ali, Giulio Argenio, Semra Demirli Atici, Goran Augustin, Efstratia Baili, Lovenish Bains, Miklosh Bala, Edoardo Baldini, Oussama Baraket, Mirko Barone, Alan Biloslavo, null Roberto Bini, Cristina Bombardini, Giuseppe Brisinda, Luis Buonomo, Fausto Catena, Marco Ceresoli, Maria Michela Chiarello, Christos Chouliaras, Fabrizio D'Acapito, Dimitrios Damaskos, Belinda De Simone, Daniele Delogu, Zaza Demetrashvili, Isidoro Di Carlo, Mario D'Oria, Virginia María Durán-Muñoz-Cruzado, Patrice Forget, Laura Fortuna, Pietro Fransvea, Christian Frey, Olga Gapejeva, Pierre Garcon, Jörn-Markus Gass, Ricardo Alessandro Teixeira Gonsaga, Ewen Griffiths, Kursat Gundogan, Mohan Gurjar, Hytham K.S. Hamid, Juan Ignacio Silesky Jiménez, Karri Kase, Syed Sajid Hussain Kazmi, Aristotelis Kechagias, Vladimir Khokha, Yoshiro Kobe, Dimitrios P. Korkolis, Andrey Litvin, Eftychios Lostoridis, Hans Alexander Mahendran, Fabio Marino, Andres Martinuzzi, Cristian Mesina, Vincenzo Neri, Marina Panisic, Ciro Paolillo, Nikolaos Pararas, Gennaro Perrone, Antonio Pesce, Biagio Picardi, Charlotte Pither, Mauro Podda, Tomas Poskus, Florian Poullenot, Matras Przemyslaw, Massimo Sartelli, Diego Sasia, Maximilian Scheiterle, Fotios Seretis, Kjetil Søreide, Ruslan Sydorchuk, Kinga Szczepanek, Zsolt Bodnar, Fabienne Tamion, Antonio Tarasconi, Martin Teraa, Matti Tolonen, Tim Vanuytsel, Massimiliano Veroux, Lars Vinter-Jensen, Diego Visconti, Lukas Widmer, Andee Dzulkarnaen Zakaria, Nadezhda Zubareva, null Endorsing International Societies, null ESICM (European Society of Intensive Care Medicine), null WSES (World Society of Emergency Surgery), null WSACS (The Abdominal Compartment Society), null In-principle support, null WFICC (World Federation of Intensive and Critical Care), Endocrinology, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Lucerne Cantonal Hospital [Luzern, Switzerland], University of Tartu, Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Aalborg University [Denmark] (AAU), Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology (MCMCC), Alma Mater Studiorum Università di Bologna [Bologna] (UNIBO), Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), Universiteit van Amsterdam (UvA), Nutrition, Métabolismes et Cancer (NuMeCan), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), None, Hess, B, Cahenzli, M, Forbes, A, Burgos, R, Coccolini, F, Corcos, O, Holst, M, Irtun, Ø, Klek, S, Pironi, L, Rasmussen, H, Serlie, M, Thibault, R, Gabe, S, Reintam Blaser, A, Akin, E, Ali, S, Argenio, G, Atici, S, Augustin, G, Baili, E, Bains, L, Bala, M, Baldini, E, Baraket, O, Barone, M, Biloslavo, A, Roberto, B, Bombardini, C, Brisinda, G, Buonomo, L, Catena, F, Ceresoli, M, Chiarello, M, Chouliaras, C, D'Acapito, F, Damaskos, D, De Simone, B, Delogu, D, Demetrashvili, Z, Di Carlo, I, D'Oria, M, Durán-Muñoz-Cruzado, V, Forget, P, Fortuna, L, Fransvea, P, Frey, C, Gapejeva, O, Garcon, P, Gass, J, Teixeira Gonsaga, R, Griffiths, E, Gundogan, K, Gurjar, M, Hamid, H, Silesky Jiménez, J, Kase, K, Hussain Kazmi, S, Kechagias, A, Khokha, V, Kobe, Y, Korkolis, D, Litvin, A, Lostoridis, E, Mahendran, H, Marino, F, Martinuzzi, A, Mesina, C, Neri, V, Panisic, M, Paolillo, C, Pararas, N, Perrone, G, Pesce, A, Picardi, B, Pither, C, Podda, M, Poskus, T, Poullenot, F, Przemyslaw, M, Sartelli, M, Sasia, D, Scheiterle, M, Seretis, F, Søreide, K, Sydorchuk, R, Szczepanek, K, Bodnar, Z, Tamion, F, Tarasconi, A, Teraa, M, Tolonen, M, Vanuytsel, T, Veroux, M, Vinter-Jensen, L, Visconti, D, Widmer, L, Zakaria, A, Zubareva, N, Endorsing International, S, Institut Català de la Salut, [Hess B, Cahenzli M] Department of Intensive Care Medicine, Lucerne Cantonal Hospital, Lucerne, Switzerland. [Forbes A] Department of Anaesthesiology and Intensive Care, University of Tartu, Tartu, Estonia. [Burgos R] Unitat de Suport Nutricional, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Coccolini F] General, Emergency and Trauma Surgery Department, Pisa University Hospital, Pisa, Italy. [Corcos O] Intestinal Vascular Emergencies Structure (SURVI), Beaujon Hospital/Assistance Publique, Hopitaux de Paris, France, and Vall d'Hebron Barcelona Hospital Campus
Subjects: Investigative Techniques::Epidemiologic Methods::Data Collection::Surveys and Questionnaires [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], Occlusive intestinal ischaemia, Nutrition and Dietetics, Acute mesenteric ischaemia, [SDV]Life Sciences [q-bio], Endocrinology, Diabetes and Metabolism, NOMI (Non-occlusive mesentericandnbsp, enfermedades del sistema digestivo::enfermedades gastrointestinales::enfermedades intestinales::isquemia mesentérica [ENFERMEDADES], Otros calificadores::/diagnóstico [Otros calificadores], Isquèmia intestinal - Tractament, 610 Medicine & health, técnicas de investigación::métodos epidemiológicos::recopilación de datos::encuestas y cuestionarios [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Acute mesenteric infarction, Intestinal failure, Enquestes, Treatment, Isquèmia intestinal - Diagnòstic, Other subheadings::/diagnosis [Other subheadings], NOMI (Non-occlusive mesenteric ischaemia), Survey, Digestive System Diseases::Gastrointestinal Diseases::Intestinal Diseases::Mesenteric Ischemia [DISEASES], ischaemia)
Abstract: Background: Acute mesenteric ischaemia (AMI) is a condition with high mortality. This survey assesses current attitudes and practices to manage AMI worldwide.Methods: A questionnaire survey about the practices of diagnosing and managing AMI, endorsed by several specialist societies, was sent to different medical specialists and hospitals worldwide. Data from individual health care professionals and from medical teams were collected.Results: We collected 493 individual forms from 71 countries and 94 team forms from 34 countries. Almost half of respondents were surgeons, and most of the responding teams (70%) were led by surgeons. Most of the respondents indicated that diagnosis of AMI is often delayed but rarely missed. Emergency revascularisation is often considered for patients with AMI but rarely in cases of transmural ischaemia (intestinal infarction). Responses from team hospitals with a dedicated special unit (14 team forms) indicated more aggressive revascularisation. Abdominopelvic CT-scan with intravenous contrast was suggested as the most useful diagnostic test, indicated by approximately 90% of respondents. Medical history and risk factors were thought to be more important in diagnosis of AMI without transmural ischaemia, whereas for intestinal infarction, plasma lactate concentrations and surgical exploration were considered more useful. In elderly patients, a palliative approach is often chosen over extensive bowel resection. There was a large variability in anticoagulant treatment, as well as in timing of surgery to restore bowel continuity.Conclusions: Delayed diagnosis of AMI is common despite wide availability of an adequate imaging modality, i.e. CT-scan. Large variability in treatment approaches exists, indicating the need for updated guidelines. Increased awareness and knowledge of AMI may improve current practice until more robust evidence becomes available. Adherence to the existing guidelines may help in improving differences in treatment and outcomes. Background: Acute mesenteric ischaemia (AMI) is a condition with high mortality. This survey assesses current attitudes and practices to manage AMI worldwide.Methods: A questionnaire survey about the practices of diagnosing and managing AMI, endorsed by several specialist societies, was sent to different medical specialists and hospitals worldwide. Data from individual health care professionals and from medical teams were collected.Results: We collected 493 individual forms from 71 countries and 94 team forms from 34 countries. Almost half of respondents were surgeons, and most of the responding teams (70%) were led by surgeons. Most of the respondents indicated that diagnosis of AMI is often delayed but rarely missed. Emergency revascularisation is often considered for patients with AMI but rarely in cases of transmural ischaemia (intestinal infarction). Responses from team hospitals with a dedicated special unit (14 team forms) indicated more aggressive revascularisation. Abdominopelvic CT-scan with intravenous contrast was suggested as the most useful diagnostic test, indicated by approximately 90% of respondents. Medical history and risk factors were thought to be more important in diagnosis of AMI without transmural ischaemia, whereas for intestinal infarction, plasma lactate concentrations and surgical exploration were considered more useful. In elderly patients, a palliative approach is often chosen over extensive bowel resection. There was a large variability in anticoagulant treatment, as well as in timing of surgery to restore bowel continuity.Conclusions: Delayed diagnosis of AMI is common despite wide availability of an adequate imaging modality, i.e. CT-scan. Large variability in treatment approaches exists, indicating the need for updated guidelines. Increased awareness and knowledge of AMI may improve current practice until more robust evidence becomes available. Adherence to the existing guidelines may help in improving differences in treatment and outcomes.
Published: 2023
Full Text: View/download PDF

2. Best practices for the management of local-regional recurrent chordoma: a position paper by the chordoma global consensus group

Author: Vittoria Colia, Bernd Kasper, R. Imai, Michael Baumann, Stéphanie Bolle, R. Capanna, Riccardo Casadei, Paolo G. Casali, Claire Alapetite, P. A. Gardner, C. L. A. Vleggeert-Lankamp, C. Heery, Elena Tamborini, Anant Desai, Stefano Radaelli, Alessandro Gronchi, Nadia Hindi, Akira Kawai, Daniel Vanel, C. Sen, Francesco Doglietto, Nicolas Penel, Ziya L. Gokaslan, S. Froelich, Katherine Anne Thornton, Carlo Morosi, Hans Gelderblom, Francis J. Hornicek, O. J. Norum, M. Uhl, Palma Dileo, Sandip Pravin Patel, Piero Fossati, J. Martin Broto, Peter Hohenberger, Rick L. Haas, Andreas Leithner, Toru Akiyama, F. Ricchini, Robin L. Jones, Valter Torri, Josh Sommer, Peter Pal Varga, Y. Yamada, Per-Ulf Tunn, J.-Y. Blay, Augusto Caraceni, Piotr Rutkowski, Jürgen Debus, Lee Jeys, Adrienne M. Flanagan, Diego Mazzatenta, I. Logowska, Marco Krengli, Damien C. Weber, Thomas F. DeLaney, Susanne Scheipl, P. Picci, Beate Timmermann, Piero Nicolai, S. Pilotti, P. Bruzzi, Silvia Stacchiotti, Stefano Boriani, S. Dijkstra, Fondazione IRCCS Istituto Nazionale Tumori - National Cancer Institute [Milan], European Institute of Oncology [Milan] (ESMO), Saitama University, Institut Curie [Paris], University of Dresden Medical School, Centre Léon Bérard [Lyon], Institut Gustave Roussy (IGR), University of Pisa - Università di Pisa, University Medical Center Heidelberg, Massachusetts General Hospital [Boston], Queen Elizabeth Hospital, University College London Hospitals (UCLH), Universiteit Leiden [Leiden], University of Brescia, Cancer Research UK London Research Institute, Hôpital Lariboisière, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), University of Pittsburgh School of Medicine, Pennsylvania Commonwealth System of Higher Education (PCSHE), Providence University, Netherlands Cancer Institute (NKI), Antoni van Leeuwenhoek Hospital, National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH), Hospital Universitario Virgen del Rocío [Sevilla], University of Heidelberg, Medical Faculty, Harvard Medical School [Boston] (HMS), Chiba University Hospital, Queens Elizabeth Hospital [Birmingham], Royal Marsden NHS Foundation Trust, National Cancer Center Research Institute [Tokyo], Università del Piemonte Orientale - Dipartimento DISIT Italy, Medical University Graz, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology (MCMCC), MD Anderson Cancer Center [Houston], The University of Texas Health Science Center at Houston (UTHealth), Evaluation des technologies de santé et des pratiques médicales - ULR 2694 (METRICS), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), University Hospital Graz, New York University Langone Medical Center (NYU Langone Medical Center), NYU System (NYU), University of Duisbourg-Essen, Helios Klinikum [Erfurt], Memorial Sloane Kettering Cancer Center [New York], SwissFEL, Paul Scherrer Institut, Leiden University Medical Center (LUMC), Universiteit Leiden, CHU Lille, Université de Lille, METRICS : Evaluation des technologies de santé et des pratiques médicales - ULR 2694, European Institute of Oncology [Milan] [ESMO], Institut Gustave Roussy [IGR], University College London Hospitals [UCLH], Netherlands Cancer Institute [NKI], National Cancer Institute [Bethesda] [NCI-NIH], Harvard Medical School [Boston] [HMS], Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology [MCMCC], Evaluation des technologies de santé et des pratiques médicales - ULR 2694 [METRICS], New York University Langone Medical Center [NYU Langone Medical Center], Leiden University Medical Center [LUMC], Stacchiotti, S., Gronchi, A., Fossati, P., Akiyama, T., Alapetite, C., Baumann, M., Blay, J. Y., Bolle, S., Boriani, S., Bruzzi, P., Capanna, R., Caraceni, A., Casadei, R., Colia, V., Debus, J., Delaney, T., Desai, A., Dileo, P., Dijkstra, S., Doglietto, F., Flanagan, A., Froelich, S., Gardner, P. A., Gelderblom, H., Gokaslan, Z. L., Haas, R., Heery, C., Hindi, N., Hohenberger, P., Hornicek, F., Imai, R., Jeys, L., Jones, R. L., Kasper, B., Kawai, A., Krengli, M., Leithner, A., Logowska, I., Martin Broto, J., Mazzatenta, D., Morosi, C., Nicolai, P., Norum, O. J., Patel, S., Penel, N., Picci, P., Pilotti, S., Radaelli, S., Ricchini, F., Rutkowski, P., Scheipl, S., Sen, C., Tamborini, E., Thornton, K. A., B., Timmermann, Torri, V., Tunn, P. U., Uhl, M., Yamada, Y., Weber, D. C., Vanel, D., Varga, P. P., Vleggeert-Lankamp, C. L. A., Casali, P. G., and Sommer, J.
Subjects: sarcoma, [SDV]Life Sciences [q-bio], Medizin, chemotherapy, Patient advocacy, surgery, 0302 clinical medicine, Neoplasm Recurrence, Medicine, chordoma, relapse, radiotherapy, Relapse, Sarcoma, Hematology, 3. Good health, Oncology, 030220 oncology & carcinogenesis, Practice Guidelines as Topic, chordoma, consensus, recurrence, Sacral Chordoma, musculoskeletal diseases, medicine.medical_specialty, recurrence, Best practice, MEDLINE, Reviews, 610 Medicine & health, 03 medical and health sciences, Chordoma, Humans, Chemotherapy, Medical physics, Radiotherapy, business.industry, medicine.disease, Cervical spine, consensus, Family medicine, Position paper, Surgery, Neoplasm Recurrence, Local, business, 030217 neurology & neurosurgery
Abstract: Chordomas are rare, malignant bone tumors of the skull-base and axial skeleton. Until recently, there was no consensus among experts regarding appropriate clinical management of chordoma, resulting in inconsistent care and suboptimal outcomes for many patients. To address this shortcoming, the European Society of Medical Oncology (ESMO) and the Chordoma Foundation, the global chordoma patient advocacy group, convened a multi-disciplinary group of chordoma specialists to define by consensus evidence-based best practices for the optimal approach to chordoma. In January 2015, the first recommendations of this group were published, covering the management of primary and metastatic chordomas. Additional evidence and further discussion were needed to develop recommendations about the management of local-regional failures. Thus, ESMO and CF convened a second consensus group meeting in November 2015 to address the treatment of locally relapsed chordoma. This meeting involved over 60 specialists from Europe, the United States and Japan with expertise in treatment of patients with chordoma. The consensus achieved during that meeting is the subject of the present publication and complements the recommendations of the first position paper.
Published: 2017
Full Text: View/download PDF

3. Occupational Exposure to Polycyclic Aromatic Hydrocarbons and Lung Cancer Risk: Results from a Pooled Analysis of Case–Control Studies (SYNERGY)

Author: Olsson, Ann, Guha, Neela, Bouaoun, Liacine, Kromhout, Hans, Peters, Susan, Siemiatycki, Jack, Ho, Vikki, Gustavsson, Per, Boffetta, Paolo, Vermeulen, Roel, Behrens, Thomas, Bruning, Thomas, Kendzia, Benjamin, Guénel, Pascal, Luce, Danièle, Karrasch, Stefan, Wichmann, Heinz-Erich, Consonni, Dario, Landi, Maria Teresa, Caporaso, Neil E, Merletti, Franco, Mirabelli, Dario, Richiardi, Lorenzo, Jöckel, Karl-Heinz, Ahrens, Wolfgang, Pohlabeln, Hermann, Tardon, Adonina, Zaridze, David, Field, John K, Lissowska, Jolanta, Świątkowska, Beata, McLaughlin, John R, Demers, Paul A, Bencko, Vladimir, Foretova, Lenka, Janout, Vladimir, Pandics, Tamas, Fabianova, Eleonora, Mates, Dana, Forastiere, Francesco, Bueno-de-Mesquita, Bas, Schüz, Joachim, Straif, Kurt, IRAS OH Epidemiology Chemical Agents, dIRAS RA-2, IRAS OH Epidemiology Chemical Agents, dIRAS RA-2, Centre International de Recherche contre le Cancer - International Agency for Research on Cancer (CIRC - IARC), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Utrecht University [Utrecht], Université de Montréal (UdeM), Karolinska Institutet [Stockholm], University of Bologna/Università di Bologna, Stony Brook University [SUNY] (SBU), State University of New York (SUNY), Institute for Prevention and Occupational Medicine of the German Social Accident Insurance (IPA), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-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 ), École des Hautes Études en Santé Publique [EHESP] (EHESP), Ludwig Maximilian University [Munich] (LMU), Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH), Department of Medical Sciences [Turin, Italy] (DMS), Università degli studi di Torino = University of Turin (UNITO), Universitätsklinikum Essen [Universität Duisburg-Essen] (Uniklinik Essen), Universität Bremen, Leibniz Institute for Prevention Research and Epidemiology - BIPS, Leibniz Association, University of Oviedo, N.N. Blokhin National Medical Research Center of Oncology, University of Liverpool, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology (MCMCC), Nofer Institute of Occupational Medicine (NIOM), University of Toronto, Occupational Cancer Research Centre, First Faculty of Medicine, Charles University [Prague] (CU), Masaryk Memorial Cancer Institute (MMCI), Faculty of Health Sciences [UEF, Kuopio, Finland], University of Eastern Finland, National Public Health Center, National Institute of Public Health [Romania] (INSP), Azienda Sanitaria Locale [ROMA] (ASL), National Institute for Public Health and the Environment [Bilthoven] (RIVM), Instituto de Salud Global - Institute For Global Health [Barcelona] (ISGlobal), Boston College (BC), and Chard-Hutchinson, Xavier
Subjects: Male, Lung Neoplasms, Epidemiology, Medizin, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, [SDV.CAN] Life Sciences [q-bio]/Cancer, Oncology, polycyclic aromatic hydrocarbons, benzo[a]pyrene, lung cancer, occupational exposures, case-control study, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Case-Control Studies, Occupational Exposure, Carcinogens, Humans, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Polycyclic Aromatic Hydrocarbons, Lung
Abstract: German Social Accident Insurance (DGUV) between 2007 and 2011, Olsson A, Guha N, Bouaoun L, Kromhout H, Peters S, Siemiatycki J, Ho V, Gustavsson P, Boffetta P, Vermeulen R, Behrens T, Brüning T, Kendzia B, Guénel P, Luce D, Karrasch S, Wichmann HE, Consonni D, Landi MT, Caporaso NE, Merletti F, Mirabelli D, Richiardi L, Jöckel KH, Ahrens W, Pohlabeln H, Tardón A, Zaridze D, Field JK, Lissowska J, Świątkowska B, McLaughlin JR, Demers PA, Bencko V, Foretova L, Janout V, Pándics T, Fabianova E, Mates D, Forastiere F, Bueno-de-Mesquita B, Schüz J, Straif K
Published: 2022
Full Text: View/download PDF

4. Pharmacokinetics of oral vinorelbine in French children with recurrent or progressive primary low‐grade glioma

Author: Alicia Probst, Emilie De Carli, Isabelle Aerts, Pascal Chastagner, Natacha Entz-Werle, Caroline Solas, Anne-Isabelle Bertozzi-Salamon, Nicolas André, Anne Pagnier, Emmanuelle Tresch-Bruneel, Pierre Leblond, Jacques Grill, Didier Frappaz, Mourad Hamimed, Florence Gattacceca, Méthodes computationnelles pour la prise en charge thérapeutique en oncologie : Optimisation des stratégies par modélisation mécaniste et statistique (COMPO), Inria Sophia Antipolis - Méditerranée (CRISAM), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Simulation and Modeling of Adaptive Response for Therapeutics in Cancer (SMARTc), Centre de Recherche en Cancérologie de Marseille (CRCM), Pédiatrie et oncologie pédiatrique [Hôpital de la Timone - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER, Centre Hospitalier Universitaire de Nancy (CHU Nancy), Centre Hospitalier Universitaire [Grenoble] (CHU), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Laboratoire de Bioimagerie et Pathologies (LBP), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), CHU Strasbourg, Vectorologie et thérapeutiques anti-cancéreuses [Villejuif] (UMR 8203), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Centre National de la Recherche Scientifique (CNRS), Département de cancérologie de l'enfant et de l'adolescent [Gustave Roussy], Institut Gustave Roussy (IGR), Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology (MCMCC), Centre Léon Bérard [Lyon], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Unité des Virus émergents [Marseille] (UVE - Faculté de Médecine), Université de la Méditerranée - Aix-Marseille 2-Faculté de Médecine [Marseille], Université de la Méditerranée - Aix-Marseille 2, and Hôpital de la Timone [CHU - APHM] (TIMONE)
Subjects: medicine.medical_specialty, Adolescent, Phases of clinical research, Vinorelbine, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Pharmacokinetics, Bayesian multivariate linear regression, Glioma, Internal medicine, Humans, Medicine, Pharmacology (medical), Child, Infusions, Intravenous, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Pharmacology, Body surface area, Volume of distribution, 0303 health sciences, business.industry, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, medicine.disease, 3. Good health, 030220 oncology & carcinogenesis, Low-Grade Glioma, Neoplasm Recurrence, Local, business, Half-Life, medicine.drug
Abstract: AIM There is a crucial need for pharmacokinetic (PK) data of oral vinorelbine (VNR) in pediatric population. The aim of this work was to assess the PK profile of orally administered VNR in children with recurrent/progressive primary low-grade glioma (LGG). METHODS A multicentric, open-label, single-arm intervention phase II study was conducted. Patients, aged between 6 and 18 years, with histologically confirmed recurrent or progressive primary LGG or non-documented typical optic pathway tumors, were included. PK parameters were estimated by non-compartmental analysis using Phoenix WinNonlin® software (version 8.0, Certara, Inc.). The Influence of demographic and biological covariates on VNR PK parameters was investigated using a multivariate linear regression analysis. RESULTS PK analysis included 36 patients with a median age (range) of 11 (6-17) years. Estimates of apparent oral clearance (CL/F), apparent volume of distribution (V/F), half-life (t1/2 ) and their between-subject variability (CV%) at 60 mg.m-2 dose level, were 472 L.h-1 (51.8%), 7002 L (57.9%) and 10 h (21.0%), respectively. Negligible accumulation of VNR between C1 and C2 was observed. CL/F and V/F were found to increase with body surface area (BSA) (p = 0.004). Lower area under the concentration-time curve (AUC) levels were observed among children in comparison to adults. CONCLUSION Higher doses may be necessary for children with LGG. BSA showed a significant impact on VNR systemic exposure. We believe that our findings will serve as a basis for further studies to better characterize the concentration-response relationships of VNR among pediatric patients.
Published: 2021
Full Text: View/download PDF

5. A polygenic risk score for multiple myeloma risk prediction

Author: Angelica Macauda, Matteo Pelosini, Krzysztof Jamroziak, Mario Petrini, Annette Juul Vangsted, Chiara Piredda, Stephane Minvielle, Marek Dudziński, Hervé Avet-Loiseau, Aleksandra Butrym, Ulla Vogel, Niels Abildgaard, Fabienne Lesueur, Waldemar Tomczak, Vibeke Andersen, Herlander Marques, Daniele Campa, Judit Várkonyi, Rui Manuel Reis, Katalin Kadar, Gabriele Buda, Małgorzata Raźny, Charles Dumontet, Juan Sainz, Anna Suska, Enrico Orciuolo, Agnieszka Druzd-Sitek, Marcin Kruszewski, Daria Zawirska, Niels Frost Andersen, Artur Jurczyszyn, Grzegorz Mazur, Marcin Rymko, Federica Gemignani, Edyta Subocz, Federico Canzian, Katia Beider, Jan Maciej Zaucha, Marzena Wątek, Arnon Nagler, Genomic Epidemiology Group [Heidelberg, Germany] (GEP / DKFZ), German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), University of Pisa - Università di Pisa, University Hospital of Cracow/Szpital Uniwersytecki w Krakowie [Poland] (SUK), Aarhus University Hospital, Chaim Sheba Medical Center, Sea Hospital [Gdynia, Poland] (SH), Wroclaw Medical University [Wrocław, Pologne] (WMU), Hospices Civils de Lyon (HCL), Holycross Cancer Center of Kelce, Hematology Clinic, Kielce, Institute of Hematology and Transfusion Medicine [Warsaw, Poland] (IHTM), Centre for Genomics and Oncological Research Pfizer [Granada, Spain] (GENYO), University of Granada [Granada]-Andalusian Regional Government [Granada, Spain], Hospital Universitario Virgen de las Nieves [Granada, Spain] (HUVN), Semmelweis University [Budapest], Odense University Hospital (OUH), 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), Teaching Hospital No 1 [Rzeszów, Poland] (TH1), University of Copenhagen = Københavns Universitet (KU), Military Institute of Medicine [Warsaw, Poland] (MIM), Rydygier Specialistic Hospital [Cracow, Poland] (RSH), University of Minho [Braga], Jagiellonian University Medical College [Cracow, Poland] (JUMC), Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology (MCMCC), The National Research Center for Work Environment [Copenhagen, Denmark] (NRCWE), University of Southern Denmark (SDU), ICVS/3B's - PT Government Associate Laboratory [Braga/Guimarães, Portugal] (AL), Barretos Cancer Hospital [São Paulo, Brazil] (BCH), 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), University Hospital Bydgoszcz [Bydgoszcz, Poland] (UHB), Medical University of Lublin, N. Copernicus Town Hospital [Torun, Poland] (NCTH), Integrative Oncogenomics of Multiple Myeloma Pathogenesis and Progression (CRCINA-ÉQUIPE 11), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Bernardo, Elizabeth, Wrocław Medical University, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Universidad de Granada = University of Granada (UGR)-Andalusian Regional Government [Granada, Spain], 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), University of Copenhagen = Københavns Universitet (UCPH), Uniwersytet Jagielloński w Krakowie = Jagiellonian University (UJ), 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), and Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)
Subjects: Oncology, medicine.medical_specialty, Population, [SDV.CAN]Life Sciences [q-bio]/Cancer, Single-nucleotide polymorphism, Genome-wide association study, Polymorphism, Single Nucleotide, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Risk Factors, Internal medicine, Genetics, medicine, Genetic predisposition, Humans, Genetic Predisposition to Disease, education, Genetics (clinical), Multiple myeloma, 030304 developmental biology, Genetic association, 0303 health sciences, education.field_of_study, business.industry, medicine.disease, Penetrance, 3. Good health, 030220 oncology & carcinogenesis, Polygenic risk score, Multiple Myeloma, business, Genome-Wide Association Study
Abstract: This work was partially supported by intramural funds of the University of Pisa, DKFZ, and University Hospital of Southern Jutland, Denmark, and by a grant of the French National Cancer Institute (INCA). The authors wish to thank Dr. Dominic Edelmann (Division of Biostatistics, DKFZ) for helpful advice about data analysis., There is overwhelming epidemiologic evidence that the risk of multiple myeloma (MM) has a solid genetic background. Genome-wide association studies (GWAS) have identified 23 risk loci that contribute to the genetic susceptibility of MM, but have low individual penetrance. Combining the SNPs in a polygenic risk score (PRS) is a possible approach to improve their usefulness. Using 2361 MM cases and 1415 controls from the International Multiple Myeloma rESEarch (IMMEnSE) consortium, we computed a weighted and an unweighted PRS. We observed associations with MM risk with OR = 3.44, 95% CI 2.53-4.69, p = 3.55 x 10(-15) for the highest vs. lowest quintile of the weighted score, and OR = 3.18, 95% CI 2.1 = 34-4.33, p = 1.62 x 10(-13) for the highest vs. lowest quintile of the unweighted score. We found a convincing association of a PRS generated with 23 SNPs and risk of MM. Our work provides additional validation of previously discovered MM risk variants and of their combination into a PRS, which is a first step towards the use of genetics for risk stratification in the general population., University of Pisa, DKFZ, University Hospital of Southern Jutland, Denmark, Institut National du Cancer (INCA) France
Published: 2021
Full Text: View/download PDF

6. The Transcription Factor Encyclopedia

Author: Yusuf, Dimas, Butland, Stefanie L., Swanson, Magdalena I., Bolotin, Eugene, Ticoll, Amy, Cheung, Warren A., Zhang, Xiao Yu Cindy, Dickman, Christopher T. D., Fulton, Debra L., Lim, Jonathan S., Schnabl, Jake M., Ramos, Oscar H. P., Vasseur-Cognet, Mireille, de Leeuw, Charles N., Simpson, Elizabeth M., Ryffel, Gerhart U., Lam, Eric W.-F., Kist, Ralf, Wilson, Miranda S. C., Marco-Ferreres, Raquel, Brosens, Jan J., Beccari, Leonardo L., Bovolenta, Paola, Benayoun, Bérénice A., Monteiro, Lara J, Schwenen, Helma D C, Grontved, Lars, Wederell, Elizabeth, Mandrup, Susanne, Veitia, Reiner A, Chakravarthy, Harini, Hoodless, Pamela A., Mancarelli, M Michela, Torbett, Bruce E, Banham, Alison H, Reddy, Sekhar P, Cullum, Rebecca L, Liedtke, Michaela, Tschan, Mario P, Vaz, Michelle, Rizzino, Angie, Zannini, Mariastella, Frietze, Seth, Farnham, Peggy J, Eijkelenboom, Astrid, Brown, Philip J, Laperrière, David, Leprince, Dominique, de Cristofaro, Tiziana, Prince, Kelly L, Putker, Marrit, del Peso, Luis, Camenisch, Gieri, Wenger, Roland H, Mikula, Michal, Rozendaal, Marieke, Mader, Sylvie, Ostrowski, Jerzy, Rhodes, Simon J, Van Rechem, Capucine, Boulay, Gaylor, Olechnowicz, Sam W Z, Breslin, Mary B, Lan, Michael S, Nanan, Kyster K, Wegner, Michael, Hou, Juan, Mullen, Rachel D, Colvin, Stephanie C, Noy, Peter John, Webb, Carol F, Witek, Matthew E, Ferrell, Scott, Daniel, Juliet M, Park, Jason, Waldman, Scott A, Peet, Daniel J, Taggart, Michael, Jayaraman, Padma-Sheela, Karrich, Julien J, Blom, Bianca, Vesuna, Farhad, O'Geen, Henriette, Sun, Yunfu, Gronostajski, Richard M, Woodcroft, Mark W, Hough, Margaret R, Chen, Edwin, Europe-Finner, G Nicholas, Karolczak-Bayatti, Magdalena, Bailey, Jarrod, Hankinson, Oliver, Raman, Venu, LeBrun, David P, Biswal, Shyam, Harvey, Christopher J, DeBruyne, Jason P, Hogenesch, John B, Hevner, Robert F, Héligon, Christophe, Luo, Xin M, Blank, Marissa Cathleen, Millen, Kathleen Joyce, Sharlin, David S, Forrest, Douglas, Dahlman-Wright, Karin, Zhao, Chunyan, Mishima, Yuriko, Sinha, Satrajit, Chakrabarti, Rumela, Portales-Casamar, Elodie, Sladek, Frances M, Bradley, Philip H, Wasserman, Wyeth W, Cindy Zhang, Xiao, Department of Medical Genetics, Faculty of Medicine-Child and Family Research Institute-Centre for Molecular Medicine and Therapeutics-University of British Columbia (UBC), Evaluation and Research Services, Fraser Health Authority, Children's Hospital Oakland, Oakland Research Institute, Computational Biology Program, Fred Hutchinson Cancer Research Center [Seattle] (FHCRC), Department of Bioinformatics, Child and Family Research Institute-Centre for Molecular Medicine and Therapeutics-University of British Columbia (UBC), Department of Biology, University of Western Ontario (UWO), Genetics Program, Department of Cell Biology and Neuroscience [Riverside] (CBNS), University of California [Riverside] (UC Riverside), University of California (UC)-University of California (UC), Service d'Ingénierie Moléculaire pour la Santé (ex SIMOPRO) (SIMoS), Médicaments et Technologies pour la Santé (MTS), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut für Zellbiologie, Universität Duisburg-Essen [Essen]-Universitätsklinikum Essen, Department of Surgery and Cancer, Imperial College London-Division of Cancer, Centre for Oral Health Research, Newcastle University [Newcastle]-Medical School-School of Dental Sciences, Department of Development and Differentiation, Centro de Biología Molecular Severo Ochoa [Madrid] (CBMSO), Universidad Autónoma de Madrid (UAM)-Consejo Superior de Investigaciones Científicas [Madrid] (CSIC)-Universidad Autónoma de Madrid (UAM)-Consejo Superior de Investigaciones Científicas [Madrid] (CSIC)-CIBER de Enfermedades Raras (CIBERER), Division of Reproductive Health, University of Warwick [Coventry]-Warwick Medical School, University of Warwick [Coventry], Neurobiologia Molecular Celular y del desarrollo, Institut Jacques Monod (IJM (UMR_7592)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Department of Biochemistry and Molecular Biology, University of Southern Denmark (SDU), Terry Fox Laboratory, BC Cancer Agency (BCCRC)-Provincial Health Services Authority, Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, University of Nebraska System-University of Nebraska System, Department of Molecular Experimental Medicine, The Scripps Research Institute [La Jolla, San Diego], Departments of Molecular and Experimental Medicine and Immunology and Microbial Sciences (MEM 131), Nuffield Department of Clinical Laboratory Sciences, University of Oxford- John Radcliffe Hospital [Oxford University Hospital]-Oxford NIHR Biomedical Research Centre, Department of Pediatrics, College of Medicine-Department of pediatrics-University of Illinois [Chicago] (UIC), University of Illinois System-University of Illinois System, Division of Hematology [Stanford], Stanford Medicine, Stanford University-Stanford University, Department of Medicine, University of Bern, Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine [Baltimore]-Johns Hopkins University School of Medicine [Baltimore]-Johns Hopkins University School of Medicine, Institute of Experimental Endocrinology and Oncology (IEOS), Consiglio Nazionale delle Ricerche (CNR), University of Southern California (USC)-Norris Comprehensive Cancer Center, Department of Molecular Cancer Research, University Medical Center [Utrecht]-Utrecht University [Utrecht], University of Oxford- John Radcliffe Hospital [Oxford University Hospital]-Medical Sciences Division, Molecular Targeting in Breast Cancer research unit, Institut de Recherche en Immunologie et en Cancérologie [UdeM-Montréal] (IRIC), Université de Montréal (UdeM)-Université de Montréal (UdeM), Institut de biologie de Lille - IBL (IBLI), Université de Lille, Sciences et Technologies-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique (CNRS), Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indiana University System-Indiana University System, Department of Physiological Chemistry, Department of Biochemistry, Universidad Autónoma de Madrid (UAM)-School of Medicine, Institute of Physiology, Universität Zürich [Zürich] = University of Zurich (UZH)-Zurich Center for Integrative Human Physiology, Department of Oncological Genetics, Institute of Oncology-Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology (MCMCC)-Medical Center of Postgraduate Education [Warsaw] (MCPE), Indiana University [Bloomington], Indiana University System-Indiana University System-School of Science, Harvard Medical School [Boston] (HMS)-Massachusetts General Hospital [Boston]-Cancer Center, University of Adelaide-School of Molecular and Biomedical Science, Department of Pediatrics and Biochemistry and Molecular Biology, Louisiana State University (LSU)-Research Institute for Children-Children's Hospital at New Orleans, Departments of Pediatrics and Genetics, Department of Pathology and Molecular Medicine, Queen's University [Kingston, Canada]-Queen's Cancer Research Institute, School of Medicine [Erlangen], Friedrich-Alexander Universität Erlangen-Nürnberg (FAU)-Institut fuer Biochemie-Emil-Fischer-Zentrum, Department of Molecular Biology and Biochemistry, University Indianapolis-Indiana University School of Medicine, Department of Immunity and Infection, School of Medical and Dental Sciences-University of Birmingham [Birmingham], Immunobiology and Cancer Program, Oklahoma Medical Research Foundation (OMRF), Radiation Oncology, Department of Pharmacology and Experimental Therapeutics-Jefferson University Hospitals, Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center (OUHSC), McMaster University [Hamilton, Ontario], School of Medicine, Johns Hopkins University (JHU), Department of Pharmacology and Experimental Therapeutics, Thomas Jefferson University-Jefferson Medical College, Discipline of Biochemistry, Institute of Cellular Medicine, Newcastle University [Newcastle]-Faculty of Medicine-Medical School, Department of Immunity and Immunology, Department of Cell Biology and Histology, Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA)-University of Amsterdam [Amsterdam] (UvA)-Center for Immunology Amsterdam, Division of Cancer Imaging Research, Johns Hopkins University (JHU)-School of Medicine-Department of Radiology, Genome Center [UC Davis], University of California [Davis] (UC Davis), School of Biological Sciences [Univ California San Diego] (UC San Diego), University of California [San Diego] (UC San Diego), Department of Biochemistry and Developmental Genomics Group, University at Buffalo [SUNY] (SUNY Buffalo), State University of New York (SUNY)-State University of New York (SUNY)-Center of Excellence in Bioinformatics and Life Sciences, Department of Molecular and Cellular Biology, University of Toronto-Sunnybrook Health Sciences Centre-Department of Laboratory Medicine and Pathobiology, Faculty of Medical Sciences, Newcastle University [Newcastle]-Medical School-Institute of Cellular Medicine, Department of Pathology and Laboratory Medicine, University of California [Los Angeles] (UCLA), University of California (UC)-University of California (UC)-David Geffen School of Medicine [Los Angeles], Radiology and Oncology, Johns Hopkins University (JHU)-School of Medicine, Department of Environmental Health Sciences, Johns Hopkins University (JHU)-Johns Hopkins Bloomberg School of Public Health [Baltimore], Department of Pharmacology and Toxicology, Neuroscience Institute-Morehouse School of Medicine, Department of Pharmacology, University of Pennsylvania-Perelman School of Medicine, University of Pennsylvania, Department of Neurological Surgery, University of Washington [Seattle]-Seattle Children's Research Institute, Faculty of Biology and Medicine, Université de Lausanne = University of Lausanne (UNIL)-Center for Integrated Genomics, Department of Biomedical Sciences and Pathobiology, Virginia Polytechnic Institute and State University [Blacksburg]-Virginia-Maryland College of Veterinary Medicine, Department of Molecular Genetics and Cell Biology, University of Illinois [Chicago] (UIC), Center for Integrative Brain Research, University of Washington [Seattle], Clinical Endocrinology Branch, National Institutes of Health (NIH)-National Institute of Diabetes, Digestive, and Kidney Disorders, Department of Biosciences and Nutrition, Karolinska Institutet [Stockholm], State University of New York (SUNY)-State University of New York (SUNY), BMC, Ed., Universität Duisburg-Essen = University of Duisburg-Essen [Essen]-Universitätsklinikum Essen, National Research Council of Italy | Consiglio Nazionale delle Ricerche (CNR), UAM. Departamento de Bioquímica, Faculty of Medicine-Child and Family Research Institute-Centre for Molecular Medicine and Therapeutics-University of British Columbia ( UBC ), Fred Hutchinson Cancer Research Center [Seattle] ( FHCRC ) -Public Health Sciences Division, Child and Family Research Institute-Centre for Molecular Medicine and Therapeutics-University of British Columbia ( UBC ), University of Western Ontario ( UWO ), Department of Cell Biology and Neuroscience [Riverside] ( CBNS ), University of California [Riverside] ( UCR ), Service d'Ingénierie Moléculaire des Protéines ( SIMOPRO ), Département Médicaments et Technologies pour la Santé ( DMTS ), Direction de Recherche Fondamentale (CEA) ( DRF (CEA) ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) ( DRF (CEA) ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay, Institut Cochin ( UM3 (UMR 8104 / U1016) ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), CIBER de Enfermedades Raras (CIBERER)-Consejo Superior de Investigaciones Científicas [Spain] ( CSIC ) -Centro de Biologia Molecular Severo Ochoa (CBMSO), Consejo Superior de Investigaciones Científicas [Spain] ( CSIC ) -Centro de Biologia Molecular Severo Ochoa (CBMSO)-CIBER de Enfermedades Raras (CIBERER), Service de Pathologies moléculaire et cellulaire, Institut Jacques Monod ( IJM ), Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS ), UNIVERSITY OF SOUTHERN DENMARK, BC Cancer Agency ( BCCRC ) -Provincial Health Services Authority, Scripps Research Institute, Departments of Molecular and Experimental Medicine and Immunology and Microbial Sciences ( MEM 131 ), University of Oxford [Oxford]- John Radcliffe Hospital [Oxford University Hospital]-Oxford NIHR Biomedical Research Centre, College of Medicine-Department of pediatrics-University of Illinois at Chicago ( UIC ), Department of Medicine/Hematology, Stanford University School of Medicine, Institute of Experimental Endocrinology and Oncology ( IEOS ), CNR - National Research Council, University of Southern California ( USC ) -Norris Comprehensive Cancer Center, Utrecht University [Utrecht]-University Medical Center Utrecht, University of Oxford [Oxford]- John Radcliffe Hospital [Oxford University Hospital]-Medical Sciences Division, Université de Montréal-Institute for Research in Immunology and Cancer, Institut de biologie de Lille - IBL ( IBLI ), Réseau International des Instituts Pasteur ( RIIP ) -Réseau International des Instituts Pasteur ( RIIP ) -Centre National de la Recherche Scientifique ( CNRS ) -Université de Lille, Droit et Santé, Utrecht University [Utrecht]-University Medical Centre Utrecht, Universidad Autonoma de Madrid ( UAM ) -School of Medicine, University of Zürich [Zürich] ( UZH ) -Zurich Center for Integrative Human Physiology, Institute of Oncology-Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology ( MCMCC ) -Medical Center of Postgraduate Education [Warsaw] ( MCPE ), Indiana University [Bloomington]-School of Science, Harvard Medical School [Boston] ( HMS ) -Cancer Center-Massachusetts General Hospital, Louisiana State University Health Sciences Center-Research Institute for Children-Children's Hospital at New Orleans, Queen's University [Kingston]-Queen's Cancer Research Institute, Institut fuer Biochemie-Emil-Fischer-Zentrum-Friedrich-Alexander Universitaet Erlangen-Nuernberg, Indiana University School of Medicine-University Indianapolis, Oklahoma Medical Research Foundation, Department of Pharmacology and Experimental Therapeutics-Jefferson University Hospital, University of Oklahoma Health Sciences Center ( OUHSC ), Johns Hopkins University ( JHU ), Academic Medical Center [Amsterdam] ( AMC ), University of Amsterdam [Amsterdam] ( UvA ) -University of Amsterdam [Amsterdam] ( UvA ) -Center for Immunology Amsterdam, Johns Hopkins University ( JHU ) -School of Medicine-Department of Radiology, University of California at Davis, Division of Biological Sciences [San Diego], University of California [San Diego] ( UC San Diego ), State University of New York at Buffalo ( SUNY Buffalo ) -Center of Excellence in Bioinformatics and Life Sciences, University of California at Los Angeles [Los Angeles] ( UCLA ) -David Geffen School of Medicine, Johns Hopkins University ( JHU ) -School of Medicine, Johns Hopkins University ( JHU ) -Johns Hopkins Bloomberg School of Public Health, University of Pennsylvania [Philadelphia]-Perelman School of Medicine, University of Lausanne-Center for Integrated Genomics, Virginia Polytechnic Institute and State University [Blacksburg]-VA-MD Regional College of Veterinary Medicine, University of Illinois at Chicago ( UIC ), State University of New York at Buffalo ( SUNY Buffalo ) -University of Buffalo School of Medicine and Biomedical Sciences, University of California [Riverside] (UCR), University of California-University of California, Universidad Autonoma de Madrid (UAM)-Consejo Superior de Investigaciones Científicas [Madrid] (CSIC)-Universidad Autonoma de Madrid (UAM)-Consejo Superior de Investigaciones Científicas [Madrid] (CSIC)-CIBER de Enfermedades Raras (CIBERER), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Johns Hopkins University School of Medicine-The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine [Baltimore]-Johns Hopkins University School of Medicine [Baltimore], Utrecht University [Utrecht]-University Medical Center [Utrecht], Universidad Autonoma de Madrid (UAM)-School of Medicine, Cancer Center-Harvard Medical School [Boston] (HMS)-Massachusetts General Hospital [Boston], Friedrich-Alexander Universität Erlangen-Nürnberg (FAU)-Emil-Fischer-Zentrum-Institut fuer Biochemie, School of Molecular and Biomedical Science-University of Adelaide, School of Medicine-Department of Radiology-Johns Hopkins University (JHU), University of California-University of California-David Geffen School of Medicine [Los Angeles], Johns Hopkins Bloomberg School of Public Health [Baltimore], Johns Hopkins University (JHU)-Johns Hopkins University (JHU), University of Pennsylvania [Philadelphia], Université de Lausanne (UNIL)-Center for Integrated Genomics, AII - Amsterdam institute for Infection and Immunity, and Cell Biology and Histology
Subjects: Encyclopedias as Topic, INFORMATION, WIKI, Transcription, Genetic, 05 Environmental Sciences, Medizin, [SDV.GEN] Life Sciences [q-bio]/Genetics, Automate Content, Web API, ANNOTATION, Mini review, Mice, 0302 clinical medicine, Portable Document Format, GENETICS & HEREDITY, Databases, Protein, Informática, 0303 health sciences, PROTEIN DATA-BANK, Application programming interface, BIOTECHNOLOGY & APPLIED MICROBIOLOGY, MENDELIAN-INHERITANCE, ddc:57, [ SDV.BBM.GTP ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], 030220 oncology & carcinogenesis, Application Programming Interface, Encyclopedia, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], The Internet, Transcription (software), Transcription, Life Sciences & Biomedicine, KNOWLEDGEBASE, Medicina, DATABASE, Bioinformatics, Biology, Medizinische Fakultät » Universitätsklinikum Essen » Institut für Zellbiologie (Tumorforschung), World Wide Web, Access to Information, 03 medical and health sciences, Databases, Genetic, Protein Data Bank, ddc:570, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], ddc:61, Animals, Humans, ddc:610, MeSH Term, Transcription factor, 030304 developmental biology, Internet, 08 Information And Computing Sciences, [SDV.GEN]Life Sciences [q-bio]/Genetics, Science & Technology, GENE-REGULATION, business.industry, Protein, Computational Biology, 06 Biological Sciences, Compendium, EVOLUTION, Rats, Evolutionary biology, UPDATE, business, [ SDV.GEN ] Life Sciences [q-bio]/Genetics, Software, Transcription Factors
Abstract: Here we present the Transcription Factor Encyclopedia (TFe), a new web-based compendium of mini review articles on transcription factors (TFs) that is founded on the principles of open access and collaboration. Our consortium of over 100 researchers has collectively contributed over 130 mini review articles on pertinent human, mouse and rat TFs. Notable features of the TFe website include a high-quality PDF generator and web API for programmatic data retrieval. TFe aims to rapidly educate scientists about the TFs they encounter through the delivery of succinct summaries written and vetted by experts in the field. TFe is available at http://www.cisreg.ca/tfe.
Published: 2012
Full Text: View/download PDF

7. Should anti-thymocyte globulin be added in post-transplant cyclophosphamide based matched unrelated donor peripheral blood stem cell transplantation for acute myeloid leukemia? A study on behalf of the Acute Leukemia Working Party of the EBMT

Author: Alexandros Spyridonidis, Myriam Labopin, Eolia Brissot, Ivan Moiseev, Jan Cornelissen, Goda Choi, Fabio Ciceri, Jan Vydra, Péter Reményi, Montserrat Rovira, Ellen Meijer, Hélène Labussière-Wallet, Didier Blaise, Gwendolyn van Gorkom, Nicolaus Kröger, Yener Koc, Sebastian Giebel, Ali Bazarbachi, Bipin Savani, Arnon Nagler, Mohamad Mohty, Hematology, Interne Geneeskunde, MUMC+: MA Hematologie (9), RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, General University Hospital of Patras, CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Erasmus University Medical Center [Rotterdam] (Erasmus MC), University of Groningen [Groningen], San Raffaele Scientific Institute, Vita-Salute San Raffaele University and Center for Translational Genomics and Bioinformatics, Hospital Clínic de Barcelona [Catalonia, Spain], VU University Medical Center [Amsterdam], Hospices Civils de Lyon (HCL), Service d’Hématologie [Institut Paoli Calmettes, Marseille], Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), University Hospital Hamburg-Eppendorf, Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), Medicana International [Istanbul, Turkey], Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology (MCMCC), American University of Beirut [Beyrouth] (AUB), Vanderbilt University Medical Center [Nashville], Vanderbilt University [Nashville], Chaim Sheba Medical Center, and CCA - Cancer Treatment and quality of life
Subjects: Transplantation, Peripheral Blood Stem Cell Transplantation, PHASE-3, IMPACT, [SDV]Life Sciences [q-bio], BONE-MARROW, MULTICENTER, Hematopoietic Stem Cell Transplantation, Graft vs Host Disease, Hematology, HEMATOLOGICAL MALIGNANCIES, OPEN-LABEL, PREVENTION, PROPHYLAXIS, Leukemia, Myeloid, Acute, Recurrence, VERSUS-HOST-DISEASE, Humans, DEPLETION, Unrelated Donors, Cyclophosphamide, Antilymphocyte Serum, Retrospective Studies
Abstract: Background: Post-transplant cyclophosphamide (PTCY) is increasingly used for allogeneic peripheral blood stem cell transplantation (allo-PBSCT) from an HLA-matched unrelated donor (MUD) as an alternative to the standard anti-thymocyte globulin (ATG) graft-versus-host disease (GvHD) prophylaxis. Following the demonstration that the use of PBSC haploidentical grafts results in more GvHD than bone marrow grafts, groups have attempted to reduce GvHD in haploidentical-PBSCT by adding ATG to PTCY. The experience of combined PTCY+ATG in the MUD allo-PBSCT is minimal and whether ATG brings any added value when PTCY is used in this setting is still unclear. Methods: In this registry-based study, we compared outcomes of 421 patients with PTCY and 151 patients with PTCY+ATG who underwent a first MUD allo-PBSCT for acute myeloid leukemia (AML) in complete remission. Results: Characteristics of PTCY and PTCY+ATG patients were well balanced, including the number of additional immunosuppressive drugs, with the only significant difference between the two cohorts being the median year of transplant, and the follow-up period (19.6 versus 31.1 months, respectively, pConclusions: To date, the question of the best combination of GvHD-preventing drugs in the MUD-PBSCT setting remains unanswered. Our results highlight that in PTCY-based MUD-PBSCT for AML, the addition of ATG does not provide any extra benefit in terms of further GvHD reduction, better GRFS or better survival.
Published: 2022
Full Text: View/download PDF

8. Post-transplant cyclophosphamide versus anti-thymocyte globulin for graft-versus-host disease prevention in haploidentical transplantation for adult acute lymphoblastic leukemia

Author: Mutlu Arat, Fabio Ciceri, Myriam Labopin, Arnon Nagler, Zinaida Peric, Yener Koc, Bipin N. Savani, Johanna Tischer, Emanuele Angelucci, Boris V. Afanasyev, Zafer Gulbas, Hakan Ozdogu, Mohamad Mohty, Pietro Pioltelli, Abraham S. Kanate, Depei Wu, William Arcese, Sebastian Giebel, Nagler, Arnon, Kanate, Abraham S, Labopin, Myriam, Ciceri, Fabio, Angelucci, Emanuele, Koc, Yener, Gülbas, Zafer, Arcese, William, Tischer, Johanna, Pioltelli, Pietro, Ozdogu, Hakan, Afanasyev, Bori, Wu, Depei, Arat, Mutlu, Peric, Zinaida, Giebel, Sebastian, Savani, Bipin, Mohty, Mohamad, Chaim Sheba Medical Center, West Virginia University [Morgantown], Centre International des greffes [CHU Saint-Antoine] (EBMT), 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), CEREST-TC [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Ospedale San Raffaele, Ospedale Policlinico San Martino [Genoa], Anadolu [Turkey], Università degli Studi di Roma Tor Vergata [Roma], Università degli Studi di Milano-Bicocca [Milano] (UNIMIB), Başkent University Hospital [Adana, Turkey], Pavlov First Saint Petersburg State Medical University [St. Petersburg], Soochow University, University of Zagreb, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology (MCMCC), Vanderbilt University Medical Center [Nashville], Vanderbilt University [Nashville], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Adult, medicine.medical_specialty, Transplantation Conditioning, Cyclophosphamide, [SDV]Life Sciences [q-bio], Graft vs Host Disease, Gastroenterology, Article, 03 medical and health sciences, 0302 clinical medicine, Refractory, immune system diseases, Internal medicine, medicine, Humans, Antilymphocyte Serum, business.industry, Incidence (epidemiology), Hematopoietic Stem Cell Transplantation, Hematology, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Settore MED/15, medicine.disease, 3. Good health, Anti-thymocyte globulin, Transplantation, Adult Acute Lymphoblastic Leukemia, surgical procedures, operative, medicine.anatomical_structure, Graft-versus-host disease, Graft-versus-Host-Disease, 030220 oncology & carcinogenesis, Transplantation, Haploidentical, Bone marrow, business, Stem Cell Transplantation, 030215 immunology, medicine.drug
Abstract: Graft-versus-host disease (GvHD) prophylaxis for unmanipulated haploidentical hematopoietic cell transplantation includes posttransplant cyclophosphamide (PTCy) and anti-thymocyte globulin (ATG). Utilizing data in the European Society for Blood and Marrow Transplantation registry, we compared ATG- versus PTCy-based GvHD prophylaxis in 434 adults with acute lymphoblastic leukemia undergoing haploidentical hematopoietic cell transplantation. Of the 434 patients included in this study, ATG was used in 98 and PTCy in 336.. The median follow-up was approximately 2 years. The baseline characteristics of the patients were similar between the groups except that the ATG group was more likely to have had relapsed/refractory acute lymphoblastic leukemia (P=0.008), had conditioning not including total body irradiation (P
Published: 2020
Full Text: View/download PDF

9. Encapsulation of granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor in liposomes prepared by thin film hydration and their transfer to mesenchymal stem cells and cord blood hematopoietic stem cells

Author: Jacek Z. Kubiak, Aneta Lewicka, Marek Saracyn, Sławomir Lewicki, Marta Grodzik, Agnieszka Sobolewska-Ruta, Monika Leśniak, Eugeniusz K Machaj, Zygmunt Pojda, Military Institute of Medicine, Warsaw, Warsaw University of Life Sciences (SGGW), National Institute of Public Health - National Institute of Hygiene [Poland], Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology (MCMCC), USA Defense Advanced Research Project Agency [N10PC20038], and Polish Ministry of National Defense project [571/2016/DA]
Subjects: liposomes, Liposome, business.industry, [SDV]Life Sciences [q-bio], Mesenchymal stem cell, protein transfer to cells in vitro, General Medicine, delivery to stem cells, Thin film hydration, Granulocyte colony-stimulating factor, Cell biology, Haematopoiesis, Granulocyte macrophage colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, Cord blood, medicine, Stem cell, granulocyte colony-stimulating factor, business, medicine.drug
Abstract: IntroductionCytokines are important immune modulator factors controlling homeostasis of the body and are involved in tissue regeneration after wound healing. The encapsulation of cytokines in liposomes has many advantages potentially useful for their transfer to the cells. Liposomes protect cytokines from neutralization, improving their pharmacokinetics or biologic activity in vivo. They are targeted to specific cell types and may delay the release of cytokines, allowing their sustained paracrine delivery. Their physicochemical characteristics such as size, shape, charge, and stability are important parameters improving bio-distribution and prolonged pharmacokinetics of encapsulated cytokines.Material and methodsWe developed an efficient protocol for the encapsulation of two types of cytokines, granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF), in liposomes that can be stored long term in the active state.ResultsThis method allows for the encapsulation of 12–13% of the total amount of cytokines and 50% of encapsulated cytokines are entrapped in liposomes of more than ≤ 600 nm in diameter. We show that in the studied cell lines the liposome-encapsulated cytokines do not affect cell morphology, proliferation or mortality.ConclusionsThe G-CSF or GM-CSF can be delivered to the cells in working concentrations through the encapsulation in the liposomes. Before the clinical application, the efficiency of these liposomes should be confirmed by an in vivo study.
Published: 2022
Full Text: View/download PDF

10. European Reference Network for rare adult solid cancers, statement and integration to health care systems of member states

Author: Blay, J-Y, Casali, P, Bouvier, C, Dehais, C, Galloway, I, Gietema, J, Halámková, J, Hindi, N, Idbaih, A, Kinloch, E, Klümpen, H-J, Kolarova, T, Kopeckova, K, Lovey, J, Magalhaes, M, Oselin, K, Piperno-Neumann, S, Ravnsbaek, A, Rogasik, M, Safwat, A, Scheipl, S, Seckl, M, Taylor, J, Temnyk, M, Trama, A, Urbonas, M, Wartenberg, M, Weinman, A, EURACAN Network, Oncology, CCA - Cancer Treatment and Quality of Life, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Léon Bérard [Lyon], University of Milan, Fondazione IRCCS Istituto Nazionale Tumori - National Cancer Institute [Milan], Royal Free Hospital [London, UK], Service de neurologie 2 [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), University Medical Center Groningen [Groningen] (UMCG), Masaryk Memorial Cancer Institute (RECAMO), Hospital Universitario Virgen del Rocío [Sevilla], University of Amsterdam [Amsterdam] (UvA), University Hospital Motol [Prague], National Institute of Oncology [Budapest, Hungary], Centro Hospitalar do Porto, North Estonia Medical Center, Institut Curie [Paris], Aarhus University Hospital, Karl-Franzens-Universität [Graz, Autriche], Charing Cross Hospital & Imperial College, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology (MCMCC), Kaunas University of Technology (KTU), EURORDIS-Rare Diseases Europe (Bureau de Paris), EURORDIS - Plateforme Maladies Rares [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), and University of Graz
Subjects: Cancer Research, medicine.medical_specialty, Statement (logic), MEDLINE, [SDV.CAN]Life Sciences [q-bio]/Cancer, News, GUIDELINES, DIAGNOSIS, 03 medical and health sciences, 0302 clinical medicine, EURACAN Network, Health care, medicine, 030212 general & internal medicine, ComputingMilieux_MISCELLANEOUS, business.industry, Member states, 3. Good health, Oncology, 030220 oncology & carcinogenesis, Family medicine, SURVIVAL, Position paper, SARCOMA PATIENTS, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, BURDEN
Abstract: International audience
Published: 2021
Full Text: View/download PDF

11. 20-Year Steady Increase in Survival of Adult Patients with Relapsed Philadelphia-Positive Acute Lymphoblastic Leukemia Post Allogeneic Hematopoietic Cell Transplantation

Author: Ali Bazarbachi, Myriam Labopin, Mahmoud Aljurf, Riitta Niittyvuopio, Marie Balsat, Didier Blaise, Ibrahim Yakoub-Agha, Anna Grassi, Hans Christian Reinhardt, Stig Lenhoff, Pavel Jindra, Jakob Passweg, Iman Abou Dalle, Michael Stadler, Bruno Lioure, Patrice Ceballos, Eolia Brissot, Sebastian Giebel, Arnon Nagler, Christoph Schmid, Mohamad Mohty, American University of Beirut [Beyrouth] (AUB), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), King Faisal Specialist Hospital and Resarch Centre [Riyadh, Saudi Arabia] (KFSHRC), Helsinki University Central Hospital [Finland] (HUCH), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Service d’Hématologie [Institut Paoli Calmettes, Marseille], Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), CHU Lille, Institute for Translational Research in Inflammation - U 1286 (INFINITE (Ex-Liric)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Azienda Ospedaliera Ospedale Papa Giovanni XXIII [Bergamo, Italy], Universität Duisburg-Essen = University of Duisburg-Essen [Essen], Department of Hematology, University Hospital Lund, Medicine Charles University and General Faculty Hospital in Prague, University Hospital Basel [Basel], Hannover Medical School [Hannover] (MHH), CHU Strasbourg, Hôpital Lapeyronie [Montpellier] (CHU), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology (MCMCC), Chaim Sheba Medical Center, and University of Augsburg (UNIA)
Subjects: Adult, Cancer Research, Transplantation Conditioning, Oncology, Recurrence, [SDV]Life Sciences [q-bio], Acute Disease, Medizin, Hematopoietic Stem Cell Transplantation, Humans, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Retrospective Studies
Abstract: Purpose: Relapse after allogeneic hematopoietic cell transplantation (allo-HCT) remains the first cause of transplant failure in patients with Philadelphia-positive (Ph+) acute lymphoblastic leukemia (ALL). In other hematologic malignancies, therapeutic advances resulted in significant improvement over time in survival of patients relapsing after transplant. Experimental Design: We compared outcomes at European Society for Blood and Marrow Transplantation (EBMT) participating centers of 899 adult patients with Ph+ ALL who relapsed between 2000 and 2019 after allo-HCT performed in first complete remission. Median follow-up for alive patients was 56 months. Results: Overall, 116 patients relapsed between 2000 and 2004, 225 between 2005 and 2009, 294 between 2010 and 2014, and 264 between 2015 and 2019. Patient and transplant characteristics were similar over the four time periods except for a progressive increase in unrelated donors, peripheral blood stem cells, reduced intensity conditioning, and in vivo T-cell depletion and a progressive decrease in total body irradiation. The 2-year overall survival (OS) after relapse increased from 27.8% for patients relapsing between 2000 and 2004 to 54.8% for 2015 and 2019 (P = 0.001). A second allo-HCT within 2 years after relapse was performed in 13.9% of patients resulting in a 2-year OS of 35.9%. In multivariate analysis, OS from relapse was positively affected by a longer time from transplant to relapse and the year of relapse. Conclusions: We observed a major progressive improvement in OS from posttransplant relapse for patients with Ph+ ALL over the years, likely multifactorial including transplant-related factors, posttransplant salvage, and improvement in supportive care. These large-scale real-world data can serve as a benchmark for future studies in this setting. See related commentary by Gale, p. 813
Published: 2021
Full Text: View/download PDF

12. Adjuvant pembrolizumab versus placebo in resected stage III melanoma (EORTC 1325-MG/KEYNOTE-054): distant metastasis-free survival results from a double-blind, randomised, controlled, phase 3 trial

Author: Christoph Hoeller, Marie-Francoise Avril, Pietro Quaglino, François Aubin, Lars Bastholt, Takashi Inozume, Virginia Ferraresi, Michael B. Jameson, Kevin B. Kim, Oliver Bechter, Dirk Schadendorf, Kenji Yokota, Carmen Loquai, Maria-Jose Passos, Inge Marie Svane, Michele Maio, Catherine Barrow, Frank Meiss, Nageatte Ibrahim, Andrzej Mackiewicz, Phillip Parente, Tatsuya Takenouchi, Caroline Dutriaux, Piotr Rutkowski, Alfonsus J M van den Eertwegh, Paola Queirolo, Catriona M. McNeil, Peter Mohr, Felix Kiecker, Susana Puig, Friedegund Meier, Lutz Kretschmer, Alexander C.J. van Akkooi, Alex Menzies, Timothy Crook, Christian U. Blank, Suzana Matkovic, Michael C. Brown, Ragini R. Kudchadkar, Max Levin, Rüdiger Hein, Tanja Skytta, Gerald P. Linette, Clemens Krepler, Adnan Khattak, Ernest Marshall, Joseph Kerger, Oddbjorn Straume, Laurent Mortier, Jochen Utikal, Micaela Hernberg, James Larkin, Yoshio Kiyohara, Mario Mandalà, Henrik Schmidt, Daniil Stroyakovskiy, Pablo Luis Ortiz Romero, Naoya Yamazaki, John Walker, Anna Maria Di Giacomo, Lionel Geoffrois, Jean-Philippe Lacour, Caroline Robert, Vincent Descamps, Shahneen Sandhu, Gil Bar-Sela, Paul C. Nathan, Marcin Dzienis, Ralf Gutzmer, Claus Garbe, Andrey Meshcheryakov, Patrick Combemale, Martin Fehr, Guzel Mukhametshina, Helena Kapiteijn, Geke A. P. Hospers, Jun Aoi, Andrew Haydon, Rutger H. T. Koornstra, Marie-Thérèse Leccia, Sigrun Hallmeyer, Pier Francesco Ferrucci, Jean-Jacques Grob, Leonel Hernandez-Aya, Jan-Christoph Simon, Vanna Chiarion Sileni, Alain Algazi, Lidija Sekulovic, Sandrine Marreaud, Bernard Fitzharris, Jacob Schachter, Xinni Song, Wolf-Henning Boehncke, Rahima Jamal, Paul Lorigan, Maureen J.B. Aarts, Reinhard Dummer, Mike McCrystal, César Martins, Reiner Hofmann-Wellenhof, Alexander M.M. Eggermont, Carola Berking, Elaine Dunwoodie, Bernard Guillot, Michal Kicinski, Philippe Saiag, Céleste Lebbé, Thierry Lesimple, Stefan Suciu, Michal Lotem, Paula Ferreira, Mohammed M. Milhem, Laurent Machet, Patrick Terheyden, Anna Katharina Winge-Main, Peter Hersey, Jean-Francois Baurain, Axel Hauschild, Stéphane Dalle, Jean-Philippe Arnault, Paolo A. Ascierto, Gerard Groenewegen, Florent Grange, Georgina V. Long, Victoria Atkinson, Philippa Corrie, Matteo S. Carlino, Thomas Jouary, Daniel Hendler, Richard Casasola, Ashita Waterston, Jessica C. Hassel, University Medical Center [Utrecht], Azienda Ospedaliera Ospedale Papa Giovanni XXIII [Bergamo, Italy], The University of Sydney, Princess Alexandra Hospital, Brisbane, University of Queensland [Brisbane], 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-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), N.N. Blokhin National Medical Research Center of Oncology, Edith Cowan University (ECU), Royal Marsden NHS Foundation Trust, Universitat de Barcelona (UB), Instituto de Salud Carlos III [Madrid] (ISC), Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology (MCMCC), Universitätsklinikum Essen [Universität Duisburg-Essen] (Uniklinik Essen), Radboud University Medical Center [Nijmegen], Washington University School of Medicine in St. Louis, Washington University in Saint Louis (WUSTL), University Hospital of Siena, Amsterdam UMC - Amsterdam University Medical Center, Hôpital de la Timone [CHU - APHM] (TIMONE), Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hannover Medical School [Hannover] (MHH), Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM), The Christie NHS Foundation Trust [Manchester, Royaume-Uni], Merck & Co. Inc, European Organisation for Research and Treatment of Cancer [Bruxelles] (EORTC), European Cancer Organisation [Bruxelles] (ECCO), Institut Gustave Roussy (IGR), Oncologie dermatologique, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université de Montpellier (UM), Internal medicine, and CCA - Cancer Treatment and quality of life
Subjects: Male, Skin Neoplasms, Medizin, Pembrolizumab, law.invention, Cancer development and immune defence Radboud Institute for Health Sciences [Radboudumc 2], MESH: Aged, 80 and over, 0302 clinical medicine, Randomized controlled trial, law, Monoclonal, 80 and over, MESH: Double-Blind Method, 030212 general & internal medicine, Neoplasm Metastasis, Humanized, Melanoma, MESH: Aged, Aged, 80 and over, education.field_of_study, MESH: Middle Aged, Hazard ratio, MESH: Neoplasm Staging, Middle Aged, Oncology, 030220 oncology & carcinogenesis, Female, Adult, Aged, Antibodies, Monoclonal, Humanized, Double-Blind Method, Humans, Neoplasm Staging, medicine.medical_specialty, MESH: Melanoma, Population, [SDV.CAN]Life Sciences [q-bio]/Cancer, Placebo, Antibodies, 03 medical and health sciences, All institutes and research themes of the Radboud University Medical Center, Internal medicine, medicine, Adjuvant therapy, education, Cancer staging, MESH: Humans, business.industry, MESH: Skin Neoplasms, MESH: Adult, MESH: Neoplasm Metastasis, MESH: Male, Clinical trial, MESH: Antibodies, Monoclonal, Humanized, business, MESH: Female
Abstract: Background: The European Organisation for Research and Treatment of Cancer (EORTC) 1325/KEYNOTE-054 trial assessed pembrolizumab versus placebo in patients with resected high-risk stage III melanoma. At 15-month median follow-up, pembrolizumab improved recurrence-free survival (hazard ratio [HR] 0·57 [98·4% CI 0·43–0·74], p1 mm), IIIB, or IIIC (without in-transit metastasis), and with an Eastern Cooperative Oncology Group performance status of 0 or 1 were eligible. Patients were randomly assigned (1:1) via a central interactive voice response system to receive intravenous pembrolizumab 200 mg or placebo every 3 weeks for up to 18 doses or until disease recurrence or unacceptable toxicity. Randomisation was stratified according to disease stage and region, using a minimisation technique, and clinical investigators, patients, and those collecting or analysing the data were masked to treatment assignment. The two coprimary endpoints were recurrence-free survival in the intention-to-treat (ITT) population and in patients with PD-L1-positive tumours. The secondary endpoint reported here was distant metastasis-free survival in the ITT and PD-L1-positive populations. This study is registered with ClinicalTrials.gov, NCT02362594, and EudraCT, 2014-004944-37. Findings: Between Aug 26, 2015, and Nov 14, 2016, 1019 patients were assigned to receive either pembrolizumab (n=514) or placebo (n=505). At an overall median follow-up of 42·3 months (IQR 40·5–45·9), 3·5-year distant metastasis-free survival was higher in the pembrolizumab group than in the placebo group in the ITT population (65·3% [95% CI 60·9–69·5] in the pembrolizumab group vs 49·4% [44·8–53·8] in the placebo group; HR 0·60 [95% CI 0·49–0·73]; p
Published: 2021
Full Text: View/download PDF

13. Adjuvant pembrolizumab versus placebo in resected stage III melanoma (EORTC 1325-MG/KEYNOTE-054): health-related quality-of-life results from a double-blind, randomised, controlled, phase 3 trial

Author: Bottomley, A., Coens, C., Mierzynska, J., Blank, C. U., Mandalà, M., Long, G. V., Atkinson, V. G., Dalle, S., Haydon, A. M., Meshcheryakov, A., Khattak, A., Carlino, M. S., Sandhu, S., Puig, S., Ascierto, P. A., Larkin, J., Lorigan, P. C., Rutkowski, P., Schadendorf, D., Koornstra, R., Hernandez-Aya, L., Di Giacomo, A. M., van den Eertwegh, A. J. M., Grob, J. -J., Gutzmer, R., Jamal, R., van Akkooi, A. C. J., Krepler, C., Ibrahim, N., Marreaud, S., Kicinski, M., Suciu, S., Robert, C., Eggermont, A. M. M., EORTC Melanoma Group, Lesimple, T., Maio, M., Linette, G., Mortier, L., Svane, I. M., Schachter, J., Brown, M., Hersey, P., Barrow, C., Kudchadkar, R., Dutriaux, C., Song, X., Quaglino, P., Queirolo, P., Meier, F., Stroyakovskiy, D., Guillot, B., Romero, P. L. O., Bastholt, L., Garbe, C., Grange, F., Mohr, P., Algazi, A., Bechter, O., Hernberg, M., Loquai, C., Meiss, F., Chiarion Sileni, V., Bar-Sela, G., Fitzharris, B., Saiag, P., Arnault, J. -P., Simon, J. -C., Stephens, R., Baurain, J. -F., Lebbe, C., Combemale, P., Dummer, R., Hauschild, A., Parente, P., Yamazaki, N., Milhem, M., Leccia, M. -T., Geoffrois, L., Kretschmer, L., Dunwoodie, E., Walker, J., Lotem, M., Hendler, D., Mackiewicz, A., Sekulovic, L., Dzienis, M., Hospers, G. A. P., Siano, M., Hassel, J., Corrie, P., Passos, M. -J., Levin, M., Hoeller, C., Machet, L., Hallmeyer, S., Waterston, A., Descamps, V., Kiecker, F., Aarts, M., Schmidt, H., Raimundo, A., Nyakas, M., Lacour, J. -P., Berking, C., Ferrucci, P. F., Jameson, M., Kim, K., Yokota, K., Kerger, J., Aubin, F., Groenewegen, G., Kapiteijn, H., Boehncke, W. -H., Utikal, J., Casasola, R., Marshall, E., Ferraresi, V., Richtig, E., Matkovic, S., Inozume, T., Crook, T., Mcneil, C., Kiyohara, Y., Avril, M. -F., Hein, R., Terheyden, P., Nathan, P., Aoi, J., Skytta, T., Jouary, T., Takenouchi, T., Straume, O., Martins, C., Mukhametshina, G., Boehncke, Wolf-Henning, Internal medicine, CCA - Cancer Treatment and quality of life, European Organisation for Research and Treatment of Cancer [Bruxelles] (EORTC), European Cancer Organisation [Bruxelles] (ECCO), Ospedale 'Santa Maria della Misericordia' = University Hospital 'Santa Maria della Misericordia', The University of Sydney, Princess Alexandra Hospital, Brisbane, University of Queensland [Brisbane], 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-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Edith Cowan University (ECU), Universitat de Barcelona (UB), The Christie NHS Foundation Trust [Manchester, Royaume-Uni], Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology (MCMCC), Radboud University Medical Center [Nijmegen], Washington University School of Medicine in St. Louis, Washington University in Saint Louis (WUSTL), University Hospital of Siena, Amsterdam UMC - Amsterdam University Medical Center, Hôpital de la Timone [CHU - APHM] (TIMONE), Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hannover Medical School [Hannover] (MHH), Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM), Merck & Co. Inc, AP-HP. Université Paris Saclay, Institut Gustave Roussy (IGR), University Medical Center [Utrecht], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université de Montpellier (UM), Merck Sharp & Dohme., and Guided Treatment in Optimal Selected Cancer Patients (GUTS)
Subjects: Male, Skin Neoplasms, Medizin, Skin Neoplasms / drug therapy, Pembrolizumab, law.invention, Cancer development and immune defence Radboud Institute for Health Sciences [Radboudumc 2], MESH: Aged, 80 and over, 0302 clinical medicine, Melanoma / pathology, Randomized controlled trial, law, Monoclonal, 80 and over, Clinical endpoint, MESH: Double-Blind Method, 030212 general & internal medicine, Humanized, Melanoma, MESH: Aged, ddc:616, Aged, 80 and over, education.field_of_study, MESH: Middle Aged, Antibodies, Monoclonal, Humanized, Neoplasm Staging, Quality of Life, Double-Blind Method, Adult, Aged, Middle aged, Humans [MeSH], Hazard ratio, MESH: Neoplasm Staging, Middle Aged, Oncology, 030220 oncology & carcinogenesis, Female, Humans, medicine.medical_specialty, Melanoma / psychology, Skin Neoplasms / psychology, MESH: Melanoma, Antibodies, Monoclonal, Humanized / therapeutic use, Population, [SDV.CAN]Life Sciences [q-bio]/Cancer, Placebo, Antibodies, Melanoma / mortality, 03 medical and health sciences, Internal medicine, medicine, Adjuvant therapy, education, Skin Neoplasms / pathology, MESH: Humans, Melanoma / drug therapy, business.industry, MESH: Skin Neoplasms, MESH: Quality of Life, MESH: Adult, Skin Neoplasms / mortality, MESH: Male, Clinical trial, MESH: Antibodies, Monoclonal, Humanized, business, MESH: Female
Abstract: Background: The European Organisation for Research and Treatment of Cancer (EORTC) 1325-MG/KEYNOTE-054 trial in patients with resected, high-risk stage III melanoma demonstrated improved recurrence-free survival with adjuvant pembrolizumab compared with placebo (hazard ratio 0·57 [98·4% CI 0·43-0·74]; pMethods: This double-blind, randomised, controlled, phase 3 trial was done at 123 academic centres and community hospitals across 23 countries. Patients aged 18 years or older with previously untreated histologically confirmed stage IIIA, IIIB, or IIIC resected cutaneous melanoma, and an Eastern Cooperative Oncology Group performance status score of 1 or 0 were eligible. Patients were randomly assigned (1:1) using a central interactive voice-response system on the basis of a minimisation technique stratified for stage and geographic region to receive intravenously 200 mg pembrolizumab or placebo. Treatment was administered every 3 weeks for 1 year, or until disease recurrence, unacceptable toxicity, or death. The primary endpoint of the trial was recurrence-free survival (reported elsewhere). HRQOL was a prespecified exploratory endpoint, with global health/quality of life (GHQ) over 2 years measured by the EORTC QLQ-C30 as the primary analysis. Analyses were done in the intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT02362594, and EudraCT, 2014-004944-37, and long-term follow-up is ongoing.Findings: Between Aug 26, 2015, and Nov 14, 2016, 1019 patients were assigned to pembrolizumab (n=514) or placebo (n=505). Median follow-up was 15·1 months (IQR 12·8-16·9) at the time of this analysis. HRQOL compliance was greater than 90% at baseline, greater than 70% during the first year, and greater than 60% thereafter for both groups. Because of low absolute compliance numbers at later follow-up, the analysis was truncated to week 84. Baseline GHQ scores were similar between groups (77·55 [SD 18·20] in the pembrolizumab group and 76·54 [17·81] in the placebo group) and remained stable over time. The difference in average GHQ score between the two groups over the 2 years was -2·2 points (95% CI -4·3 to -0·2). The difference in average score during treatment was -1·1 points (95% CI -3·2 to 0·9) and the difference in average score after treatment was -2·2 points (-4·8 to 0·4). These differences are within the 5-point clinical relevance threshold for the QLQ-C30 and are therefore clinically non-significant.Interpretation: Pembrolizumab does not result in a clinically significant decrease in HRQOL compared with placebo when given as adjuvant therapy for patients with resected, high-risk stage III melanoma. These results support the use of adjuvant pembrolizumab in this setting. placebo when given as adjuvant therapy for patients with resected, high-risk stage III melanoma. These results support the use of adjuvant pembrolizumab in this setting. placebo when given as adjuvant therapy for patients with resected, high-risk stage III melanoma. These results support the use of adjuvant pembrolizumab in this setting.
Published: 2021
Full Text: View/download PDF

14. Thiotepa-busulfan-fludarabine (TBF) conditioning regimen in patients undergoing allogeneic hematopoietic cell transplantation for myelofibrosis: an outcome analysis from the Chronic Malignancies Working Party of the EBMT

Author: Giuseppe Marotta, Didier Blaise, Matjaz Sever, Patrizia Chiusolo, Ibrahim Yakoub-Agha, Tomasz Czerw, Carlos Solano, Giorgia Battipaglia, Nicolaus Kröger, Stella Santarone, Marie-Thérèse Rubio, Maria Laura Fox, Anna Paola Iori, William Arcese, Patrick Hayden, Mohamad Mohty, Liesbeth C. de Wreede, Yves Chalandon, Lotus Wendel, Juan Carlos Hernández-Boluda, Renato Fanin, Pietro Pioltelli, Emanuele Angelucci, Donal P. McLornan, Katya Mauff, Nathalie Contentin, University of Naples Federico II = Università degli studi di Napoli Federico II, European Society for Blood and Marrow Transplantation (EBMT), Ospedale Policlinico San Martino [Genoa], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Università degli Studi di Roma Tor Vergata [Roma], Service d'Hématologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Vall d'Hebron Institute of Oncology [Barcelone] (VHIO), Vall d'Hebron University Hospital [Barcelona], Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), Università degli Studi di Udine - University of Udine [Italie], Hôpitaux Universitaires de Genève (HUG), Azienda Ospedaliera Universitaria Senese, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università cattolica del Sacro Cuore = Catholic University of the Sacred Heart [Roma] (Unicatt), University Medical Centre Ljubljana [Ljubljana, Slovenia] (UMCL), University of Ljubljana, Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Leiden University Medical Center (LUMC), Universiteit Leiden, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology (MCMCC), Trinity College Dublin, NHS Foundation Trust [London], The Royal Marsden, Institute for Translational Research in Inflammation - U 1286 (INFINITE (Ex-Liric)), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)
Subjects: medicine.medical_specialty, Transplantation Conditioning, Platelet Engraftment, [SDV]Life Sciences [q-bio], Vidarabine / analogs & derivatives, Graft vs Host Disease, ThioTEPA, Gastroenterology, Conditioning regimen, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Neoplasms, medicine, Humans, In patient, Vidarabine / therapeutic use, Myelofibrosis, Busulfan, ComputingMilieux_MISCELLANEOUS, Retrospective Studies, ddc:616, Transplantation, Hematopoietic cell, business.industry, Hematopoietic Stem Cell Transplantation, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy, Hematology, Middle Aged, Settore MED/15, medicine.disease, surgical procedures, operative, Primary Myelofibrosis, 030220 oncology & carcinogenesis, Stem cell, business, Thiotepa, Vidarabine, 030215 immunology, medicine.drug
Abstract: Allogeneic hematopoietic cell transplantation (allo-HCT) remains the only curative option in MF. There is no consensus on the optimal conditioning regimen. We report outcomes of 187 patients with MF transplanted between 2010 and 2017 conditioned with TBF. Median age was 58 years. Median interval from diagnosis to allo-HCT was 44 months. Donors were haploidentical (41%), unrelated (36%) or HLA-identical siblings (23%). Stem cell source was PB in 60%. Conditioning was myeloablative in 48% of cases. Antithymocyte globulin (ATG) was used in 41% of patients. At 100 days, neutrophil and platelet engraftment were 91% and 63% after a median of 21 and 34 days, respectively. Grade II-IV and III-IV acute GVHD occurred in 24% and 12%, while at 3 years, all grade chronic GVHD and chronic extensive GVHD had been diagnosed in 38% and 11%. At 3 years, OS, RFS and GRFS were 55%, 49% and 43%, respectively. RI and NRM were 17% and 33%. On multivariate analysis, poor KPS and the use of unrelated donors were associated with worse GRFS and a higher grade II-IV acute GVHD, respectively. Neither donor type nor intensity of the conditioning regimen influenced survival outcomes. TBF is a feasible conditioning regimen in allo-HCT for MF in all donor settings although longer term outcomes are required.
Published: 2020
Full Text: View/download PDF

15. Post-transplant cyclophosphamide versus antithymocyte globulin in patients with acute myeloid leukemia in first complete remission undergoing allogeneic stem cell transplantation from 10/10 HLA-matched unrelated donors

Author: Gwendolyn Van Gorkom, Montserrat Rovira, Edouard Forcade, Myriam Labopin, Eolia Brissot, Annalisa Ruggeri, Alexandros Spyridonidis, Eric Deconinck, Martin Mistrik, Jan J. Cornelissen, Claude Eric Bulabois, Ian Moiseev, Ellen Meijer, Stephan Mielke, Laimonas Griskevicius, Sebastian Giebel, Didier Blaise, Riitta Niittyvuopio, Bipin N. Savani, Fabio Ciceri, Arnon Nagler, Jaime Sanz, Mohamad Mohty, Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hematology, Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service d'hématologie clinique et de thérapie cellulaire [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), CEREST-TC [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Pavlov First Saint Petersburg State Medical University [St. Petersburg], Erasmus University Medical Center [Rotterdam] (Erasmus MC), VU University Medical Center [Amsterdam], Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht], University of Barcelona, IRCCS Ospedale San Raffaele [Milan, Italy], Universita Vita Salute San Raffaele = Vita-Salute San Raffaele University [Milan, Italie] (UniSR), Vilnius University [Vilnius], Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Comenius University in Bratislava, University Hospital of Würzburg, Centre Hospitalier Universitaire [Grenoble] (CHU), Hôpital JeanMinjoz, Universitat de València (UV), General University Hospital of Patras, Vanderbilt University Medical Center [Nashville], Vanderbilt University [Nashville], Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology (MCMCC), Gestionnaire, Hal Sorbonne Université, Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), 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), HUS Comprehensive Cancer Center, Clinicum, Department of Oncology, Brissot, E., Labopin, M., Moiseev, I., Cornelissen, J. J., Meijer, E., Van Gorkom, G., Rovira, M., Ciceri, F., Griskevicius, L., Blaise, D., Forcade, E., Mistrik, M., Mielke, S., Bulabois, C. E., Niittyvuopio, R., Deconinck, E., Ruggeri, A., Sanz, J., Spyridonidis, A., Savani, B., Giebel, S., Nagler, A., Mohty, M., RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, Interne Geneeskunde, MUMC+: MA Hematologie (9), CCA - Cancer Treatment and quality of life, and CHU Saint-Antoine [AP-HP]
Subjects: Oncology, Male, Cancer Research, BLOOD, [SDV]Life Sciences [q-bio], MULTICENTER, Graft vs Host Disease, Kaplan-Meier Estimate, HEMATOLOGICAL MALIGNANCIES, PROPHYLAXIS, 0302 clinical medicine, antithymocyte globulin, prevention, Recurrence, immune system diseases, Cause of Death, hemic and lymphatic diseases, Antineoplastic Combined Chemotherapy Protocols, skin allograft tolerance, Medicine, Cumulative incidence, ComputingMilieux_MISCELLANEOUS, free survival, Hematology, Incidence (epidemiology), Incidence, Graft Survival, Remission Induction, Hematopoietic Stem Cell Transplantation, Myeloid leukemia, lcsh:Diseases of the blood and blood-forming organs, Middle Aged, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Allografts, Combined Modality Therapy, 3. Good health, [SDV] Life Sciences [q-bio], Leukemia, Myeloid, Acute, surgical procedures, operative, 030220 oncology & carcinogenesis, Histocompatibility, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Post-transplant cyclophosphamide, Unrelated Donors, Immunosuppressive Agents, medicine.drug, Adult, medicine.medical_specialty, Cyclophosphamide, Adolescent, post-transplant cyclophosphamide, 3122 Cancers, matched unrelated donor, Human leukocyte antigen, acute myeloid leukemia, open-label, lcsh:RC254-282, Disease-Free Survival, MECHANISMS, versus-host-disease, 03 medical and health sciences, Young Adult, Internal medicine, Humans, Matched unrelated donor, Propensity Score, Molecular Biology, Aged, Antilymphocyte Serum, Retrospective Studies, Acute myeloid leukemia, business.industry, lcsh:RC633-647.5, Research, Transplantation, Propensity score matching, Antithymocyte globulin, business, 030215 immunology
Abstract: International audience; Full text linksfull-text provider logoActionsFavoritesSharePage navigation Title & authors Abstract Conflict of interest statement Figures References Related information LinkOut - more resourcesJ Hematol Oncol. 2020 Jul 3;13(1):87.doi: 10.1186/s13045-020-00923-0.Post-transplant cyclophosphamide versus antithymocyte globulin in patients with acute myeloid leukemia in first complete remission undergoing allogeneic stem cell transplantation from 10/10 HLA-matched unrelated donorsEolia Brissot 1 2 , Myriam Labopin 3 , Ian Moiseev 4 , J J Cornelissen 5 , Ellen Meijer 6 , Gwendolyn Van Gorkom 7 , Montserrat Rovira 8 , Fabio Ciceri 9 10 , Laimonas Griskevicius 11 , Didier Blaise 12 , Edouard Forcade 13 , Martin Mistrik 14 , Stephan Mielke 15 , Claude Eric Bulabois 16 , Riitta Niittyvuopio 17 , Eric Deconinck 18 , Annalisa Ruggeri 9 10 , Jaime Sanz 19 20 , Alexandros Spyridonidis 21 , Bipin Savani 22 , Sebastian Giebel 23 , Arnon Nagler 24 , Mohamad Mohty 25 26Affiliations PMID: 32620146 PMCID: PMC7333262 DOI: 10.1186/s13045-020-00923-0 Free PMC articleAbstractBackground: Graft-versus-host disease (GVHD) remains a major contributor to mortality and morbidity after allogeneic stem-cell transplantation (allo-HSCT). The updated recommendations suggest that rabbit antithymocyte globulin or anti-T-lymphocyte globulin (ATG) should be used for GVHD prophylaxis in patients undergoing matched-unrelated donor (MUD) allo-HSCT. More recently, using post-transplant cyclophosphamide (PTCY) in the haploidentical setting has resulted in low incidences of both acute (aGVHD) and chronic GVHD (cGVHD). Therefore, the aim of our study was to compare GVHD prophylaxis using either PTCY or ATG in patients with acute myeloid leukemia (AML) who underwent allo-HSCT in first remission (CR1) from a 10/10 HLA-MUD.Methods: Overall, 174 and 1452 patients from the EBMT registry receiving PTCY and ATG were included. Cumulative incidence of aGVHD and cGVHD, leukemia-free survival, overall survival, non-relapse mortality, cumulative incidence of relapse, and refined GVHD-free, relapse-free survival were compared between the 2 groups. Propensity score matching was also performed in order to confirm the results of the main analysis RESULTS: No statistical difference between the PTCY and ATG groups was observed for the incidence of grade II-IV aGVHD. The same held true for the incidence of cGVHD and for extensive cGVHD. In univariate and multivariate analyses, no statistical differences were observed for all other transplant outcomes. These results were also confirmed using matched-pair analysis.Conclusion: These results highlight that, in the10/10 HLA-MUD setting, the use of PTCY for GVHD prophylaxis may provide similar outcomes to those obtained with ATG in patients with AML in CR1.
Published: 2020
Full Text: View/download PDF

16. Management of patients with acute leukemia during the COVID-19 outbreak: practical guidelines from the acute leukemia working party of the European Society for Blood and Marrow Transplantation

Author: Myriam Labopin, Sebastian Giebel, Annalisa Ruggeri, Zinaida Peric, Jordi Esteve, Mohamad Mohty, Norbert Claude Gorin, Jurjen Versluis, Jaime Sanz, Gesine Bug, Eolia Brissot, Arnon Nagler, Ali Bazarbachi, Maria H. Gilleece, Fabio Ciceri, Frédéric Baron, Francesco Lanza, Roni Shouval, Christoph Schmid, Bipin N. Savani, Alexandros Spyridonidis, Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université de Liège, American University of Beirut Faculty of Medicine and Medical Center (AUB), Goethe-University Frankfurt am Main, Universita Vita Salute San Raffaele = Vita-Salute San Raffaele University [Milan, Italie] (UniSR), Barcelona Centre for International Health Research, Hospital Clinic (CRESIB), Universitat de Barcelona (UB), Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology (MCMCC), Leeds Institute of Cancer and Pathology [U.K.], Service d'hématologie clinique et de thérapie cellulaire [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Alma Mater Studiorum University of Bologna (UNIBO), University Hospital Center Rebro, Universitat de València (UV), Vanderbilt University Medical Center [Nashville], Vanderbilt University [Nashville], Universität Augsburg [Augsburg], Memorial Sloane Kettering Cancer Center [New York], General University Hospital of Patras, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Chaim Sheba Medical Center, Hematology, Gestionnaire, HAL Sorbonne Université 5, Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Brissot, E., Labopin, M., Baron, F., Bazarbachi, A., Bug, G., Ciceri, F., Esteve, J., Giebel, S., Gilleece, M. H., Gorin, N. -C., Lanza, F., Peric, Z., Ruggeri, A., Sanz, J., Savani, B. N., Schmid, C., Shouval, R., Spyridonidis, A., Versluis, J., Nagler, A., and Mohty, M.
Subjects: 2019-20 coronavirus outbreak, medicine.medical_specialty, Tissue and Organ Procurement, Coronavirus disease 2019 (COVID-19), [SDV]Life Sciences [q-bio], Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), chemotherapy, NO, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Internal medicine, medicine, Leukaemia, Humans, Acute leukemia, COVID-19, chemotherapy, aplasia, immune-deficiency, Pandemics, Societies, Medical, ComputingMilieux_MISCELLANEOUS, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Acute leukemia, Transplantation, Leukemia, SARS-CoV-2, business.industry, Marrow transplantation, Hematopoietic Stem Cell Transplantation, COVID-19, Outbreak, Hematology, Precursor Cell Lymphoblastic Leukemia-Lymphoma, 3. Good health, Europe, [SDV] Life Sciences [q-bio], Leukemia, Myeloid, Acute, aplasia, 030220 oncology & carcinogenesis, Perspective, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, immune-deficiency, business, Haematological diseases, 030215 immunology
Abstract: International audience
Published: 2020
Full Text: View/download PDF

17. Safety, efficacy and patient-reported outcomes with trifluridine/tipiracil in pretreated metastatic colorectal cancer: results of the PRECONNECT study

Author: Loick Vidot, Julien Taieb, Irfan Cicin, Ahmet Ozet, Martin Becquart, Fabienne Portales, Timothy J. Price, Chiara Cremolini, Dan Atlan, Jean-Marc Phelip, Jean-Baptiste Bachet, Nadjat Mounedji, Eric Van Cutsem, Alfredo Falcone, Lucjan Wyrwicz, Service d'Hépato-Gastro-Entérologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology (MCMCC), Queen Elizabeth Hospital, University of Pisa - Università di Pisa, Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), 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), Gazi University, Trakya Universitesi [Edirne], Institut de Recherches Internationales Servier [Suresnes] (IRIS), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), 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), Gestionnaire, Hal Sorbonne Université, and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: Male, Vascular Endothelial Growth Factor A, Cancer Research, Pyrrolidines, Colorectal cancer, [SDV]Life Sciences [q-bio], Trifluridine, trifluridine tipiracil, chemistry.chemical_compound, 0302 clinical medicine, Quality of life, Antineoplastic Combined Chemotherapy Protocols, Clinical endpoint, colorectal cancer, metastatic, quality of life, safety, Original Research, 0303 health sciences, Middle Aged, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, 3. Good health, [SDV] Life Sciences [q-bio], Oncology, 030220 oncology & carcinogenesis, Female, medicine.symptom, Colorectal Neoplasms, medicine.drug, medicine.medical_specialty, Nausea, Placebo, lcsh:RC254-282, 03 medical and health sciences, Internal medicine, medicine, Humans, Patient Reported Outcome Measures, Adverse effect, 030304 developmental biology, Tipiracil, Aged, business.industry, medicine.disease, chemistry, business, Thymine
Abstract: BACKGROUND: In RECOURSE (, trifluridine/tipiracil significantly improved overall survival and progression-free survival (PFS) versus placebo in patients with pretreated metastatic colorectal cancer (mCRC). PRECONNECT was designed to further characterise safety and clinical use of trifluridine/tipiracil. METHODS: In this ongoing, international, multicentre, open-label trial, patients with pretreated mCRC received oral trifluridine/tipiracil 35 mg/m2 twice daily on days 1-5 and 8-12 of each 28-day cycle. The primary endpoint was safety; secondary endpoints included PFS and quality of life (QoL). RESULTS: 793 patients (median age 62 years) from 13 countries received trifluridine/tipiracil for a median of 2.84 months (IQR 2.64). Adverse events (AEs) were experienced by 96.7%; the most common (≥20% of patients) were neutropaenia, asthenia/fatigue, nausea, anaemia and diarrhoea. Grade ≥3 AEs occurred in 73.9% of patients, with the most common being neutropaenia (39.1% of patients), anaemia (9.8%) and asthenia/fatigue (5.0%). Median PFS was 2.8 months (95% CI 2.7 to 2.9). Median time to Eastern Cooperative Oncology Group performance status deterioration (≥2) was 8.9 months (range 0.03-14.72). There was no clinically relevant change from baseline in QoL. CONCLUSIONS: PRECONNECT showed consistent results with the previously demonstrated safety and efficacy profile of trifluridine/tipiracil, with no new safety concerns identified. QoL was maintained during treatment. TRIAL REGISTRATION NUMBER: NCT03306394. ispartof: ESMO OPEN vol:5 issue:3 ispartof: location:England status: published
Published: 2020
Full Text: View/download PDF

18. Preoperative radiotherapy plus surgery versus surgery alone for patients with primary retroperitoneal sarcoma (EORTC-62092: STRASS): a multicentre, open-label, randomised, phase 3 trial

Author: Sandrine Marreaud, Hans Gelderblom, Pierre Meeus, Marco Rastrelli, Antonino De Paoli, Claudia Sangalli, Alessandro Gronchi, Elizabeth H. Baldini, Piotr Rutkowski, Jean-Yves Blay, Chandrajit P. Raut, Frits van Coevorden, Charles Honoré, Marco Fiore, Aisha Miah, Rick L. Haas, Angelo Paolo Dei Tos, Carol Jane Swallow, Dirk C. Strauss, Daphne Hompes, Eberhard Stoeckle, Sylvie Bonvalot, Cécile Le Péchoux, Jean Jacques Stelmes, Saskia Litière, Peter Chung, Stephan Stoldt, Université Paris sciences et lettres (PSL), Fondazione Ospedale San Camillo [Venezia] (IRCCS), Département d'hématologie [Gustave Roussy], Institut Gustave Roussy (IGR), Département de radiothérapie [Gustave Roussy], Princess Margaret Hospital, University of Toronto, Centre Léon Bérard [Lyon], Netherlands Cancer Institute (NKI), Antoni van Leeuwenhoek Hospital, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology (MCMCC), Veneto Institute of Oncology IOV-IRCCS [Padua, Italy], Dana-Farber Cancer Institute [Boston], Harvard Medical School [Boston] (HMS), Centro San Giovanni di Dio, Fatebenefratelli, Brescia (IRCCS), Università degli Studi di Brescia [Brescia], European Organisation for Research and Treatment of Cancer [Bruxelles] (EORTC), European Cancer Organisation [Bruxelles] (ECCO), and Leiden University Medical Center (LUMC)
Subjects: Male, medicine.medical_specialty, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Population, Phases of clinical research, Disease-Free Survival, 03 medical and health sciences, 0302 clinical medicine, Clinical endpoint, Medicine, Humans, 030212 general & internal medicine, Retroperitoneal Neoplasms, Adverse effect, education, ComputingMilieux_MISCELLANEOUS, Aged, education.field_of_study, Performance status, business.industry, Hazard ratio, Sarcoma, Middle Aged, Neoadjuvant Therapy, 3. Good health, Surgery, Clinical trial, Radiation therapy, Europe, Treatment Outcome, Oncology, 030220 oncology & carcinogenesis, North America, Female, Radiotherapy, Adjuvant, Radiotherapy, Conformal, business
Abstract: Summary Background Unlike for extremity sarcomas, the efficacy of radiotherapy for retroperitoneal sarcoma is not established. The aim of this study was to evaluate the impact of preoperative radiotherapy plus surgery versus surgery alone on abdominal recurrence-free survival. Methods EORTC-62092 is an open-label, randomised, phase 3 study done in 31 research institutions, hospitals, and cancer centres in 13 countries in Europe and North America. Adults (aged ≥18 years) with histologically documented, localised, primary retroperitoneal sarcoma that was operable and suitable for radiotherapy, who had not been previously treated and had a WHO performance status and American Society of Anesthesiologists score of 2 or lower, were centrally randomly assigned (1:1), using an interactive web response system and a minimisation algorithm, to receive either surgery alone or preoperative radiotherapy followed by surgery. Randomisation was stratified by hospital and performance status. Radiotherapy was delivered as 50·4 Gy (in 28 daily fractions of 1·8 Gy) in either 3D conformal radiotherapy or intensity modulated radiotherapy, and the objective of surgery was a macroscopically complete resection of the tumour mass with en-bloc organ resection as necessary. The primary endpoint was abdominal recurrence-free survival, as assessed by the investigator, and was analysed in the intention-to-treat population. Safety was analysed in all patients who started their allocated treatment. This trial is registered with ClinicalTrials.gov , NCT01344018 . Findings Between Jan 18, 2012 and April 10, 2017, 266 patients were enrolled, of whom 133 were randomly assigned to each group. The median follow-up was 43·1 months (IQR 28·8–59·2). 128 (96%) patients from the surgery alone group had surgery, and 119 (89%) patients in the radiotherapy and surgery group had both radiotherapy and surgery. Median abdominal recurrence-free survival was 4·5 years (95% CI 3·9 to not estimable) in the radiotherapy plus surgery group and 5·0 years (3·4 to not estimable) in the surgery only group (hazard ratio 1·01, 95% CI 0·71–1·44; log rank p=0·95). The most common grade 3–4 adverse events were lymphopenia (98 [77%] of 127 patients in the radiotherapy plus surgery group vs one [1%] of 128 patients in the surgery alone group), anaemia (15 [12%] vs ten [8%]), and hypoalbuminaemia (15 [12%] vs five [4%]). Serious adverse events were reported in 30 (24%) of 127 patients in the radiotherapy plus surgery group, and in 13 (10%) of 128 patients in the surgery alone group. One (1%) of 127 patients in the radiotherapy plus surgery group died due to treatment-related serious adverse events (gastropleural fistula), and no patients in the surgery alone group died due to treatment-related serious adverse events. Interpretation Preoperative radiotherapy should not be considered as standard of care treatment for retroperitoneal sarcoma. Funding European Organisation for Research and Treatment of Cancer, and European Clinical Trials in Rare Sarcomas.
Published: 2020
Full Text: View/download PDF

19. Overall survival at 5 years of follow-up in a phase III trial comparing ipilimumab 10 mg/kg with 3 mg/kg in patients with advanced melanoma

Author: Vanna Chiarion-Sileni, Céleste Lebbé, Catriona M. McNeil, Joanna Pikiel, Jean-Jacques Grob, Luc Thomas, Lars Bastholt, Andrzej Mackiewicz, Michele Maio, Omid Hamid, Virginia Ferraresi, Marta Nyakas, Caroline Robert, Michelle Del Vecchio, Burcin Simsek, Michael Smylie, Laurent Mortier, Dirk Schadendorf, Carmen Loquai, Inge Marie Svane, Ana Arance, Gabriella Liszkay, Fareeda Hosein, Piotr Rutkowski, Paolo A. Ascierto, Florent Grange, Christoph Hoeller, Brigitte Dréno, Ralf Gutzmer, Claus Garbe, Istituto Nazionale Tumori IRCCS Fondazione G. Pascale [Naples, Italy] (INT-FGP), IRCCS Istituto Nazionale dei Tumori [Milano], Poznan University of Medical Sciences [Poland] (PUMS), Institut Gustave Roussy (IGR), Université Paris-Sud - Paris 11 (UP11), Oncologie dermatologique, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Istituto Oncologico Veneto I.R.C.C.S. [Padova, Italy], Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona (UB), CIC Saint Louis (CIC-1427), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Herlev and Gentofte Hospital, Copenhagen University Hospital, Royal Prince Alfred Hospital [Camperdown, Australia] (RPAH), Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology (MCMCC), University Medical Center [Mainz], Thérapies Laser Assistées par l'Image pour l'Oncologie - U 1189 (ONCO-THAI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital Claude Huriez [Lille], CHU Lille, Odense University Hospital (OUH), Centre hospitalier universitaire de Nantes (CHU Nantes), University Hospital [Essen, Germany], German Cancer Consortium [Heidelberg] (DKTK), Eberhard Karls Universität Tübingen = Eberhard Karls University of Tuebingen, Oslo University Hospital [Oslo], Aix Marseille Université (AMU), Assistance Publique - Hôpitaux de Marseille (APHM), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), National Institute of Oncology [Budapest, Hungary], Cross Cancer Institute [Edmonton, AB, Canada], Medizinische Universität Wien = Medical University of Vienna, Regina Elena National Cancer Institute [Rome], Centre Hospitalier Universitaire de Reims (CHU Reims), Medizinische Hochschule Hannover (MHH), Wojewodzkie Centrum Oncologii [Gdańsk, Poland], Bristol-Myers Squibb [Princeton], University Hospital of Siena, and Malbec, Odile
Subjects: Cancer Research, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Immunology, Medizin, Ipilimumab, randomized trials, Gastroenterology, Asymptomatic, law.invention, immunology, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Internal medicine, medicine, Clinical endpoint, Immunology and Allergy, 030212 general & internal medicine, Adverse effect, RC254-282, Clinical/Translational Cancer Immunotherapy, Pharmacology, business.industry, Incidence (epidemiology), Melanoma, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, oncology, [SDV] Life Sciences [q-bio], Oncology, 030220 oncology & carcinogenesis, Molecular Medicine, medicine.symptom, business, Brain metastasis, medicine.drug
Abstract: BackgroundWe have previously reported significantly longer overall survival (OS) with ipilimumab 10 mg/kg versus ipilimumab 3 mg/kg in patients with advanced melanoma, with higher incidences of adverse events (AEs) at 10 mg/kg. This follow-up analysis reports a 5-year update of OS and safety.MethodsThis randomized, multicenter, double-blind, phase III trial included patients with untreated or previously treated unresectable stage III or IV melanoma. Patients were randomly assigned (1:1) to ipilimumab 10 mg/kg or 3 mg/kg every 3 weeks for 4 doses. The primary end point was OS.ResultsAt a minimum follow-up of 61 months, median OS was 15.7 months (95% CI 11.6 to 17.8) at 10 mg/kg and 11.5 months (95% CI 9.9 to 13.3) at 3 mg/kg (HR 0.84, 95% CI 0.71 to 0.99; p=0.04). In a subgroup analysis, median OS of patients with asymptomatic brain metastasis was 7.0 months (95% CI 4.0 to 12.8) in the 10 mg/kg group and 5.7 months (95% CI 4.2 to 7.0) in the 3 mg/kg group. In patients with wild-type or mutantBRAFtumors, median OS was 13.8 months (95% CI 10.2 to 17.0) and 33.2 months (95% CI 19.4 to 45.2) in the 10 mg/kg group, and 11.2 months (95% CI 9.2 to 13.8) and 19.7 months (95% CI 11.6 to 25.3) in the 3 mg/kg group, respectively. The incidence of grade 3/4 treatment-related AEs was 36% in the 10 mg/kg group vs 20% in the 3 mg/kg group, and deaths due to treatment-related AEs occurred in four (1%) and two patients (1%), respectively.ConclusionsThis 61-month follow-up of a phase III trial showed sustained long-term survival in patients with advanced melanoma who started metastatic treatment with ipilimumab monotherapy, and confirmed the significant benefit for those who received ipilimumab 10 mg/kg vs 3 mg/kg. These results suggest the emergence of a plateau in the OS curve, consistent with previous ipilimumab studies.Trial registration numberNCT01515189.
Published: 2020
Full Text: View/download PDF

20. Radiotherapy-Induced Changes in the Systemic Immune and Inflammation Parameters of Head and Neck Cancer Patients

Author: Udo S. Gaipl, Eric Andreas Rutten, Serge M. Candéias, Géza Sáfrány, Benjamin Frey, Enikő Kis, Katalin Lumniczky, Zsuzsa S Kocsis, Zsolt Jurányi, Enikő Noémi Bogdándi, Katalin Balázs, Christophe Badie, Piotr Widlak, Lourdes Cruz Garcia, Iwona Domińczyk, Department of Radiation Medicine, Centre for Radiation, Chemical and Environmental Hazards, Public Health England [London], Protéomique, Métaux et Différenciation (ProMD ), Laboratoire de Chimie et Biologie des Métaux (LCBM - UMR 5249), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology (MCMCC), Department of Radiation Oncology, Department of Radiobiology and Diagnostic Onco-Cytogenetics, Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])
Subjects: 0301 basic medicine, Oncology, Cancer Research, medicine.medical_specialty, regulatory T cell, Regulatory T cell, dendritic cell, medicine.medical_treatment, Inflammation, [SDV.CAN]Life Sciences [q-bio]/Cancer, lcsh:RC254-282, Article, Natural killer cell, 03 medical and health sciences, 0302 clinical medicine, Immune system, immune phenotyping, Medizinische Fakultät, Internal medicine, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], medicine, ddc:610, radiotherapy, business.industry, Head and neck cancer, PBMC, Dendritic cell, natural killer cell, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, Blood proteins, 3. Good health, Radiation therapy, 030104 developmental biology, medicine.anatomical_structure, [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, 030220 oncology & carcinogenesis, gene expression, head and neck cancer, medicine.symptom, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, plasma proteins
Abstract: International audience; Though radiotherapy is a local therapy, it has systemic effects mainly influencing immune and inflammation processes. This has important consequences in the long-term prognosis and therapy individualization. Our objective was to investigate immune and inflammation-related changes in the peripheral blood of head and neck cancer patients treated with radiotherapy. Peripheral blood cells, plasma and blood cell-derived RNA were isolated from 23 patients before and at two time points after radiotherapy and cellular immune parameters, plasma protein changes and gene expression alterations were studied. Increased regulatory T cells and increased CTLA4 and PD-1 expression on CD4 cells indicated an immune suppression induced by the malignant condition, which was accentuated by radiotherapy. Circulating dendritic cells were strongly elevated before treatment and were not affected by radiotherapy. Decreased endoglin levels in the plasma of patients before treatment were further decreased by radiotherapy. Expression of the FXDR, SESN1, GADD45, DDB2 and MDM2 radiation-response genes were altered in the peripheral blood cells of patients after radiotherapy. All changes were long-lasting, detectable one month after radiotherapy. In conclusion we demonstrated radiotherapy-induced changes in systemic immune parameters of head and neck cancer patients and proposed markers suitable for patient stratification worth investigating in larger patient cohorts.
Published: 2019
Full Text: View/download PDF

21. Addition of high-dose cytarabine to immunochemotherapy before autologous stem-cell transplantation in patients aged 65 years or younger with mantle cell lymphoma (MCL Younger): a randomised, open-label, phase 3 trial of the European Mantle Cell Lymphoma Network

Author: Georg Maschmeyer, Bernd Metzner, Corinne Haioun, Richard Delarue, Thomas Fischer, Ulrich Dührsen, Michal Szymczyk, Jan Walewski, Mathias Hänel, Michael Unterhalt, Catherine Thieblemont, Norma Peter, Kamal Bouabdallah, Christiane Pott, Michael Hallek, Vincent Ribrag, Stephan Stilgenbauer, André Bosly, Catherine Sebban, Josef Birkmann, Christian Schmidt, Marie-Hélène Delfau-Larue, Jürgen Finke, Wolfgang Hiddemann, Nicole Brousse, Elizabeth Macintyre, Gilles Salles, Pierre Feugier, Wolfram Klapper, Roswitha Forstpointner, Eva Hoster, Michael Kneba, Rene-Olivier Casasnovas, Martin Dreyling, Lothar Kanz, Reda Bouabdallah, Olivier Hermine, Imagine - Institut des maladies génétiques ( IMAGINE - U1163 ), Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ), Department of Internal Medicine III, University of Munich, Institute of Oncology, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology ( MCMCC ), CHU Dinant-Godinne UCL Namur, Internal Medicine III, Universität Ulm, APHP Hôpital Saint Louis, Institut Charles Gerhardt Montpellier - Institut de Chimie Moléculaire et des Matériaux de Montpellier ( ICGM ICMMM ), Université Montpellier 1 ( UM1 ) -Université Montpellier 2 - Sciences et Techniques ( UM2 ) -Ecole Nationale Supérieure de Chimie de Montpellier ( ENSCM ) -Université de Montpellier ( UM ) -Centre National de la Recherche Scientifique ( CNRS ), Département d'Hematologie, Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Second Medical Department, University Hospital Schleswig-Holstein, University of Cologne, Service d'hématologie [Hôpital Edouard Herriot - HCL], Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ), Nutrition-Génétique et Exposition aux Risques Environnementaux ( NGERE ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Lorraine ( UL ), Hématologie, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy ( IGR ) -Institut Gustave Roussy ( IGR ), Paracelsus Medical University, Ludwig-Maximilians University Hospital, Service d'hématologie clinique, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Klinikum Chemnitz, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), University Hospital Freiburg, Carl Thiem Hospital Cottbus, Université Mohamed Boudiaf de M'sila, Centre Léon Bérard [Lyon], Agence départementale d’architecture et d’urbanisme du Haut-Rhin ( ADAUHR ), University Hospital Essen, Medizinische Klinik, Hämatologie und Onkologie, Klinikum Ernst von Bergmann, Department of Internal Medicine II (Oncology, Hematology, Immunology, Rheumatology, Pulmonology), University Hospital Tuebingen, Service d'immuno-hématologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Laboratoire d'anatomie pathologique [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Department of Pathology, Hematopathology Section and Lymph Node Registry, Universityhospital Schleswig-Holstein, Campus Kiel, Institut Mondor de Recherche Biomédicale ( IMRB ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Service d'immunologie biologique, University Hospital Schleswig–Holstein, III. Medizinische Klinik, Technische Universität München [München] ( TUM ), Institut Imagine (UMR 1163), Laboratory of Cellular and Molecular Mechanisms of Hemathological Disorders and Therapeutic Implication, Maria Sklodowska-Curie Memorial Cancer Center, Institut Charles Gerhardt - Institut de Chimie Moléculaire et des Matériaux de Montpellier (ICG ICMMM), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM) - Université Montpellier 2 - Sciences et Techniques (UM2) - Université Montpellier 1 (UM1) - Centre National de la Recherche Scientifique (CNRS), Institut Paoli Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC) - Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Service de Radio-Oncologie [Lyon], Hospices Civils de Lyon - Centre Hospitalier Lyon Sud [Pierre Bénite], Hôpital Edouard Herriot, Hospices Civils de Lyon - Hôpital Edouard Herriot, Institut Gustave Roussy (IGR), Assistance publique - Hôpitaux de Paris (AP-HP) - Hôpital Henri Mondor - Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service d'Hématologie Clinique (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), University Medical Centre Freiburg, Centre Hospitalier Universitaire de Bordeaux, Agence départementale d’architecture et d’urbanisme du Haut-Rhin (ADAUHR), Laboratoire d'Informatique de l'Université du Maine (LIUM), Université du Maine (UM), Service d'hématologie biologique, Assistance publique - Hôpitaux de Paris (AP-HP) - Université Paris Descartes - Paris 5 (UPD5) - AP-HP Hôpital Necker - Enfants Malades [Paris], AP-HP Hôpital Necker - Enfants Malades [Paris], Service hématologie, Assistance publique - Hôpitaux de Paris (AP-HP) - Groupe Hospitalier Necker-Enfants Malades, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM) - IFR10 - Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), and Technische Universität München [München] (TUM)
Subjects: Adult, Male, medicine.medical_specialty, Vincristine, Transplantation Conditioning, Medizin, Lymphoma, Mantle-Cell, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, 03 medical and health sciences, 0302 clinical medicine, Autologous stem-cell transplantation, International Prognostic Index, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Treatment Failure, Cyclophosphamide, ComputingMilieux_MISCELLANEOUS, business.industry, Cytarabine, Hematopoietic Stem Cell Transplantation, General Medicine, Middle Aged, medicine.disease, Combined Modality Therapy, Surgery, Transplantation, Doxorubicin, 030220 oncology & carcinogenesis, Prednisone, Female, Rituximab, Mantle cell lymphoma, Immunotherapy, business, Immunosuppressive Agents, Febrile neutropenia, 030215 immunology, medicine.drug
Abstract: Summary Background Mantle cell lymphoma is characterised by a poor long-term prognosis. The European Mantle Cell Lymphoma Network aimed to investigate whether the introduction of high-dose cytarabine to immunochemotherapy before autologous stem-cell transplantation (ASCT) improves outcome. Methods This randomised, open-label, parallel-group, phase 3 trial was done in 128 haemato-oncological hospital departments or private practices in Germany, France, Belgium, and Poland. Patients aged 65 years or younger with untreated stage II–IV mantle cell lymphoma were centrally randomised (1:1), with computer-assisted random block selection, to receive either six courses of R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) followed by myeloablative radiochemotherapy and ASCT (control group), or six courses of alternating R-CHOP or R-DHAP (rituximab plus dexamethasone, high-dose cytarabine, and cisplatin) followed by a high-dose cytarabine-containing conditioning regimen and ASCT (cytarabine group). Patients were stratified by study group and international prognostic index. The primary outcome was time to treatment failure from randomisation to stable disease after at least four induction cycles, progression, or death from any cause. Patients with stage II–IV mantle cell lymphoma were included in the primary analysis if treatment was started according to randomisation. For safety analyses, patients were assessed according to the treatment actually started. This study is registered with ClinicalTrials.gov, number NCT00209222. Findings Of 497 patients (median age 55 years [IQR 49–60]) randomised from July 20, 2004, to March 18, 2010, 234 of 249 in the control group and 232 of 248 in the cytarabine group were included in the primary analysis. After a median follow-up of 6·1 years (95% CI 5·4–6·4), time to treatment failure was significantly longer in the cytarabine group (median 9·1 years [95% CI 6·3–not reached], 5 year rate 65% [95% CI 57–71]) than in the control group (3·9 years [3·2–4·4], 40% [33–46]; hazard ratio 0·56; p=0·038). During induction immunochemotherapy, patients who received high-dose cytarabine had increased grade 3 or 4 haematological toxicity (haemoglobin 71 [29%] of 241m vs 19 [8%] of 227 controls; platelets 176 [73%] of 240 vs 21 [9%] of 225), grade 3 or 4 febrile neutropenia (39 [17%] of 230 vs 19 [8%] of 224), and grade 1 or 2 renal toxicity (creatinine 102 [43%] of 236 vs 22 [10%] of 224). The number of ASCT-related deaths was similar (eight [3·4%]) in both groups. Interpretation Immunochemotherapy containing high-dose cytarabine followed by ASCT should be considered standard of care in patients aged 65 years or younger with mantle cell lymphoma. Funding European Commission, Lymphoma Research Foundation, and Roche.
Published: 2016
Full Text: View/download PDF

22. Five-year outcomes from a phase 3 METRIC study in patients with BRAF V600 E/K-mutant advanced or metastatic melanoma

Author: Mohammed M. Milhem, Peter Mohr, Paul Nathan, Piotr Rutkowski, Anthony D'Amelio, Peter Hersey, Felix Kiecker, Jochen Utikal, Lev V. Demidov, Caroline Robert, Reinhard Dummer, Claus Garbe, Dirk Schadendorf, Jessica C. Hassel, Bijoyesh Mookerjee, James Larkin, Keith T. Flaherty, Department of Dermatology (CHU Besançon), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), N.N. Blokhin Russian Cancer Research Center, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology (MCMCC), German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Novartis Pharmaceutical Corporation, University of Zurich, and Robert, Caroline
Subjects: 0301 basic medicine, Oncology, Male, Cancer Research, Skin Neoplasms, Time Factors, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Medizin, Phases of clinical research, Targeted therapy, 0302 clinical medicine, Antineoplastic Combined Chemotherapy Protocols, 1306 Cancer Research, Melanoma, Trametinib, Aged, 80 and over, Brain Neoplasms, MEK inhibitor, Hazard ratio, 10177 Dermatology Clinic, Middle Aged, Prognosis, 3. Good health, Dacarbazine, Survival Rate, 030220 oncology & carcinogenesis, 2730 Oncology, Female, medicine.drug, Adult, Proto-Oncogene Proteins B-raf, medicine.medical_specialty, Paclitaxel, Pyridones, 610 Medicine & health, Pyrimidinones, 03 medical and health sciences, Young Adult, Internal medicine, medicine, Humans, Adverse effect, Aged, Chemotherapy, business.industry, 030104 developmental biology, Mutation, business, Follow-Up Studies
Abstract: Background Primary findings from the METRIC (TMT212A2301) study demonstrated that trametinib improved progression-free survival (PFS) and overall survival (OS) compared with chemotherapy in patients with unresectable or metastatic cutaneous melanoma with a BRAF V600 E/K mutation. However, clinical data characterising the long-term use of these therapies in combination with BRAF inhibitors or as monotherapies are limited. Methods In this open-label, phase 3 study, 322 patients with BRAF V600 E/K–mutant metastatic melanoma were randomised in a 2:1 ratio to receive trametinib (2 mg orally, once daily; n = 214) or chemotherapy (dacarbazine [1000 mg/m2] or paclitaxel [175 mg/m2] intravenously, every 3 weeks; n = 108). Patients who progressed on chemotherapy were allowed to cross over and receive trametinib. Five-year results of efficacy and safety analyses are reported. Results The median PFS was 4.9 months in the trametinib arm versus 1.5 months in the chemotherapy arm (hazard ratio, 0.54; 95% confidence interval, 0.41–0.73). Landmark OS rates for trametinib versus chemotherapy arms at 1 year, 2 years and 5 years were 60.9% versus 49.6%, 32.0% versus 29.4% and 13.3% versus 17.0%, respectively. Most patients (n = 70 [65%]) from the chemotherapy arm crossed over to the trametinib arm early in their treatment. No unexpected adverse events were reported. Conclusions This 5-year follow-up of patients with BRAF V600 E/K–mutant metastatic melanoma on a targeted therapy demonstrates that long-term use of trametinib is possible with no new or unexpected adverse events. Some patients experienced long-term survival benefit with trametinib monotherapy (METRIC ClinicalTrials.gov number, NCT01245062.).
Published: 2018
Full Text: View/download PDF

23. Analysis of shared heritability in common disorders of the brain

Author: Brainstorm Consortium, Anttila, Verneri, Bulik-Sullivan, Brendan, Finucane, Hilary K, Walters, Raymond K, Bras, Jose, Duncan, Laramie, Escott-Price, Valentina, Falcone, Guido J, Gormley, Padhraig, Malik, Rainer, Patsopoulos, Nikolaos A, Ripke, Stephan, Wei, Zhi, Yu, Dongmei, Lee, Phil H, Turley, Patrick, Grenier-Boley, Benjamin, Chouraki, Vincent, Kamatani, Yoichiro, Berr, Claudine, Letenneur, Luc, Hannequin, Didier, Amouyel, Philippe, Boland, Anne, Deleuze, Jean-François, Duron, Emmanuelle, Vardarajan, Badri N, Reitz, Christiane, Goate, Alison M, Huentelman, Matthew J, Kamboh, M Ilyas, Larson, Eric B, Rogaeva, Ekaterina, St George-Hyslop, Peter, Hakonarson, Hakon, Kukull, Walter A, Farrer, Lindsay A, Barnes, Lisa L, Beach, Thomas G, Demirci, F Yesim, Head, Elizabeth, Hulette, Christine M, Jicha, Gregory A, Kauwe, John SK, Kaye, Jeffrey A, Leverenz, James B, Levey, Allan I, Lieberman, Andrew P, Pankratz, Vernon S, Poon, Wayne W, Quinn, Joseph F, Saykin, Andrew J, Schneider, Lon S, Smith, Amanda G, Sonnen, Joshua A, Stern, Robert A, Van Deerlin, Vivianna M, Van Eldik, Linda J, Harold, Denise, Russo, Giancarlo, Rubinsztein, David C, Bayer, Anthony, Tsolaki, Magda, Proitsi, Petra, Fox, Nick C, Hampel, Harald, Owen, Michael J, Mead, Simon, Passmore, Peter, Morgan, Kevin, Nöthen, Markus M, Rossor, Martin, Lupton, Michelle K, Hoffmann, Per, Kornhuber, Johannes, Lawlor, Brian, McQuillin, Andrew, Al-Chalabi, Ammar, Bis, Joshua C, Ruiz, Agustin, Boada, Mercè, Seshadri, Sudha, Beiser, Alexa, Rice, Kenneth, Van Der Lee, Sven J, De Jager, Philip L, Geschwind, Daniel H, Riemenschneider, Matthias, Riedel-Heller, Steffi, Rotter, Jerome I, Ransmayr, Gerhard, Hyman, Bradley T, Cruchaga, Carlos, Alegret, Montserrat, Winsvold, Bendik, Palta, Priit, Farh, Kai-How, Cuenca-Leon, Ester, Furlotte, Nicholas, Kurth, Tobias, Ligthart, Lannie, Terwindt, Gisela M, Freilinger, Tobias, Ran, Caroline, Gordon, Scott D, Borck, Guntram, Adams, Hieab HH, Lehtimäki, Terho, Wedenoja, Juho, Buring, Julie E, Schürks, Markus, Hrafnsdottir, Maria, Hottenga, Jouke-Jan, Penninx, Brenda, Artto, Ville, Kaunisto, Mari, Vepsäläinen, Salli, Martin, Nicholas G, Montgomery, Grant W, Kurki, Mitja I, Hämäläinen, Eija, Huang, Hailiang, Huang, Jie, Sandor, Cynthia, Webber, Caleb, Muller-Myhsok, Bertram, Schreiber, Stefan, Salomaa, Veikko, Loehrer, Elizabeth, Göbel, Hartmut, Macaya, Alfons, Pozo-Rosich, Patricia, Hansen, Thomas, Werge, Thomas, Kaprio, Jaakko, Metspalu, Andres, Kubisch, Christian, Ferrari, Michel D, Belin, Andrea C, Van Den Maagdenberg, Arn MJM, Zwart, John-Anker, Boomsma, Dorret, Eriksson, Nicholas, Olesen, Jes, Chasman, Daniel I, Nyholt, Dale R, Avbersek, Andreja, Baum, Larry, Berkovic, Samuel, Bradfield, Jonathan, Buono, Russell J, Catarino, Claudia B, Cossette, Patrick, De Jonghe, Peter, Depondt, Chantal, Dlugos, Dennis, Ferraro, Thomas N, French, Jacqueline, Hjalgrim, Helle, Jamnadas-Khoda, Jennifer, Kälviäinen, Reetta, Kunz, Wolfram S, Lerche, Holger, Leu, Costin, Lindhout, Dick, Lo, Warren, Lowenstein, Daniel, McCormack, Mark, Møller, Rikke S, Molloy, Anne, Ng, Ping-Wing, Oliver, Karen, Privitera, Michael, Radtke, Rodney, Ruppert, Ann-Kathrin, Sander, Thomas, Schachter, Steven, Schankin, Christoph, Scheffer, Ingrid, Schoch, Susanne, Sisodiya, Sanjay M, Smith, Philip, Sperling, Michael, Striano, Pasquale, Surges, Rainer, Thomas, G Neil, Visscher, Frank, Whelan, Christopher D, Zara, Federico, Heinzen, Erin L, Marson, Anthony, Becker, Felicitas, Stroink, Hans, Zimprich, Fritz, Gasser, Thomas, Gibbs, Raphael, Heutink, Peter, Martinez, Maria, Morris, Huw R, Sharma, Manu, Ryten, Mina, Mok, Kin Y, Pulit, Sara, Bevan, Steve, Holliday, Elizabeth, Attia, John, Battey, Thomas, Boncoraglio, Giorgio, Thijs, Vincent, Chen, Wei-Min, Mitchell, Braxton, Rothwell, Peter, Sharma, Pankaj, Sudlow, Cathie, Vicente, Astrid, Markus, Hugh, Kourkoulis, Christina, Pera, Joana, Raffeld, Miriam, Silliman, Scott, Boraska Perica, Vesna, Thornton, Laura M, Huckins, Laura M, William Rayner, N, Lewis, Cathryn M, Gratacos, Monica, Rybakowski, Filip, Keski-Rahkonen, Anna, Raevuori, Anu, Hudson, James I, Reichborn-Kjennerud, Ted, Monteleone, Palmiero, Karwautz, Andreas, Mannik, Katrin, Baker, Jessica H, O'Toole, Julie K, Trace, Sara E, Davis, Oliver SP, Helder, Sietske G, Ehrlich, Stefan, Herpertz-Dahlmann, Beate, Danner, Unna N, Van Elburg, Annemarie A, Clementi, Maurizio, Forzan, Monica, Docampo, Elisa, Lissowska, Jolanta, Hauser, Joanna, Tortorella, Alfonso, Maj, Mario, Gonidakis, Fragiskos, Tziouvas, Konstantinos, Papezova, Hana, Yilmaz, Zeynep, Wagner, Gudrun, Cohen-Woods, Sarah, Herms, Stefan, Julià, Antonio, Rabionet, Raquel, Dick, Danielle M, Ripatti, Samuli, Andreassen, Ole A, Espeseth, Thomas, Lundervold, Astri J, Steen, Vidar M, Pinto, Dalila, Scherer, Stephen W, Aschauer, Harald, Schosser, Alexandra, Alfredsson, Lars, Padyukov, Leonid, Halmi, Katherine A, Mitchell, James, Strober, Michael, Bergen, Andrew W, Kaye, Walter, Szatkiewicz, Jin Peng, Cormand, Bru, Ramos-Quiroga, Josep Antoni, Sánchez-Mora, Cristina, Ribasés, Marta, Casas, Miguel, Hervas, Amaia, Arranz, Maria Jesús, Haavik, Jan, Zayats, Tetyana, Johansson, Stefan, Williams, Nigel, Dempfle, Astrid, Rothenberger, Aribert, Kuntsi, Jonna, Oades, Robert D, Banaschewski, Tobias, Franke, Barbara, Buitelaar, Jan K, Arias Vasquez, Alejandro, Doyle, Alysa E, Reif, Andreas, Lesch, Klaus-Peter, Freitag, Christine, Rivero, Olga, Palmason, Haukur, Romanos, Marcel, Langley, Kate, Rietschel, Marcella, Witt, Stephanie H, Dalsgaard, Soeren, Børglum, Anders D, Waldman, Irwin, Wilmot, Beth, Molly, Nikolas, Bau, Claiton HD, Crosbie, Jennifer, Schachar, Russell, Loo, Sandra K, McGough, James J, Grevet, Eugenio H, Medland, Sarah E, Robinson, Elise, Weiss, Lauren A, Bacchelli, Elena, Bailey, Anthony, Bal, Vanessa, Battaglia, Agatino, Betancur, Catalina, Bolton, Patrick, Cantor, Rita, Celestino-Soper, Patrícia, Dawson, Geraldine, De Rubeis, Silvia, Duque, Frederico, Green, Andrew, Klauck, Sabine M, Leboyer, Marion, Levitt, Pat, Maestrini, Elena, Mane, Shrikant, De-Luca, Daniel Moreno, Parr, Jeremy, Regan, Regina, Reichenberg, Abraham, Sandin, Sven, Vorstman, Jacob, Wassink, Thomas, Wijsman, Ellen, Cook, Edwin, Santangelo, Susan, Delorme, Richard, Rogé, Bernadette, Magalhaes, Tiago, Arking, Dan, Schulze, Thomas G, Thompson, Robert C, Strohmaier, Jana, Matthews, Keith, Melle, Ingrid, Morris, Derek, Blackwood, Douglas, McIntosh, Andrew, Bergen, Sarah E, Schalling, Martin, Jamain, Stéphane, Maaser, Anna, Fischer, Sascha B, Reinbold, Céline S, Fullerton, Janice M, Guzman-Parra, José, Mayoral, Fermin, Schofield, Peter R, Cichon, Sven, Mühleisen, Thomas W, Degenhardt, Franziska, Schumacher, Johannes, Bauer, Michael, Mitchell, Philip B, Gershon, Elliot S, Rice, John, Potash, James B, Zandi, Peter P, Craddock, Nick, Ferrier, I Nicol, Alda, Martin, Rouleau, Guy A, Turecki, Gustavo, Ophoff, Roel, Pato, Carlos, Anjorin, Adebayo, Stahl, Eli, Leber, Markus, Czerski, Piotr M, Cruceanu, Cristiana, Jones, Ian R, Posthuma, Danielle, Andlauer, Till FM, Forstner, Andreas J, Streit, Fabian, Baune, Bernhard T, Air, Tracy, Sinnamon, Grant, Wray, Naomi R, MacIntyre, Donald J, Porteous, David, Homuth, Georg, Rivera, Margarita, Grove, Jakob, Middeldorp, Christel M, Hickie, Ian, Pergadia, Michele, Mehta, Divya, Smit, Johannes H, Jansen, Rick, De Geus, Eco, Dunn, Erin, Li, Qingqin S, Nauck, Matthias, Schoevers, Robert A, Beekman, Aartjan Tf, Knowles, James A, Viktorin, Alexander, Arnold, Paul, Barr, Cathy L, Bedoya-Berrio, Gabriel, Bienvenu, O Joseph, Brentani, Helena, Burton, Christie, Camarena, Beatriz, Cappi, Carolina, Cath, Danielle, Cavallini, Maria, Cusi, Daniele, Darrow, Sabrina, Denys, Damiaan, Derks, Eske M, Dietrich, Andrea, Fernandez, Thomas, Figee, Martijn, Freimer, Nelson, Gerber, Gloria, Grados, Marco, Greenberg, Erica, Hanna, Gregory L, Hartmann, Andreas, Hirschtritt, Matthew E, Hoekstra, Pieter J, Huang, Alden, Huyser, Chaim, Illmann, Cornelia, Jenike, Michael, Kuperman, Samuel, Leventhal, Bennett, Lochner, Christine, Lyon, Gholson J, Macciardi, Fabio, Madruga-Garrido, Marcos, Malaty, Irene A, Maras, Athanasios, McGrath, Lauren, Miguel, Eurípedes C, Mir, Pablo, Nestadt, Gerald, Nicolini, Humberto, Okun, Michael S, Pakstis, Andrew, Paschou, Peristera, Piacentini, John, Pittenger, Christopher, Plessen, Kerstin, Ramensky, Vasily, Ramos, Eliana M, Reus, Victor, Richter, Margaret A, Riddle, Mark A, Robertson, Mary M, Roessner, Veit, Rosário, Maria, Samuels, Jack F, Sandor, Paul, Stein, Dan J, Tsetsos, Fotis, Van Nieuwerburgh, Filip, Weatherall, Sarah, Wendland, Jens R, Wolanczyk, Tomasz, Worbe, Yulia, Zai, Gwyneth, Goes, Fernando S, McLaughlin, Nicole, Nestadt, Paul S, Grabe, Hans-Jorgen, Depienne, Christel, Konkashbaev, Anuar, Lanzagorta, Nuria, Valencia-Duarte, Ana, Bramon, Elvira, Buccola, Nancy, Cahn, Wiepke, Cairns, Murray, Chong, Siow A, Cohen, David, Crespo-Facorro, Benedicto, Crowley, James, Davidson, Michael, DeLisi, Lynn, Dinan, Timothy, Donohoe, Gary, Drapeau, Elodie, Duan, Jubao, Haan, Lieuwe, Hougaard, David, Karachanak-Yankova, Sena, Khrunin, Andrey, Klovins, Janis, Kučinskas, Vaidutis, Lee Chee Keong, Jimmy, Limborska, Svetlana, Loughland, Carmel, Lönnqvist, Jouko, Maher, Brion, Mattheisen, Manuel, McDonald, Colm, Murphy, Kieran C, Nenadic, Igor, Van Os, Jim, Pantelis, Christos, Pato, Michele, Petryshen, Tracey, Quested, Digby, Roussos, Panos, Sanders, Alan R, Schall, Ulrich, Schwab, Sibylle G, Sim, Kang, So, Hon-Cheong, Stögmann, Elisabeth, Subramaniam, Mythily, Toncheva, Draga, Waddington, John, Walters, James, Weiser, Mark, Cheng, Wei, Cloninger, Robert, Curtis, David, Gejman, Pablo V, Henskens, Frans, Mattingsdal, Morten, Oh, Sang-Yun, Scott, Rodney, Webb, Bradley, Breen, Gerome, Churchhouse, Claire, Bulik, Cynthia M, Daly, Mark, Dichgans, Martin, Faraone, Stephen V, Guerreiro, Rita, Holmans, Peter, Kendler, Kenneth S, Koeleman, Bobby, Mathews, Carol A, Price, Alkes, Scharf, Jeremiah, Sklar, Pamela, Williams, Julie, Wood, Nicholas W, Cotsapas, Chris, Palotie, Aarno, Smoller, Jordan W, Sullivan, Patrick, Rosand, Jonathan, Corvin, Aiden, Neale, Benjamin M, Schott, Jonathan M, Anney, Richard, Elia, Josephine, Grigoroiu-Serbanescu, Maria, Edenberg, Howard J, Murray, Robin, Massachusetts General Hospital [Boston], Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], UK Dementia Research Institute (UK DRI), University College of London [London] (UCL), School of Psychology [Cardiff University], Cardiff University, Institute for Stroke and Dementia Research (ISD), Klinikum der Universität [München]-Ludwig Maximilian University [Munich] (LMU), New Jersey Institute of Technology [Newark] (NJIT), Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 (RID-AGE), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), RIKEN Center for Integrative Medical Sciences [Yokohama] (RIKEN IMS), RIKEN - Institute of Physical and Chemical Research [Japon] (RIKEN), Neuropsychiatrie : recherche épidémiologique et clinique (PSNREC), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Laboratoire de Biotechnologie et Microbiologie Appliquée (LBMA), Université Bordeaux Segalen - Bordeaux 2-Institut National de la Recherche Agronomique (INRA), 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), Service de neurologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Institut de Biologie François JACOB (JACOB), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Gériatrie générale et aigüe [Paris], AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Columbia University [New York], Dpt of Neuroscience [New York], Icahn School of Medicine at Mount Sinai [New York] (MSSM), University of Pittsburgh (PITT), Pennsylvania Commonwealth System of Higher Education (PCSHE), University of Washington [Seattle], Tanz Center Research in Neurodegenerative Diseases [Toronto], University of Toronto, Children’s Hospital of Philadelphia (CHOP ), University of Kentucky (UK), School of medicine, Duke University [Durham], College of medicine, Brigham Young University (BYU), Oregon Health and Science University [Portland] (OHSU), Cleveland Clinic, Department of Neurology, Emory University [Atlanta, GA], Medical School, University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, Health sciences center, The University of New Mexico [Albuquerque], Institute for Memory Impairments and Neurological Disorders [Irvine], University of California [Irvine] (UC Irvine), University of California (UC)-University of California (UC), Indiana University - Purdue University Indianapolis (IUPUI), Indiana University System, Keck School of Medicine [Los Angeles], University of Southern California (USC), University of South Florida [Tampa] (USF), University of Utah School of Medicine [Salt Lake City], Boston University School of Medicine (BUSM), Boston University [Boston] (BU), Perelman School of Medicine, University of Pennsylvania, Dublin City University [Dublin] (DCU), Functional Genomics Center Zurich, Universität Zürich [Zürich] = University of Zurich (UZH)- Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), Cambridge Institute for Medical Research (CIMR), University of Cambridge [UK] (CAM), Aristotle University of Thessaloniki, Maurice Wohl Clinical Neuroscience Institut, King‘s College London, Dementia Research Centre [London] (DRC), Groupe de recherche clinique Alzheimer Precision Medicine (GRC 21 - APM), Sorbonne Université (SU), MRC Centre for Neuropsychiatric Genetics and Genomics, Medical Research Council-Cardiff University, MRC Prion Unit [London], Queen's University [Belfast] (QUB), School of Life Sciences, University of Nottingham, UK (UON), Rheinische Friedrich-Wilhelms-Universität Bonn, Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), QIMR Berghofer Medical Research Institute, Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), School of Medicine [Dublin], Trinity College Dublin, Department of Medicine, University of Texas Health Science Center, The University of Texas Health Science Center at Houston (UTHealth), School of Public Health [Boston], Erasmus University Medical Center [Rotterdam] (Erasmus MC), Columbia University Medical Center (CUMC), David Geffen School of Medicine [Los Angeles], University of California [Los Angeles] (UCLA), Saarland University [Saarbrücken], Universität Leipzig, School of Medicine [Los Angeles], Johannes Kepler Universität Linz - Johannes Kepler University Linz [Autriche] (JKU), Department of Neurology [Boston], Harvard Medical School [Boston] (HMS)-Massachusetts General Hospital [Boston], School of Medecine, Washington University in Saint Louis (WUSTL), Oslo University Hospital [Oslo], Institute for Molecular Medicine Finland [Helsinki] (FIMM), Helsinki Institute of Life Science (HiLIFE), Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Helsingin yliopisto = Helsingfors universitet = University of Helsinki, 23andMe Inc., Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Department of Biological Psychology [Amsterdam], Vrije Universiteit Amsterdam [Amsterdam] (VU), Leiden University Medical Center (LUMC), Universiteit Leiden, University-Hospital Munich-Großhadern [München], Karolinska Institutet [Stockholm], Universität Ulm - Ulm University [Ulm, Allemagne], Faculty of Medicine and Life Sciences [Tampere], University of Tampere [Finland], Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Brigham & Women’s Hospital [Boston] (BWH), Harvard Medical School [Boston] (HMS), Landspitali National University Hospital of Iceland, VU University Medical Center [Amsterdam], Boston VA Research Institute (BVARI), Department of Physiology, Anatomy and Genetics [Oxford], University of Oxford, Max Planck Institute of Psychiatry, Max-Planck-Gesellschaft, Christian-Albrechts-Universität zu Kiel (CAU), Institute of Clinical Molecular Biology, Kiel University, National Institute for Health and Welfare [Helsinki], Harvard T.H. Chan School of Public Health, Universitat Autònoma de Barcelona (UAB), Vall d'Hebron University Hospital [Barcelona], University of Tartu, Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), Center for Human and Clinical Genetics, Universiteit Leiden-Universiteit Leiden, University of Copenhagen = Københavns Universitet (UCPH), Institute of Health and Biomedical Innovation (IHBI), Queensland University of Technology [Brisbane] (QUT), Discipline of Psychiatry [Dublin], Trinity College Dublin-Trinity College Dublin, Institute of Neurology [London], The University of Hong Kong (HKU), University of Melbourne, Cooper Medical School of Rowan University [Camden] (CMSRU), Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM), University of Antwerp (UA), Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), New York University School of Medicine (NYU), New York University School of Medicine, NYU System (NYU)-NYU System (NYU), University of Eastern Finland, Universitätsklinikum Bonn (UKB), Hertie Institute for Clinical Brain Research [Tubingen], University of Tübingen, NIHR Biomedical Research Centre [London], Guy's and St Thomas' NHS Foundation Trust-King‘s College London, University Medical Center [Utrecht], Ohio State University [Columbus] (OSU), University of California [San Francisco] (UC San Francisco), University of California (UC), Royal College of Surgeons in Ireland (RCSI), University of Southern Denmark (SDU), United Christian Hospital [Hong Kong] (UCH), University of Cincinnati (UC), University of Cologne, Inselspital Bern, University of Wales, Jefferson University Hospitals, University of Liverpool, Medizinische Universität Wien = Medical University of Vienna, National Institutes of Health [Bethesda] (NIH), German Research Center for Neurodegenerative Diseases - Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Institut de Recherche en Santé Digestive (IRSD ), Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Lincoln, University of Newcastle [Callaghan, Australia] (UoN), Fondazione IRCCS Istituto Neurologico 'Carlo Besta', University of Virginia, University of Maryland [Baltimore County] (UMBC), University of Maryland System, Royal Holloway [University of London] (RHUL), University of Edinburgh, Universidade de Lisboa = University of Lisbon (ULISBOA), Uniwersytet Jagielloński w Krakowie = Jagiellonian University (UJ), University of Split, University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC), Center for Genomic Regulation (CRG-UPF), CIBER de Epidemiología y Salud Pública (CIBERESP), McLean Hospital [Belmont, Ma.], Norwegian Institute of Public Health [Oslo] (NIPH), Università degli Studi di Salerno = University of Salerno (UNISA), University of Bristol [Bristol], Technische Universität Dresden = Dresden University of Technology (TU Dresden), Rheinisch-Westfälische Technische Hochschule Aachen University (RWTH), Utrecht University [Utrecht], Azienda Ospedaliera di Padova, Université de Liège, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology (MCMCC), Università degli Studi di Perugia = University of Perugia (UNIPG), Università degli studi della Campania 'Luigi Vanvitelli' = University of the Study of Campania Luigi Vanvitelli, National and Kapodistrian University of Athens (NKUA), Charles University [Prague] (CU), SURFACES, Institut de recherches sur la catalyse et l'environnement de Lyon (IRCELYON), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Flinders University [Adelaide, Australia], Virginia Commonwealth University (VCU), University of Oslo (UiO), University of Bergen (UiB), Weill Medical College of Cornell University [New York], University of North Dakota [Grand Forks] (UND), Oregon Research Institute (ORI), University of California [San Diego] (UC San Diego), Universitat de Barcelona (UB), Centro de Investigación Biomédica en Red Salud Mental [Madrid] (CIBER-SAM), Hospital Universitario Mutua de Terrassa, School of Computer Science and Communication [Stockholm], Royal Institute of Technology [Stockholm] (KTH ), Jefferson (Philadelphia University + Thomas Jefferson University), University Medical Center Göttingen (UMG), Universität Heidelberg [Heidelberg] = Heidelberg University, Radboud University Medical Center [Nijmegen], Universitätsklinikum Frankfurt, Maastricht University [Maastricht], Institute of Psychological Medicine and Clinical Neurosciences, Aarhus University [Aarhus], University of Iowa [Iowa City], Universidade Federal do Rio Grande do Sul [Porto Alegre] (UFRGS), The Hospital for sick children [Toronto] (SickKids), Hospital de Clínicas de Porto Alegre (HCPA), Alma Mater Studiorum Università di Bologna [Bologna] (UNIBO), University of British Columbia (UBC), IRCCS Fondazione Stella Maris [Pisa], Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Neuroscience Paris Seine (NPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Universidade de Coimbra [Coimbra], Academic Centre on Rare Diseases (ACoRD), University College Dublin [Dublin] (UCD), Our Lady's Children's Hospital Crumlin (OLCHC), German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Children’s Hospital Los Angeles [Los Angeles], Yale University [New Haven], Brown University, Institute of Neuroscience [Newcastle] (ION), Newcastle University [Newcastle], Department of Medical Epidemiology and Biostatistics (MEB), Division of Medical Genetics [Seattle], University of Illinois [Chicago] (UIC), University of Illinois System, Maine Medical Center Research Institute (MMCRI), Génétique humaine et fonctions cognitives - Human Genetics and Cognitive Functions (GHFC (UMR_3571 / U-Pasteur_1)), Institut Pasteur [Paris] (IP)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Centre d’Etudes et de Recherches en Psychopathologie et Psychologie de la Santé (CERPPS), Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université de Toulouse (UT)-Toulouse Mind & Brain Institut (TMBI), Université de Toulouse (UT)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Johns Hopkins University School of Medicine [Baltimore], Ludwig Maximilian University [Munich] (LMU), University of Michigan System, Department of Genetic Epidemiology in Psychiatry [Mannhein], Universität Heidelberg [Heidelberg] = Heidelberg University-Central Institute of Mental Health Mannheim, University of Dundee, National University of Ireland [Galway] (NUI Galway), University Hospital Basel [Basel], Neuroscience Research Australia (NeuRA), Forschungszentrum Jülich GmbH | Centre de recherche de Juliers, Helmholtz-Gemeinschaft = Helmholtz Association, UNSW Faculty of Medicine [Sydney], University of New South Wales [Sydney] (UNSW), University of Chicago, Johns Hopkins University (JHU), Johns Hopkins Bloomberg School of Public Health [Baltimore], Dalhousie University [Halifax], Montreal Neurological Institute and Hospital, McGill University = Université McGill [Montréal, Canada], State University of New York (SUNY), University Hospital of Cologne [Cologne], University of Adelaide, James Cook University (JCU), Institute for Molecular Bioscience, University of Queensland [Brisbane], Greifswald University Hospital, The University of Sydney, University Medical Center Groningen [Groningen] (UMCG), University of Calgary, University Health Network, Universidad de Antioquia = University of Antioquia [Medellín, Colombia], Universidade de São Paulo = University of São Paulo (USP), Ospedale San Raffaele, University of Amsterdam [Amsterdam] (UvA), University of Groningen [Groningen], Yale School of Medicine [New Haven, Connecticut] (YSM), Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), University of Cape Town, Cold Spring Harbor Laboratory (CSHL), Universidad de Sevilla / University of Sevilla, University of Florida [Gainesville] (UF), University of Denver, Purdue University [West Lafayette], Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), Moscow Institute of Physics and Technology [Moscow] (MIPT), Sunnybrook Health Sciences Centre, Federal Institute of São Paulo (IFSP), Democritus University of Thrace (DUTH), Universiteit Gent = Ghent University (UGENT), Medical University of Warsaw - Poland, Sorbonne Université - Faculté de Médecine - Département d'Enseignement et de Recherche en Médecine Générale, Universitätsklinikum Essen [Universität Duisburg-Essen] (Uniklinik Essen), Vanderbilt University Medical Center [Nashville], Vanderbilt University [Nashville], Institute of Mental Health [Singapore], Universidad de Cantabria [Santander], Tel Aviv University (TAU), University College Cork (UCC), University of Rochester [USA], Statens Serum Institut [Copenhagen], Софийски университет = Sofia University, Russian Academy of Sciences [Moscow] (RAS), Latvian Biomedical Research and Study Centre [Rīga], Vilnius University [Vilnius], Nanyang Technological University [Singapour], Department of Life Sciences, Imperial College London, Jena University Hospital [Jena], Oxford University Hospitals NHS Trust, Schizophrenia Research Institute [Sydney], Faculty of Science, Medicine and Health [Wollongong], University of Wollongong [Australia], City University of Hong Kong [Hong Kong] (CUHK), Lawrence Berkeley National Laboratory [Berkeley] (LBNL), This work was supported by grants 1R01MH10764901 and 5U01MH09443203 from the National Institute of Mental Health, as well as the Orion Farmos Research Foundation (V.A.) and the Fannie and John Hertz Foundation (H.K.F.). Consortium specific funding is detailed in the supplementary materials ('Study-specific acknowledgments')., Brainstorm Consortium, University of Kentucky, University of California [Irvine] (UCI), University of California-University of California, University of Pennsylvania [Philadelphia], Alzheimer Precision Medicine [CHU Pitié-Salpétriêre] (GRC 21 AMP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Universität Leipzig [Leipzig], Johannes Kepler University Linz [Linz] (JKU), University of Helsinki-University of Helsinki, University of Helsinki, University of Oxford [Oxford], University of Copenhagen = Københavns Universitet (KU), University of California [San Francisco] (UCSF), University of California, Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Newcastle [Australia] (UoN), University of Virginia [Charlottesville], Universidade de Lisboa (ULISBOA), Università degli Studi di Salerno (UNISA), Rheinisch-Westfälische Technische Hochschule Aachen (RWTH), Università degli Studi di Perugia (UNIPG), Università degli studi della Campania 'Luigi Vanvitelli', Universität Heidelberg [Heidelberg], Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris]-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Universität Heidelberg [Heidelberg]-Central Institute of Mental Health Mannheim, VU University Amsterdam, Universidade de São Paulo (USP), Yale University School of Medicine, Universidad de Sevilla, Universiteit Gent = Ghent University [Belgium] (UGENT), Service de Psychiatrie de l'Enfant et de l'Adolescent [CHU Pitié-Salpêtrière] (SPEA), Tel Aviv University [Tel Aviv], University of Sofia, Anttila, Verneri, Bulik-Sullivan, Brendan, Finucane, Hilary K., Walters, Raymond K., Bras, Jose, Duncan, Laramie, Escott-Price, Valentina, Falcone, Guido J., Gormley, Padhraig, Malik, Rainer, Patsopoulos, Nikolaos A., Ripke, Stephan, Wei, Zhi, Yu, Dongmei, Lee, Phil H., Turley, Patrick, Grenier-Boley, Benjamin, Chouraki, Vincent, Kamatani, Yoichiro, Berr, Claudine, Letenneur, Luc, Hannequin, Didier, Amouyel, Philippe, Boland, Anne, Deleuze, Jean-Françoi, Duron, Emmanuelle, Vardarajan, Badri N., Reitz, Christiane, Goate, Alison M., Huentelman, Matthew J., Ilyas Kamboh, M., Larson, Eric B., Rogaeva, Ekaterina, George-Hyslop, Peter St, Hakonarson, Hakon, Kukull, Walter A., Farrer, Lindsay A., Barnes, Lisa L., Beach, Thomas G., Yesim Demirci, F., Head, Elizabeth, Hulette, Christine M., Jicha, Gregory A., Kauwe, John S.K., Kaye, Jeffrey A., Leverenz, James B., Levey, Allan I., Lieberman, Andrew P., Pankratz, Vernon S., Poon, Wayne W., Quinn, Joseph F., Saykin, Andrew J., Schneider, Lon S., Smith, Amanda G., Sonnen, Joshua A., Stern, Robert A., Van Deerlin, Vivianna M., Van Eldik, Linda J., Harold, Denise, Russo, Giancarlo, Rubinsztein, David C., Bayer, Anthony, Tsolaki, Magda, Proitsi, Petra, Fox, Nick C., Hampel, Harald, Owen, Michael J., Mead, Simon, Passmore, Peter, Morgan, Kevin, Nöthen, Markus M., Rossor, Martin, Lupton, Michelle K., Hoffmann, Per, Kornhuber, Johanne, Lawlor, Brian, McQuillin, Andrew, Al-Chalabi, Ammar, Bis, Joshua C., Ruiz, Agustin, Boada, Mercè, Seshadri, Sudha, Beiser, Alexa, Rice, Kenneth, Van Der Lee, Sven J., De Jager, Philip L., Geschwind, Daniel H., Riemenschneider, Matthia, Riedel-Heller, Steffi, Rotter, Jerome I., Ransmayr, Gerhard, Hyman, Bradley T., Cruchaga, Carlo, Alegret, Montserrat, Winsvold, Bendik, Palta, Priit, Farh, Kai-How, Cuenca-Leon, Ester, Furlotte, Nichola, Kurth, Tobia, Ligthart, Lannie, Terwindt, Gisela M., Freilinger, Tobia, Ran, Caroline, Gordon, Scott D., Borck, Guntram, Adams, Hieab H.H., Lehtimäki, Terho, Wedenoja, Juho, Buring, Julie E., Schürks, Marku, Hrafnsdottir, Maria, Hottenga, Jouke-Jan, Penninx, Brenda, Artto, Ville, Kaunisto, Mari, Vepsäläinen, Salli, Martin, Nicholas G., Montgomery, Grant W., Kurki, Mitja I., Hämäläinen, Eija, Huang, Hailiang, Huang, Jie, Sandor, Cynthia, Webber, Caleb, Muller-Myhsok, Bertram, Schreiber, Stefan, Salomaa, Veikko, Loehrer, Elizabeth, Göbel, Hartmut, Macaya, Alfon, Pozo-Rosich, Patricia, Hansen, Thoma, Werge, Thoma, Kaprio, Jaakko, Metspalu, Andre, Kubisch, Christian, Ferrari, Michel D., Belin, Andrea C., Van Den Maagdenberg, Arn M. J. M., Zwart, John-Anker, Boomsma, Dorret, Eriksson, Nichola, Olesen, Je, Chasman, Daniel I., Nyholt, Dale R., Avbersek, Andreja, Baum, Larry, Berkovic, Samuel, Bradfield, Jonathan, Buono, Russell, Catarino, Claudia B., Cossette, Patrick, De Jonghe, Peter, Depondt, Chantal, Dlugos, Denni, Ferraro, Thomas N., French, Jacqueline, Hjalgrim, Helle, Jamnadas-Khoda, Jennifer, Kälviäinen, Reetta, Kunz, Wolfram S., Lerche, Holger, Leu, Costin, Lindhout, Dick, Lo, Warren, Lowenstein, Daniel, McCormack, Mark, Møller, Rikke S., Molloy, Anne, Ng, Ping-Wing, Oliver, Karen, Privitera, Michael, Radtke, Rodney, Ruppert, Ann-Kathrin, Sander, Thoma, Schachter, Steven, Schankin, Christoph, Scheffer, Ingrid, Schoch, Susanne, Sisodiya, Sanjay M., Smith, Philip, Sperling, Michael, Striano, Pasquale, Surges, Rainer, Neil Thomas, G., Visscher, Frank, Whelan, Christopher D., Zara, Federico, Heinzen, Erin L., Marson, Anthony, Becker, Felicita, Stroink, Han, Zimprich, Fritz, Gasser, Thoma, Gibbs, Raphael, Heutink, Peter, Martinez, Maria, Morris, Huw R., Sharma, Manu, Ryten, Mina, Mok, Kin Y., Pulit, Sara, Bevan, Steve, Holliday, Elizabeth, Attia, John, Battey, Thoma, Boncoraglio, Giorgio, Thijs, Vincent, Chen, Wei-Min, Mitchell, Braxton, Rothwell, Peter, Sharma, Pankaj, Sudlow, Cathie, Vicente, Astrid, Markus, Hugh, Kourkoulis, Christina, Pera, Joana, Raffeld, Miriam, Silliman, Scott, Perica, Vesna Boraska, Thornton, Laura M., Huckins, Laura M., William Rayner, N., Lewis, Cathryn M., Gratacos, Monica, Rybakowski, Filip, Keski-Rahkonen, Anna, Raevuori, Anu, Hudson, James I., Reichborn-Kjennerud, Ted, Monteleone, Palmiero, Karwautz, Andrea, Mannik, Katrin, Baker, Jessica H., O'Toole, Julie K., Trace, Sara E., Davis, Oliver S. P., Helder, Sietske G., Ehrlich, Stefan, Herpertz-Dahlmann, Beate, Danner, Unna N., Van Elburg, Annemarie A., Clementi, Maurizio, Forzan, Monica, Docampo, Elisa, Lissowska, Jolanta, Hauser, Joanna, Tortorella, Alfonso, Maj, Mario, Gonidakis, Fragisko, Tziouvas, Konstantino, Papezova, Hana, Yilmaz, Zeynep, Wagner, Gudrun, Cohen-Woods, Sarah, Herms, Stefan, Julia, Antonio, Rabionet, Raquel, Dick, Danielle M., Ripatti, Samuli, Andreassen, Ole A., Espeseth, Thoma, Lundervold, Astri J., Steen, Vidar M., Pinto, Dalila, Scherer, Stephen W., Aschauer, Harald, Schosser, Alexandra, Alfredsson, Lar, Padyukov, Leonid, Halmi, Katherine A., Mitchell, Jame, Strober, Michael, Bergen, Andrew W., Kaye, Walter, Szatkiewicz, Jin Peng, Cormand, Bru, Ramos-Quiroga, Josep Antoni, Sánchez-Mora, Cristina, Ribasés, Marta, Casas, Miguel, Hervas, Amaia, Arranz, Maria Jesú, Haavik, Jan, Zayats, Tetyana, Johansson, Stefan, Williams, Nigel, Dempfle, Astrid, Rothenberger, Aribert, Kuntsi, Jonna, Oades, Robert D., Banaschewski, Tobia, Franke, Barbara, Buitelaar, Jan K., Vasquez, Alejandro Aria, Doyle, Alysa E., Reif, Andrea, Lesch, Klaus-Peter, Freitag, Christine, Rivero, Olga, Palmason, Haukur, Romanos, Marcel, Langley, Kate, Rietschel, Marcella, Witt, Stephanie H., Dalsgaard, Soeren, Børglum, Anders D., Waldman, Irwin, Wilmot, Beth, Molly, Nikola, Bau, Claiton H.D., Crosbie, Jennifer, Schachar, Russell, Loo, Sandra K., McGough, James J., Grevet, Eugenio H., Medland, Sarah E., Robinson, Elise, Weiss, Lauren A., Bacchelli, Elena, Bailey, Anthony, Bal, Vanessa, Battaglia, Agatino, Betancur, Catalina, Bolton, Patrick, Cantor, Rita, Celestino-Soper, Patrícia, Dawson, Geraldine, De Rubeis, Silvia, Duque, Frederico, Green, Andrew, Klauck, Sabine M., Leboyer, Marion, Levitt, Pat, Maestrini, Elena, Mane, Shrikant, Moreno-De-Luca, Daniel, Parr, Jeremy, Regan, Regina, Reichenberg, Abraham, Sandin, Sven, Vorstman, Jacob, Wassink, Thoma, Wijsman, Ellen, Cook, Edwin, Santangelo, Susan, Delorme, Richard, Roge, Bernadette, Magalhaes, Tiago, Arking, Dan, Schulze, Thomas G., Thompson, Robert C., Strohmaier, Jana, Matthews, Keith, Melle, Ingrid, Morris, Derek, Blackwood, Dougla, McIntosh, Andrew, Bergen, Sarah E., Schalling, Martin, Jamain, Stéphane, Maaser, Anna, Fischer, Sascha B., Reinbold, Céline S., Fullerton, Janice M., Guzman-Parra, José, Mayoral, Fermin, Schofield, Peter R., Cichon, Sven, Mühleisen, Thomas W., Degenhardt, Franziska, Schumacher, Johanne, Bauer, Michael, Mitchell, Philip B., Gershon, Elliot S., Rice, John, Potash, James B., Zandi, Peter P., Craddock, Nick, Nicol Ferrier, I., Alda, Martin, Rouleau, Guy A., Turecki, Gustavo, Ophoff, Roel, Pato, Carlo, Anjorin, Adebayo, Stahl, Eli, Leber, Marku, Czerski, Piotr M., Cruceanu, Cristiana, Jones, Ian R., Posthuma, Danielle, Andlauer, Till F.M., Forstner, Andreas J., Streit, Fabian, Baune, Bernhard T., Air, Tracy, Sinnamon, Grant, Wray, Naomi R., MacIntyre, Donald J., Porteous, David, Homuth, Georg, Rivera, Margarita, Grove, Jakob, Middeldorp, Christel M., Hickie, Ian, Pergadia, Michele, Mehta, Divya, Smit, Johannes H., Jansen, Rick, De Geus, Eco, Dunn, Erin, Li, Qingqin S., Nauck, Matthia, Schoevers, Robert A., Beekman, Aartjan TF, Knowles, James A., Viktorin, Alexander, Arnold, Paul, Barr, Cathy L., Bedoya-Berrio, Gabriel, Joseph Bienvenu, O., Brentani, Helena, Burton, Christie, Camarena, Beatriz, Cappi, Carolina, Cath, Danielle, Cavallini, Maria, Cusi, Daniele, Darrow, Sabrina, Denys, Damiaan, Derks, Eske M., Dietrich, Andrea, Fernandez, Thoma, Figee, Martijn, Freimer, Nelson, Gerber, Gloria, Grados, Marco, Greenberg, Erica, Hanna, Gregory L., Hartmann, Andrea, Hirschtritt, Matthew E., Hoekstra, Pieter J., Huang, Alden, Huyser, Chaim, Illmann, Cornelia, Jenike, Michael, Kuperman, Samuel, Leventhal, Bennett, Lochner, Christine, Lyon, Gholson J., Macciardi, Fabio, Madruga-Garrido, Marco, Malaty, Irene A., Maras, Athanasio, McGrath, Lauren, Miguel, Eurípedes C., Mir, Pablo, Nestadt, Gerald, Nicolini, Humberto, Okun, Michael S., Pakstis, Andrew, Paschou, Peristera, Piacentini, John, Pittenger, Christopher, Plessen, Kerstin, Ramensky, Vasily, Ramos, Eliana M., Reus, Victor, Richter, Margaret A., Riddle, Mark A., Robertson, Mary M., Roessner, Veit, Rosário, Maria, Samuels, Jack F., Sandor, Paul, Stein, Dan J., Tsetsos, Foti, Van Nieuwerburgh, Filip, Weatherall, Sarah, Wendland, Jens R., Wolanczyk, Tomasz, Worbe, Yulia, Zai, Gwyneth, Goes, Fernando S., McLaughlin, Nicole, Nestadt, Paul S., Grabe, Hans-Jorgen, Depienne, Christel, Konkashbaev, Anuar, Lanzagorta, Nuria, Valencia-Duarte, Ana, Bramon, Elvira, Buccola, Nancy, Cahn, Wiepke, Cairns, Murray, Chong, Siow A., Cohen, David, Crespo-Facorro, Benedicto, Crowley, Jame, Davidson, Michael, DeLisi, Lynn, Dinan, Timothy, Donohoe, Gary, Drapeau, Elodie, Duan, Jubao, Haan, Lieuwe, Hougaard, David, Karachanak-Yankova, Sena, Khrunin, Andrey, Klovins, Jani, Kučinskas, Vaiduti, Keong, Jimmy Lee Chee, Limborska, Svetlana, Loughland, Carmel, Lönnqvist, Jouko, Maher, Brion, Mattheisen, Manuel, McDonald, Colm, Murphy, Kieran C., Nenadic, Igor, Van Os, Jim, Pantelis, Christo, Pato, Michele, Petryshen, Tracey, Quested, Digby, Roussos, Pano, Sanders, Alan R., Schall, Ulrich, Schwab, Sibylle G., Sim, Kang, So, Hon-Cheong, Stögmann, Elisabeth, Subramaniam, Mythily, Toncheva, Draga, Waddington, John, Walters, Jame, Weiser, Mark, Cheng, Wei, Cloninger, Robert, Curtis, David, Gejman, Pablo V., Henskens, Fran, Mattingsdal, Morten, Oh, Sang-Yun, Scott, Rodney, Webb, Bradley, Breen, Gerome, Churchhouse, Claire, Bulik, Cynthia M., Daly, Mark, Dichgans, Martin, Faraone, Stephen V., Guerreiro, Rita, Holmans, Peter, Kendler, Kenneth S., Koeleman, Bobby, Mathews, Carol A., Price, Alke, Scharf, Jeremiah, Sklar, Pamela, Williams, Julie, Wood, Nicholas W., Cotsapas, Chri, Palotie, Aarno, Smoller, Jordan W., Sullivan, Patrick, Rosand, Jonathan, Corvin, Aiden, Neale, Benjamin M., Epidemiology, Radiology & Nuclear Medicine, Anttila, V, Bulik-Sullivan, B, Finucane, H, Walters, R, Bras, J, Duncan, L, Escott-Price, V, Falcone, G, Gormley, P, Malik, R, Patsopoulos, N, Ripke, S, Wei, Z, Yu, D, Lee, P, Turley, P, Grenier-Boley, B, Chouraki, V, Kamatani, Y, Berr, C, Letenneur, L, Hannequin, D, Amouyel, P, Boland, A, Deleuze, J, Duron, E, Vardarajan, B, Reitz, C, Goate, A, Huentelman, M, Ilyas Kamboh, M, Larson, E, Rogaeva, E, George-Hyslop, P, Hakonarson, H, Kukull, W, Farrer, L, Barnes, L, Beach, T, Yesim Demirci, F, Head, E, Hulette, C, Jicha, G, Kauwe, J, Kaye, J, Leverenz, J, Levey, A, Lieberman, A, Pankratz, V, Poon, W, Quinn, J, Saykin, A, Schneider, L, Smith, A, Sonnen, J, Stern, R, Van Deerlin, V, Van Eldik, L, Harold, D, Russo, G, Rubinsztein, D, Bayer, A, Tsolaki, M, Proitsi, P, Fox, N, Hampel, H, Owen, M, Mead, S, Passmore, P, Morgan, K, Nöthen, M, Rossor, M, Lupton, M, Hoffmann, P, Kornhuber, J, Lawlor, B, Mcquillin, A, Al-Chalabi, A, Bis, J, Ruiz, A, Boada, M, Seshadri, S, Beiser, A, Rice, K, Van Der Lee, S, De Jager, P, Geschwind, D, Riemenschneider, M, Riedel-Heller, S, Rotter, J, Ransmayr, G, Hyman, B, Cruchaga, C, Alegret, M, Winsvold, B, Palta, P, Farh, K, Cuenca-Leon, E, Furlotte, N, Kurth, T, Ligthart, L, Terwindt, G, Freilinger, T, Ran, C, Gordon, S, Borck, G, Adams, H, Lehtimäki, T, Wedenoja, J, Buring, J, Schürks, M, Hrafnsdottir, M, Hottenga, J, Penninx, B, Artto, V, Kaunisto, M, Vepsäläinen, S, Martin, N, Montgomery, G, Kurki, M, Hämäläinen, E, Huang, H, Huang, J, Sandor, C, Webber, C, Muller-Myhsok, B, Schreiber, S, Salomaa, V, Loehrer, E, Göbel, H, Macaya, A, Pozo-Rosich, P, Hansen, T, Werge, T, Kaprio, J, Metspalu, A, Kubisch, C, Ferrari, M, Belin, A, Van Den Maagdenberg, A, Zwart, J, Boomsma, D, Eriksson, N, Olesen, J, Chasman, D, Nyholt, D, Avbersek, A, Baum, L, Berkovic, S, Bradfield, J, Buono, R, Catarino, C, Cossette, P, De Jonghe, P, Depondt, C, Dlugos, D, Ferraro, T, French, J, Hjalgrim, H, Jamnadas-Khoda, J, Kälviäinen, R, Kunz, W, Lerche, H, Leu, C, Lindhout, D, Lo, W, Lowenstein, D, Mccormack, M, Møller, R, Molloy, A, Ng, P, Oliver, K, Privitera, M, Radtke, R, Ruppert, A, Sander, T, Schachter, S, Schankin, C, Scheffer, I, Schoch, S, Sisodiya, S, Smith, P, Sperling, M, Striano, P, Surges, R, Neil Thomas, G, Visscher, F, Whelan, C, Zara, F, Heinzen, E, Marson, A, Becker, F, Stroink, H, Zimprich, F, Gasser, T, Gibbs, R, Heutink, P, Martinez, M, Morris, H, Sharma, M, Ryten, M, Mok, K, Pulit, S, Bevan, S, Holliday, E, Attia, J, Battey, T, Boncoraglio, G, Thijs, V, Chen, W, Mitchell, B, Rothwell, P, Sharma, P, Sudlow, C, Vicente, A, Markus, H, Kourkoulis, C, Pera, J, Raffeld, M, Silliman, S, Perica, V, Thornton, L, Huckins, L, William Rayner, N, Lewis, C, Gratacos, M, Rybakowski, F, Keski-Rahkonen, A, Raevuori, A, Hudson, J, Reichborn-Kjennerud, T, Monteleone, P, Karwautz, A, Mannik, K, Baker, J, O'Toole, J, Trace, S, Davis, O, Helder, S, Ehrlich, S, Herpertz-Dahlmann, B, Danner, U, Van Elburg, A, Clementi, M, Forzan, M, Docampo, E, Lissowska, J, Hauser, J, Tortorella, A, Maj, M, Gonidakis, F, Tziouvas, K, Papezova, H, Yilmaz, Z, Wagner, G, Cohen-Woods, S, Herms, S, Julia, A, Rabionet, R, Dick, D, Ripatti, S, Andreassen, O, Espeseth, T, Lundervold, A, Steen, V, Pinto, D, Scherer, S, Aschauer, H, Schosser, A, Alfredsson, L, Padyukov, L, Halmi, K, Mitchell, J, Strober, M, Bergen, A, Kaye, W, Szatkiewicz, J, Cormand, B, Ramos-Quiroga, J, Sánchez-Mora, C, Ribasés, M, Casas, M, Hervas, A, Arranz, M, Haavik, J, Zayats, T, Johansson, S, Williams, N, Dempfle, A, Rothenberger, A, Kuntsi, J, Oades, R, Banaschewski, T, Franke, B, Buitelaar, J, Vasquez, A, Doyle, A, Reif, A, Lesch, K, Freitag, C, Rivero, O, Palmason, H, Romanos, M, Langley, K, Rietschel, M, Witt, S, Dalsgaard, S, Børglum, A, Waldman, I, Wilmot, B, Molly, N, Bau, C, Crosbie, J, Schachar, R, Loo, S, Mcgough, J, Grevet, E, Medland, S, Robinson, E, Weiss, L, Bacchelli, E, Bailey, A, Bal, V, Battaglia, A, Betancur, C, Bolton, P, Cantor, R, Celestino-Soper, P, Dawson, G, De Rubeis, S, Duque, F, Green, A, Klauck, S, Leboyer, M, Levitt, P, Maestrini, E, Mane, S, Moreno-De-Luca, D, Parr, J, Regan, R, Reichenberg, A, Sandin, S, Vorstman, J, Wassink, T, Wijsman, E, Cook, E, Santangelo, S, Delorme, R, Roge, B, Magalhaes, T, Arking, D, Schulze, T, Thompson, R, Strohmaier, J, Matthews, K, Melle, I, Morris, D, Blackwood, D, Mcintosh, A, Bergen, S, Schalling, M, Jamain, S, Maaser, A, Fischer, S, Reinbold, C, Fullerton, J, Guzman-Parra, J, Mayoral, F, Schofield, P, Cichon, S, Mühleisen, T, Degenhardt, F, Schumacher, J, Bauer, M, Mitchell, P, Gershon, E, Rice, J, Potash, J, Zandi, P, Craddock, N, Nicol Ferrier, I, Alda, M, Rouleau, G, Turecki, G, Ophoff, R, Pato, C, Anjorin, A, Stahl, E, Leber, M, Czerski, P, Cruceanu, C, Jones, I, Posthuma, D, Andlauer, T, Forstner, A, Streit, F, Baune, B, Air, T, Sinnamon, G, Wray, N, Macintyre, D, Porteous, D, Homuth, G, Rivera, M, Grove, J, Middeldorp, C, Hickie, I, Pergadia, M, Mehta, D, Smit, J, Jansen, R, De Geus, E, Dunn, E, Li, Q, Nauck, M, Schoevers, R, Beekman, A, Knowles, J, Viktorin, A, Arnold, P, Barr, C, Bedoya-Berrio, G, Joseph Bienvenu, O, Brentani, H, Burton, C, Camarena, B, Cappi, C, Cath, D, Cavallini, M, Cusi, D, Darrow, S, Denys, D, Derks, E, Dietrich, A, Fernandez, T, Figee, M, Freimer, N, Gerber, G, Grados, M, Greenberg, E, Hanna, G, Hartmann, A, Hirschtritt, M, Hoekstra, P, Huang, A, Huyser, C, Illmann, C, Jenike, M, Kuperman, S, Leventhal, B, Lochner, C, Lyon, G, Macciardi, F, Madruga-Garrido, M, Malaty, I, Maras, A, Mcgrath, L, Miguel, E, Mir, P, Nestadt, G, Nicolini, H, Okun, M, Pakstis, A, Paschou, P, Piacentini, J, Pittenger, C, Plessen, K, Ramensky, V, Ramos, E, Reus, V, Richter, M, Riddle, M, Robertson, M, Roessner, V, Rosário, M, Samuels, J, Sandor, P, Stein, D, Tsetsos, F, Van Nieuwerburgh, F, Weatherall, S, Wendland, J, Wolanczyk, T, Worbe, Y, Zai, G, Goes, F, Mclaughlin, N, Nestadt, P, Grabe, H, Depienne, C, Konkashbaev, A, Lanzagorta, N, Valencia-Duarte, A, Bramon, E, Buccola, N, Cahn, W, Cairns, M, Chong, S, Cohen, D, Crespo-Facorro, B, Crowley, J, Davidson, M, Delisi, L, Dinan, T, Donohoe, G, Drapeau, E, Duan, J, Haan, L, Hougaard, D, Karachanak-Yankova, S, Khrunin, A, Klovins, J, Kučinskas, V, Keong, J, Limborska, S, Loughland, C, Lönnqvist, J, Maher, B, Mattheisen, M, Mcdonald, C, Murphy, K, Nenadic, I, Van Os, J, Pantelis, C, Pato, M, Petryshen, T, Quested, D, Roussos, P, Sanders, A, Schall, U, Schwab, S, Sim, K, So, H, Stögmann, E, Subramaniam, M, Toncheva, D, Waddington, J, Walters, J, Weiser, M, Cheng, W, Cloninger, R, Curtis, D, Gejman, P, Henskens, F, Mattingsdal, M, Oh, S, Scott, R, Webb, B, Breen, G, Churchhouse, C, Bulik, C, Daly, M, Dichgans, M, Faraone, S, Guerreiro, R, Holmans, P, Kendler, K, Koeleman, B, Mathews, C, Price, A, Scharf, J, Sklar, P, Williams, J, Wood, N, Cotsapas, C, Palotie, A, Smoller, J, Sullivan, P, Rosand, J, Corvin, A, Neale, B, Kauwe, John S. K., Mcquillin, Andrew, Adams, Hieab H. H., Mccormack, Mark, Bau, Claiton H. D., Mcgough, James J., Mcintosh, Andrew, Andlauer, Till F. M., Macintyre, Donald J., Mcgrath, Lauren, Mclaughlin, Nicole, Delisi, Lynn, Mcdonald, Colm, Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Vrije universiteit = Free university of Amsterdam [Amsterdam] (VU), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement (Inserm U1167 - RID-AGE - Institut Pasteur), RIKEN Center for Integrative Medical Science, Neuropsychiatrie : recherche épidémiologique et clinique, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 1 (UM1)-Université de Montpellier (UM), University of South Florida (USF), University of Zürich [Zürich] (UZH)-Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology in Zürich [Zürich] (ETH Zürich), Alzheimer Precision Medicine GRC n°21 (APM), CHU Pitié-Salpêtrière [APHP], Cardiff University-Medical Research Council, 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), Johannes Kepler University Linz [linz] (JKU), Washington University in St Louis, Charité - Universitätsmedizin Berlin / Charite - University Medicine Berlin, Universitat Autònoma de Barcelona [Barcelona] (UAB), Hôpital Erasme (Bruxelles), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Jagiellonian University [Krakow] (UJ), Technische Universität Dresden (TUD), National and Kapodistrian University of Athens = University of Athens (NKUA | UoA), Charles University [Prague], Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), University of Bergen (UIB), University Medicine Goettingen, Università di Bologna [Bologna] (UNIBO), Forschungszentrum Jülich GmbH, UNSW Medicine [Sydney], McGill University, Universidad de Antioquia, University of Florida [Gainesville], Universiteit Gent [Ghent], Service Psychiatrie de l'Enfant et de l'Adolescent [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], University of Wollongong, Alzheimer Precision Medicine [CHU Pitié-Salpétriêre] (GRC 21 APM), Anttila, Verneri [0000-0002-0073-4675], Finucane, Hilary K [0000-0003-3864-9828], Walters, Raymond K [0000-0001-8422-6530], Duncan, Laramie [0000-0003-1131-661X], Escott-Price, Valentina [0000-0003-1784-5483], Falcone, Guido J [0000-0002-6407-0302], Gormley, Padhraig [0000-0002-8908-6968], Malik, Rainer [0000-0001-9212-2520], Ripke, Stephan [0000-0003-3622-835X], Wei, Zhi [0000-0001-6059-4267], Yu, Dongmei [0000-0001-7901-4365], Lee, Phil H [0000-0003-1770-3100], Breen, Gerome [0000-0003-2053-1792], Bulik, Cynthia M [0000-0001-7772-3264], Daly, Mark [0000-0002-0949-8752], Dichgans, Martin [0000-0002-0654-387X], Faraone, Stephen V [0000-0002-9217-3982], Holmans, Peter [0000-0003-0870-9412], Koeleman, Bobby [0000-0001-7749-182X], Mathews, Carol A [0000-0003-2208-7058], Sklar, Pamela [0000-0001-9715-4943], Williams, Julie [0000-0002-4069-0259], Wood, Nicholas W [0000-0002-9500-3348], Cotsapas, Chris [0000-0002-7772-5910], Smoller, Jordan W [0000-0002-0381-6334], Sullivan, Patrick [0000-0002-6619-873X], Rosand, Jonathan [0000-0002-1014-9138], Corvin, Aiden [0000-0001-6717-4089], Neale, Benjamin M [0000-0003-1513-6077], and Apollo - University of Cambridge Repository
Subjects: Etiology, [SDV]Life Sciences [q-bio], MESH: Brain Diseases, body-mass index, genetics [Mental Disorders], Disorders of the Brain, Risks factors, classification [Mental Disorders], MESH: Quantitative Trait, Heritable, MESH: Risk Factors, Risk Factors, MESH: Genetic Variation, alzheimers-disease, 610 Medicine & health, bipolar disorder, Brain Diseases, deficit hyperactivity disorder, Multidisciplinary, Mental Disorders, genetics [Brain Diseases], Brain Disease, Brain, Genetic Variation, Genome-Wide Association Study, Humans, Phenotype, Quantitative Trait, Heritable, Psychiatric Disorders, anorexia-nervosa, Mental Disorder, Psychiatric Genomics, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], long-term survival, Engineering sciences. Technology, Human, General Science & Technology, population-based twin, diagnosis [Mental Disorders], MESH: Phenotype, Neurological Disorders, Quantitative Trait, MD Multidisciplinary, MESH: Mental Disorders, diagnosis [Brain Diseases], Heritable, genetic correlations, [SDV.GEN]Life Sciences [q-bio]/Genetics, MESH: Humans, major depressive disorder, Risk Factor, Brain Diseases/classification, Brain Diseases/diagnosis, Brain Diseases/genetics, Mental Disorders/classification, Mental Disorders/diagnosis, Mental Disorders/genetics, classification [Brain Diseases], Perturbações do Desenvolvimento Infantil e Saúde Mental, ddc:320, MESH: Genome-Wide Association Study, genome-wide association, Brainstorm Consortium, Genetic Factors, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: INTRODUCTION Brain disorders may exhibit shared symptoms and substantial epidemiological comorbidity, inciting debate about their etiologic overlap. However, detailed study of phenotypes with different ages of onset, severity, and presentation poses a considerable challenge. Recently developed heritability methods allow us to accurately measure correlation of genome-wide common variant risk between two phenotypes from pools of different individuals and assess how connected they, or at least their genetic risks, are on the genomic level. We used genome-wide association data for 265,218 patients and 784,643 control participants, as well as 17 phenotypes from a total of 1,191,588 individuals, to quantify the degree of overlap for genetic risk factors of 25 common brain disorders. RATIONALE Over the past century, the classification of brain disorders has evolved to reflect the medical and scientific communities’ assessments of the presumed root causes of clinical phenomena such as behavioral change, loss of motor function, or alterations of consciousness. Directly observable phenomena (such as the presence of emboli, protein tangles, or unusual electrical activity patterns) generally define and separate neurological disorders from psychiatric disorders. Understanding the genetic underpinnings and categorical distinctions for brain disorders and related phenotypes may inform the search for their biological mechanisms. RESULTS Common variant risk for psychiatric disorders was shown to correlate significantly, especially among attention deficit hyperactivity disorder (ADHD), bipolar disorder, major depressive disorder (MDD), and schizophrenia. By contrast, neurological disorders appear more distinct from one another and from the psychiatric disorders, except for migraine, which was significantly correlated to ADHD, MDD, and Tourette syndrome. We demonstrate that, in the general population, the personality trait neuroticism is significantly correlated with almost every psychiatric disorder and migraine. We also identify significant genetic sharing between disorders and early life cognitive measures (e.g., years of education and college attainment) in the general population, demonstrating positive correlation with several psychiatric disorders (e.g., anorexia nervosa and bipolar disorder) and negative correlation with several neurological phenotypes (e.g., Alzheimer’s disease and ischemic stroke), even though the latter are considered to result from specific processes that occur later in life. Extensive simulations were also performed to inform how statistical power, diagnostic misclassification, and phenotypic heterogeneity influence genetic correlations. CONCLUSION The high degree of genetic correlation among many of the psychiatric disorders adds further evidence that their current clinical boundaries do not reflect distinct underlying pathogenic processes, at least on the genetic level. This suggests a deeply interconnected nature for psychiatric disorders, in contrast to neurological disorders, and underscores the need to refine psychiatric diagnostics. Genetically informed analyses may provide important “scaffolding” to support such restructuring of psychiatric nosology, which likely requires incorporating many levels of information. By contrast, we find limited evidence for widespread common genetic risk sharing among neurological disorders or across neurological and psychiatric disorders. We show that both psychiatric and neurological disorders have robust correlations with cognitive and personality measures. Further study is needed to evaluate whether overlapping genetic contributions to psychiatric pathology may influence treatment choices. Ultimately, such developments may pave the way toward reduced heterogeneity and improved diagnosis and treatment of psychiatric disorders.
Published: 2018
Full Text: View/download PDF

24. Influence of Confounding Factors on Radiation Dose Estimation Using In Vivo Validated Transcriptional Biomarkers

Author: Antoine Laval, Grzegorz Woźniak, Navita Somaiah, Piotr Widlak, Lucyna Ponge, Ellen M. Donovan, Grainne O’Brien, Leszek Miszczyk, Lone Gothard, Serge M. Candéias, Isabelle Testard, Elizabeth A. Ainsbury, Christophe Badie, Lourdes Cruz-Garcia, Sue Boyle, Centre for Radiation, Chemical and Environmental Hazards, Public Health England [London], Centre for Vision, Speech and Signal Processing (CVSSP), University of Surrey (UNIS), Institute for Cancer Research/Royal Marsden NHS Foundation Trust, Laboratoire de Chimie et Biologie des Métaux (LCBM - UMR 5249), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology (MCMCC), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)
Subjects: 0301 basic medicine, Adult, Lipopolysaccharides, Male, Curcumin, Epidemiology, Cyclin G1, Health, Toxicology and Mutagenesis, [SDV.CAN]Life Sciences [q-bio]/Cancer, Antineoplastic Agents, Pharmacology, Article, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, In vivo, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Neoplasms, Gene expression, Medicine, Humans, Radiology, Nuclear Medicine and imaging, Transcription factor, Aged, Regulation of gene expression, Aged, 80 and over, business.industry, Confounding, Cancer, Radiotherapy Dosage, Middle Aged, medicine.disease, Phosphoric Monoester Hydrolases, 3. Good health, Gene Expression Regulation, Neoplastic, 030104 developmental biology, chemistry, 13. Climate action, 030220 oncology & carcinogenesis, Case-Control Studies, Female, Radiotherapy, Intensity-Modulated, business, Ex vivo, Biomarkers
Abstract: International audience; For triage purposes following a nuclear accident, blood-based gene expression biomarkers can provide rapid dose estimates for a large number of individuals. Ionizing-radiation-responsive genes are regulated through the DNA damage-response pathway, which includes activation of multiple transcription factors. Modulators of this pathway could potentially affect the response of these biomarkers and consequently compromise accurate dose estimation calculations. In the present study, four potential confounding factors were selected: cancer condition, sex, simulated bacterial infection (lipopolysaccharide), and curcumin, an anti-inflammatory/antioxidant agent. Their potential influence on the transcriptional response to radiation of the genes CCNG1 and PHPT1, two biomarkers of radiation exposure ex vivo, was assessed. First, both CCNG1 and PHPT1 were detected in vivo in blood samples from radiotherapy patients and as such were validated as biomarkers of exposure. Importantly, their basal expression level was slightly but significantly affected in vivo by patients' cancer condition. Moreover, lipopolysaccharide stimulation of blood irradiated ex vivo led to a significant modification of CCNG1 and PHPT1 transcriptional response in a dose- and time-dependent manner with opposite regulatory effects. Curcumin also affected CCNG1 and PHPT1 transcriptional response counteracting some of the radiation induction. No differences were observed based on sex. Dose estimations calculated using linear regression were affected by lipopolysaccharide and curcumin. In conclusion, several confounding factors tested in this study can indeed modulate the transcriptional response of CCNG1 and PHPT1 and consequently can affect radiation exposure dose estimations but not to a level which should prevent the biomarkers' use for triage purposes.
Published: 2018
Full Text: View/download PDF

25. Lung cancer and socioeconomic status in a pooled analysis of case-control studies

Author: Hovanec, J., Siemiatycki, J., Conway, D. I., Olsson, A., Stücker, I., Guida, F., Jockel, K. -H., Pohlabeln, H., Ahrens, W., Brüske, I., Wichmann, H. -E., Gustavsson, P., Consonni, D., Merletti, F., Richiardi, L., Simonato, L., Fortes, C., Parent, M. -E., McLaughlin, J., Demers, P., L, i, M. T., Caporaso, N., Tardón, A., Zaridze, D., Szeszenia-Dabrowska, N., Rudnai, P., Lissowska, J., Fabianova, E., Field, J., Dumitru, R. S., Bencko, V., Foretova, L., Janout, V., Kromhout, H., Vermeulen, R., Boffetta, P., Straif, K., Schüz, J., Kendzia, B., Pesch, B., Brüning, T., Behrens, T., Hovanec, J. and Siemiatycki, J. and Conway, D.I. and Olsson, A. and Stücker, I. and Guida, F. and Jockel, K.-H. and Pohlabeln, H. and Ahrens, W. and Brüske, I. and Wichmann, H.-E. and Gustavsson, P. and Consonni, D. and Merletti, F. and Richiardi, L. and Simonato, L. and Fortes, C. and Parent, M.-E. and McLaughlin, J. and Demers, P. and Landi, M.T. and Caporaso, N. and Tardón, A. and Zaridze, D. and Szeszenia-Dabrowska, N. and Rudnai, P. and Lissowska, J. and Fabianova, E. and Field, J. and Dumitru, R.S. and Bencko, V. and Foretova, L. and Janout, V. and Kromhout, H. and Vermeulen, R. and Boffetta, P. and Straif, K. and Schüz, J. and Kendzia, B. and Pesch, B. and Brüning, T. and Behrens, T., Ruhr-Universität Bochum [Bochum], Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM), University of Glasgow, Karolinska Institutet [Stockholm], Centre de recherche en épidémiologie et santé des populations (CESP), 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), Universitätsklinikum Essen [Universität Duisburg-Essen] (Uniklinik Essen), Leibniz Institute for Prevention Research and Epidemiology - BIPS, Leibniz Association, University of Bremen, Helmholtz-Zentrum München (HZM), Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, University of Turin, Universita degli Studi di Padova, Istituto Dermopatico dell'Immacolata, Institut Armand Frappier (INRS-IAF), Institut National de la Recherche Scientifique [Québec] (INRS)-Réseau International des Instituts Pasteur (RIIP), Public Health Ontario - Santé publique Ontario, Occupational Cancer Research Centre, National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH), CIBER de Epidemiología y Salud Pública (CIBERESP), Russian Cancer Research Centre, Nofer Institute of Occupational Medicine (NIOM), National center for public health [Hungary], Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology (MCMCC), Regional Authority of Public Health [Slovaquia] (RAPH), Ministry of Health of the Slovak Republic [Slovaquia], University of Liverpool, National Institute of Public Health [Romania] (INSP), Charles University [Prague] (CU), Masaryk University [Brno] (MUNI), Palacky University Olomouc, Ostravská univerzita / University of Ostrava, Utrecht University [Utrecht], Icahn School of Medicine at Mount Sinai [New York] (MSSM), Centre International de Recherche contre le Cancer - International Agency for Research on Cancer (CIRC - IARC), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), This study was supported by the German Social Accident Insurance, grant number FP 271. Grant sponsors of the individual studies were the Canadian Institutes for Health Research and Guzzo-SRC Chair in Environment and Cancer, National Cancer Institute of Canada, Canadian Cancer Society, Occupational Cancer Research Centre, Workplace Safety and Insurance Board, Canadian Cancer Society, and Cancer Care Ontario, Grant sponsor: European Commission’s INCO Copernicus program, Grant number: IC15-CT96-0313, Grant sponsor: European Union Nuclear Fission Safety Program, Grant number: F14P-CT96-0055, Grant sponsors: French Agency of Health Security (ANSES), Fondation de France, French National Research Agency (ANR), National Institute of Cancer (INCA), Fondation pour la Recherche Medicale, French Institute for Public Health Surveillance (InVS), Health Ministry (DGS), Organization for the Research on Cancer (ARC), and FrenchMinistry of work, solidarity, and public function (DGT), Grant sponsor: Federal Ministry of Education, Science, Research, and Technology, Grant number: 01 HK 173/0), Grant sponsor: Federal Ministry of Science, Grant number: 01 HK 546/8, Grant sponsor: Ministry of Labour and Social Affairs, Grant number: IIIb7-27/13, Grant sponsor: Research Grants Council of the Hong Kong Special Administrative Region, China, Grant number: CUHK4460/03M, Grant sponsors: Environmental Epidemiology Program of the Lombardy Region, INAIL, Italian Association for Cancer Research, Region Piedmont, Compagnia di San Paolo, Lazio Region, Health Research Council of New Zealand, New Zealand Department of Labour, Lottery Health Research, Cancer Society of New Zealand, Grant sponsor: Polish State Committee for Scientific Research, Grant number: SPUB-M-COPERNICUS/P-05/DZ-30/99/2000, Grant sponsors: Instituto Universitario de Oncologia, Universidad de Oviedo, Asturias, Fondo de Investigacion Sanitaria (FIS) and Ciber de Epidemiologia y Salud Publica (CIBERESP), Swedish Council for Work Life Research and Swedish Environmental Protection Agency, Dutch Ministry of Health, Welfare and Sports, National Institute of Public Health and the Environment, and Europe Against Cancer Program, Roy Castle Foundation, and Intramural Research Program of the National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics, Bethesda, Maryland., Nofer Institute of Occupational Medicine, Lodz, Poland, Courcelles, Michel, 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), Helmholtz Zentrum München = German Research Center for Environmental Health, Università degli studi di Torino = University of Turin (UNITO), Università degli Studi di Padova = University of Padua (Unipd), One Health Chemisch, and dIRAS RA-2
Subjects: Genetics and Molecular Biology (all), Male, Lung Neoplasms, Economics, [SDV]Life Sciences [q-bio], Medizin, lcsh:Medicine, Social Sciences, MESH: Logistic Models, Sex Factor, cancer risk, Biochemistry, MESH: Occupational Exposure, Lung and Intrathoracic Tumors, lung tumor, Geographical Locations, Habits, Small Cell Lung Cancer, Biochemistry, Genetics and Molecular Biology (all), Agricultural and Biological Sciences (all), MESH: Risk Factors, Risk Factors, middle aged, Medicine and Health Sciences, Smoking Habits, Odds Ratio, Public and Occupational Health, lcsh:Science, health care economics and organizations, MESH: Aged, MESH: Middle Aged, adult, Age Factors, Socioeconomic Aspects of Health, educational statu, [SDV] Life Sciences [q-bio], Europe, Professions, female, Oncology, Anatomy, Research Article, Employment, MESH: Smoking, Canada, Histology, Logistic Model, sex difference, education, Jobs, Article, smoking, statistical model, Age Factor, MESH: Social Class, Sex Factors, MESH: Sex Factors, MESH: Canada, Occupational Exposure, Humans, controlled study, human, social cla, Aged, MESH: Age Factors, Behavior, MESH: Humans, meta analysi, Risk Factor, lcsh:R, disease association, high risk population, Small cell lung cancer, Smoking habits, Lung and intrathoracic tumors, Socioeconomic aspects of health, Cancers and Neoplasms, Biology and Life Sciences, case control study, lung carcinogenesi, social statu, MESH: Male, MESH: Odds Ratio, MESH: Lung Neoplasms, Health Care, Lung Neoplasm, lung cancer, Logistic Models, age, Social Class, Labor Economics, People and Places, lcsh:Q, Population Groupings, pathology, MESH: Europe, MESH: Female
Abstract: An association between low socioeconomic status (SES) and lung cancer has been observed in several studies, but often without adequate control for smoking behavior. We studied the association between lung cancer and occupationally derived SES, using data from the international pooled SYNERGY study. Twelve case-control studies from Europe and Canada were included in the analysis. Based on occupational histories of study participants we measured SES using the International Socio-Economic Index of Occupational Status (ISEI) and the European Socio-economic Classification (ESeC). We divided the ISEI range into categories, using various criteria. Stratifying by gender, we calculated odds ratios (OR) and 95% confidence intervals (CI) by unconditional logistic regression, adjusting for age, study, and smoking behavior. We conducted analyses by histological subtypes of lung cancer and subgroup analyses by study region, birth cohort, education and occupational exposure to known lung carcinogens. The analysis dataset included 17,021 cases and 20,885 controls. There was a strong elevated OR between lung cancer and low SES, which was attenuated substantially after adjustment for smoking, however a social gradient persisted. SES differences in lung cancer risk were higher among men (lowest vs. highest SES category: ISEI OR 1.84 (95% CI 1.61-2.09); ESeC OR 1.53 (95% CI 1.44-1.63)), than among women (lowest vs. highest SES category: ISEI OR 1.54 (95% CI 1.20-1.98); ESeC OR 1.34 (95% CI 1.19-1.52)). SES remained a risk factor for lung cancer after adjustment for smoking behavior. Funding: This study was supported by the German Social Accident Insurance, grant number FP 271. Grant sponsors of the individual studies were the Canadian Institutes for Health Research and Guzzo-SRC Chair in Environment and Cancer, National Cancer Institute of Canada, Canadian Cancer Society, Occupational Cancer Research Centre, Workplace Safety and Insurance Board, Canadian Cancer Society, and Cancer Care Ontario; Grant sponsor: European Commission’s INCO Copernicus program; Grant number: IC15-CT96-0313; Grant sponsor: European Union Nuclear Fission Safety Program; Grant number: F14P-CT96-0055; Grant sponsors: French Agency of Health Security (ANSES), Fondation de France, French National Research Agency (ANR), National Institute of Cancer (INCA), Fondation pour la Recherche Medicale, French Institute for Public Health Surveillance (InVS), Health Ministry (DGS), Organization for the Research on Cancer (ARC), and FrenchMinistry of work, solidarity, and public function (DGT); Grant sponsor: Federal Ministry of Education, Science, Research, and Technology; Grant number: 01 HK 173/0); Grant sponsor: Federal Ministry of Science; Grant number: 01 HK 546/8; Grant sponsor: Ministry of Labour and Social Affairs; Grant number: IIIb7-27/13; Grant sponsor: Research Grants Council of the Hong Kong Special Administrative Region, China; Grant number: CUHK4460/03M; Grant sponsors: Environmental Epidemiology Program of the Lombardy Region, INAIL, Italian Association for Cancer Research, Region Piedmont, Compagnia di San Paolo, Lazio Region, Health Research Council of New Zealand, New Zealand Department of Labour, Lottery Health Research, Cancer Society of New Zealand; Grant sponsor: Polish State Committee for Scientific Research; Grant number: SPUB-M-COPERNICUS/P-05/DZ-30/99/2000; Grant sponsors: Instituto Universitario de Oncologia, Universidad de Oviedo, Asturias, Fondo de Investigacion Sanitaria (FIS) and Ciber de Epidemiologia y Salud Publica (CIBERESP), Swedish Council for Work Life Research and Swedish Environmental Protection Agency, Dutch Ministry of Health, Welfare and Sports, National Institute of Public Health and the Environment, and Europe Against Cancer Program, Roy Castle Foundation, and Intramural Research Program of the National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics, Bethesda, Maryland.
Published: 2018
Full Text: View/download PDF

26. Treatment for patients with relapsed/refractory mantle cell lymphoma: European-based recommendations

Author: Steven Le Gouill, Jan Walewski, Pier Luigi Zinzani, Marek Trněný, Francesco Zaja, Carlo Visco, Martin Dreyling, Igor Aurer, Georg Hess, Olivier Hermine, Vincent Ribrag, Mats Jerkeman, Sergio Cortelazzo, Dreyling, Martin, Aurer, Igor, Cortelazzo, Sergio, Hermine, Olivier, Hess, Georg, Jerkeman, Mat, Le Gouill, Steven, Ribrag, Vincent, TrnÄ›nÃ½, Marek, Visco, Carlo, Walewski, Jan, Zaja, Francesco, Zinzani, Pier Luigi, III. Medizinische Klinik, Technische Universität München [München] ( TUM ), Department of Oncology and Hematology, University of Modena and Reggio Emilia, Imagine - Institut des maladies génétiques ( IMAGINE - U1163 ), Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ), Department of Oncology and Pathology [Lund], Lund University [Lund], Centre hospitalier universitaire de Nantes ( CHU Nantes ), Département d'hématologie [Gustave Roussy], Institut Gustave Roussy ( IGR ), Charles University and General University Hospital, Department of Hematology, Ospedale San Bortolo, Institute of Oncology, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology ( MCMCC ), L. and A. Seràgnoli Hospital, University of Bologna, Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), and Trněný, Marek
Subjects: Oncology, Cancer Research, Lymphoma, Drug Resistance, Lymphoma, Mantle-Cell, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, chemistry.chemical_compound, 0302 clinical medicine, immune system diseases, hemic and lymphatic diseases, Antineoplastic Combined Chemotherapy Protocols, Medicine, Chemotherapy, clinical trials, mantle cell lymphoma, molecular targeted therapy, Bortezomib, Combination chemotherapy, clinical trial, Hematology, Temsirolimus, Europe, Local, 030220 oncology & carcinogenesis, Ibrutinib, Practice Guidelines as Topic, Rituximab, medicine.drug, medicine.medical_specialty, 03 medical and health sciences, Clinical Trials, Phase II as Topic, Internal medicine, Humans, Lenalidomide, business.industry, Phase II as Topic, Mantle-Cell, medicine.disease, Clinical trial, Drug Resistance, Neoplasm, Neoplasm Recurrence, Local, Neoplasm Recurrence, chemistry, Neoplasm, Mantle cell lymphoma, business, 030215 immunology
Abstract: International audience; Patients with mantle cell lymphoma (MCL) usually respond to initial combination chemotherapy, but the disease inevitably relapses and often follows an aggressive course. Here, clinical study results published since 2008 for patients with relapsed/refractory MCL were reviewed to compare available evidence for treatment guidance. Most trials identified were non-randomized, phase II studies performed at a limited number of sites, and many evaluated MCL as one of multiple non-Hodgkin lymphoma subtypes. Additional randomized, comparative trials are needed. Treatment selection generally depends on patient need, age and fitness, time of relapse, and line of therapy. Combination regimens typically produce higher response rates than single agents, and adding rituximab generally improves outcomes. The inclusion of ibrutinib, lenalidomide, temsirolimus, and bortezomib, represents an important advance for patients ineligible for, unable to tolerate, or failing high-intensity combination chemotherapy. A high need for effective treatments in relapsed/refractory MCL remains, particularly for elderly and frail patients.
Published: 2017
Full Text: View/download PDF

27. Correlation of KIT and PDGFRA mutational status with clinical benefit in patients with gastrointestinal stromal tumor treated with sunitinib in a worldwide treatment-use trial

Author: Sudeep Gupta, Peter Reichardt, George D. Demetri, Jochen Schuette, Piotr Rutkowski, Seock-Ah Im, Jean-Yves Blay, Xin Huang, Michael Heinrich, Yoon-Koo Kang, Denis Soulières, Jean-Francois Martini, Kolette D. Fly, Patrick Schöffski, Maria Jose Lechuga, David Goldstein, Hans Gelderblom, Massimo Corsaro, Leids Universitair Medisch Centrum [Leiden, The Netherlands], Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology (MCMCC), Tata Memorial Centre, Asan Medical Center [Seoul], University of Ulsan, Department of General Medical Oncology [Leuven], University Hospitals Leuven [Leuven], Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM), 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), Department of Remote Sensing, School of Remote Sensing and Information Engineering Wuhan University, and Wuhan University [China]
Subjects: Male, 0301 basic medicine, Oncology, Cancer Research, Indoles, Receptor, Platelet-Derived Growth Factor alpha, Survival, analysis, Growth, 0302 clinical medicine, Belgium, Germany, Sunitinib, Overall survival, Stromal tumor, Aged, 80 and over, Platelet-Derived Growth Factor, education.field_of_study, GiST, Imatinib-resistant GIST, Progression-free survival, KIT, Middle Aged, Prognosis, 3. Good health, Berlin, Proto-Oncogene Proteins c-kit, Italy, 030220 oncology & carcinogenesis, Medicine, Female, France, secondary, Research Article, medicine.drug, GIST, Adult, medicine.medical_specialty, Canada, Adolescent, Genotype, Patients, Gastrointestinal Stromal Tumors, Population, KIT mutation, [SDV.CAN]Life Sciences [q-bio]/Cancer, PDGFRA, Disease-Free Survival, methods, Time, 03 medical and health sciences, Internal medicine, medicine, Genetics, Humans, Pyrroles, education, Protein Kinase Inhibitors, Aged, therapy, business.industry, Imatinib, digestive system diseases, Clinical trial, 030104 developmental biology, Drug Resistance, Neoplasm, Immunology, Mutation, business, Laboratories
Abstract: Background Several small studies indicated that the genotype of KIT or platelet-derived growth factor receptor-α (PDGFRA) contributes in part to the level of clinical effectiveness of sunitinib in gastrointestinal stromal tumor (GIST) patients. This study aimed to correlate KIT and PDGFRA mutational status with clinical outcome metrics (progression-free survival [PFS], overall survival [OS], objective response rate [ORR]) in a larger international patient population. Methods This is a non-interventional, retrospective analysis in patients with imatinib-resistant or intolerant GIST who were treated in a worldwide, open-label treatment-use study (Study 1036; NCT00094029) in which sunitinib was administered at a starting dose of 50 mg/day on a 4-week-on, 2-week-off schedule. Molecular status was obtained in local laboratories with tumor samples obtained either pre-imatinib, post-imatinib/pre-sunitinib, or post-sunitinib treatment, and all available data were used in the analyses regardless of collection time. The primary analysis compared PFS in patients with primary KIT exon 11 versus exon 9 mutations (using a 2-sided log-rank test) and secondary analyses compared OS (using the same test) and ORR (using a 2-sided Pearson χ2 test) in the same molecular subgroups. Results Of the 1124 sunitinib-treated patients in the treatment-use study, 230 (20 %) were included in this analysis, and baseline characteristics were similar between the two study populations. Median PFS was 7.1 months. A significantly better PFS was observed in patients with a primary mutation in KIT exon 9 (n = 42) compared to those with a primary mutation in exon 11 (n = 143; hazard ratio = 0.59; 95 % confidence interval, 0.39–0.89; P = 0.011), with median PFS times of 12.3 and 7.0 months, respectively. Similarly, longer OS and higher ORR were observed in patients with a primary KIT mutation in exon 9 versus exon 11. The data available were limited to investigate the effects of additional KIT or PDGFRA mutations on the efficacy of sunitinib treatment. Conclusions This large retrospective analysis confirms the prognostic significance of KIT mutation status in patients with GIST. This analysis also confirms the effectiveness of sunitinib as a post-imatinib therapy, regardless of mutational status. Trial registration NCT01459757. Electronic supplementary material The online version of this article (doi:10.1186/s12885-016-2051-5) contains supplementary material, which is available to authorized users.
Published: 2016
Full Text: View/download PDF

28. Lenalidomide versus investigator's choice in relapsed or refractory mantle cell lymphoma (MCL-002; SPRINT): a phase 2, randomised, multicentre trial

Author: David Belada, Boris V. Afanasyev, Jiri Mayer, Agnieszka Giza, Simon Rule, Marek Trněný, Kazimierz Kuliczkowski, Julia Alexeeva, Antoine Thyss, Lorenz Trümper, Tsvetan Biyukov, Franck Morschhauser, Wojciech Jurczak, John Radford, Jan Walewski, Caterina Stelitano, K. D. Kaplanov, Sergey Voloshin, Marie Laure Casadebaig Bravo, Reinhard Marks, Meera Patturajan, Noel Milpied, Thierry Lamy, Alexej Kuzmin, Luca Arcaini, Jonchère, Laurent, Department of Hematology and Oncology, Georg-August-University = Georg-August-Universität Göttingen, Division of Hematology, Fondazione IRCCS Policlinico San Matteo, Università degli Studi di Pavia = University of Pavia (UNIPV), Charles University Hospital, Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Institute of Oncology, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology (MCMCC), Department of Internal Medicine, Hemato-Oncology, Faculty of Medicine [Brno] (MED / MUNI), Masaryk University [Brno] (MUNI)-Masaryk University [Brno] (MUNI), Medical Oncology, The University of Manchester and Christie NHS Foundation Trust, Service d'hématologie, Hôpital Claude Huriez [Lille], CHU Lille-CHU Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Department of Haematology, Derriford Hospital, Haematology, Centre Hospitalier Universitaire de Nice (CHU Nice), Klinika Haematologii, Akademia Medyczna w Wroclawiu, Service d'Hématologie et Thérapie Cellulaire, CHU Bordeaux [Bordeaux]-Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Divisione di Ematologia, Pres. Osp. Riuniti 'Bianchi, Melacrito, Morelli', Georg-August-University [Göttingen], University of Pavia, Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Male, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Population, Angiogenesis Inhibitors, Antineoplastic Agents, Kaplan-Meier Estimate, Lymphoma, Mantle-Cell, Disease-Free Survival, Drug Administration Schedule, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Confidence Intervals, medicine, Clinical endpoint, Humans, Neoplasm Invasiveness, Prospective Studies, education, Lenalidomide, Aged, Neoplasm Staging, Proportional Hazards Models, education.field_of_study, Dose-Response Relationship, Drug, business.industry, Middle Aged, medicine.disease, Survival Analysis, Thalidomide, 3. Good health, Surgery, Transplantation, [SDV] Life Sciences [q-bio], Treatment Outcome, Oncology, 030220 oncology & carcinogenesis, Refractory Mantle Cell Lymphoma, Female, Mantle cell lymphoma, Neoplasm Recurrence, Local, business, Progressive disease, Follow-Up Studies, 030215 immunology, medicine.drug
Abstract: Summary Background Lenalidomide, an immunomodulatory drug with antineoplastic and antiproliferative effects, showed activity in many single-group studies in relapsed or refractory mantle cell lymphoma. The aim of this randomised study was to examine the efficacy and safety of lenalidomide versus best investigator's choice of single-agent therapy in relapsed or refractory mantle cell lymphoma. Methods The MCL-002 (SPRINT) study was a randomised, phase 2 study of patients with mantle cell lymphoma aged 18 years or older at 67 clinics and academic centres in 12 countries who relapsed one to three times, had Eastern Cooperative Oncology Group performance status of 0–2, at least one measurable lesion to be eligible, and who were ineligible for intensive chemotherpy or stem-cell transplantation. Using a centralised interactive voice response system, we randomly assigned (2:1) patients in a permuted block size of six to receive lenalidomide (25 mg orally on days 1–21 every 28 days) until progressive disease or intolerability, or single-agent investigator's choice of either rituximab, gemcitabine, fludarabine, chlorambucil, or cytarabine. Randomisation was stratified by time from diagnosis, time from last anti-lymphoma therapy, and previous stem-cell transplantation. Individual treatment assignment between lenalidomide and investigator's choice was open label, but investigators had to register their choice of comparator drug before randomly assigning a patient. Patients who progressed on investigator's choice could cross over to lenalidomide treatment. We present the prespecified primary analysis results in the intention-to-treat population for the primary endpoint of progression-free survival, defined as the time from randomisation to progressive disease or death, whichever occurred first. Patient enrolment is complete, although treatment and collection of additional time-to-event data are ongoing. This study is registered with ClinicalTrials.gov, number NCT00875667. Findings Between April 30, 2009, and March 7, 2013, we enrolled 254 patients in the intention-to-treat population (170 [67%] were randomly assigned to receive lenalidomide, 84 [33%] to receive investigator's choice monotherapy). Patients had a median age of 68·5 years and received a median of two previous regimens. With a median follow-up of 15·9 months (IQR 7·6–31·7), lenalidomide significantly improved progression-free survival compared with investigator's choice (median 8·7 months [95% CI 5·5–12·1] vs 5·2 months [95% CI 3·7–6·9]) with a hazard ratio of 0·61 (95% CI 0·44–0·84; p=0·004). In the 167 patients in the lenalidomide group and 83 patients in the investigator's choice group who received at least one dose of treatment the most common grade 3–4 adverse events included neutropenia (73 [44%] of 167 vs 28 [34%] of 83) without increased risk of infection, thrombocytopenia (30 [18%] vs 23 [28%]), leucopenia (13 [8%] vs nine [11%]), and anaemia (14 [8%] vs six [7%]). Interpretation Patients with relapsed or refractory mantle cell lymphoma ineligible for intensive chemotherapy or stem-cell transplantation have longer progression-free survival, with a manageable safety profile when treated with lenalidomide compared with monotherapy investigator's choice options. Funding Celgene Corporation.
Published: 2016
Full Text: View/download PDF

29. Genomic Grade Index predicts postoperative clinical outcome of GIST

Author: Jerzy Ostrowski, H.J. Kim, David Jérémie Birnbaum, Annalisa Astolfi, W K Kim, Marcin Polkowski, François Bertucci, Pascal Finetti, Maria Abbondanza Pantaleo, Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology (MCMCC), Yonsei University College of Medicine [Seoul, Republic of Korea], University of Bologna/Università di Bologna, Medical Center of Postgraduate Education [Warsaw] (MCPE), FINETTI, Pascal, Bertucci F, Finetti P, Ostrowski J, Kim WK, Kim H, Pantaleo MA, Astolfi A, Polkowski M, and Birnbaum D
Subjects: Male, Oncology, Cancer Research, medicine.medical_specialty, Pathology, Multivariate analysis, Gastrointestinal Stromal Tumors, Expression Signature, Antineoplastic Agents, [SDV.CAN]Life Sciences [q-bio]/Cancer, DNA microarray, Gene expression, GIST, Imatinib, Profiling, Prognosis, Piperazines, NO, Text mining, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, medicine, Humans, Relapse risk, [INFO.INFO-BI] Computer Science [cs]/Bioinformatics [q-bio.QM], Oligonucleotide Array Sequence Analysis, GiST, business.industry, Gene Expression Profiling, Genetics and Genomics, Middle Aged, Pyrimidines, Treatment Outcome, imatinib, Benzamides, gene expression, Imatinib Mesylate, Genomic grade index, Learning set, Female, profiling, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], business, medicine.drug
Abstract: International audience; Background: Prognosis of localised gastrointestinal stromal tumour (GIST) is heterogeneous, notably for patients with AFIP intermediate or high risk of relapse, who are candidates to adjuvant imatinib. We hypothesised that gene expression profiles might improve the prognostication and help to refine the indications for imatinib.Methods: We collected gene expression and histoclinical data of 146 pre-treatment localised GIST samples treated with surgery alone. We searched for a gene expression signature (GES) predictive for relapse-free survival (RFS) and compared its performances to that of three published prognostic proliferation-based GES (Genomic Grade Index (GGI), 16-Kinase, and CINSARC) and AFIP classification. We also analysed a data set from 28 patients with advanced GIST treated with neo-adjuvant imatinib.Results: We identified a 275-gene GES (gene expression signature) predictive of RFS in a learning set and validated its robustness in an independent set. However, the GGI outperformed its prognostic performances, and those of the two other signatures and the AFIP intermediate-risk classification in two independent tests sets in uni- and multivariate analyses. Importantly, GGI could split the AFIP intermediate/high-risk samples into two groups with different RFS. Genomic Grade Index 'high-risk' tumours were more proliferative and genetically unstable than 'low-risk' tumours, and more sensitive to imatinib.Conclusion: GGI refines the prediction of RFS in localised GIST and might help tailor adjuvant imatinib.
Published: 2012
Full Text: View/download PDF

30. Exposure-Response Analyses of Asbestos and Lung Cancer Subtypes in a Pooled Analysis of Case-Control Studies

Author: Olsson, Ann C, Vermeulen, Roel, Schüz, Joachim, Kromhout, Hans, Pesch, Beate, Peters, Susan, Behrens, Thomas, Portengen, Lützen, Mirabelli, Dario, Gustavsson, Per, Kendzia, Benjamin, Almansa, Josue, Luzon, Veronique, Vlaanderen, Jelle, Stücker, Isabelle, Guida, Florence, Consonni, Dario, Caporaso, Neil, Landi, Maria Teresa, Field, John, Brüske, Irene, Wichmann, Heinz-Erich, Siemiatycki, Jack, Parent, Marie-Elise, Richiardi, Lorenzo, Merletti, Franco, Jöckel, Karl-Heinz, Ahrens, Wolfgang, Pohlabeln, Hermann, Plato, Nils, Tardón, Adonina, Zaridze, David, McLaughlin, John, Demers, Paul, Szeszenia-Dabrowska, Neonila, Lissowska, Jolanta, Rudnai, Peter, Fabianova, Eleonora, Stanescu Dumitru, Rodica, Bencko, Vladimir, Foretova, Lenka, Janout, Vladimir, Boffetta, Paolo, Bueno-de-Mesquita, Bas, Forastiere, Francesco, Brüning, Thomas, Straif, Kurt, LS IRAS EEPI GRA (Gezh.risico-analyse), LS IRAS EEPI EXAS (Arb.hyg+bl.st.kar.), Sub IRAS EEPI Algemeen, dIRAS RA-2, Nofer Institute of Occupational Medicine, Łódź, Poland, Olsson, A.C., Vermeulen, R., Schüz, J., Kromhout, H., Pesch, B., Peters, S., Behrens, T., Portengen, L., Mirabelli, D., Gustavsson, P., Kendzia, B., Almansa, J., Luzon, V., Vlaanderen, J., Stücker, I., Guida, F., Consonni, D., Caporaso, N., Landi, M.T., Field, J., Brüske, I., Wichmann, H.-E., Siemiatycki, J., Parent, M.-E., Richiardi, L., Merletti, F., Jöckel, K.-H., Ahrens, W., Pohlabeln, H., Plato, N., Tardon, A., Zaridze, D., McLaughlin, J., Demers, P., Szeszenia-Dabrowska, N., Lissowska, J., Rudnai, P., Fabianova, E., Stanescu Dumitru, R., Bencko, V., Foretova, L., Janout, V., Boffetta, P., Bueno-De-Mesquita, B., Forastiere, F., Brüning, T., Straif, K., LS IRAS EEPI GRA (Gezh.risico-analyse), LS IRAS EEPI EXAS (Arb.hyg+bl.st.kar.), Sub IRAS EEPI Algemeen, dIRAS RA-2, Centre International de Recherche contre le Cancer - International Agency for Research on Cancer (CIRC - IARC), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Karolinska Institutet [Stockholm], Institute for Risk Assessment Sciences, Utrecht University [Utrecht], Institute for Prevention and Occupational Medicine of the German Social Accident Insurance (IPA), The University of Western Australia (UWA), University of Turin, Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Université Paris-Sud - Paris 11 (UP11), Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH), Institute of Translational Medicine, University of Liverpool, Helmholtz-Zentrum München (HZM), Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM), Institut Armand Frappier (INRS-IAF), Réseau International des Instituts Pasteur (RIIP)-Institut National de la Recherche Scientifique [Québec] (INRS), Universität Duisburg-Essen [Essen], Bremen Institute for Prevention Research and Social Medicine (BIPS), CIBER de Epidemiología y Salud Pública (CIBERESP), Russian Cancer Research Centre, Public Health Ontario - Santé publique Ontario, Cancer Care Ontario, Nofer Institute of Occupational Medicine (NIOM), Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology (MCMCC), National center for public health [Hungary], Regional Authority of Public Health [Slovaquia] (RAPH), Ministry of Health of the Slovak Republic [Slovaquia], National Institute of Public Health [Romania] (INSP), Charles University [Prague] (CU), Masaryk University [Brno] (MUNI), Palacky University Olomouc, Icahn School of Medicine at Mount Sinai [New York] (MSSM), National Institute for Public Health and the Environment [Bilthoven] (RIVM), Azienda Sanitaria Locale [ROMA] (ASL), The SYNERGY project is funded by the German Social Accident Insurance (DGUV), Grant FP 271. The original studies were funded as follows: in Canada by Canadian Institutes for Health Research and Guzzo-SRC Chair in Environment and Cancer, National Cancer Institute of Canada, Canadian Cancer Society, Occupational Cancer Research Centre, Workplace Safety and Insurance Board, Canadian Cancer Society, and Cancer Care Ontario, in France by the French Agency of Health Security (ANSES), Fondation de France, French National Research Agency (ANR), National Institute of Cancer (INCA), Fondation pour la Recherche Médicale, French Institute for Public Health Surveillance (InVS), Health Ministry (DGS), Organization for the Research on Cancer (ARC), and French Ministry of work, solidarity, and public function (DGT), in Germany by Federal Ministry of Education, Science, Research, and Technology (Grant 01 HK 173/0), Federal Ministry of Science (Grant 01 HK 546/8), and the Ministry of Labour and Social Affairs (Grant IIIb7-27/13), in Italy by Environmental Epidemiology Program of the Lombardy Region, INAIL, Italian Association for Cancer Research, Region Piedmont, Compagnia di San Paolo, and Lazio Region, in Poland by Polish State Committee for Scientific Research (Grant SPUB-M-COPERNICUS/P-05/ DZ-30/99/2000), in Czech Republic by MH CZ - DRO (MMCI, 00209805), in Spain by Instituto Universitario de Oncologia, Universidad de Oviedo, Asturias, Fondo de Investigacion Sanitaria (FIS) and Ciber de Epidemiologia y Salud Publica (CIBERESP), in Sweden by Swedish Council for Work Life Research and Swedish Environmental Protection Agency, in the Netherlands by Dutch Ministry of Health, Welfare and Sports, National Institute of Public Health and the Environment, and Europe Against Cancer Program, in the UK by Roy Castle Foundation, in the USA by Intramural Research Program of the National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics, Bethesda, MD, the IARC multicenter study in Central and Eastern Europe was funded by the European Commission’s INCO Copernicus program (Contract IC15-CT96-0313)., and Joachim Schüz and Kurt Straif are part of a collaborative study with the State Russian Institute of Occupational Health (SRIOH) on asbestos and cancer risk, which includes financial support from SRIOH to IARC. Paolo Boffetta acted as expert witness for Edison SpA in asbestos-related litigation, outside the submitted work. Beate Pesch, Thomas Behrens, Benjamin Kendzia, and Thomas Brüning, as staff of the Institute for Prevention and Occupational Medicine (IPA), are employed at the 'Berufsgenossenschaft Rohstoffe und chemische Industrie' (BG RCI), a public body, which is a member of the study’s main sponsor, the German Social Accident Insurance (DGUV). IPA is an independent research institute of the Ruhr-Universität Bochum. The authors are independent from the German Social Accident Insurance in study design, access to the collected data, responsibility for data analysis and interpretation, and the right to publish
Subjects: Adult, Male, Canada, Pathology, medicine.medical_specialty, Lung Neoplasms, Epidemiology, [SDV]Life Sciences [q-bio], Population, Medizin, Cumulative Exposure, [SDV.CAN]Life Sciences [q-bio]/Cancer, medicine.disease_cause, Asbestos, 03 medical and health sciences, asbestos exposure, 0302 clinical medicine, Occupational Exposure, Odds Ratio, medicine, Humans, 030212 general & internal medicine, Lung cancer, education, Aged, education.field_of_study, business.industry, Occupational asbestos exposure, lung cancer, Smoking, Case-control study, Absolute risk reduction, Odds ratio, Middle Aged, Occupational Epidemiology, medicine.disease, Small Cell Lung Carcinoma, 030210 environmental & occupational health, Confidence interval, 3. Good health, Europe, lung cancer, Logistic Models, Case-Control Studies, ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, Carcinoma, Squamous Cell, Female, business, Demography
Abstract: Supplemental Digital Content is available in the text., Background: Evidence is limited regarding risk and the shape of the exposure–response curve at low asbestos exposure levels. We estimated the exposure–response for occupational asbestos exposure and assessed the joint effect of asbestos exposure and smoking by sex and lung cancer subtype in general population studies. Methods: We pooled 14 case–control studies conducted in 1985–2010 in Europe and Canada, including 17,705 lung cancer cases and 21,813 controls with detailed information on tobacco habits and lifetime occupations. We developed a quantitative job-exposure-matrix to estimate job-, time period-, and region-specific exposure levels. Fiber-years (ff/ml-years) were calculated for each subject by linking the matrix with individual occupational histories. We fit unconditional logistic regression models to estimate odds ratios (ORs), 95% confidence intervals (CIs), and trends. Results: The fully adjusted OR for ever-exposure to asbestos was 1.24 (95% CI, 1.18, 1.31) in men and 1.12 (95% CI, 0.95, 1.31) in women. In men, increasing lung cancer risk was observed with increasing exposure in all smoking categories and for all three major lung cancer subtypes. In women, lung cancer risk for all subtypes was increased in current smokers (ORs ~two-fold). The joint effect of asbestos exposure and smoking did not deviate from multiplicativity among men, and was more than additive among women. Conclusions: Our results in men showed an excess risk of lung cancer and its subtypes at low cumulative exposure levels, with a steeper exposure–response slope in this exposure range than at higher, previously studied levels. (See video abstract at, http://links.lww.com/EDE/B161.)
Published: 2017
Full Text: View/download PDF

31. Molecular remission is an independent predictor of clinical outcome in patients with mantle cell lymphoma after combined immunochemotherapy: a European MCL intergroup study.: MRD after immunochemotherapy in mantle-cell lymphoma

Author: Pott, Christiane, Hoster, Eva, Delfau-Larue, Marie-Hélène, Beldjord, Kheira, Böttcher, Sebastian, Asnafi, Vahid, Plonquet, Anne, Siebert, Reiner, Callet-Bauchu, Evelyne, Andersen, Niels, van Dongen, Jacques, Klapper, Wolfram, Berger, Françoise, Ribrag, Vincent, van Hoof, Achiel, Trneny, Marek, Walewski, Jan, Dreger, Peter, Unterhalt, Michael, Hiddemann, Wolfgang, Kneba, Michael, Kluin-Nelemans, Hanneke, Hermine, Olivier, Macintyre, Elizabeth, Dreyling, Martin, Second Medical Department, University Hospital Schleswig-Holstein, Department of Internal Medicine III, University of Munich, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service d'immunologie biologique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Laboratoire d'hématologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institute of Human Genetics, Service d'hématologie [Hôpital Edouard Herriot - HCL], Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Department of Hematology, Rigshospitalet [Copenhagen], Copenhagen University Hospital-Copenhagen University Hospital, Department of Immunology, Department of Hematopathology, Schleswig-Holstein University Hospitals, Département de pathologie, Hospices Civils de Lyon (HCL), Laboratoire de recherche translationnelle, Direction de la recherche [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), University Hospital St Jan, 1st Dept. of Medicine, Charles University [Prague] (CU), Institute of Oncology, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology (MCMCC), Department of Internal Medicine V, Heidelberg University Hospital [Heidelberg], University of Groningen [Groningen], Cytokines, hématopoïèse et réponse immune (CHRI), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), This work was supported by the European Community within the European MCL Network LSHC-CT 2004-503351 (CP, EM, MHDL, RS) and by the Lymphoma Research Foundation (CP, SB, MD) Correlative Research grant, ARC (association de recherche contre le Cancer) Subvention number 3730 (MHDL), Fondation de France (FDF) comité Leucémie, Subvention number 2004004029 (MHDL), ARTGIL (Association de recherche sur le traitement, la genétique et l'immunologie des lymphomes) (MHDL), European Project: 26849,EUROPEAN MCL NETWORK, Guellaen, Georges, and European Mantle Cell Lymphoma Network: Tranlational determination of molecular prognostic factors and pharmacogenomics in a European interdisciplinary collaboration - EUROPEAN MCL NETWORK - 26849 - OLD
Subjects: immunochemotherapy, [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, autologous stem cell transplantation, MRD, hemic and lymphatic diseases, RQ-PCR, mantle cell lymphoma, minimal residual disease, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology
Abstract: International audience; The prognostic impact of minimal residual disease (MRD) was analyzed in 259 patients with mantle cell lymphoma (MCL) treated within 2 randomized trials of the European MCL Network (MCL Younger and MCL Elderly trial). After rituximab-based induction treatment, 106 of 190 evaluable patients (56%) achieved a molecular remission (MR) based on blood and/or bone marrow (BM) analysis. MR resulted in a significantly improved response duration (RD; 87% vs 61% patients in remission at 2 years, P = .004) and emerged to be an independent prognostic factor for RD (hazard ratio = 0.4, 95% confidence interval, 0.1-0.9, P = .028). MR was highly predictive for prolonged RD independent of clinical response (complete response [CR], complete response unconfirmed [CRu], partial response [PR]; RD at 2 years: 94% in BM MRD-negative CR/CRu and 100% in BM MRD-negative PR, compared with 71% in BM MRD-positive CR/CRu and 51% in BM MRD-positive PR, P = .002). Sustained MR during the postinduction period was predictive for outcome in MCL Younger after autologous stem cell transplantation (ASCT; RD at 2 years 100% vs 65%, P = .001) and during maintenance in MCL Elderly (RD at 2 years: 76% vs 36%, P = .015). ASCT increased the proportion of patients in MR from 55% before high-dose therapy to 72% thereafter. Sequential MRD monitoring is a powerful predictor for treatment outcome in MCL. These trials are registered at www.clinicaltrials.gov as #NCT00209222 and #NCT00209209.
Published: 2010
Full Text: View/download PDF

32. Molecular remission is an independent predictor of clinical outcome in patients with mantle cell lymphoma after combined immunochemotherapy: a European MCL intergroup study.: MRD after immunochemotherapy in mantle-cell lymphoma

Author: Pott, Christiane, Hoster, Eva, Delfau-Larue, Marie-Hélène, Beldjord, Kheira, Böttcher, Sebastian, Asnafi, Vahid, Plonquet, Anne, Siebert, Reiner, Callet-Bauchu, Evelyne, Andersen, Niels, Van Dongen, Jacques, Klapper, Wolfram, Berger, Françoise, Ribrag, Vincent, Van Hoof, Achiel, Trneny, Marek, Walewski, Jan, Dreger, Peter, Unterhalt, Michael, Hiddemann, Wolfgang, Kneba, Michael, Kluin-Nelemans, Hanneke, Hermine, Olivier, Macintyre, Elizabeth, Dreyling, Martin, Second Medical Department, University Hospital Schleswig-Holstein, Department of Internal Medicine III, University of Munich, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service d'immunologie biologique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Laboratoire d'hématologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institute of Human Genetics, Service d'hématologie [Hôpital Edouard Herriot - HCL], Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Department of Hematology, Rigshospitalet [Copenhagen], Copenhagen University Hospital-Copenhagen University Hospital, Department of Immunology, Department of Hematopathology, Schleswig-Holstein University Hospitals, Département de pathologie, Hospices Civils de Lyon (HCL), Laboratoire de recherche translationnelle, Direction de la recherche [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), University Hospital St Jan, 1st Dept. of Medicine, Charles University [Prague] (CU), Institute of Oncology, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology (MCMCC), Department of Internal Medicine V, Heidelberg University Hospital [Heidelberg], University of Groningen [Groningen], Cytokines, hématopoïèse et réponse immune (CHRI), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), This work was supported by the European Community within the European MCL Network LSHC-CT 2004-503351 (CP, EM, MHDL, RS) and by the Lymphoma Research Foundation (CP, SB, MD) Correlative Research grant, ARC (association de recherche contre le Cancer) Subvention number 3730 (MHDL), Fondation de France (FDF) comité Leucémie, Subvention number 2004004029 (MHDL), ARTGIL (Association de recherche sur le traitement, la genétique et l'immunologie des lymphomes) (MHDL), and European Project: 26849,EUROPEAN MCL NETWORK
Subjects: immunochemotherapy, autologous stem cell transplantation, MRD, hemic and lymphatic diseases, RQ-PCR, mantle cell lymphoma, minimal residual disease, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology
Abstract: International audience; The prognostic impact of minimal residual disease (MRD) was analyzed in 259 patients with mantle cell lymphoma (MCL) treated within 2 randomized trials of the European MCL Network (MCL Younger and MCL Elderly trial). After rituximab-based induction treatment, 106 of 190 evaluable patients (56%) achieved a molecular remission (MR) based on blood and/or bone marrow (BM) analysis. MR resulted in a significantly improved response duration (RD; 87% vs 61% patients in remission at 2 years, P = .004) and emerged to be an independent prognostic factor for RD (hazard ratio = 0.4, 95% confidence interval, 0.1-0.9, P = .028). MR was highly predictive for prolonged RD independent of clinical response (complete response [CR], complete response unconfirmed [CRu], partial response [PR]; RD at 2 years: 94% in BM MRD-negative CR/CRu and 100% in BM MRD-negative PR, compared with 71% in BM MRD-positive CR/CRu and 51% in BM MRD-positive PR, P = .002). Sustained MR during the postinduction period was predictive for outcome in MCL Younger after autologous stem cell transplantation (ASCT; RD at 2 years 100% vs 65%, P = .001) and during maintenance in MCL Elderly (RD at 2 years: 76% vs 36%, P = .015). ASCT increased the proportion of patients in MR from 55% before high-dose therapy to 72% thereafter. Sequential MRD monitoring is a powerful predictor for treatment outcome in MCL. These trials are registered at www.clinicaltrials.gov as #NCT00209222 and #NCT00209209.
Published: 2010
Full Text: View/download PDF

Catalog

Books, media, physical & digital resources

See catalog results

Searchworks

Select search scope, currently: Articles

Catalog

books, media & more in Jio Institute collections

Articles

journal articles & other e-resources

Refine your results

32 results on '"Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology ( MCMCC )"'

1. Management of acute mesenteric ischaemia: Results of a worldwide survey

2. Best practices for the management of local-regional recurrent chordoma: a position paper by the chordoma global consensus group

3. Occupational Exposure to Polycyclic Aromatic Hydrocarbons and Lung Cancer Risk: Results from a Pooled Analysis of Case–Control Studies (SYNERGY)

4. Pharmacokinetics of oral vinorelbine in French children with recurrent or progressive primary low‐grade glioma

5. A polygenic risk score for multiple myeloma risk prediction

6. The Transcription Factor Encyclopedia

7. Should anti-thymocyte globulin be added in post-transplant cyclophosphamide based matched unrelated donor peripheral blood stem cell transplantation for acute myeloid leukemia? A study on behalf of the Acute Leukemia Working Party of the EBMT

8. Post-transplant cyclophosphamide versus anti-thymocyte globulin for graft-versus-host disease prevention in haploidentical transplantation for adult acute lymphoblastic leukemia

9. Encapsulation of granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor in liposomes prepared by thin film hydration and their transfer to mesenchymal stem cells and cord blood hematopoietic stem cells

10. European Reference Network for rare adult solid cancers, statement and integration to health care systems of member states

11. 20-Year Steady Increase in Survival of Adult Patients with Relapsed Philadelphia-Positive Acute Lymphoblastic Leukemia Post Allogeneic Hematopoietic Cell Transplantation

12. Adjuvant pembrolizumab versus placebo in resected stage III melanoma (EORTC 1325-MG/KEYNOTE-054): distant metastasis-free survival results from a double-blind, randomised, controlled, phase 3 trial

13. Adjuvant pembrolizumab versus placebo in resected stage III melanoma (EORTC 1325-MG/KEYNOTE-054): health-related quality-of-life results from a double-blind, randomised, controlled, phase 3 trial

14. Thiotepa-busulfan-fludarabine (TBF) conditioning regimen in patients undergoing allogeneic hematopoietic cell transplantation for myelofibrosis: an outcome analysis from the Chronic Malignancies Working Party of the EBMT

15. Post-transplant cyclophosphamide versus antithymocyte globulin in patients with acute myeloid leukemia in first complete remission undergoing allogeneic stem cell transplantation from 10/10 HLA-matched unrelated donors

16. Management of patients with acute leukemia during the COVID-19 outbreak: practical guidelines from the acute leukemia working party of the European Society for Blood and Marrow Transplantation

17. Safety, efficacy and patient-reported outcomes with trifluridine/tipiracil in pretreated metastatic colorectal cancer: results of the PRECONNECT study

18. Preoperative radiotherapy plus surgery versus surgery alone for patients with primary retroperitoneal sarcoma (EORTC-62092: STRASS): a multicentre, open-label, randomised, phase 3 trial

19. Overall survival at 5 years of follow-up in a phase III trial comparing ipilimumab 10 mg/kg with 3 mg/kg in patients with advanced melanoma

20. Radiotherapy-Induced Changes in the Systemic Immune and Inflammation Parameters of Head and Neck Cancer Patients

21. Addition of high-dose cytarabine to immunochemotherapy before autologous stem-cell transplantation in patients aged 65 years or younger with mantle cell lymphoma (MCL Younger): a randomised, open-label, phase 3 trial of the European Mantle Cell Lymphoma Network

22. Five-year outcomes from a phase 3 METRIC study in patients with BRAF V600 E/K-mutant advanced or metastatic melanoma

23. Analysis of shared heritability in common disorders of the brain

24. Influence of Confounding Factors on Radiation Dose Estimation Using In Vivo Validated Transcriptional Biomarkers

25. Lung cancer and socioeconomic status in a pooled analysis of case-control studies

26. Treatment for patients with relapsed/refractory mantle cell lymphoma: European-based recommendations

27. Correlation of KIT and PDGFRA mutational status with clinical benefit in patients with gastrointestinal stromal tumor treated with sunitinib in a worldwide treatment-use trial

28. Lenalidomide versus investigator's choice in relapsed or refractory mantle cell lymphoma (MCL-002; SPRINT): a phase 2, randomised, multicentre trial

29. Genomic Grade Index predicts postoperative clinical outcome of GIST

30. Exposure-Response Analyses of Asbestos and Lung Cancer Subtypes in a Pooled Analysis of Case-Control Studies

31. Molecular remission is an independent predictor of clinical outcome in patients with mantle cell lymphoma after combined immunochemotherapy: a European MCL intergroup study.: MRD after immunochemotherapy in mantle-cell lymphoma

32. Molecular remission is an independent predictor of clinical outcome in patients with mantle cell lymphoma after combined immunochemotherapy: a European MCL intergroup study.: MRD after immunochemotherapy in mantle-cell lymphoma

Catalog

Searchworks

Select search scope, currently: Articles Catalog books, media & more in Jio Institute collections Articles journal articles & other e-resources

Search

Search Constraints

Refine your results

Search Limiters

Topic

Publication Year Range

Language

Journal

Database

Publisher

32 results on '"Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology ( MCMCC )"'

Search Results

Catalog

Select search scope, currently: Articles

Catalog

books, media & more in Jio Institute collections

Articles

journal articles & other e-resources