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1. Dynamic evaluation of circulating tumour cells in patients with advanced gastric and oesogastric junction adenocarcinoma: Prognostic value and early assessment of therapeutic effects

Author: Jaafar Bennouna, Christophe Borg, Cécile Badoual, Jean-Baptiste Bachet, Julien Taieb, François Ghiringhelli, Florence Castan, Elie Marcheteau, Sophie Gourgou, Aurélie Cazes, Christelle De La Fouchardiere, Simon Pernot, Olivier Bouché, Trevor Stanbury, Eric Francois, Emmanuelle Samalin, Magali Terme, David Malka, Michel Ducreux, Unité Fonctionnelle de Pharmacogénétique et Oncologie Moléculaire [AP-HP Hôpital Européen Georges Pompidou] (Service de Biochimie), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Paris-Centre de Recherche Cardiovasculaire (PARCC - UMR-S U970), Université Paris Descartes - Paris 5 (UPD5)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d’anatomo‑pathologie [AP-HP Hôpital Européen Georges Pompidou] (Centre de Ressources biologiques), Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Reims (CHU Reims), Institut de Cancérologie de l'Ouest, Centre Antoine Lacassagne, CRLCC Antoine Lacassagne, Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc (CRLCC - CGFL), Centre Léon Bérard [Lyon], CRLC Val d'Aurelle-Paul Lamarque, CRLCC Val d'Aurelle - Paul Lamarque, CHU Pitié-Salpêtrière [APHP], Service d'Oncologie Médicale [CHRU Besançon], Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Université de Franche-Comté (UFC), Institut Gustave Roussy (IGR), Oncologie digestive, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), UNICANCER - Institut régional du Cancer [Montpellier] (ICM), Unité Fonctionnelle de Pharmacogénétique et Oncologie Moléculaire [AP-HP Hôpital Européen Georges Pompidou] ( Service de Biochimie ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Européen Georges Pompidou [APHP] ( HEGP ), Paris-Centre de Recherche Cardiovasculaire ( PARCC - U970 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Hôpital Européen Georges Pompidou [APHP] ( HEGP ), Service d’anatomo‑pathologie [AP-HP Hôpital Européen Georges Pompidou] ( Centre de Ressources biologiques ), Hôpital Européen Georges Pompidou [APHP] ( HEGP ), Institut de Recherche en Cancérologie de Montpellier ( IRCM - U1194 Inserm - UM ), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Montpellier ( UM ), Centre Hospitalier Universitaire de Reims ( CHU Reims ), Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc ( CRLCC - CGFL ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Université de Franche-Comté ( UFC ), Institut Gustave Roussy ( IGR ), Institut Gustave Roussy ( IGR ) -Institut Gustave Roussy ( IGR ), UNICANCER - Institut régional du Cancer [Montpellier] ( ICM ), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), and UNICANCER - Institut régional du Cancer Montpellier Val d'Aurelle (ICM)
Subjects: Male, 0301 basic medicine, Oncology, Cancer Research, Pathology, Esophageal Neoplasms, Organoplatinum Compounds, MESH : Antineoplastic Combined Chemotherapy Protocols, Leucovorin, Cell Count, MESH : Leucovorin, Kaplan-Meier Estimate, MESH : Cell Count, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, 0302 clinical medicine, Prostate, Circulating tumour cells, Antineoplastic Combined Chemotherapy Protocols, MESH : Stomach Neoplasms, MESH : Esophagogastric Junction, MESH : Female, MESH: Treatment Outcome, MESH : Prognosis, MESH: Organoplatinum Compounds, MESH: Stomach Neoplasms, Neoplastic Cells, Circulating, Prognosis, 3. Good health, Oxaliplatin, Clinical trial, MESH: Antineoplastic Combined Chemotherapy Protocols, Treatment Outcome, medicine.anatomical_structure, 030220 oncology & carcinogenesis, MESH: Esophageal Neoplasms, Monoclonal, Disease Progression, MESH : Fluorouracil, MESH : Disease-Free Survival, Adenocarcinoma, Female, MESH: Disease Progression, Esophagogastric Junction, Fluorouracil, MESH: Esophagogastric Junction, medicine.drug, medicine.medical_specialty, MESH : Male, Stomach neoplasms, [SDV.CAN]Life Sciences [q-bio]/Cancer, MESH : Treatment Outcome, MESH: Neoplastic Cells, Circulating, Antibodies, Monoclonal, Humanized, MESH : Organoplatinum Compounds, Disease-Free Survival, MESH : Antibodies, Monoclonal, Humanized, MESH: Prognosis, MESH : Kaplan-Meier Estimate, 03 medical and health sciences, Internal medicine, medicine, Humans, In patient, Clinical significance, MESH: Kaplan-Meier Estimate, MESH: Humans, MESH: Cell Count, business.industry, MESH : Humans, Therapeutic effect, MESH : Disease Progression, medicine.disease, MESH: Male, 030104 developmental biology, MESH: Antibodies, Monoclonal, Humanized, MESH : Neoplastic Cells, Circulating, MESH: Disease-Free Survival, MESH : Esophageal Neoplasms, MESH: Leucovorin, business, MESH: Female, MESH: Fluorouracil, Biomarkers
Abstract: IF 6.029; International audience; Background: The identification of dynamic biomarkers in advanced gastric and oesogastric junction adenocarcinoma (GOA) could help to tailor strategies for each patient. Enumeration of circulating tumour cells (CTCs) is approved by the US Food and Drug Administration in breast, colon and prostate cancer but is not in advanced GOA. Our study aims to establish the optimal threshold and the clinical significance of CTC count in advanced GOA before and during treatment.Methods: One hundred six patients with untreated advanced GOA were included in the ancillary study of the PRODIGE 17-ACCORD 20 trial. CTCs were detected in the peripheral blood using the CellSearch system on day 0 (D0) and day 28 (D28). The prognostic value of CTCs at D0 and D28 was analysed by testing several thresholds.Results: At baseline, median CTC count was 1 (range, 0-415). While CTCs >= 1, 2 or 3 at D0 were all significantly associated with worse overall survival (OS) and progression-free survival (PFS), CTCs >2 were the optimal threshold, on D0 or D28. CTCs >2 at D28 were also predictive of disease control. Taking into account both D0 and D28 CTC count defined 3 groups (low/low, high/low and low-high/high) with significantly different PFS (p = 0.0002) and OS (p = 0.003).Conclusion: Quantification of CTCs at baseline and during treatment may be a useful prognostic tool in advanced GOA, as it is associated with worse PFS and OS. A threshold >= 2 CTCs seems to have the best discriminant value. Change in CTC count between baseline and D28 could help to tailor treatment to each individual patient. (C) 2017 Elsevier Ltd. All rights reserved.
Published: 2017
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2. Cardiac rehabilitation and 5-year mortality after acute coronary syndromes: The 2005 French FAST-MI study

Author: Didier Carrié, Jean-Bernard Ruidavets, Marion Pouche, Luc Lorgis, Nicolas Danchin, Hervé Douard, Tabassome Simon, Philippe Brunel, Vincent Bataille, Jean Ferrières, Marie-Christine Iliou, Epidémiologie et analyses en santé publique : risques, maladies chroniques et handicaps (LEASP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Service de cardiologie [Toulouse], Hôpital de Rangueil, CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Réadaptation Cardiaque et Prévention Secondaire [Hôpital Corentin-Celton], Hôpital Corentin Celton [Issy-les-Moulineaux], Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), hôpital cardiologique (CHU de Bordeaux), CHU Bordeaux [Bordeaux], Laboratoire de Physiopathologie et Pharmacologie Cardio-Métaboliques (U866, Lipides et nutrition, équipe 5) (LPPCM), Lipides - Nutrition - Cancer (U866) (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), Service de Cardiologie [CHU de Dijon], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Nouvelles Cliniques Nantaises, CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Paris-Centre de Recherche Cardiovasculaire (PARCC - UMR-S U970), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Pfizer, Servier, Caisse nationale d'assurance maladie des travailleurs salariés, Épidémiologie et analyses en santé publique : risques, maladies chroniques et handicaps, Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital de Rangueil, CHU Toulouse [Toulouse], Hôpitaux Universitaires Paris Ouest - Hôpital Corentin Celton [Issy-les-Moulineaux], Laboratoire de Physiopathologie et Pharmacologie Cardio-Métaboliques (U866, Lipides et nutrition, équipe 5) ( LPPCM ), Lipides - Nutrition - Cancer (U866) ( LNC ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ) -Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Plateforme de recherche clinique de l'est parisien ( URCEST-CRCEST ), CHU Saint-Antoine [APHP], Paris-Centre de Recherche Cardiovasculaire ( PARCC - U970 ), Hôpital Européen Georges Pompidou [APHP] ( HEGP ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service Cardiologie [CHU Toulouse], Pôle Cardiovasculaire et Métabolique [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Université Paris Descartes - Paris 5 (UPD5)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Epidémiologie et analyses en santé publique : risques, maladies chroniques et handicaps [Toulouse], Université Paul Sabatier - Toulouse 3 ( UPS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Paul Sabatier - Toulouse 3 ( UPS ) -CHU Toulouse [Toulouse]-Hôpital de Rangueil, and Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Hôpital Européen Georges Pompidou [APHP] ( HEGP )
Subjects: Male, MESH: Chi-Square Distribution, medicine.medical_treatment, MESH : Acute Coronary Syndrome, Myocardial Infarction, MESH : Aged, MESH : Prospective Studies, Cardiac rehabilitation, MESH: Risk Assessment, 0302 clinical medicine, Myocardial infarction, Prospective Studies, Referral and Consultation, MESH: Treatment Outcome, Rehabilitation, MESH: Middle Aged, General Medicine, MESH: Follow-Up Studies, 3. Good health, MESH: Myocardial Infarction, MESH : Patient Discharge, Cardiology and Cardiovascular Medicine, medicine.medical_specialty, Acute myocardial infarction, Mortalité, Risk Assessment, 03 medical and health sciences, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Humans, MESH : Middle Aged, Acute Coronary Syndrome, MESH: Kaplan-Meier Estimate, Aged, Chi-Square Distribution, MESH: Humans, MESH : Chi-Square Distribution, Proportional hazards model, MESH: Patient Discharge, MESH : Humans, Patient survival, MESH : Follow-Up Studies, medicine.disease, MESH : Proportional Hazards Models, MESH: Acute Coronary Syndrome, ST-segment elevation myocardial infarction, MESH: Female, Time Factors, MESH: Registries, Kaplan-Meier Estimate, 030204 cardiovascular system & hematology, MESH : Referral and Consultation, MESH: Proportional Hazards Models, Older patients, Risk Factors, MESH: Risk Factors, MESH : Female, 030212 general & internal medicine, Registries, MESH : Risk Assessment, MESH: Aged, Ejection fraction, Non–ST-segment elevation myocardial infarction, Middle Aged, [ SDV.MHEP.CSC ] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, MESH : Risk Factors, Patient Discharge, Treatment Outcome, Female, France, MESH : Time Factors, MESH : Male, MESH : Treatment Outcome, MESH: Multivariate Analysis, MESH : Kaplan-Meier Estimate, MESH: Referral and Consultation, Internal medicine, Infarctus du myocarde sans sus-décalage du segment ST, medicine, In patient, cardiovascular diseases, Medical prescription, Mortality, Réadaptation cardiaque, MESH : France, Proportional Hazards Models, business.industry, Infarctus du myocarde avec sus-décalage du segment ST, MESH: Time Factors, MESH : Multivariate Analysis, MESH: Male, MESH: Prospective Studies, Surgery, MESH: France, Infarctus du myocarde aigu, Multivariate Analysis, MESH : Myocardial Infarction, business, MESH : Registries, Follow-Up Studies
Abstract: IF 2.271; International audience; Background. - Clinical studies have shown a beneficial effect of cardiac rehabilitation (CR) on mortality.Objective. - To study the effect of CR prescription at discharge on 5-year mortality in patients with acute myocardial infarction (AMI).Methods. - Participants, from the 2005 French FAST-MI hospital registry, were 2894 survivors at discharge, divided according to AMI type: ST-segment elevation myocardial infarction (STEMI; n=1523) and non-STEMI (NSTEMI; n=1371). The effect of CR prescription on mortality was analysed using a Cox proportional hazards model.Results. - At discharge, 22.1% of patients had a CR prescription. Patients referred to CR were younger (62.4 vs. 67.5 years), were more frequently men and more had presented with STEMI (67.8% vs. 48.3%) than non-referred patients. Ninety-four (14.7%) deaths occurred among patients referred to CR and 585 (25.9%) among non-referred patients (P= 60 years) and AMI type showed that the inverse association was stronger in men (HR 0.64, 95% CI 0.48-0.87) than in women (HR 0.95, 95% CI 0.64-1.39), in younger (HR 0.34, 95% CI 0.15-0.77) than in older patients (HR 0.84, 95% CI 0.65-1.07) and in NSTEMI (HR 0.63, 95% CI 0.46-0.88) than in STEMI (HR 0.99, 95% CI 0.69-1.40).Conclusion. - After hospitalization for AMI, referral to CR remains a significant predictor of improved patient survival; some subgroups seem to gain greater benefit. (C) 2015 Elsevier Masson SAS. All rights reserved.
Published: 2016
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3. Therapeutic vaccination with TG4010 and first-line chemotherapy in advanced non-small-cell lung cancer: a controlled phase 2B trial

Author: Didier Debieuvre, Jean-Marc Limacher, Elisabeth Quoix, A. Madroszyk, Marc Buyse, Jean-Yves Bonnefoy, Z. Papai, Erich Stoelben, Gisèle Lacoste, Piotr Koralewski, Hervé Lena, Denis Braun, Alain Rivière, Marie-Pierre Chenard, Bérangère Bastien, Jean-Luc Breton, Annette Tavernaro, Rodryg Ramlau, Bruce Acres, Nadine Bizouarne, Virginie Westeel, Service de pneumologie, CHU Strasbourg-Hopital Civil, Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC ( CEF2P / CARCINO ), Université Bourgogne Franche-Comté ( UBFC ) -Université de Franche-Comté ( UFC ) -Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ), Laboratoire d'Ingénierie des Systèmes Mécaniques et des MAtériaux ( LISMMA ), Université Paris 8 Vincennes-Saint-Denis ( UP8 ) -SUPMECA - Institut supérieur de mécanique de Paris, Centre Hospitalier de Belfort-Montbéliard, Service de Pneumologie, CHI de la Haute-Saône, International Drug Development Institute ( IDDI ), Service d'Anatomie Pathologique Générale, CHU Strasbourg-Hôpital de Hautepierre [Strasbourg], Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (EA 3181) (CEF2P / CARCINO), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Laboratoire d'Ingénierie des Systèmes Mécaniques et des MAtériaux (LISMMA), Université Paris 8 Vincennes-Saint-Denis (UP8)-SUPMECA - Institut supérieur de mécanique de Paris (SUPMECA), CH Belfort-Montbéliard, and International Drug Development Institute (IDDI)
Subjects: Male, Lung Neoplasms, MESH: Chi-Square Distribution, MESH : Antineoplastic Combined Chemotherapy Protocols, medicine.medical_treatment, MESH: Membrane Glycoproteins, MESH : Aged, MESH: Risk Assessment, Deoxycytidine, Gastroenterology, MESH: Cancer Vaccines, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, 0302 clinical medicine, Antineoplastic Combined Chemotherapy Protocols, MESH: Vaccinia virus, Clinical endpoint, MESH : Neoplasm Staging, MESH: Treatment Outcome, Vaccines, Synthetic, 0303 health sciences, Membrane Glycoproteins, MESH: Middle Aged, MESH : Vaccinia virus, MESH : Antimetabolites, Antineoplastic, MESH : Chemotherapy, Adjuvant, 3. Good health, MESH: Antineoplastic Combined Chemotherapy Protocols, Oncology, 030220 oncology & carcinogenesis, Antimetabolites, Antineoplastic, medicine.medical_specialty, MESH: Vaccines, Synthetic, Risk Assessment, Disease-Free Survival, MESH : Cisplatin, 03 medical and health sciences, Humans, MESH : Middle Aged, MESH : Lung Neoplasms, MESH : Vaccines, Synthetic, Adverse effect, MESH: Kaplan-Meier Estimate, Aged, Chi-Square Distribution, MESH: Humans, MESH : Carcinoma, Non-Small-Cell Lung, MESH : Chi-Square Distribution, MESH: Deoxycytidine, MESH : Humans, MESH: Adult, MESH: Interleukin-2, MESH : Proportional Hazards Models, medicine.disease, MESH: Lung Neoplasms, MESH: Disease-Free Survival, Cisplatin, MESH: Female, MESH: Mucin-1, Time Factors, MESH : Membrane Glycoproteins, Kaplan-Meier Estimate, MESH: Proportional Hazards Models, Risk Factors, MESH: Risk Factors, Carcinoma, Non-Small-Cell Lung, MESH : Female, MESH : Risk Assessment, MESH: Aged, MESH: Antimetabolites, Antineoplastic, MESH : Cancer Vaccines, MESH: Neoplasm Staging, Middle Aged, MESH : Adult, MESH : Risk Factors, Europe, Treatment Outcome, Chemotherapy, Adjuvant, MESH: Chemotherapy, Adjuvant, MESH : Mucin-1, MESH : Disease-Free Survival, Female, MESH : Time Factors, medicine.drug, Adult, Combination therapy, MESH : Male, MESH : Europe, Vaccinia virus, [SDV.CAN]Life Sciences [q-bio]/Cancer, MESH : Treatment Outcome, Neutropenia, Cancer Vaccines, MESH : Interleukin-2, MESH : Kaplan-Meier Estimate, MESH : Deoxycytidine, Internal medicine, medicine, Lung cancer, Neoplasm Staging, Proportional Hazards Models, 030304 developmental biology, Chemotherapy, Performance status, business.industry, Mucin-1, MESH: Time Factors, Gemcitabine, MESH: Male, Surgery, MESH: Cisplatin, Interleukin-2, MESH: Europe, business, MESH: Carcinoma, Non-Small-Cell Lung
Abstract: International audience; BACKGROUND: Chemotherapy is the standard of care for advanced stages of non-small-cell lung cancer (NSCLC). TG4010 is a targeted immunotherapy based on a poxvirus (modified vaccinia virus Ankara) that codes for MUC1 tumour-associated antigen and interleukin 2. This study assessed TG4010 in combination with first-line chemotherapy in advanced NSCLC. METHODS: 148 patients with advanced (stage IIIB [wet] or IV) NSCLC expressing MUC1 by immunohistochemistry, and with performance status 0 or 1, were enrolled in parallel groups in this open-label, phase 2B study. 74 patients were allocated to the combination therapy group, and received TG4010 (10(8) plaque forming units) plus cisplatin (75 mg/m(2) on day 1) and gemcitabine (1250 mg/m(2) on days 1 and 8) repeated every 3 weeks for up to six cycles. 74 patients allocated to the control group received the same chemotherapy alone. Patients were allocated using a dynamic minimisation procedure stratified by centre, performance status, and disease stage. The primary endpoint was 6-month progression-free survival (PFS), with a target rate of 40% or higher in the experimental group. Analyses were done on an intention-to-treat basis. This study is completed and is registered with ClinicalTrials.gov, number NCT00415818. FINDINGS: 6-month PFS was 43*2% (32 of 74; 95% CI 33*4-53*5) in the TG4010 plus chemotherapy group, and 35*1% (26 of 74; 25*9-45*3) in the chemotherapy alone group. Fever, abdominal pain, and injection-site pain of any grade according to National Cancer Institute Common Toxicity Criteria were more common in the TG4010 group than in the chemotherapy alone group: 17 of 73 patients (23*3%) versus six of 72 (8*3%), 12 (16*4%) versus two (2*8%), and four (5*5%) versus zero (0%), respectively. The most common grade 3-4 adverse events were neutropenia (33 [45*2%] of patients in the TG4010 plus chemotherapy group vs 31 [43*1%] in the chemotherapy alone group) and fatigue (18 [24*7%] vs 13 [18*1%]); the only grade 3-4 events that differed significantly between groups were anorexia (three [4*1%] vs 10 [13*9%]) and pleural effusion (none vs four [5*6%]). 38 of 73 patients (52*1%) in the TG4010 plus chemotherapy group and 34 of 72 (47*2%) in the chemotherapy alone group had at least one serious adverse event. INTERPRETATION: This phase 2B study suggests that TG4010 enhances the effect of chemotherapy in advanced NSCLC. A confirmatory phase 2B-3 trial has been initiated. FUNDING: Transgene SA, Advanced Diagnostics for New Therapeutic Approaches (ADNA)/OSEO.
Published: 2011
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4. Early surgery for failure after chemoradiation in operable thoracic oesophageal cancer. Analysis of the non-randomised patients in FFCD 9102 phase III trial: Chemoradiation followed by surgery versus chemoradiation alone

Author: Julie, Vincent, Christophe, Mariette, Denis, Pezet, Emmanuel, Huet, Franck, Bonnetain, Olivier, Bouché, Thierry, Conroy, Bernard, Roullet, Jean-François, Seitz, Jean-Philippe, Herr, Frédéric, Di Fiore, Jean-Louis, Jouve, Laurent, Bedenne, M, Ducreux, CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Hôpital Claude Huriez [Lille], CHU Lille, CHU Clermont-Ferrand, Nutrition, inflammation et dysfonctionnement de l'axe intestin-cerveau (ADEN), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Normandie Université (NU), Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de chirurgie digestive [CHU Rouen], Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Fédération Francophone de la Cancérologie Digestive, FFCD, Hôpital Robert Debré, Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims (CHU Reims), Maladies chroniques, santé perçue, et processus d'adaptation (APEMAC), Université Paris Descartes - Paris 5 (UPD5)-Université de Lorraine (UL), Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), UNICANCER, Hôpital de la Milétrie, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Hôpital de la Timone [CHU - APHM] (TIMONE), Hôpital privé Sainte-Marie - Ramsay Générale de Santé, Hôpital Charles Nicolle [Rouen], Butel J, Desselle P, Brice JC, Tissot B, Votte-Lambert A, Joly J, Burtin P, Arnaud JP, Cellier P, Estermann F, Chauvet B, Maringe E, Ozanne F, Varlet F, Becouarn Y, Avril A, Rougier P, Nordlinger B, Vincendet M, Charneau J, Pillon D, Stremsdoerfer N, Pelletier M, Clavero-Fabri MC, Leduc B, Segol P, Argouach LP, Roussel A, Maurel J, Salame R, Lacourt J, Janoray P, Ruget O, Baudet-Klepping D, Dupont G, Bommelaer G, Ruszniewski P, Hammel P, Chaussade S, Dousset B, Denis B, Wagner JD, Tamby E, Petit T, Weiss AM, Barbare JC, Jouve JL, Phelip JM, Senesse P, Michiels C, Maingon P, Coudert B, Fraisse J, Queuniet A, Gasnault L, Gstach JH, Guichard B, Howaizi M, Geoffroy P, Picot C, Fournet J, Mousseau M, Stampfli C, Michel P, Doll J, Durand S, Buffet C, Triboulet JP, Denimal F, Hebbar M, Quandalle P, Mirabel X, Lledo G, Giovannini M, Souillac P, Untereiner M, Leroy-Terquem E, Lacroix H, Francois E, Lagasse JP, Breteau N, Legoux JL, Etienne JC, Delattre JF, Lubrano D, Levy-Chazal N, Palot JP, Nasca S, Demange L, Nguyen TD, Seng S, Michel P, Teniere P, Thevenet P, Le Brise H, Fleury J, Kammerer J, Cosme H, Novello P, Avignon JP, Berton C, Legueul, Parisot P, Aunis G, Vetter D, Platini C, Cals L, Rouhier D, Robin B, Champetier T, Cartalat A, Marchal C, Guillemin F, Flamenbaum M, Cassan D, Ducreux M., Hôpital Claude Huriez, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU - HÔTEL-DIEU Clermont-Ferrand, Service de chirurgie digestive [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Institut de Cancérologie de Lorraine - Alexis Vautrin (ICL), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims ( CHU Reims ), Maladies chroniques, santé perçue, et processus d'adaptation. Approches épidémiologiques et psychologiques. ( APEMAC - EA 4360 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Université de Lorraine ( UL ), Institut de Cancérologie de Lorraine - Alexis Vautrin ( ICL ), CHU de Poitiers, and Hôpital de la Timone [CHU - APHM] ( TIMONE )
Subjects: Male, Cancer Research, Time Factors, Esophageal Neoplasms, Kaplan-Meier Estimate, MESH: Esophagectomy, law.invention, MESH: Proportional Hazards Models, MESH : Adenocarcinoma, 0302 clinical medicine, Randomized controlled trial, law, Risk Factors, MESH : Esophagectomy, MESH: Risk Factors, MESH : Neoplasm Staging, MESH : Female, MESH : Carcinoma, Squamous Cell, MESH: Treatment Outcome, MESH: Chemoradiotherapy, Randomised controlled trial, education.field_of_study, Hazard ratio, [ SDV.SPEE ] Life Sciences [q-bio]/Santé publique et épidémiologie, MESH: Carcinoma, Squamous Cell, Chemoradiotherapy, MESH : Chemoradiotherapy, MESH: Neoplasm Staging, MESH : Risk Factors, Neoadjuvant Therapy, 3. Good health, Oesophageal neoplasms, Treatment Outcome, Oncology, Chemoradiation, 030220 oncology & carcinogenesis, MESH: Esophageal Neoplasms, Carcinoma, Squamous Cell, 030211 gastroenterology & hepatology, Female, Esophageal Squamous Cell Carcinoma, France, MESH : Time Factors, medicine.medical_specialty, MESH: Radiotherapy, Adjuvant, MESH : Male, Population, MESH: Neoadjuvant Therapy, Locally advanced, MESH : Treatment Outcome, Adenocarcinoma, MESH : Radiotherapy, Adjuvant, MESH : Kaplan-Meier Estimate, 03 medical and health sciences, Early surgery, medicine, Humans, Basal cell, Salvage surgery, education, MESH : France, Contraindication, MESH: Kaplan-Meier Estimate, Neoplasm Staging, Proportional Hazards Models, MESH: Humans, business.industry, MESH : Humans, MESH: Adenocarcinoma, MESH: Time Factors, Cancer, medicine.disease, MESH : Proportional Hazards Models, MESH: Male, Surgery, Esophagectomy, MESH: France, Radiotherapy, Adjuvant, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, MESH : Esophageal Neoplasms, business, MESH : Neoadjuvant Therapy, MESH: Female
Abstract: International audience; BACKGROUND:Two randomised trials concerning thoracic oesophageal cancer concluded that for squamous cell carcinoma, chemoradiation alone leads to the same overall survival (OS) as chemoradiation followed by surgery. One of these trials, FFCD 9102, randomised only fit, compliant and operable responders to induction chemoradiation between continuation of chemoradiation and surgery. In the present analysis, the outcome in the patients not eligible for randomisation was calculated to determine if attempt of surgery should be recommended.METHODS:Eligible patients had operable T3-N0/N1-M0 thoracic oesophageal cancer. After initial chemoradiation, patients with no clinical response, or with contraindication to follow any attributed treatment, were not randomised. OS was studied first in the whole population of not randomised patients, and then specifically in clinical non-responders. The impact of surgery on OS was studied in these two populations.FINDINGS:Of the 451 registered patients in the trial, 192 were not randomised. Among them, 111 were clinical non-responders. Median OS was significantly shorter for non-randomised patients (11.5 months) than for randomised patients (18.9 months; p=0.0024). However, for the 112 non-randomised patients who underwent surgery, median OS was not different from that in randomised patients: 17.3 versus 18.9 months (p=0.58). Concerning clinical non-responders, median OS was longer for those who underwent surgery compared to non-operated patients: 17.0 versus 5.5 months (hazard ratio (HR)=0.39 [0.25-0.61]; p
Published: 2015
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5. Toward a NOTCH1/FBXW7/RAS/PTEN-based oncogenetic risk classification of adult T-cell acute lymphoblastic leukemia: a Group for Research in Adult Acute Lymphoblastic Leukemia study

Author: Raouf Ben Abdelali, Véronique Lhéritier, Jean-Yves Cahn, Françoise Huguet, Norbert Ifrah, Agnès Buzyn, Noémie de Gunzburg, Elizabeth Macintyre, Vahid Asnafi, Dominique Payet-Bornet, Sébastien Maury, Jonathan Bond, Thibaud Leguay, Amélie Trinquand, Bertrand Nadel, André Delannoy, Kheira Beldjord, Hervé Dombret, Xavier Thomas, Jérôme Lambert, Ludovic Lhermitte, Hossein Mossafa, Etienne Lengliné, Yves Chalandon, Caroline Bonmati, Aline Tanguy-Schmidt, Centre d'Immunologie de Marseille - Luminy ( CIML ), Aix Marseille Université ( AMU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire de Cytogénétique - Pasteur-Cerba, Laboratoire Pasteur-Cerba, Laboratoire d'Hématologie [Purpan], Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Institut Cochin ( UMR_S567 / UMR 8104 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), TheREx, Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications [Grenoble] ( TIMC-IMAG ), Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut polytechnique de Grenoble - Grenoble Institute of Technology ( Grenoble INP ) -IMAG-Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ) -Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut polytechnique de Grenoble - Grenoble Institute of Technology ( Grenoble INP ) -IMAG-Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ), Centre de Recherche en Cancérologie de Lyon ( CRCL ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon ( HCL ), Hôpital de Jolimont, Haine-Saint-Paul and Cliniques Universitaires St Luc, Service hématologie, Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Service d'hématologie clinique [Avicenne], Université Paris 13 ( UP13 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Avicenne, Lymphocyte et cancer, IFR105-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Imagine - Institut des maladies génétiques ( IMAGINE - U1163 ), Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service Hématologie - IUCT-Oncopole [CHU Toulouse], Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle IUCT [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Institut Cochin (UMR_S567 / UMR 8104), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), 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), Hospices Civils de Lyon (HCL), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], IFR105-Institut National de la Santé et de la Recherche Médicale (INSERM), Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Université Toulouse III - Paul Sabatier (UT3), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5), Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-IMAG-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-IMAG-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Centre de Recherche en Cancérologie de Lyon (CRCL), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Avicenne, Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Male, Ras Proteins/genetics, Oncology, Pathology, MESH : F-Box Proteins, DNA Mutational Analysis, Cell Cycle Proteins, MESH : Gene Deletion, MESH: Receptor, Notch1, 0302 clinical medicine, MESH : Cell Cycle Proteins, Receptor, Notch1, MESH: DNA Mutational Analysis, Young adult, ddc:616, 0303 health sciences, Hazard ratio, PTEN Phosphohydrolase/genetics, hemic and immune systems, 3. Good health, MESH : Phenotype, MESH: Young Adult, 030220 oncology & carcinogenesis, Predictive value of tests, Cohort, F-Box Proteins/genetics, MESH : Proto-Oncogene Proteins, MESH: Membrane Proteins, MESH: ras Proteins, medicine.medical_specialty, MESH : Young Adult, MESH : DNA Mutational Analysis, MESH: Phenotype, MESH: PTEN Phosphohydrolase, Disease-Free Survival, Proto-Oncogene Proteins p21(ras), 03 medical and health sciences, MESH: Cell Cycle Proteins, Humans, PTEN, Ubiquitin-Protein Ligases/genetics, MESH : Predictive Value of Tests, MESH: Kaplan-Meier Estimate, Cell Cycle Proteins/genetics, Receptor, Notch1/genetics, [ SDV.IMM.II ] Life Sciences [q-bio]/Immunology/Innate immunity, MESH: Humans, Proportional hazards model, F-Box Proteins, MESH : Humans, MESH: Adult, MESH : Proportional Hazards Models, MESH: Ubiquitin-Protein Ligases, MESH : Membrane Proteins, MESH: Disease-Free Survival, Mutation, ras Proteins, Adult Acute Lymphoblastic Leukemia, MESH : Genetic Predisposition to Disease, MESH : Ubiquitin-Protein Ligases, MESH : GTP Phosphohydrolases, MESH: Female, Gene Deletion, Cancer Research, F-Box-WD Repeat-Containing Protein 7, Time Factors, MESH : Precursor T-Cell Lymphoblastic Leukemia-Lymphoma, Kaplan-Meier Estimate, MESH : PTEN Phosphohydrolase, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, GTP Phosphohydrolases, MESH: Proportional Hazards Models, MESH: Risk Factors, Risk Factors, hemic and lymphatic diseases, MESH : Female, biology, MESH : Receptor, Notch1, MESH: Genetic Predisposition to Disease, MESH : Adult, MESH : Risk Factors, MESH: Predictive Value of Tests, MESH: Precursor T-Cell Lymphoblastic Leukemia-Lymphoma, Phenotype, MESH : Disease-Free Survival, Female, MESH : Mutation, MESH : Time Factors, Adult, MESH: Mutation, MESH: GTP Phosphohydrolases, Ubiquitin-Protein Ligases, MESH : Male, MESH: F-Box Proteins, MESH: Multivariate Analysis, MESH : Kaplan-Meier Estimate, Young Adult, Predictive Value of Tests, Proto-Oncogene Proteins, Internal medicine, medicine, Genetic Predisposition to Disease, Membrane Proteins/genetics, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/classification/genetics/mortality/therapy, Proportional Hazards Models, 030304 developmental biology, business.industry, MESH: Time Factors, PTEN Phosphohydrolase, Membrane Proteins, MESH : Multivariate Analysis, GTP Phosphohydrolases/genetics, MESH: Male, MESH: Proto-Oncogene Proteins, Proto-Oncogene Proteins/genetics, MESH: Gene Deletion, Multivariate Analysis, biology.protein, MESH : ras Proteins, business
Abstract: Purpose The Group for Research in Adult Acute Lymphoblastic Leukemia (GRAALL) recently reported a significantly better outcome in T-cell acute lymphoblastic leukemia (T-ALL) harboring NOTCH1 and/or FBXW7 (N/F) mutations compared with unmutated T-ALL. Despite this, one third of patients with N/F-mutated T-ALL experienced relapse. Patients and Methods In a series of 212 adult T-ALLs included in the multicenter randomized GRAALL-2003 and -2005 trials, we searched for additional N/K-RAS mutations and PTEN defects (mutations and gene deletion). Results N/F mutations were identified in 143 (67%) of 212 patients, and lack of N/F mutation was confirmed to be associated with a poor prognosis. K-RAS, N-RAS, and PTEN mutations/deletions were identified in three (1.6%) of 191, 17 (8.9%) of 191, and 21 (12%) of 175 patients, respectively. The favorable prognostic significance of N/F mutations was restricted to patients without RAS/PTEN abnormalities. These observations led us to propose a new T-ALL oncogenetic classifier defining low-risk patients as those with N/F mutation but no RAS/PTEN mutation (97 of 189 patients; 51%) and all other patients (49%; including 13% with N/F and RAS/PTEN mutations) as high-risk patients. In multivariable analysis, this oncogenetic classifier remained the only significant prognostic covariate (event-free survival: hazard ratio [HR], 3.2; 95% CI, 1.9 to 5.15; P < .001; and overall survival: HR, 3.2; 95% CI, 1.9 to 5.6; P < .001). Conclusion These data demonstrate that the presence of N/F mutations in the absence of RAS or PTEN abnormalities predicts good outcome in almost 50% of adult T-ALL. Conversely, the absence of N/F or presence of RAS/PTEN alterations identifies the remaining cohort of patients with poor prognosis.
Published: 2013
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6. Prognostic factors of survival in patients with non-infectious mixed cryoglobulinaemia vasculitis: data from 242 cases included in the CryoVas survey

Author: Isabelle Marie, Jean-Marc Léger, Estibaliz Lzaro, Xavier Mariette, Adeline Lacraz, Thomas Quemeneur, Olivier Hermine, Franck Bridoux, Olivier Hinschberger, P. Rullier, Jean-Emmanuel Kahn, Fabrice Carrat, Patrice Cacoub, Thierry Zenone, Christian Pagnoux, P. Belenotti, Fabrice Bonnet, Patricia Senet, Luc de Saint Martin, Guillaume Le Guenno, Antoine Huart, Aurélie Hummel, Evguenia Krastinova, Elisabeth Diot, Benjamin Terrier, Emmanuelle Plaisier, David Launay, Immunologie - Immunopathologie - Immunothérapeutique (I3), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Médecine Interne, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5), Epidémiologie des maladies infectieuses et modélisation (ESIM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Service de Médecine Interne [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Physiopathologie et biothérapies des maladies inflammatoires et autoimmunes, Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Internal Medicine, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de Néphrologie-Transplantation-Dialyse, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Service de Médecine Interne (MARSEILLE - Med Int), Assistance Publique - Hôpitaux de Marseille (APHM), Département de Médecine Interne et Pneumologie [Brest] (DMIP - Brest), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Groupe d'Etude de la Thrombose de Bretagne Occidentale (GETBO), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO), Département de Médecine Interne (VALENCIENNES - Med Int), CH Valenciennes, Service de Néphrologie et Immunopathologie Clinique, Centre Hospitalier Universitaire de Toulouse, PRES Université de Toulouse, Foie, métabolismes et cancer, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CHU Clermont-Ferrand, Laboratoire d'Immunologie (EA 2686), Université de Lille, Droit et Santé, Département de Médecine Interne (MULHOUSE - Med Int), Centre Hospitalier Emile Muller [Mulhouse] (CH E.Muller Mulhouse), Groupe Hospitalier de Territoire Haute Alsace (GHTHA)-Groupe Hospitalier de Territoire Haute Alsace (GHTHA), Service de Médecine Interne B, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Hôpital Bretonneau, Service de médecine interne et centre de référence des maladies rares [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Contrôle de la Réponse Immune B et des Lymphoproliférations (CRIBL), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Centre National de la Recherche Scientifique (CNRS), Service de néphrologie - hémodialyse et transplantation rénale, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Médecine Interne (VALENCE - Med Int), Centre hospitalier de Valence, 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), Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-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), Régulation de la réponse immune, infection VIH-1 et autoimmunité, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de dermatologie et allergologie [CHU Tenon], CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Remodelage et Reparation du Tissu Renal, Service de médecine interne [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Biologie et thérapeutique des pathologies immunitaires (BTPI), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP]-Université Paris Descartes - Paris 5 (UPD5), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Médecine Interne [Rouen], Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Université de Brest (UBO), Centre Hospitalier Universitaire Estaing, CHU Estaing, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP], Service de neurologie 1 [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Service de Dermatologie [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Tenon [APHP], Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC), Immunologie - Immunopathologie - Immunothérapeutique ( I3 ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Cochin [AP-HP]-Université Paris Descartes - Paris 5 ( UPD5 ), Epidémiologie des maladies infectieuses et modélisation ( ESIM ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre de recherche en épidémiologie et santé des populations ( CESP ), Université de Versailles Saint-Quentin-en-Yvelines ( UVSQ ) -Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -CHU Rouen, Normandie Université ( NU ) -Normandie Université ( NU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Service de Médecine Interne ( MARSEILLE - Med Int ), Assistance Publique - Hôpitaux de Marseille ( APHM ), Département de Médecine Interne et Pneumologie [Brest] ( DMIP - Brest ), Centre Hospitalier Régional Universitaire de Brest ( CHRU Brest ), Groupe d'Etude de la Thrombose de Bretagne Occidentale ( GETBO ), Université de Brest ( UBO ), Département de Médecine Interne ( VALENCIENNES - Med Int ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Laboratoire d'Immunologie ( EA 2686 ), Département de Médecine Interne ( MULHOUSE - Med Int ), Centre Hospitalier Emile Muller [Mulhouse] ( CH E.Muller Mulhouse ), Groupe Hospitalier de Territoire Haute Alsace ( GHTHA ) -Groupe Hospitalier de Territoire Haute Alsace ( GHTHA ), Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Cochin [AP-HP], Contrôle de la Réponse Immune B et des Lymphoproliférations ( CRIBL ), Université de Limoges ( UNILIM ) -Génomique, Environnement, Immunité, Santé, Thérapeutique ( GEIST FR CNRS 3503 ) -Centre National de la Recherche Scientifique ( CNRS ), Université de Poitiers-Centre hospitalier universitaire de Poitiers ( CHU Poitiers ), Médecine Interne ( VALENCE - Med Int ), 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 ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], Université Paris-Sud - Paris 11 ( UP11 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Tenon [APHP], Biologie et thérapeutique des pathologies immunitaires ( BTPI ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Centre National de la Recherche Scientifique ( CNRS ), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Service Médecine interne et immunopathologie clinique [CHU Toulouse], Pôle IUCT [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO)-Université de Brest (UBO), Centre National de la Recherche Scientifique (CNRS)-Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: Male, MESH : Retrospective Studies, [SDV]Life Sciences [q-bio], MESH : Aged, 030232 urology & nephrology, Kaplan-Meier Estimate, medicine.disease_cause, Severity of Illness Index, 0302 clinical medicine, Epidemiology, Immunology and Allergy, MESH : Female, MESH: Data Collection, MESH: Aged, MESH : Prognosis, MESH: Middle Aged, Data Collection, Mortality rate, MESH: Vasculitis, Middle Aged, Prognosis, 3. Good health, MESH : Vasculitis, Cryoglobulinemia, Area Under Curve, Female, MESH : Severity of Illness Index, MESH : Data Collection, Vasculitis, medicine.medical_specialty, MESH: Genetic Diseases, Inborn, MESH: Cryoglobulinemia, MESH : Male, Hepatitis C virus, Immunology, Renal function, General Biochemistry, Genetics and Molecular Biology, MESH: Prognosis, MESH : Kaplan-Meier Estimate, 03 medical and health sciences, MESH : Genetic Diseases, Inborn, Rheumatology, Internal medicine, MESH: Severity of Illness Index, Severity of illness, medicine, Humans, MESH : Middle Aged, In patient, MESH: Kaplan-Meier Estimate, Aged, Retrospective Studies, 030203 arthritis & rheumatology, MESH: Humans, [ SDV ] Life Sciences [q-bio], business.industry, MESH : Humans, Genetic Diseases, Inborn, Retrospective cohort study, MESH: Retrospective Studies, medicine.disease, MESH : Cryoglobulinemia, MESH: Male, Surgery, MESH: Area Under Curve, MESH : Area Under Curve, business, MESH: Female
Abstract: International audience; BACKGROUND: Data on the prognosis of non-infectious mixed cryoglobulinaemia vasculitis (CryoVas) in the era of hepatitis C virus screening are lacking. METHODS: The French multicentre and retrospective CryoVas survey included 242 patients with non-infectious mixed CryoVas. Causes of death and prognostic factors of survival were assessed and a prognostic score was determined to predict survival at 5 years. RESULTS: After a median follow-up of 35 months, 42 patients (17%) died. Causes of death were mainly serious infections (50%) and vasculitis flare (19%). One-, 2-, 5- and 10-year overall survival rates were 91%, 89%, 79% and 65%, respectively. A prognostic score, the CryoVas score (CVS), for the prediction of survival at 5 years was devised. Pulmonary and gastrointestinal involvement, glomerular filtration rate 65 years were independently associated with death. At 5 years the death rates were 2.6%, 13.1%, 29.6% and 38.5% for a CVS of 0, 1, 2 and ≥3, respectively. At 1 year the death rates were 0%, 3.2%, 18.5% and 30.8% for a CVS of 0, 1, 2 and ≥3, respectively. The CVS was strongly correlated with the Five Factor Score (FFS) 2009, another prognostic score validated in primary necrotising vasculitis (r=0.82; p65 years, pulmonary and gastrointestinal involvement and renal failure. A score including these variables is significantly associated with the prognosis.
Published: 2013
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7. Rituximab induction immunotherapy for first-line low-tumor-burden follicular lymphoma: survival analyses with 7-year follow-up

Author: Gilles Salles, Philippe Colombat, Charles Foussard, Franck Morschhauser, F. Lazreg, Pierre Soubeyran, Corinne Haioun, Vincent Delwail, Nicole Brousse, Catherine Sebban, Pauline Brice, Philippe Solal-Celigny, Hervé Tilly, Catherine Thieblemont, Loïc Bergougnoux, Eric Deconinck, Service d'hématologie [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Service d'anatomie pathologique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Service d'Hematologie, Hospices Civils de Lyon (HCL)-Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Service d'hématologie, Hôpital Claude Huriez-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service d'hématologie-oncologie adultes, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Plateforme de génétique moléculaire des cancers d'Aquitaine, Institut Bergonié - CRLCC Bordeaux, Service d'Anatomie et de Cytologie Pathologiques [Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Hôpital Jean Minjoz, Service d'hématologie clinique, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel Dieu, Service d'Oncologie Médicale, Centre Léon Bérard [Lyon], Service d'oncologie, CRLCC Henri Becquerel, Service d'Hématologie, Roche, Onco-radiothérapie, hématologie, Centre Jean Bernard, CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Claude Huriez [Lille], CHU Lille-CHU Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Bergonié [Bordeaux], UNICANCER-UNICANCER, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Centre Jean Bernard [Institut Inter-régional de Cancérologie - Le Mans], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Hôpital Bretonneau-CHRU Tours, Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Hospices Civils de Lyon ( HCL ) -Centre Hospitalier Lyon Sud [CHU - HCL] ( CHLS ), Hospices Civils de Lyon ( HCL ), Hôpital Claude Huriez-Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ) -Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Université de Poitiers-Centre hospitalier universitaire de Poitiers ( CHU Poitiers ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -hopital Jean Minjoz, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), CHU Angers-Hôtel Dieu, and Saas, Philippe
Subjects: Male, MESH : Immunization, Passive, MESH : Induction Chemotherapy, Follicular lymphoma, Kaplan-Meier Estimate, Gastroenterology, Antibodies, Monoclonal, Murine-Derived, MESH: Lymphoma, Follicular, 0302 clinical medicine, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, MESH : Female, Lymphoma, Follicular, MESH: Treatment Outcome, education.field_of_study, MESH: Middle Aged, MESH : Neoplasm Recurrence, Local, Induction Chemotherapy, Hematology, MESH: Follow-Up Studies, MESH : Adult, Middle Aged, MESH: Induction Chemotherapy, 3. Good health, MESH : Antineoplastic Agents, Treatment Outcome, Oncology, 030220 oncology & carcinogenesis, MESH : Disease-Free Survival, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Rituximab, MESH: Immunization, Passive, MESH: Neoplasm Recurrence, Local, medicine.drug, Adult, medicine.medical_specialty, [SDV.IMM] Life Sciences [q-bio]/Immunology, MESH : Male, Population, Antineoplastic Agents, MESH : Treatment Outcome, Disease-Free Survival, MESH : Kaplan-Meier Estimate, 03 medical and health sciences, Internal medicine, medicine, Humans, MESH : Middle Aged, Progression-free survival, education, MESH: Kaplan-Meier Estimate, MESH: Humans, business.industry, MESH : Lymphoma, Follicular, MESH : Humans, Immunization, Passive, Induction chemotherapy, MESH : Follow-Up Studies, MESH: Adult, medicine.disease, MESH: Male, MESH : Antibodies, Monoclonal, Murine-Derived, Lymphoma, Surgery, MESH: Antibodies, Monoclonal, Murine-Derived, MESH: Disease-Free Survival, MESH: Antineoplastic Agents, Neoplasm Recurrence, Local, business, Diffuse large B-cell lymphoma, MESH: Female, Progressive disease, Follow-Up Studies, 030215 immunology
Abstract: International audience; BACKGROUND: The purpose of this study was to report long-term results of rituximab induction monotherapy in patients with low-tumor-burden follicular lymphoma (LTBFL). PATIENTS AND METHODS: Of 49 first-line LTBFL patients who received weekly doses of rituximab (375 mg/m(2)), 46 have been followed with a long-term analysis of clinical and molecular responses. RESULTS: Best clinical response (at any staging within a year following treatment) was 80%, 24 (52%) patients had complete or unconfirmed complete response, 13 (28%) had partial response and 9 (20%) had stable or progressive disease. Of 31 patients having a positive bcl2-JH rearrangement, 15 (48%) became negative following treatment. After 83.9 months of follow-up (95% confidence interval 6.4-92.8 months), the median progression-free survival is 23.5 months and overall survival (OS) is 91.7%. Five patients died (one progression, one myelodysplasia, one diffuse large B-cell lymphoma and two solid tumors). Seven patients (15%) are progression-free including five who are bcl2 informative. No unexpected long-term adverse event has been observed. CONCLUSION: A significant proportion of patients remain progression-free 7 years after a single 4-dose rituximab treatment in first-line LTBFL. The 7-year overall survivalOS is very high in this selected population of patients.
Published: 2012
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8. Lenalidomide maintenance after stem-cell transplantation for multiple myeloma

Author: Attal, Michel, Lauwers-Cances, Valerie, Marit, Gerald, Caillot, Denis, Moreau, Philippe, Facon, Thierry, Stoppa, Anne Marie, Hulin, Cyrille, Benboubker, Lofti, Garderet, Laurent, Decaux, Olivier, Leyvraz, Serge, Vekemans, Marie-Christiane, Voillat, Laurent, Michallet, Mauricette, Pegourie, Brigitte, Dumontet, Charles, Roussel, Murielle, Leleu, Xavier, Mathiot, Claire, Payen, Catherine, Avet-Loiseau, Hervé, Harousseau, Jean-Luc, Renseigné, Non, Laboratoire d'Hématologie [Purpan], Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Service d'épidémiologie [Toulouse], Service des maladies du sang, CHU Bordeaux [Bordeaux]-Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux]-Groupe Hospitalier Sud, CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Hématologie et oncologie pédiatrique, 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), Hôpital Claude Huriez [Lille], CHU Lille, Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service Hématologie thérapie cellulaire, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Institut Cochin (UMR_S567 / UMR 8104), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5), Service de Médecine interne et immunologie clinique [Rennes] = internal medicine and clinical immunology [Rennes], CHU Pontchaillou [Rennes], Service d'hématologie [Hôpital Edouard Herriot - HCL], Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'hématologie clinique, Hôpital Hôtel-Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), Hôpital Claude Huriez, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de médecine interne, Centre de Recherche en Cancérologie de Lyon (CRCL), 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 de Recherche en Cancérologie / Nantes - Angers (CRCNA), Centre hospitalier universitaire de Nantes (CHU Nantes)-Faculté de Médecine d'Angers-Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Centre National de la Recherche Scientifique (CNRS)-Hôpital Laennec-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôtel-Dieu de Nantes, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Toulouse III - Paul Sabatier ( UPS ), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), 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 ), Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), CHRU Tours, Institut Cochin ( UMR_S567 / UMR 8104 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ), Centre de Recherche en Cancérologie de Lyon ( 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 de Recherche en Cancérologie / Nantes - Angers ( CRCNA ), and CHU Angers-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Hôpital Laennec-Centre National de la Recherche Scientifique ( CNRS ) -Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes ( CHU Nantes )
Subjects: medicine.medical_treatment, MESH : Aged, MESH: Multiple Myeloma, MESH : Maintenance Chemotherapy, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, 0302 clinical medicine, Maintenance therapy, MESH : Female, MESH: Double-Blind Method, MESH : Neoplasms, Second Primary, Multiple myeloma, MESH: Aged, MESH: Middle Aged, Standard treatment, Hazard ratio, MESH: Thalidomide, General Medicine, MESH: Follow-Up Studies, MESH : Adult, 3. Good health, MESH : Antineoplastic Agents, MESH: Maintenance Chemotherapy, MESH: Young Adult, 030220 oncology & carcinogenesis, MESH : Disease-Free Survival, MESH: Stem Cell Transplantation, medicine.drug, medicine.medical_specialty, MESH: Neoplasms, Second Primary, MESH : Male, MESH : Young Adult, [SDV.CAN]Life Sciences [q-bio]/Cancer, Placebo, MESH : Stem Cell Transplantation, MESH : Thalidomide, MESH : Kaplan-Meier Estimate, 03 medical and health sciences, Internal medicine, medicine, MESH : Double-Blind Method, MESH : Middle Aged, MESH: Kaplan-Meier Estimate, Lenalidomide, Chemotherapy, MESH: Humans, business.industry, MESH : Humans, MESH : Follow-Up Studies, MESH: Adult, medicine.disease, MESH: Male, Surgery, Transplantation, MESH: Disease-Free Survival, MESH: Antineoplastic Agents, MESH : Multiple Myeloma, business, MESH: Female, 030215 immunology
Abstract: BACKGROUND: High-dose chemotherapy with autologous stem-cell transplantation is a standard treatment for young patients with multiple myeloma. Residual disease is almost always present after transplantation and is responsible for relapse. This phase 3, placebocontrolled trial investigated the efficacy of lenalidomide maintenance therapy after transplantation. METHODS:We randomly assigned 614 patients younger than 65 years of age who had nonprogressive disease after first-line transplantation to maintenance treatment with either lenalidomide (10 mg per day for the first 3 months, increased to 15 mg if tolerated) or placebo until relapse. The primary end point was progression-free survival. RESULTS:Lenalidomide maintenance therapy improved median progression-free survival (41 months, vs. 23 months with placebo; hazard ratio, 0.50; P
Published: 2012
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9. A randomized study of defibrillator lead implantations in the right ventricular mid-septum versus the apex: the SEPTAL study

Author: Pascal Defaye, Dominique Babuty, Jean-Pierre Cebron, Philippe Mabo, Frédéric Anselme, Jean-Claude Daubert, Olivier Paziaud, Elisabeth Mouton, Jean Marc Davy, Pierre Mondoly, Aude Tassin, Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), Cardiac Stimulation and Rhythmology, CHU Grenoble, CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service de cardiologie [CHU HEGP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Service de cardiologie [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Laboratoire Traitement du Signal et de l'Image ( LTSI ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Européen Georges Pompidou [APHP] ( HEGP ), Service de cardiologie [Rouen], CHU Rouen-Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ), and Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Male, medicine.medical_treatment, MESH : Aged, heart failure, MESH: Logistic Models, Electrocardiography, 0302 clinical medicine, MESH: Treatment Outcome, MESH: Middle Aged, MESH: Ventricular Septum, MESH : Electric Countershock, Cardiac Pacing, Artificial, Implantable cardioverter-defibrillator, 3. Good health, Defibrillators, Implantable, MESH : Electrocardiography, Ventricular Fibrillation, Cardiology and Cardiovascular Medicine, medicine.medical_specialty, Heart Ventricles, Electric Countershock, MESH: Cardiac Pacing, Artificial, Sudden death, MESH: Defibrillators, Implantable, Disease-Free Survival, 03 medical and health sciences, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Physiology (medical), Humans, MESH : Middle Aged, MESH: Kaplan-Meier Estimate, Aged, MESH: Humans, MESH : Humans, MESH: Adult, medicine.disease, MESH: Single-Blind Method, MESH : Prosthesis Design, Logistic Models, MESH: Disease-Free Survival, MESH : Heart Ventricles, Feasibility Studies, MESH: Tachycardia, Ventricular, MESH: Heart Ventricles, MESH: Feasibility Studies, MESH: Female, right ventricular apex, MESH : Logistic Models, Tachycardia, implantable cardioverter defibrillator, Time Factors, MESH : Single-Blind Method, MESH: Electric Countershock, Kaplan-Meier Estimate, 030204 cardiovascular system & hematology, Implantable defibrillator, MESH : Ventricular Septum, MESH : Female, right ventricular mid-septum, Single-Blind Method, 030212 general & internal medicine, [ SDV.IB ] Life Sciences [q-bio]/Bioengineering, MESH: Aged, leads, Ejection fraction, pacing, medicine.diagnostic_test, MESH : Adult, [ SDV.MHEP.CSC ] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Middle Aged, MESH: Ventricular Fibrillation, Treatment Outcome, MESH : Disease-Free Survival, [SDV.IB]Life Sciences [q-bio]/Bioengineering, Female, France, medicine.symptom, MESH: Prosthesis Design, MESH : Time Factors, Adult, MESH : Feasibility Studies, MESH : Ventricular Fibrillation, MESH : Male, sudden death, MESH : Treatment Outcome, Ventricular Septum, MESH : Tachycardia, Ventricular, Prosthesis Design, MESH : Kaplan-Meier Estimate, medicine, MESH : France, business.industry, MESH: Time Factors, MESH: Male, Surgery, MESH : Cardiac Pacing, Artificial, MESH: Electrocardiography, MESH: France, Heart failure, Tachycardia, Ventricular, Implant, business, MESH : Defibrillators, Implantable
Abstract: Impact of Recalls on ICD Utilization. Introduction: The study was designed to evaluate the feasibility and performance of right ventricular (RV) mid-septal versus apical implantable defibrillator (ICD) lead placement. Methods and Results: SEPTAL is a randomized, noninferiority trial, which randomly assigned patients to implantation of ICD leads in the RV mid-septum versus apex, with a primary objective of comparing the implant success rate of implant at each site, based on strict electrical predefined criteria. We also compared the (1) pacing lead characteristics, (2) rates of appropriate and inappropriate ICD therapies, and (3) all-cause mortality between the 2 sites at 1 year. The trial enrolled 215 patients (mean age = 59.7 ± 12.4 years, mean LVEF = 34.0 ± 14.2%, 84.2% men), of whom 148 (68.8%) presented with ischemic heart disease. The ICD indication was primary prevention in 117 patients (54.4%). The lead was successfully implanted in 96/107 patients (89.7%) assigned to the RV mid-septum, and in 99/108 (91.7%) assigned to the apex (ns). The 1-year rate of lead-related adverse events was similar in both groups. A total of 8 first inappropriate ICD therapies (7.9%) were delivered in the RV mid-septal group, versus 8 (7.8%) in the apical group (ns), while first appropriate therapies were delivered to 22 (21.4%) and 24 patients (23.8%), respectively (ns). All-cause mortality was 7.9% in the RV mid-septal versus 2.9% in the RV apical group (ns). Conclusion: This study confirmed the technical feasibility and noninferior performance of ICD leads implanted in the RV mid-septum versus the apex. (J Cardiovasc Electrophysiol, Vol. 23, pp. 853-860, August 2012)
Published: 2012
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10. Mutational characterization of individual breast tumors: TP53 and PI3K pathway genes are frequently and distinctively mutated in different subtypes

Author: Sandrine Boyault, Thomas Bachelot, Alain Puisieux, Christine Lasset, Claudine Navarro, Isabelle Treilleux, Youenn Drouet, Eric Tabone, Qing Wang, Génomique Fonctionnelle des Tumeurs Solides (U1162), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Biostatistiques santé, Département biostatistiques et modélisation pour la santé et l'environnement [LBBE], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), 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), Equipe de prévention et épidémiologie génétique, Centre Léon Bérard [Lyon], Biologie Fonctionnelle, Insectes et Interactions (BF2I), Institut National de la Recherche Agronomique (INRA)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA), Luzhou Medical college, Department of spinal surgery, Eq 11, Oncogénèse et progression tumorale, Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-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 de Recherche en Cancérologie de Lyon (CRCL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Département de Médecine Nucléaire, Eq 09, Centre de Recherche en Cancérologie de Lyon (CRCL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Département de Biopathologie, Centre Léon Bérard [Lyon]-Hospices Civils de Lyon (HCL)-Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL)-Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Eq 02, Institut Universitaire de France (IUF), Ministère de l'Education nationale, de l’Enseignement supérieur et de la Recherche (M.E.N.E.S.R.)-Ministère de l'Education nationale, de l’Enseignement supérieur et de la Recherche (M.E.N.E.S.R.)-Centre de Recherche en Cancérologie de Lyon (CRCL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Département de Médecine Nucléaire, 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]-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)-Département de Biopathologie, Ministère de l'Education nationale, de l’Enseignement supérieur et de la Recherche (M.E.N.E.S.R.)-Ministère de l'Education nationale, de l’Enseignement supérieur et de la Recherche (M.E.N.E.S.R.)-Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Genomique Fonctionnelle des Tumeurs Solides, Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ) -IFR105-Université Paris Diderot - Paris 7 ( UPD7 ), Laboratoire de Biométrie et Biologie Evolutive ( LBBE ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique ( Inria ) -Centre National de la Recherche Scientifique ( CNRS ), 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 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 de Recherche en Cancérologie de Lyon ( CRCL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Département de Médecine Nucléaire, Centre de Recherche en Cancérologie de Lyon ( CRCL ), 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]-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 ) -Département de Biopathologie, Centre Léon Bérard [Lyon]-Hospices Civils de Lyon ( HCL ) -Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ) -Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon ( HCL ), Biologie Fonctionnelle, Insectes et Interactions ( BF2I ), Institut National de la Recherche Agronomique ( INRA ) -Institut National des Sciences Appliquées de Lyon ( INSA Lyon ), Université de Lyon-Institut National des Sciences Appliquées ( INSA ) -Université de Lyon-Institut National des Sciences Appliquées ( INSA ), Institut Universitaire de France ( IUF ), Ministère de l'Éducation nationale, de l’Enseignement supérieur et de la Recherche ( M.E.N.E.S.R. ) -Ministère de l'Éducation nationale, de l’Enseignement supérieur et de la Recherche ( M.E.N.E.S.R. ) -Centre de Recherche en Cancérologie de Lyon ( CRCL ), and Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS )
Subjects: MESH: Signal Transduction, Receptors, Steroid, Cancer Research, DNA Mutational Analysis, MESH : Aged, AKT1, Kaplan-Meier Estimate, MESH : PTEN Phosphohydrolase, MESH : Breast Neoplasms, Gene mutation, MESH: Cadherins, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, CDH1, Phosphatidylinositol 3-Kinases, 0302 clinical medicine, MESH: Carcinoma, Lobular, MESH : Female, MESH: DNA Mutational Analysis, MESH: Tumor Suppressor Protein p53, MESH: Genetic Association Studies, Genetics, MESH: Aged, 0303 health sciences, MESH: Middle Aged, Carcinoma, Ductal, Breast, MESH : Carcinoma, Lobular, Middle Aged, MESH : Adult, Cadherins, 3. Good health, MESH : Proto-Oncogene Proteins c-akt, Oncology, 030220 oncology & carcinogenesis, Female, MESH : Cadherins, Signal Transduction, Adult, Class I Phosphatidylinositol 3-Kinases, Breast Neoplasms, [SDV.CAN]Life Sciences [q-bio]/Cancer, MESH : DNA Mutational Analysis, Biology, MESH: PTEN Phosphohydrolase, MESH : Kaplan-Meier Estimate, 03 medical and health sciences, Breast cancer, Antigens, CD, medicine, Humans, PTEN, MESH : Middle Aged, Gene, Genetic Association Studies, PI3K/AKT/mTOR pathway, MESH: Kaplan-Meier Estimate, Aged, 030304 developmental biology, MESH : Signal Transduction, MESH: Humans, MESH: Proto-Oncogene Proteins c-akt, MESH : Humans, PTEN Phosphohydrolase, MESH : Carcinoma, Ductal, Breast, MESH : Phosphatidylinositol 3-Kinases, MESH: Adult, MESH : Genetic Association Studies, medicine.disease, MESH: Carcinoma, Ductal, Breast, Carcinoma, Lobular, MESH : Tumor Suppressor Protein p53, MESH: Phosphatidylinositol 3-Kinases, biology.protein, Tumor Suppressor Protein p53, Proto-Oncogene Proteins c-akt, MESH : Receptors, Steroid, MESH: Female, MESH: Breast Neoplasms, MESH: Receptors, Steroid
Abstract: International audience; Understanding how cancer genes are mutated in individual tumors is an important issue with potential clinical and therapeutic impact. This is especially relevant with recently developed targeted therapies since mutated genes can be targets and/or predictors. However, to date, gene mutation profiling in individual tumors is still underexplored. Breast cancer is composed of various subtypes. We presumed that this heterogeneity reflected the involvement of different molecular mechanisms including gene mutations that affect defined signaling pathways. Unlike the majority of published mutational studies, this study was aimed to draw a mutation profile in individual tumors by screening a panel of cancer genes in the same tumor. Thus, five genes frequently mutated in breast cancers: TP53, PIK3CA, PTEN, CDH1, and AKT1 were screened in each of 120 human primary breast tumors. Mutations in at least one of these genes were found in 62.5% of the tumors, of which the majority carried a single-gene mutation. Interestingly, a substantial proportion of tumors carried mutations either in TP53 or in genes of the PI3K pathway (PIK3CA or PTEN or AKT1). These two distinct mutation patterns were significantly associated to hormone receptor expression but independent of HER2 status.
Published: 2012
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11. Phase II study of the mammalian target of rapamycin inhibitor ridaforolimus in patients with advanced bone and soft tissue sarcomas

Author: John W. Loewy, George D. Demetri, Lori Berk, Laurence H. Baker, Victor M. Rivera, Arthur P. Staddon, Gina Z. D'Amato, Tim Clackson, Monica M. Mita, Kamalesh Kumar Sankhala, Frank G. Haluska, Scott M. Schuetze, Jean-Yves Blay, Anthony W. Tolcher, Sant P. Chawla, International Institute of Clinical Studies, Pennsylvania Oncology Hematology Associates, 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), Centre Léon Bérard [Lyon], Department of Cancer Biology, Dana-Farber Cancer Institute [Boston], Centre de Recherche en Cancérologie de Lyon ( CRCL ), Université Claude Bernard Lyon 1 ( UCBL ), and Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS )
Subjects: Male, Vascular Endothelial Growth Factor A, Oncology, Cancer Research, Pathology, MESH : Aged, Phases of clinical research, Kaplan-Meier Estimate, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, chemistry.chemical_compound, 0302 clinical medicine, MESH : Tumor Markers, Biological, Clinical endpoint, Medicine, MESH : Female, Infusions, Intravenous, MESH: Treatment Outcome, MESH: Aged, 0303 health sciences, education.field_of_study, MESH: Middle Aged, TOR Serine-Threonine Kinases, Soft tissue, Sarcoma, MESH : Infusions, Intravenous, Middle Aged, MESH : Adult, MESH: Bone Neoplasms, 3. Good health, MESH : Antineoplastic Agents, Treatment Outcome, 030220 oncology & carcinogenesis, MESH : Vascular Endothelial Growth Factor A, MESH : TOR Serine-Threonine Kinases, MESH : Disease-Free Survival, Female, Adult, medicine.medical_specialty, MESH : Male, MESH : Sex Factors, Population, MESH : Drug Administration Schedule, Antineoplastic Agents, Bone Neoplasms, [SDV.CAN]Life Sciences [q-bio]/Cancer, MESH : Treatment Outcome, Bone Sarcoma, MESH: Drug Administration Schedule, MESH : Sarcoma, Disease-Free Survival, Drug Administration Schedule, Ridaforolimus, MESH : Kaplan-Meier Estimate, 03 medical and health sciences, Sex Factors, MESH: Sex Factors, Internal medicine, Biomarkers, Tumor, Humans, MESH : Middle Aged, education, MESH: Infusions, Intravenous, MESH: TOR Serine-Threonine Kinases, MESH: Kaplan-Meier Estimate, Aged, 030304 developmental biology, MESH : Bone Neoplasms, Sirolimus, MESH: Humans, Errata, Akt/PKB signaling pathway, business.industry, MESH : Sirolimus, MESH: Vascular Endothelial Growth Factor A, MESH : Humans, MESH: Adult, MESH: Male, Clinical trial, chemistry, MESH: Sarcoma, MESH: Tumor Markers, Biological, MESH: Disease-Free Survival, MESH: Antineoplastic Agents, MESH: Sirolimus, business, MESH: Female
Abstract: Purpose Ridaforolimus is an inhibitor of mammalian target of rapamycin, an integral component of the phosphatidyl 3-kinase/AKT signaling pathway, with early evidence of activity in sarcomas. This multicenter, open-label, single-arm, phase II trial was conducted to assess the antitumor activity of ridaforolimus in patients with distinct subtypes of advanced sarcomas. Patients and Methods Patients with metastatic or unresectable soft tissue or bone sarcomas received ridaforolimus 12.5 mg administered as a 30-minute intravenous infusion once daily for 5 days every 2 weeks. The primary end point was clinical benefit response (CBR) rate (complete response or partial response [PR] or stable disease ≥ 16 weeks). Safety, progression-free survival (PFS), overall survival (OS), time to progression, and duration of response were also evaluated. Results A total of 212 patients were treated in four separate histologic cohorts. In this heavily pretreated population, 61 patients (28.8%) achieved CBR. Median PFS was 15.3 weeks; median OS was 40 weeks. Response Evaluation Criteria in Solid Tumors (RECIST) confirmed response rate was 1.9%, with four patients achieving confirmed PR (two with osteosarcoma, one with spindle cell sarcoma, and one with malignant fibrous histiocytoma). Archival tumor protein markers analyzed were not correlated with CBR. Related adverse events were generally mild or moderate and consisted primarily of stomatitis, mucosal inflammation, mouth ulceration, rash, and fatigue. Conclusion Single-agent ridaforolimus in patients with advanced and pretreated sarcomas led to PFS results that compare favorably with historical metrics. A phase III trial based on these data will further define ridaforolimus activity in sarcomas.
Published: 2012
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12. Pediatric-inspired intensified therapy of adult T-ALL reveals the favorable outcome of NOTCH1/FBXW7 mutations, but not of low ERG/BAALC expression: a GRAALL study

Author: Ben Abdelali, Raouf, Asnafi, Vahid, Leguay, Thibaut, Boissel, Nicolas, Buzyn, Agnès, Chevallier, Patrice, Thomas, Xavier, Lepretre, Stephane, Huguet, Françoise, Vey, Norbert, Escoffre-Barbe, Martine, Tavernier, Emmanuelle, Reman, Oumedaly, Fegueux, Nathalie, Turlure, Pascal, Rousselot, Philippe, Cahn, Jean-Yves, Lheritier, Veronique, Chalandon, Yves, Béné, Marie-Christine, Macintyre, Elizabeth, Dombret, Hervé, Ifrah, Norbert, Renseigné, Non, Université Paris Descartes - Paris 5 (UPD5), Institut Cochin (UMR_S567 / UMR 8104), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), equipe 14, 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)-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)-Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Groupe d'étude des proliférations lymphoïdes (GPL), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire d'Hématologie [Purpan], Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Hematology (IPC-Marseille), Service d'hématologie clinique, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou, Service d'hématologie et oncologie médicale, Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie-Université de Montpellier (UM), Service d'Hématologie clinique et thérapie cellulaire [CHU Limoges], CHU Limoges, Hematology, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, Service d'Immunologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service 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), Lymphocyte et cancer, IFR105-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'hématologie clinique [Avicenne], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris 13 (UP13)-Hôpital Avicenne [AP-HP], 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]-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)-Hôpital Edouard Herriot [CHU - HCL], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), Hôpital Lapeyronie-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université Montpellier 1 (UM1)-Université de Montpellier (UM), Université Paris Descartes - Paris 5 ( UPD5 ), Institut Cochin ( UMR_S567 / UMR 8104 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Centre de Recherche en Cancérologie de Lyon ( 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]-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 ) -Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ), Groupe d'étude des proliférations lymphoïdes ( GPL ), Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Toulouse III - Paul Sabatier ( UPS ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Hôpital Pontchaillou, Université Montpellier 1 ( UM1 ) -Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ) -Hôpital Lapeyronie, Université Joseph Fourier - Grenoble 1 ( UJF ) -CHU Grenoble, Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], IFR105-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Paris 13 ( UP13 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Avicenne, Cytokines, hématopoïèse et réponse immune (CHRI), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service Hématologie - IUCT-Oncopole [CHU Toulouse], Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle IUCT [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Rennes (UR)-Hôpital Pontchaillou, Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5), Centre de Recherche en Cancérologie de Lyon (CRCL), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Avicenne, and Université Paris Descartes - Paris 5 (UPD5) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Centre National de la Recherche Scientifique (CNRS)
Subjects: Oncology, Male, MESH : F-Box Proteins, MESH : Prospective Studies, Cell Cycle Proteins, MESH: Receptor, Notch1, Biochemistry, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, 0302 clinical medicine, MESH : Cell Cycle Proteins, Neoplasm Proteins/genetics, MESH : Child, Clinical Protocols, MESH: Child, Mutational status, Favorable outcome, Prospective Studies, MESH: Leukemia-Lymphoma, Adult T-Cell, Receptor, Notch1, Child, ComputingMilieux_MISCELLANEOUS, MESH: Treatment Outcome, ddc:616, 0303 health sciences, Mutation, MESH : Trans-Activators, MESH: Middle Aged, Prognosis, Neoplasm Proteins, MESH: Young Adult, 030220 oncology & carcinogenesis, F-Box Proteins/genetics, Erg, medicine.medical_specialty, MESH: Gene Expression, Immunology, MESH : Young Adult, Disease-Free Survival, MESH: Prognosis, 03 medical and health sciences, MESH : Neoplasm Proteins, MESH: Cell Cycle Proteins, MESH : Adolescent, Humans, MESH : Middle Aged, Ubiquitin-Protein Ligases/genetics, MESH : Predictive Value of Tests, MESH : Clinical Protocols, MESH: Kaplan-Meier Estimate, Cell Cycle Proteins/genetics, MESH: Adolescent, Receptor, Notch1/genetics, MESH: Humans, F-Box Proteins, MESH : Humans, MESH: Adult, Leukemia-Lymphoma, Adult T-Cell/classification/drug therapy/genetics, MESH: Ubiquitin-Protein Ligases, MESH : Leukemia-Lymphoma, Adult T-Cell, MESH : Gene Expression, MESH: Disease-Free Survival, Adult Acute Lymphoblastic Leukemia, MESH : Ubiquitin-Protein Ligases, Carcinogenesis, MESH: Female, MESH: Neoplasm Proteins, Multivariate analysis, F-Box-WD Repeat-Containing Protein 7, Gene Expression, Kaplan-Meier Estimate, medicine.disease_cause, Bioinformatics, MESH: Clinical Protocols, Leukemia-Lymphoma, Adult T-Cell, MESH : Female, BAALC, MESH : Prognosis, MESH : Receptor, Notch1, Hematology, MESH : Adult, Middle Aged, MESH: Predictive Value of Tests, Treatment Outcome, MESH : Disease-Free Survival, Female, MESH : Mutation, Adult, MESH: Mutation, Adolescent, MESH: Trans-Activators, MESH : Male, Ubiquitin-Protein Ligases, MESH: F-Box Proteins, [SDV.CAN]Life Sciences [q-bio]/Cancer, MESH : Treatment Outcome, Trans-Activators/genetics, MESH : Kaplan-Meier Estimate, Young Adult, Transcriptional Regulator ERG, Predictive Value of Tests, Internal medicine, medicine, 030304 developmental biology, business.industry, Cell Biology, MESH: Male, MESH: Prospective Studies, Trans-Activators, business
Abstract: Despite recent progress in the understanding of acute lymphoblastic leukemia (T-ALL) oncogenesis, few markers are sufficiently frequent in large subgroups to allow their use in therapeutic stratification. Low ERG and BAALC expression (E/Blow) and NOTCH1/FBXW7 (N/F) mutations have been proposed as powerful prognostic markers in large cohorts of adult T-ALL. We therefore compared the predictive prognostic value of N/F mutations versus E/Blow in 232 adult T-ALLs enrolled in the LALA-94 and Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL) protocols. The outcome of T-ALLs treated in the pediatric-inspired GRAALL trials was significantly superior to the LALA-94 trial. Overall, 43% and 69% of adult T-ALL patients were classified as E/Blow and N/F mutated, respectively. Strikingly, the good prognosis of N/F mutated patients was stronger in more intensively treated, pediatric-inspired GRAALL patients. The E/B expression level did not influence the prognosis in any subgroup. N/F mutation status and the GRAALL trial were the only 2 independent factors that correlated with longer overall survival by multivariate analysis. This study demonstrates that the N/F mutational status and treatment protocol are major outcome determinants for adults with T-ALL, the benefit of pediatric inspired protocols being essentially restricted to the N/F mutated subgroup.
Published: 2011
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13. Nomograms for predicting local recurrence, distant metastases, and overall survival for patients with locally advanced rectal cancer on the basis of European randomized clinical trials

Author: Guido Lammering, Marek Bębenek, Bruce D. Minsky, Krzysztof Bujko, M.C. Barba, Maria Antonietta Gambacorta, Aldo Sainato, Jean Pierre Gerard, Philippe Lambin, Ruud G.P.M. van Stiphout, Vincenzo Valentini, Laurence Collette, Rolf Sauer, Luca Cionini, Jean François Bosset, Franck Bonnetain, Claus Rödel, Centre d'épidémiologie des populations (CEP), Université de Bourgogne (UB)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER, Service d'Oncologie Médicale [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (EA 3181) (CEF2P / CARCINO), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Centre de Recherche en Physique de la Matière et du Rayonnement [Namur] (PMR), Université de Namur [Namur] (UNamur), Centre d'épidémiologie des populations ( CEP ), Université de Bourgogne ( UB ) -Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc ( CRLCC - CGFL ), Service d'oncologie Médicale, Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Hôpital Jean Minjoz, Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC ( CEF2P / CARCINO ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Université Bourgogne Franche-Comté ( UBFC ) -Université de Franche-Comté ( UFC ), Centre Antoine Lacassagne, CRLCC Antoine Lacassagne, Centre de Recherche en Physique de la Matière et du Rayonnement [Namur] ( PMR ), and Université de Namur [Namur]
Subjects: Oncology, Male, Cancer Research, Colorectal cancer, MESH : Aged, Kaplan-Meier Estimate, MESH : Randomized Controlled Trials as Topic, law.invention, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, 0302 clinical medicine, Randomized controlled trial, law, MESH : Female, Stage (cooking), Neoplasm Metastasis, MESH: Models, Theoretical, MESH : Rectal Neoplasms, Settore MED/36 - DIAGNOSTICA PER IMMAGINI E RADIOTERAPIA, Randomized Controlled Trials as Topic, MESH: Aged, 0303 health sciences, MESH: Middle Aged, MESH : Neoplasm Recurrence, Local, Age Factors, Middle Aged, MESH : Adult, 3. Good health, Europe, 030220 oncology & carcinogenesis, MESH : Neoplasm Metastasis, Female, MESH: Neoplasm Recurrence, Local, Adult, medicine.medical_specialty, MESH : Sex Factors, MESH : Male, MESH : Europe, [SDV.CAN]Life Sciences [q-bio]/Cancer, MESH : Kaplan-Meier Estimate, 03 medical and health sciences, RECTAL CANCER, Sex Factors, MESH: Sex Factors, Internal medicine, medicine, Humans, MESH : Middle Aged, Survival analysis, MESH: Kaplan-Meier Estimate, 030304 developmental biology, Aged, MESH: Age Factors, MESH: Humans, Proportional hazards model, business.industry, Rectal Neoplasms, MESH : Models, Theoretical, MESH : Humans, MESH: Rectal Neoplasms, MESH: Adult, Nomogram, Models, Theoretical, medicine.disease, MESH: Neoplasm Metastasis, MESH: Male, Surgery, Clinical trial, MESH: Randomized Controlled Trials as Topic, MESH : Age Factors, MESH: Europe, Neoplasm Recurrence, Local, business, MESH: Female, Chemoradiotherapy
Abstract: Purpose The purpose of this study was to develop accurate models and nomograms to predict local recurrence, distant metastases, and survival for patients with locally advanced rectal cancer treated with long-course chemoradiotherapy (CRT) followed by surgery and to allow for a selection of patients who may benefit most from postoperative adjuvant chemotherapy and close follow-up. Patients and Methods All data (N = 2,795) from five major European clinical trials for rectal cancer were pooled and used to perform an extensive survival analysis and to develop multivariate nomograms based on Cox regression. Data from one trial was used as an external validation set. The variables used in the analysis were sex, age, clinical tumor stage stage, tumor location, radiotherapy dose, concurrent and adjuvant chemotherapy, surgery procedure, and pTNM stage. Model performance was evaluated by the concordance index (c-index). Risk group stratification was proposed for the nomograms. Results The nomograms are able to predict events with a c-index for external validation of local recurrence (LR; 0.68), distant metastases (DM; 0.73), and overall survival (OS; 0.70). Pathologic staging is essential for accurate prediction of long-term outcome. Both preoperative CRT and adjuvant chemotherapy have an added value when predicting LR, DM, and OS rates. The stratification in risk groups allows significant distinction between Kaplan-Meier curves for outcome. Conclusion The easy-to-use nomograms can predict LR, DM, and OS over a 5-year period after surgery. They may be used as decision support tools in future trials by using the three defined risk groups to select patients for postoperative chemotherapy and close follow-up ( http://www.predictcancer.org ).
Published: 2011
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14. Renal cell carcinoma (RCC) in patients with end-stage renal disease exhibits many favourable clinical, pathologic, and outcome features compared with RCC in the general population

Author: Laurent Salomon, Lionel Badet, Georges Karam, Jacques Tostain, Pierre Bigot, Nathalie Rioux-Leclercq, Sébastien Barbet, Jean-Etienne Terrier, Bernard Escudier, Michel Soulié, Hicham Elkentaoui, Abdel-Rahmène Azzouzi, Fabrice Dugardin, Yann Neuzillet, Jean-Christophe Bernhard, Jacques Hubert, Aurélien Descazeaux, Karim Fehri, Nicolas Brichart, Philippe Paparel, J.M. Boutin, Laurent Guy, Baptiste Tisserand, Arnaud Mejean, Ismaël Galliot, Marc-Olivier Timsit, Laurence Bastien, Jérôme Rigaud, Antoine Valeri, Jacques Petit, Laurent Zini, Benoit Barrou, Christian Pfister, Xavier Tillou, Franck Bruyère, Fabien Saint, Herve Lang, Jean-Jacques Patard, Marie-Dominique Azemar, Denis Chautard, Julien Branchereau, Hervé Wallerand, Pascal Rischmann, Laura Poissonnier, Charles Deruelle, Lucille Martin, Laurence Albiges, Jacques Irani, Arnauld Villers, Thierry Lebret, Hervé Baumert, François Kleinclauss, Nicolas Terrier, Jean-Alexandre Long, Pierre-Etienne Theveniaud, M. Gigante, Frédéric Staerman, Jean-Marie Ferriere, Romain Mathieu, Morgan Rouprêt, F. Sallusto, Benoit Feuillu, Service d'urologie, Hôpital Foch [Suresnes], CHU Amiens-Picardie, Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Hôpital Pontchaillou-CHU Pontchaillou [Rennes], CHU Grenoble-Hôpital Michallon, Service d'urologie-andrologie, CHU Saint-Etienne-Université Jean Monnet [Saint-Étienne] ( UJM ) -Hôpital nord, Service d'urologie [Centre Hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] ( CHLS ), Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ), Hôpital Saint-Joseph, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy ( IGR ), CHU Strasbourg, Service d'anatomie et cytologie pathologiques [Rennes], Université d'Angers ( UA ) -CHU Angers, Service d'urologie, andrologie et transplantation rénale, Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Institut Mondor de recherche biomédicale ( IMRB ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Service d'urologie [Tours], Hôpital Bretonneau-CHRU Tours, Hôtel-Dieu, Service d'Urologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), Hôpital Huriez-Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Service de Chirurgie urologique et andrologie [CHU Limoges], CHU Limoges, Service d'urologie et transplantation rénales [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], Service de Néphrologie et Urologie, Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Hôpital Saint-Jacques, Service d'urologie [Rouen], CHU Rouen-Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ), Université de Reims Champagne-Ardenne ( URCA ), Centre hospitalier universitaire de Poitiers ( CHU Poitiers ) -Hôpital La Milétrie, Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Descartes - Paris 5 ( UPD5 ) -CHU Necker - Enfants Malades [AP-HP], Service d'Urologie - Transplantation Rénale - Andrologie, CHU Toulouse [Toulouse]-Hôpital de Rangueil, CHU Toulouse [Toulouse], CHU Clermont-Ferrand-Hôpital Gabriel Montpied, Université de Brest ( UBO ) -Centre Hospitalier Régional Universitaire de Brest ( CHRU Brest ), Service d'urologie [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Bicêtre, members of the Comité de Transplantation de l'Association Française d'Urologie, the Comité de Cancérologie de l'Association Française d'Urologie, Service d'urologie [Rennes], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], CHU Saint-Etienne-Université Jean Monnet [Saint-Étienne] (UJM)-Hôpital nord, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Institut Gustave Roussy (IGR), Université d'Angers (UA)-Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Institut Mondor de recherche biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital Bretonneau-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Hôpital Huriez-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service d'urologie et transplantation rénales [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Hôpital Saint-Jacques, CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Université de Reims Champagne-Ardenne (URCA), Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Hôpital La Milétrie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Brest (UBO)-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital Bicêtre-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11), Service d'urologie [Rennes] = Urology [Rennes], Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Service d'anatomie et cytologie pathologiques [Rennes] = Anatomy and Cytopathology [Rennes], CHU Pontchaillou [Rennes], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Service d'Urologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Hôpital Saint-Jacques, CHU Clermont-Ferrand-CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, De Villemeur, Hervé, CHU Saint-Etienne-Université Jean Monnet - Saint-Étienne (UJM)-Hôpital nord, Département d'Urologie-Andrologie et Transplantation Rénale [CHU Toulouse], Pôle Urologie - Néphrologie - Dialyse - Transplantations - Brûlés - Chirurgie plastique - Explorations fonctionnelles et physiologiques [CHU Toulouse], and Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)
Subjects: Male, [ SDV.MHEP.UN ] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, MESH: Chi-Square Distribution, Time Factors, MESH : Retrospective Studies, 030232 urology & nephrology, MESH : Aged, Kaplan-Meier Estimate, MESH: Risk Assessment, urologic and male genital diseases, Gastroenterology, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, MESH: Proportional Hazards Models, MESH : Carcinoma, Renal Cell, 0302 clinical medicine, Renal cell carcinoma, MESH: Risk Factors, Risk Factors, MESH : Female, MESH : Neoplasm Staging, MESH : Risk Assessment, MESH: Treatment Outcome, MESH: Aged, education.field_of_study, Univariate analysis, MESH: Middle Aged, MESH: Carcinoma, Renal Cell, MESH: Neoplasm Staging, Middle Aged, MESH : Adult, MESH : Survival Rate, MESH : Risk Factors, Kidney Neoplasms, 3. Good health, Survival Rate, Treatment Outcome, MESH: Kidney Failure, Chronic, 030220 oncology & carcinogenesis, Female, France, MESH : Time Factors, Adult, medicine.medical_specialty, MESH: Survival Rate, Urology, MESH : Male, Population, [SDV.CAN]Life Sciences [q-bio]/Cancer, MESH : Treatment Outcome, Risk Assessment, MESH : Kidney Failure, Chronic, End stage renal disease, MESH : Kaplan-Meier Estimate, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, medicine, Humans, MESH : Middle Aged, education, MESH : France, Survival rate, Carcinoma, Renal Cell, MESH: Kaplan-Meier Estimate, Aged, Neoplasm Staging, Proportional Hazards Models, Retrospective Studies, MESH: Humans, Chi-Square Distribution, MESH : Chi-Square Distribution, business.industry, MESH: Time Factors, MESH : Humans, MESH: Adult, MESH: Retrospective Studies, medicine.disease, MESH : Proportional Hazards Models, [SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, MESH: Male, MESH : Kidney Neoplasms, Surgery, Transplantation, MESH: France, Kidney Failure, Chronic, MESH: Kidney Neoplasms, business, Kidney cancer, MESH: Female, Kidney disease
Abstract: International audience; BACKGROUND: Patients with end-stage renal disease (ESRD) are at risk of developing renal tumours. OBJECTIVE: Compare clinical, pathologic, and outcome features of renal cell carcinomas (RCCs) in ESRD patients and in patients from the general population. DESIGN, SETTING, AND PARTICIPANTS: Twenty-four French university departments of urology participated in this retrospective study. INTERVENTION: All patients were treated according to current European Association of Urology guidelines. MEASUREMENTS: Age, sex, symptoms, tumour staging and grading, histologic subtype, and outcome were recorded in a unique database. Categoric and continuous variables were compared by using chi-square and student statistical analyses. Cancer-specific survival (CSS) was assessed by Kaplan-Meier and Cox methods. RESULTS AND LIMITATIONS: The study included 1250 RCC patients: 303 with ESRD and 947 from the general population. In the ESRD patients, age at diagnosis was younger (55 ± 12 yr vs 62 ± 12 yr); mean tumour size was smaller (3.7 ± 2.6 cm vs 7.3 ± 3.8 cm); asymptomatic (87% vs 44%), low-grade (68% vs 42%), and papillary tumours were more frequent (37% vs 7%); and poor performance status (PS; 24% vs 37%) and advanced T categories (≥ 3) were more rare (10% vs 42%). Consistently, nodal invasion (3% vs 12%) and distant metastases (2% vs 15%) occurred less frequently in ESRD patients. After a median follow-up of 33 mo (range: 1-299 mo), 13 ESRD patients (4.3%), and 261 general population patients (27.6%) had died from cancer. In univariate analysis, histologic subtype, symptoms at diagnosis, poor PS, advanced TNM stage, high Fuhrman grade, large tumour size, and non-ESRD diagnosis context were adverse predictors for survival. However, only PS, TNM stage, and Fuhrman grade remained independent CSS predictors in multivariate analysis. The limitation of this study is related to the retrospective design. CONCLUSIONS: RCC arising in native kidneys of ESRD patients seems to exhibit many favourable clinical, pathologic, and outcome features compared with those diagnosed in patients from the general population.
Published: 2011
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15. Locally advanced unresectable pancreatic cancer: Induction chemoradiotherapy followed by maintenance gemcitabine versus gemcitabine alone: Definitive results of the 2000-2001 FFCD/SFRO phase III trial

Author: Barhoumi , M., Mornex , F., Bonnetain , Franck, Rougier , P., Mariette , C., Bouché , O., Bosset , J.-F., Aparicio , T., Mineur , L., Azzedine , A., Hammel , P., Butel , J., Stremsdoerfer , N., Maingon , P., Bedenne , L., Chauffert , B., Matrice extracellulaire et dynamique cellulaire - UMR 7369 (MEDyC), Université de Reims Champagne-Ardenne (URCA)-SFR CAP Santé (Champagne-Ardenne Picardie Santé), Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Epidémiologie et d'Ecologie parasitaire, Institut Pasteur de Tunis, Institut Pasteur de Tunis, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Grand Accélérateur National d'Ions Lourds (GANIL), Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (EA 3181) (CEF2P / CARCINO), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Institut Pasteur de Tunis-Réseau International des Instituts Pasteur ( RIIP ), Grand Accélérateur National d'Ions Lourds ( GANIL ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Institut National de Physique Nucléaire et de Physique des Particules du CNRS ( IN2P3 ) -Centre National de la Recherche Scientifique ( CNRS ), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC ( CEF2P / CARCINO ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Université Bourgogne Franche-Comté ( UBFC ) -Université de Franche-Comté ( UFC ), and Maquart, François-Xavier
Subjects: Male, MESH : Hematologic Diseases, MESH: Remission Induction, MESH: Combined Modality Therapy, Gastrointestinal Diseases, MESH : Antineoplastic Combined Chemotherapy Protocols, MESH : Aged, Kaplan-Meier Estimate, MESH : Gastrointestinal Diseases, Deoxycytidine, MESH : Radiotherapy, Conformal, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, MESH: Proportional Hazards Models, MESH: Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols, MESH : Female, ComputingMilieux_MISCELLANEOUS, Aged, 80 and over, MESH: Aged, MESH : Carcinoma, Pancreatic Ductal, MESH: Antimetabolites, Antineoplastic, MESH: Middle Aged, MESH : Antimetabolites, Antineoplastic, Remission Induction, Middle Aged, MESH : Adult, MESH: Hematologic Diseases, Combined Modality Therapy, MESH: Antineoplastic Combined Chemotherapy Protocols, MESH: Radiotherapy, Conformal, Disease Progression, MESH : Fluorouracil, Female, MESH: Disease Progression, Fluorouracil, MESH: Pancreatic Neoplasms, Carcinoma, Pancreatic Ductal, Adult, Antimetabolites, Antineoplastic, MESH : Male, [SDV.CAN]Life Sciences [q-bio]/Cancer, MESH : Cisplatin, MESH : Kaplan-Meier Estimate, MESH : Deoxycytidine, Humans, MESH : Middle Aged, MESH : Aged, 80 and over, MESH: Gastrointestinal Diseases, MESH: Kaplan-Meier Estimate, Aged, Proportional Hazards Models, MESH : Remission Induction, MESH: Humans, MESH: Carcinoma, Pancreatic Ductal, MESH : Humans, MESH: Deoxycytidine, MESH: Adult, MESH : Disease Progression, MESH : Proportional Hazards Models, Hematologic Diseases, Gemcitabine, MESH: Male, Pancreatic Neoplasms, MESH: Cisplatin, Cisplatin, Radiotherapy, Conformal, MESH : Combined Modality Therapy, MESH: Female, MESH: Fluorouracil, MESH : Pancreatic Neoplasms
Abstract: International audience; PURPOSE: To compare chemoradiation with systemic chemotherapy to chemotherapy alone in locally advanced pancreatic cancer. PATIENTS AND METHODS: One hundred and nineteen patients with locally advanced pancreatic cancer, with World Health Organization performance status of zero to two were randomly assigned to either the induction chemoradiation group (60 Gy, 2 Gy/fraction; concomitant 5-fluoro-uracil infusion, 300 mg/m(2) per day, days 1-5 for 6 weeks; cisplatin, 20 mg/m(2) per day, days 1-5 during weeks 1 and 5) or the induction gemcitabine group (GEM: 1000 mg/m(2) weekly for 7 weeks). Maintenance gemcitabine (1000 mg/m(2) weekly, 3/4 weeks) was given in both arms until disease progression or toxicity. RESULTS: Overall survival was shorter in the chemoradiation than in the gemcitabine arm (median survival 8.6 [99% confidence interval 7.1-11.4] and 13 months [8,9,9-18], p=0.03). One-year survival was, respectively, 32 and 53%. These results were confirmed in a per-protocol analysis for patients who received 75% or more of the planned dose of radiotherapy. More overall grades 3-4 toxic effects were recorded in the chemoradiation arm, both during induction (36 versus 22%) and maintenance (32 versus 18%). CONCLUSION: This intensive induction schedule of chemoradiation was more toxic and less effective than gemcitabine alone.
Published: 2011
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16. High levels of antibodies against merkel cell polyomavirus identify a subset of patients with merkel cell carcinoma with better clinical outcome

Author: Gérard Lorette, Eve Maubec, Agnès Carlotti, Annabel Maruani, Marie-Françoise Avril, Maxime Fleury, Raphaël Cazal, Serge Guyétant, Mauro Tognon, Flore Rozenberg, Françoise Arnold, Antoine Touzé, Emmanuelle Le Bidre, François Aubin, Pierre Coursaget, Hélène Laude, Laboratoire Analyse, Géométrie et Applications (LAGA), Université Paris 8 Vincennes-Saint-Denis (UP8)-Centre National de la Recherche Scientifique (CNRS)-Institut Galilée-Université Paris 13 (UP13), Immunité et cancer (U932), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de dermatologie, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Hôpital Saint-Jacques-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (EA 3181) (CEF2P / CARCINO), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Service de Dermatologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire de Virologie, Hôpital Saint-Vincent de Paul, Laboratoire Analyse, Géométrie et Applications ( LAGA ), Université Paris 8 Vincennes-Saint-Denis ( UP8 ) -Université Paris 13 ( UP13 ) -Université Sorbonne Paris Cité ( USPC ) -Institut Galilée-Centre National de la Recherche Scientifique ( CNRS ), Immunité et cancer ( U932 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut Curie-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Hôpital Saint-Jacques-Université de Franche-Comté ( UFC ), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC ( CEF2P / CARCINO ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Université Bourgogne Franche-Comté ( UBFC ) -Université de Franche-Comté ( UFC ), Service de Dermatologie, Hôpital Cochin, AP-HP, Paris, Université Paris 8 Vincennes-Saint-Denis (UP8)-Université Paris 13 (UP13)-Institut Galilée-Université Sorbonne Paris Cité (USPC)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Curie-Université Paris Descartes - Paris 5 (UPD5), Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Hôpital Saint-Jacques-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Université de Franche-Comté (UFC), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP], Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (EA 3181) ( CEF2P / CARCINO ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Université Bourgogne Franche-Comté [COMUE] ( UBFC ) -Université de Franche-Comté ( UFC ), and Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Cochin [AP-HP]
Subjects: Pathology, MESH: Chi-Square Distribution, MESH: Lymphatic Metastasis, MESH: Polyomavirus, MESH : Aged, MESH : Prospective Studies, MESH: Risk Assessment, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, Merkel cell carcinoma, 0302 clinical medicine, MESH: Up-Regulation, MESH : Neoplasm Staging, MESH : Up-Regulation, MESH: Capsid Proteins, 0303 health sciences, MESH: Middle Aged, Antibody titer, food and beverages, MESH : Lymphatic Metastasis, MESH : Enzyme-Linked Immunosorbent Assay, MESH: Case-Control Studies, MESH : Polyomavirus, 3. Good health, Oncology, 030220 oncology & carcinogenesis, MESH: RNA, Viral, VIRUS, Antibody, MESH : Case-Control Studies, medicine.medical_specialty, MESH: Prognosis, 03 medical and health sciences, MESH : Middle Aged, MESH : Predictive Value of Tests, MESH : Aged, 80 and over, MESH: Kaplan-Meier Estimate, MESH: Humans, MESH : Chi-Square Distribution, MESH : Humans, MESH: Adult, MESH : Proportional Hazards Models, medicine.disease, MESH: Tumor Markers, Biological, MESH: Disease-Free Survival, MESH: Female, SKIN, MESH: Antibodies, Viral, Cancer Research, MESH : Capsid Proteins, Merkel cell polyomavirus, Human skin, antibody, immune system, outcome, MESH: Proportional Hazards Models, MESH: Aged, 80 and over, MESH: Risk Factors, MESH : Tumor Markers, Biological, INFECTION, EPIDEMIOLOGY, MESH : Female, MESH : Risk Assessment, MESH : Carcinoma, Merkel Cell, MESH: Aged, MESH : Prognosis, biology, MESH: Enzyme-Linked Immunosorbent Assay, MESH: Neoplasm Staging, MESH : Adult, MESH : Risk Factors, MESH: Predictive Value of Tests, ETIOLOGY, MESH : Disease-Free Survival, MESH : Time Factors, circulatory and respiratory physiology, MESH : Antibodies, Viral, EXPRESSION, TISSUES, MESH : Male, [SDV.CAN]Life Sciences [q-bio]/Cancer, MESH : Kaplan-Meier Estimate, medicine, MESH : RNA, Viral, MESH : France, 030304 developmental biology, Insect cell, business.industry, MESH: Skin Neoplasms, MESH : Skin Neoplasms, MESH: Time Factors, Cancer, MESH: Carcinoma, Merkel Cell, biology.organism_classification, MESH: Male, MESH: Prospective Studies, MESH: France, Geometric mean titer, MCV, biology.protein, business
Abstract: Purpose A new human polyomavirus, Merkel cell polyomavirus (MCV), was identified in 2008 in tumor tissue of patients with Merkel cell carcinoma (MCC), a relatively rare human skin cancer. In this study, we investigated patients with MCC and controls for the presence of antibodies against MCV and their association with clinical characteristics. Patients and Methods Antibodies against MCV were investigated by enzyme-linked immunosorbent assay in 68 patients with MCC and 82 controls using VP1 virus-like particles produced in insect cells. Results Antibodies against MCV were detected in all patients with MCC and in 85% of controls. However, high antibody titers (> 10,000) were rarely observed in controls (7.3%) and they were detected in 64.7% of patients with MCC (P < .001) in contrast to the absence of VP1 expression in tumor samples. In addition, the geometric mean titer of anti-MCV in patients with MCC was around 14 times higher than that observed in MCV-positive controls (P < .001) and was not correlated with tumor viral load. High antibody titers were not found to be associated with any subject or tumor characteristics, but better progression-free survival was observed in patients with high antibody titers (hazard ratio, 4.6; 95% CI, 1.7 to 12.2; P = .002). Conclusion High titers of MCV antibodies in a much higher proportion of patients with MCC than in controls confirmed the association between MCV infection and MCC. The findings also indicated that a better progression-free survival occurred in patients with high MCV antibody titers and suggested that there are at least two distinct etiologic causes of MCC.
Published: 2011
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17. Pharmacokinetics for once-daily versus twice-daily tacrolimus formulations in de novo liver transplantation: a randomized, open-label trial

Author: Pavel Trunecka, Nasrullah Undre, Bruno Gridelli, Andrés Valdivieso, Stephen V. Lynch, Evaristo Varo, Lutz Fischer, André Roy, Karim Boudjema, Carmen Karpf, Daniel Seehofer, Alessandro Vitale, Bo Göran Ericzon, Didier Samuel, Liver Transplantation Unit, Hospital de Cruces, Department of Surgery, School of Medicine, Universidad del Pais Vasco / Euskal Herriko Unibertsitatea [Espagne] (UPV/EHU), Service d'hépatologie, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Paul Brousse-Université Paris Descartes - Paris 5 (UPD5), Service de Chirurgie Hépatobiliaire et Digestive, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Foie, métabolismes et cancer, Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Université Paris Descartes - Paris 5 (UPD5), Service de Chirurgie Hépatobiliaire et Digestive [Rennes] = Hepatobiliary and Digestive Surgery [Rennes], CHU Pontchaillou [Rennes], Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Universidad del País Vasco, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Paul Brousse-Université Paris Descartes - Paris 5 ( UPD5 ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Hôpital Pontchaillou-CHU Pontchaillou [Rennes], and Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )
Subjects: Graft Rejection, Male, medicine.medical_treatment, MESH : Prospective Studies, MESH : Aged, 030230 surgery, Liver transplantation, Pharmacology, law.invention, 0302 clinical medicine, MESH : Therapeutic Equivalency, Prospective Studies, MESH : Immunosuppressive Agents, MESH: Treatment Outcome, MESH: Middle Aged, Graft Survival, 3. Good health, MESH: Young Adult, Area Under Curve, MESH: Administration, Oral, Drug Therapy, Combination, 030211 gastroenterology & hepatology, [ SDV.MHEP.HEG ] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, MESH: Immunosuppressive Agents, medicine.medical_specialty, MESH: Liver Transplantation, MESH: Graft Survival, MESH: Delayed-Action Preparations, MESH : Drug Administration Schedule, Urology, MESH : Young Adult, MESH: Graft Rejection, MESH: Drug Administration Schedule, Drug Administration Schedule, Tacrolimus, 03 medical and health sciences, Pharmacokinetics, MESH: Canada, Humans, MESH : Middle Aged, Adverse effect, MESH: Kaplan-Meier Estimate, Aged, MESH: Humans, MESH : Humans, Australia, MESH : Graft Rejection, MESH: Adult, medicine.disease, Delayed-Action Preparations, Surgery, MESH : Australia, MESH: Female, Administration, Oral, Kaplan-Meier Estimate, Randomized controlled trial, law, MESH : Female, Kidney transplantation, MESH : Graft Survival, MESH: Aged, Area under the curve, Immunosuppression, Middle Aged, MESH : Adult, Europe, MESH : Canada, Treatment Outcome, surgical procedures, operative, Female, Immunosuppressive Agents, Adult, Canada, MESH : Male, MESH : Europe, MESH: Australia, chemical and pharmacologic phenomena, MESH : Treatment Outcome, MESH: Therapeutic Equivalency, MESH : Kaplan-Meier Estimate, Young Adult, medicine, MESH : Delayed-Action Preparations, MESH: Tacrolimus, Transplantation, MESH : Administration, Oral, Hepatology, business.industry, MESH : Drug Therapy, Combination, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, MESH : Tacrolimus, MESH: Male, MESH: Prospective Studies, Liver Transplantation, MESH: Drug Therapy, Combination, Therapeutic Equivalency, MESH: Area Under Curve, MESH : Area Under Curve, MESH: Europe, MESH : Liver Transplantation, business
Abstract: International audience; Tacrolimus, a cornerstone immunosuppressant, is available as a twice-daily formulation (tacrolimus bid). A once-daily prolonged-release formulation (tacrolimus qd) has been developed. This 6-week, randomized, phase 2, multicenter, open-label, prospective trial in primary liver transplant recipients investigated and compared the pharmacokinetics (PK) of tacrolimus for qd and bid formulations. All patients received tacrolimus-based immunosuppression (tacrolimus qd, n = 67; bid, n = 62). PK data were available for 77 patients (tacrolimus qd, n = 45; bid, n = 32). Tacrolimus area under the curve (AUC) from 0 to 24 hours (AUC(0-24) ) at equivalent doses was approximately 50% lower for tacrolimus qd than for bid on day 1 (146 versus 264 ng * h/mL, respectively), but by day 14 was comparable between treatments (324 and 287 ng * h/mL, respectively) with higher tacrolimus qd doses. There was a strong correlation between AUC(0-24) and concentration at 24 hours for tacrolimus qd and bid (r = 0.92 and r = 0.76, respectively). Furthermore, the relationship between these 2 parameters (ie, the slope of the line) was also similar for the 2 formulations. Efficacy endpoints were comparable for both formulations at 6 weeks with no marked differences in incidence, nature, or severity of adverse events between treatments (although the study was not powered to draw efficacy conclusions). These results suggest that targeting the same trough levels will achieve similar total AUC over 24 hours for both tacrolimus qd and tacrolimus bid in de novo liver transplant recipients.
Published: 2011
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18. Prognostic value of microvascular damage determined by cardiac magnetic resonance in non ST-segment elevation myocardial infarction: comparison between first-pass and late gadolinium-enhanced images

Author: Alexandre Cochet, Marianne Zeller, Claude Touzery, Luc Lorgis, Yves Cottin, François Brunotte, Jean-Claude Beer, Jean-Eric Wolf, Alain Lalande, Paul Walker, Laboratoire Electronique, Informatique et Image [UMR6306] (Le2i), Université de Bourgogne (UB)-École Nationale Supérieure d'Arts et Métiers (ENSAM), Arts et Métiers Sciences et Technologies, HESAM Université (HESAM)-HESAM Université (HESAM)-Arts et Métiers Sciences et Technologies, HESAM Université (HESAM)-HESAM Université (HESAM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), Observatoire RICO (ObseRvatoire des Infarctus de Côte d’Or) [Dijon], Observatoire des Infarctus de Côte-d'Or (RICO) [Dijon], Lipides - Nutrition - Cancer (U866) (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), Service de Médecine Nucléaire, Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER, Service de Cardiologie [CHU de Dijon], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), CHU Dijon, Laboratoire Electronique, Informatique et Image ( Le2i ), Université de Bourgogne ( UB ) -Centre National de la Recherche Scientifique ( CNRS ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Lipides - Nutrition - Cancer (U866) ( LNC ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ), Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc ( CRLCC - CGFL ), and Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon )
Subjects: Male, Time Factors, Gadolinium, Myocardial Infarction, MESH : Aged, MESH: Logistic Models, Kaplan-Meier Estimate, 030204 cardiovascular system & hematology, MESH : Gadolinium, 030218 nuclear medicine & medical imaging, [ SDV.IB.MN ] Life Sciences [q-bio]/Bioengineering/Nuclear medicine, 0302 clinical medicine, MESH: Aged, 80 and over, Odds Ratio, ST segment, Radionuclide imaging, MESH : Female, Myocardial infarction, MESH: Incidence, First pass, Aged, 80 and over, MESH: Aged, MESH: Statistics, Nonparametric, MESH : Prognosis, MESH: Middle Aged, medicine.diagnostic_test, Incidence, General Medicine, MESH: Magnetic Resonance Imaging, Cine, Middle Aged, MESH : Adult, MESH: Confidence Intervals, musculoskeletal system, Prognosis, MESH : Magnetic Resonance Imaging, Cine, MESH : Incidence, MESH: Myocardial Infarction, MESH: Microvessels, cardiovascular system, Cardiology, Female, MESH : Time Factors, Adult, medicine.medical_specialty, MESH : Male, chemistry.chemical_element, Magnetic Resonance Imaging, Cine, [SDV.IB.MN]Life Sciences [q-bio]/Bioengineering/Nuclear medicine, Statistics, Nonparametric, MESH: Multivariate Analysis, MESH: Prognosis, MESH : Confidence Intervals, MESH : Kaplan-Meier Estimate, 03 medical and health sciences, Internal medicine, medicine, Confidence Intervals, Humans, Radiology, Nuclear Medicine and imaging, MESH : Middle Aged, cardiovascular diseases, Radionuclide Imaging, MESH : Aged, 80 and over, MESH : Statistics, Nonparametric, MESH: Kaplan-Meier Estimate, Aged, MESH: Humans, business.industry, MESH : Humans, MESH: Time Factors, MESH : Multivariate Analysis, Magnetic resonance imaging, MESH: Adult, medicine.disease, MESH: Male, MESH: Odds Ratio, Surgery, Logistic Models, chemistry, MESH : Microvessels, Microvessels, Multivariate Analysis, MESH : Odds Ratio, Myocardial infarction diagnosis, MESH : Myocardial Infarction, business, Cardiac magnetic resonance, MESH: Gadolinium, MESH: Female, MESH : Logistic Models
Abstract: International audience; OBJECTIVES: To compare 2 cardiac magnetic resonance (CMR) techniques for the evaluation of the prognostic significance of microvascular damage after non ST-segment elevation myocardial infarction (NSTEMI). MATERIALS AND METHODS: CMR was performed at 3T in 61 patients within the week following their first NSTEMI. A first-pass saturation-recovery gradient-echo perfusion sequence was started during the infusion of contrast material to evaluate the extent of microvascular obstruction (MO) during the first 2 minutes after injection (MO(
Published: 2010
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19. Characteristics and prospective 2-year follow-up of children with pulmonary arterial hypertension in France

Author: Pierre Clerson, Damien Bonnet, Virginie Gressin, Xavier Jaïs, Maurice Beghetti, M. Voisin, Jean-Marc Schleich, Alain Fraisse, Sylvie Di Filippo, François Godart, Pascale Maragnès, Claire Dauphin, Service de cardiologie Pédiatrique [Marseille], Hôpital de la Timone [CHU - APHM] (TIMONE), Service de cardiologie et maladies vasculaires, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Service de Cardiologie Pédiatrique, Hospices Civils de Lyon (HCL)-Hôpital Louis Pradel [CHU - HCL], Hospices Civils de Lyon (HCL), Pediatric Cardiology Unit, Hôpital Universitaire de Genève, Actelion Pharmaceuticals, Actelion Pharmaceuticals France, Orgamétrie biostatistiques, Service de cardiologie Pédiatrique [Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre de Référence M3C Malformations Cardiaques Congénitales Complexes, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-PRES Sorbonne Paris Cité-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de cardiologie et maladies vasculaires [Rennes] = Cardiac, Thoracic, and Vascular Surgery [Rennes], CHU Pontchaillou [Rennes], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5)-PRES Sorbonne Paris Cité-CHU Necker - Enfants Malades [AP-HP], Hôpital de la Timone [CHU - APHM] ( TIMONE ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Hospices Civils de Lyon ( HCL ) -Hôpital Louis Pradel [CHU - HCL], Hospices Civils de Lyon ( HCL ), Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), and Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Descartes - Paris 5 ( UPD5 ) -PRES Sorbonne Paris Cité-CHU Necker - Enfants Malades [AP-HP]
Subjects: Male, MESH : Hypertension, Pulmonary, Heart disease, MESH : Prevalence, Epidemiology, MESH : Prospective Studies, Pulmonary arterial hypertension, MESH : Antihypertensive Agents, 0302 clinical medicine, MESH : Child, Surveys and Questionnaires, MESH: Child, Prospective Studies, Child, MESH: Treatment Outcome, MESH : Hemodynamics, Congenital heart defect, MESH : Infant, General Medicine, MESH: Follow-Up Studies, MESH: Infant, 3. Good health, Child, Preschool, épidémiologie, Cardiology and Cardiovascular Medicine, Artery, Heart Defects, Congenital, medicine.medical_specialty, MESH: Hemodynamics, Hypertension, Pulmonary, Disease-Free Survival, 03 medical and health sciences, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, MESH : Adolescent, Humans, MESH : Heart Defects, Congenital, MESH: Kaplan-Meier Estimate, MESH: Prevalence, MESH: Adolescent, MESH: Humans, MESH: Hypertension, Pulmonary, MESH: Questionnaires, MESH : Humans, Qualité de vie, MESH: Child, Preschool, Infant, MESH : Follow-Up Studies, MESH: Heart Defects, Congenital, medicine.disease, 030228 respiratory system, MESH: Disease-Free Survival, MESH : Genetic Predisposition to Disease, MESH: Educational Status, MESH: Exercise Test, MESH: Female, MESH : Educational Status, [ SDV.MHEP.PSR ] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Pediatrics, Time Factors, [ SDV.MHEP.PED ] Life Sciences [q-bio]/Human health and pathology/Pediatrics, Hemodynamics, Kaplan-Meier Estimate, MESH : Child, Preschool, 030204 cardiovascular system & hematology, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Risk Factors, MESH: Risk Factors, Prevalence, MESH : Female, [ SDV.IB ] Life Sciences [q-bio]/Bioengineering, Prospective cohort study, Respiratory disease, MESH: Genetic Predisposition to Disease, MESH : Questionnaires, Hypertension artérielle pulmonaire, [ SDV.MHEP.CSC ] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, MESH : Risk Factors, Treatment Outcome, medicine.anatomical_structure, Paediatric, Cardiology, MESH : Disease-Free Survival, Educational Status, Portal hypertension, Female, [SDV.IB]Life Sciences [q-bio]/Bioengineering, France, MESH : Time Factors, Quality of life, Adolescent, MESH : Male, Pédiatrie, MESH : Treatment Outcome, MESH : Kaplan-Meier Estimate, Internal medicine, medicine, Genetic Predisposition to Disease, MESH : France, Cardiopathie congénitale, Antihypertensive Agents, MESH: Antihypertensive Agents, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, business.industry, MESH: Time Factors, MESH: Quality of Life, MESH : Quality of Life, Pulmonary hypertension, MESH: Male, MESH: Prospective Studies, MESH: France, MESH : Exercise Test, Exercise Test, business, Follow-Up Studies
Abstract: International audience; BACKGROUND: Limited data are available describing paediatric pulmonary arterial hypertension. AIMS: To characterize the epidemiology, management and impact on quality of life and outcome of paediatric pulmonary arterial hypertension, excluding persistent pulmonary hypertension of the newborn and pulmonary arterial hypertension caused by congenital heart disease. METHODS: In this multicentre study, children with pulmonary arterial hypertension were included and followed prospectively for two years at 21 referral centres in France. WHO functional class, 6-minute walk distance and quality of life (CHQ-PF50 questionnaire) were evaluated. RESULTS: Fifty children were included with a mean age of 8.9 +/- 5.4 years from May 2005 until June 2006. The estimated prevalence for pulmonary arterial hypertension was 3.7 cases/million. Patients had idiopathic pulmonary arterial hypertension (60%), familial pulmonary arterial hypertension (10%), pulmonary arterial hypertension associated with, but not caused by, congenital heart disease (24%), pulmonary arterial hypertension associated with connective tissue disease (4%) or portal hypertension (2%). During follow-up, the combination of pulmonary arterial hypertension-specific therapies was increasingly prescribed (44% patients versus 22% at inclusion). Patients remained stable regarding clinical status, 6-minute walk distance and quality of life. Survival estimates after one and two years were 86% (95% CI 76, 96) and 82% (95% CI 71, 93), respectively. CONCLUSIONS: In children, idiopathic/familial pulmonary arterial hypertension accounts for the majority of cases. A specific pulmonary arterial hypertension group in conjunction with congenital heart disease can be identified that resembles patients with idiopathic pulmonary arterial hypertension. Combined pulmonary arterial hypertension-specific therapies may have contributed to disease stability and favourable survival.
Published: 2010
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20. Telmisartan to prevent recurrent stroke and cardiovascular events

Author: Yusuf, S, Diener, Hc, Sacco, Rl, Cotton, D, Ounpuu, S, Lawton, Wa, Palesch, Y, Martin, Rh, Albers, Gw, Bath, P, Bornstein, N, Chan, Bp, Chen, St, Cunha, L, Dahlöf, B, DE KEYSER, J, Donnan, Ga, Estol, C, Gorelick, P, Gu, V, Hermansson, K, Hilbrich, L, Kaste, M, Lu, C, Machnig, T, Pais, P, Roberts, R, Skvortsova, V, Teal, P, Toni, Danilo, Vandermaelen, C, Voigt, T, Weber, M, Yoon, Bw, Lembo, Giuseppe, Rasura, Maurizia, Sacchetti, Maria Luisa, Hamilton General Hospital, Population Health Research Institute, McMaster University [Hamilton, Ontario]-Hamilton General Hospital, Universität Duisburg-Essen [Essen], Miller School of Medicine, University of Miami [Coral Gables], Institute of Medicine, Sahlgrenska University Hospital, Helsinki University, Institut de Génétique Moléculaire de Montpellier ( IGMM ), Université de Montpellier ( UM ) -Centre National de la Recherche Scientifique ( CNRS ), Neuroépidémiologie Tropicale et Comparée ( NETEC ), Génomique, Environnement, Immunité, Santé, Thérapeutique ( GEIST FR CNRS 3503 ) -Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Université de Limoges ( UNILIM ), Service de Neurologie [CHU Limoges], CHU Limoges, University of Miami Leonard M. Miller School of Medicine (UMMSM), Sahlgrenska University Hospital [Gothenburg], University of Helsinki, Institut de Génétique Moléculaire de Montpellier (IGMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Yusuf, S, Diener, Hc, Sacco, Rl, Cotton, D, Ounpuu, S, Lawton, Wa, Palesch, Y, Martin, Rh, Albers, Gw, Bath, P, Bornstein, N, Chan, Bp, Chen, St, Cunha, L, Dahlof, B, De Keyser, J, Donnan, Ga, Estol, C, Gorelick, P, Gu, V, Hermansson, K, Hilbrich, L, Kaste, M, Lu, C, Machnig, T, Pais, P, Roberts, R, Skvortsova, V, Teal, P, Toni, D, Vandermaelen, C, Voigt, T, Weber, M, Yoon, Bw, Comi, Giancarlo, PRoFESS Stuy, Group, Gerontology, and Faculteit Medische Wetenschappen/UMCG
Subjects: Male, MESH: Treatment Failure, MESH : Recurrence, Myocardial Infarction, MESH : Aged, Angiotensin-Converting Enzyme Inhibitors, Blood Pressure, BLOOD-PRESSURE, 0302 clinical medicine, DESIGN, Secondary Prevention, MESH : Cardiovascular Diseases, Myocardial infarction, MESH: Middle Aged, Hazard ratio, General Medicine, MESH: Follow-Up Studies, MESH: Blood Pressure, 3. Good health, MESH: Myocardial Infarction, MESH : Diabetes Mellitus, Cardiovascular Diseases, Creatinine, MESH : Angiotensin-Converting Enzyme Inhibitors, Ramipril, medicine.medical_specialty, MESH: Diabetes Mellitus, MESH: Creatinine, [ SDV.MHEP.GEG ] Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, Article, MESH: Stroke, 03 medical and health sciences, MESH : Treatment Failure, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Diabetes Mellitus, Humans, MESH : Middle Aged, COMBINATION, MESH: Kaplan-Meier Estimate, Aged, Heart Failure, MESH: Humans, VASCULAR EVENTS, MORTALITY, MESH : Humans, MESH : Creatinine, MESH: Cardiovascular Diseases, MESH : Follow-Up Studies, medicine.disease, MESH: Benzoates, RAMIPRIL, Blood pressure, MESH : Potassium, Potassium, Benzimidazoles, MESH : Heart Failure, MESH: Female, 030217 neurology & neurosurgery, MESH : Stroke, RATIONALE, Kaplan-Meier Estimate, 030204 cardiovascular system & hematology, Benzoates, RANDOMIZED TRIAL, DOUBLE-BLIND, MESH : Female, sartani, ictus, trial clinico, Telmisartan, Treatment Failure, Stroke, MESH: Aged, [SDV.MHEP.GEG]Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, MESH: Angiotensin-Converting Enzyme Inhibitors, Middle Aged, [ SDV.MHEP.CSC ] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, MESH : Benzimidazoles, Cardiology, Female, medicine.drug, MESH : Benzoates, MESH : Male, MESH : Kaplan-Meier Estimate, Internal medicine, Diabetes mellitus, medicine, MESH : Blood Pressure, HIGH-RISK PATIENTS, business.industry, Angiotensin II, MESH: Male, Surgery, MESH: Recurrence, MESH: Heart Failure, MESH: Potassium, MESH : Myocardial Infarction, business, MESH: Benzimidazoles, Follow-Up Studies
Abstract: Background: Prolonged lowering of blood pressure after a stroke reduces the risk of recurrent stroke. In addition, inhibition of the renin-angiotensin system in high-risk patients reduces the rate of subsequent cardiovascular events, including stroke. However, the effect of lowering of blood pressure with a renin-angiotensin system inhibitor soon after a stroke has not been clearly established. We evaluated the effects of therapy with an angiotensin-receptor blocker, telmisartan, initiated early after a stroke.Methods: In a multicenter trial involving 20,332 patients who recently had an ischemic stroke, we randomly assigned 10,146 to receive telmisartan (80 mg daily) and 10,186 to receive placebo. The primary outcome was recurrent stroke. Secondary outcomes were major cardiovascular events (death from cardiovascular causes, recurrent stroke, myocardial infarction, or new or worsening heart failure) and new-onset diabetes.Results: The median interval from stroke to randomization was 15 days. During a mean follow-up of 2.5 years, the mean blood pressure was 3.8/2.0 mm Hg lower in the telmisartan group than in the placebo group. A total of 880 patients (8.7%) in the telmisartan group and 934 patients (9.2%) in the placebo group had a subsequent stroke (hazard ratio in the telmisartan group, 0.95; 95% confidence interval [CI], 0.86 to 1.04; P=0.23). Major cardiovascular events occurred in 1367 patients (13.5%) in the telmisartan group and 1463 patients (14.4%) in the placebo group (hazard ratio, 0.94; 95% CI, 0.87 to 1.01; P=0.11). New-onset diabetes occurred in 1.7% of the telmisartan group and 2.1% of the placebo group (hazard ratio, 0.82; 95% CI, 0.65 to 1.04; P=0.10).Conclusions: Therapy with telmisartan initiated soon after an ischemic stroke and continued for 2.5 years did not significantly lower the rate of recurrent stroke, major cardiovascular events, or diabetes. (ClinicalTrials.gov number, NCT00153062.).
Published: 2008
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20 results on '"MESH : Kaplan-Meier Estimate"'

1. Dynamic evaluation of circulating tumour cells in patients with advanced gastric and oesogastric junction adenocarcinoma: Prognostic value and early assessment of therapeutic effects

2. Cardiac rehabilitation and 5-year mortality after acute coronary syndromes: The 2005 French FAST-MI study

3. Therapeutic vaccination with TG4010 and first-line chemotherapy in advanced non-small-cell lung cancer: a controlled phase 2B trial

4. Early surgery for failure after chemoradiation in operable thoracic oesophageal cancer. Analysis of the non-randomised patients in FFCD 9102 phase III trial: Chemoradiation followed by surgery versus chemoradiation alone

5. Toward a NOTCH1/FBXW7/RAS/PTEN-based oncogenetic risk classification of adult T-cell acute lymphoblastic leukemia: a Group for Research in Adult Acute Lymphoblastic Leukemia study

6. Prognostic factors of survival in patients with non-infectious mixed cryoglobulinaemia vasculitis: data from 242 cases included in the CryoVas survey

7. Rituximab induction immunotherapy for first-line low-tumor-burden follicular lymphoma: survival analyses with 7-year follow-up

8. Lenalidomide maintenance after stem-cell transplantation for multiple myeloma

9. A randomized study of defibrillator lead implantations in the right ventricular mid-septum versus the apex: the SEPTAL study

10. Mutational characterization of individual breast tumors: TP53 and PI3K pathway genes are frequently and distinctively mutated in different subtypes

11. Phase II study of the mammalian target of rapamycin inhibitor ridaforolimus in patients with advanced bone and soft tissue sarcomas

12. Pediatric-inspired intensified therapy of adult T-ALL reveals the favorable outcome of NOTCH1/FBXW7 mutations, but not of low ERG/BAALC expression: a GRAALL study

13. Nomograms for predicting local recurrence, distant metastases, and overall survival for patients with locally advanced rectal cancer on the basis of European randomized clinical trials

14. Renal cell carcinoma (RCC) in patients with end-stage renal disease exhibits many favourable clinical, pathologic, and outcome features compared with RCC in the general population

15. Locally advanced unresectable pancreatic cancer: Induction chemoradiotherapy followed by maintenance gemcitabine versus gemcitabine alone: Definitive results of the 2000-2001 FFCD/SFRO phase III trial

16. High levels of antibodies against merkel cell polyomavirus identify a subset of patients with merkel cell carcinoma with better clinical outcome

17. Pharmacokinetics for once-daily versus twice-daily tacrolimus formulations in de novo liver transplantation: a randomized, open-label trial

18. Prognostic value of microvascular damage determined by cardiac magnetic resonance in non ST-segment elevation myocardial infarction: comparison between first-pass and late gadolinium-enhanced images

19. Characteristics and prospective 2-year follow-up of children with pulmonary arterial hypertension in France

20. Telmisartan to prevent recurrent stroke and cardiovascular events

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