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1. Measuring cell displacements in opaque tissues: dynamic light scattering in the multiple scattering regime

Author

Romain Pierrat, Vincent Levy, Benjamin Brunel, Arnaud Millet, Antoine Delon, Monika E. Dolega, Giovanni Cappello, Cappello, Giovanni, Laboratoire Interdisciplinaire de Physique [Saint Martin d’Hères] (LIPhy ), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Equipe U1205 Inserm 'Mechano-biology, Immunity and Cancer', BrainTech Laboratory [CHU Grenoble Alpes - Inserm U1205] (Brain Tech Lab ), CHU Grenoble-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-CHU Grenoble-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Institut Langevin - Ondes et Images (UMR7587) (IL), Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Paris (UP)-Centre National de la Recherche Scientifique (CNRS)

Subjects
[PHYS.PHYS.PHYS-OPTICS] Physics [physics]/Physics [physics]/Optics [physics.optics], Opacity, Forward scatter, [PHYS.PHYS.PHYS-BIO-PH]Physics [physics]/Physics [physics]/Biological Physics [physics.bio-ph], 01 natural sciences, Article, Quantitative Biology::Cell Behavior, 010309 optics, 03 medical and health sciences, Optics, Dynamic light scattering, Optical coherence tomography, 0103 physical sciences, medicine, Diffusion (business), Spectroscopy, 030304 developmental biology, Physics, 0303 health sciences, [PHYS.PHYS.PHYS-OPTICS]Physics [physics]/Physics [physics]/Optics [physics.optics], medicine.diagnostic_test, [PHYS.PHYS.PHYS-BIO-PH] Physics [physics]/Physics [physics]/Biological Physics [physics.bio-ph], Scattering, business.industry, Atomic and Molecular Physics, and Optics, Millimeter, business, Biotechnology
Abstract

International audience; Coherent light scattered by tissues brings structural and dynamic information, at depth, that standard imaging techniques cannot reach. Dynamics of cells or sub-cellular elements can be measured thanks to dynamic light scattering in thin samples (single scattering regime) or thanks to diffusive wave spectroscopy in thick samples (diffusion regime). Here, we address the intermediate regime and provide an analytical relationship between scattered light fluctuations and the distribution of cell displacements as a function of time. We illustrate our method by characterizing cell motility inside half millimeter thick multicellular aggregates.

Published
2020
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2. Phase II Study of Pembrolizumab As First-Line, Single-Drug Therapy for Patients With Unresectable Cutaneous Squamous Cell Carcinomas

Author

Coralie Bloch-Queyrat, Florent Grange, Lydia Deschamps, Sandrine Mansard, Nicole Basset-Seguin, Annick Tibi, Vincent Levy, Sarah Guégan, D. Legoupil, Jean-Philippe Arnault, Henri Montaudié, Marouane Boubaya, Olivier Dereure, Yannick Le Corre, A. Stefan, François Aubin, Céline Alloux, Jean-Jacques Grob, Peter Petrow, Soufian Cherbal, Groupe de cancérologie cutanée, Philippe Saiag, Nicolas Meyer, Isabelle Lopez, Marie Beylot-Barry, Eve Maubec, Marie-Thérèse Leccia, Brigitte Dréno, Ouidad Zehou, Laurent Machet, Julie De Quatrebarbes, Sophie Dalac, Monica Dinulescu, E. Wierzbicka-Hainaut, Isabelle Scheer-Senyarich, Herrada, Anthony, Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris 13 (UP13), Polyclinique Saint Côme, Institut Curie [Paris], CHU Bordeaux [Bordeaux], Hopital Saint-Louis [AP-HP] (AP-HP), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Hôpital de la Timone [CHU - APHM] (TIMONE), Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Grenoble, CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Hôpital Ambroise Paré [AP-HP], Hôpital Robert Debré, Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims (CHU Reims), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre Hospitalier Annecy-Genevois [Saint-Julien-en-Genevois], Centre Eugène Marquis (CRLCC), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Pathogénèse et contrôle des infections chroniques (PCCI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre Hospitalier Universitaire de Montpellier (CHU Montpellier ), Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre Hospitalier Universitaire de Nice (CHU Nice), Hôpital de la Milétrie, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), CHU Clermont-Ferrand, Hôpital Cochin [AP-HP], CHU Amiens-Picardie, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Agence Générale des Equipements et Produits de Santé [Paris] (AGEPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Toulouse [Toulouse], and Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS)

Subjects
Male, 0301 basic medicine, Oncology, Cancer Research, Skin Neoplasms, Time Factors, MESH: Immune Checkpoint Inhibitors, Cell, Phases of clinical research, Pembrolizumab, B7-H1 Antigen, Antineoplastic Agents, Immunological, 0302 clinical medicine, MESH: Aged, 80 and over, MESH: Progression-Free Survival, MESH: B7-H1 Antigen, Medicine, Immune Checkpoint Inhibitors, Aged, 80 and over, MESH: Aged, MESH: Middle Aged, MESH: Carcinoma, Squamous Cell, Middle Aged, Progression-Free Survival, 3. Good health, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Monoclonal, Carcinoma, Squamous Cell, Disease Progression, Female, MESH: Disease Progression, France, Adult, medicine.medical_specialty, [SDV.CAN]Life Sciences [q-bio]/Cancer, Antibodies, Monoclonal, Humanized, 03 medical and health sciences, Pharmacotherapy, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, Carcinoma, Humans, Progression-free survival, Aged, MESH: Humans, business.industry, MESH: Skin Neoplasms, MESH: Time Factors, MESH: Quality of Life, MESH: Adult, medicine.disease, MESH: Antineoplastic Agents, Immunological, MESH: Male, Clinical trial, MESH: France, 030104 developmental biology, MESH: Antibodies, Monoclonal, Humanized, Quality of Life, business, MESH: Female
Abstract

PURPOSE To evaluate first-line pembrolizumab monotherapy efficacy and safety in patients with unresectable cutaneous squamous cell carcinomas (CSCCs). PATIENTS AND METHODS Patients, predominantly men, with their CSSCs’ immunohistochemically determined programmed cell death-ligand 1 (PD-L1) status determined (tumor proportion score threshold, 1%), received pembrolizumab (200 mg every 3 weeks). The primary endpoint was the 39-patient primary cohort’s objective response rate at week 15 (ORRW15). Secondary objectives were best ORR, overall survival (OS), progression-free survival (PFS), duration of response (DOR), safety, ORR according to PD-L1 status and health-related quality of life using Functional Assessment of Cancer Therapy–General (FACT-G) score. An 18-patient expansion cohort, recruited to power the study to evaluate the ORRW15 difference between PD-L1+ and PD-L1– patients, was assessed for ORR, disease control rate, and safety, but not survival. RESULTS Median age of all patients was 79 years. The primary cohort’s ORRW15 was 41% (95% CI, 26% to 58%), including 13 partial and 3 complete responses. Best responses were 8 partial and 8 complete responses. At a median follow-up of 22.4 months, respective median PFS, DOR, and OS were 6.7 months, not reached, and 25.3 months, respectively. Pembrolizumab-related adverse events affected 71% of the patients, and 4 (7%) were grade ≥ 3. One death was related to rapid CSCC progression; another resulted from a fatal second aggressive head and neck squamous cell carcinoma diagnosed 15 weeks postinclusion. ORRW15 for the entire population was 42%; it was significantly higher for PD-L1+ patients (55%) versus PD-L1– patients (17%; P = .02). Responders’ W15 total FACT-G score had improved ( P = .025) compared with nonresponders. CONCLUSION First-line pembrolizumab monotherapy exhibited promising anti-CSCC activity, with durable responses and manageable safety. PD-L1 positivity appears to be predictive of pembrolizumab efficacy.

Published
2020
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3. Diagnosis and Treatment of Chronic Lymphocytic Leukemia: Recommendations of the French CLL Study Group (FILO)

Author

Anne Quinquenel, Olivier Tournilhac, Stéphane Leprêtre, Aline Clavert, Thérèse Aurran-Schleinitz, Anne-Sophie Michallet, Vincent Levy, Caroline Dartigeas, Florence Cymbalista, Xavier Troussard, Luc-Matthieu Fornecker, Alain Delmer, Cécile Tomowiak, Florence Nguyen-Khac, Pierre Feugier, Rémi Letestu, Frederic Davi, Loic Ysebaert, David Ghez, Sophie de Guibert, Kamel Laribi, Romain Guieze, Veronique Leblond, Marie-Sarah Dilhuydy, Role of intra-Clonal Heterogeneity and Leukemic environment in ThErapy Resistance of chronic leukemias (CHELTER), and Université Clermont Auvergne [2017-2020] (UCA [2017-2020])

Subjects
Richter syndrome, Pediatrics, medicine.medical_specialty, Chronic lymphocytic leukemia, MEDLINE, Relapsed CLL, 03 medical and health sciences, 0302 clinical medicine, Daily practice, hemic and lymphatic diseases, Guideline Article - Expert opinion, medicine, ComputingMilieux_MISCELLANEOUS, lcsh:RC633-647.5, business.industry, Autoimmune Cytopenia, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, lcsh:Diseases of the blood and blood-forming organs, Hematology, medicine.disease, 3. Good health, Leukemia, 030220 oncology & carcinogenesis, business, 030215 immunology
Abstract

As a result of significant recent developments, the management of patients with chronic lymphocytic leukemia (CLL) is changing, and new therapeutic options will continue to emerge in the near future. The recommendations of the French Innovative Leukemia Organization (FILO-CLL) group presented here are intended to provide practical recommendations for physicians taking care of CLL patients, taking into account the availability of both biological tests and therapies in daily practice in France at the time of publication. This text details the documented information and guidelines on diagnosis, indications for treatment, infectious complications and therapeutic strategies in frontline and relapsed CLL as well as in particular conditions such as autoimmune cytopenia or Richter syndrome.

Published
2020
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4. Maintenance of Long-Term Undetectable Minimal Residual Disease after Combination of Ibrutinib with Abbreviated Chemotherapy in the Icll-07 Filo Trial

Author

Anne Banos, Vincent Levy, Magali Le Garff-Tavernier, Veronique Leblond, Sophie de Guibert, Valérie Rouille, Loic Ysebaert, Philippe Carassou, Bruno Villemagne, Kamel Laribi, Alain Delmer, Frederique Orsini, Beatrice Mahe, Michel Ticchioni, Gilles Salles, Marie-Sarah Dilhuydy, Thérèse Aurran, Carmen Aanaei, Florence Nguyen-Khac, Brigitte Pegourie, Rémi Letestu, Fabien Subtil, Luc Mathieu Fornecker, Caroline Dartigeas, Jean Pierre Vilque, Cécile Tomowiak, Guillaume Cartron, Florence Cymbalista, Margot Truchan, Anne-Sophie Michallet, Christelle Portois, Pierre Feugier, Olivier Tournilhac, Stéphane Leprêtre, Role of intra-Clonal Heterogeneity and Leukemic environment in ThErapy Resistance of chronic leukemias (CHELTER), Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), and CHADEYRON, DOMINIQUE

Subjects
Oncology, [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, medicine.medical_specialty, Cyclophosphamide, medicine.medical_treatment, Immunology, Biochemistry, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Obinutuzumab, Internal medicine, medicine, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, Chemotherapy, business.industry, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Cell Biology, Hematology, Chemotherapy regimen, Minimal residual disease, 3. Good health, Fludarabine, chemistry, Ibrutinib, Rituximab, business, 030215 immunology, medicine.drug
Abstract

Introduction In previously untreated, medically fit patients with chronic lymphocytic leukaemia (CLL) and no 17p deletion, there is current research interest in improving survival outcomes and potentially sparing some patients from the standard 6 cycles of fludarabine, cyclophosphamide and rituximab (FCR). The phase II ICLL-07 (NCT02666898) trial, conducted by the French Innovative Leukemia Organization (FILO), aimed to explore the efficacy of obinutuzumab and ibrutinib treatment induction for 9 months, followed by a minimal residual disease (MRD)-driven strategy. Methods Following assessment at Month 9, patients in complete response (CR) with bone marrow (BM) MRD ResultsBetween 10/2015 and 05/2017, 135 patients were enrolled. At Month 9, only 8% of patients reached CR with BM MRD Conclusion These findings from the ICLL-07 trial demonstrated that, in previously untreated, medically fit patients with CLL and no 17p deletion, treatment induction with obinutuzumab and ibrutinib followed by an MRD-driven strategy yielded a high rate of CR with BM and PB MRD Disclosures Salles: Roche, Janssen, Gilead, Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Educational events; Amgen: Honoraria, Other: Educational events. Leblond:Gilead: Honoraria, Speakers Bureau; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Honoraria, Speakers Bureau; Astra Zeneca: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Cartron:Roche, Celgene: Consultancy; Sanofi, Gilead, Janssen, Roche, Celgene: Honoraria. Cymbalista:Sunesis: Research Funding; Roche: Research Funding; Janssen: Honoraria; Abbvie: Honoraria; AstraZeneca: Honoraria; Gilead: Honoraria. Le Garff-Tavernier:Alexion: Consultancy, Honoraria. Letestu:Alexion: Membership on an entity's Board of Directors or advisory committees, Other: speaker fee, expert contracts; Roche: Membership on an entity's Board of Directors or advisory committees, Other: speaker fee, expert contracts; Janssen: Membership on an entity's Board of Directors or advisory committees, Other: speaker fee, expert contracts; Abbvie: Membership on an entity's Board of Directors or advisory committees, Other: speaker fee, expert contracts. Feugier:janssen: Honoraria, Research Funding, Speakers Bureau; gilead: Honoraria, Research Funding, Speakers Bureau; abbvie: Honoraria, Research Funding, Speakers Bureau; roche: Honoraria, Research Funding, Speakers Bureau.

Published
2019

5. Obesity survival paradox in cancer patients: Results from the Physical Frailty in older adult cancer patients (PF-EC) study

Author

Philippe Wind, Frédéric Pamoukdjian, Boris Duchemann, Laurent Zelek, Nathalie Ganne, Florence Canoui-Poitrine, Elena Paillaud, Georges Sebbane, Thomas Aparicio, Vincent Levy, Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Gastro-entérologie [Avicenne], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Sorbonne Paris Nord, Clinical Epidemiology and Ageing : Geriatrie Soins Primaires et Santé Publique (CEpiA), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Unité de recherche clinique [Avicenne], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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), Université Paris Descartes - Paris 5 (UPD5), Hôpital Jean Verdier [AP-HP], UFR Santé, Médecine et Biologie Humaine (UFR SMBH), Université Sorbonne Paris Nord, Equipe 3: EREN- Equipe de Recherche en Epidémiologie Nutritionnelle (CRESS - U1153), Institut National de la Recherche Agronomique (INRA)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Paris 13 (UP13)-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Réseau National Alimentation Cancer Recherche (réseau NACRe), Université Paris 13 (UP13)-Institut National de la Recherche Agronomique (INRA)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), CCSD, Accord Elsevier, Oncogeriatric Coordination Unit, Geriatric Department, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Hôpital avicenne, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Sorbonne Paris Nord, Department of Gastroenterology, Department of Medical Oncology, Clinical Research Unit and Clinical Research Centre, Department of Surgery, Université Paris 13 (UP13), Université Paris 13 (UP13)-Institut National de la Recherche Agronomique (INRA)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), and Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)

Subjects
0301 basic medicine, Male, medicine.medical_specialty, Paris, Frail Elderly, 030209 endocrinology & metabolism, Comorbidity, Critical Care and Intensive Care Medicine, Metastasis, Body Mass Index, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, Risk Factors, Internal medicine, Neoplasms, medicine, Humans, Obesity, Prospective Studies, Lung cancer, Aged, Cancer, 2. Zero hunger, Aged, 80 and over, 030109 nutrition & dietetics, Nutrition and Dietetics, Frailty, Obesity survival paradox, business.industry, Mortality rate, medicine.disease, Survival Analysis, Geriatric assessment, 3. Good health, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, C-Reactive Protein, Female, Older people, business, Body mass index, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Cohort study
Abstract

International audience; Background & aims: the obesity survival paradox is an emergent issue in oncology, but its existence remains unclear particularly in older cancer patients. We aimed to assess the obesity survival paradox in older cancer patients.Methods: all consecutive cancer outpatients 65 years and older referred for geriatric assessment (GA) before a decision on cancer treatment between November 2013 and September 2016 were enrolled in the PF-EC cohort study. The main outcome was 6-month mortality. A Cox univariate and multivariate proportional hazard regression models were performed with baseline GA, oncological variables (cancer site, extension and treatment modalities) and C-reactive protein (CRP). We assessed the prognostic value of body mass index categories (i.e. malnutrition = 30 kg/m(2)) in the whole study population and according to the metastatic status.Results: 433 patients with a mean age of 81.2 +/- 6.0 years were included, 51% were women, 44.3% had digestive cancers, 18% breast cancer and 14.5% lung cancer and 45% metastatic cancers. Eighty-eight of these patients (20.3%) were obese at baseline. Mortality rate was 17% during the 6-month follow-up period. After adjustment for sex, gait speed, Mini-Mental State Examination, cancer site and exclusive supportive care, obesity (compared to normal weight) was independently and negatively associated with 6-month mortality only in metastatic patients (aHR 0.17, 95% CI [0.03-0.92], P = 0.04).Conclusion: our study confirms the obesity survival paradox in older cancer patients only in the metastatic group. (C) 2018 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism.

Published
2019
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6. Prevalence of BTK and PLCG2 mutations in a real-life CLL cohort still on ibrutinib after 3 years: a FILO group study

Author

Vincent Levy, Marie-Sarah Dilhuydy, Gregory Lazarian, Anne Quinquenel, Rémi Letestu, Carole Fleury, Delphine Nollet, Florence Cymbalista, Luc-Matthieu Fornecker, Damien Roos-Weil, Alain Delmer, Katia Hormigos, Lise Willems, Romain Guieze, Anne-Sophie Michallet, Loic Ysebaert, Pierre Feugier, Fanny Baran-Marszak, Centre Hospitalier Universitaire de Reims (CHU Reims), Université de Reims Champagne-Ardenne (URCA), Hôpital Robert Debré, Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims (CHU Reims), Les Hôpitaux Universitaires de Strasbourg (HUS), Interface de Recherche Fondamentale et Appliquée en Cancérologie (IRFAC - Inserm U1113), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Paul Strauss : Centre Régional de Lutte contre le Cancer (CRLCC)-Fédération de Médecine Translationelle de Strasbourg (FMTS), Groupe Hospitalier Universitaire Paris Seine-Saint-Denis (GHUPSSD), Adaptateurs de signalisation en hématologie (ASIH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Sorbonne Paris Nord, UFR Santé, Médecine et Biologie Humaine (UFR SMBH), Université Sorbonne Paris Nord, Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Bordeaux [Bordeaux], CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), CHU Clermont-Ferrand, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Pierre et Marie Curie - Paris 6 (UPMC), Sorbonne Universités (COMUE), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Léon Bérard [Lyon], Médecine Personnalisée, Pharmacogénomique, Optimisation Thérapeutique (MEPPOT - U1147), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Faculté des Sciences Fondamentales et Biomédicales (UPD5 Sciences), Université Paris Descartes - Paris 5 (UPD5), CHADEYRON, DOMINIQUE, Role of intra-Clonal Heterogeneity and Leukemic environment in ThErapy Resistance of chronic leukemias (CHELTER), and Université Clermont Auvergne [2017-2020] (UCA [2017-2020])

Subjects
Oncology, [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, medicine.medical_specialty, Lymphocytosis, Chronic lymphocytic leukemia, Immunology, Biochemistry, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, immune system diseases, hemic and lymphatic diseases, Internal medicine, medicine, Bruton's tyrosine kinase, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, biology, business.industry, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Cell Biology, Hematology, medicine.disease, 3. Good health, Leukemia, chemistry, Specimen collection, 030220 oncology & carcinogenesis, Ibrutinib, Cohort, biology.protein, Sample collection, medicine.symptom, business
Abstract

Mutational analyses performed following acquired ibrutinib resistance have suggested that chronic lymphocytic leukemia (CLL) progression on ibrutinib is linked to mutations in Bruton tyrosine kinase (BTK) and/or phospholipase Cγ2 (PLCG2) genes. Mutational information for patients still on ibrutinib is limited. We report a study aimed to provide a “snapshot” of the prevalence of mutations in a real-life CLL cohort still on ibrutinib after at least 3 years of treatment. Of 204 patients who initiated ibrutinib via an early-access program at 29 French Innovative Leukemia Organization (FILO) centers, 63 (31%) were still on ibrutinib after 3 years and 57 provided a fresh blood sample. Thirty patients had a CLL clone ≥0.5 × 109/L, enabling next-generation sequencing (NGS); BTK and PLCG2 mutations were detected in 57% and 13% of the NGS samples, respectively. After median follow-up of 8.5 months from sample collection, the presence of a BTK mutation was significantly associated with subsequent CLL progression (P = .0005 vs no BTK mutation). Our findings support that mutational analysis should be considered in patients receiving ibrutinib who have residual clonal lymphocytosis, and that clinical trials are needed to evaluate whether patients with a BTK mutation may benefit from an early switch to another treatment.

Published
2019
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7. Evaluating abbreviated induction with fludarabine, cyclophosphamide, and dose-dense rituximab in elderly patients with chronic lymphocytic leukemia

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Thérèse Aurran, Xavier Troussard, Bruno Cazin, Sophie de Guibert, Philippe Colombat, Florence Nguyen-Khac, Hervé Maisonneuve, Marie-Christine Béné, Roselyne Delepine, Elsa Tavernier, Véronique Leblond, Olivier Tournilhac, Florence Cymbalista, Stéphane Leprêtre, Christian Berthou, Caroline Dartigeas, Anne-Sophie Michallet, Pierre Feugier, Marie-Sarah Dilhuydy, Rémi Letestu, Eric Van Den Neste, Vincent Levy, Kamel Laribi, Jean-Pierre Vilque, Alain Delmer, Nutrition, croissance et cancer (U 1069) (N2C), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHRU Brest - Service d'Hématologie (CHU-Brest-Hemato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Immunologie et Pathologie (EA2216), Université de Brest (UBO)-IFR148, Service d'hématologie, Centre hospitalier La Roche-Sur-Yon, 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), Service des maladies du sang, CHU Bordeaux [Bordeaux]-Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux]-Groupe Hospitalier Sud, Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de Recherche des Cordeliers (CRC), Université Pierre et Marie Curie - Paris 6 (UPMC)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Adaptateurs de signalisation en hématologie (ASIH), Université Paris 13 (UP13)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Service d'Hématologie Clinique Adulte et de Thérapie Cellulaire, CHU Clermont-Ferrand, EA7283, CIC501, Université d'Auvergne - Clermont-Ferrand I (UdA), Service d'hématologie et immunologie pédiatrique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), Service d'Hématologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service d'Hematologie, Hospices Civils de Lyon (HCL)-Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), AP HP, Clin Res Unit, Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Registre général des cancers du Tarn, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Registre des hémopathies malignes de Basse-Normandie [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Service d'hématologie [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Service d'Hématologie, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), Université Pierre et Marie Curie - Paris 6 (UPMC)-École pratique des hautes études (EPHE), Service d'hématologie biologique [CHU Pitié-Salpêtrière], Université Pierre et Marie Curie - Paris 6 (UPMC)-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), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Sorbonne Paris Cité (USPC)-Université Paris 13 (UP13), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Université Paris Diderot - Paris 7 (UPD7)-Hôpital Robert Debré-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Francim : Réseau français des registres des cancers, CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Bordeaux [Bordeaux]-Groupe Hospitalier Sud-Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Nutrition, croissance et cancer (U 1069) ( N2C ), Université de Tours-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Department of Clinical Haematology, Institute of Cancerology and Hematology, University Hospital Brest, Immunologie et Pathologie ( EA2216 ), Université de Brest ( UBO ) -IFR148, 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 ), Centre hospitalier universitaire de Nantes ( CHU Nantes ), Centre de Recherche des Cordeliers ( CRC ), Université Paris Diderot - Paris 7 ( UPD7 ) -École pratique des hautes études ( EPHE ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service d'hématologie biologique, Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], Adaptateurs de signalisation en hématologie ( ASIH ), Université Paris 13 ( UP13 ) -Université Sorbonne Paris Cité ( USPC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre d'Investigation Clinique [Rennes] ( CIC ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre François Baclesse, Centre Hospitalier Universitaire de Clermont-Ferrand, Université d'Auvergne - Clermont-Ferrand I ( UdA ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 ( UPD7 ), Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), Nutrition-Génétique et Exposition aux Risques Environnementaux ( NGERE ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Lorraine ( UL ), Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Hospices Civils de Lyon ( HCL ) -Centre Hospitalier Lyon Sud [CHU - HCL] ( CHLS ), Hospices Civils de Lyon ( HCL ), Hôpital Avicenne, Registre des hémopathies malignes de Basse-Normandie, Hôpital Bretonneau-CHRU Tours, Centre Hospitalier Régional Universitaire de Tours ( CHRU TOURS ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Tours, Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Centre Régional de Lutte contre le Cancer François Baclesse (CRLC François Baclesse ), Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), Université Paris Diderot - Paris 7 (UPD7)-Hôpital Robert Debré-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Université de Lorraine (UL)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Hôpital Bretonneau-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)

Subjects
Cancer Research, medicine.medical_specialty, Cyclophosphamide, lymphoid leukemias, Chronic lymphocytic leukemia, [SDV]Life Sciences [q-bio], Purine analogue, Neutropenia, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, hemic and lymphatic diseases, medicine, Frail elderly, Chemotherapeutic approaches, immunotherapeutic approaches, [ SDV ] Life Sciences [q-bio], business.industry, Hematology, medicine.disease, Minimal residual disease, 3. Good health, Fludarabine, Oncology, 030220 oncology & carcinogenesis, Immunology, chronic lymphocytic leukemia, Rituximab, business, purine analogues, 030215 immunology, medicine.drug
Abstract

International audience; Elderly patients with chronic lymphocytic leukemia (CLL) are underrepresented in trials evaluating fludarabine, cyclophosphamide, and rituximab (FCR). We assessed four cycles of FCR with two additional rituximab doses on day 14 of cycles 1 and 2 in 194 untreated CLL patients \textgreater 65 years (median age 71.2) without del17p. Four FCR cycles were administered to 90.7% (176/194), with (n = 74) or without (n = 102) dose-delay and/or dose-reduction. A total of 50% grade 3/4 neutropenia occurred after each cycle. Only 6.2% cycles were associated with severe infection. Complete remission (CR) was achieved in 19.7%, and partial remission (PR) in 73.9% of patients. Minimal residual disease (MRD) was negative in 36.7%. Overall survival at 36 months was estimated at 87.4%. Oral FC and dose-dense rituximab is feasible and active in fit elderly CLL patients. However, myelosuppression is significant and frequent dose adaptations are required implying that these results cannot be generalized to unfit or frail elderly CLL

Published
2016
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8. Outcomes in critically ill chronic lymphocytic leukemia patients

Author

François Vincent, Michael Darmon, Aliénor Xhaard, Vincent Levy, David Schnell, Loïc Epelboin, Elie Azoulay, Marion Malphettes, Service de greffe de moelle osseuse [Saint-Louis], Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Unité des Maladies Infectieuses et Tropicales (UMIT), Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], Université de Guyane (UG), Department of Pharmacology and Toxicology, Universität Regensburg (UR), Centre d'Investigations Cliniques 9504, Université Paris Diderot - Paris 7 (UPD7)-Hopital Saint-Louis [AP-HP] (AP-HP), Service d'Immunopathologie [Hôpital Saint-Louis, Paris], Hôpital Saint-Louis, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Université Paris Diderot - Paris 7 (UPD7)-CHU Saint Louis [APHP], and Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)

Subjects
Male, medicine.medical_specialty, Chronic lymphocytic leukemia, [SDV]Life Sciences [q-bio], Antineoplastic Agents, Hospital mortality, Antibodies, Monoclonal, Humanized, Antibodies, Monoclonal, Murine-Derived, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, hemic and lymphatic diseases, MESH: Leukemia, Lymphocytic, Chronic, B-Cell/therapy, Humans, Medicine, Hospital Mortality, Intensive care medicine, Alemtuzumab, Aged, Retrospective Studies, business.industry, Critically ill, Cancer, Middle Aged, Prognosis, medicine.disease, Leukemia, Lymphocytic, Chronic, B-Cell, 3. Good health, Fludarabine, Intensive Care Units, Leukemia, Logistic Models, Treatment Outcome, Oncology, 030220 oncology & carcinogenesis, Female, Rituximab, business, Vidarabine, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030215 immunology, medicine.drug
Abstract

International audience; BACKGROUND:Although recent studies have demonstrated an improvement in the prognosis of critically ill cancer patients, little is known regarding the prognosis of patients with non-aggressive underlying malignancies. The aims of this study were to assess the prognosis of critically ill patients with chronic lymphocytic leukemia (CLL) and to evaluate risk factors for hospital mortality.METHODS:In retrospective mono-center cohort study, consecutive adult patients with CLL requiring ICU admission from 1997 to 2008 were included.RESULTS:Sixty-two patients of 67 years (62-75) were included. Median time interval between CLL diagnosis and ICU admission was 6.7 years (2.6-10.8). Nine patients (15 %) had stage C disease at the time of ICU admission, and seven patients (11 %) had Richter syndrome. Most ICU admissions were related to bacterial or fungal pulmonary infections (n = 47; 76 %). ICU, in-hospital, and 90-day mortality were 35 % (n = 22), 42 % (n = 26), and 58 % (n = 36), respectively. Only three factors were independently associated with in-hospital mortality: oxygen saturation lower than 95 % when breathing room air (odds ratio (OR) 5.80; 95 % confidence interval (CI) 1.23-27.33), need for vasopressors (OR 27.94; 95 % CI 5.37-145.4), and past history of infection (OR 6.62; 95 % CI 1.34-32.68). The final model did not change when disease-related variables (Binet classification, Richter syndrome, long-term steroids) or treatment-related variables (fludarabine, rituximab, or alemtuzumab) were included.CONCLUSION:Acute pulmonary infections remain the leading cause of ICU admission in patients with CLL. The severity at ICU admission and past history of infection were the only factors associated with hospital mortality. Neither disease characteristics nor previous cancer treatments were associated with outcome.

Published
2013
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