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1. Progressive multifocal leukoencephalopathy: MRI findings in HIV-infected patients are closer to rituximab- than natalizumab-associated PML

Author: Caroline Papeix, Elisabeth Maillart, Morgane Solis, Caroline Houillier, Philippe Kerschen, Manel Alleg, Jerome Tamburini Bonnefoy, Xavier Roussel, Bertrand Bourre, Céline Kennel, Stéphane Kremer, Jean-Pierre Marolleau, Philippe Agape, Guido Ahle, Adrien Chauchet, François Cotton, Alexis Caulier, Xavier Leclerc, Patrick Vermersch, Cécile Chabrot, Béatrice Claise, Guillaume Martin-Blondel, Sandra Malak, Samira Fafi-Kremer, Seyyid Baloglu, Jérôme De Seze, Fabrice Bonneville, Jean-Pierre Pruvo, Les Hôpitaux Universitaires de Strasbourg (HUS), Laboratoire de Virologie [Strasbourg], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier de Luxembourg [Luxembourg] (CHL), CHU Rouen, Normandie Université (NU), Service de Neurologie [Hôpitaux Civils de Colmar], Hôpitaux Civils Colmar, Lille Neurosciences & Cognition - U 1172 (LilNCog), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Departement de Neuroradiologie [Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU), CHU Clermont-Ferrand, Institut Curie - Saint Cloud (ICSC), Service Maladies infectieuses et tropicales [CHU Toulouse], Pôle Inflammation, infection, immunologie et loco-moteur [CHU Toulouse] (Pôle I3LM Toulouse), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre de Physiopathologie Toulouse Purpan (CPTP), 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)-Centre National de la Recherche Scientifique (CNRS), Service Neuroradiologie Diagnostique et Thérapeutique [CHU Toulouse], Pôle imagerie médicale [CHU Toulouse], Laboratoire d'Hématologie [CHU Amiens], CHU Amiens-Picardie, AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, CHU Limoges, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Hôpital de Hautepierre [Strasbourg], Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie (ICube), École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Université de Strasbourg (UNISTRA)-Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Les Hôpitaux Universitaires de Strasbourg (HUS)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-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)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Lille Neurosciences & Cognition - U 1172 (LilNCog (ex-JPARC)), Service de neurologie 1 [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), Service de neurologie 2 [CHU Pitié-Salpêtrière], Institut Curie [Saint-Cloud], Service des maladies infectieuses et tropicales [Toulouse], Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de neuroradiologie [CHU Toulouse], CHU Toulouse [Toulouse], Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Réseau nanophotonique et optique, Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Matériaux et nanosciences d'Alsace (FMNGE), Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Strasbourg (UNISTRA), Service de Radiologie (Hôpitaux Universitaires de Strasbourg), Laboratoire de Virologie Médicale [Strasbourg], CHU Strasbourg, Université de Lyon, Centre Hospitalier Universitaire de Rouen, University of Rouen, Rouen, France, University of Lille, Univ. Lille, Inserm, CHU Lille, U1172 - Lille Neurosciences & Cognition, F-59000 Lille, France, Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Lille, Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université, Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU de Clermont-Ferrand, université Clermont-Auvergne, Service des maladies infectieuses et tropicales[Toulouse], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], Service d'Hématologie Clinique [CHU Amiens], Centre Hospitalier Universitaire de Besançon (CHU Besançon), Service of Neurologie - Centres Mémoire de Ressources et de Recherche (Hôpitaux Universitaires de Strasbourg ) (CMRR), Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Matériaux et nanosciences d'Alsace, Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Strasbourg (UNISTRA), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: MESH: Leukoencephalopathy, Progressive Multifocal* / diagnostic imaging, medicine.medical_specialty, Pathology, medicine.medical_treatment, [SDV]Life Sciences [q-bio], viruses, MESH: Natalizumab / adverse effects, HIV Infections, 030218 nuclear medicine & medical imaging, MESH: Magnetic Resonance Imaging, Lesion, 03 medical and health sciences, 0302 clinical medicine, Natalizumab, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Progressive multifocal leukoencephalopathy, medicine, MESH: HIV Infections* / complications, Humans, Radiology, Nuclear Medicine and imaging, Neuroradiology, Retrospective Studies, Chemotherapy, MESH: Humans, business.industry, Leukoencephalopathy, Progressive Multifocal, virus diseases, Brain, Immunosuppression, MESH: Retrospective Studies, General Medicine, MESH: HIV Infections* / drug therapy, medicine.disease, Magnetic Resonance Imaging, MESH: Rituximab / adverse effects, 3. Good health, 030220 oncology & carcinogenesis, MESH: Leukoencephalopathy, Progressive Multifocal* / chemically induced, Rituximab, MESH: Brain / diagnostic imaging, Radiology, medicine.symptom, Neuro, Complication, business, medicine.drug
Abstract: To compare brain MRI findings in progressive multifocal leukoencephalopathy (PML) associated to rituximab and natalizumab treatments and HIV infection. In this retrospective, multicentric study, we analyzed brain MRI exams from 72 patients diagnosed with definite PML: 32 after natalizumab treatment, 20 after rituximab treatment, and 20 HIV patients. We compared T2- or FLAIR-weighted images, diffusion-weighted images, T2*-weighted images, and contrast enhancement features, as well as lesion distribution, especially gray matter involvement. The three PML entities affect U-fibers associated with low signal intensities on T2*-weighted sequences. Natalizumab-associated PML showed a punctuate microcystic appearance in or in the vicinity of the main PML lesions, a potential involvement of the cortex, and contrast enhancement. HIV and rituximab-associated PML showed only mild contrast enhancement, punctuate appearance, and cortical involvement. The CD4/CD8 ratio showed a trend to be higher in the natalizumab group, possibly mirroring a more efficient immune response. Imaging features of rituximab-associated PML are different from those of natalizumab-associated PML and are closer to those observed in HIV-associated PML. • Nowadays, PML is emerging as a complication of new effective therapies based on monoclonal antibodies. • Natalizumab-associated PML shows more inflammatory signs, a perivascular distribution “the milky way,” and more cortex involvement than rituximab- and HIV-associated PML. • MRI differences are probably related to higher levels of immunosuppression in HIV patients and those under rituximab therapy.
Published: 2020

2. Treatment and outcomes of older versus younger women with HER2-positive metastatic breast cancer in the real-world national ESME database

Author: Carine Bellera, Christophe Perrin, Sophie Abadie-Lacourtoisie, Lisa Gauquelin, Marianne Leheurteur, Eric Francois, Catherine Terret, V. Servent, Romain Geiss, Veronique Lorgis, Christelle Jouannaud, Lionel Uwer, Suzette Delaloge, Anthony Gonçalves, Mony Ung, Etienne Brain, Thierry Petit, Olivier Villacroux, Florence Joly, Mylène Annonay, Coralie Courtinard, Pierre Soubeyran, Laurence Cristol-Dalstein, Johan Le Fel, Loïc Campion, Marie-Ange Mouret-Reynier, Institut Bergonié [Bordeaux], UNICANCER, Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Santé Publique, d'Epidémiologie et de Développement (ISPED), Université Bordeaux Segalen - Bordeaux 2, Institut Curie [Saint-Cloud], Institut Claudius Regaud, Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut du Cancer de Montpellier (ICM), Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Centre Eugène Marquis (CRLCC), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université Lille Nord de France (COMUE)-UNICANCER, Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), CRLCC Jean Godinot, Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Centre Paul Strauss, CRLCC Paul Strauss, Centre Léon Bérard [Lyon], Institut Gustave Roussy (IGR), Institut Curie - Saint Cloud (ICSC), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Lille-UNICANCER, Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), 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), Département de médecine oncologique [Gustave Roussy], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Admin, Oskar
Subjects: Receptor, ErbB-2, medicine.medical_treatment, Population, Breast Neoplasms, computer.software_genre, 03 medical and health sciences, 0302 clinical medicine, Elderly, HER2, Antineoplastic Combined Chemotherapy Protocols, Overall survival, Medicine, Humans, In patient, 030212 general & internal medicine, education, skin and connective tissue diseases, RC254-282, Aged, Retrospective Studies, Chemotherapy, education.field_of_study, Database, business.industry, Confounding, Endocrine therapy, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Neoplasms, Second Primary, General Medicine, medicine.disease, Metastatic breast cancer, Progression-Free Survival, 3. Good health, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, 030220 oncology & carcinogenesis, Surgery, Female, Original Article, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, computer
Abstract: Background Treatment and outcomes of patients with HER2-positive (HER2+) metastatic breast cancer (MBC) have dramatically improved over the past 20 years. This work evaluated treatment patterns and outcomes according to age. Methods Women who initiated a treatment for HER2+ MBC between 2008 and 2016 in one of the 18 French comprehensive centers part of the ESME program were included. Objectives were the description of first-line treatment patterns, overall survival (OS), first-line progression-free survival (PFS), and prognostic factors among patients aged 70 years or more (70+), or less than 70 (, Highlights • Only 65% of women aged 70+ with HER2+ MBC receive a standard first-line treatment. • Median PFS1 of women 70+ with HER2+ MBC is 11.1 months (95% CI, 10.0–12.3) vs 13.2 (95% CI, 12.7–13.9) for younger ones. • Non-standard first-line treatment has a detrimental time-varying effect on both OS and PFS.
Published: 2021

3. Outcome beyond third-line chemotherapy for metastatic triple-negative breast cancer in the French ESME program

Author: Geneviève Perrocheau, Carine Laurent, Matthieu Carton, Audrey Hennequin, Lilian Laborde, Thierry Petit, Agnes Loeb, Laurence Vanlemnens, Damien Parent, Claire Labreveux, Thomas Bachelot, Michel Debled, Marie-Ange Mouret-Reynier, E. Chamorey, Florence Lerebours, Barbara Pistilli, Christelle Levy, Thibault De La Motte Rouge, Luc Cabel, Florence Dalenc, Mathieu Robain, Mario Campone, William Jacot, Institut Curie [Saint-Cloud], Institut Gustave Roussy (IGR), Institut Claudius Regaud, Service d'Hématologie [IUCT Toulouse], Université Fédérale Toulouse Midi-Pyrénées-Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université Lille Nord de France (COMUE)-UNICANCER, Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Institut du Cancer de Montpellier (ICM), Institut Bergonié [Bordeaux], UNICANCER, Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), Centre Eugène Marquis (CRLCC), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Institut Jean Godinot [Reims], Centre Paul Strauss, CRLCC Paul Strauss, Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER [Paris], Centre Léon Bérard [Lyon], COLO, Mouniati, Institut Curie - Saint Cloud (ICSC), 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 Lille-UNICANCER, and Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)
Subjects: Adult, Oncology, medicine.medical_specialty, Multivariate analysis, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Breast Neoplasms, Triple Negative Breast Neoplasms, Prognostic factors, lcsh:RC254-282, Disease-Free Survival, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, Chemotherapy, Humans, Medicine, Prospective Studies, 030212 general & internal medicine, Triple-negative breast cancer, ComputingMilieux_MISCELLANEOUS, Aged, Aged, 80 and over, business.industry, Real-life, Cancer, General Medicine, Middle Aged, Nomogram, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Metastatic breast cancer, Prognosis, medicine.disease, 3. Good health, [SDV] Life Sciences [q-bio], Treatment Outcome, 030220 oncology & carcinogenesis, Cohort, Original Article, Female, Surgery, France, business, Heavily pretreated
Abstract: Purpose Among metastatic breast cancer (MBC) patients, those with a triple-negative breast cancer phenotype (mTNBC) have the worst prognosis, but the benefit of chemotherapy beyond second line on outcome remains uncertain. The purpose of this study was to identify predictive factors of outcome after third- or fourth-line chemotherapy. Methods The ESME-MBC database is a French prospective real-life cohort with homogeneous data collection, including patients who initiated first-line treatment for MBC (2008–2016) in 18 cancer centers. After selection of mTNBC cases, we searched for independent predictive factors (Cox proportional-hazards regression models) for overall survival (OS) on third- and fourth-line chemotherapy (OS3, OS4). We built prognostic nomograms based on the main prognostic factors identified. Results Of the 22,266 MBC cases in the ESME cohort, 2903 were mTNBC, 1074 (37%) and 598 (20%) of which had received at least 3 or 4 lines of chemotherapy. PFS after first- and second-line chemotherapy (PFS1, PFS2) and number of metastatic sites ≥3 at baseline were identified by multivariate analysis as prognostic factors for both OS3 (HR = 0.76 95%CI[0.66–0.88], HR = 0.55 95%CI[0.46–0.65], HR = 1.36 95%CI[1.14–1.62], respectively), and OS4 (HR = 0.76 95%CI[0.63–0.91], HR = 0.56 95%CI[0.45–0.7], HR = 1.37 95%CI[1.07–1.74]), respectively. In addition, metastasis-free interval was identified as a prognostic factor for OS3 (p = 0.01), while PFS3 influenced OS4 (HR = 0.75 95%CI[0.57–0.98]). Nomograms predicting OS3 and OS4 achieved a C-index of 0.62 and 0.61, respectively. Conclusion The duration of each previous PFS is a major prognostic factor for OS in mTNBC patients receiving third- or fourth-line chemotherapy. The clinical utility of nomograms including this information was not demonstrated., Highlights • After 3rd- or 4th-line therapy, PFS remained linear in the majority of women with metastatic triple-negative breast cancer. • The duration of each previous PFS had an impact on the OS associated with subsequent lines. • PFS2 was more strongly predictive of outcome than PFS1 for third-line therapy. • PFS2 and PFS3 had an impact on outcome irrespective of PFS1 for fourth-line therapy. • The clinical utility of nomograms including duration of each previous PFS to predict OS was not sufficient.
Published: 2021

4. CinéBreast-factors influencing the time to first metastatic recurrence in breast cancer: Analysis of real-life data from the French ESME MBC database

Author: Lionel Uwer, A. Gonçalves, A. Hennequin, C. Le Tourneau, Paul Gougis, Thomas Bachelot, C. Levy, Grégory Simon, William Jacot, Matthieu Carton, Corinne Tchokothe, M.-A. Mouret-Reynier, M. Saghatchian, Thierry Petit, Marc Debled, Christian Cailliot, M. Leheurteur, Audrey Mailliez, Christophe Perrin, M. Campone, Florence Dalenc, J.-C. Eymard, E. Chamorey, Centre d'investigation clinique Paris Est [CHU Pitié Salpêtrière] (CIC Paris-Est), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-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)-Sorbonne Université (SU), Institut Curie [Paris], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Curie - Saint Cloud (ICSC), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Institut Claudius Regaud, Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER, Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Institut du Cancer de Montpellier (ICM), Institut Bergonié [Bordeaux], Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Centre Léon Bérard [Lyon], Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), Centre Eugène Marquis (CRLCC), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), CRLCC Jean Godinot, Centre Paul Strauss, CRLCC Paul Strauss, Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), R&D Unicancer [Paris], Cancer et génome: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, Mines Paris - PSL (École nationale supérieure des mines de Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'investigation clinique pluridisciplinaire [CHU Pitié Salpêtrière] (CIC-P 1421), 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)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-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)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CCSD, Accord Elsevier, Centre d'investigation clinique Paris Est (CIC Paris-Est), Institut Curie [Saint-Cloud], MINES ParisTech - École nationale supérieure des mines de Paris, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Vieillissement et Maladies chroniques : approches épidémiologique et de santé publique (VIMA), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Bureau de Recherches Géologiques et Minières (BRGM) (BRGM), Centre Hospitalier Universitaire de Montpellier (CHU Montpellier ), Hydrosystèmes et Bioprocédés (UR HBAN), Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA), Nutrition, obésité et risque thrombotique (NORT), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), CEA-Direction des Energies (ex-Direction de l'Energie Nucléaire) (CEA-DES (ex-DEN)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Biostatistics Unit, UNICANCER-Université Côte d'Azur (UCA)-UNICANCER-Université Côte d'Azur (UCA), Biologie et écologie tropicale et méditerranéenne [2007-2010] (BETM), Université de Perpignan Via Domitia (UPVD)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Aix Marseille Université (AMU)-Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Curie [Paris]-MINES ParisTech - École nationale supérieure des mines de Paris, and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Time Factors, Databases, Factual, [SDV]Life Sciences [q-bio], Estrogen receptor, Triple Negative Breast Neoplasms, Real-life data, computer.software_genre, Metastasis, 0302 clinical medicine, Breast cancer, Risk Factors, Epidemiology, 030212 general & internal medicine, Neoplasm Metastasis, skin and connective tissue diseases, Aged, 80 and over, Database, General Medicine, Middle Aged, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Metastatic breast cancer, Progression-Free Survival, 3. Good health, [SDV] Life Sciences [q-bio], 030220 oncology & carcinogenesis, Cohort, Original Article, Female, Metastatic recurrence, France, Adult, medicine.medical_specialty, Breast Neoplasms, [SDV.CAN]Life Sciences [q-bio]/Cancer, lcsh:RC254-282, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, Median follow-up, Biomarkers, Tumor, medicine, Humans, Aged, Retrospective Studies, Growth rate, business.industry, Cancer, medicine.disease, Survival Analysis, Surgery, Neoplasm Recurrence, Local, business, computer, Follow-Up Studies
Abstract: Purpose The Time to First Metastatic Recurrence (TFMR) could be considered as an indirect reflection of the tumour growth kinetics which plays an important role in cancer. Molecular subtypes such as expression of estrogen receptor are known predictive factors of TFMR. The CinéBreast study aimed to identify predictive factors of the time to TFMR. Methods The French Epidemiological Strategy and Medical Economics (ESME) Metastatic Breast Cancer (MBC) Database (NCT03275311) was used, which contains data from a cohort of metastatic breast cancer patients from 2008 to 2016 using retrospective data collection. It is a national multi-centre database. The impact of TFMR on overall survival (OS) since first metastasis was also evaluated. Results Among 16 702 patients recorded in the ESME MBC database, 10 595 had an initially localised breast cancer with hormone receptor (HR) and HER2 status available, with a metastatic recurrence. Median follow up was 56 months. Median TFMR was 59 months (120: 24%). HER2+ and TNBC were respectively 4 times and 12 times (p, Highlights • ESME is a large-scale real-life database of 16 702 metastatic breast cancer patients. • A short time to first metastatic recurrence is associated with poor overall survival. • Triple-negative tumours were more likely to recur early than HR+ and HER2+ tumours.
Published: 2020

5. Oral etoposide in heavily pre-treated metastatic breast cancer: results from the ESME cohort and comparison with other chemotherapy regimens

Author: Jean-Marc Ferrero, Jean-Yves Pierga, Marc Debled, Luc Cabel, Florence Dalenc, Irwin Piot, Bianca Cheaib, Isabelle Desmoulins, Christelle Levy, David Pérol, Anthony Gonçalves, Audrey Mailliez, Marie-Ange Mouret-Reynier, Matthieu Carton, Florence Lerebours, Gaëtane Simon, Claudia Lefeuvre, Jean-Christophe Eymard, Thierry Petit, Marianne Leheurteur, William Jacot, Geneviève Perrocheau, Lionel Uwer, Institut Curie [Saint-Cloud], Pathologie mammaire, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Centre de Recherches en Cancérologie de Toulouse (CRCT), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CRLCC Institut Claudius Regaud, CRLCC Oscar Lambret, Centre Régional de Lutte contre le Cancer François Baclesse (CRLC François Baclesse ), Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), 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), Institut Bergonié - Département de médecine, Université Bordeaux Segalen - Bordeaux 2-Centre régional de lutte contre le cancer [CRLCC], Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Département d'oncologie médicale [Centre Georges-François Leclerc], Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc (CRLCC - CGFL), CRLCC Eugène Marquis (CRLCC), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Institut de Cancérologie de Lorraine - Alexis Vautrin (ICL), Centre Antoine Lacassagne, CRLCC Antoine Lacassagne, Institut Jean Godinot, CRLCC Jean Godinot, CRLCC Paul Strauss, CRLCC Jean Perrin, Institut de cancérologie de l'Ouest - Nantes (ICO Nantes), CRLCC Paul Papin-CRLCC René Gauducheau, UNICANCER - Institut régional du Cancer [Montpellier] (ICM), CRLCC Val d'Aurelle - Paul Lamarque, Centre Léon Bérard [Lyon], Institut Claudius Regaud, Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université Lille Nord de France (COMUE)-UNICANCER, Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Institut Bergonié [Bordeaux], UNICANCER, Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER, Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Institut Jean Godinot [Reims], Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER - Institut régional du Cancer Montpellier Val d'Aurelle (ICM), Institut Curie - Saint Cloud (ICSC), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Lille-UNICANCER, and Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)
Subjects: 0301 basic medicine, Oncology, Cancer Research, medicine.medical_specialty, Receptor, ErbB-2, medicine.medical_treatment, Administration, Oral, [SDV.CAN]Life Sciences [q-bio]/Cancer, Breast Neoplasms, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, Oral administration, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, Medicine, Humans, Topoisomerase II Inhibitors, skin and connective tissue diseases, Etoposide, Retrospective Studies, Chemotherapy, business.industry, Proportional hazards model, Middle Aged, medicine.disease, Metastatic breast cancer, Progression-Free Survival, 3. Good health, 030104 developmental biology, 030220 oncology & carcinogenesis, Propensity score matching, Cohort, Oral drug, Female, business, medicine.drug, Follow-Up Studies
Abstract: HER2-negative metastatic breast cancer (MBC) is a common setting in which chemotherapy could be effective even in later lines of treatment. Oral etoposide has demonstrated clinical activity in this setting in small-scale studies, but its efficacy has not been compared to that of other chemotherapy regimens. We used the ESME database (Epidemiological Strategy and Medical Economics), a real-life national French multicentre cohort of MBC patients initiating therapy between 1 January 2008 to 31 December 2014. HER2-negative MBC patients who received oral etoposide as > 3rd chemotherapy line and for more than 14 days were included. Primary objective was progression-free survival (PFS); secondary objectives were overall survival (OS), and propensity-score matched Cox models including comparison with other therapies in the same setting. Three hundred forty-five out of 16,702 patients received oral etoposide and 222 were eligible. Median PFS was 3.2 months [95% CI 2.8–4] and median OS 7.3 months [95% CI 5.7–10.3]. Median PFS did not significantly differ according to the therapeutic line. The only prognostic factor for both PFS and OS was the MBC phenotype (hormone receptor-positive versus triple-negative, HR = 0.71 [95% CI 0.52–0.97], p = 0.028 for PFS and HR = 0.65 [0.46–0.92], p = 0.014 for OS). After matching for the propensity score, no differential effect on PFS or OS was observed between oral etoposide and other chemotherapy regimens administered in the same setting (HR = 0.94 [95% CI 0.77–1.15], p = 0.55 for PFS and HR = 1.10 [95% CI 0.88–1.37], p = 0.40 for OS). Oral etoposide retains some efficacy in selected heavily pre-treated patients with HER2-negative MBC, with the advantages of oral administration.
Published: 2018

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

Author: Laurence Vanlemmens, Marc Debled, Christian Cailliot, Elisa Gobbini, Thomas Bachelot, Monia Ezzalfani, Christelle Jouannaud, Suzette Delaloge, Magali Lacroix-Triki, Anne Patsouris, Thierry Petit, Simone Mathoulin-Pélissier, Veronique Lorgis, William Jacot, Marie Ange Mouret-Reynier, Mathieu Robain, C. Lefeuvre-Plesse, Florence Dalenc, Audrey Lardy Cleaud, Etienne Brain, Christelle Levy, David Pérol, C. Courtinard, Véronique Diéras, Marianne Leheurteur, Lionel Uwer, Anthony Gonçalves, Jean Marc Ferrero, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR), Cancer et génome: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, Institut Curie [Paris]-MINES ParisTech - École nationale supérieure des mines de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute Curie, Centre Léon Bérard [Lyon], Institut Curie [Saint-Cloud], Service d'Oncologie Médicale, CRLCC Haute Normandie-Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), CRLC Val d'Aurelle-Paul Lamarque, CRLCC Val d'Aurelle - Paul Lamarque, Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), École nationale supérieure d'architecture de Toulouse (ENSA Toulouse), Centre de Recherches en Cancérologie de Toulouse (CRCT), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Service d'Oncologie médicale [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Service d'Oncologie Médicale [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université Lille Nord de France (COMUE)-UNICANCER, Department of Medical Oncology, CRLCC Eugène Marquis (CRLCC), Centre d'Investigation Clinique - Epidemiologie Clinique / Essais Cliniques Bordeaux, Institut National de la Santé et de la Recherche Médicale (INSERM), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), CRLCC Jean Godinot, Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), Département de biologie et pathologie médicales [Gustave Roussy], Cancer et génôme: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, MINES ParisTech - École nationale supérieure des mines de Paris-Institut Curie-Institut National de la Santé et de la Recherche Médicale (INSERM), CRLCC Haute Normandie-CRLCC Henri Becquerel, CRLCC Val d'Aurelle - Paul Lamarque-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Imagerie Moléculaire et Stratégies Théranostiques - Clermont Auvergne (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA), Institut de cancérologie de l'Ouest - Paul Papin (ICO - Paul Papin), Service d'oncologie Médicale, Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Hôpital Jean Minjoz, Center Oscar Lambret, CRLCC Oscar Lambret, Institut de Cancérologie de Lorraine - Alexis Vautrin (ICL), Mines Paris - PSL (École nationale supérieure des mines de Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Curie - Saint Cloud (ICSC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Université de Lille-UNICANCER
Subjects: Adult, Cancer Research, medicine.medical_specialty, Multivariate analysis, Time Factors, Receptor, ErbB-2, [SDV.CAN]Life Sciences [q-bio]/Cancer, Breast Neoplasms, Triple Negative Breast Neoplasms, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Cancer Survivors, Risk Factors, HER2, Internal medicine, polycyclic compounds, Overall survival, Biomarkers, Tumor, Medicine, Humans, 030212 general & internal medicine, Neoplasm Metastasis, skin and connective tissue diseases, Aged, Retrospective Studies, Subtypes, Aged, 80 and over, business.industry, Time trends, Hazard ratio, Middle Aged, Metastatic breast cancer, medicine.disease, Confidence interval, 3. Good health, Treatment Outcome, Oncology, Receptors, Estrogen, 030220 oncology & carcinogenesis, Cohort, Observational study, Female, France, business, Receptors, Progesterone
Abstract: Real-life analysis of overall survival (OS) trends among metastatic breast cancer (MBC) patients may help define medical needs and evaluate the impact of public health investments. The present study aimed to evaluate the independent impact of the year of MBC diagnosis on OS in the Epidemio-Strategy-Medical-Economical (ESME)-MBC cohort.ESME-MBC (NCT03275311) is a French, national, multicentre, observational cohort including 16,702 consecutive newly diagnosed MBC patients (01 January 2008-31 December 2014). Of 16,680 eligible patients, 15,085 had full immunohistochemistry data, allowing classification as hormone receptor-positive and HER2-negative (HR+/HER2-, N = 9907), HER2-positive (HER2+, N = 2861) or triple-negative (HR-/HER2-, N = 2317) subcohorts. Multivariate analyses of OS were conducted among the full ESME cohort and subcohorts.Median OS of the whole cohort was 37.22 months (95% confidence interval [CI], 36.3-38.04). Year of diagnosis was an independent predictor of OS (hazard ratio 0.98 [95% CI, 0.97-1.00], P = .01) together with age, subtype, disease-free interval, visceral metastases and number of organs involved. Median OS of HR+/HER2-, HER2+ and HR-/HER2- subcohorts was, respectively, 42.12 (95% CI, 40.90-43.10), 44.91 (95% CI, 42.51-47.90) and 14.52 (95% CI, 13.70-15.24) months. Year of diagnosis was a strong independent predictor of OS in HER2+ subcohort (hazard ratio 0.91 [95% CI, 0.88-0.94], P .001), but not in HR+/HER2- nor HR-/HER2- subcohorts (hazard ratio 1.00 [95% CI, 0.98-1.01], P = .80 and 1.00 [95% CI, 0.97-1.02], P = .90, respectively).The OS of MBC patients has slightly improved over the past decade. However, this effect is confined to HER2+ cases, highlighting the need of new strategies in the other subtypes.
Published: 2018

7. Quelles mesures pour maîtriser le risque infectieux chez les patients immunodéprimés ? Recommandations formalisées d’experts

Author: Zahar, R., Jolivet, S., Adam, H., Dananché, C., Lizon, J., Alfandari, S., Boulestreau, H., Baghdadi, N., Bay, J.-O., Bénéteau, M., Bougnoux, M., Brenier-Pinchart, P., Dalle, J.-H., Fournier, Sébastien, Fuzibet, J.-G., Kauffmann-Lacroix, C., Le Guinche, I., Lepelletier, D., Loukili, N., Lory, A., Morvan, M., Oumedaly, R., Ribaud, P., Rohrlich, P., Vanhems, Philippe, Aho, S., Vanjak, D., Gangneux, J.-P., Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CIC - CHU Bichat, Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'épidémiologie et d'hygiène hospitalières (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Laboratoire des pathogènes émergents -- Emerging Pathogens Laboratory (LPE-Fondation Mérieux), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service de Réanimation polyvalente et des Maladies infectieuses, Centre Hospitalier Gustave Dron, Service d'Hygiène Hospitalière, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Clermont-Ferrand, Institut Curie [Saint-Cloud], Biologie et Pathogénicité fongiques, Institut Pasteur [Paris]-Institut National de la Recherche Agronomique (INRA), Service de Microbiologie Clinique [Paris], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Hôpital Robert Debré Paris, Hôpital Robert Debré, Centre Hospitalier Universitaire de Nice (CHU Nice), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de bactériologie et hygiène hospitalière [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut d'Hématologie de Basse-Normandie (IHBN), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)-Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER, Service greffe de moelle osseuse, Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Curie [Paris], Service de Parasitologie-Mycologie [Rennes], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Curie - Saint Cloud (ICSC), Biologie et Pathogénicité fongiques (BPF), Institut National de la Recherche Agronomique (INRA)-Institut Pasteur [Paris] (IP), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-UNICANCER, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Université de Rennes (UR)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC), Service d'Epidémiologie et Hygiène Hospitalière, Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS 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)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Agronomique (INRA)-Institut Pasteur [Paris], Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)-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)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Institut Curie
Subjects: Immunocompromised Host, Infection Control, Risk Factors, Practice Guidelines as Topic, Air Microbiology, Humans, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Disease Susceptibility, France, Infections
Abstract: International audience; The increase use of immunosuppressive treatments in patients with solid cancer and/or inflammatory diseases requires revisiting our practices for the prevention of infectious risk in the care setting. A review of the literature by a multidisciplinary working group at the beginning of 2014 wished to answer the following 4 questions to improve healthcare immunocompromised patients: (I) How can we define immunocompromised patients with high, intermediate and low infectious risk, (II) which air treatment should be recommended for this specific population? (III) What additional precautions should be recommended for immunocompromised patients at risk for infection? (IV) Which global environmental control should be recommended? Based on data from the literature and using the GRADE method, we propose 15 recommendations that could help to reduce the risk of infection in these exposed populations.; L’intensification des traitements immunosuppresseurs et la généralisation de leur utilisation aux patients atteints de cancer solide et/ou de maladies inflammatoires nécessitent de revisiter nos pratiques de prévention du risque infectieux en milieu de soin. Cette révision est justifiée aussi par les modifications de nos pratiques avec une intensification des prises en charge en structures de soins de suites réhabilitation et en ambulatoire. Une revue de la littérature menée par un groupe de travail multidisciplinaire réuni début 2014 a souhaité répondre aux 4 questions suivantes : (i) Quelle définition des patients immunodéprimés à risque infectieux élevé, intermédiaire et faible, (ii) Quel traitement d’air recommander pour les patients immunodéprimés à risque d’infections ? (iii) Quelles précautions complémentaires recommander pour les patients immunodéprimés à risque d’infections ? (iv) Quelle maîtrise globale de l’environnement recommander pour les patients immunodéprimés à risque d’infections ? À partir des données de la littérature et en utilisant la méthode GRADE, nous proposons 15 recommandations qui permettront de réduire le risque infectieux dans ces populations exposées.
Published: 2017

8. Molecular and clinical diversity in primary central nervous system lymphoma

Author: Hernández-Verdin, I., Kirasic, E., Wienand, K., Mokhtari, K., Eimer, S., Loiseau, H., Rousseau, A., Paillassa, J., Ahle, G., Lerintiu, F., Uro-Coste, E., Oberic, L., Figarella-Branger, D., Chinot, O., Gauchotte, G., Taillandier, L., Marolleau, J.-P., Polivka, M., Adam, C., Ursu, R., Schmitt, A., Barillot, N., Nichelli, L., Lozano-Sánchez, F., Ibañez-Juliá, M.-J., Peyre, M., Mathon, B., Abada, Y., Charlotte, F., Davi, F., Stewart, C., de Reyniès, A., Choquet, S., Soussain, C., Houillier, C., Chapuy, B., Hoang-Xuan, K., Alentorn, A., Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-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)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), University Medical Center Göttingen (UMG), Freie Universität Berlin, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de pathologie [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, CHU Bordeaux [Bordeaux], Imagerie moléculaire et thérapies innovantes en oncologie (IMOTION), Université de Bordeaux (UB), 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), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Service de Neurologie [Hôpitaux Civils de Colmar], Hôpitaux Civils Colmar, Hôpitaux Civils de Colmar, Centre de Recherches en Cancérologie de Toulouse (CRCT), 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)-Centre National de la Recherche Scientifique (CNRS), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital de la Timone [CHU - APHM] (TIMONE), Institut de neurophysiopathologie (INP), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), 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 de Nancy (CHRU Nancy), CHU Amiens-Picardie, HEMATIM - Hématopoïèse et immunologie - UR UPJV 4666 (HEMATIM), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Université Paris Diderot - Paris 7 (UPD7), Hopital Saint-Louis [AP-HP] (AP-HP), Institut Bergonié [Bordeaux], UNICANCER, Sorbonne Université (SU), Centre Hospitalier Saint Jean de Perpignan, Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Institut Curie - Saint Cloud (ICSC), DESSAIVRE, Louise, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d’Anatomie Pathologique [CHRU Nancy], and École pratique des hautes études (EPHE)
Subjects: [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Oncology, tumor heterogeneity, Hematology, multi-omics, microenvironment, PCNSL, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Primary central nervous system lymphoma (PCNSL) is a rare and distinct entity within diffuse large B-cell lymphoma presenting with variable response rates probably to underlying molecular heterogeneity.To identify and characterize PCNSL heterogeneity and facilitate clinical translation, we carried out a comprehensive multi-omic analysis [whole-exome sequencing, RNA sequencing (RNA-seq), methylation sequencing, and clinical features] in a discovery cohort of 147 fresh-frozen (FF) immunocompetent PCNSLs and a validation cohort of formalin-fixed, paraffin-embedded (FFPE) 93 PCNSLs with RNA-seq and clinico-radiological data.Consensus clustering of multi-omic data uncovered concordant classification of four robust, non-overlapping, prognostically significant clusters (CS). The CS1 and CS2 groups presented an immune-cold hypermethylated profile but a distinct clinical behavior. The 'immune-hot' CS4 group, enriched with mutations increasing the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) and nuclear factor-κB activity, had the most favorable clinical outcome, while the heterogeneous-immune CS3 group had the worse prognosis probably due to its association with meningeal infiltration and enriched HIST1H1E mutations. CS1 was characterized by high Polycomb repressive complex 2 activity and CDKN2A/B loss leading to higher proliferation activity. Integrated analysis on proposed targets suggests potential use of immune checkpoint inhibitors/JAK1 inhibitors for CS4, cyclin D-Cdk4,6 plus phosphoinositide 3-kinase (PI3K) inhibitors for CS1, lenalidomide/demethylating drugs for CS2, and enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2) inhibitors for CS3. We developed an algorithm to identify the PCNSL subtypes using RNA-seq data from either FFPE or FF tissue.The integration of genome-wide data from multi-omic data revealed four molecular patterns in PCNSL with a distinctive prognostic impact that provides a basis for future clinical stratification and subtype-based targeted interventions.
Published: 2023

9. Circulating tumour cells and pathological complete response: independent prognostic factors in inflammatory breast cancer in a pooled analysis of two multicentre phase II trials (BEVERLY-1 and -2) of neoadjuvant chemotherapy combined with bevacizumab

Author: Charlotte Proudhon, E. Charafe-Jaufret, A-C. Hardy-Bessard, Aurélie Autret, J-M Ferrero, J.-C. Eymard, Florence Dalenc, M. Campone, François-Clément Bidard, François Bertucci, Alain Lortholary, Patrick Soulié, Thomas Bachelot, Fabrice Andre, Jacques Bonneterre, Jean-Yves Pierga, Patrice Viens, Jean-Marie Boher, Christelle Levy, Gilles Romieu, Joseph Gligorov, Pierre Kerbrat, Thierry Petit, Jérôme Lemonnier, Marie-Ange Mouret-Reynier, Florence Lerebours, Département d'Oncologie Médicale [Institut Curie, Paris], Institut Curie [Paris], Centre de Recherche en Cancérologie de Marseille (CRCM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), CRLCC Paul Strauss, Biomarqueurs prédictifs et nouvelles stratégies moléculaires en thérapeutique anticancéreuse (U981), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Pathologie mammaire, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), 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 Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université Lille Nord de France (COMUE)-UNICANCER, Institut Curie [Saint-Cloud], Centre Léon Bérard [Lyon], Centre Eugène Marquis (CRLCC), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Institut Jean Godinot [Reims], Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), Centre Armoricain de Radiothérapie, d'Imagerie médicale et d'Oncologie [Plérin, Saint-Brieuc] (CARIO), Département de Radio-Oncologie [Nantes] (Centre Catherine de Sienne), Centre Catherine-de-Sienne [Nantes] (CCS), Aix Marseille Université (AMU), R&D UNICANCER, Fédération Nationale des Centres de Lutte Contre le Cancer (FNCLCL/UNICANCER), UNICANCER-UNICANCER, Roche, La Ligue Nationale Contre le Cancer, Chugai Pharma, Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Université de Lille-UNICANCER, Institut Curie - Saint Cloud (ICSC), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Lissalde, Claire
Subjects: 0301 basic medicine, Oncology, circulating endothelial cells, Receptor, ErbB-2, medicine.medical_treatment, Phases of clinical research, Docetaxel, 0302 clinical medicine, Trastuzumab, Antineoplastic Combined Chemotherapy Protocols, Neoadjuvant therapy, Hematology, Middle Aged, Neoplastic Cells, Circulating, Prognosis, Chemotherapy regimen, Neoadjuvant Therapy, 3. Good health, Bevacizumab, Chemotherapy, Adjuvant, 030220 oncology & carcinogenesis, Female, Inflammatory Breast Neoplasms, Taxoids, medicine.drug, neoadjuvant chemotherapy, Adult, medicine.medical_specialty, circulating tumour cells, education, [SDV.CAN]Life Sciences [q-bio]/Cancer, Inflammatory breast cancer, Disease-Free Survival, 03 medical and health sciences, Young Adult, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, medicine, Humans, neoplasms, Cyclophosphamide, Aged, Epirubicin, Chemotherapy, business.industry, medicine.disease, 030104 developmental biology, business, inflammatory breast cancer
Abstract: International audience; Background: We present a pooled analysis of predictive and prognostic values of circulating tumour cells (CTC) and circulating endothelial cells (CEC) in two prospective trials of patients with inflammatory breast cancer (IBC) treated with neoadjuvant chemotherapy combined with neoadjuvant and adjuvant bevacizumab. Patients and methods: Nonmetastatic T4d patients were enrolled in two phase II multicentre trials, evaluating bevacizumab in combination with sequential neoadjuvant chemotherapy of four cycles of FEC followed by four cycles of docetaxel in HER2-negative tumour (BEVERLY-1) or docetaxel and trastuzumab in HER2-positive tumour (BEVERLY-2). CTC and CEC were detected in 7.5 and 4 ml of blood, respectively, with the CellSearch System. Results: From October 2008 to September 2010, 152 patients were included and 137 were evaluable for CTC and CEC. At baseline, 55 patients had detectable CTC (39%). After four cycles of chemotherapy, a dramatic drop in CTC to a rate of 9% was observed (P < 0.01). Pathological complete response (pCR) rate was 40%. No correlation was found between CTC or CEC levels and pCR rate. Median follow-up was 43 months. CTC detection (1 CTC/7.5 ml) at baseline was associated with shorter 3-year disease-free survival (39% versus 70% for patients without CTC, P < 0.01, HR 2.80) and shorter 3-year overall survival (OS) (P < 0.01). In multivariate analysis, independent prognostic parameters for shorter survival were absence of hormonal receptors , no pCR and CTC detection at baseline. CEC level at baseline or variations during treatment had no prognostic value. Conclusion: In this pooled analysis of two prospective trials in nonmetastatic IBC, detection rate of CTC was 39% with a strong and independent prognostic value for survival. Combination of pCR after neoadjuvant treatment with no CTC detection at baseline isolated a subgroup of IBC with excellent OS (94% 3-year OS), suggesting that CTC count could be part of IBC stratification in prospective trials.
Published: 2017

10. Dynamics of Long-Term Patient-Reported Quality of Life and Health Behaviors After Adjuvant Breast Cancer Chemotherapy

Author: Antonio Di Meglio, Julie Havas, Arnauld S. Gbenou, Elise Martin, Mayssam El-Mouhebb, Barbara Pistilli, Gwenn Menvielle, Agnes Dumas, Sibille Everhard, Anne-Laure Martin, Paul H. Cottu, Florence Lerebours, Charles Coutant, Anne Lesur, Olivier Tredan, Patrick Soulie, Laurence Vanlemmens, Florence Joly, Suzette Delaloge, Patricia A. Ganz, Fabrice André, Ann H. Partridge, Lee W. Jones, Stefan Michiels, Ines Vaz-Luis, Institut Gustave Roussy (IGR), Prédicteurs moléculaires et nouvelles cibles en oncologie (PMNCO), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Epidémiologie Clinique et Evaluation Economique Appliquées aux Populations Vulnérables (ECEVE (U1123 / UMR_S_1123)), Institut National de la Santé et de la Recherche Médicale (INSERM)-AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), UNICANCER, Institut Curie [Paris], Institut Curie - Saint Cloud (ICSC), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), Centre Léon Bérard [Lyon], CRLCC Paul Papin, Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER, Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Département de médecine oncologique [Gustave Roussy], University of California [Los Angeles] (UCLA), University of California (UC), Dana-Farber Cancer Institute [Boston], Memorial Sloane Kettering Cancer Center [New York], Service de biostatistique et d'épidémiologie (SBE), Direction de la recherche clinique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Oncostat (U1018 (Équipe 2)), Institut Gustave Roussy (IGR)-Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, and ANR-18-IBHU-0002,PRISM,PRecISion Medicine Institute in oncology(2018)
Subjects: Cancer Research, Prevention, [SDV]Life Sciences [q-bio], Health Behavior, Clinical Sciences, Oncology and Carcinogenesis, Breast Neoplasms, Oncology, Chemotherapy, Adjuvant, Clinical Research, Breast Cancer, Behavioral and Social Science, Quality of Life, Humans, Chemotherapy, Female, Patient Reported Outcome Measures, Oncology & Carcinogenesis, Adjuvant, Cancer
Abstract: PURPOSE We aimed to characterize long-term quality of life (QOL) trajectories among patients with breast cancer treated with adjuvant chemotherapy and to identify related patterns of health behaviors. METHODS Female stage I-III breast cancer patients receiving chemotherapy in CANTO (CANcer TOxicity; ClinicalTrials.gov identifier: NCT01993498 ) were included. Trajectories of QOL (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire–C30 Summary Score) and associations with trajectory group membership were identified by iterative estimations of group-based trajectory models and multivariable multinomial logistic regression, respectively. RESULTS Four trajectory groups were identified (N = 4,131): excellent (51.7%), very good (31.7%), deteriorating (10.0%), and poor (6.6%) QOL. The deteriorating trajectory group reported fairly good baseline QOL (mean [95% CI], 78.3/100 [76.2 to 80.5]), which significantly worsened at year-1 (58.1/100 [56.4 to 59.9]) and never recovered to pretreatment values through year-4 (61.1/100 [59.0 to 63.3]) postdiagnosis. Healthy behaviors were associated with better performing trajectory groups. Obesity (adjusted odds ratio [aOR] v lean, 1.51 [95% CI, 1.28 to 1.79]; P < .0001) and current smoking (aOR v never, 1.52 [95% CI, 1.27 to 1.82]; P < .0001) at diagnosis were associated with membership to the deteriorating group, which was also characterized by a higher prevalence of patients with excess body weight and insufficient physical activity through year-4 and by frequent exposure to tobacco smoking during chemotherapy. Additional factors associated with membership to the deteriorating group included younger age (aOR, 1-year decrement 1.01 [95% CI, 1.01 to 1.02]; P = .043), comorbidities (aOR v no, 1.22 [95% CI, 1.06 to 1.40]; P = .005), lower income (aOR v wealthier households, 1.21 [95% CI, 1.07 to 1.37]; P = .002), and endocrine therapy (aOR v no, 1.14 [95% CI, 1.01 to 1.30]; P = .047). CONCLUSION This latent-class analysis identified some patients with upfront poor QOL and a high-risk cluster with severe, persistent postchemotherapy QOL deterioration. Screening relevant patient-level characteristics may inform tailored interventions to mitigate the detrimental impact of chemotherapy and preserve QOL, including early addressal of behavioral concerns and provision of healthy lifestyle support programs.
Published: 2022

11. Dépistage du cancer du sein : en route vers le futur

Author: Charles Coutant, Roman Rouzier, Frédérique Penault-Lorca, Marc Debled, David Azria, Bernard Asselain, Etienne Brain, Anne Tardivon, Thomas Bachelot, Patrick Arveux, Marc Espié, Anne-Claire Hardy-Bessard, Christelle Levy, William Jacot, Jérôme Lemonnier, Joseph Gligorov, David G. Cox, Corinne Balleyguier, Fabrice Andre, Jean-Philippe Jacquin, Hugues Bourgeois, Mario Campone, François-Clément Bidard, Anthony Gonçalves, Hervé Bonnefoi, Bruno Coudert, Florence Dalenc, J. Grenier, Johanna Arvis, Martine Castro, Thierry Petit, Gérard Ganem, Suzette Delaloge, Alain Lortholary, Laurence Venat-Bouvet, Biomarqueurs prédictifs et nouvelles stratégies moléculaires en thérapeutique anticancéreuse (U981), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Pathologie mammaire, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Université Paris-Saclay, Département de Cancérologie Médicale [Lyon], Centre Léon Bérard : Centre Régional de Lutte Contre le Cancer Lyon Rhône-Alpes, Université de recherche Paris, sciences et lettres [Institut Curie, Paris], Institut Curie [Paris], Hôpital Saint-Louis, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Institut Curie [Saint-Cloud], Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Institut Bergonié [Bordeaux], UNICANCER, Centre de Recherche Saint-Antoine (UMRS893), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Armoricain de Radiothérapie, d'Imagerie médicale et d'Oncologie [Plérin, Saint-Brieuc] (CARIO), 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), Institut de Cancérologie de la Loire Lucien Neuwirth, Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), R&D Unicancer [Paris], Centre de Recherche en Cancérologie de Marseille (CRCM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), Centre Jean Bernard [Institut Inter-régional de Cancérologie - Le Mans], Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), Centre Paul Strauss, CRLCC Paul Strauss, Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), 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), Institut d'oncologie de l'Ouest [CHU Nantes], Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Centre Catherine-de-Sienne [Nantes] (CCS), Service d'Oncologie médicale [CHU Limoges], CHU Limoges, Institut Sainte Catherine [Avignon], Ligue nationale contre le cancer [Cahors] (comité du Lot), Europadonna France [Paris], 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), Registre de Côte d'Or [Dijon] (centre Georges-François-Leclerc - CGFL), Département d'imagerie médicale [Gustave Roussy], Institut Gustave Roussy (IGR), Intergroupe National de Recherche Sur Le Cancer Du Sein Unicancer, Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Registre des Cancers du Sein et autres Cancers Gynécologiques de Côte d'Or - Breast and Gynaecologic Cancer Registry of Côte d’Or, 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-Université de Bourgogne (UB)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER, Centre Léon Bérard [Lyon], Institut Curie - Saint Cloud (ICSC), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Bernardo, Elizabeth
Subjects: Risk, Cancer Research, medicine.medical_specialty, Personalized, [SDV.CAN]Life Sciences [q-bio]/Cancer, Disease, Risque, 03 medical and health sciences, Breast cancer screening, 0302 clinical medicine, Breast cancer, [SDV.CAN] Life Sciences [q-bio]/Cancer, Personnalisé, medicine, Mammography, Radiology, Nuclear Medicine and imaging, 030212 general & internal medicine, Intensive care medicine, Screening procedures, Cancer du sein, Biomarqueurs, Cancer prevention, medicine.diagnostic_test, business.industry, Hematology, General Medicine, medicine.disease, 3. Good health, Clinical trial, Oncology, Dépistage, 030220 oncology & carcinogenesis, Screening, Biomarker (medicine), business, Biomarkers
Abstract: Breast cancer remains a potentially lethal disease, which requires aggressive treatments and is associated with long-term consequences. Its prognosis is linked to both tumor biology and burden at diagnosis. Although treatments have allowed important improvements in prognosis over the past 20 years, breast cancer screening remains necessary. Mammographic screening allows earlier stage diagnoses and a decrease of breast cancer specific mortality. However, breast cancer screening modalities should be revised with the objective to address demonstrated limitations of mammographic screening (limited benefit, imperfect sensitivity and specificity, overdiagnoses, radiation-induced morbidity). Furthermore, both objective and perceived performances of screening procedures should be improved. Numerous large international efforts are ongoing, leading to scientific progresses that should have rapid clinical implications in this area. Among them is improvement of imaging techniques performance, development of real time diagnosis, and development of new non radiological screening techniques such as the search for circulating tumor DNA, development of biomarkers able to allow precise risk evaluation and stratified screening. As well, overtreatment is currently addressed by biomarker-based de-escalation clinical trials. These advances need to be associated with strong societal support, as well as major paradigm changes regarding the way health and cancer prevention is perceived by individuals, Le cancer du sein demeure une maladie grave, associée à des séquelles à long terme et ses traitements sont lourds, même à un stade précoce. Son pronostic est lié à la biologie et à la masse tumorale au diagnostic. Même si les traitements ont permis des avancées importantes, le dépistage du cancer du sein reste donc une nécessité. La mammographie de dépistage permet un diagnostic à un stade plus précoce et une diminution du risque de décès par cancer du sein. Cependant, les modalités du dépistage du cancer du sein doivent être révisées pour diminuer considérablement les limites associées à la mammographie (bénéfice limité, spécificité et sensibilité imparfaite, surdiagnostics, morbidité de la technique elle-même). Il est nécessaire d'améliorer à la fois les performances objectives de ce dépistage et les performances ressenties par la population, souvent décalées. De nombreuses pistes d'amélioration, fruits de très abondants travaux internationaux, permettent d'espérer des implications cliniques rapides : outre l'amélioration des performances de l'imagerie et les possibilités de diagnostic en temps réel, de nouvelles techniques de dépistage non radiologiques sont en développement (ADN tumoral circulant par exemple), ainsi que des biomarqueurs permettant l'estimation des risques individuels et l'avènement de stratégies de dépistage stratifiées sur ceux-ci. Enfin, les progrès de la biologie et des essais cliniques de désescalade en cours permettent d'espérer une diminution des surtraitements. Ces avancées ne peuvent aller sans un accompagnement sociétal fort et des changements de paradigmes des rapports des individus à leur santé et à la prévention du cancer.
Published: 2016

12. Soluble VE-cadherin in metastatic breast cancer: an independent prognostic factor for both progression-free survival and overall survival

Author: Helena Polena, Thomas Bachelot, Olivier Tredan, Isabelle Vilgrain, François-Clément Bidard, Jean-Yves Pierga, Camille Schiffler, Abir Khalil-Mgharbel, Etienne Brain, Sylvie Chabaud, Pauline Rochefort, Centre Léon Bérard [Lyon], Service d'Oncologie Médicale, Institut Curie [Paris], Institut Curie - Saint Cloud (ICSC), Laboratoire de développement et vieillissement de l'endothélium, Université Joseph Fourier - Grenoble 1 (UJF)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Oncogénèse et progression tumorale, Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Curie [Saint-Cloud], and Institut National de la Santé et de la Recherche Médicale (INSERM)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Joseph Fourier - Grenoble 1 (UJF)
Subjects: 0301 basic medicine, Oncology, Adult, Cancer Research, Prognostic variable, medicine.medical_specialty, Colorectal cancer, [SDV.CAN]Life Sciences [q-bio]/Cancer, Breast Neoplasms, survival, Disease-Free Survival, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, [SDV.SP.MED]Life Sciences [q-bio]/Pharmaceutical sciences/Medication, Antigens, CD, Internal medicine, medicine, Biomarkers, Tumor, Humans, Progression-free survival, Neoplasm Metastasis, skin and connective tissue diseases, Lung cancer, prognostic factor, Molecular Diagnostics, Survival analysis, Aged, Aged, 80 and over, business.industry, soluble VE-cadherin, Middle Aged, medicine.disease, Cadherins, Prognosis, Metastatic breast cancer, Survival Analysis, 3. Good health, 030104 developmental biology, 030220 oncology & carcinogenesis, Disease Progression, Female, metastatic breast cancer, business, Liver cancer
Abstract: Background: Patients with metastatic breast cancer (MBC) represent a heterogeneous group, with large differences in outcomes from individual patients. VE-cadherin, an endothelial-specific cadherin, was shown to promote tumour proliferation and angiogenesis. Soluble VE-cadherin has been recently associated to breast cancer progression. This study was designed to investigate the prognosis significance of soluble VE-cadherin in hormone-refractory MBC. Methods: Between 2004 and 2007, 150 patients with a fully documented history of hormone-refractory MBC were included in the prospective SEMTOF study. Serum concentrations of VE-cadherin were measured at inclusion for 141 patients and 6 weeks after the beginning of chemotherapy, using a sandwich enzyme immunoassay. Results: The presence of high levels of serum VE-cadherin was significantly correlated to a shorter progression-free (PFS) and overall survival (OS). In a multivariate analysis along with clinical and biologic prognostic parameters, high serum VE-cadherin level was an independent adverse prognostic variable for PFS (median PFS 9.7 (IC95: 8; 11.9) vs 5.8 (IC95: 4.1; 8) months P=0.0008) and OS (median OS 34 (IC95: 26.6; 47.1) vs 14.8 (IC95: 9.3; 21.4) months P=0.0007). Moreover, VE-cadherin decrease during chemotherapy was also associated with good prognosis. Conclusions: Serum VE-cadherin levels correlate to poorer survival in patients with hormone-refractory MBC. As sVE-cadherin reflects tumour angiogenesis, this could have therapeutic implications for antiangiogenic treatment.
Published: 2016

13. Curative high‐dose reirradiation for patients with recurrent head and neck squamous cell carcinoma using IMRT or proton therapy: Outcomes and analysis of patterns of failure

Author: Arnaud Beddok, Caroline Saint‐Martin, Samar Krhili, Catherine Ala Eddine, Laurence Champion, Anne Chilles, Farid Goudjil, Sofia Zefkili, Malika Amessis, Dominique Peurien, Olivier Choussy, Christophe le Tourneau, Remi Dendale, Irene Buvat, Gilles Créhange, Valentin Calugaru, Institut Curie [Paris], Laboratoire d'Imagerie Translationnelle en Oncologie (LITO ), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Curie Centre de Protonthérapie d'Orsay, Institut Curie - Saint Cloud (ICSC), Université Paris sciences et lettres (PSL), Cancer et génome: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, Mines Paris - PSL (École nationale supérieure des mines de Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), and Buvat, Irène
Subjects: Squamous Cell Carcinoma of Head and Neck, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, toxicity, Radiotherapy Dosage, [SDV.CAN]Life Sciences [q-bio]/Cancer, head and neck carcinoma, Re-Irradiation, Reirradiation head and neck carcinoma IMRT proton therapy toxicity, [SDV.IB.IMA] Life Sciences [q-bio]/Bioengineering/Imaging, [SDV.CAN] Life Sciences [q-bio]/Cancer, Otorhinolaryngology, Head and Neck Neoplasms, Carcinoma, Squamous Cell, proton therapy, Humans, Radiotherapy, Intensity-Modulated, Neoplasm Recurrence, Local, IMRT, Reirradiation
Abstract: International audience; Purpose: To analyze outcomes of patients treated with curative reirradiation (reRT), with intensity-modulated radiation therapy (IMRT) or proton therapy (PT) for recurrent head and neck squamous cell carcinoma (HNSCC). Materials: Among the 55 patients reirradiated for head and neck cancer from 30/08/2012 to 08/04/2019, 23 had HNSCC and received IMRT (52.2%) or PT (47.8%) at a median maximum dose to the CTV of 66 Gy. Results: After a median follow-up of 41.3 months, 18 patients developed a locoregional recurrence (LR), of which eight (44.4%) occurred within the previously reirradiated volume. Two-year locoregional failure-free survival and overall survival were 18.3%[95%CI:7.1%-47.1%] and 42.5%[95%CI:26.2%-69.1%], respectively. Disease-free survival was significantly longer in the PT group (p = 0.031). Main late grade ≥2 toxicities were dysphagia and trismus. Conclusion: Curative reRT in HNSCC is possible for selected cases, but the LR rate in the irradiated field and the risk of toxicity grade ≥2 remain high.
Published: 2022

14. Breast Cancer Risk Associated with Estrogen Exposure and Truncating Mutation Location in BRCA1/2 Carriers

Author: Nadine Andrieu, Laurence Gladieff, Olivier Caron, Laurence Venat-Bouvet, Dominique Stoppa-Lyonnet, Pascaline Berthet, Catherine Noguès, Véronique Mari, Alain Lortholary, Jean-Pierre Fricker, Emmanuelle Mouret-Fourme, Elisabeth Luporsi, Dominique Leroux, Paul Gesta, Valérie Bonadona, Laurence Faivre, Christine Lasset, Pascal Pujol, François Eisinger, Isabelle Coupier, Chrystelle Colas, Julie Lecarpentier, Julie Tinat, Christine Maugard, Marion Gauthier-Villars, Bruno Buecher, Cancer et génome: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, Mines Paris - PSL (École nationale supérieure des mines de Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Curie - Saint Cloud (ICSC), Institut Curie [Paris], Unité de génétique et biologie des cancers (U830), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Léon Bérard [Lyon], 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), CRLCC Paul Strauss, Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Onco-génétique, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital Arnaud de Villeneuve [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service d'oncogénétique [Centre georges-François Leclerc], Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER, Centre Hospitalier Georges Renon [Niort] (CH Georges Renon Niort), Centre Investigations Préventives et Cliniques (IPC), CPAM, Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U912 INSERM - Aix Marseille Univ - IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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 Claudius Regaud, Centre Catherine-de-Sienne [Nantes] (CCS), Service d'oncologie médicale [ICL Alexis Vautrin], Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), UNICANCER, Service de génétique médicale CHU Grenoble Hôpital Couple Enfant, CHU Grenoble, CHU Dupuytren, Nouvel Hôpital Civil, Laboratoire de Diagnostic Génétique, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Rouen, Normandie Université (NU), The GENEPSO study is supported by the Fondation de France and the Ligue Nationale Contre le Cancer., JL has been supported by Fondation de France., Lissalde, Claire, Institut Curie [Paris]-MINES ParisTech - École nationale supérieure des mines de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Curie [Saint-Cloud], UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Institut de Recherche pour le Développement (IRD)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), Service d'Hématologie [IUCT Toulouse], Université Fédérale Toulouse Midi-Pyrénées-Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: Epidemiology, Physiology, phenotype-genotype correlation, 0302 clinical medicine, Breast cancer, Risk Factors, skin and connective tissue diseases, Reproductive History, Aged, 80 and over, 0303 health sciences, education.field_of_study, BRCA1 Protein, Hazard ratio, Absolute risk reduction, Middle Aged, 3. Good health, Menopause, Oncology, risk factor, 030220 oncology & carcinogenesis, Menarche, Female, Adult, Heterozygote, medicine.medical_specialty, Adolescent, Population, interaction, Breast Neoplasms, [SDV.CAN]Life Sciences [q-bio]/Cancer, estrogen exposure, Young Adult, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, medicine, Humans, Genetic Predisposition to Disease, Risk factor, education, Aged, Proportional Hazards Models, 030304 developmental biology, BRCA2 Protein, Gynecology, business.industry, Proportional hazards model, Estrogens, medicine.disease, BRCA1, BRCA2, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Mutation, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business
Abstract: Background: Mutations in BRCA1/2 confer a high risk of breast cancer, but literature values of this risk vary. A genotype–phenotype correlation has been found in both genes, and the effect of reproductive factors differs according to mutation location. Therefore, we hypothesize that such a variation may exist for other factors related to estrogen exposure. Methods: We used a weighted Cox regression model to assess variation in breast cancer risk with these factors using location of mutation in homogeneous breast cancer risk region of BRCA1/2 in the GENEPSO study. Results: We found that late age at menarche reduced breast cancer risk by 31% and that among BRCA1 carriers, a long or a short menstrual cycle increased risk (by 65% and 73%, respectively). Among premenopausal women, overweight was associated with a 45% decrease in risk whereas underweight was associated with an increased risk (HR, 2.40). A natural menopause, mainly after age 50, was associated with a high breast cancer risk (HR, 2.46), and a significant interaction between menopause status and the location of mutations was found leading up to 10% variation in absolute risk according to the age at menopause. Conclusions: As observed in the general population, a late menarche, a long or a short menstrual cycle, over- or underweight, and being postmenopausal were associated with breast cancer risk in BRCA1/2 carriers. The association with the menopause was observed only when the mutation was located in the “high-risk” zones. Impact: Taking into account modifier factors, location of mutation might be important for the clinical management of BRCA1/2 mutation carriers. Cancer Epidemiol Biomarkers Prev; 24(4); 698–707. ©2015 AACR.
Published: 2015

15. Voxel‐wise supervised analysis of tumors with multimodal engineered features to highlight interpretable biological patterns

Author: Thibault Escobar, Sébastien Vauclin, Fanny Orlhac, Christophe Nioche, Pascal Pineau, Laurence Champion, Hervé Brisse, Irène Buvat, Buvat, Irène, Laboratoire d'Imagerie Translationnelle en Oncologie (LITO ), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), DOSIsoft, Institut Curie - Saint Cloud (ICSC), and Institut Curie [Paris]
Subjects: Lung Neoplasms, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, Sarcoma, General Medicine, Magnetic Resonance Imaging, machine learning, [SDV.IB.IMA] Life Sciences [q-bio]/Bioengineering/Imaging, radiomics, Positron Emission Tomography Computed Tomography, voxel-wise, Humans, sub-region, Neural Networks, Computer, interpretability
Abstract: International audience; Background: Translation of predictive and prognostic image-based learning models to clinical applications are challenging due in part to their lack of interpretability. Some deep-learningbased methods provide information about the regions driving the model output. Yet, due to the high-level abstraction of deep features, these methods do not completely solve the interpretation challenge. In addition, low sample size cohorts can lead to instabilities and suboptimal convergence for models involving a large number of parameters such as convolutional neural networks. Purpose: Here, we propose a method for designing radiomic models that combines the interpretability of handcrafted radiomics with a sub-regional analysis. Materials and Methods: Our approach relies on voxel-wise engineered radiomic features with average global aggregation and logistic regression. The method is illustrated using a small dataset of 51 soft tissue sarcoma (STS) patients where the task is to predict the risk of lung metastasis occurrence during the follow-up period. Results: Using PET/CT and two MRI sequences separately to build two radiomic models, we show that our approach produces quantitative maps that highlight the signal that contributes to the decision within the tumor region of interest. In our STS example, the analysis of these maps identified two biological patterns that are consistent with STS grading systems and knowledge: necrosis development and glucose metabolism of the tumor. Conclusions: We demonstrate how that method makes it possible to spatially and quantitatively interpret radiomic models amenable to sub-regions identification and biological interpretation for patient stratification.
Published: 2022

16. Intensive chemotherapy followed by autologous stem cell transplantation in primary central nervous system lymphomas (PCNSLs). Therapeutic outcomes in real life—experience of the French Network

Author: Schenone, Laurence, Houillier, Caroline, Tanguy, Marie Laure, Choquet, Sylvain, Agbetiafa, Kossi, Ghesquières, Hervé, Damaj, Gandhi, Schmitt, Anna, Bouabdallah, Krimo, Ahle, Guido, Gressin, Remy, Cornillon, Jérôme, Houot, Roch, Marolleau, Jean-Pierre, Fornecker, Luc-Matthieu, Chinot, Olivier, Peyrade, Frédéric, Bouabdallah, Reda, Moluçon-Chabrot, Cécile, Gyan, Emmanuel, Chauchet, Adrien, Casasnovas, Olivier, Oberic, Lucie, Delwail, Vincent, Abraham, Julie, Roland, Virginie, Waultier-Rascalou, Agathe, Willems, Lise, Morschhauser, Franck, Fabbro, Michel, Ursu, Renata, Thieblemont, Catherine, Jardin, Fabrice, Tempescul, Adrian, Malaise, Denis, Touitou, Valérie, Nichelli, Lucia, Le Garff-Tavernier, Magali, Plessier, Aurélie, Bourget, Philippe, Bonmati, Caroline, Wantz-Mézières, Sophie, Giordan, Quentin, Dorvaux, Véronique, Charron, Cyril, Jabeur, Waliyde, Hoang-Xuan, Khê, Taillandier, Luc, Soussain, Carole, Service d'Hématologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-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)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut Gustave Roussy (IGR), Service de biostatistique et d'épidémiologie (SBE), Direction de la recherche clinique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Département d'hématologie, Institut Curie, Site Saint-Cloud, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Institut Bergonié [Bordeaux], UNICANCER, CHU Bordeaux [Bordeaux], Service de Neurologie [Hôpitaux Civils de Colmar], Hôpitaux Civils Colmar, Centre Hospitalier Universitaire [Grenoble] (CHU), Institut de Cancérologie Lucien Neuwirth, Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), 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 ), Microenvironment and B-cells: Immunopathology,Cell Differentiation, and Cancer (MOBIDIC), Université de Rennes (UR)-Etablissement français du sang [Rennes] (EFS Bretagne)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Amiens-Picardie, HEMATIM - Hématopoïèse et immunologie - UR UPJV 4666 (HEMATIM), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Strasbourg, Institut de neurophysiopathologie (INP), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Hôpital de la Timone [CHU - APHM] (TIMONE), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Service d’Hématologie Biologique [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Hôpital Bretonneau, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), CIC - Poitiers, Université de Poitiers-Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Dupuytren [CHU Limoges], Centre Hospitalier Saint Jean de Perpignan, Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut du Cancer de Montpellier (ICM), Hopital Saint-Louis [AP-HP] (AP-HP), NF-kappaB, Différenciation et Cancer (OncokappaB (URP_7324)), Université Paris Cité (UPCité), Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Département d'Oncologie Chirurgicale [Institut Curie], Institut Curie [Paris], Laboratoire d'Imagerie Translationnelle en Oncologie (LITO ), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Beaujon [AP-HP], CHU Necker - Enfants Malades [AP-HP], Biology, genetics and statistics (BIGS), Inria Nancy - Grand Est, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Institut Élie Cartan de Lorraine (IECL), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Institut Élie Cartan de Lorraine (IECL), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Hôpital de Mercy, Centre hospitalier régional Metz-Thionville (CHR Metz-Thionville), Hôpital Ambroise Paré [AP-HP], Maladies neurodéveloppementales et neurovasculaires (NeuroDiderot (UMR_S_1141 / U1141)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Centre de Recherche en Automatique de Nancy (CRAN), Institut Curie - Saint Cloud (ICSC), Immunité et cancer (U932), and We thank the clinicians involved in the French National 'Lymphome Oculo-Cérébral' LOC network, part of the network for rare cancers of the central nervous system, 'RENOCLIP-LOC Network', approved by the French National Institute of Cancer (INCa).
Subjects: Transplantation, Hematology, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; We analysed the therapeutic outcomes of all consecutive patients with primary central nervous system lymphoma (PCNSL) registered in the prospective French database for PCNSL and treated with intensive chemotherapy (IC) followed by autologous stem cell transplantation (IC-ASCT) between 2011 and November 2019 (271 patients recruited, 266 analysed). In addition, treatment-related complications of thiotepa-based IC-ASCT were analysed from the source files of 85 patients from 3 centers. Patients had received IC-ASCT either in first-line treatment (n\,=\,147) or at relapse (n\,=\,119). The median age at IC-ASCT was 57 years (range: 22-74). IC consisted of thiotepa-BCNU (n\,=\,64), thiotepa-busulfan (n\,=\,24), BCNU-etoposide-cytarabine-melphalan (BEAM, n\,=\,36) and thiotepa-busulfan-cyclophosphamide (n\,=\,142). In multivariate analysis, BEAM and ASCT beyond the first relapse were adverse prognostic factors for relapse risk. The risk of treatment-related mortality was higher for ASCT performed beyond the first relapse and seemed higher for thiotepa-busulfan-cyclophosphamide. Thiotepa-BCNU tends to result in a higher relapse rate than thiotepa-busulfan-cyclophosphamide and thiotepa-busulfan. This study confirms the role of IC-ASCT in first-line treatment and at first-relapse PCNSL (5-year overall survival rates of 80 and 50%, respectively). The benefit/risk ratio of thiotepa-busulfan/thiotepa-busulfan-cyclophosphamide-ASCT could be improved by considering ASCT earlier in the course of the disease and dose adjustment of the IC.
Published: 2022

17. Correlation between efficacy endpoints in patients with advanced biliary tract cancer treated by systemic second-line therapies: Analysis of aggregated data from a systematic literature review

Author: Cindy Neuzillet, David Malka, Astrid Lièvre, Inderpreet Singh Khurana, Dewi Vernerey, Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Université Paris-Saclay, Institut Curie - Saint Cloud (ICSC), Institut Mutualiste de Montsouris (IMM), Oncogenesis, Stress, Signaling (OSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Pôle cancérologie (CHRU Besançon), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), and Sponsor of the systematic literature review: Incyte Biosciences UK. Sponsor of the correlation analyses (honorarium for conceptualization of the project and realization of statistical analyzes): Incyte Biosciences France. No payment has been done for authoring.
Subjects: Hepatology, Gastroenterology, [SDV.CAN]Life Sciences [q-bio]/Cancer, Endpoint, Progression-Free Survival, Correlation, Cholangiocarcinoma, Targeted therapy, Treatment Outcome, Biliary Tract Neoplasms, Antineoplastic Combined Chemotherapy Protocols, Humans, Chemotherapy, Immunotherapy
Abstract: International audience; BACKGROUND: Overall response rate (ORR) and progression-free survival (PFS) are commonly used as endpoints for phase II trials. However, the ultimate goal is to bring survival benefit for the patients. We aimed to assess the correlation between ORR, median PFS and overall survival (OS) using aggregated data from a systematic review of second-line systemic therapies in advanced biliary tract cancer (BTC) patients. METHODS: Clinical trials were identified using Medline database. Studies only enrolling patients with gallbladder cancer were not included. Searches were last updated on April 2020. Eligible studies reported OS, PFS and/or ORR data for BTC patients receiving second-line systemic chemotherapy. Pearson weighted correlation was estimated between OS and ORR and between median OS and PFS. RESULTS: Seventeen studies (N = 912 patients) were selected. There was a strong correlation between median OS/ORR in the overall analysis (r = 0.85; P
Published: 2022

18. Apport de l'immunothérapie dans le traitement des cancers des voies biliaires avancés

Author: Matthieu Delaye, Astrid Lièvre, Cindy Neuzillet, Institut Curie - Saint Cloud (ICSC), Oncogenesis, Stress, Signaling (OSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), and CHU Pontchaillou [Rennes]
Subjects: Biomarqueurs, Cancers des voies, Cancer Research, MESH: Humans, MESH: Immunotherapy, Immunothérapie, [SDV]Life Sciences [q-bio], [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Hematology, General Medicine, MESH: Bile Duct Neoplasms, Oncology, Biliary tract cancer, Radiology, Nuclear Medicine and imaging, MESH: Biliary Tract Neoplasms, Immunotherapy, biliaires, Biomarkers
Abstract: International audience; Contribution of immunotherapy in the treatment of advanced biliary tract cancer Biliary tract cancers (BTC) are rare tumors with a poor prognosis. Their treatment, at an advanced stage, relies on combinations of chemotherapies, which have a limited range and duration of benefit. Immunotherapy has emerged in recent years as a new therapeutic approach for BTC. However, the benefit with currently available treatments seems more modest than in other tumor locations and the predictive markers of response to these treatments remain to be identified. This review article summarizes the rationale, current data, and prospects and challenges for the development of immunotherapy in BTC.
Published: 2022

19. Isolated intraocular relapses of primary cerebral lymphomas: An loc network study

Author: Nadia Younan, Carole Soussain, Sylvain Choquet, Nathalie Cassoux, Valérie Touitou, Anna Schmitt, Olivier Chinot, Lucie Oberic, Gandhi Damaj, Roch Houot, Hervé Ghesquières, Kamel Laribi, Guido Ahle, Luc Taillandier, Jérôme Paillassa, Emmanuel Gyan, Fabrice Jardin, Vincent Delwail, Jean‐Pierre Marolleau, Adrian Tempescul, Philippe Agapé, Marie Bourniquel, Fabienne Vacheret, Ibrahim Jdid, Magali Le Garff‐Tavernier, Denis Malaise, Agusti Alentorn, Khê Hoang Xuan, Caroline Houillier, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Curie - Saint Cloud (ICSC), Immunité et cancer (U932), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de recherche de l'Institut Curie [Paris], Institut Curie [Paris], Institut Bergonié [Bordeaux], UNICANCER, Institut de neurophysiopathologie (INP), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Hôpital de la Timone [CHU - APHM] (TIMONE), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Microenvironment and B-cells: Immunopathology,Cell Differentiation, and Cancer (MOBIDIC), Université de Rennes (UR)-Etablissement français du sang [Rennes] (EFS Bretagne)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Centre Hospitalier Le Mans (CH Le Mans), Service de Neurologie [Hôpitaux Civils de Colmar], Hôpitaux Civils Colmar, Centre de Recherche en Automatique de Nancy (CRAN), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Hôpital Bretonneau, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), CIC - Poitiers, Université de Poitiers-Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Amiens-Picardie, HEMATIM - Hématopoïèse et immunologie - UR UPJV 4666 (HEMATIM), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), Hopital d'instruction des armées Sainte-Anne [Toulon] (HIA), Service d'Hématologie [CH Perpignan], CH Perpignan, CHU Orléans, Département d'Oncologie Chirurgicale [Institut Curie], Laboratoire d'Imagerie Translationnelle en Oncologie (LITO ), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-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)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), DESSAIVRE, Louise, Service d'Onco-neurologie = Département de neurologie 2 [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), Service d'Ophtalmologie [CHU Pitié-Salpêtrière], Service de Biochimie Métabolique [CHU Pitié-Salpêtrière], and 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)
Subjects: relapse, Cancer Research, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, primary CNS lymphoma, Oncology, [SDV.CAN] Life Sciences [q-bio]/Cancer, ocular lymphoma, hemic and lymphatic diseases, [SDV.CAN]Life Sciences [q-bio]/Cancer, Hematology, General Medicine, prognosis, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Most relapses of primary central nervous system lymphoma (PCNSL) occur in the brain and are associated with a poor prognosis. Isolated intraocular relapses (IIORs) are rare and poorly described. We retrospectively selected from the French Lymphome Oculo-Cérébral database PCNSL patients who initially presented with cerebral localization and who experienced IIOR during the course of the disease. Of the 1472 patients included in the database, 55 patients presented an IIOR. Their median age was 68 years, and median Karnofsky Performance Status 80. IL-10 levels in the aqueous humor and/or in the vitreous were increased in 42/46 patients. 45/55 patients received systemic chemotherapy, and 11/55 received high-dose chemotherapy with autologous stem cell transplantation (HCT-ASCT) as consolidation treatment. After a median follow-up of 69 months, 42/55 patients had relapsed, including 90% of the patients who did not receive HCT-ASCT at IIOR and 40% of the patients who received HCT-ASCT at IIOR (p 0.001). The first relapse after the initial IIOR was exclusively in the eye in 23/42 patients, and 29/42 patients had a subsequent brain relapse during the course of the disease. The median progression-free survival, brain-free survival and overall survival from IIOR were 12.2, 48.6 and 57.1 months, respectively. Isolated intraocular relapse is not exceptional in the course of PCNSL and deserves systematic ophthalmological follow-up. Its prognosis is much better than the prognosis of brain relapse, with an evolution close to that of primary vitreoretinal lymphoma. With the exception of patients who received HCT-ASCT at IIOR, almost all patients subsequently relapsed, often with other IIORs.
Published: 2022

20. Treatment, outcome, and prognostic factors in non-metastatic anal cancer: The French nationwide cohort study FFCD-ANABASE

Author: Vendrely, Véronique, Lemanski, Claire, Pommier, Pascal, Le Malicot, Karine, Saint, Angélique, Rivin del Campo, Eleonor, Regnault, Pauline, Baba-Hamed, Nabil, Ronchin, Philippe, Crehange, Gilles, Tougeron, David, Menager-Tabourel, Elodie, Diaz, Olivia, Hummelsberger, Michael, Minsat, Mathieu, Drouet, Franck, Larrouy, Anne, Peiffert, Didier, Lievre, Astrid, Zasadny, Xavier, Hautefeuille, Vincent, Mornex, Françoise, Lepage, Côme, Quero, Laurent, BoRdeaux Institute in onCology (Inserm U1312 - BRIC), Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Bordeaux [Bordeaux], Institut du Cancer de Montpellier (ICM), Centre Léon Bérard [Lyon], Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Agro Dijon, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU), Clinique Tivoli Ducos [Bordeaux], Centre hospitalier Saint-Joseph [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Azuréen de Cancérologie [Mougins, France], Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon (CHD Vendée), Institut Daniel Hollard [Grenoble], Centre de radiothérapie et d'oncologie médicale privée (Béziers), Institut Curie - Saint Cloud (ICSC), Clinique Mutualiste de l'Estuaire (Saint Nazaire), Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), Oncogenesis, Stress, Signaling (OSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Polyclinique de Limoges - site François Chénieux [Limoges], CHU Amiens-Picardie, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Ecotaxie, microenvironnement et développement lymphocytaire (EMily (UMR_S_1160 / U1160)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Hopital Saint-Louis [AP-HP] (AP-HP), and Fédération Francophone de Cancérologie Digestive.
Subjects: Oncology, [SDV.CAN]Life Sciences [q-bio]/Cancer, Radiology, Nuclear Medicine and imaging, Chemoradiotherapy, Hematology, Anal cancer, IMRT, Observational cohort
Abstract: International audience; Introduction: International guidelines regarding the treatment of squamous cell carcinoma of the anus (SCCA) recommend intensity-modulated radiotherapy (IMRT) combined with mitomycin-based chemotherapy (CT). The French FFCD-ANABASE cohort aimed at evaluating clinical practices, treatment, and outcomes of SCCA patients.Methods: This prospective multicentric observational cohort included all non-metastatic SCCA patients treated in 60 French centers from January 2015 to April 2020. Patients and treatment characteristics, colostomy-free survival (CFS), disease-free survival (DFS), overall survival (OS), and prognostic factors were analyzed.Results: Among 1015 patients (male: 24.4 %; female: 75.6 %; median age: 65 years), 43.3 %presented with early-stage(T1-2, N0) and 56.7 % with locally advanced stage (T3-4 or N + ) tumors. IMRT was used for 815 patients (80.3 %) and a concurrent CT was administered in 781 patients, consisting of mitomycin-based CT for 80 %. The median follow-up was 35.5 months. DFS, CFS, and OS at 3 years were 84.3 %, 85.6 %, and 91.7 % respectively in the early-stage group compared to 64.4 %, 66.9 %, and 78.2 % in the locally-advanced group (p < 0.001). In multivariate analyses, male gender, locally-advanced stage, and ECOG PS ≥ 1 were associated with poorer DFS, CFS, and OS. IMRT was significantly associated with a better CFS in the whole cohort and almost reached significance in the locally-advanced group.Conclusion: Treatment of SCCA patients showed good respect for current guidelines. Significant differences in outcomes advocate for personalized strategies by either de-escalation for early-stage tumors or treatment intensification for locally-advanced tumors.
Published: 2023

21. Identification of potential prognostic biomarkers for node-negative breast tumours by proteomic analysis: a multicentric 2004 national PHRC study

Author: Agnès Chassevent, Marjorie Adams, Mario Campone, Gabriel Ricolleau, Loïc Campion, Isabelle Zanella-Cleon, Florence Lerebours, Catherine Guette, Françoise Descotes, Frédérique Spyratos, Marie-Lise Jourdan, Catherine Guérin-Charbonnel, Jean André, Catherine Grenot, Pascal Jézéquel, Pierre-Marie Martin, Antoine Carlioz, Didier Lanoë, Hospices Civils de Lyon (HCL), CRLCC René Gauducheau, Institut Curie - Saint Cloud (ICSC), Hôpital Nord [CHU - APHM], CRLCC Paul Papin, Clinique d'Oncologie et de Radiothérapie [Tours] (CORAD), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Hôpital Bretonneau, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), SFR Biosciences, École normale supérieure de Lyon (ENS de 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), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Univ Angers, Okina, Institut Curie [Saint-Cloud], and Hôpital Bretonneau-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)
Subjects: Oncology, Proteomics, Cancer Research, [SDV]Life Sciences [q-bio], Gene Expression, 0302 clinical medicine, Ductal, Electrophoresis, Gel, Two-Dimensional, Breast, Tumor Markers, 0303 health sciences, education.field_of_study, Gel, Carcinoma, Ductal, Breast, Middle Aged, Prognosis, 3. Good health, Blot, [SDV] Life Sciences [q-bio], 030220 oncology & carcinogenesis, Lymphatic Metastasis, Two-Dimensional, Female, Adult, Electrophoresis, medicine.medical_specialty, In silico, Population, Molecular Sequence Data, Breast Neoplasms, Biology, Peptide Mapping, 03 medical and health sciences, Breast cancer, Internal medicine, Biomarkers, Tumor, medicine, Humans, Amino Acid Sequence, education, 030304 developmental biology, Aged, Retrospective Studies, Oncogene, Carcinoma, Cancer, medicine.disease, Biological, Molecular medicine, Peptide Fragments
Abstract: We used a 2D-electrophoresis (2-DE) proteomic approach to identify novel biomarkers in node-negative breast cancers. This retrospective study focused on a population of patients with ductal pN0M0 tumours. A subset of patients who developed metastases and in whose tumours were found high levels of uPA and PAI-1 (metastatic relapse, MR: n=20) were compared to another subset in whom no metastatic relapse occurred and whose tumours were found to have low levels of uPA and PAI-1 (no relapse, NR: n=21). We used a 2-DE coupled with MS approach to screen cytosol fractions using two pH-gradient scales, a broad scale (3.0-11.0) and a narrower scale focussing in on a protein rich region (5.0-8.0). This study was conducted on 41 cytosol specimens analyzed in duplicate on two platforms. The differential analysis of more than 2,000 spots in 2-DE gels, obtained on the two platforms, allowed the identification of 13 proteins which were confirmed by western blotting. Two proteins, GPDA and FABP4 were down-regulated in the MR subset whereas all the others were up-regulated. An in silico analysis revealed that GMPS (GUAA), GAPDH (G3P), CFL1 (COF1) and FTL (FRIL), the most informative genes, displayed a proliferation profile (high expression in basal-like, HER2+ and luminal B molecular subtypes). Inversely, similar to FABP4, GPD1 [GPDA] displayed a high expression in luminal A subtype, a profile characteristic of tumour suppressor genes. Despite the small size of our cohort, the 2-DE analysis gave interesting results which were confirmed by the in silico analysis showing that some of the corresponding genes had a strong prognostic impact in breast cancer, mostly because of their link with proliferation: GMPS, GAPDH, FTL and GPD1. A validation phase on a larger cohort is now needed before these biomarkers could be considered for use in clinical practice.
Published: 2012

22. [18F]-FDG PET and MRI radiomic signatures to predict the risk and the location of tumor recurrence after re-irradiation in head and neck cancer

Author: Arnaud Beddok, Fanny Orlhac, Valentin Calugaru, Laurence Champion, Catherine Ala Eddine, Christophe Nioche, Gilles Créhange, Irène Buvat, Laboratoire d'Imagerie Translationnelle en Oncologie (LITO ), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Curie [Orsay], Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris sciences et lettres (PSL), Institut Curie [Paris], Université Paris sciences et lettres (PSL), Institut Curie - Saint Cloud (ICSC), and Buvat, Irène
Subjects: re-irradiation, [SDV.IB.IMA] Life Sciences [q-bio]/Bioengineering/Imaging, radiomics, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, Radiology, Nuclear Medicine and imaging, head and neck cancer, multimodal imaging, General Medicine
Abstract: International audience; Purpose: To evaluate whether radiomics from [18F]-FDG PET and/or MRI before re-irradiation (reRT) of recurrent head and neck cancer (HNC) could predict the occurrence and the location "in-field" or "outside" of a second locoregional recurrence (LR). Methods: Among the 55 patients re-irradiated at curative intend for HNC from 2012 to 2019, 48 had an MRI and/or PET before the start of the reRT. Thirty-nine radiomic features (RF) were extracted from the reirradiated GTV (rGTV) using LIFEx software. Student t-tests and Spearman Correlation Coefficient were used to select the RF that best separate patients who recurred from those who did not, and "in-field" from "outside" recurrences. Principal component analysis involving these features only was used to create a prediction model. Leave-oneout cross-validation was performed to evaluate the models. Results: After a median follow-up of 17 months, 40/55 patients had developed a second LR, including 18 "in-field" and 22 "outside" recurrences. From pre-reRT MRI, a model based on three RF (GLSZM_SZHGLE, GLSZM_LGLZE and skewness) predicted whether patients would recur with a balanced accuracy (BA) of 83.5%. Another model from pre-reRT MRI based on three other RF (GLSZM_ LZHGE, NGLDM_Busyness and GLZLM_SZE) predicted whether patients would recur "in-field" or "outside" with a BA of 78.5%. From pre-reRT PET, a model based on four RF (Kurtosis, SUVbwmin, GLCM_Correlation and GLCM_Contrast) predicted the LR location with a BA of 84.5%. Conclusion: RF characterizing tumor heterogeneity extracted from pre-reRT PET and MRI predicted whether patients would recur, and whether they would recur "in-field" or "outside".
Published: 2022

23. Deep Learning identifies new morphological patterns of Homologous Recombination Deficiency in luminal breast cancers from whole slide images

Author: Marc-Henri Stern, Etienne Decencière, Thomas Walter, François-Clément Bidard, Tristan Lazard, Guillaume Bataillon, Dominique Stoppa-Lyonnet, Tatiana Popova, Peter Naylor, Anne Vincent Salomon, Centre de Bioinformatique (CBIO), Mines Paris - PSL (École nationale supérieure des mines de Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), Cancer et génome: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de génétique et biologie des cancers (U830), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Curie - Saint Cloud (ICSC), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Centre de Morphologie Mathématique (CMM), Université Paris sciences et lettres (PSL), Génétique et Biologie du Développement, Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), ANR-17-CONV-0005,Q-LIFE,Institut Q-LIFE(2017), ANR-19-P3IA-0001,PRAIRIE,PaRis Artificial Intelligence Research InstitutE(2019), Walter, Thomas, Institut Q-LIFE - - Q-LIFE2017 - ANR-17-CONV-0005 - CONV - VALID, and PaRis Artificial Intelligence Research InstitutE - - PRAIRIE2019 - ANR-19-P3IA-0001 - P3IA - VALID
Subjects: Genome instability, homologous recombination deficiency (HRD), bias, whole slide images, Computational biology, Biology, breast cancer, [INFO.INFO-CV] Computer Science [cs]/Computer Vision and Pattern Recognition [cs.CV], visualization, [INFO.INFO-BI] Computer Science [cs]/Bioinformatics [q-bio.QM], Interpretability, [SDV.BIBS] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], business.industry, Deep learning, deep learning, [INFO.INFO-CV]Computer Science [cs]/Computer Vision and Pattern Recognition [cs.CV], prediction, artificial intelligence, molecular subtype, Phenotype, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], [INFO.INFO-TI] Computer Science [cs]/Image Processing [eess.IV], [INFO.INFO-TI]Computer Science [cs]/Image Processing [eess.IV], PARP inhibitor, Artificial intelligence, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], interpretability, Homologous recombination, business, Homologous Recombination Deficiency, computational pathology
Abstract: Homologous Recombination DNA-repair deficiency (HRD) is a well-recognized marker of platinum-salt and PARP inhibitor chemotherapies in ovarian and breast cancers (BC). Causing high genomic instability, HRD is currently determined by BRCA1/2 sequencing or by genomic signatures, but its morphological manifestation is not well understood. Deep Learning (DL) is a powerful machine learning technique that has been recently shown to be capable of predicting genomic signatures from stained tissue slides. However, DL is known to be sensitive to dataset biases and lacks interpretability. Here, we present and evaluate a strategy to control for biases in retrospective cohorts. We train a deep-learning model to predict the HRD in a controlled cohort with unprecedented accuracy (AUC: 0.86) and we develop a new visualization technique that allows for automatic extraction of new morphological features related to HRD. We analyze in detail the extracted morphological patterns that open new hypotheses on the phenotypic impact of HRD.
Published: 2022

24. Prolonged in‐hospital stay and higher mortality after Covid‐19 among patients with <scp>non‐Hodgkin</scp> lymphoma treated with B‐cell depleting immunotherapy

Author: Roberta Di Blasi, Laure Philippe, Thomas Hueso, Catherine Thieblemont, Karine Lacombe, Bénédicte Deau Fischer, Serge Bologna, Caroline Besson, Guillemette Fouquet, Sylvain Choquet, Milena Kohn, Rémy Duléry, Carole Soussain, Bernard Drenou, Pierre Feugier, Etienne Daguindau, Marc Delord, Nicolas Noel, Adrien Chauchet, Sylvain Lamure, Sandra Malak, Cédric Rossi, Bertrand Joly, Guillaume Cartron, Yassine Taoufik, Service d'hématologie clinique et de thérapie cellulaire [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Institut de Génétique Moléculaire de Montpellier (IGMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Département d’Hématologie Clinique [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Hospitalier de Versailles André Mignot (CHV), Service d'hématologie-oncologie adultes, 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)-Université de Paris (UP), Service d'hématologie, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Institut Gustave Roussy (IGR), Service d'Hématologie Clinique (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Groupe hospitalier de la région de Mulhouse Sud-Alsace (GHRMSA), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Curie [Saint-Cloud], Service d'Hématologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Service d'Hématologie clinique [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre d'Oncologie de Gentilly, Centre Hospitalier Sud Francilien, CH Evry-Corbeil, Service d'Hématologie [CH Annecy], CH Annecy, Hôpital Bicêtre, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Sorbonne Université (SU)-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)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Roche, Takeda Pharmaceutical Company, TPC, We thank all the clinicians and patients in the participating centers for their contributions to this multicenter study. We are grateful to the Centre Hospitalier de Versailles, in particular Philippe Rousselot and Laure Morisset for promoting the research and for supporting the editing. We thank France Lymphome Espoir for reviewing the study material, LYSA for discussions on the design of this study, and Sophie Rigaudeau and C?cile Laur?ana for their contribution to the collection of the cases., Rémy Duléry reports personal fees from Takeda, Novartis, and Biotest and non‐financial support from Gilead outside the submitted work. Roberta Di Blasi reports personal fees from Gilead and Novartis outside the submitted work. Serge Bologna reports personal fees from Janssen and Roche outside the submitted work. Guillaume Cartron reports personal fees from Roche, Celgene, Sanofi, Gilead, Janssen, and Abbvie outside the submitted work. Karine Lacombe reports personal fees and non‐financial support from Gilead, MSD, Abbvie, ViiV Healthcare, and Janssen outside the submitted work. Caroline Besson reports research funding from Roche and non‐financial support from Takeda and Roche outside the submitted work., HAL UVSQ, Équipe, Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), Groupe hospitalier de la région de Mulhouse et Sud-Alsace, Département d'Oncologie Médicale [Centre René-Huguenin, Saint-Cloud], Hôpital René HUGUENIN (Saint-Cloud), Centre Hospitalier Annecy-Genevois [Saint-Julien-en-Genevois], and Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)
Subjects: [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, Male, [SDV]Life Sciences [q-bio], MESH: COVID-19 / complications, Comorbidity, MESH: Lymphoma, Non-Hodgkin / complications, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Risk Factors, hemic and lymphatic diseases, Antineoplastic Combined Chemotherapy Protocols, MESH: Age Factors, Young adult, Research Articles, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Aged, 80 and over, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, B-Lymphocytes, education.field_of_study, Lymphoma, Non-Hodgkin, MESH: SARS-CoV-2, Hazard ratio, Age Factors, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, Middle Aged, Combined Modality Therapy, MESH: Antigens, CD20 / immunology, 3. Good health, 030220 oncology & carcinogenesis, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Female, Rituximab, B-cell depleting immunotherapy, Immunotherapy, [SDV.IMM.IMM] Life Sciences [q-bio]/Immunology/Immunotherapy, Research Article, medicine.drug, Adult, medicine.medical_specialty, Population, lymphoma, [SDV.CAN]Life Sciences [q-bio]/Cancer, anti-CD20 therapy, Young Adult, MESH: Rituximab / administration & dosage, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, MESH: COVID-19 / mortality, Internal medicine, medicine, Humans, education, MESH: B-Lymphocytes / drug effects, Survival analysis, Aged, Proportional Hazards Models, Retrospective Studies, MESH: Aged, 80 and over, SARS-CoV-2, Proportional hazards model, business.industry, COVID-19, Retrospective cohort study, [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy, MESH: Combined Modality Therapy, Length of Stay, vaccination, Antigens, CD20, medicine.disease, Survival Analysis, Lymphoma, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Drug Resistance, Neoplasm, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, 030215 immunology
Abstract: International audience; Prolonged Covid-19 is an emerging issue for patients with lymphoma or immune deficiency. We aimed to examine prolonged length of in-hospital stay (LOS) due to Covid-19 among patients with lymphoma and assess its determinants and outcomes. Adult patients with lymphoma admitted for Covid-19 to 16 French hospitals in March and April, 2020 were included. Length of in-hospital stay was analyzed as a competitor vs death. The study included 111 patients. The median age was 65 years (range, 19–92). Ninety-four patients (85%) had B-cell non-Hodgkin lymphoma. Within the 12 months prior to hospitalization for Covid-19, 79 patients (71%) were treated for their lymphoma. Among them, 63 (57%) received an anti-CD20 therapy. Fourteen patients (12%) had relapsed/refractory disease. The median LOS was 14 days (range, 1–235). After a median follow-up of 191 days (3–260), the 6-month overall survival was 69%. In multivariable analyses, recent administration of anti-CD20 therapy was associated with prolonged LOS (subdistribution hazard ratio 2.26, 95% confidence interval 1.42–3.6, p < 0.001) and higher risk of death (hazard ratio 2.17, 95% confidence interval 1.04–4.52, p = 0.039). An age ≥ 70 years and relapsed/refractory lymphoma were also associated with prolonged LOS and decreased overall survival. In conclusion, an age ≥ 70 years, a relapsed/refractory lymphoma and recent administration of anti-CD20 therapy are risk factors for prolonged LOS and death for lymphoma patients hospitalized for Covid-19. These findings may contribute to guide the management of lymphoma during the pandemic, support evaluating specific therapeutic approaches, and raise questions on the efficacy and timing of vaccination of this particular population.
Published: 2021

25. Cost-Effectiveness Analysis of Trastuzumab (Herceptin) in HER2-Overexpressed Metastatic Breast Cancer

Author: Patrice Viens, Anne-Gaëlle Le Corroller-Soriano, Michel Marty, Henri Roché, Veronique Girre, Jocelyne Jacquemier, Jean-Paul Moatti, Etienne Brain, Anthony Gonçalves, Carole Perez-Ellis, Dupuis, Christine, Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U912 INSERM - Aix Marseille Univ - IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département d’Oncologie Médicale [IPC, Marseille], Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Université de la Méditerranée - Aix-Marseille 2, Département de Biopathologie [Marseille], Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR), Département d'Oncologie Médicale [Institut Curie, Paris], Institut Curie [Paris], Département d'oncologie médicale, Institut Claudius Regaud, Institut Curie - Saint Cloud (ICSC), Département d'Oncologie Médicale [Centre René-Huguenin, Saint-Cloud], Hôpital René HUGUENIN (Saint-Cloud), Supported by a grant from the French Ministry of Health STIC 2002 and a fellowship grant from the 'French League against Cancer.', Institut de Recherche pour le Développement (IRD)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), and Institut Curie [Saint-Cloud]
Subjects: Oncology, Cancer Research, Receptor, ErbB-2, Cost-Benefit Analysis, 0302 clinical medicine, Trastuzumab, Medicine, 030212 general & internal medicine, Neoplasm Metastasis, skin and connective tissue diseases, health care economics and organizations, education.field_of_study, biology, Cost-effectiveness analysis, Middle Aged, Metastatic breast cancer, 3. Good health, 030220 oncology & carcinogenesis, Female, France, medicine.drug, Adult, medicine.medical_specialty, Population, Antineoplastic Agents, Breast Neoplasms, [SDV.CAN]Life Sciences [q-bio]/Cancer, Antibodies, Monoclonal, Humanized, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, Humans, education, neoplasms, Survival analysis, Aged, Retrospective Studies, Gynecology, business.industry, Euros, Retrospective cohort study, Genes, erbB-2, biology.organism_classification, medicine.disease, Survival Analysis, Confidence interval, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business
Abstract: Objective: In women with Human Epidermal growth Receptor 2 (HER2)-positive metastatic breast cancer (MBC), Trastuzumab has become the standard of care but previous studies have raised doubts about its economic acceptability. We carried out the first cost-effectiveness study for Trastuzumab in MBC patients, in France, that is based on observed resource use and outcomes in clinical practice. Methods: We retrospectively analyzed 47 HER2-positive MBC patients in a before-and-after design study. Nineteen patients did not receive Trastuzumab ("before" Trastuzumab introduction in clinical practice) and 28 patients received Trastuzumab (the "after" population). Direct medical costs were estimated on the basis of the physical quantities reported in the patient medical records, for the period from first metastatic progression until death or date of patient last news. Monetary values (2002 French francs) were attributed to these quantities on the basis of unit costs and incremental cost-effectiveness ratios were calculated. Results: In the Trastuzumab group, median overall survival was significantly higher (37 months vs. 19 months in the non-Ttrastuzumab group, P = 0.001) but total treatment costs were 3 times higher (39,608 Euros vs. 12,795 Euros). The cost per additional life-year saved by Trastuzumab treatment was estimated to be 27,492 Euros (95% confidence interval: *20,964 Euros-34,020 Euros/year of life [bootstrapped estimation]). Conclusions: Our data suggest that despite its high unit price, Trastuzumab should be considered cost-effective in MBC patients to the extent that its incremental cost per life-year saved remains lower than gross domestic product per capita in countries like France.
Published: 2009

26. Characterization of Depressive Symptoms Trajectories After Breast Cancer Diagnosis in Women in France

Author: Cécile Charles, Aurélie Bardet, Alicia Larive, Philip Gorwood, Nicolas Ramoz, Emilie Thomas, Alain Viari, Marina Rousseau-Tsangaris, Agnès Dumas, Gwenn Menvielle, Sibille Everhard, Anne-Laure Martin, Seyive-yvon-arnauld Gbenou, Julie Havas, Mayssam El-Mouhebb, Antonio Di Meglio, Fabrice André, Barbara Pistilli, Charles Coutant, Paul Cottu, Asma Mérimèche, Florence Lerebours, Olivier Tredan, Laurence Vanlemmens, Christelle Jouannaud, Christelle Levy, Ines Vaz-Luis, Stefan Michiels, Sarah Dauchy, Institut Bergonié [Bordeaux], UNICANCER, Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Gustave Roussy (IGR), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Service de biostatistique et d'épidémiologie (SBE), Direction de la recherche clinique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Centre Hospitalier Sainte Anne [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Synergie Lyon Cancer-Platform of Bioinformatics-Gilles Thomas, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre Léon Bérard [Lyon]-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), Epidémiologie Clinique et Evaluation Economique Appliquées aux Populations Vulnérables (ECEVE (U1123 / UMR_S_1123)), Institut National de la Santé et de la Recherche Médicale (INSERM)-AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), Prédicteurs moléculaires et nouvelles cibles en oncologie (PMNCO), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), Institut Curie [Paris], Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), Institut Curie - Saint Cloud (ICSC), Centre Léon Bérard [Lyon], Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER, Institut Jean Godinot [Reims], Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), and Martinez Rico, Clara
Subjects: Male, Depression, [SDV.MHEP.PSM] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Breast Neoplasms, [SDV.CAN]Life Sciences [q-bio]/Cancer, General Medicine, Middle Aged, Cohort Studies, [SDV.CAN] Life Sciences [q-bio]/Cancer, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Prevalence, Quality of Life, Humans, Female, Child
Abstract: International audience; Importance: Breast cancer (BC) diagnosis and treatment expose patients to a 5-fold higher risk of depression compared with the general population, with an estimated prevalence of 10% to 25%. A depressive episode in patients with BC has implications for the tolerance of and adherence to treatment, impairing quality of life and reducing life expectancy.Objective: To identify and characterize distinct longitudinal patterns of depressive symptoms in patients with BC from diagnosis to 3 years after treatment.Design, settings, and participants: The CANTO-DEePRESS (Deeper in the Understanding and Prevention of Depression in Breast Cancer Patients) cohort study included women in the French multicenter CANTO (CANcer TOxicities) cohort study (conducted between March 20, 2012 and December 11, 2018), who were 18 years or older with invasive stage I to III BC and no previous BC treatment. The study aimed to characterize toxicities over a 5-year period following stage I to III primary BC treatment. Assessments of depressive symptoms were performed on a subset of patients with available data at diagnosis and at least 2 other time points. All data were extracted from the CANTO database on October 1, 2020.Main outcomes and measures: The primary outcome was the level of depressive symptoms at each assessment time point measured with the Hospital Anxiety and Depression Scale and depression subscale at BC diagnosis and at 3 to 6, 12, and 36 months after the end of treatment. The group-based trajectory modeling was used to identify trajectory groups, and multinomial logistic regression models were used to characterize the following factors associated with trajectory group affiliation: demographic, socioeconomic, clinical, lifestyle, and quality-of-life data.Results: A total of 4803 women (mean [SD] age, 56.2 [11.2] years; 2441 patients [50.8%] with stage I BC) were included in the study. Six trajectory groups that described the heterogeneity in the expression of depressive symptoms were identified: noncases with no expression of symptoms (n = 2634 [54.8%]), intermediate worsening (1076 [22.4%]), intermediate improvement (480 [10.0%]), remission (261 [5.4%]), delayed occurrence (200 [4.2%]), and stable depression (152 [3.2%]). HADS-D scores at diagnosis were consistently associated with the 5 depressive trajectory group affiliations, with an estimated higher probability per point increase of experiencing subthreshold or clinically significant depressive symptoms between diagnosis and the 3 years after the end of BC treatment. The higher probabilities ranged from 1.49 (95% CI, 1.43-1.54) for the intermediate worsening group to 10.53 (95% CI, 8.84-12.55) for the stable depression group. Trajectory groups with depressive symptoms differed from the noncases group without symptoms by demographic and clinical factors, such as having dependent children, lower household income, cancer stage, family history of BC, previous psychiatric hospitalizations, obesity, smoking status, higher levels of fatigue, and depression at diagnosis.Conclusions and relevance: In this cohort study, nearly a third of patients with BC experienced temporary or lasting significant depressive symptoms during and after treatment. Improving early identification of women at risk of developing long-term or delayed depression is therefore critical to increase quality of life and overall survival. Subjected to validation, this study is an important first step toward personalized care of patients with BC at risk of depression.
Published: 2022

27. Activité physique après diagnostic de cancer du sein et survie : revue de la littérature

Author: Claire Bonneau, Roman Rouzier, Eleonora Salakos, Louise Maumy, Grégoire Rocher, Cindy Neuzillet, Thuraya Al Mamari, Antoine Elies, Institut Curie - Saint Cloud (ICSC), Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Cancer et génome: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, Mines Paris - PSL (École nationale supérieure des mines de Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), and CCSD, Accord Elsevier
Subjects: 0301 basic medicine, Cancer Research, Physical activity, Secondary prevention, [SDV.CAN]Life Sciences [q-bio]/Cancer, Hematology, General Medicine, 3. Good health, Activité physique, 03 medical and health sciences, Breast cancer, 030104 developmental biology, 0302 clinical medicine, Survie globale, Revue de la littérature, [SDV.CAN] Life Sciences [q-bio]/Cancer, Oncology, Recurrence, Prévention secondaire, 030220 oncology & carcinogenesis, Systematic review, Overall survival, Récidive, Radiology, Nuclear Medicine and imaging, Cancer du sein
Abstract: Introduction: The benefits of physical activity (PA) in breast cancer are currently recognized in primary prevention. The World Cancer Research Fund (WCRF) and then the National Cancer Institute (INCa) have reported conflicting results regarding the impact of post-diagnosis PA on breast cancer outcomes. The aim of this systematic review is to assess the association between PA after breast cancer diagnosis and overall mortality, specific mortality and risk of breast cancer recurrence in the literature. Methods: Randomized trials, prospective cohorts and meta-analyses studying post-diagnosis PA and overall mortality, breast cancer mortality or risk of recurrence after breast cancer published between January 1, 2014 and October 1, 2019 were included. The articles selected by the INCa report prior to 2014 were included in the literature review. Results: Eighteen articles have been selected. Studies unanimously concluded that overall mortality was reduced by post-diagnosis PA practice. For specific mortality, 5 meta-analyses showed a significant decrease in breast cancer mortality and 2 found a decrease in the risk of recurrence. Conclusion: Post-diagnosis PA reduces overall mortality and appears to impact specific breast cancer mortality and risk of recurrence. However, these results need to be confirmed by larger randomized trials., Introduction :Les bénéfices de l’activité physique (AP) dans le cancer du sein sont actuellement reconnus en prévention primaire. Le World Cancer Research Fund (WCRF), puis l’Institut national du cancer (INCa) ont rapporté des résultats contradictoires concernant l’impact de l’activité physique après diagnostic sur le pronostic du cancer du sein. L’objectif de cette revue de la littérature est d’évaluer l’association entre l’activité physique après le diagnostic de cancer du sein et la mortalité globale, la mortalité spécifique ainsi que le risque de récidive de cancer du sein dans la littérature.Méthodes :Les essais randomisés, cohortes prospectives et méta-analyses, étudiant l’activité physique postdiagnostic et la mortalité globale, la mortalité liée au cancer du sein ou le risque de récidive après cancer du sein, publiés entre le 1er janvier 2014 et le 1er octobre 2019, ont été inclus. Les articles sélectionnés, par le rapport de l’INCa antérieurs à 2014, ont été intégrés à la revue de la littérature.Résultats :Dix-huit articles ont été sélectionnés. Les études ont conclu de façon unanime à une diminution de la mortalité globale par la pratique d’une activité physique postdiagnostic. Pour la mortalité spécifique, 5 méta-analyses ont montré une diminution significative de la mortalité par cancer du sein et 2 ont retrouvé une diminution du risque de récidive.Conclusion :L’activité physique postdiagnostic d’un cancer du sein diminue la mortalité globale et semble impacter la mortalité spécifique par cancer du sein et le risque de récidive. Ces résultats nécessitent, cependant, d’être confirmés par de plus larges essais randomisés.
Published: 2020

28. Impact of age at diagnosis of metastatic breast cancer on overall survival in the real-life ESME metastatic breast cancer cohort

Author: Frank, Sophie, Carton, Matthieu, Dubot, Coraline, Campone, Mario, Pistilli, Barbara, Dalenc, Florence, Mailliez, Audrey, Lévy, Christelle, D'Hondt, Veronique, Debled, Marc, Vermeulin, Thomas, Coudert, Benoit, Perrin, Christophe, Gonçalves, Anthony, Uwer, Lionel, Ferrero, Jean-Marc, Eymard, Jean-Christophe, Petit, Thierry, Mouret-Reynier, Marie-Ange, Patsouris, Anne, Guesmia, Tahar, Bachelot, Thomas, Robain, Mathieu, Cottu, Paul, D’Hondt, Véronique, Institut Curie [Paris], Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Hôpital Guillaume-et-René-Laennec [Saint-Herblain], Institut Gustave Roussy (IGR), Département de médecine oncologique [Gustave Roussy], Institut Claudius Regaud, Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER, Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Institut du Cancer de Montpellier (ICM), Institut Bergonié [Bordeaux], Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), Centre Eugène Marquis (CRLCC), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Institut Jean Godinot [Reims], Centre Paul Strauss, CRLCC Paul Strauss, Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), Centre Léon Bérard [Lyon], Institut Curie [Saint-Cloud], French Breast Cancer Intergroup - UCBG [Paris] (R&D UNICANCER), R&D Unicancer [Paris], Cohortes épidémiologiques en population (CONSTANCES), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université de Paris (UP), Département d'Oncologie Médicale [Institut Curie, Paris], Centre de Lutte Contre le Cancer Nantes Atlantique 'René Gauducheau' (CLCC), Université Lille Nord de France (COMUE)-UNICANCER, Service d'Oncologie médicale [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Université Catholique de Louvain = Catholic University of Louvain (UCL), Service d'Oncologie Médicale, UNICANCER-UNICANCER, Hôpital Charles Nicolle [Tunis], Département d'oncologie médicale [Rennes], CRLCC Eugène Marquis (CRLCC), Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), Senescence Escape and Soluble Markers of Cancer Progression (CRCINA-ÉQUIPE 12), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Oncogénèse et progression tumorale, Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de recherche translationnelle, 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), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université Paris Cité (UPC), Université Côte d'Azur (UCA)-UNICANCER, and Centre hospitalier universitaire de Nantes (CHU Nantes)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes (UN)-Université d'Angers (UA)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes (UN)-Université d'Angers (UA)
Subjects: Adult, Oncology, medicine.medical_specialty, Receptor, ErbB-2, [SDV]Life Sciences [q-bio], Age at diagnosis, Breast Neoplasms, Triple Negative Breast Neoplasms, [SDV.CAN]Life Sciences [q-bio]/Cancer, lcsh:RC254-282, Cohort Studies, Metastatic disease, 03 medical and health sciences, Age Distribution, Breast cancer, Age, 0302 clinical medicine, Internal medicine, Overall survival, Humans, Medicine, 030212 general & internal medicine, Stage (cooking), skin and connective tissue diseases, Early Detection of Cancer, Retrospective Studies, business.industry, Cancer, General Medicine, Middle Aged, Prognosis, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, Survival Analysis, Metastatic breast cancer, Real-world data, 3. Good health, Young age, 030220 oncology & carcinogenesis, Cohort, Original Article, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Surgery, France, business
Abstract: Background Young age is a poor prognostic factor in early stage breast cancer (BC) but its value is less established in metastatic BC (MBC). We evaluated the impact of age at MBC diagnosis on overall survival (OS) across three age groups ( 60 years(y)). Methods ESME MBC database is a national cohort, collecting retrospective data from 18 participating French cancer centers between January 01, 2008 and December 31, 2014. Results Among 14 403 women included, 1077 (7.5%), 6436 (44.7%) and 6890 (47.8%) pts were 60 y respectively. Pts 60y) and triple negative subtypes (27.4 vs 14.6% in >60y), and more frequent visceral involvement (36.3 vs 29.8% in >60y). At a median follow-up of 48 months, median OS differed across age groups: 38.8, 38.4 and 35.6 months for pts 60y, respectively (p 60y, respectively (p, Highlights • Young age is a poor prognosis factor in early stage breast cancer. • Young age is associated with an aggressive presentation in metastatic breast cancer. • Young age had no impact on overall survivall in metastatic breast cancer. • Oppositely, older women (>60y) had a stightly poorer prognosis at the metastatic stage.
Published: 2020

29. Temozolomide is effective and well tolerated in patients with primary vitreoretinal lymphoma

Author: Nathalie Cassoux, Pierre Soubeyran, Karim Maloum, Anne Lavaud, Carole Soussain, Christine Fardeau, Caroline Houillier, Marie-Laure Le Lez, Marion Blaizeau, Bahram Bodaghi, Magali Le Garff-Tavernier, Marie-Hélène Errera, Myrto Costopoulos, Damien Roos-Weil, Valérie Touitou, Lisa Belin, Veronique Leblond, Khê Hoang-Xuan, Emmanuel Gyan, Marine Baron, Sylvain Choquet, Gestionnaire, Hal Sorbonne Université, Service d'Hématologie clinique [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Département de Biostatistique, Santé Publique et Information Médicale [CHU Pitié-Salpêtrière] (BIOSPIM ), Université Paris Descartes - Paris 5 (UPD5), Service d'Ophtalmologie [CHU Pitié-Salpêtrière], CHU Bordeaux [Bordeaux], Institut Curie - Saint Cloud (ICSC), Service d'Onco-neurologie = Département de neurologie 2 [CHU Pitié Salpêtrière], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Institut Bergonié [Bordeaux], UNICANCER, Service d'Hématologie Biologique [CHU Pitié-Salpêtrière], and Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts (CHNO)
Subjects: Adult, Male, Oncology, medicine.medical_specialty, Drug-Related Side Effects and Adverse Reactions, Lymphoma, [SDV]Life Sciences [q-bio], Retinal Neoplasms, Immunology, MEDLINE, Biochemistry, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Temozolomide, medicine, Humans, In patient, Aged, Retrospective Studies, Aged, 80 and over, business.industry, Eye Neoplasms, Cell Biology, Hematology, Middle Aged, humanities, [SDV] Life Sciences [q-bio], Vitreous Body, Treatment Outcome, Female, business, 030217 neurology & neurosurgery, 030215 immunology, Vitreoretinal lymphoma, medicine.drug
Abstract: Baron et al report excellent responses to temozolomide in 21 patients (19 relapsed/refractory) with primary vitreoretinal lymphoma. Treatment is well tolerated, even in elderly patients.
Published: 2020

30. Therapeutic Challenges in Patients with Gynecologic Carcinosarcomas: Analysis of a Multicenter National Cohort Study from the French Prospective TMRG Network

Author: Clémence Romeo, Olivia Le Saux, Margaux Jacobs, Florence Joly, Gwenael Ferron, Laure Favier, Jean-David Fumet, Nicolas Isambert, Pierre-Emmanuel Colombo, Renaud Sabatier, Ludovic Bastide, Amandine Charreton, Mojgan Devouassoux-Shisheboran, Witold Gertych, Coraline Dubot, Diana Bello Roufai, Guillaume Bataillon, Dominique Berton, Elsa Kalbacher, Patricia Pautier, Christophe Pomel, Caroline Cornou, Isabelle Treilleux, Audrey Lardy-Cleaud, Isabelle Ray-Coquard, Centre Léon Bérard [Lyon], Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Groupe d'Investigateurs Nationaux pour l'Étude des Cancers de l'Ovaire et du sein [Paris] (GINECO), Institut Claudius Regaud, Département d'oncologie médicale [Centre Georges-François Leclerc], Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER, Institut du Cancer de Montpellier (ICM), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Institut Curie - Saint Cloud (ICSC), Institut Curie [Paris], Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Institut Gustave Roussy (IGR), Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon
Subjects: Cancer Research, rare cancer, adjuvant treatment, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, [SDV.CAN]Life Sciences [q-bio]/Cancer, TMRG network, [SDV.MHEP.GEO]Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, uterine carcinosarcoma, chemotherapy, ovarian carcinosarcoma, cytotoxic agent, Article, Oncology, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, RC254-282
Abstract: Simple Summary Gynecologic carcinosarcomas are rare and aggressive diseases with a poor prognosis. The rarity of these tumors explains the lack of robust and specific data available in the literature. Using the data from the French National Rare Malignant Gynecological Tumors (TMRG) network, we conducted a multicentric cohort study to explore several burned questions. The main objective was to assess the outcome of patients with carcinosarcomas recorded in the network and to investigate the efficacy of initial adjuvant treatment and recurrent therapeutic strategies in a real-life setting. Four hundred and twenty-five patients were analyzed including 313 uterine and 112 ovarian carcinosarcomas. Our data suggest positive impact of adjuvant chemotherapy on survival in all stages (including FIGO IA uterine carcinosarcomas) and the importance of platinum-based combination for the treatment of relapse. In addition we report median PFS for various therapeutic strategies in the relapse setting. Abstract Background: Gynecological carcinosarcomas are rare and aggressive diseases, with a poor prognosis. The rarity of these tumors explains the lack of robust and specific data available in the literature. The objective of this study was to investigate the impact of initial adjuvant treatment and recurrent therapeutic strategies. Patients and methods: A multicentric cohort study within the French national prospective Rare Malignant Gynecological Tumors (TMRG) network was conducted. Data from all included carcinosarcomas diagnosed between 2011 and 2018 were retrospectively collected. Results: 425 cases of uterine and ovarian carcinosarcomas (n = 313 and n = 112, respectively) were collected and analyzed from 12 participating centers. At diagnosis, 140 patients (48%) had a FIGO stage III–IV uterine carcinosarcoma (UCS) and 88 patients (83%) had an advanced ovarian carcinosarcoma (OCS) (FIGO stage ≥ III). Two hundred sixty-seven patients (63%) received adjuvant chemotherapy, most preferably carboplatin-paclitaxel regimen (n = 227, 86%). After a median follow-up of 47.4 months, the median progression-free survival (mPFS) was 15.1 months (95% CI 12.3–20.6) and 14.8 months (95% CI 13.1–17.1) for OCS and UCS, respectively. The median overall survival for OCS and UCS was 37.1 months (95% CI 22.2–49.2) and 30.6 months (95% CI 24.1–40.9), respectively. With adjuvant chemotherapy followed by radiotherapy, mPFS was 41.0 months (95% CI 17.0–NR) and 18.9 months (95% CI 14.0–45.6) for UCS stages I–II and stages III–IV, respectively. In the early stage UCS subgroup (i.e., stage IA, n = 86, 30%), mPFS for patients treated with adjuvant chemotherapy (n = 24) was not reached (95% CI 22.2–NR), while mPFS for untreated patients (n = 62) was 19.9 months (95% IC 13.9–72.9) (HR 0.44 (0.20–0.95) p = 0.03). At the first relapse, median PFS for all patients was 4.2 months (95% CI 3.5–5.3). In the first relapse, mPFS was 6.7 months (95% CI 5.1–8.5) and 2.2 months (95% CI 1.9–2.9) with a combination of chemotherapy or monotherapy, respectively (p < 0.001). Conclusions: Interestingly, this vast prospective cohort of gynecological carcinosarcoma patients from the French national Rare Malignant Gynecological Tumors network (i) highlights the positive impact of adjuvant CT on survival in all localized stages (including FIGO IA uterine carcinosarcomas), (ii) confirms the importance of platinum-based combination as an option for relapse setting, and (iii) reports median PFS for various therapeutic strategies in the relapse setting.
Published: 2022
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31. TAKTIC: A prospective, multicentre, uncontrolled, phase IB/II study of LY2780301, a p70S6K/AKT inhibitor, in combination with weekly paclitaxel in HER2-negative advanced breast cancer patients

Author: Arnaud Guille, Jihane Pakradouni, Max Chaffanet, Séverine Garnier, Christelle Levy, Marie Robert, Jean Marie Boher, Anthony Gonçalves, Cecile Vicier, Cornel Popovici, José Adélaïde, Daniel Birnbaum, Florence Dalenc, Patrick Sfumato, Nadine Carbuccia, Renaud Sabatier, Keyvan Rezai, Nicolas Isambert, Emmanuelle Charafe-Jauffret, François Bertucci, Magali Provansal, Department of Medical Oncology, Institut Paoli-Calmettes, 232 Boulevard Sainte Marguerite, 13009 Marseille, France., Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Sabatier, Renaud, Dupuis, Christine, Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, Institut Claudius Regaud, Centre de Recherches en Cancérologie de Toulouse (CRCT), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), CRLCC René Gauducheau, Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Institut Curie - Saint Cloud (ICSC), Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Adult, Oncology, Cancer Research, medicine.medical_specialty, Paclitaxel, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Population, Triple Negative Breast Neoplasms, P70-S6 Kinase 1, [SDV.CAN]Life Sciences [q-bio]/Cancer, PI3K, chemistry.chemical_compound, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Enzyme Inhibitors, Adverse effect, education, ComputingMilieux_MISCELLANEOUS, Aged, Chemotherapy, education.field_of_study, business.industry, AKT, Ribosomal Protein S6 Kinases, 70-kDa, Cancer, Middle Aged, Metastatic breast cancer, medicine.disease, [SDV] Life Sciences [q-bio], chemistry, Toxicity, Female, business, Proto-Oncogene Proteins c-akt
Abstract: International audience; Background: Hormone-resistant HER2-negative or triple-negative advanced breast cancers (ABC) are routinely treated with paclitaxel chemotherapy. LY2780301 is a dual inhibitor of p70 ribosomal protein S6 kinase and AKT. The TAKTIC study aimed at exploring the combination of paclitaxel and LY2780301 in this population.Methods: In this multicentric phase Ib/II trial, we enrolled patients with HER2-negative ABC, with (phase IB) or without (phase II) prior to cytotoxic treatment for advanced disease. Oral LY2780301 was administered once daily in combination with intravenous weekly paclitaxel. Primary endpoints were to determine the recommended phase II dose (RP2D) of the combination of LY2780301 with weekly paclitaxel (phase Ib), and to estimate a 6 months objective response rate (ORR) (phase II) in patients with HER2-negative ABC, both in the overall patient population and in cases with activation of the PI3K/AKT pathway (PI3KAKT+).Results: A total of 51 patients were enrolled; RP2D was LY2780301 500 mg QD+ paclitaxel 80 mg/m2. Main drug-related adverse events noted in phase Ib included neuropathy (75% of patients, grade 3-4 in 8%), asthenia (58% of patients, no grade 3-4), and ungual toxicity (50% of patients, grade 3-4 in 25%). They were similar in the phase II part, except that 14% of patients experienced pneumonia (grade 3-4 in 6%). In the phase II part, 6-month ORR in the overall population and in PI3KAKT+ subgroup were, respectively, 63.9% [48.8-76.8] and 55% [35-73.7].Conclusion: Combining LY2780301 and weekly paclitaxel in patients with HER2-negative ABC was feasible with preliminary evidence of efficacy in both the overall population and the PI3KAKT+ subgroup.Trial registration id: NCT01980277.
Published: 2021

32. Primary vitreoretinal lymphoma: a diagnostic and management challenge

Author: Soussain, Carole, Malaise, Denis, Cassoux, Nathalie, Institut Curie - Saint Cloud (ICSC), Immunité et cancer (U932), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Département d'Oncologie Chirurgicale [Institut Curie], Institut Curie [Paris], Laboratoire d'Imagerie Translationnelle en Oncologie (LITO ), Biologie Cellulaire et Cancer, Institut Curie [Paris]-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), and Malaise, Denis
Subjects: [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, [SDV.CAN] Life Sciences [q-bio]/Cancer, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Primary vitreoretinal lymphoma (PVRL) is a rare form of primary central nervous system (CNS) lymphoma (PCNSL) arising in the intraocular compartment without brain involvement. Despite its apparent indolent clinical course, PVRL can cause permanent vision loss and CNS relapse, the major cause of death in patients with PVRL. The pathophysiology of PVRL is unknown. As in PCNSL, the transformation of the tumor cells likely originates outside the CNS, before the cells migrate to the eye and proliferate within an immune-permissive microenvironment. PVRL exhibits a biased immunoglobulin repertoire, suggesting underlying antigen selection. The diagnosis remains challenging, requiring close coordination between ophthalmologists and cytologists. Because of their rarity and fragility in the vitreous, lymphoma cells cannot always be identified. Interleukin levels, molecular biology, and imaging are used in combination with clinical ophthalmological examination to support the diagnosis of PVRL. Multi-institutional prospective studies are urgently needed to validate the equivocal conclusions regarding treatments drawn from heterogeneous retrospective or small cohort studies. Intravitreal injection of methotrexate or rituximab or local radiotherapy is effective at clearing tumor cells within the eyes but does not prevent CNS relapse. Systemic treatment based on high-dose methotrexate chemotherapy, with or without local treatment, might reduce this risk. At relapse, intensive consolidation chemotherapy followed by stem cell transplantation can be considered. Single-agent ibrutinib, lenalidomide, and temozolomide treatments are effective in patients with relapsed PVRL and should be tested as first-line treatments. Therapeutic response assessment based on clinical examination is improved by measuring cytokine levels but still needs to be refined.
Published: 2021

33. Prevalence and prognostic impact of cachexia among older patients with cancer: a nationwide cross‐sectional survey (NutriAgeCancer)

Author: Damien Heitz, Florence Canoui-Poitrine, Heidi Solem-Laviec, Evelyne Liuu, Anne Chah Wakilian, Hayat Medjenah, Mathilde Gisselbrecht, Catherine Cattenoz, Johanne Poisson, Rabia Boulahssass, Marie Laurent, Anne-Laure Couderc, Claire Falandry, Gilles Albrand, Romain Geiss, F. Pamoukdjian, Laure de Decker, Pascaline Boudou-Rouquette, Olivier Guillem, Elena Paillaud, Valery Antoine, Cedric Gaxatte, Claudia Martinez-Tapia, Pierre André Natella, Paris-Centre de Recherche Cardiovasculaire (PARCC - UMR-S U970), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), IMRB - CEPIA/'Clinical Epidemiology And Ageing : Geriatrics, Primary Care and Public Health' [Créteil] (U955 Inserm - UPEC), 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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Pôle de Gériatrie, CHU Strasbourg, Institut Curie - Saint Cloud (ICSC), Hôpital Antoine Charial [CHU - HCL], Hospices Civils de Lyon (HCL), AP-HP, Hôpital Européen Georges-Pompidou (HEGP), Onco-Geriatric Department, Paris, France, Assistance Publique - Hôpitaux de Marseille (APHM), Geriatric Coordination Unit for Geriatric Oncology [Nice], Centre Hospitalier Universitaire de Nice (CHU Nice), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Geriatric Department, Broca Hospital, Paris Centre Hospitals, Paris Descartes University, Pôle de gérontologie [CHRU de Lille], Hôpital Roger Salengro [Lille]-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), APHP, Hôpital Avicenne, Geriatric department, Coordination Unit in Geriatric Oncology, Bobigny, France, Clinical Gerontology Department, Nantes University Hospital Center, Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Service de gériatrie, CHU Pontchaillou [Rennes], Geriatric Oncology Unit, Oncology Supportive Care Department, François Baclesse Regional Cancer Center, Caen, France, Geriatric Medicine Unite, Partenaires INRAE, AP-HP, hôpital Henri-Mondor, Clinical Research Unit (URC Mondor), F-94010 Creteil, France, and Tapia, Claudia
Subjects: Male, medicine.medical_specialty, Cachexia, Colorectal cancer, [SDV.CAN]Life Sciences [q-bio]/Cancer, Diseases of the musculoskeletal system, Elderly, [SDV.CAN] Life Sciences [q-bio]/Cancer, Interquartile range, Weight loss, Physiology (medical), Internal medicine, medicine, Prevalence, Humans, Orthopedics and Sports Medicine, Nutritional support, Aged, Gastrointestinal Neoplasms, Cancer, business.industry, QM1-695, Malnutrition, Original Articles, medicine.disease, Prognosis, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, Cross-Sectional Studies, RC925-935, Geriatric oncology, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Sarcopenia, Human anatomy, Screening, Original Article, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, medicine.symptom, business, Body mass index, Prognostic value, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract: Background Nutritional impairment is common in cancer patients and is associated with poor outcomes. Only few studies focused on cachexia. We assessed the prevalence of cachexia in older cancer patients, identified associated risk factors, and evaluated its impact on 6 month overall mortality. Methods A French nationwide cross‐sectional survey (performed in 55 geriatric oncology clinics) of older cancer patients aged ≥70 referred for geriatric assessment prior to treatment choice and initiation. Demographic, clinical, and nutritional data were collected. The first outcome was cachexia, defined as loss of more than 5% of bodyweight over the previous 6 months, or a body mass index below 20 kg/m2 with weight loss of more than 2%, or sarcopenia (an impaired Strength, Assistance with walking, Rise from chair, Climb stairs and Falls score) with weight loss of more than 2%. The second outcome was 6 month overall mortality. Results Of the 1030 patients included in the analysis [median age (interquartile range): 83 (79–87); males: 48%; metastatic cancer: 42%; main cancer sites: digestive tract (29%) and breast (16%)], 534 [52% (95% confidence interval: 49–55%)] had cachexia. In the multivariate analysis, patients with breast (P
Published: 2021

34. Primary vitreoretinal lymphoma: short review of the literature, results of a European survey and French guidelines of the LOC network for diagnosis, treatment and follow-up

Author: Anne Vincent-Salomon, Denis Malaise, Nathalie Cassoux, Khê Hoang-Xuan, Sylvain Choquet, Carole Soussain, Karim Maloum, Loïc Feuvret, Frederic Davi, Caroline Houillier, Valérie Touitou, Magali Le Garff-Tavernier, Laboratoire d'Imagerie Translationnelle en Oncologie (LITO ), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Curie [Paris], Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-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)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Biologie Cellulaire et Cancer, Institut Curie [Paris]-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut Curie - Saint Cloud (ICSC), Immunité et cancer (U932), and Malaise, Denis
Subjects: [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, Cancer Research, medicine.medical_specialty, Lymphoma, Retinal Neoplasms, MEDLINE, [SDV.CAN]Life Sciences [q-bio]/Cancer, primary vitreoretinal lymphoma, [SDV.CAN] Life Sciences [q-bio]/Cancer, medicine, Humans, guidelines, Intensive care medicine, Lenalidomide, diagnosis and management challenges, Temozolomide, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, treatment, business.industry, European mapping, Optimal treatment, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, medicine.disease, Vitreous Body, Oncology, Diagnosis treatment, Rituximab, Neoplasm Recurrence, Local, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, medicine.drug, Vitreoretinal lymphoma, Follow-Up Studies
Abstract: International audience; Purpose of review. The aim of this study was to highlight the diagnostic and management challenges of primary vitreoretinal lymphoma (PVRL) through a review of the literature and a European survey on real-life practices for PVRL.Recent findings. The care of PVRL patients is heterogeneous between specialists and countries. Upfront systemic treatment based on highdose methotrexate chemotherapy, with or without local treatment, might reduce or delay the risk of brain relapse. Ibrutinib, lenalidomide with or without rituximab, and temozolomide are effective for patients with relapsed/refractory PVRL and should be tested as first-line treatments.Summary. The prognosis of PVRL remains dismal. No firm conclusion regarding optimal treatment can yet be drawn. The risk of brain relapse remains high. Diagnostic procedures and assessment of therapeutic responses need to be homogenized. Collaboration between specialists involved in PVRL and multicentric prospective therapeutic studies are strongly needed. The recommendations of the French group for primary oculocerebral lymphoma (LOC network) are provided, as a basis for further European collaborative work.
Published: 2021

35. Quality of life of survivors 1 year after the diagnosis of diffuse large B-cell lymphoma: a LYSA study

Author: Fabrice Jardin, Krimo Bouabdallah, Sandra Malak, Corinne Haioun, Alexandra-Cristina Paunescu, Vincent Ribrag, Gerhard Rumpold, Christiane Copie, Nicolas Mounier, David Sibon, Caroline Besson, Marie Preau, Steven Le Gouill, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Institut Gustave Roussy (IGR), CHU Henri Mondor, Institut Curie - Saint Cloud (ICSC), Regulation of Bcl2 and p53 Networks in Multiple Myeloma and Mantle Cell Lymphoma (CRCINA-ÉQUIPE 10), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre hospitalier universitaire de Nantes (CHU Nantes), Département d'hématologie [Gustave Roussy], CHU Bordeaux [Bordeaux], Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Innsbruck Medical University = Medizinische Universität Innsbruck (IMU), Groupe de Recherche en Psychologie Sociale (GRePS), Université Lumière - Lyon 2 (UL2), Institut de Psychologie, Hôpital l'Archet, 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 Hospitalier de Versailles André Mignot (CHV), Bernardo, Elizabeth, and Innsbruck Medical University [Austria] (IMU)
Subjects: Adult, Male, medicine.medical_specialty, Lymphoma, Health Status, [SDV.CAN]Life Sciences [q-bio]/Cancer, Disease, Hospital Anxiety and Depression Scale, Comorbidities, Young Adult, [SDV.CAN] Life Sciences [q-bio]/Cancer, Quality of life, Cancer Survivors, Internal medicine, Bayesian multivariate linear regression, Surveys and Questionnaires, medicine, Chemotherapy, Humans, Survivors, Depression (differential diagnoses), Aged, Aged, 80 and over, Posttraumatic growth, business.industry, Hematology, General Medicine, Middle Aged, medicine.disease, humanities, Quality of Life, Original Article, Female, Lymphoma, Large B-Cell, Diffuse, business, Diffuse large B-cell lymphoma, Psychosocial
Abstract: Health-related quality of life (HRQoL) is a multidimensional concept including physical, emotional, social, and cognitive functions, disease symptoms, and side effects of treatment. Differences in HRQoL due to gender, existence of comorbidities, and number of chemotherapy cycles are little explored in diffuse large B-cell lymphoma (DLBCL) survivors. Our objective was to investigate whether differences in HRQoL in function of these factors exist 1 year after the diagnosis of DLBCL. One hundred and one patients, enrolled in the RT3 (Real-Time Tailored Therapy) Study, answered self-administrated European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30), EORTC High-Grade Non-Hodgkin Lymphoma (NHL-HG29), Hospital Anxiety and Depression Scale (HADS), Post Traumatic Growth Inventory (PTGI), and Multidimensional Fatigue Inventory (MFI) questionnaires. Adjusted means of scores were calculated in multivariate linear regression models. Fifty-seven survivors (mean age of 58.5 years) answered all questionnaires. Women have significantly higher scores of posttraumatic growth and lower physical functioning than men (P < 0.04). Survivors with comorbidities have increased physical fatigue and symptom burden, increased emotional impact, mental fatigue and depression, and reduced physical functioning and global health status (all P < 0.05). A greater number of cycles of chemotherapy increase the level of symptoms (pain, neuropathy, and dyspnoea; P < 0.05). The various aspects related to HRQoL should be discussed with DLBCL patients and investigated, with the aim of developing strategies to ensure appropriate psychosocial and supportive care and to improve the HRQoL in these patients. Supplementary Information The online version contains supplementary material available at 10.1007/s00277-021-04689-4.
Published: 2021

36. Progressive multifocal leukoencephalopathy: MRI findings in HIV-infected patients are closer to rituximab- than natalizumab-associated PML

Author: Alleg, Manel, Solis, Morgane, Baloglu, Seyyid, Cotton, François, Kerschen, Philippe, Bourre, Bertrand, Ahle, Guido, Pruvo, Jean-Pierre, Leclerc, Xavier, Vermersch, Patrick, Papeix, Caroline, Maillart, Élisabeth, Houillier, Caroline, Chabrot, Cécile Moluçon, Claise, Béatrice, Malak, Sandra, Martin-Blondel, Guillaume, Bonneville, Fabrice, Caulier, Alexis, Marolleau, Jean-Pierre, Bonnefoy, Jérôme Tamburini, Agape, Philippe, Kennel, Céline, Roussel, Xavier, Chauchet, Adrien, de Seze, Jérôme, Fafi-Kremer, Samira, Kremer, Stéphane, Les Hôpitaux Universitaires de Strasbourg (HUS), Laboratoire de Virologie [Strasbourg], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier de Luxembourg [Luxembourg] (CHL), CHU Rouen, Normandie Université (NU), Service de Neurologie [Hôpitaux Civils de Colmar], Hôpitaux Civils Colmar, Lille Neurosciences & Cognition - U 1172 (LilNCog), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Departement de Neuroradiologie [Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), 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), Sorbonne Université (SU), Service d'Onco-neurologie = Département de neurologie 2 [CHU Pitié Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], CHU Clermont-Ferrand, Institut Curie - Saint Cloud (ICSC), Service Maladies infectieuses et tropicales [CHU Toulouse], Pôle Inflammation, infection, immunologie et loco-moteur [CHU Toulouse] (Pôle I3LM Toulouse), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service Neuroradiologie Diagnostique et Thérapeutique [CHU Toulouse], Pôle imagerie médicale [CHU Toulouse], Laboratoire d'Hématologie [CHU Amiens], CHU Amiens-Picardie, AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, CHU Limoges, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Hôpital de Hautepierre [Strasbourg], Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie (ICube), École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Université de Strasbourg (UNISTRA)-Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Les Hôpitaux Universitaires de Strasbourg (HUS)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), and PINIER, CHRISTINE
Subjects: MESH: Leukoencephalopathy, Progressive Multifocal* / diagnostic imaging, MESH: Humans, Natalizumab, [SDV]Life Sciences [q-bio], virus diseases, MESH: Natalizumab / adverse effects, MESH: Retrospective Studies, MESH: HIV Infections* / drug therapy, MESH: Rituximab / adverse effects, MESH: Magnetic Resonance Imaging, [SDV] Life Sciences [q-bio], Progressive multifocal leukoencephalopathy, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, MESH: Leukoencephalopathy, Progressive Multifocal* / chemically induced, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, MESH: HIV Infections* / complications, MESH: Brain / diagnostic imaging, Rituximab
Abstract: International audience; Objectives: To compare brain MRI findings in progressive multifocal leukoencephalopathy (PML) associated to rituximab and natalizumab treatments and HIV infection.Materials and methods: In this retrospective, multicentric study, we analyzed brain MRI exams from 72 patients diagnosed with definite PML: 32 after natalizumab treatment, 20 after rituximab treatment, and 20 HIV patients. We compared T2- or FLAIR-weighted images, diffusion-weighted images, T2*-weighted images, and contrast enhancement features, as well as lesion distribution, especially gray matter involvement.Results: The three PML entities affect U-fibers associated with low signal intensities on T2*-weighted sequences. Natalizumab-associated PML showed a punctuate microcystic appearance in or in the vicinity of the main PML lesions, a potential involvement of the cortex, and contrast enhancement. HIV and rituximab-associated PML showed only mild contrast enhancement, punctuate appearance, and cortical involvement. The CD4/CD8 ratio showed a trend to be higher in the natalizumab group, possibly mirroring a more efficient immune response.Conclusion: Imaging features of rituximab-associated PML are different from those of natalizumab-associated PML and are closer to those observed in HIV-associated PML.
Published: 2021

37. Absenteeism and indirect costs during the year following the diagnosis of an operable breast cancer: A prospective multicentric cohort study

Author: Delphine Hequet, Bernard Asselain, Sandrine Baffert, Roman Rouzier, Clement Ferrier, Pierre Levy, Clémence Thebaut, Administrateur, Paris Dauphine-PSL, Département d'Oncologie Chirurgicale [Institut Curie], Institut Curie [Paris], Laboratoire d'Economie et de Gestion des Organisations de Santé (Legos), Université Paris Dauphine-PSL, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), Laboratoire d'Economie de Dauphine (LEDa), Institut de Recherche pour le Développement (IRD)-Université Paris Dauphine-PSL, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), CEMKA-EVAL, Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania [Philadelphia]-University of Pennsylvania [Philadelphia]-Abramson Cancer Center, Department of Surgery [Saint-Cloud], Institut Curie [Saint-Cloud], and Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Dauphine-PSL
Subjects: Reoperation, medicine.medical_treatment, Personnel Staffing and Scheduling, JEL: J - Labor and Demographic Economics/J.J1 - Demographic Economics/J.J1.J17 - Value of Life • Forgone Income, Breast Neoplasms, Economic burden, Cohort Studies, 03 medical and health sciences, Indirect costs, Return to Work, 0302 clinical medicine, Breast cancer, Cost of Illness, JEL: J - Labor and Demographic Economics/J.J2 - Demand and Supply of Labor/J.J2.J24 - Human Capital • Skills • Occupational Choice • Labor Productivity, Absenteeism, Humans, Medicine, Neoplasm Invasiveness, Occupations, Mastectomy, 030219 obstetrics & reproductive medicine, Health economics, [QFIN]Quantitative Finance [q-fin], business.industry, Obstetrics and Gynecology, Middle Aged, medicine.disease, [QFIN] Quantitative Finance [q-fin], 3. Good health, JEL: I - Health, Education, and Welfare/I.I1 - Health/I.I1.I12 - Health Behavior, J.J2.J24, JEL: I - Health, Education, and Welfare/I.I1 - Health/I.I1.I11 - Analysis of Health Care Markets, Reproductive Medicine, Chemotherapy, Adjuvant, 030220 oncology & carcinogenesis, Sick leave, Cohort, Female, France, Sick Leave, business, Demography, Cohort study
Abstract: Background Diseases consequence on individual work as much as consequences of being absent from work are matters of interest for decision makers. Methods We analyzed lengths of absenteeism and related indirect costs for patients with a paid activity in the year following the diagnosis of early stage breast cancer, in the prospective OPTISOINS01 cohort. Both human capital and friction costs approach were considered for the valuation of lost working days (LWD). For the analysis, the friction period was estimated from recent French data. The statistical analysis included simple and multiple linear regression to search for the determinants of absenteeism and indirect costs. Results 93 % of the patients had at least one period of sick leave, with on average 2 period and 186 days of sick leave. 24 % of the patients had a part-time resumption after their sick leave periods, during 114 days on average (i.e. 41 LWD). Estimated indirect costs were 22,722.00 € and 7,724.00 € per patient, respectively for the human capital and the friction cost approach. In the multiple linear regression model, factors associated with absenteeism were: the invasive nature of the tumor (p = .043), a mastectomy (p = .038), a surgery revision (p = .002), a chemotherapy (p = .027), being a manager (p = .025) or a craftsman (p = .005). Conclusion Breast cancer lead to important lengths of absenteeism in the year following the diagnosis, but almost all patients were able to return to work. Using the friction cost or the human capital approach in the analysis led to an important gap in the results, highlighting the importance of considering both for such studies.
Published: 2021

38. Circulating Tumor Cells and Bevacizumab Pharmacokinetics during Neoadjuvant Treatment Combining Chemotherapy and Bevacizumab for Early Breast Cancer: Ancillary Analysis of the AVASTEM Trial

Author: Patrick Sfumato, Jean-Marc Extra, Jean-Yves Pierga, Hervé Curé, Rakan Abulnaja, Anthony Gonçalves, Eric Lambaudie, François-Clément Bidard, Renaud Sabatier, Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Institut Curie [Paris], Institut Curie - Saint Cloud (ICSC), Institut Jean Godinot [Reims], UNICANCER, and Sabatier, Renaud
Subjects: 0301 basic medicine, Oncology, Cancer Research, medicine.medical_specialty, Bevacizumab, medicine.medical_treatment, circulating tumor cells and pharmacokinetics, [SDV.CAN]Life Sciences [q-bio]/Cancer, bevacizumab, lcsh:RC254-282, Article, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, Circulating tumor cell, [SDV.CAN] Life Sciences [q-bio]/Cancer, Pharmacokinetics, Internal medicine, Medicine, early breast cancer, Pathological, Early breast cancer, Chemotherapy, business.industry, medicine.disease, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, 030104 developmental biology, 030220 oncology & carcinogenesis, Stem cell, business, medicine.drug, neoadjuvant chemotherapy
Abstract: The phase II AVASTEM trial explored the impact of chemotherapy-bevacizumab combination on breast cancer stem cells in the neoadjuvant setting. We aimed to identify biological features associated with preoperative chemotherapy efficacy and prognosis by analyses of circulating tumor cells (CTCs) and bevacizumab pharmacokinetics (PK). The main objective was to assess the prognostic (relapse-free survival and overall survival) and predictive (pathological complete response, pCR) values of CTCs (CellSearch technology) and bevacizumab PK (ELISA). Seventy-five patients were included. Out of them 50 received bevacizumab-chemotherapy and 25 received chemotherapy alone. CTC results were available for 60 patients and PK data for 29 patients in the experimental arm. The absence of CTC at inclusion was correlated to better outcome. Five-years overall survival (OS) was 91% for CTC-negative patients vs. 54% for CTC-positive cases (HR = 6.21, 95%CI (1.75&ndash, 22.06), p = 0.001, log-rank test). Similar results were observed for RFS with 5 y-RFS of 78% vs. 44% (HR = 3.51, 95%CI (1.17&ndash, 10.52), p = 0.017, log-rank test). However, CTC status at baseline was not predictive of pCR (p = 0.74). CTC status after one cycle was not a significant prognostic factor (HR = 1.56, 95%CI (0.19&ndash, 12.67), p = 0.68 for OS and HR = 2.76, 95%CI (0.60&ndash, 12.61), p = 0.17 for RFS, log-rank test). Bevacizumab serum levels could not predict pCR and survival. PK values were not associated with treatment-related toxicities. In conclusion, CTCs detection at baseline is a prognostic marker for breast cancer receiving a neoadjuvant chemotherapy-bevacizumab combination independently of tumor response.
Published: 2021

39. Efficacy of Circulating Tumor Cell Count–Driven vs Clinician-Driven First-line Therapy Choice in Hormone Receptor–Positive, ERBB2-Negative Metastatic Breast Cancer

Author: Bidard, François-Clément, Jacot, William, Kiavue, Nicolas, Dureau, Sylvain, Kadi, Amir, Brain, Etienne, Bachelot, Thomas, Bourgeois, Hugues, Gonçalves, Anthony, Ladoire, Sylvain, Naman, Hervé, Dalenc, Florence, Gligorov, Joseph, Espié, Marc, Emile, George, Ferrero, Jean-Marc, Loirat, Delphine, Frank, Sophie, Cabel, Luc, Diéras, Véronique, Cayrefourcq, Laure, Simondi, Cécile, Berger, Frédérique, Alix-Panabières, Catherine, Pierga, Jean-Yves, Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Université Paris-Saclay, Institut Curie - Saint Cloud (ICSC), CIC1428 IGR-CURIE, Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut du Cancer de Montpellier (ICM), 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), Institut Curie [Paris], Université Paris sciences et lettres (PSL), Centre Léon Bérard [Lyon], Clinique Victor Hugo [Le Mans], Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, Centre Azuréen de Cancérologie [Mougins, France], Institut Claudius Regaud, CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Centre Eugène Marquis (CRLCC), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université de Montpellier (UM), and Daulat, Avais
Subjects: [SDV.CAN] Life Sciences [q-bio]/Cancer, [SDV.CAN]Life Sciences [q-bio]/Cancer
Abstract: International audience; Importance: The choice between chemotherapy and endocrine therapy as first-line treatment for hormone receptor-positive, ERBB2 (also known as HER2)-negative metastatic breast cancer is usually based on the presence of clinical features associated with a poor prognosis. In this setting, a high circulating tumor cell (CTC) count (≥5 CTCs/7.5 mL) is a strong adverse prognostic factor for overall survival and progression-free survival (PFS).Objective: To compare the efficacy of a clinician-driven treatment choice vs a CTC-driven choice for first-line treatment.Interventions: In the CTC arm, patients received chemotherapy or endocrine therapy according to the CTC count (chemotherapy if ≥5 CTCs/7.5 mL; endocrine therapy if
Published: 2021

40. Multimodal liquid biopsy for early monitoring and outcome prediction of chemotherapy in metastatic breast cancer

Author: Charlotte Proudhon, Jérôme Lemonnier, Anthony Gonçalves, Frédérique Berger, Shufang Renault, Jean-Yves Pierga, François-Clément Bidard, Marie-Laure Tanguy, Christelle Levy, Marc Debled, Isabelle Desmoulins, Elodie Girard, Sylvain Baulande, Coraline Dubot, Christelle Jouannaud, Amanda Bortolini Silveira, Caroline Hego, Benoit Albaud, William Jacot, Maria Rios, Jean-Marc Ferrero, Florence Dalenc, Olivier Tredan, Marie-Ange Mouret-Reynier, Aurore Rampanou, CIC1428 IGR-CURIE, Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Université Paris-Saclay, Institut Curie [Paris], Cancer et génome: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, Mines Paris - PSL (École nationale supérieure des mines de Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Léon Bérard [Lyon], Departement d'Oncologie médicale [Paris], Institut du Cancer de Montpellier (ICM), 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 de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Département d'oncologie médicale, Institut Bergonié [Bordeaux], UNICANCER-UNICANCER, Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Institut Jean Godinot [Reims], UNICANCER, Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), Institut Claudius Regaud, Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département d'oncologie médicale [Centre Georges-François Leclerc], Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), Génétique et Biologie du Développement, Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Université Paris Cité (UPCité), ANR-10-EQPX-0031,FIT,Internet du Futur (des Objets)(2010), ANR-10-INBS-0009,France-Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010), 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), COLO, Mouniati, Internet du Futur (des Objets) - - FIT2010 - ANR-10-EQPX-0031 - EQPX - VALID, Organisation et montée en puissance d'une Infrastructure Nationale de Génomique - - France-Génomique2010 - ANR-10-INBS-0009 - INBS - VALID, Institut Curie [Saint-Cloud], Institut Curie [Paris]-MINES ParisTech - École nationale supérieure des mines de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM), MINES ParisTech - École nationale supérieure des mines de Paris, Université Paris sciences et lettres (PSL), Institut de recherche en cancérologie de Montpellier (IRCM - U896 Inserm - UM1), Université Montpellier 1 (UM1)-CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université de Paris (UP)
Subjects: Oncology, medicine.medical_specialty, Bevacizumab, medicine.medical_treatment, [SDV.CAN]Life Sciences [q-bio]/Cancer, Predictive markers, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, Circulating tumor cell, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, medicine, Pharmacology (medical), Radiology, Nuclear Medicine and imaging, Liquid biopsy, RC254-282, 030304 developmental biology, 0303 health sciences, Chemotherapy, business.industry, GATA3, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, Metastatic breast cancer, 3. Good health, 030220 oncology & carcinogenesis, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Outcome prediction, business, medicine.drug
Abstract: Circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) are two cancer-derived blood biomarkers that inform on patient prognosis and treatment efficacy in breast cancer. We prospectively evaluated the clinical validity of quantifying both CTCs (CellSearch) and ctDNA (targeted next-generation sequencing). Their combined value as prognostic and early monitoring markers was assessed in 198 HER2-negative metastatic breast cancer patients. All patients were included in the prospective multicenter UCBG study COMET (NCT01745757) and treated by first-line chemotherapy with weekly paclitaxel and bevacizumab. Blood samples were obtained at baseline and before the second cycle of chemotherapy. At baseline, CTCs and ctDNA were respectively detected in 72 and 74% of patients and were moderately correlated (Kendall’s τ = 0.3). Only 26 (13%) patients had neither detectable ctDNA nor CTCs. Variants were most frequently observed in TP53 and PIK3CA genes. KMT2C/MLL3 variants detected in ctDNA were significantly associated with a lower CTC count, while the opposite trend was seen with GATA3 alterations. Both CTC and ctDNA levels at baseline and after four weeks of treatment were correlated with survival. For progression-free and overall survival, the best multivariate prognostic model included tumor subtype (triple negative vs other), grade (grade 3 vs other), ctDNA variant allele frequency (VAF) at baseline (per 10% increase), and CTC count at four weeks (≥5CTC/7.5 mL). Overall, this study demonstrates that CTCs and ctDNA have nonoverlapping detection profiles and complementary prognostic values in metastatic breast cancer patients. A comprehensive liquid-biopsy approach may involve simultaneous detection of ctDNA and CTCs.
Published: 2021

41. Review of clinical applications of radiation-enhancing nanoparticles

Author: E. Chajon, Valentin Calugaru, N. Scher, C. Le Tourneau, Sylvie Bonvalot, Juliette Thariat, C. Verry, Institut Curie [Paris], Cancer et génome: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, Mines Paris - PSL (École nationale supérieure des mines de Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Curie - Saint Cloud (ICSC), Centre Eugène Marquis (CRLCC), CHU Grenoble, Synchrotron Radiation for Biomedicine = Rayonnement SynchroTROn pour la Recherche BiomédicalE (STROBE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Radiothérapie [Centre François Baclesse], Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), CCSD, Accord Elsevier, and MINES ParisTech - École nationale supérieure des mines de Paris
Subjects: 0106 biological sciences, Oncology, medicine.medical_specialty, Gadolinium, medicine.medical_treatment, [SDV]Life Sciences [q-bio], lcsh:Biotechnology, chemistry.chemical_element, Review Article, 01 natural sciences, Applied Microbiology and Biotechnology, 03 medical and health sciences, 010608 biotechnology, Internal medicine, lcsh:TP248.13-248.65, medicine, 030304 developmental biology, Radiothérapie, Cancer, Cervical cancer, 0303 health sciences, Radiotherapy, business.industry, Nanoparticules, medicine.disease, Head and neck squamous-cell carcinoma, 3. Good health, Clinical trial, Radiation therapy, [SDV] Life Sciences [q-bio], chemistry, Nanoparticles, Sarcoma, Liver cancer, business, Biotechnology
Abstract: Highlights • Inorganic nanoparticles activated by radiotherapy (RT) increase dose deposition within cancer cells compared to RT alone. • Recently, clinical evidence of the radiation-enhancing effects of NP has emerged. • Two radio-enhancement NP are currently under investigation in clinical trials: hafnium oxide NP and gadolinium-based NP. • So far, 229 patients have been treated with NP and RT for soft tissue sarcoma, head and neck cancers or liver cancer. • Intratumoral hafnium oxide nanoparticles were safe and improved efficacy in locally advanced sarcoma., Purpose Clinical evidence of the radiation-enhancing effects of nanoparticles has emerged. Materials and methods We searched the literature in English and French on PubMed up to October 2019. The search term was “nanoparticle” AND “radiotherapy”, yielding 1270 results. Results The two main NP used in clinical trials were hafnium oxide and gadolinium involving a total of 229 patients. Hafnium oxide NP were used in three phase 1/2 trials on sarcoma, head and neck squamous cell carcinoma or liver cancer and one phase 2/3 trial. There are six ongoing phase 1/2 clinical trials to evaluate the combination of gadolinium-based NP and RT for the treatment of brain metastases and cervical cancer. Conclusion So far, intratumoral hafnium oxide nanoparticles were safe and improved efficacy in locally advanced sarcoma.
Published: 2020

42. PELICAN-IPC 2015-016/Oncodistinct-003: A Prospective, Multicenter, Open-Label, Randomized, Non-Comparative, Phase II Study of Pembrolizumab in Combination With Neo Adjuvant EC-Paclitaxel Regimen in HER2-Negative Inflammatory Breast Cancer

Author: Alexandre Bertucci, François Bertucci, Christophe Zemmour, Florence Lerebours, Jean-Yves Pierga, Christelle Levy, Florence Dalenc, Julien Grenier, Thierry Petit, Marguerite Berline, Anthony Gonçalves, Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Department of Medical Oncology [Saint-Cloud], Institut Curie [Saint-Cloud], Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Institut Claudius Regaud, Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Sainte Catherine [Avignon], Centre Paul Strauss, CRLCC Paul Strauss, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Bertucci, François
Subjects: Oncology, medicine.medical_specialty, Cancer Research, medicine.medical_treatment, Population, immune checkpoint inhibitor, [SDV.CAN]Life Sciences [q-bio]/Cancer, Pembrolizumab, lcsh:RC254-282, Inflammatory breast cancer, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, PDL1, medicine, Clinical endpoint, neoadjuvant therapy, education, skin and connective tissue diseases, Neoadjuvant therapy, education.field_of_study, business.industry, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, Clinical Trial, Clinical trial, Regimen, Tolerability, pembrolizumab, business, inflammatory breast cancer
Abstract: Inflammatory breast cancer (IBC) is a highly aggressive entity with a poor outcome and relative resistance to treatment. Despite progresses achieved during the last decades, the survival remains significantly lower than non-IBC. Recent clinical trials assessing PD-1/PD-L1 inhibitors showed promising results in non-IBC. Pembrolizumab, an anti-PD-1 monoclonal antibody, revolutionized the treatment of different cancers. Several recent studies suggested a potential interest of targeting the immune system in IBC by revealing a more frequent PD-L1 expression and an enriched immune microenvironment when compared with non-IBC. Here, we describe the rationale and design of PELICAN-IPC 2015-016/Oncodistinct-003 trial, an open-label, randomized, non-comparative, phase II study assessing efficacy, and safety of pembrolizumab in combination with anthracycline-containing neoadjuvant chemotherapy in HER2-negative IBC. The trial is ongoing. The primary endpoint is the pCR rate (ypT0/Tis, ypN0) in overall population and the co-primary endpoint is safety profile during a run-in phase. Key secondary objectives include tolerability, invasive disease-free, event-free and overall survivals, as well as collection of tumor and blood samples for translational research.Clinical Trial Registrationhttps://clinicaltrials.gov/ (NCT03515798).
Published: 2020

43. Plasma thymidine kinase 1 activity and outcome of ER+ HER2− metastatic breast cancer patients treated with palbociclib and endocrine therapy

Author: Paul Cottu, Anne Bethune, Anne Donnadieu, Manuel Rodrigues, Marie Laure Tanguy, François-Clément Bidard, Delphine Loirat, Florence Lerebours, Nicolas Kiavue, Dan Rosenblum, Mattias Bergqvist, Jean-Yves Pierga, Etienne Brain, Luc Cabel, Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), and Institut Curie [Saint-Cloud]
Subjects: Oncology, Pyridines, Receptor, ErbB-2, Piperazines, CDK4/6 inhibitor, 0302 clinical medicine, Surgical oncology, Antineoplastic Combined Chemotherapy Protocols, Thymidine kinase 1, Medicine, Prospective Studies, Neoplasm Metastasis, Prospective cohort study, Fulvestrant, Aged, 80 and over, 0303 health sciences, Middle Aged, Prognosis, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Metastatic breast cancer, 3. Good health, Survival Rate, 030220 oncology & carcinogenesis, Letrozole, Biomarker (medicine), Female, Research Article, Adult, medicine.medical_specialty, medicine.drug_class, Breast Neoplasms, [SDV.CAN]Life Sciences [q-bio]/Cancer, Palbociclib, Thymidine Kinase, lcsh:RC254-282, 03 medical and health sciences, Breast cancer, Internal medicine, Biomarkers, Tumor, Humans, 030304 developmental biology, Aged, business.industry, Estrogen Receptor alpha, Biomarker, medicine.disease, Tamoxifen, Estrogen, business
Abstract: Purpose Previous cohort studies have reported plasma TK1 activity (pTKa) as a potential prognostic biomarker in estrogen receptor-positive (ER+) HER2-negative (HER2−) metastatic breast cancer (MBC). In this prospective study, we report here the prognostic impact of pTKa in ER+/HER2− MBC patients treated with endocrine therapy and CDK4/6 inhibitor. Experimental design Patients were included into the prospective, ethics committee-approved ALCINA study (NCT02866149). Eligibility criteria were patients with ER+/HER2− MBC treated at Institut Curie with endocrine therapy and palbociclib. Plasma samples were obtained at baseline and after 4 weeks of treatment. pTKa was quantified by the DiviTum® assay (Biovica, Sweden). Results From May 2016 to August 2018, 103 patients treated with endocrine therapy and palbociclib were included. Patients had received a median of two prior systemic therapies for MBC (range 0–14). Median follow-up was 13.8 months (range 6–31), with median PFS and OS of 9.6 months (95%CI [7.0–11.3]) and 28 months (95%CI [23–not reached]), respectively. Median baseline pTKa was 292 Du/L (range 20–27,312 Du/L, IQR [89–853]). After adjusting for other prognostic factors, baseline pTKa remained an independent prognostic factor for both PFS (HR = 1.3 95%CI [1.1–1.4], p = 0.0005) and OS (HR = 1.3 95%CI [1.2–1.6], p p Conclusion This study demonstrates the clinical validity of pTKa as a new circulating prognostic marker in ER+/HER2− MBC patients treated with endocrine therapy and palbociclib.
Published: 2020

44. Prognostic value of the Residual Cancer Burden index according to breast cancer subtype: Validation on a cohort of BC patients treated by neoadjuvant chemotherapy

Author: Marie Osdoit, Jean-Guillaume Feron, Marick Laé, Jean-Yves Pierga, Florence Lerebours, Clemence Evrevin, Lauren Darrigues, Anne-Sophie Hamy, Fabien Reyal, Lucie Laot, Lucian Topciu, Enora Laas, Diane De Croze, Matthieu Faron, Sonia Rozette, Giang-Thanh Lam, Residual Tumor & Response to Treatment Laboratory [Paris] (RT2Lab), Immunité et cancer (U932), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Medical Oncology [Saint-Cloud], Institut Curie [Saint-Cloud], Department of Surgery [Paris], Université Paris Descartes - Faculté de Médecine (UPD5 Médecine), Université Paris Descartes - Paris 5 (UPD5)-Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris], Department of Tumor Biology [Saint-Cloud], Department of Tumor Biology [Paris], Institut Curie [Paris], Geneva University Hospital (HUG), Department of biostatistics and epidemiology [Villejuif], 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)-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), Oncostat team [Villejuif], Institut Gustave Roussy (IGR), We thank Roche France for financial support for the construction of the Institut Curie neoadjuvant database (NEOREP). Funding was also obtained from the Site de Recherche Integrée en Cancérologie/Institut National du Cancer (Grant No. INCa-DGOS-4654). A-S Hamy-Petit was supported by an ITMO-INSERM-AVIESAN translational cancer research grant., Oncostat (U1018 (Équipe 2)), Institut Gustave Roussy (IGR)-Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, and Bodescot, Myriam
Subjects: 0301 basic medicine, Oncology, Neoplasm, Residual, Receptor, ErbB-2, Residual cancer, medicine.medical_treatment, Cancer Treatment, Triple Negative Breast Neoplasms, Disease, Pathology and Laboratory Medicine, Biochemistry, 0302 clinical medicine, Breast Tumors, Medicine and Health Sciences, Lipid Hormones, Triple negative, Progesterone, Aged, 80 and over, 0303 health sciences, Multidisciplinary, Pharmaceutics, Middle Aged, Prognosis, 3. Good health, 030220 oncology & carcinogenesis, Cohort, Medicine, Female, Adjuvant, Research Article, Clinical Oncology, Adult, medicine.medical_specialty, Clinical Pathology, Science, Residual cancer burden index, Surgical and Invasive Medical Procedures, Breast Neoplasms, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.MHEP.GEO]Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, Cancer Chemotherapy, 03 medical and health sciences, Breast cancer, Drug Therapy, [SDV.CAN] Life Sciences [q-bio]/Cancer, Diagnostic Medicine, Internal medicine, Breast Cancer, medicine, Chemotherapy, Humans, Survival analysis, Aged, Retrospective Studies, 030304 developmental biology, business.industry, Cancers and Neoplasms, Biology and Life Sciences, Estrogens, Retrospective cohort study, Breast cancer subtype, medicine.disease, Survival Analysis, Hormones, [SDV.MHEP.GEO] Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, 030104 developmental biology, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Clinical Medicine, Neoplasm Recurrence, Local, business
Abstract: IntroductionThe Residual Cancer Burden (RCB) quantifies residual disease after neoadjuvant chemotherapy (NAC). Its predictive value has not been validated on large cohorts with long-term follow up. The objective of this work is to independently evaluate the prognostic value of the RCB index depending on BC subtypes (Luminal, HER2-positive and triple negative (TNBCs)).MethodsWe retrospectively evaluated the RCB index on surgical specimens from a cohort of T1-T3NxM0 BC patients treated with NAC between 2002 and 2012. We analyzed the association between RCB index and relapse-free survival (RFS), overall survival (OS) among the global population, after stratification by BC subtypes.Results717 patients were included (luminal BC (n = 222, 31%), TNBC (n = 319, 44.5%), HER2-positive (n = 176, 24.5%)). After a median follow-up of 99.9 months, RCB index was significantly associated with RFS. The RCB-0 patients displayed similar prognosis when compared to the RCB-I group, while patients from the RCB-II and RCB-III classes were at increased risk of relapse (RCB-II versus RCB-0: HR=3.25 CI [2.1-5.1] pversus RCB-0: HR=5.6 CI [3.5-8.9] pHER2-positive cancers; but not for luminal cancers (Pinteraction = 0.07). The prognosis of RCB-III patients was poor (8-years RFS: 52.7%, 95% CI [44.8 – 62.0]) particularly in the TNBC subgroup, where the median RFS was 12.7 months.ConclusionRCB index is a reliable prognostic score. RCB accurately identifies patients at a high risk of recurrence (RCB-III) with TNBC or HER2-positive BC who must be offered second-line adjuvant therapies.
Published: 2020

45. Surgical Margins and Adjuvant Therapies in Malignant Phyllodes Tumors of the Breast: A Multicenter Retrospective Study

Author: Jean-Yves Blay, Sophie Piperno-Neumann, Mehdi Brahmi, Fabien Reyal, Marick Laé, Clémentine Owen, Nicolas Penel, Sébastien Salas, Thibaud Valentin, S. Thezenas, Emmanuelle Bompas, Camille Chakiba, Charles Honoré, Isabelle Ray-Coquard, A. Michot, Nelly Firmin, Mathias Neron, Esma Saada-Bouzid, Christophe Sajous, François Bertucci, Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Centre Léon Bérard [Lyon], Institut du Cancer de Montpellier (ICM), Département d'Oncologie Médicale [Institut Curie, Paris], Institut Curie [Paris], Department of Medical Oncology [Saint-Cloud], Institut Curie [Saint-Cloud], Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Département d'oncologie médicale, Institut Bergonié [Bordeaux], UNICANCER-UNICANCER, UNICANCER, Université de Lille, Département d'hématologie [Gustave Roussy], Institut Gustave Roussy (IGR), Département de chirurgie viscérale [Gustave Roussy], CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital de la Timone [CHU - APHM] (TIMONE), Medical Oncology Department [Nice], Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA)-UNICANCER-Université Côte d'Azur (UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), 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), Département d'oncologie Médicale, and CRLCC Val d'Aurelle - Paul Lamarque
Subjects: Adult, medicine.medical_specialty, Adolescent, medicine.medical_treatment, Breast Neoplasms, [SDV.CAN]Life Sciences [q-bio]/Cancer, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Surgical oncology, Phyllodes Tumor, medicine, Humans, Survival rate, Mastectomy, ComputingMilieux_MISCELLANEOUS, Aged, Retrospective Studies, Aged, 80 and over, Chemotherapy, business.industry, Margins of Excision, Retrospective cohort study, Chemoradiotherapy, Adjuvant, Middle Aged, medicine.disease, Prognosis, Combined Modality Therapy, Surgery, Radiation therapy, Survival Rate, Oncology, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, Female, Sarcoma, Neoplasm Recurrence, Local, business, Chemoradiotherapy, Follow-Up Studies
Abstract: The optimal threshold of surgical margins for breast malignant phyllodes tumors (MPTs) and the impact of adjuvant chemotherapy and radiotherapy were investigated.We conducted a multicenter nationwide retrospective study of all MPT cases with central pathological review within the French Sarcoma Group. Endpoints were local recurrence-free survival (LRFS), metastasis-free survival (MFS), and overall survival (OS) rates.Overall, 212 patients were included in the study. All non-metastatic patients underwent primary surgical treatment, including 58.6% of conservative surgeries. An R0 resection was achieved in 117 patients (59.4%: 26.9% of patients with 1-2 mm margins, 12.2% of patients with 3-7 mm margins, 20.3% of patients with ≥ 8 mm margins). Ninety-four patients (45%) underwent a second surgery (SS) to obtain R0 margins, with a final mastectomy rate of 72.6%. Radiotherapy and chemotherapy were performed in 91 (43.1%) and 23 patients (10.9%), respectively, but were not associated with better outcomes. Mastectomy was significantly associated with better LRFS (p 0.001). Margins of 0, 1, or 2 mm with SS were associated with better MFS (hazard ratio [HR] 0.3, p = 0.005) and OS (HR 0.32, p = 0.005) compared with margins of 0-1-2 mm without SS. Wider margins ( 8 mm) were not superior to margins of 3-7 mm (3-7 mm vs. 8 mm; HR 0.81, p = 0.69). Age (HR 2.14, p = 0.038) and tumor necrosis (HR 1.96, p = 0.047) were found to be poor prognostic factors and were associated with MFS.This study suggests that 3 mm margins are necessary and sufficient for surgical management of MPTs, and emphasizes the importance of SS to obtain clear margins in case of 0-1-2 mm margins. No impact of adjuvant chemotherapy or radiotherapy was detected in this study.
Published: 2020

46. COVID-19 in breast cancer patients: a cohort at the Institut Curie hospitals in the Paris area

Author: Vuagnat, Perrine, Frelaut, Maxime, Ramtohul, Toulsie, Basse, Clémence, Diakite, Sarah, Noret, Aurélien, Bellesoeur, Audrey, Servois, Vincent, Hequet, Delphine, Laas, Enora, Kirova, Youlia M., Cabel, Luc, Pierga, Jean Yves, Alimi, Aurélia, Belotti, Muriel, Bensaoula, Okba, Bertrand, Ophélie, Bilger, Geoffroy, Brain, Étienne G.C., Brisse, Hervé, Buecher, Bruno, Chanas, Laetitia, Chapus, Caroline, Charles-Massar, Isabelle, Chérel, Pascal J.P., Créhange, Gilles, Colas, Christelle, Delhomelle, Hélène, Frederic-Moreau, Thomas, Fourme, Emmanuelle, Fumoleau, Pierre, Gauthier-Villars, Marion, Lantz, Olivier, Lassalle, Sophie, Le Mentec, Marine, Lerebours, Florence, Loirat, Delphine, Minsat, Mathieu, Pauline, Moreau, De Pauw, Antoine, Priour, Maël, Reyal, Fabien, Rouzier, Roman, Saad, Mary, Saule, Claire, Sebbag, Clara, Stoppa-Lyonnet, Dominique, Tardivon, Anne A., Takanen, Silvia, Vanjak, Dominíque, Villy, Marie Charlotte, Vincent-Salomon, Anne, Warcoin, Mathilde, Bozec, Laurence, Paoletti, Xavier, Cottu, Paul Henri, Bidard, François Clément, Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Institut Curie [Paris], Institut Curie [Saint-Cloud], Cancer et génome: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, MINES ParisTech - École nationale supérieure des mines de Paris, and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Survival, medicine.medical_treatment, law.invention, 0302 clinical medicine, Breast cancer, law, Risk Factors, Cause of Death, 030212 general & internal medicine, Lung, Outcome, Mortality rate, Middle Aged, Prognosis, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Intensive care unit, Metastatic breast cancer, 3. Good health, Hospitalization, Treatment Outcome, 030220 oncology & carcinogenesis, RNA, Viral, Female, France, Coronavirus Infections, Research Article, medicine.medical_specialty, Pneumonia, Viral, [SDV.CAN]Life Sciences [q-bio]/Cancer, Breast Neoplasms, lcsh:RC254-282, 03 medical and health sciences, Betacoronavirus, Radiologic sign, Internal medicine, medicine, Humans, Medical history, Pandemics, Aged, COVID-19, SARS-CoV-2, business.industry, Cancer, medicine.disease, Radiation therapy, business, Tomography, X-Ray Computed
Abstract: Background Cancer patients have been reported to be at higher risk of COVID-19 complications and deaths. We report the characteristics and outcome of patients diagnosed with COVID-19 during breast cancer treatment at Institut Curie hospitals (ICH, Paris area, France). Methods An IRB-approved prospective registry was set up at ICH on March 13, 2020, for all breast cancer patients with COVID-19 symptoms or radiologic signs. Registered data included patient history, tumor characteristics and treatments, COVID-19 symptoms, radiological features, and outcome. Data extraction was done on April 25, 2020. COVID-19 patients were defined as those with either a positive RNA test or typical, newly appeared lung CT scan abnormalities. Results Among 15,600 patients actively treated for early or metastatic breast cancer during the last 4 months at ICH, 76 patients with suspected COVID-19 infection were included in the registry and followed. Fifty-nine of these patients were diagnosed with COVID-19 based on viral RNA testing (N = 41) or typical radiologic signs: 37/59 (63%) COVID-19 patients were treated for metastatic breast cancer, and 13/59 (22%) of them were taking corticosteroids daily. Common clinical features mostly consisted of fever and/or cough, while ground-glass opacities were the most common radiologic sign at diagnosis. We found no association between prior radiation therapy fields or extent of radiation therapy sequelae and extent of COVID-19 lung lesions. Twenty-eight of these 59 patients (47%) were hospitalized, and 6 (10%) were transferred to an intensive care unit. At the time of analysis, 45/59 (76%) patients were recovering or had been cured, 10/59 (17%) were still followed, and 4/59 (7%) had died from COVID-19. All 4 patients who died had significant non-cancer comorbidities. In univariate analysis, hypertension and age (> 70) were the two factors associated with a higher risk of intensive care unit admission and/or death. Conclusions This prospective registry analysis suggests that the COVID-19 mortality rate in breast cancer patients depends more on comorbidities than prior radiation therapy or current anti-cancer treatment. Special attention must be paid to comorbidities when estimating the risk of severe COVID-19 in breast cancer patients.
Published: 2020
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47. Radiation therapy to the primary tumor for de novo metastatic breast cancer and overall survival in a retrospective multicenter cohort analysis

Author: Thierry Petit, Brigitte De La Lande, Jean-Marc Ferrero, Audrey Mailliez, Amélie Lusque, Clémentine Jankowski, Nelly Firmin, Florence Dalenc, Elvire Pons-Tostivint, Lionel Uwer, David Pasquier, Marie-Ange Mouret-Reynier, Delphine Mouttet-Boizat, Thomas Filleron, N. Madranges, Anthony Gonçalves, Julien Geffrelot, Youlia M. Kirova, Mario Campone, Agathe Crouzet, Mathieu Robain, Sofia Rivera, Jean-Christophe Eymard, Thibault De La Motte Rouge, C. Courtinard, Nicolas Pouget, Département de radiothérapie oncologique [Paris], Institut Curie [Paris], Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Lutte Contre le Cancer Nantes Atlantique 'René Gauducheau' (CLCC), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Radiothérapie Moléculaire et Innovation Thérapeutique (RaMo-IT), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université Lille Nord de France (COMUE)-UNICANCER, Département d'oncologie Médicale, CRLCC Val d'Aurelle - Paul Lamarque, Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), UFR des Sciences de Santé (Université de Bourgogne), Université de Bourgogne (UB), Centre Eugène Marquis (CRLCC), Department of Surgery [Saint-Cloud], Institut Curie [Saint-Cloud], Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), UNICANCER, Institut Jean Godinot [Reims], Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), Centre Paul Strauss, CRLCC Paul Strauss, Institut Claudius Regaud, Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), and Université de Lille-UNICANCER
Subjects: Oncology, medicine.medical_specialty, Propensity score, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Breast Neoplasms, [SDV.CAN]Life Sciences [q-bio]/Cancer, 030218 nuclear medicine & medical imaging, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Humans, Radiology, Nuclear Medicine and imaging, Progression-free survival, de novo metastatic breast cancer, Retrospective Studies, Models, Statistical, business.industry, Hazard ratio, Locoregional treatment, Hematology, medicine.disease, Exclusive radiotherapy, Metastatic breast cancer, Primary tumor, 3. Good health, Survival Rate, Radiation therapy, 030220 oncology & carcinogenesis, Cohort, Propensity score matching, business, Cohort study
Abstract: The impact of locoregional treatment (LRT) on overall survival (OS) in de novo metastatic breast cancer (dnMBC) is still under debate, with very few data available regarding exclusive radiotherapy (ERT) as a therapeutic modality.We evaluated the impact of ERT, exclusive surgery, or a combination of surgery plus radiotherapy (bimodality therapy, BMT) on survival outcomes in a national real-life dnMBC cohort. The primary and secondary end points were OS and progression free survival (PFS) according to LRT (ERT, exclusive surgery, BMT) and no LRT. Sensitivity analyses were performed using propensity score matched analyses.From 2008 to 2014, 4507 dnMBC patients were identified. Only patients alive and free from progression under systemic therapy at least 1 year after diagnosis were included (n = 1965). Forty-five percent of patients (891/1965) underwent LRT: 41.1% (n = 366) ERT, 13.7% (n = 122) exclusive surgery, and 45.2% (n = 403) BMT. OS adjusted for major prognostic factors was significantly longer in the ERT and BMT group compared with no-LRT group, but not exclusive surgery (hazard ratio (HR) = 0.63, 95% confidence interval (CI) [0.49, 0.80], p 0.001, HR = 0.61, 95%CI [0.47, 0.78], p 0.001 and HR = 0.87, 95%CI [0.61, 1.26], p = 0.466 respectively). Results were similar after matching on a propensity score. ERT, surgery and BMT were all associated with a significantly better PFS in multivariable analysis.ERT was significantly associated with better OS in dnMBC, in the same magnitude as BMT, compared with no-LRT. However, even with statistical models adjusted for known prognostic factors and propensity score analysis, selection biases cannot be eliminated from observational studies.
Published: 2020

48. Contemporary outcomes of metastatic breast cancer among 22,000 women from the multicentre ESME cohort 2008–2016

Author: Laurence Vanlemmens, Marc Debled, Magali Lacroix-Triki, Christelle Levy, David Pérol, Lionel Uwer, Elise Deluche, Véronique Diéras, Thierry Petit, Veronique Lorgis, Thomas Bachelot, Simone Mathoulin-Pélissier, Anne Patsouris, Mathieu Robain, Jean Marc Ferrero, Marie Ange Mouret-Reynier, C. Courtinard, Florence Dalenc, Etienne Brain, Alison Antoine, C. Lefeuvre-Plesse, Marianne Leheurteur, Christelle Jouannaud, William Jacot, Anthony Gonçalves, Suzette Delaloge, Audrey Lardy-Cleaud, CHU Limoges, Oncogénèse et progression tumorale, Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Léon Bérard [Lyon], Medical Oncology Department, Salah Azaiz Institute, Department of Medical Oncology [Saint-Cloud], Institut Curie [Saint-Cloud], Service d'Oncologie Médicale, Institut Bergonié [Bordeaux], UNICANCER-UNICANCER, Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER, Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Institut Claudius Regaud, Senescence Escape and Soluble Markers of Cancer Progression (CRCINA-ÉQUIPE 12), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Service d'Oncologie médicale [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Service d'Oncologie Médicale [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université Lille Nord de France (COMUE)-UNICANCER, Department of Medical Oncology, CRLCC Eugène Marquis (CRLCC), Plateforme de génétique moléculaire des cancers d'Aquitaine, Centre Paul Strauss, CRLCC Paul Strauss, Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), CRLCC Haute Normandie-Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Département de Biologie et de Pathologie, Department of Biostatistics, Institut Curie [Paris], Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), and Université de Lille-UNICANCER
Subjects: 0301 basic medicine, Oncology, Cancer Research, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Real life, [SDV.CAN]Life Sciences [q-bio]/Cancer, 03 medical and health sciences, 0302 clinical medicine, Medical economics, Internal medicine, HER2, Epidemiology, Overall survival, medicine, skin and connective tissue diseases, Observational database, Subtypes, business.industry, Cancer, medicine.disease, Metastatic breast cancer, Confidence interval, 3. Good health, 030104 developmental biology, 030220 oncology & carcinogenesis, Cohort, business
Abstract: Aim Real-world data inform the outcome comparisons and help the development of new therapeutic strategies. To this end, we aimed to describe the full characteristics and outcomes in the Epidemiological Strategy and Medical Economics (ESME) cohort, a large national contemporary observational database of patients with metastatic breast cancer (MBC). Methods Women aged ≥18 years with newly diagnosed MBC and who initiated MBC treatment between January 2008 and December 2016 in one of the 18 French Comprehensive Cancer Centers (N = 22,109) were included. We assessed the full patients’ characteristics, first-line treatments, overall survival (OS) and first-line progression-free survival, as well as updated prognostic factors in the whole cohort and among the 3 major subtypes: hormone receptor positive and HER2-negative (HR+/HER2−, n = 13,656), HER2-positive (HER2+, n = 4017) and triple-negative (n = 2963) tumours. Results The median OS of the whole cohort was 39.5 months (95% confidence interval [CI], 38.7–40.3). Five-year OS was 33.8%. OS differed significantly between the 3 subtypes (p Conclusions The ESME program represents a unique large-scale real-life cohort on MBC. This study highlights important situations of high medical need within MBC patients. Database registration clinicaltrials.gov Identifier NCT032753.
Published: 2020

49. Taking care of older patients with cancer in the context of COVID-19 pandemic

Author: Rabia Boulahssass, Tristan Cudennec, Loic Mourey, Elena Paillaud, Pierre Soubeyran, Elisabeth Carola, Leila Bengrine Lefevre, Laure de Decker, Claire Falandry, Etienne Brain, Département d'oncologie médicale, Institut Claudius Regaud, Geriatrics Unit [Pierre-Bénite], Université de Lyon-Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Médecine Aiguë Gériatrique [Nantes], Université de Nantes (UN), Société Francophone d’OncoGériatrie [Saint-Herblain] (SoFOG), Centre hospitalier universitaire de Nantes (CHU Nantes), Geriatric Coordination Unit for Geriatric Oncology [Nice], Centre Hospitalier Universitaire de Nice (CHU Nice), Pôle d'Oncologie Médicale [Creil], Groupe Hospitalier Public du Sud de l'Oise [Creil] (GHPSO), Département d'oncologie médicale [Centre Georges-François Leclerc], Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER, Service de Médecine Gériatrique [Boulogne-Billancourt], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Antoine Béclère [Clamart], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Saclay, Department of Medical Oncology [Saint-Cloud], Institut Curie [Saint-Cloud], Geriatric Oncology Unit [Paris], 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), Clinical Epidemiology and Ageing Unit [Créteil], Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Department of Medical Oncology [Bordeaux], Institut Bergonié [Bordeaux], UNICANCER-UNICANCER-Université de Bordeaux (UB), Actions for OnCogenesis understanding and Target Identification in ONcology (ACTION), UNICANCER-UNICANCER-Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), and Bodescot, Myriam
Subjects: Gerontology, 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), Pneumonia, Viral, MEDLINE, Context (language use), [SDV.CAN]Life Sciences [q-bio]/Cancer, 030204 cardiovascular system & hematology, 03 medical and health sciences, Betacoronavirus, 0302 clinical medicine, Older patients, [SDV.CAN] Life Sciences [q-bio]/Cancer, Neoplasms, Pandemic, medicine, Humans, Pandemics, ComputingMilieux_MISCELLANEOUS, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MHEP.GEG] Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, business.industry, SARS-CoV-2, [SDV.MHEP.GEG]Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, Cancer, COVID-19, medicine.disease, 3. Good health, Oncology, 030220 oncology & carcinogenesis, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, business, Coronavirus Infections
Abstract: International audience
Published: 2020

50. Lymphome de Hodgkin concomitant d'une tuberculose, un challenge thérapeutique pour une prise en charge pluridisciplinaire

Author: Thibaut Cassou-Mounat, Alice Boilève, Frédérique Kuhnowski, Youlia M. Kirova, Nina Jehanno, Département d'Oncologie Médicale [Institut Curie, Paris], Institut Curie [Paris], Service d'Hématologie [Institut Curie], Département de médecine nucléaire (Institut Curie, Saint-Cloud), and Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)
Subjects: Adult, Male, Organs at Risk, medicine.medical_specialty, Tuberculosis, PET/CT, medicine.medical_treatment, Antitubercular Agents, [SDV.CAN]Life Sciences [q-bio]/Cancer, Context (language use), Vinblastine, Risk Assessment, 03 medical and health sciences, Bleomycin, Colonic Diseases, 0302 clinical medicine, hemic and lymphatic diseases, Positron Emission Tomography Computed Tomography, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Radiology, Nuclear Medicine and imaging, Helical TomoTherapy®, Lung, Tuberculosis, Pulmonary, PET-CT, Chemotherapy, business.industry, medicine.disease, Hodgkin Disease, 3. Good health, Lymphoma, Radiation therapy, Dacarbazine, tuberculosis, Oncology, Tuberculosis, Gastrointestinal, Doxorubicin, 030220 oncology & carcinogenesis, Concomitant, Hypermetabolism, Radiology, Lymph Nodes, Radiotherapy, Intensity-Modulated, business, Tomography, X-Ray Computed, Hodgkin lymphoma
Abstract: International audience; Hodgkin lymphoma (HL) is a disease characterized by a high curability rate, and the treatment benefit-risk balance must be carefully addressed to achieve complete disease control with low risk of long-term toxicities. Most patients are treated with a combination of chemotherapy and radiotherapy, after disease staging and response to treatment evaluated by FDG PET/CT. We report the case of a 28-year-old patient concomitantly diagnosed of a Hodgkin lymphoma and active tuberculosis. Initial staging was difficult due to pulmonary and abdominal tuberculosis localization that induced FDG PET/CT hypermetabolism. Anti-tuberculosis treatment was first started, allowing secondary an early accurate Hodgkin lymphoma staging by FDG PET/CT. The patient was then treated by chemotherapy and radiotherapy. Helical TomoTherapy® was used with involved site (IS) irradiation volume was performed to decrease the high doses to organs-at-risk (OAR), especially lungs in this context of tuberculosis.
Published: 2020

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