Author: "CRLCC Paul Strauss" / Topic: 030220 oncology & carcinogenesis - Searchworks@Jio Institute Digital Library Search Results

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107 results on '"CRLCC Paul Strauss"'

1. 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

2. Dosimetric comparison of mono-isocentric and multi-isocentric plans for oligobrain metastases: A single institutional experience

Author: N. Wegner, R. Matthis, L. Kuntz, S. Lutz, Centre Paul Strauss, CRLCC Paul Strauss, Department of Radiation Oncology [Munich], and Ludwig-Maximilians-Universität München (LMU)
Subjects: Adult, Male, Dose-volume histogram, [SDV]Life Sciences [q-bio], Stereotactic radiotherapy, 03 medical and health sciences, 0302 clinical medicine, Humans, Arc therapy, Medicine, Radiology, Nuclear Medicine and imaging, Radiation treatment planning, Aged, Aged, 80 and over, Tumor size, Brain Neoplasms, business.industry, Radiotherapy Planning, Computer-Assisted, Brain, Radiotherapy Dosage, Middle Aged, Volumetric modulated arc therapy, 3. Good health, Conformity index, Oncology, 030220 oncology & carcinogenesis, Female, Radiotherapy, Intensity-Modulated, Nuclear medicine, business
Abstract: To compare dosimetric plans for the treatments of oligobrains metastases (2-6) using mono-isocentric arc therapy and multi-isocentric volumetric modulated arc therapy (VMAT).A total of sixteen patients with multiple brain metastases were selected. Prescription dose was between 24 and 15Gy depending on the tumor size. For every patient,arctherapy and VMAT plans were generated respectively, with Elements Multiple Brain Mets SRS version 2.0 (BrainLab) and Eclipse SRS Treatment Planning Systeme version 15.5. The conformity index (CI), homogeinity index (HI), gradient index (GI), dose volume histogram for each organs at risk, total Monitor Units were evaluated.For coverage of the PTV, mono-isocentric plans showed a better CI and a better GI than multi-isocentric plans, respectively CI of 1.18±0.11 vs 1.41±0.20 (P0.01), and GI of 3.55±0.59 vs 4.03±1.20 (P0.01). Homogeneity index was not better with mono-isocentric plans, with respectively HI 24.32±3.87 vs 14.05±4.46 (P=1). For organs at risk, there were no statistical differences between mono and multi-isocentric plans for both eyes, both lenses, both optic nerves, chiasma, brainstem, and hippocampi.VMono-isocentric plans had a better conformity index and gradient index than multi-isocentric plans for the treatment of multiple brain metastases. Moreover, mono-isocentric techniques gave fewer doses to normal brain and used less monitor units than multi-isocentric techniques.
Published: 2020

3. Diagnostic chest X-rays and breast cancer risk among women with a hereditary predisposition to breast cancer unexplained by a BRCA1 or BRCA2 mutation

Author: Michel Longy, Christine Maugard, Elisabeth Luporsi, Capucine Delnatte, Séverine Eon-Marchais, Marion Gauthier-Villars, Juana Beauvallet, Noura Mebirouk, Muriel Belotti, Alain Lortholary, Sophie Lejeune-Dumoulin, Christine Lasset, Isabelle Mortemousque, Yves-Jean Bignon, François Eisinger, Sylvie Mazoyer, Valérie Bonadona, Jean-Marc Limacher, Anne Tardivon, Paul Gesta, Sandra Fert-Ferrer, Fabienne Lesueur, Dorothée Le Gal, Jean Chiesa, Florent Soubrier, Pascaline Berthet, Laurence Faivre, Bruno Buecher, Nadine Andrieu, Juliette Coignard, Julie Tinat, Thierry Frebourg, Isabelle Coupier, Sophie Giraud, Laure Barjhoux, Catherine Noguès, Séverine Audebert-Bellanger, Claude Adenis-Lavignasse, Chrystelle Colas, Maximiliano Ribeiro Guerra, Laurence Venat-Bouvet, Eve Cavaciuti, Anne Floquet, Pascal Pujol, Francesca Damiola, Anne Fajac, Jean-Pierre Fricker, Hélène Dreyfus, Dominique Stoppa-Lyonnet, Marie-Gabrielle Dondon, Laurence Gladieff, Olivier Caron, 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 [Paris], Université Paris sciences et lettres (PSL), Federal University of Juiz de Fora (UFIJ), Institut Gustave Roussy (IGR), AP-HP. Université Paris Saclay, Hôpital Arnaud de Villeneuve [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), 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 Catherine-de-Sienne [Nantes] (CCS), Centre Paul Strauss, CRLCC Paul Strauss, Centre Hospitalier Georges Renon [Niort] (CH Georges Renon Niort), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), 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), CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Centre hospitalier régional Metz-Thionville (CHR Metz-Thionville), Hôpital de Mercy, Centre René Gauducheau, CRLCC René Gauducheau, 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), Centre Léon Bérard [Lyon], Les Hôpitaux Universitaires de Strasbourg (HUS), Institut Bergonié [Bordeaux], Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA), Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), Ramsay Générale de Santé - Hôpital Privé La Louvière, Hôpital Dupuytren [CHU Limoges], Institut Sainte Catherine [Avignon], hôpital couple-enfant [CHU Grenoble Alpes], 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), Hôpital Bretonneau, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Hôpital Morvan [Brest], CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hospices Civils de Lyon (HCL), Groupement Hospitalier Lyon-Est (GHE), Clinique de Génétique médicale Guy Fontaine [CHRU LIlle], Hôpital pasteur [Colmar], Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), CHU de Bordeaux Pellegrin [Bordeaux], Centre Hospitalier Métropole Savoie [Chambéry], Hôpital René HUGUENIN (Saint-Cloud), CHU Rouen, Normandie Université (NU), Hôpital Edouard Herriot [CHU - HCL], Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), 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), Unité de génétique et biologie des cancers (U830), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5), MINES ParisTech - École nationale supérieure des mines de Paris, Institut de recherche en cancérologie de Montpellier (IRCM - U896 Inserm - UM1), CRLCC Val d'Aurelle - Paul Lamarque-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 1 (UM1), 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), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de recherche en neurosciences de Lyon (CRNL), 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), 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, 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), and 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)
Subjects: Adult, Risk, Oncology, medicine.medical_specialty, DNA Repair, DNA repair, [SDV]Life Sciences [q-bio], Genes, BRCA2, Genes, BRCA1, Breast Neoplasms, X-ray exposure, Logistic regression, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, Risk Factors, Surgical oncology, Internal medicine, medicine, Genetic predisposition, Humans, Genetic Predisposition to Disease, 030212 general & internal medicine, Risk factor, RC254-282, High-risk population, Pregnancy, DNA repair genes, business.industry, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Cancer, Middle Aged, medicine.disease, 3. Good health, Radiography, [SDV] Life Sciences [q-bio], Low dose, 030220 oncology & carcinogenesis, Mutation, Female, business, Research Article
Abstract: Background Diagnostic ionizing radiation is a risk factor for breast cancer (BC). BC risk increases with increased dose to the chest and decreases with increased age at exposure, with possible effect modification related to familial or genetic predisposition. While chest X-rays increase the BC risk of BRCA1/2 mutation carriers compared to non-carriers, little is known for women with a hereditary predisposition to BC but who tested negative for a BRCA1 or BRCA2 (BRCA1/2) mutation. Methods We evaluated the effect of chest X-rays from diagnostic medical procedures in a dataset composed of 1552 BC cases identified through French family cancer clinics and 1363 unrelated controls. Participants reported their history of X-ray exposures in a detailed questionnaire and were tested for 113 DNA repair genes. Logistic regression and multinomial logistic regression models were used to assess the association with BC. Results Chest X-ray exposure doubled BC risk. A 3% increased BC risk per additional exposure was observed. Being 20 years old or younger at first exposure or being exposed before first full-term pregnancy did not seem to modify this risk. Birth after 1960 or carrying a rare likely deleterious coding variant in a DNA repair gene other than BRCA1/2 modified the effect of chest X-ray exposure. Conclusion Ever/never chest X-ray exposure increases BC risk 2-fold regardless of age at first exposure and, by up to 5-fold when carrying 3 or more rare variants in a DNA repair gene. Further studies are needed to evaluate other DNA repair genes or variants to identify those which could modify radiation sensitivity. Identification of subpopulations that are more or less susceptible to ionizing radiation is important and potentially clinically relevant.
Published: 2021

4. 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

5. First-line pembrolizumab with or without platinum doublet chemotherapy in non-small-cell lung cancer patients with PD-L1 expression ≥50%

Author: Gilles Robinet, Christos Chouaid, Radj Gervais, Roland Schott, Florian Guisier, Chantal Decroisette, Jean-Bernard Auliac, Olivier Bylicki, Charles Ricordel, Laurent Greillier, Maurice Pérol, Benjamin Besse, Renaud Descourt, Hôpital Morvan - CHRU de Brest (CHU - BREST ), Service de Pneumologie [CHI Créteil], CHI Créteil, 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), Centre Léon Bérard [Lyon], Institut Gustave Roussy (IGR), Université Paris-Saclay, Département de médecine oncologique [Gustave Roussy], Méthodes computationnelles pour la prise en charge thérapeutique en oncologie : Optimisation des stratégies par modélisation mécaniste et statistique (COMPO), Inria Sophia Antipolis - Méditerranée (CRISAM), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'oncologie multidisciplinaire innovations thérapeutiques [Hôpital Nord - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital Nord [CHU - APHM], Hôpital d'Instruction des Armées Sainte Anne, Service de Santé des Armées, CHU Pontchaillou [Rennes], Centre d'Investigation Clinique [CHU Rouen] (CIC Rouen), Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Centre Paul Strauss, CRLCC Paul Strauss, Centre Hospitalier Annecy-Genevois [Saint-Julien-en-Genevois], and Hôpital Charles Nicolle [Rouen]-CHU Rouen
Subjects: Adult, Male, Oncology, Cancer Research, medicine.medical_specialty, Lung Neoplasms, First line, medicine.medical_treatment, [SDV.CAN]Life Sciences [q-bio]/Cancer, Pembrolizumab, Antibodies, Monoclonal, Humanized, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, B7-H1 Antigen, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Carcinoma, Non-Small-Cell Lung, PD-L1, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, Humans, Multicenter Studies as Topic, Medicine, Prospective Studies, 030212 general & internal medicine, Lung cancer, Lung, Response Evaluation Criteria in Solid Tumors, Randomized Controlled Trials as Topic, Chemotherapy, biology, business.industry, General Medicine, Middle Aged, medicine.disease, Progression-Free Survival, Clinical trial, Clinical Trials, Phase III as Topic, 030220 oncology & carcinogenesis, Disease Progression, biology.protein, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Pd l1 expression, business, Follow-Up Studies
Abstract: Pembrolizumab plus chemotherapy is currently used in the first-line treatment of advanced non-small-cell lung cancer withoutLay abstract Non-small-cell lung cancer (NSCLC) is the most frequent type of lung cancer. Most NSCLC patients are diagnosed with advanced disease and only 10–15% of them are alive after 5 years. In the absence of specific tumor mutations, the currently recommended treatment is a combination of chemotherapy and immunotherapy with the monoclonal antibody pembrolizumab. The goal of immunotherapy is to prevent cancer from evading the immune system by interacting with molecules expressed at the surface of tumor cells (PD-L1) or immune cells (PD-1). A study comparing chemotherapy plus pembrolizumab versus pembrolizumab alone has never been performed in patients with a high level of PD-L1 expression on tumor cells. Therefore we designed the PERSEE study to compare these treatments in advanced-stage NSCLC patients with PD-L1 expression on ≥50% of tumor cells.
Published: 2021

6. TUMOSPEC: A Nation-Wide Study of Hereditary Breast and Ovarian Cancer Families with a Predicted Pathogenic Variant Identified through Multigene Panel Testing

Author: Celine Garrec, Monique Mozelle-Nivoix, Jérôme Lemonnier, Etienne Rouleau, Tan Dat Nguyen, Dominique Vaur, Elodie Lacaze, Sarah Bonnet-Boissinot, Sophie Nambot, Jean Chiesa, Sophie Giraud, Dominique Stoppa-Lyonnet, Michel Longy, Alain Lortholary, Jean-Marc Rey, Olivier Caron, Christine Lasset, Claude Houdayer, Christine Maugard, Virginie Bubien, Véronique Mari, Marie-Emmanuelle Morin-Meschin, Nadine Andrieu, Nancy Uhrhammer, Louise Crivelli, Hélène Dreyfus, Vincent Goussot, Stephanie Chieze-Valéro, Nicolas Sevenet, Lisa Golmard, Séverine Eon-Marchais, Mathilde Martinez, Isabelle Coupier, Marie-Gabrielle Dondon, Odile Béra, Paul Vilquin, Capucine Delnatte, Odile Cohen-Haguenauer, Cornel Popovici, Christine Toulas, Laurence Gladieff, Marie-Agnès Collonge-Rame, Chrystelle Colas, Paul Gesta, Catherine Noguès, Fanny Brayotel, Audrey Mailliez, Fabienne Lesueur, Julie Tinat, Marie Bidart, Yves-Jean Bignon, Florence Coulet, Nadia Boutry-Kryza, Fabienne Prieur, Juana Beauvallet, Philippe Denizeau, 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), Institut Curie [Paris], Institut Gustave Roussy (IGR), Génétique (Biologie pathologie), Département de biologie et pathologie médicales [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Hôtel-Dieu de Nantes, CHU Rouen, Normandie Université (NU), 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 Jean Godinot [Reims], UNICANCER, Centre Eugène Marquis (CRLCC), Institut de Cancérologie de Strasbourg Europe (ICANS), Centre Paul Strauss, CRLCC Paul Strauss, Institut Bergonié [Bordeaux], Actions for OnCogenesis understanding and Target Identification in ONcology (ACTION), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Bordeaux Segalen - Bordeaux 2-Institut Bergonié [Bordeaux], UNICANCER-UNICANCER, Centre Hospitalier Georges Renon [Niort] (CH Georges Renon Niort), Genetic and Immunology Medical Institute (GIMI), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), 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), CHU de Saint-Étienne Hôpital Nord [Saint Etienne], Hôpital Nord (Saint Etienne), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), CHU Bordeaux [Bordeaux], Centre Catherine-de-Sienne [Nantes] (CCS), Hôpital privé du Confluent [Nantes], Institut Sainte Catherine [Avignon], hôpital couple-enfant [CHU Grenoble Alpes], Centre Hospitalier Universitaire [Grenoble] (CHU), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre Hospitalier de Troyes, Hospices Civils de Lyon (HCL), Groupement Hospitalier Lyon-Est (GHE), Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Hôpital Sud [CHU Rennes], CHU Pontchaillou [Rennes], Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA), Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), Immunologie humaine, physiopathologie & immunothérapie (HIPI (UMR_S_976 / U976)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université Lille Nord de France (COMUE)-UNICANCER, Hôpital Arnaud de Villeneuve [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), 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), Groupe Hospitalier du Havre, CHU de la Martinique [Fort de France], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CRLCC René Gauducheau, 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), 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), Centre Léon Bérard [Lyon], 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), Unité de génétique et biologie des cancers (U830), Institut Curie [Paris]-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 médical de Bligny, Onco-génétique, Département de médecine oncologique [Gustave Roussy], COLO, Mouniati, 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), 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), UNICANCER-UNICANCER-Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de médecine génomique et d’immunothérapie (Genomic and Immunotherapy Medical Institute) (institut GIMI), UNICANCER-UNICANCER-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-FHU TRANSLAD (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Université de Lille-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), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), 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), UNICANCER-UNICANCER-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-FHU TRANSLAD (CHU de Dijon), and Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)
Subjects: 0301 basic medicine, Cancer Research, medicine.medical_specialty, Sequencing data, [SDV.CAN]Life Sciences [q-bio]/Cancer, Context (language use), [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, [SDV.MHEP.GEO]Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, 030105 genetics & heredity, Article, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Care plan, Internal medicine, Epidemiology, medicine, RC254-282, Genetic testing, medicine.diagnostic_test, business.industry, Cancer, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, 3. Good health, genetic predisposition to breast and ovarian cancer, [SDV.MHEP.GEO] Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Oncology, 030220 oncology & carcinogenesis, multigene panels, Cancer risk, Ovarian cancer, business, cancer risk estimate, penetrance of pathogenic variants
Abstract: Simple Summary TUMOSPEC was designed for estimating the risk of cancer for carriers of a predicted pathogenic variant (PPV) in a gene usually tested in a hereditary breast and ovarian cancer context. Index cases are enrolled consecutively among patients who undergo genetic testing as part of their care plan in France. First- and second-degree relatives and cousins of PPV carriers are invited to participate whether they are affected by cancer or not, and are tested for the familial PPV. Genetic, clinical, family and epidemiological data are centralized at the coordinating centre. The three-year feasibility study included 4431 prospective index cases, with 19.1% of them carrying a PPV. This showed that the study logistics are well adapted to clinical and laboratory constraints, and collaboration between partners (clinicians, biologists, coordinating centre and participants) is smooth. Hence, TUMOSPEC is being pursued, with the aim of optimizing clinical management guidelines specific to each gene. Abstract Assessment of age-dependent cancer risk for carriers of a predicted pathogenic variant (PPV) is often hampered by biases in data collection, with a frequent under-representation of cancer-free PPV carriers. TUMOSPEC was designed to estimate the cumulative risk of cancer for carriers of a PPV in a gene that is usually tested in a hereditary breast and ovarian cancer context. Index cases are enrolled consecutively among patients who undergo genetic testing as part of their care plan in France. First- and second-degree relatives and cousins of PPV carriers are invited to participate whether they are affected by cancer or not, and genotyped for the familial PPV. Clinical, family and epidemiological data are collected, and all data including sequencing data are centralized at the coordinating centre. The three-year feasibility study included 4431 prospective index cases, with 19.1% of them carrying a PPV. When invited by the coordinating centre, 65.3% of the relatives of index cases (5.7 relatives per family, on average) accepted the invitation to participate. The study logistics were well adapted to clinical and laboratory constraints, and collaboration between partners (clinicians, biologists, coordinating centre and participants) was smooth. Hence, TUMOSPEC is being pursued, with the aim of optimizing clinical management guidelines specific to each gene.
Published: 2021

7. Cav1/EREG/YAP Axis in the Treatment Resistance of Cav1-Expressing Head and Neck Squamous Cell Carcinoma

Author: Mickaël Burgy, Alicia Thiery, Aude Jehl, Georges Noël, Sonia Ledrappier, Nelly Etienne-Selloum, Hélène Burckel, Christine Macabre, Monique Dontenwill, Ombline Conrad, Alain C. Jung, Marie-Pierre Chenard, François Fasquelle, Véronique Bruban, Christian Borel, Sophie Martin, Carole Mura, Murielle Masson, Mihaela-Alina Onea, Sophie Foppolo, Laboratoire de Bioimagerie et Pathologies (LBP), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Institut de Cancérologie de Strasbourg Europe (ICANS), Equipe 2 'Réponse au Stress Cellulaire & Thérapies Innovantes' / 'Stress Response & Innovative Therapies' (STREINTH - Inserm U1113), Interface de Recherche Fondamentale et Appliquée en Cancérologie (IRFAC - Inserm U1113), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Paul Strauss : Centre Régional de Lutte contre le Cancer (CRLCC)-Fédération de Médecine Translationelle de Strasbourg (FMTS)-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Paul Strauss : Centre Régional de Lutte contre le Cancer (CRLCC)-Fédération de Médecine Translationelle de Strasbourg (FMTS), Biotechnologie et signalisation cellulaire (BSC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut de recherche de l'Ecole de biotechnologie de Strasbourg (IREBS), CRLCC Paul Strauss, Lausanne University Hospital, CHU Strasbourg, Masson, Murielle, and Université de Strasbourg (UNISTRA)-Institut de recherche de l'Ecole de biotechnologie de Strasbourg (IREBS)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Cancer Research, medicine.medical_treatment, Aucun, [SDV.CAN]Life Sciences [q-bio]/Cancer, Sciences du Vivant [q-bio]/Cancer, Article, Targeted therapy, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, medicine, EGFR therapy, RC254-282, Chemotherapy, Cetuximab, biology, business.industry, Head and neck cancer, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, biomarkers, medicine.disease, Head and neck squamous-cell carcinoma, 3. Good health, Radiation therapy, stomatognathic diseases, 030104 developmental biology, Oncology, Apoptosis, 030220 oncology & carcinogenesis, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Cancer research, biology.protein, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, head and neck cancer, Antibody, business, medicine.drug
Abstract: Simple Summary The EGFR-targeting antibody cetuximab (CTX) combined with radiotherapy has been proven effective for the treatment of locally advanced head and neck squamous cell carcinoma (LA-HNSCC). Due to resistance to CTX, some patients do not benefit from the treatment and recurrence is observed. As caveolin-1 (Cav1) has been reported to affect the EGFR pathway, we aimed to elucidate how it might affect the response to CTX-radiotherapy. We showed that Cav1 expression conferred surviving, growing and motile capacities that protect cells against the combination of CTX-radiotherapy. The protecting effects of Cav1 are mediated by the Cav1/EREG/YAP axis. We also showed in a retrospective study that a high expression of Cav1 was predictive of locoregional relapse of LA-HNSCC. Cav1 should be taken into consideration in the future as a prognosis marker to identify the subgroup of advanced HNSCC at higher risk of recurrence, but also to help clinicians to choose the more appropriate therapeutic strategies. Abstract The EGFR-targeting antibody cetuximab (CTX) combined with radiotherapy is the only targeted therapy that has been proven effective for the treatment of locally advanced head and neck squamous cell carcinoma (LA-HNSCC). Recurrence arises in 50% of patients with HNSCC in the years following treatment. In clinicopathological practice, it is difficult to assign patients to classes of risk because no reliable biomarkers are available to predict the outcome of HPV-unrelated HNSCC. In the present study, we investigated the role of Caveolin-1 (Cav1) in the sensitivity of HNSCC cell lines to CTX-radiotherapy that might predict HNSCC relapse. Ctrl- and Cav-1-overexpressing HNSCC cell lines were exposed to solvent, CTX, or irradiation, or exposed to CTX before irradiation. Growth, clonogenicity, cell cycle progression, apoptosis, metabolism and signaling pathways were analyzed. Cav1 expression was analyzed in 173 tumor samples and correlated to locoregional recurrence and overall survival. We showed that Cav1-overexpressing cells demonstrate better survival capacities and remain proliferative and motile when exposed to CTX-radiotherapy. Resistance is mediated by the Cav1/EREG/YAP axis. Patients whose tumors overexpressed Cav1 experienced regional recurrence a few years after adjuvant radiotherapy ± chemotherapy. Together, our observations suggest that a high expression of Cav1 might be predictive of locoregional relapse of LA-HNSCC.
Published: 2021
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8. Real‐life activity of eribulin mesylate among metastatic breast cancer patients in the multicenter national observational ESME program

Author: Audrey Mailliez, Jean-Marc Ferrero, Marie Chaix, Julien Fraisse, Mathieu Robain, Sophie Gourgou, Paul Cottu, Anthony Gonçalves, Claudia Lefeuvre, Marc Debled, Séverine Guiu, Jean-Christophe Eymard, Christelle Levy, C. Courtinard, Mario Campone, Marianne Leheurteur, Pierre-Etienne Heudel, William Jacot, Lionel Uwer, Barbara Pistilli, Florence Dalenc, Thierry Petit, Marie-Ange Mouret-Reynier, 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 du Cancer de Montpellier (ICM), CRLC Val d'Aurelle-Paul Lamarque, CRLCC Val d'Aurelle - Paul Lamarque, Centre Léon Bérard [Lyon], Université de Montpellier (UM), 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 Gustave Roussy (IGR), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), 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), CRLCC 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), Institut Curie [Paris], Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), and Université Lille Nord de France (COMUE)-UNICANCER
Subjects: Oncology, Cancer Research, medicine.medical_specialty, Receptor, ErbB-2, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Population, Antineoplastic Agents, Breast Neoplasms, Disease-Free Survival, law.invention, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Breast cancer, real-life cohort, Randomized controlled trial, law, Internal medicine, Humans, Medicine, Furans, education, eribulin, Aged, Retrospective Studies, Chemotherapy, education.field_of_study, business.industry, Ketones, Middle Aged, medicine.disease, Metastatic breast cancer, Progression-Free Survival, 3. Good health, chemistry, 030220 oncology & carcinogenesis, Concomitant, Cohort, Female, metastatic breast cancer, business, Eribulin
Abstract: International audience; Eribulin mesylate (EM) was recently approved for metastatic breast cancer (MBC) chemotherapy (CT) in late lines by the FDA, with debated results in second line. We evaluated outcomes in breast cancer patients receiving EM as second, third and fourth line in a national real-life cohort of 16,703 consecutive MBC patients initiating their first metastatic therapeutic line between 2008 and 2014. Primary and secondary objectives were overall survival (OS) and progression-free survival (PFS). An imbalance was seen for HER2+ tumors and concomitant anti-HER2 targeted therapies use, we thus performed a subanalysis in HER2- patients. PFS and OS were significantly better in EM patients in third and fourth lines, compared to "Other chemotherapies" patients (PFS: 4.14 vs. 3.02 months, p = 0.0010; 3.61 vs. 2.53 months, p = 0.0102, third and fourth-line; OS: 11.27 vs. 7.65 months, p = 0.0001; 10.91 vs. 5.95 months, p
Published: 2019

9. Early evaluation using a radiomic signature of unresectable hepatic metastases to predict outcome in patients with colorectal cancer treated with FOLFIRI and bevacizumab

Author: Anthony, Dohan, Benoit, Gallix, Boris, Guiu, Karine, Le Malicot, Caroline, Reinhold, Philippe, Soyer, Jaafar, Bennouna, Francois, Ghiringhelli, Emilie, Barbier, Valérie, Boige, Julien, Taieb, Olivier, Bouché, Eric, François, Jean-Marc, Phelip, Christian, Borel, Roger, Faroux, Jean-Francois, Seitz, Stéphane, Jacquot, Meher, Ben Abdelghani, Faiza, Khemissa-Akouz, Dominique, Genet, Jean Louis, Jouve, Yves, Rinaldi, Françoise, Desseigne, Patrick, Texereau, Etienne, Suc, Come, Lepage, Thomas, Aparicio, Christine, Hoeffel, Zied, Ladhib, Service de Radiologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), McGill University Health Center [Montreal] (MUHC), l'Institut de Recherche contre les Cancers de l'Appareil Digestif (IRCAD), CHU Strasbourg, Département radiologie diagnostique et interventionnelle Saint Eloi [CHRU Montpellier], Pôle Digestif [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Fédération Francophone de la Cancérologie Digestive, FFCD, Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, Equipe EPICAD (LNC - U1231), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Institut Gustave Roussy (IGR), Oncologie digestive, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Université de Paris - UFR Médecine Paris Centre [Santé] (UP Médecine Paris Centre), Université de Paris (UP), 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), Centre Hospitalier Universitaire de Reims (CHU Reims), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Centre Paul Strauss, CRLCC Paul Strauss, Service de chirurgie digestive (CH de La Roche-sur-Yon), Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon, Service d'oncologie digestive et hépato-gastro-entérologie [Hôpital de la Timone - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Centre de Cancérologie du Grand Montpellier (CCGM), Centre Hospitalier Saint Jean de Perpignan, Polyclinique de Limoges - site François Chénieux [Limoges], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Hôpital Européen [Fondation Ambroise Paré - Marseille], Centre Léon Bérard [Lyon], CHU Mont de Marsan, Clinique Saint-Jean Languedoc [Toulouse] (CSJL), Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Centre de Recherche en Sciences et Technologies de l'Information et de la Communication - EA 3804 (CRESTIC), Université de Reims Champagne-Ardenne (URCA), and Hôpital Maison Blanche
Subjects: Male, Oncology, Colorectal cancer, medicine.medical_treatment, Leucovorin, Kaplan-Meier Estimate, 030218 nuclear medicine & medical imaging, MESH: Camptothecin / administration & dosage, Camptothecin / analogs & derivatives, Colorectal Neoplasms / drug therapy, Colorectal Neoplasms / pathology, Computational Biology, Female, 0302 clinical medicine, Antineoplastic Combined Chemotherapy Protocols, Prospective Studies, Prospective cohort study, Aged, 80 and over, Liver Neoplasms, Gastroenterology, MESH: Radiographic Image Interpretation, Computer-Assisted, Response Evaluation Criteria in Solid Tumors, Survival Rate, Tomography, X-Ray Computed, Middle Aged, Bevacizumab, 030220 oncology & carcinogenesis, Cohort, FOLFIRI, Radiographic Image Interpretation, Computer-Assisted, Fluorouracil, Colorectal Neoplasms, Clinical decision making, medicine.drug, Adult, medicine.medical_specialty, [SDV.CAN]Life Sciences [q-bio]/Cancer, MESH: Fluorouracil / administration & dosage, Humans, Leucovorin / administration & dosage, Liver Neoplasms / diagnostic imaging, Computerised image analysis, 03 medical and health sciences, Colorectal metastases, MESH: Adult, Antineoplastic Combined Chemotherapy Protocols / administration & dosage, Bevacizumab / administration & dosage, Camptothecin / administration & dosage, Predictive Value of Tests, Internal medicine, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, medicine, Chemotherapy, MESH: Liver Neoplasms / secondary, Aged, business.industry, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, medicine.disease, Log-rank test, Irinotecan, Camptothecin, business
Abstract: PurposeThe objective of this study was to build and validate a radiomic signature to predict early a poor outcome using baseline and 2-month evaluation CT and to compare it to the RECIST1·1 and morphological criteria defined by changes in homogeneity and borders.MethodsThis study is an ancillary study from the PRODIGE-9 multicentre prospective study for which 491 patients with metastatic colorectal cancer (mCRC) treated by 5-fluorouracil, leucovorin and irinotecan (FOLFIRI) and bevacizumab had been analysed. In 230 patients, computed texture analysis was performed on the dominant liver lesion (DLL) at baseline and 2 months after chemotherapy. RECIST1·1 evaluation was performed at 6 months. A radiomic signature (Survival PrEdiction in patients treated by FOLFIRI and bevacizumab for mCRC using contrast-enhanced CT TextuRe Analysis (SPECTRA) Score) combining the significant predictive features was built using multivariable Cox analysis in 120 patients, then locked, and validated in 110 patients. Overall survival (OS) was estimated with the Kaplan-Meier method and compared between groups with the logrank test. An external validation was performed in another cohort of 40 patients from the PRODIGE 20 Trial.ResultsIn the training cohort, the significant predictive features for OS were: decrease in sum of the target liver lesions (STL), (adjusted hasard-ratio(aHR)=13·7, p=1·93×10–7), decrease in kurtosis (ssf=4) (aHR=1·08, p=0·001) and high baseline density of DLL, (aHR=0·98, p0·02 had a lower OS in the training cohort (pConclusionA radiomic signature (combining decrease in STL, density and computed texture analysis of the DLL) at baseline and 2-month CT was able to predict OS, and identify good responders better than RECIST1.1 criteria in patients with mCRC treated by FOLFIRI and bevacizumab as a first-line treatment. This tool should now be validated by further prospective studies.Trial registrationClinicaltrial.gov identifier of the PRODIGE 9 study: NCT00952029.Clinicaltrial.gov identifier of the PRODIGE 20 study: NCT01900717.
Published: 2019

10. Molecular apocrine tumours in EORTC 10994/BIG 1-00 phase III study: pathological response after neoadjuvant chemotherapy and clinical outcomes

Author: Richard Iggo, Jean-Michel Picquenot, Denis Larsimont, Véronique Becette, Jonas Bergh, Gaëtan MacGrogan, Jeremy Thomas, Olivier Kerdraon, Leen Slaets, David Cameron, Fanny Pommeret, C. Poncet, Jean-Christophe Tille, Frédéric Bibeau, Hervé Bonnefoi, Alexandre Bodmer, Jean-Pierre Ghnassia, Thomas Grellety, Donnat, Martin, Validation et identification de nouvelles cibles en oncologie (VINCO), Institut Bergonié [Bordeaux], UNICANCER-UNICANCER-Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), CIC Bordeaux, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de pathologie, UNICANCER-UNICANCER, UNICANCER, European Organisation for Research and Treatment of Cancer [Bruxelles] (EORTC), European Cancer Organisation [Bruxelles] (ECCO), Actions for OnCogenesis understanding and Target Identification in ONcology (ACTION), Institut Jules Bordet [Bruxelles], Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Hôpital René HUGUENIN (Saint-Cloud), Centre René Gauducheau, CRLCC René Gauducheau, 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 Paul Strauss, CRLCC Paul Strauss, Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Cancer Research UK Edinburgh Centre [Edinburgh, UK], University of Edinburgh-MRC Institute of Genetics and Molecular Medicine [Edinburgh] (IGMM), University of Edinburgh-Medical Research Council-Medical Research Council, Hôpitaux Universitaires de Genève (HUG), Department of Oncology-Pathology [Karolinska Institutet], Karolinska Institutet [Stockholm], Bordeaux PharmacoEpi, Inserm CIC1401, Université de Bordeaux, Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Bergonié [Bordeaux], UNICANCER-UNICANCER-Université Bordeaux Segalen - Bordeaux 2, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Bordeaux Segalen - Bordeaux 2-Institut Bergonié [Bordeaux], and Swiss Group for Clinical Cancer Research (SAKK)
Subjects: Oncology, Cancer Research, medicine.medical_specialty, Receptor, ErbB-2, Concordance, medicine.medical_treatment, Breast Neoplasms, [SDV.CAN]Life Sciences [q-bio]/Cancer, ddc:616.07, Disease-Free Survival, Article, 03 medical and health sciences, Breast cancer, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Survival rate, Chemotherapy, business.industry, Gene Expression Profiling, Apocrine, medicine.disease, Immunohistochemistry, Subtyping, 3. Good health, Cancérologie, ErbB Receptors, Survival Rate, Clinical trial, Biological sciences, Treatment Outcome, Receptors, Estrogen, Chemotherapy, Adjuvant, Receptors, Androgen, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, 030220 oncology & carcinogenesis, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Female, Receptors, Progesterone, business
Abstract: Background: We explored, within the EORTC10994 study, the outcomes for patients with molecular apocrine (MA) breast cancer, and defined immunohistochemistry (IHC) as androgen-receptor (AR) positive, oestrogen (ER) and progesterone (PR) negative. We also assessed the concordance between IHC and gene expression arrays (GEA) in the identification of MA cancers. Methods: Centrally assessed biopsies for AR, ER, PR, HER2 and Ki67 by IHC were classified into six subtypes: MA, triple-negative (TN) basal-like, luminal A, luminal B HER2 negative, luminal B HER2 positive and “other”. The two main objectives were the pCR rates and survival outcomes in the overall MA subtype (and further divided by HER2 status) and the remaining five subtypes. Results: IHC subtyping was obtained in 846 eligible patients. Ninety-three (11%) tumours were classified as the MA subtype. Both IHC and GEA data were available for 64 patients. In this subset, IHC concordance was 88.3% in identifying MA tumours compared with GEA. Within the MA subtype, pCR was observed in 33.3% of the patients (95% CI: 29.4–43.9) and the 5-year recurrence-free interval was 59.2% (95% CI: 48.2–68.6). Patients with MA and TN basal-like tumours have lower survival outcomes. Conclusions: Irrespective of their HER2 status, the prognosis for MA tumours remains poor and adjuvant trials evaluating anti-androgens should be considered., SCOPUS: ar.j, info:eu-repo/semantics/published
Published: 2019

11. A DNA Repair and Cell Cycle Gene Expression Signature in Pediatric High-Grade Gliomas: Prognostic and Therapeutic Value

Author: Eric Guérin, Hélène Burckel, Georges Noël, Benoit Lhermitte, Quentin Fuchs, David Castel, Marie Pierre Chenard, Olivier Poch, Eric Van Dyck, Laetitia Poidevin, Laurence Choulier, Monique Dontenwill, Petr V. Nazarov, Natacha Entz-Werle, Laboratoire de Bioimagerie et Pathologies (LBP), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), CHU Strasbourg, Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie (ICube), 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), CRBS - Centre de Recherche en Biomédecine de Strasbourg (Inserm UMS38/UNISTRA), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Luxembourg Institute of Health (LIH), Institut de Cancérologie de Strasbourg Europe (ICANS), Université de Strasbourg (UNISTRA), UNICANCER, 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), Vectorologie et thérapeutiques anti-cancéreuses [Villejuif] (UMR 8203), Centre National de la Recherche Scientifique (CNRS)-Institut Gustave Roussy (IGR)-Université Paris-Sud - Paris 11 (UP11), 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), Centre de Recherche en Biomédecine de Strasbourg (CRBS), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Centre National de la Recherche Scientifique (CNRS), and univOAK, Archive ouverte
Subjects: [INFO.INFO-AI] Computer Science [cs]/Artificial Intelligence [cs.AI], 0301 basic medicine, Cancer Research, pediatric high-grade gliomas, DNA damage repair, prognostic clustering, PARP1, XRCC1, DNA repair, DNA damage, Biology, Article, [INFO.INFO-AI]Computer Science [cs]/Artificial Intelligence [cs.AI], Transcriptome, 03 medical and health sciences, 0302 clinical medicine, Radioresistance, Gene expression, RC254-282, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Cell cycle, Cell Cycle Gene, 3. Good health, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, Cancer research
Abstract: Simple Summary Pediatric high-grade gliomas are incurable brain tumors for which there is a critical need for new therapeutic strategies as well as treatment-predictive biomarkers. This study examined the expression of DNA repair and cell cycle genes in pediatric high-grade gliomas with distinct driving mutations. The aim is to propose a novel classification of these tumors based on sub-groups exposing therapeutic vulnerabilities. Several DNA repair factors were identified that might become new diagnostic markers. Abstract Background: Pediatric high-grade gliomas (pHGGs) are the leading cause of mortality in pediatric neuro-oncology, displaying frequent resistance to standard therapies. Profiling DNA repair and cell cycle gene expression has recently been proposed as a strategy to classify adult glioblastomas. To improve our understanding of the DNA damage response pathways that operate in pHGGs and the vulnerabilities that these pathways might expose, we sought to identify and characterize a specific DNA repair and cell-cycle gene expression signature of pHGGs. Methods: Transcriptomic analyses were performed to identify a DNA repair and cell-cycle gene expression signature able to discriminate pHGGs (n = 6) from low-grade gliomas (n = 10). This signature was compared to related signatures already established. We used the pHGG signature to explore already transcriptomic datasets of DIPGs and sus-tentorial pHGGs. Finally, we examined the expression of key proteins of the pHGG signature in 21 pHGG diagnostic samples and nine paired relapses. Functional inhibition of one DNA repair factor was carried out in four patients who derived H3.3 K27M mutant cell lines. Results: We identified a 28-gene expression signature of DNA repair and cell cycle that clustered pHGGs cohorts, in particular sus-tentorial locations, in two groups. Differential protein expression levels of PARP1 and XRCC1 were associated to TP53 mutations and TOP2A amplification and linked significantly to the more radioresistant pHGGs displaying the worst outcome. Using patient-derived cell lines, we showed that the PARP-1/XRCC1 expression balance might be correlated with resistance to PARP1 inhibition. Conclusion: We provide evidence that PARP1 overexpression, associated to XRCC1 expression, TP53 mutations, and TOP2A amplification, is a new theranostic and potential therapeutic target.
Published: 2021

12. Breast cancer patients treated with intrathecal therapy for leptomeningeal metastases in a large real-life database

Author: Lionel Uwer, Paule Augereau, Thierry Petit, Matthieu Carton, C. Levy, L. Larrouquere, Luc Cabel, M.-A. Mouret-Reynier, Florence Dalenc, M. Carausu, C. Lefeuvre-Plesse, Michaël Chevrot, Amélie Darlix, M. Campone, Benjamin Verret, A. Gonçalves, Jean-David Fumet, M. Leheurteur, Marc Debled, C. Courtinard, J-M Ferrero, Christelle Jouannaud, David Pasquier, Institut Curie [Paris], Institut du Cancer de Montpellier (ICM), Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université Lille Nord de France (COMUE)-UNICANCER, Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Institut Bergonié [Bordeaux], UNICANCER, 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 Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Institut Claudius Regaud, Institut Gustave Roussy (IGR), Département de médecine oncologique [Gustave Roussy], Centre René Gauducheau [Saint-Herblain] (CRLCC Nantes-Atlantique), Centre Régional de Lutte Contre le Cancer Nantes-Atlantique, Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), Université Côte d'Azur (UCA)-UNICANCER, Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), Centre Eugène Marquis (CRLCC), Centre Paul Strauss, CRLCC Paul Strauss, Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), Institut Jean Godinot [Reims], Centre Léon Bérard [Lyon], Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Lille-UNICANCER, 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), UNICANCER-Université Côte d'Azur (UCA), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), and Admin, Oskar
Subjects: Cancer Research, Population, Breast Neoplasms, computer.software_genre, 03 medical and health sciences, intrathecal therapy, 0302 clinical medicine, Breast cancer, breast cancer, leptomeningeal metastasis, cohort study, Medicine, Humans, Breast, education, Survival rate, Original Research, education.field_of_study, Database, business.industry, Proportional hazards model, Mortality rate, Hazard ratio, Middle Aged, medicine.disease, Prognosis, Metastatic breast cancer, 3. Good health, Oncology, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, 030220 oncology & carcinogenesis, Concomitant, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Female, Neoplasm Recurrence, Local, business, computer, Meningeal Carcinomatosis, 030217 neurology & neurosurgery
Abstract: Background Leptomeningeal metastasis (LM) is a rare complication of metastatic breast cancer (MBC), with high morbidity/mortality rates. Our study aimed to describe the largest-to-date real-life population of MBC patients treated with intrathecal (IT) therapy and to evaluate prognostic models. Methods The Epidemiological Strategy and Medical Economics (ESME) MBC database (NCT03275311) includes all consecutive patients who have initiated treatment for MBC since 2008. Overall survival (OS) of patients treated with IT therapy was estimated using the Kaplan–Meier method. Prognostic models were constructed using Cox proportional hazards models. Performance was evaluated using C-index and calibration plots. Results Of the 22 266 patients included in the database between 2008 and 2016, 312 received IT therapy and were selected for our analysis. Compared with non-IT-treated patients, IT-treated patients were younger at MBC relapse (median age: 52 years versus 61 years) and more often had lobular histology (23.4% versus 12.7%) or triple-negative subtype (24.7% versus 13.3%) (all P < 0.001). Median OS was 4.5 months [95% confidence interval (CI) 3.8-5.6] and 1-year survival rate was 25.6%. Significant prognostic factors associated with poorer outcome on multivariable analysis were triple-negative subtype (hazard ratio 1.81, 95% CI 1.32-2.47), treatment line ≥3 (hazard ratio 1.88, 95% CI 1.30-2.73), ≥3 other metastatic sites (hazard ratio 1.33, 95% CI 1.01-1.74) and IT cytarabine or thiotepa versus methotrexate (hazard ratio 1.68, 95% CI 1.28-2.22), while concomitant systemic therapy was associated with better OS (hazard ratio 0.47, 95% CI 0.35-0.62) (all P < 0.001). We validated two previously published prognostic scores, the Curie score and the Breast-graded prognostic assessment, both with C-index of 0.57. Conclusions MBC patients with LM treated with IT therapy have a poor prognosis. We could identify a subgroup of patients with better prognosis, when concomitant systemic therapy and IT methotrexate were used., Highlights • The outcome of BC patients with IT-treated LM is poor, with a median OS of 4.5 months. • Concomitant systemic therapy may improve the outcome in IT-treated patients. • Patients treated with IT methotrexate had better outcome than those treated with IT cytarabine/thiotepa. • The Curie and Breast-graded prognostic assessment scores were prognostic for IT-treated patients.
Published: 2021

13. 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

14. Phase III randomized study of carboplatin pemetrexed with or without bevacizumab with initial 'at progression' cerebral radiotherapy in advanced non squamous non-small cell lung cancer with asymptomatic brain metastasis

Author: Anne Marie Chiappa, Isabelle Monnet, Radj Gervais, Christos Chouaid, Alain Vergnenegre, S. Vieillot, Jean Bernard Auliac, Roland Schott, Gilles Robinet, Laurent Greillier, Lionel Falchero, Anne Madroszyk, R. Lamy, Pascal Thomas, Charles Ricordel, Samir Abdiche, Stephane Chouabe, Henri Berard, Chantal Decroisette, CHI Créteil, CHU Limoges, Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Hopital d'instruction des armées Sainte-Anne [Toulon] (HIA), Groupe Hospitalier Bretagne Sud (GHBS), Centre Paul Strauss, CRLCC Paul Strauss, CHU Pontchaillou [Rennes], Centre Hospitalier de Charleville-Mezières, Hôpital de GAP, Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Centre Hospitalier Libourne, CH de Quimper, and Hôpital Nord [CHU - APHM]
Subjects: 0301 basic medicine, Oncology, medicine.medical_specialty, Bevacizumab, medicine.medical_treatment, non-small–cell lung cancer, [SDV.CAN]Life Sciences [q-bio]/Cancer, bevacizumab, Asymptomatic, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, law.invention, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Randomized controlled trial, law, Internal medicine, medicine, Lung cancer, pemetrexed, radiotherapy, RC254-282, cerebral metastasis, business.industry, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, Carboplatin, Radiation therapy, 030104 developmental biology, Pemetrexed, chemistry, 030220 oncology & carcinogenesis, medicine.symptom, business, management, medicine.drug, Brain metastasis
Abstract: Background: The role and timing of whole or stereotaxic brain radiotherapy (BR) in patients with advanced non-small cell lung cancer (aNSCLC) and asymptomatic brain metastases (aBMs) are not well established. This study investigates whether deferring BR until cerebral progression was superior to upfront BR for patients with aNSCLC and aBM. Methods: This open-label, multicenter, phase III trial, randomized (1:1) aNSCLC patients with aBMs to receive upfront BR and chemotherapy: platin–pemetrexed and bevacizumab in eligible patients, followed by maintenance pemetrexed with or without bevacizumab, BR arm, or the same chemotherapy with BR only at cerebral progression, chemotherapy (ChT) arm. Primary endpoint was progression-free survival (PFS), secondary endpoints were overall survival (OS), global, extra-cerebral and cerebral objective response rate (ORR), toxicity, and quality of life [ClinicalTrials.gov identifier: NCT02162537]. Results: The trial was stopped early because of slow recruitment. Among 95 included patients, 91 were randomized in 24 centers: 45 to BR and 46 to ChT arms (age: 60 ± 8.1, men: 79%, PS 0/1: 51.7%/48.3%; adenocarcinomas: 92.2%, extra-cerebral metastases: 57.8%, without differences between arms.) Significantly more patients in the BR-arm received BR compare with those in the ChT arm (87% versus 20%; p Conclusion: The significant BR rate difference between the two arms suggests that upfront BR is not mandatory in aNSCLC with aBM but this trial failed to show that deferring BR for aBM is superior in terms of PFS from upfront BR.
Published: 2021

15. Radiosensitizing Pancreatic Cancer with PARP Inhibitor and Gemcitabine: An In Vivo and a Whole-Transcriptome Analysis after Proton or Photon Irradiation

Author: Georges Noël, Hélène Burckel, D. Jarnet, Anaïs Nicol, Waisse Waissi, Matthieu Jung, Marc Rousseau, Centre Léon Bérard [Lyon], Institut de Cancérologie de Strasbourg Europe (ICANS), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA), Département de Radiobiologie, Hadronthérapie et Imagerie Moléculaire (DRHIM-IPHC), Institut Pluridisciplinaire Hubert Curien (IPHC), Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Gaillard, Brigitte, CRLCC Paul Strauss, 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)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), and Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Cancer Research, medicine.medical_treatment, [SDV]Life Sciences [q-bio], pancreatic cancer, DNA repair, lcsh:RC254-282, Article, Olaparib, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, In vivo, Pancreatic cancer, medicine, proton therapy, transcriptome, radiotherapy, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Chemistry, gemcitabine, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, Gemcitabine, 3. Good health, Radiation therapy, [SDV] Life Sciences [q-bio], 030104 developmental biology, PARP inhibitor, Oncology, 030220 oncology & carcinogenesis, Cancer research, Growth inhibition, Chemoradiotherapy, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, medicine.drug
Abstract: Over the past few years, studies have focused on the development of targeted radiosensitizers such as poly(ADP-ribose) polymerase inhibitors. We performed an in vivo study and a whole-transcriptome analysis to determine whether PARP inhibition enhanced gemcitabine-based chemoradiosensitization of pancreatic cancer xenografts, combined with either proton or photon irradiation. NMRI mice bearing MIA PaCa-2 xenografts were treated with olaparib and/or gemcitabine and irradiated with 10 Gy photon or proton. First, a significant growth inhibition was obtained after 10 Gy proton irradiation compared to 10 Gy photon irradiation (p = 0.046). Moreover, the combination of olaparib, gemcitabine and proton therapy significantly sensitized tumor xenografts, compared to gemcitabine (p = 0.05), olaparib (p = 0.034) or proton therapy (p &lt, 0.0001) alone or to the association of olaparib, gemcitabine and radiotherapy (p = 0.024). Simultaneously, whole RNA sequencing profiling showed differentially expressed genes implicated in categories such as DNA repair, type I interferon signaling and cell cycle. Moreover, a large amount of lncRNA was dysregulated after proton therapy, gemcitabine and olaparib. This is the first study showing that addition of olaparib to gemcitabine-based chemoradiotherapy improved significantly local control in vivo, especially after proton therapy. RNA sequencing profiling analysis presented dynamic alteration of transcriptome after chemoradiation and identified a classifier of gemcitabine response.
Published: 2021

16. Impact of body mass index on overall survival in patients with metastatic breast cancer

Author: Audrey Mailliez, Khalil Saleh, Thierry Petit, Christelle Jouannaud, Etienne Brain, Matthieu Carton, Jean Marc Ferrero, Pierre-Etienne Heudel, Elise Deluche, Marc Debled, Anne Patsouris, Anthony Gonçalves, Lionel Uwer, George Emile, Alexia Savignoni, Florence Dalenc, Marianne Leheurteur, C. Courtinard, Lucie Veron, Marie-Ange Mouret-Reynier, Paul Cottu, Véronique Diéras, Véronique D'Hondt, Suzette Delaloge, Sylvain Ladoire, Mathieu Robain, Institut Gustave Roussy (IGR), Oncologie gynécologique, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Institut Curie [Paris], Centre Eugène Marquis (CRLCC), Centre Léon Bérard [Lyon], 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 de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, 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 Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), Université Côte d'Azur (UCA)-UNICANCER, Centre Paul Strauss, 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), Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), Institut Bergonié [Bordeaux], 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 Jean Godinot [Reims], Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), UNICANCER [Paris], CHU Limoges, Université de Lille-UNICANCER, UNICANCER-Université Côte d'Azur (UCA), 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, 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), and UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)
Subjects: MBC, metastatic breast cancer, BMI, body mass index, [SDV]Life Sciences [q-bio], ESME, Epidemio-Strategy-Medical-Economical, Overweight, Body Mass Index, 0302 clinical medicine, Risk Factors, Medicine, Overall survival, 030212 general & internal medicine, Underweight, TNBC, triple negative breast cancer, ComputingMilieux_MISCELLANEOUS, 2. Zero hunger, General Medicine, Prognosis, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Metastatic breast cancer, 3. Good health, [SDV] Life Sciences [q-bio], 030220 oncology & carcinogenesis, Cohort, Original Article, Female, medicine.symptom, medicine.medical_specialty, BC, breast cancer, Breast Neoplasms, lcsh:RC254-282, OS, overall survival, 03 medical and health sciences, BMI, Breast cancer, Internal medicine, Humans, Obesity, Risk factor, Retrospective Studies, business.industry, HR, hormone receptor, Cancer, nutritional and metabolic diseases, medicine.disease, Surgery, business, Body mass index, PFS, progression free-survival
Abstract: Background High Body mass index (BMI) is a risk factor for breast cancer among postmenopausal women and an adverse prognostic factor in early-stage. Little is known about its impact on clinical outcomes in patients with metastatic breast cancer (MBC). Methods The National ESME-MBC observational cohort includes all consecutive patients newly diagnosed with MBC between Jan 2008 and Dec 2016 in the 18 French comprehensive cancer centers. Results Of 22 463 patients in ESME-MBC, 12 999 women had BMI data available at MBC diagnosis. Median BMI was 24.9 kg/m2 (range 12.1–66.5); 20% of women were obese and 5% underweight. Obesity was associated with more de novo MBC, while underweight patients had more aggressive cancer features. Median overall survival (OS) of the BMI cohort was 47.4 months (95% CI [46.2–48.5]) (median follow-up: 48.6 months). Underweight was independently associated with a worse OS (median OS 33 months; HR 1.14, 95%CI, 1.02–1.27) and first line progression-free survival (HR, 1.11; 95%CI, 1.01; 1.22), while overweight or obesity had no effect. Conclusion Overweight and obesity are not associated with poorer outcomes in women with metastatic disease, while underweight appears as an independent adverse prognostic factor., Highlights • This is the first large multicenter cohort reporting BMI’s effect on outcomes among patients with metastatic breast cancer. • Overweight or obese status does not negatively influence outcome of metastatic breast cancer patients, whatever the subtype. • Underweight is a strong negative independent prognostic factor on outcomes, whatever the subtype.
Published: 2021

17. Status of Surgical Management of Borderline Ovarian Tumors in France: are Recommendations Being Followed? Multicentric French Study by the FRANCOGYN Group

Author: Martin Koskas, Justine Gantzer, Pierre Collinet, Thomas Boisramé, Cyrille Huchon, Vincent Lavoué, Eva Sangnier, Emilie Faller, Lobna Ouldamer, Virginie Bund, Cherif Akladios, Geoffroy Canlorbe, Charles Coutant, Martin Demarchi, Cyril Touboul, Pierre-Adrien Bolze, Lise Lecointre, Sofiane Bendifallah, HAL-SU, Gestionnaire, Les Hôpitaux Universitaires de Strasbourg (HUS), 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), L'Institut hospitalo-universitaire de Strasbourg (IHU Strasbourg), Institut National de Recherche en Informatique et en Automatique (Inria)-l'Institut de Recherche contre les Cancers de l'Appareil Digestif (IRCAD)-Les Hôpitaux Universitaires de Strasbourg (HUS)-La Fédération des Crédits Mutuels Centre Est (FCMCE)-L'Association pour la Recherche contre le Cancer (ARC)-La société Karl STORZ, Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Reims (CHU Reims), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Service de Gynécologie-obstétrique et médecine de la reproduction - Maternité [CHU Tenon], CHU Tenon [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), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Hôpital Jeanne de Flandres, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de Chirurgie et Cancérologie Gynécologique et Mammaire [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Centre Hospitalier Intercommunal de Créteil (CHIC), Centre hospitalier intercommunal de Poissy/Saint-Germain-en-Laye - CHIPS [Poissy], Département d'oncologie médicale [Centre Georges-François Leclerc], Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER, Centre Paul Strauss, CRLCC Paul Strauss, CHU Pontchaillou [Rennes], 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), Gynécologie-obstétrique et médecine de la reproduction - Maternité [CHU Tenon], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), centre hospitalier intercommunal de Poissy/Saint-Germain-en-Laye - CHIPS [Poissy], Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-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)-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)-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), Service de chirurgie gynécologique et mammaire [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: medicine.medical_specialty, Referral, [SDV.MHEP.CHI] Life Sciences [q-bio]/Human health and pathology/Surgery, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.MHEP.CHI]Life Sciences [q-bio]/Human health and pathology/Surgery, Carcinoma, Ovarian Epithelial, [SDV.MHEP.GEO]Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Surgical oncology, Biopsy, Humans, Medicine, Laparoscopy, Neoplasm Staging, Retrospective Studies, Ovarian Neoplasms, 030219 obstetrics & reproductive medicine, medicine.diagnostic_test, business.industry, General surgery, Gynecologic Oncology, 3. Good health, Omentectomy, Serous fluid, [SDV.MHEP.GEO] Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, Oncology, 030220 oncology & carcinogenesis, Female, Surgery, France, Borderline ovarian tumors, Neoplasm Recurrence, Local, business, Cohort study
Abstract: Background Borderline ovarian tumors (BOTs) are tumors with a favorable prognosis but whose management by consensus is essential to limit the risk of invasive recurrence. This study aimed to conduct an inventory of surgical practices for BOT in France and to evaluate the conformity of the treatment according to the current French guidelines. Methods This retrospective, multicenter cohort study included nine referral centers of France between January 2001 and December 2018. It analyzed all patients with serous and mucinous BOT who had undergone surgery. A peritoneal staging in accordance with the recommendations was defined by performance of a peritoneal cytology, an omentectomy, and at least one peritoneal biopsy. Results The study included 332 patients. A laparoscopy was performed in 79.5% of the cases. Treatment was conservative in 31.9% of the cases. The recurrence rate was significantly increased after conservative treatment (17.3% vs 3.1%; p < 0.001). Peritoneal cytology was performed for 95.5%, omentectomy for 83.1%, and at least one biopsy for 82.2% of the patients. The overall recurrence rate was 7.8%, and the recurrence was invasive in 1.2% of the cases. No link was found between the recurrence rate and the conformity of peritoneal staging. The overall rate of staging noncompliance was 22.9%. Conclusion The current standards for BOT management seem to be well applied.
Published: 2021

18. Evolution in the real-world therapeutic strategies in more than 20,000 women with breast cancer having received human epidermal growth factor receptor 2–targeted treatments: Results from the french personalized reimbursement model database (2011–2018)

Author: Xavier Pivot, Anne Doly, Julien Manson, L. Samelson, Paul Cottu, Olivier Aujoulat, Hugues Barletta, Nassera Chalabi, Bruno Coudert, David Pérol, Département d'Oncologie Médicale [Institut Curie, Paris], Institut Curie [Paris], Département d'oncologie médicale [Centre Georges-François Leclerc], Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER, Département cancer environnement (Centre Léon Bérard - Lyon), Centre Léon Bérard [Lyon], Université Clermont Auvergne (UCA), Centre Hospitalier René Dubos [Pontoise], Groupe hospitalier de la région de Mulhouse et Sud-Alsace, Hôpital privé Drôme Ardèche, groupe Ramsay générale de santé, site Pasteur, Roche France, CRLCC Paul Strauss, Neuro-Dol (Neuro-Dol), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])
Subjects: Adult, 0301 basic medicine, Oncology, Cancer Research, medicine.medical_specialty, Receptor, ErbB-2, [SDV]Life Sciences [q-bio], Breast Neoplasms, Pharmacy, Antibodies, Monoclonal, Humanized, Young Adult, 03 medical and health sciences, chemistry.chemical_compound, Antineoplastic Agents, Immunological, 0302 clinical medicine, Breast cancer, Trastuzumab, Internal medicine, HER2, Antineoplastic Combined Chemotherapy Protocols, Humans, Medicine, Molecular Targeted Therapy, Stage (cooking), skin and connective tissue diseases, Reimbursement, Trastuzumab emtansine, Aged, Retrospective Studies, Aged, 80 and over, Pertuzumab, Retrospective real-world data study, business.industry, Cancer, Middle Aged, medicine.disease, 3. Good health, 030104 developmental biology, chemistry, 030220 oncology & carcinogenesis, Female, France, business, medicine.drug
Abstract: International audience; Background: There is a growing need for real-world data on cancer treatments usage, especially to assess compliance with recommendations. We developed a French project using hospital data to analyse evolution in the therapeutic strategies implemented in patients with human epidermal growth factor receptor 2 (HER2)-overexpressed (HER2+) breast cancer (BC) and exposed to injectable HER2-targeted therapies, i.e. trastuzumab, pertuzumab or trastuzumab emtansine (T-DM1).Patients and methods: Data from 26,350 women with BC were extracted in September 2018 from the Electronic Pharmacy Record systems of 120 French randomly recruited hospitals. Evolution in the treatments used, and combination regimens were described from 2011, in accordance with the BC stage and treatment line.Results: Overall, 21,119 patients treated since 2011 were analysed: 16,398 patients with early BC (eBC) and 6030 patients with metastatic BC (mBC) including patients treated at both stages. In eBC, 89.2% of patients received trastuzumab combined with at least taxanes (trastuzumab-taxane-anthracycline: 62.6%). Patients with mBC were treated in the first line (80.3%) and/or the second line (40.1%) and/or ≥ the third line (28.3%). After its approval in 2014, pertuzumab was first used in first-line therapy combinations in 67.4% of the total cases, while trastuzumab-taxane decreased from 47.2% to 9.2%. Similarly, T-DM1 was used as the second-line treatment in 53.8% of cases.Conclusions: Given recent changes in available treatments for patients with HER2+ BC, this large French project provides robust information on real-world evolution in therapeutic strategies. Our data suggest there is room for significant improvement in optimal drug utilisation. Such data will be useful to build drug-related indicators for future value-based pricing solutions.
Published: 2020

19. Evolution of overall survival and receipt of new therapies by subtype among 20 446 metastatic breast cancer patients in the 2008-2017 ESME cohort

Author: Thomas Grinda, Marc Debled, Thomas Bachelot, Magali Lacroix-Triki, Paul-Henri Cottu, Audrey Mailliez, Anne Patsouris, Lionel Uwer, Thierry Petit, Isabelle Desmoulins, M. Robain, A. Gonçalves, Etienne Brain, Florence Dalenc, D. Perol, C. Courtinard, Suzette Delaloge, Véronique Diéras, C. Levy, Elise Deluche, C. Blaye, M.-A. Mouret-Reynier, Christelle Jouannaud, William Jacot, Alison Antoine, J-M Ferrero, Florian Clatot, Institut Gustave Roussy (IGR), Centre Léon Bérard [Lyon], Institut du Cancer de Montpellier (ICM), Institut Bergonié [Bordeaux], UNICANCER, Institut Curie [Paris], Centre Eugène Marquis (CRLCC), Institut Claudius Regaud, Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université Lille Nord de France (COMUE)-UNICANCER, Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), 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), Université Côte d'Azur (UCA)-UNICANCER, Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), Centre Paul Strauss, CRLCC Paul Strauss, Institut Jean Godinot [Reims], 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), Département de médecine oncologique [Gustave Roussy], 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), Université de Lille-UNICANCER, Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), and UNICANCER-Université Côte d'Azur (UCA)
Subjects: Oncology, Cancer Research, medicine.medical_specialty, Receptor, ErbB-2, overall survival, [SDV.CAN]Life Sciences [q-bio]/Cancer, Triple Negative Breast Neoplasms, Cohort Studies, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Breast cancer, Internal medicine, HER2, Medicine, Humans, 030212 general & internal medicine, real-life, skin and connective tissue diseases, Retrospective Studies, Original Research, Everolimus, Epidermal Growth Factor, new drugs, business.industry, Cancer, medicine.disease, Metastatic breast cancer, Penetrance, 3. Good health, chemistry, 030220 oncology & carcinogenesis, Cohort, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Pertuzumab, metastatic breast cancer, business, medicine.drug, Eribulin
Abstract: Background Treatment strategies for metastatic breast cancer (MBC) have made great strides over the past 10 years. Real-world data allow us to evaluate the actual benefit of new treatments. ESME (Epidemio-Strategy-Medico-Economical)-MBC, a nationwide observational cohort (NCT03275311), gathers data of all consecutive MBC patients who initiated their treatment in 18 French Cancer Centres since 2008. Patients and methods We evaluated overall survival (OS) in the whole cohort (N = 20 446) and among subtypes: hormone receptor positive, human epidermal growth factor 2 negative (HR+/HER2−; N = 13 590), HER2+ (N = 3919), and triple-negative breast cancer (TNBC; N = 2937). We performed multivariable analyses including year of MBC diagnosis as one of the covariates, to assess the potential OS improvement over time, and we described exposure to newly released drugs at any time during MBC history by year of diagnosis (YOD). Results The median follow-up of the whole cohort was 65.5 months (95% CI 64.6-66.7). Year of metastatic diagnosis appears as a strong independent prognostic factor for OS [Year 2016 HR 0.89 (95% CI 0.82-0.97); P = 0.009, using 2008 as reference]. This effect is driven by the HER2+ subcohort, where it is dramatic [Year 2016 HR 0.52 (95% CI 0.42-0.66); P < 0.001, using 2008 as reference]. YOD had, however, no sustained impact on OS among patients with TNBC [Year 2016 HR 0.93 (95% CI 0.77-1.11); P = 0.41, using 2008 as reference] nor among those with HR+/HER2– MBC [Year 2016 HR 1.02 (95% CI 0.91-1.13); P = 0.41, using 2008 as reference]. While exposure to newly released anti-HER2 therapies appeared very high (e.g. >70% of patients received pertuzumab from 2016 onwards), use of everolimus or eribulin was recorded in less than one-third of HR+/HER2– and TNBC cohorts, respectively, whatever YOD. Conclusion OS has dramatically improved among HER2+ MBC patients, probably in association with the release of several major HER2-directed therapies, whose penetrance was high. This trend was not observed in the other subtypes, but the impact of CDK4/6 inhibitors cannot yet be assessed., Highlights • OS of HER2+ MBC patients keeps improving over time [Year 2016 HR 0.52 (95% CI 0.42-0.66); P < 0.001, using 2008 as reference]. • This effect seems timely related to the release of drugs demonstrated to improve survival in clinical trials. • OS gains observed in real life among HER2+ MBC patients are at least equivalent to those observed in clinical trials. • YOD had no sustained impact on OS among patients with TNBC and luminal MBC. • The impact of CDK4/6 inhibitors cannot yet be assessed in this cohort.
Published: 2020

20. Situation professionnelle à long terme après un cancer : étude réalisée à partir de registres de population

Author: Michel Velten, Idlir Licaj, Florence Joly, Julien Rod, Mariette Mercier, Delphine Klein, François Gernier, Akila Saim, Université de Caen Normandie (UNICAEN), Normandie Université (NU), Unité de recherche interdisciplinaire pour la prévention et le traitement des cancers (ANTICIPE), 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-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de recherche clinique [Centre François Baclesse], Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Service de Pédiatrie Médicale [Caen], Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Progression tumorale et microenvironnement. Approches translationnelles et épidémiologie, Institut Régional du Cancer-Université de Strasbourg (UNISTRA)-CHU Strasbourg-Les Hôpitaux Universitaires de Strasbourg (HUS)-Centre Paul Strauss : Centre Régional de Lutte contre le Cancer (CRLCC), Interface de Recherche Fondamentale et Appliquée en Cancérologie (IRFAC - Inserm U1113), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Paul Strauss : Centre Régional de Lutte contre le Cancer (CRLCC)-Fédération de Médecine Translationelle de Strasbourg (FMTS), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (EA 3181) (CEF2P / CARCINO), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), 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), CCSD, Accord Elsevier, Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Centre Paul Strauss, CRLCC Paul Strauss, Les Hôpitaux Universitaires de Strasbourg (HUS), EA3430, Registre des cancers du Bas-Rhin, Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (UR 3181) (CEF2P / CARCINO), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC)
Subjects: 0301 basic medicine, Gynecology, Quality of life, Cancer Research, medicine.medical_specialty, business.industry, [SDV]Life Sciences [q-bio], Registry-based study, Hematology, General Medicine, 3. Good health, [SDV] Life Sciences [q-bio], 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Oncology, Employment status, 030220 oncology & carcinogenesis, medicine, Radiology, Nuclear Medicine and imaging, business, Cancer
Abstract: Resume Introduction Peu d’etudes ont explore la situation professionnelle a long terme apres un cancer. Notre objectif etait d’etudier le statut d’emploi des patients en longue remission d’un cancer a cinq, dix ou quinze ans apres diagnostic et de le comparer a celui des sujets sans antecedent de cancer. Methodes A partir des donnees d’une etude transversale, realisee aupres de patients en longue remission d’un cancer du sein, du col uterin ou du cancer colorectal tires au sort a partir de trois registres des cancers en France et compares a des sujets sans antecedent de cancer tires au sort sur liste electorale, nous avons selectionne les participants actifs âges de moins de 60 ans au moment de l’enquete. Nous avons etudie le statut d’emploi des cas et des temoins et les facteurs associes a ce statut. Resultats Cinq, dix ou quinze ans apres le diagnostic, nous n’observions pas de difference significative concernant le statut d’emploi entre les cas et les temoins. Parmi les cas, 17 % avaient perdu leur emploi. Etaient associes a une perte d’emploi: un âge plus avance, des revenus plus faibles, un niveau d’education plus bas, un contrat de travail de courte duree, la presence de comorbidites, de fatigue et une qualite de vie plus degradee. Discussion Bien que le statut d’emploi des cas etait comparable a la population temoin, il faut intensifier les efforts pour faciliter le retour a l’emploi des patients en longue remission d’un cancer.
Published: 2020

21. Palliative care delivery according to age in 12,000 women with metastatic breast cancer: Analysis in the multicentre ESME-MBC cohort 2008-2016

Author: Thomas Bachelot, Lionel Uwer, Marianne Leheurteur, Anne Patsouris, Florence Dalenc, Virginie Perotin, Laurence Vanlemmens, Jean S Frenel, Camille Sabathe, Carole Bouleuc, Marie Ange Mouret-Reynier, Suzette Delaloge, C. Courtinard, Anne Jaffre, Anthony Gonçalves, Jean Marc Ferrero, Isabelle Desmoulins, Matthieu Frasca, Jean C Eymard, Thierry Petit, Simone Mathoulin-Pélissier, Angéline Galvin, Christelle Levy, Véronique Diéras, Michaël Chevrot, 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), 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), UNICANCER, Centre Paul Strauss, and CRLCC Paul Strauss
Subjects: 0301 basic medicine, Cancer Research, medicine.medical_specialty, Palliative care, [SDV]Life Sciences [q-bio], Psychological intervention, Breast Neoplasms, [SDV.CAN]Life Sciences [q-bio]/Cancer, History, 21st Century, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Older patients, Internal medicine, parasitic diseases, medicine, Humans, cardiovascular diseases, Neoplasm Metastasis, ComputingMilieux_MISCELLANEOUS, Aged, Inpatient care, business.industry, Palliative Care, Age Factors, Cancer, EPICENE, medicine.disease, Metastatic breast cancer, Confidence interval, 3. Good health, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, Cohort, Female, business
Abstract: Patients with metastatic breast cancer (MBC) often require inpatient palliative care (IPC). However, mounting evidence suggests age-related disparities in palliative care delivery. This study aimed to assess the cumulative incidence function (CIF) of IPC delivery, as well as the influence of age.The national ESME (Epidemio-Strategy-Medical-Economical)-MBC cohort includes consecutive MBC patients treated in 18 French Comprehensive Cancer Centres. ICD-10 palliative care coding was used for IPC identification.Our analysis included 12,375 patients, 5093 (41.2%) of whom were aged 65 or over. The median follow-up was 41.5 months (95% confidence interval [CI], 40.5-42.5). The CIF of IPC was 10.3% (95% CI, 10.2-10.4) and 24.8% (95% CI, 24.7-24.8) at 2 and 8 years, respectively. At 2 years, among triple-negative patients, young patients (65 yo) had a higher CIF of IPC than older patients after adjusting for cancer characteristics, centre and period (65+/65: β = -0.05; 95% CI, -0.08 to -0.01). Among other tumour sub-types, older patients received short-term IPC more frequently than young patients (65+/65: β = 0.02; 95% CI, 0.01 to 0.03). At 8 years, outside large centres, IPC was delivered less frequently to older patients adjusted to cancer characteristics and period (65+/65: β = -0.03; 95% CI, -0.06 to -0.01).We found a relatively low CIF of IPC and that age influenced IPC delivery. Young triple-negative and older non-triple-negative patients needed more short-term IPCs. Older patients diagnosed outside large centres received less long-term IPC. These findings highlight the need for a wider implementation of IPC facilities and for more age-specific interventions.
Published: 2020

22. Calibration of pathogenicity due to variant-induced leaky splicing defects by using BRCA2 exon 3 as a model system

Author: Gaia Castelain, Capucine Delnatte, Pascaline Gaildrat, Myriam Vezain, Laëtitia Meulemans, Nadia Boutry-Kryza, Teresa Sullivan, Dominique Stoppa-Lyonnet, Julie Hauchard, Pascal Pujol, Thierry Frebourg, Séverine Audebert-Bellanger, Daniela Di Giacomo, Danièle Muller, Aurélie Drouet, Hélène Tubeuf, Susan W. Reid, Julie Rondeaux, Mélanie Léoné, Violaine Bourdon, Françoise Bonnet-Dorion, Françoise Révillion, Hélène Larbre, Shyam K. Sharan, Omar Soukarieh, Sandrine M. Caputo, Alice Fiévet, Laurence Venat-Bouvet, Virginie Caux-Moncoutier, Alexandra Martins, Fátima Vaz, Angela R. Solano, Claude Houdayer, Eileen Southon, Chrystelle Colas, Marine Guillaud-Bataille, Linda Cleveland, Sophie Krieger, 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 recherche de l'Institut Curie [Paris], Institut Curie [Paris], Université Paris sciences et lettres (PSL), National Cancer Institute Frederick, Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Unité de génétique et biologie des cancers (U830), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR), Département de biologie et pathologie médicales [Gustave Roussy], Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER, Hospices Civils de Lyon (HCL), Centre hospitalier universitaire de Nantes (CHU Nantes), Actions for OnCogenesis understanding and Target Identification in ONcology (ACTION), Institut Bergonié [Bordeaux], UNICANCER-UNICANCER-Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Institut Jean Godinot [Reims], UNICANCER, Centre Paul Strauss, CRLCC Paul Strauss, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Hôpital Morvan - CHRU de Brest (CHU - BREST ), Hôpital Dupuytren [CHU Limoges], Centro de Educación Médica e Investigaciones Clínicas (CEMIC), and This work was funded by a translational research grant from the French National Cancer Institute and the Direction Générale de l’Offre des Soins (INCa/DGOS, AAP/CFB/CI), by the OpenHealth Institute, the Groupement des Entreprises Fran¸caises dans la Lutte contre le Cancer (Gefluc), the Fédération Hospitalo-Universitaire (FHU) Normandy Centre for Genomic and Personalized Medicine (NGP), the European Union and Region Normandie as well as by the Intramural Research Program from the Center for Cancer Research of the NCI, NIH. Europe gets involved in Normandie with European Regional Development Fund (ERDF). H. Tubeuf was funded by a CIFRE PhD fellowship (#2015/0335) from the French Association Nationale de la Recherche et de la Technologie (ANRT) in the context of a public–private partnership between INSERM and Interactive Biosoftware and by two short-term fellowship from EMBO (#3436) and Cancéropôle Nord-Ouest. J. Hauchard and G. Castelain were sponsored by the French INCa.
Subjects: 0301 basic medicine, Cancer Research, endocrine system diseases, In silico, Genes, BRCA2, [SDV.CAN]Life Sciences [q-bio]/Cancer, Breast Neoplasms, Biology, MESH: Protein Isoforms, Article, 03 medical and health sciences, Exon, Mice, 0302 clinical medicine, Protein-fragment complementation assay, Animals, Humans, Protein Isoforms, MESH: Animals, Genetic Predisposition to Disease, skin and connective tissue diseases, Gene, MESH: Mice, Genetics, Ovarian Neoplasms, MESH: Humans, MESH: Alternative Splicing, MESH: Genetic Predisposition to Disease, RNA, Exons, MESH: Ovarian Neoplasms, Alternative Splicing, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, RNA splicing, Female, Haploinsufficiency, MESH: Exons, MESH: Female, MESH: Breast Neoplasms, MESH: Genes, BRCA2, Minigene
Abstract: BRCA2 is a clinically actionable gene implicated in breast and ovarian cancer predisposition that has become a high priority target for improving the classification of variants of unknown significance (VUS). Among all BRCA2 VUS, those causing partial/leaky splicing defects are the most challenging to classify because the minimal level of full-length (FL) transcripts required for normal function remains to be established. Here, we explored BRCA2 exon 3 (BRCA2e3) as a model for calibrating variant-induced spliceogenicity and estimating thresholds for BRCA2 haploinsufficiency. In silico predictions, minigene splicing assays, patients' RNA analyses, a mouse embryonic stem cell (mESC) complementation assay and retrieval of patient-related information were combined to determine the minimal requirement of FL BRCA2 transcripts. Of 100 BRCA2e3 variants tested in the minigene assay, 64 were found to be spliceogenic, causing mild to severe RNA defects. Splicing defects were also confirmed in patients' RNA when available. Analysis of a neutral leaky variant (c.231T>G) showed that a reduction of approximately 60% of FL BRCA2 transcripts from a mutant allele does not cause any increase in cancer risk. Moreover, data obtained from mESCs suggest that variants causing a decline in FL BRCA2 with approximately 30% of wild-type are not pathogenic, given that mESCs are fully viable and resistant to DNA-damaging agents in those conditions. In contrast, mESCs producing lower relative amounts of FL BRCA2 exhibited either null or hypomorphic phenotypes. Overall, our findings are likely to have broader implications on the interpretation of BRCA2 variants affecting the splicing pattern of other essential exons. Significance: These findings demonstrate that BRCA2 tumor suppressor function tolerates substantial reduction in full-length transcripts, helping to determine the pathogenicity of BRCA2 leaky splicing variants, some of which may not increase cancer risk.
Published: 2020

23. Real-world Evaluation of Oral Vinorelbine in the Treatment of Metastatic Breast Cancer: An ESME-MBC Study

Author: Marie-Ange Mouret-Reynier, Véronique D'Hondt, Audrey Mailliez, Gaëtane Simon, Damien Parent, Silvia Ilie, N. Madranges, Christelle Levy, David Pérol, Gaëlle Chenuc, Pierre Heudel, Thomas Vermeulin, Lionel Uwer, Paule Augereau, Thierry Petit, Suzette Delaloge, Florence Dalenc, Christophe Perrin, Etienne Brain, Jean-Sebastien Frenel, Anthony Gonçalves, Jean-Christophe Eymard, Jean-Marc Ferrero, Mathieu Robain, Marie-Paule Sablin, Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER, 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 Paul Strauss, and CRLCC Paul Strauss
Subjects: Adult, Male, Oncology, Cancer Research, medicine.medical_specialty, Databases, Factual, Combination therapy, [SDV]Life Sciences [q-bio], Population, Administration, Oral, Breast Neoplasms, Vinorelbine, Breast Neoplasms, Male, Capecitabine, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Neoplasm Metastasis, education, ComputingMilieux_MISCELLANEOUS, Aged, Retrospective Studies, 030304 developmental biology, 0303 health sciences, education.field_of_study, business.industry, Cancer, Retrospective cohort study, General Medicine, Middle Aged, medicine.disease, Metastatic breast cancer, Progression-Free Survival, 3. Good health, Clinical trial, 030220 oncology & carcinogenesis, Female, business, medicine.drug
Abstract: Background/aim Vinorelbine is indicated for use in the treatment of MBC as a single agent or in combination but there is little real world data on this molecule and even less on its oral form. We exploited the Unicancer Epidemiology Strategy Medical-Economics (ESME) metastatic breast cancer (MBC) database to investigate current patterns of use of oral vinorelbine (OV), as well as outcomes of patients receiving this drug. Patients and methods Data were collected retrospectively from women and men treated for MBC between 2008 and 2014 at one of 18 French Comprehensive Cancer Centres. The efficacy of OV was evaluated in terms of progression-free (PFS) and overall survival (OS) and treatment duration. The population and patterns of OV usage were also described. Results A total of 1806 patients (11% of the ESME MBC database) were included in this analysis. OV was prescribed as monotherapy (46%) or in combination (29%), especially with capecitabine. mainly in later treatment lines. Median PFS was 3.3 months: 2.9 months for single agent, 3.6 months for combination therapy. Median OS was 40.9 months. Conclusion Real-world data offer complementary results to the data from traditional clinical trials, but they concern a much larger population. In this ESME MBC cohort, OV was only prescribed to a small subset of MBC patients. OV was mainly given as single agent to patients with heavily pre-treated MBC; less commonly, it was co-administered with capecitabine or anti-HER2, in earlier lines of therapy. PFS was modest but in line with previous reports.
Published: 2020

24. Cancer Among Adolescents and Young Adults Between 2000 and 2016 in France: Incidence and Improved Survival

Author: Laetitia Daubisse-Marliac, Brigitte Lacour, Tania d'Almeida, Karima Hammas, Olivier Ganry, Alain Monnereau, Emmanuel Desandes, Nicolas Boissel, Brigitte Trétarre, Isabelle Baldi, Anne-Valérie Guizard, Anne Cowppli-Bony, Patricia Delafosse, Thomas Raze, Jacqueline Clavel, G. Coureau, Michel Velten, Sandrine Plouvier, Gautier Defossez, Xavier Troussard, Simona Bara, Véronique Bouvier, Anne-Sophie Woronoff, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Registre National des Tumeurs Solides de l'Enfant (RNTSE), Equipe 7 : EPICEA - Epidémiologie des cancers de l'enfant et de l'adolescent (CRESS - U1153), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Registre National des Cancers de l'Enfant - National Registry of Childhood Cancers [Villejuif & CHU Nancy] (RNCE), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM), French network of cancer registries [Toulouse] (Francim), Registre des cancers de Loire‐Atlantique et Vendée, Imaging and Longitudinal Investigations to Ameliorate Decision-making [Nantes] (ILIAD), Site de Recherche Intégrée sur le Cancer [Nantes] (SIRIC), Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre hospitalier universitaire de Nantes (CHU Nantes), FRANCIM, Réseau des registres français du cancer, Registre des cancers de l’Isère [CHU de Grenoble], Centre Hospitalier Universitaire [Grenoble] (CHU)-Université Grenoble Alpes (UGA), CRLCC Paul Strauss, Registre des Tumeurs de l'Hérault, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), 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), MethodS in Patients-centered outcomes and HEalth ResEarch (SPHERE), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Université de Nantes (UN)-Université de Nantes (UN), Registre des tumeurs du Doubs et du Territoire de Belfort [CHRU Besançon], Pôle cancérologie (CHRU Besançon), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), CHU Amiens-Picardie, CHirurgie, IMagerie et REgénération tissulaire de l’extrémité céphalique - Caractérisation morphologique et fonctionnelle - UR UPJV 7516 (CHIMERE), Université de Picardie Jules Verne (UPJV), Registre général des cancers de Lille et de sa région (GCS-C2RC), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Hôpital Albert Calmette [Lille], 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), Registre Général des Tumeurs du Calvados, CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-UNICANCER, Unité de recherche interdisciplinaire pour la prévention et le traitement des cancers (ANTICIPE), 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), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM), Registre des cancers de la Manche [CHPC - Site Louis Pasteur], Site Louis Pasteur [CHPC], CH Centre Hospitalier Public du Cotentin (CHPC)-CH Centre Hospitalier Public du Cotentin (CHPC), A&O (Apprentissage et Optimisation) (A&O), Laboratoire Interdisciplinaire des Sciences du Numérique (LISN), Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Science des Données (SDD), Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Algorithmes, Apprentissage et Calcul (AAC), Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Epidémiologie et analyses en santé publique : risques, maladies chroniques et handicaps (LEASP), 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 Hospitalier Universitaire de Toulouse (CHU Toulouse), Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Université Sorbonne Paris Nord, Cancer environnement (EPICENE ), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Registre National des Hémopathies malignes de l'Enfant (RNHE), and Institut de Veille Sanitaire (INVS)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Male, Pediatrics, medicine.medical_specialty, Survival, Adolescent, Lymphoma, [SDV]Life Sciences [q-bio], Population, Improved survival, Adolescents, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Neoplasms, Medicine, Humans, 030212 general & internal medicine, Registries, Young adult, education, Melanoma, Cancer, education.field_of_study, business.industry, Incidence (epidemiology), Incidence, Cancer survival, Neoplasms, Germ Cell and Embryonal, medicine.disease, humanities, Young Adults, Survival Rate, Oncology, 030220 oncology & carcinogenesis, Pediatrics, Perinatology and Child Health, Female, France, Trends, business
Abstract: International audience; Purpose: This study was undertaken to determine cancer survival and describe the spectrum of cancers diagnosed among French adolescent and young adult (AYA) population.Methods: All cases of cancer diagnosed in 15-24 years, recorded by all French population-based registries (18% of the French population), over the 2000-2016 period, were included. Age-standardized incidences rates (ASR), conventional annual percentage change (cAPC) of incidence over time, and 5-year overall survival (5yOS) were calculated.Results: We analyzed 2,734 cancer diagnoses in adolescents and 4,199 in young adults. Overall incidence rates were 231.9/106 in 15-19 year olds and 354.0/106 in 20-24 year olds. The most frequently diagnosed cancers in male AYA were malignant gonadal germ-cell tumors (GCT), Hodgkin lymphoma (HL), and malignant melanoma, and were HL, thyroid carcinoma, and malignant melanoma in females. Cancer incidence was stable over time with a cAPC of 0.8% (p=0.72). For all cancers combined, 5yOS was 86.6% (95%CI: 85.8-87.4), greater than 85% for HL, non-Hodgkin lymphomas (NHL), GCT, thyroid carcinomas, and malignant melanomas, and around 60% and lower for osteosarcomas, Ewing tumors, hepatic carcinomas, and rhabdomyosarcomas. The 5yOS has significantly improved from 2000-2007 to 2008-2015 for all cancers pooled, with a substantial gain of 4% for 15-19 year-olds, and 3% for 20-24 year-olds.Conclusion: Notwithstanding the encouraging results for some cancers, and overall, persistent poorer survivals in AYA were shown compared to children for acute lymphoblastic leukemia, osteosarcoma, Ewing tumor, rhabdomyosarcoma and malignant hepatic tumors. These disparities require further investigation to identify and address the causes of these inferior outcomes.
Published: 2020

25. Anti-MUC1-C Antibody-Conjugated Nanoparticles Potentiate the Efficacy of Fractionated Radiation Therapy

Author: Peter P. Ghoroghchian, Alexandre Detappe, Caining Jin, Marie-Charlotte Diringer, Clelia Mathieu, Vu-Long Tran, Michael P. Agius, Donald Kufe, Olivier Tillement, Xavier Pivot, François Lux, Dana-Farber Cancer Institute [Boston], Centre Paul Strauss, CRLCC Paul Strauss, Formation, élaboration de nanomatériaux et cristaux (FENNEC), Institut Lumière Matière [Villeurbanne] (ILM), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Institut de Cancérologie de Strasbourg Europe (ICANS), Institut Universitaire de France (IUF), and Ministère de l'Education nationale, de l’Enseignement supérieur et de la Recherche (M.E.N.E.S.R.)
Subjects: Cancer Research, Immunoconjugates, Lung Neoplasms, medicine.medical_treatment, Gadolinium, chemistry.chemical_element, Mice, Nude, Triple Negative Breast Neoplasms, Pharmacology, Article, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, [SPI]Engineering Sciences [physics], Mice, 0302 clinical medicine, Pharmacokinetics, In vivo, Cell Line, Tumor, medicine, Tumor Microenvironment, [CHIM]Chemical Sciences, Animals, Humans, Immunologic Factors, Radiology, Nuclear Medicine and imaging, MUC1, ComputingMilieux_MISCELLANEOUS, [PHYS]Physics [physics], Tumor microenvironment, Mice, Inbred BALB C, Radiation, business.industry, Mucin-1, Washout, Antibodies, Monoclonal, 3. Good health, Radiation therapy, Oncology, chemistry, 030220 oncology & carcinogenesis, Nanoparticles, Female, Dose Fractionation, Radiation, business, Conjugate, DNA Damage
Abstract: PURPOSE: Heavy-metal chelators and inorganic nanoparticles (NPs) have been examined as potential radioenhancers to increase the efficacy of external beam radiation therapy for various cancers. Most of these agents have, unfortunately, displayed relatively poor pharmacokinetic properties, which limit the percentage of injected dose (%ID/g) that localizes to tumors and which shorten the window for effective radiation enhancement due to rapid tumor washout. METHODS AND MATERIALS: To address these challenges, we sought to conjugate gadolinium-based ultrasmall (
Published: 2020

26. 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

27. 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

28. 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

29. Leveraging Immunotherapy with Nanomedicine

Author: Mainak Banerjee, Alexandre Detappe, Xavier Pivot, Vincent Mittelheisser, Loïc J. Charbonnière, Jacky G. Goetz, Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Paul Strauss, CRLCC Paul Strauss, Institut de Cancérologie de Strasbourg Europe (ICANS), Département Sciences Analytiques et Interactions Ioniques et Biomoléculaires (DSA-IPHC), Institut Pluridisciplinaire Hubert Curien (IPHC), Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), and Charbonnière, Loïc
Subjects: Pharmacology, 0303 health sciences, business.industry, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Biochemistry (medical), Pharmaceutical Science, Medicine (miscellaneous), Immunotherapy, 3. Good health, [SDV] Life Sciences [q-bio], 03 medical and health sciences, 0302 clinical medicine, Immune system, 030220 oncology & carcinogenesis, medicine, Cancer research, Nanomedicine, Pharmacology (medical), business, Genetics (clinical), 030304 developmental biology
Abstract: International audience; Considerable progress has been made in the development and understanding of immunotherapy, notably with the emergence of novel chimeric antigen receptor T cells (CAR‐T) which changed the perception of personalized therapy. However, cell‐based immunotherapy not only lacks therapeutic efficiency in various solid cancers but also raises concerns related to important side effects. The convergence of immunotherapy and nanomedicine is timely as nanoparticles can now be easily conjugated to various antibodies and peptides enabling outstanding abilities to target specific cell populations in vivo. Here, the state of the art of immunonanotherapy that activates the immune system in vivo, by acting either as vaccines or as tumor microenvironment (TME) activators is described. Then, the development of ex vivo immune‐cell surface labeling strategies is discussed to exploit immune cells as trojan horses and thereby improving the delivery of the therapeutics in the TME. Such a strategy is likely to considerably amplify the efficacy of immunotherapy.
Published: 2020

30. BRCAness, SLFN11, and RB1 loss predict response to topoisomerase I inhibitors in triple-negative breast cancers

Author: Petra ter Brugge, Laetitia Fuhrmann, Fabien Reyal, Rania El-Botty, Thibaut Larcher, Laura Sourd, Sophie Château-Joubert, Agnès Noël, Jean-Luc Servely, Léa Huguet, Ivan Bièche, Pierre Foidart, Jos Jonkers, Philippe La Rosa, Pierre Painsec, Sophie Leboucher, Ludivine Morisset, Fariba Nemati, Georges Lucotte, Elodie Montaudon, Didier Decaudin, Christopher R. Mueller, Florence Coussy, Ahmed Dahmani, Marc-Henri Stern, Marie-France Poupon, Nor Eddine Sounni, Sophie Vacher, Adrien Briaux, Yves Pommier, Anne Vincent Salomon, Elisabetta Marangoni, Cécile Reyes, Tatiana Popova, Translational Research Department,Medical Oncology Department, Genetics Department, Institut Curie, Translational Research Department, BioPôle Alfort, École nationale vétérinaire d'Alfort (ENVA), PSL Research University, UMR3306, Département Physiologie Animale et Systèmes d'Elevage (PHASE), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Physiopathologie Animale et bioThérapie du muscle et du système nerveux (PAnTher), Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Genetics Department, University of Santiago de Compostela, Université Paris sciences et lettres (PSL), 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), U830, Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratory of Tumor and Developmental Biology, Groupe Interdisciplinaire de Génoprotéomique Appliqué-Cancer (GIGA-Cancer), Université de Liège, Translational Research Department, Medical Oncology Department, Department of Pathology, University of Veterinary and Animal Sciences, Lahore, Surgery Department, CRLCC Paul Strauss, U932, Immunity and Cancer, Queen's cancer reserach institute, Queen's University, Division of Molecular Pathology and Cancer Genomics Centre Netherlands, Netherlands Cancer Institute, Developmental Therapeutics Branch and Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, ProdInra, Archive Ouverte, École nationale vétérinaire - Alfort (ENVA), École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Universidade de Santiago de Compostela [Spain] (USC ), 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), Biologie du développement et reproduction (BDR), École nationale vétérinaire d'Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS), Développement et Pathologie du Tissu Musculaire (DPTM), Ecole Nationale Vétérinaire de Nantes-Institut National de la Recherche Agronomique (INRA), PSL Research University, U900, and Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Nantes
Subjects: Anthracycline, DNA repair, Ubiquitin-Protein Ligases, [SDV]Life Sciences [q-bio], Triple Negative Breast Neoplasms, Topoisomerase-I Inhibitor, Irinotecan, Article, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, CHEK1, skin and connective tissue diseases, 030304 developmental biology, 0303 health sciences, biology, Retinoblastoma, business.industry, Topoisomerase, Nuclear Proteins, General Medicine, medicine.disease, eye diseases, 3. Good health, [SDV] Life Sciences [q-bio], Retinoblastoma Binding Proteins, 030220 oncology & carcinogenesis, Cancer research, biology.protein, Topoisomerase I Inhibitors, business, Schlafen family member 11, medicine.drug
Abstract: Topoisomerase I (TOP1) inhibitors trap TOP1 cleavage complexes resulting in DNA double-strand breaks (DSBs) during replication, which are repaired by homologous recombination (HR). Triple-negative breast cancer (TNBC) could be eligible for TOP1 inhibitors given the considerable proportion of tumors with a defect in HR-mediated repair (BRCAness). The TOP1 inhibitor irinotecan was tested in 40 patient-derived xenografts (PDXs) of TNBC. BRCAness was determined with a single-nucleotide polymorphism (SNP) assay, and expression of Schlafen family member 11 (SLFN11) and retinoblastoma transcriptional corepressor 1 (RB1) was evaluated by real-time polymerase chain reaction (RT-PCR) and immunohistochemistry analyses. In addition, the combination of irinotecan and the ataxia telangiectasia and Rad3-related protein (ATR) inhibitor VE-822 was tested in SLFN11-negative PDXs, and two clinical non-camptothecin TOP1 inhibitors (LMP400 and LMP776) were tested. Thirty-eight percent of the TNBC models responded to irinotecan. BRCAness combined with high SLFN11 expression and RB1 loss identified highly sensitive tumors, consistent with the notion that deficiencies in cell cycle checkpoints and DNA repair result in high sensitivity to TOP1 inhibitors. Treatment by the ATR inhibitor VE-822 increased sensitivity to irinotecan in SLFN11-negative PDXs and abolished irinotecan-induced phosphorylation of checkpoint kinase 1 (CHK1). LMP400 (indotecan) and LMP776 (indimitecan) showed high antitumor activity in BRCA1-mutated or BRCAness-positive PDXs. Last, low SLFN11 expression was associated with poor survival in 250 patients with TNBC treated with anthracycline-based chemotherapy. In conclusion, a substantial proportion of TNBC respond to irinotecan. BRCAness, high SLFN11 expression, and RB1 loss are highly predictive of response to irinotecan and the clinical indenoisoquinoline TOP1 inhibitors.
Published: 2020

31. Treatment and outcomes in patients with central nervous system metastases from breast cancer in the real-life ESME MBC cohort

Author: Christelle Jouannaud, David Pasquier, Guillaume Louvel, Jean Marc Ferrero, William Jacot, Jean Sébastien Fresnel, Paule Augereau, Thierry Petit, Marianne Leheurteur, Thomas Bachelot, Jean-David Fumet, Julien Geffrelot, Florence Dalenc, Elise Deluche, Anthony Gonçalves, Paul Cottu, Véronique Diéras, Raphaëlle Mouttet-Audouard, Marie Ange Mouret-Reynier, Julien Fraisse, C. Courtinard, Lionel Uwer, I. Lecouillard, Amélie Darlix, Adeline Petit, Mathieu Robain, Etienne Brain, Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER, Centre de Recherche en Informatique, Signal et Automatique de Lille - UMR 9189 (CRIStAL), Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS), 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), CRLCC Eugène Marquis (CRLCC), Unité de biostatistiques, CRLCC Val d'Aurelle - Paul Lamarque, Department of Medical Oncology [Saint-Cloud], Institut Curie [Saint-Cloud], Département de radiothérapie [Bordeaux], Institut Bergonié [Bordeaux], UNICANCER-UNICANCER, 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), UNICANCER, Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Institut Claudius Regaud, CHU Limoges, 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 Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Département d'oncologie médicale [Centre Georges-François Leclerc], Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), Service de radiothérapie, Département de Recherche Translationnelle, Institut Curie [Paris], Centre Paul Strauss, CRLCC Paul Strauss, Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), CRLCC Jean Godinot, Service d'Oncologie Médicale, CRLCC Haute Normandie-Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Medical Oncology Department, Salah Azaiz Institute, 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), Université Lille Nord de France (COMUE)-UNICANCER, Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), and Département de recherche translationnelle
Subjects: 0301 basic medicine, Cancer Research, medicine.medical_specialty, medicine.medical_treatment, Neurological progression-free survival, [SDV]Life Sciences [q-bio], Breast Neoplasms, [SDV.CAN]Life Sciences [q-bio]/Cancer, Stereotactic radiation therapy, Central Nervous System Neoplasms, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, Internal medicine, Epidemiology, medicine, Humans, skin and connective tissue diseases, Retrospective Studies, Proportional hazards model, business.industry, Retrospective cohort study, Brain metastases, Middle Aged, medicine.disease, Metastatic breast cancer, Progression-Free Survival, 3. Good health, Radiation therapy, Treatment Outcome, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, Cohort, Female, business
Abstract: The aims of the present study were to describe treatment patterns and survival outcomes in patients with central nervous system metastases (CNSM) selected among metastatic breast cancer (MBC) patients included in a retrospective study from the Epidemiological Strategy and Medical Economics (ESME) MBC cohort.Neurological progression-free survival (NPFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Signiﬁcant contributors to NPFS were determined using a multivariate Cox proportional hazards model.After a median follow-up of 42.8 months, of 16 701 patients included in the ESME MBC database, CNSM were diagnosed in 24.6% of patients. The most frequent treatments after diagnosis of CNSM were whole-brain radiotherapy (WBRT) (45.2%) and systemic treatment (59.3%). Median OS and NPFS were 7.9 months (95% CI: 7.2-8.4) and 5.5 months (95% CI: 5.2-5.8), respectively. In multivariate analysis, age70 years (vs50 years; HR = 1.40; 95% CI: 1.24-1.57), triple-negative tumours (vs HER2-/HR+; HR = 1.87; 95% CI: 1.71-2.06), HER2+/HR-tumours (vs HER2-/HR+; HR = 1.14; 95% CI: 1.02-1.27), ≥3 metastatic sites (vs 3; HR = 1.32; 95% CI: 1.21-1.43) and ≥3 previous treatment lines (vs 3; HR = 1.75; 95% CI: 1.56-1.96) were detrimental for NPFS. A time interval between selection and CNSM diagnosis superior to 18 months (vs9 months; HR = 0.88; 95% CI: 0.78-0.98) was associated with longer NPFS.This study describes current treatment patterns of MBC patients in a "real life" setting. Despite advances in stereotactic radiation therapy, most of the patients still received WBRT. More research is warranted to identify patient subsets for tailored treatment strategies.
Published: 2020

32. Single-arm phase II trial to evaluate efficacy and tolerance of regorafenib monotherapy in patients over 70 with previously treated metastatic colorectal adenocarcinoma FFCD 1404 - REGOLD

Author: Gaetan Des Guetz, Thomas Aparicio, Denis Smith, Bruno Valenza, Nathalie Baize, Côme Lepage, Catherine Delbaldo, Denis Père Verge, Olivier Romano, Frédéric Pamoukdjian, Emmanuelle Norguet Monnereau, Anthony Dohan, Claire Falandry, L. Cany, Ariane Darut-Jouve, Christine Le Foll, Pascal Artru, Yves Rinaldi, Carole Monterymard, E. Maillard, Meher Ben Abdelghani, Faiza Khemissa Akouz, Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Clinique Drévon, Service de hépato-gastro-entérologie - cancérologie digestive [CH de Perpignan], Centre Hospitalier Saint Jean de Perpignan, Fédération Francophone de la Cancérologie Digestive, FFCD, Service Biostatistiques et Informatique Médicale (CHU de Dijon) (DIM), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Clinique Jean-Mermoz, Hôpital privé Jean Mermoz, Polyclinique Francheville, Site de Recherche Intégrée en Cancérologie (SIRIC-ONCOLille), Université de Lille, Sciences et Technologies-Université de Lille, Sciences Humaines et Sociales-Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université Lille Nord de France (COMUE)-UNICANCER-Université Lille Nord de France (COMUE)-UNICANCER-Cancéropole Nord-Ouest-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Groupe Hospitalier Diaconesses Croix Saint-Simon, Laboratoire de Biologie Moléculaire de la Cellule (LBMC), 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, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), CRLCC Paul Strauss, IRCER - Axe 1 : procédés céramiques (IRCER-AXE1), Institut de Recherche sur les CERamiques (IRCER), Institut des Procédés Appliqués aux Matériaux (IPAM), Université de Limoges (UNILIM)-Université de Limoges (UNILIM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut des Procédés Appliqués aux Matériaux (IPAM), Université de Limoges (UNILIM)-Université de Limoges (UNILIM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Service de gastro-entérologie (Hôpital Européen de Marseille), Hôpital Européen [Fondation Ambroise Paré - Marseille], Service d'Oncologie médicale [CHU Limoges], CHU Limoges, Service d'hépato-gastroentérologie et cancérologie digestive (CHU de Dijon), Institut de Cancérologie de Bourgogne, Hôpital privé Jean Mermoz [Lyon], Clinique Francheville [Périgueux], Université de Lille-UNICANCER-Université de Lille-UNICANCER-Cancéropole Nord-Ouest-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Hospitalier Intercommunal Fréjus - St Raphaël (CHI Fréjus - St Raphaël), Grand Hôpital de l'Est Francilien (GHEF), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Hôpital de la Timone [CHU - APHM] (TIMONE), CHU Bordeaux [Bordeaux], Hôpital Européen de Marseille (HEM), Service de Gastro entérologie [Hôpital Paris Saint-Joseph], Hôpital Paris Saint-Joseph, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Centre Hospitalier Annecy-Genevois [Saint-Julien-en-Genevois], Hôpital Cochin [AP-HP], Hôpital Dupuytren [CHU Limoges], Hôpital Avicenne [AP-HP], Equipe EPICAD (LNC - U1231), 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)-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), CCSD, Accord Elsevier, 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), Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: medicine.medical_specialty, Colorectal cancer, Pyridines, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Adenocarcinoma, Gastroenterology, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Quality of life, Regorafenib, Internal medicine, medicine, Clinical endpoint, Humans, 030212 general & internal medicine, Adverse effect, Chemotherapy, business.industry, Phenylurea Compounds, medicine.disease, 3. Good health, [SDV] Life Sciences [q-bio], Diarrhea, Oncology, chemistry, 030220 oncology & carcinogenesis, Toxicity, Quality of Life, Geriatrics and Gerontology, medicine.symptom, business, Colorectal Neoplasms
Abstract: International audience; BACKGROUND: Regorafenib significantly increases overall survival (OS) in patients with metastatic colorectal cancer previously treated but gives toxicities. OBJECTIVES: to assess the efficacy and safety of regorafenib at it's approved dose in the older population. PATIENTS AND METHODS: This multicenter single-arm phase II enrolled patients ≥70 years old after the failure of fluoropyrimidine-based chemotherapy, anti-VEGF, and anti-EGFR treatment. The primary endpoint was disease control rate (DCR) 2 months after initiation of regorafenib (160 mg/day, 3 weeks on/1 week off). RESULTS: Forty-three patients were enrolled, with a median age of 77 years. The 2 months DCR was 31.4% in the 35 evaluable patients. For the 42 patients that received at least one dose of regorafenib, median progression-free survival and OS were 2.2 and 7.5 months. The median time to autonomy degradation and quality of life degradation was 3.1 and 3.2 months, respectively. A grade 3-4 treatment-related adverse events was observed in 35/42 patients, notably: fatigue (45.2%), hand-foot skin reaction (19.0%), hypertension (21.4%), and diarrhea (7.1%). There is a trend to achieve DCR in patients ≤80 years and a trend to discontinue the study due to toxicity in patients with ECOG ≥1, over 80 years and with impaired baseline autonomy. CONCLUSION: Treatment with regorafenib in pretreated patients ≥70 years is feasible and demonstrate similar efficacy that was observed in previous studies in young patients. Fatigue is the most frequent severe adverse event. However, caution should be taken for older patients with ECOG ≥1, over 80 years, and with impaired baseline autonomy.
Published: 2020

33. Clinical Medicine Impact of Lymphadenectomy on Survival of Patients with Serous Advanced Ovarian Cancer After Neoadjuvant Chemotherapy: A French National Multicenter Study (FRANCOGYN)

Author: Justine Gantzer, Lise Lecointre, Cherif Akladios, Martin Demarchi, Cyrille Huchon, Vincent Lavoué, Marcos Ballester, Thomas Boisramé, Pierre Collinet, Cyril Touboul, Pierre-Adrien Bolze, Martin Koskas, Geoffroy Canlorbe, Emilie Faller, Charles Coutant, Virginie Bund, Michel Velten, Lobna Ouldamer, Sofiane Bendifallah, Jean-Jacques Baldauf, Les Hôpitaux Universitaires de Strasbourg (HUS), 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)-Centre National de la Recherche Scientifique (CNRS)-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)-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)-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), L'Institut hospitalo-universitaire de Strasbourg (IHU Strasbourg), Institut National de Recherche en Informatique et en Automatique (Inria)-l'Institut de Recherche contre les Cancers de l'Appareil Digestif (IRCAD)-Les Hôpitaux Universitaires de Strasbourg (HUS)-La Fédération des Crédits Mutuels Centre Est (FCMCE)-L'Association pour la Recherche contre le Cancer (ARC)-La société Karl STORZ, Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Gynécologie-obstétrique et médecine de la reproduction - Maternité [CHU Tenon], CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CIC Hôpital Bichat, Institut National de la Santé et de la Recherche Médicale (INSERM)-UFR de Médecine-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Hôpital Jeanne de Flandres, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service d'Oncologie médicale [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Service de chirurgie gynécologique et mammaire [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Intercommunal de Créteil (CHIC), CHI Poissy-Saint-Germain, Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, Centre Paul Strauss, CRLCC Paul Strauss, Groupe Hospitalier Diaconesses Croix Saint-Simon, CHU Pontchaillou [Rennes], 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), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Service de Chirurgie et Cancérologie Gynécologique et Mammaire [CHU Pitié-Salpêtrière], 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), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), AP-HP - Hôpital Bichat - Claude Bernard [Paris], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-UFR de Médecine
Subjects: medicine.medical_specialty, medicine.medical_treatment, Population, lcsh:Medicine, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.MHEP.CHI]Life Sciences [q-bio]/Human health and pathology/Surgery, [SDV.MHEP.GEO]Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, Sciences du Vivant [q-bio]/Cancer, Article, 03 medical and health sciences, 0302 clinical medicine, Ovarian carcinoma, Internal medicine, medicine, systematic lymphadenectomy, 030212 general & internal medicine, education, Chemotherapy, education.field_of_study, business.industry, Proportional hazards model, lcsh:R, General Medicine, Debulking, 3. Good health, ovarian carcinoma, Serous fluid, 030220 oncology & carcinogenesis, Lymphadenectomy, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Cohort study, neoadjuvant chemotherapy
Abstract: Background: The population of interest to this study comprised individuals with advanced-stage ovarian carcinoma who were exposed to neoadjuvant chemotherapy (NAC) followed by interval debulking surgery (IDS). Those who had not received systematic lymphadenectomy (SL, Group 1) were compared to those who had received SL (Group 2). Outcome measures included progression-free survival (PFS), overall survival (OS), and surgical complications. Methods: This was a retrospective, multicenter cohort study in nine referral centers of France between January 2000 and June 2017. OS analysis using the multivariate Cox regression model was performed. PFS and surgery-related morbidity were analyzed. Results: Of the 255 patients included, 100 were in Group 1 and 155 in Group 2. Patient majority was, on average, younger and less comorbid, with predominant R0 surgery in Group 2. Dindo&ndash, Clavien score was similar between the two groups (p = 0.15). Median OS was 26.8 months in Group 2 and 27.6 months in Group 1. SL was not statistically significant on OS (p = 0.7). Median PFS was 18.3 months in Group 2 and 16.6 months in Group 1. SL had positive impact on PFS (p = 0.005). Conclusions: patients who had received SL (Group 2) had significantly higher PFS regardless of node-positivity status when compared to those who had not received SL (Group 1).
Published: 2020

34. Transmission of breast cancer polygenic risk based on single nucleotide polymorphisms

Author: Xavier Pivot, David G. Cox, Julie Henry, Pierre-Etienne Heudel, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Léon Bérard [Lyon], Triangle : action, discours, pensée politique et économique (TRIANGLE), École normale supérieure - Lyon (ENS Lyon)-Université Lumière - Lyon 2 (UL2)-Sciences Po Lyon - Institut d'études politiques de Lyon (IEP Lyon), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Centre National de la Recherche Scientifique (CNRS), Centre Paul Strauss, CRLCC Paul Strauss, Centre National de la Recherche Scientifique (CNRS)-Sciences Po Lyon - Institut d'études politiques de Lyon (IEP Lyon), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Université Lumière - Lyon 2 (UL2)-École normale supérieure - Lyon (ENS Lyon), 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 de Lyon (ENS de Lyon)-Université Lumière - Lyon 2 (UL2)-Sciences Po Lyon - Institut d'études politiques de Lyon (IEP Lyon), and Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Risk, 0301 basic medicine, Multifactorial Inheritance, media_common.quotation_subject, education, Population, Mothers, [SDV.CAN]Life Sciences [q-bio]/Cancer, Breast Neoplasms, Single-nucleotide polymorphism, Polymorphism, Single Nucleotide, Risk Assessment, Nuclear Family, 03 medical and health sciences, breast cancer, 0302 clinical medicine, Breast cancer, Humans, Medicine, Genetic Predisposition to Disease, Nuclear family, Allele frequency, Alleles, media_common, Daughter, education.field_of_study, Framingham Risk Score, business.industry, [SHS.PHIL]Humanities and Social Sciences/Philosophy, General Medicine, medicine.disease, 030104 developmental biology, 030220 oncology & carcinogenesis, Female, Surgery, business, Risk assessment, Demography
Abstract: Aim The goal of the present study was to further refine how polygenic risk scores may be used in a large population and to quantify the transmission of risk score through generations. Methods Allele frequencies from the 1000 Genomes data for 159 single nucleotide polymorphisms associated with breast cancer risk were used. A breast cancer risk score was calculated among 100,000 people. Choosing two “parents” and the alleles they transmit at random, 100,000 “daughters” were simulated. The population was divided by deciles of risk score. Comparing mean risk score in the mother and daughter populations provided information regarding the general relationship at a population level. By examining the distribution of daughter's risk score within each decile of maternal risk score, the transmission was evaluated at the subject level. Results Mean values of risk score were 85.1 (St Dev = 7.5) and 85.0 (St Dev = 7.5) for the populations of mothers and daughters, respectively (mean absolute difference = 0.02, p = 0.48). When examining the transmission of risk score from mothers to daughters in specific deciles of risk, statistically significant differences were observed in all deciles (ranged between 0.001 and Conclusion The relationship at the subject level will not provide information regarding prevention and screening of offspring based on the knowledge of parents' risk score alone. The present results show that risk estimation by polygenic risk scores is personal, and evaluation of risk score is required for each individual.
Published: 2018

35. Cost-effectiveness analysis of stereotactic body radiotherapy and surgery for medically operable early stage non small cell lung cancer

Author: A. Paix, Pierre-Emmanuel Falcoz, Georges Noël, Pierre Levy, Centre Paul Strauss, CRLCC Paul Strauss, Département de Radiations Oncologie [Centre Paul Strauss, Strasbourg], Centre Paul Strauss : Centre Régional de Lutte contre le Cancer (CRLCC), Progression tumorale et microenvironnement. Approches translationnelles et épidémiologie, Université de Strasbourg (UNISTRA)-CHU Strasbourg-Les Hôpitaux Universitaires de Strasbourg (HUS)-Institut Régional du Cancer-Centre Paul Strauss : Centre Régional de Lutte contre le Cancer (CRLCC), Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA), Marqueurs pronostiques et facteurs de régulations des pathologies cardiaques et vasculaires - UFC ( EA 3920) (PCVP / CARDIO), 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), Dpt chirurgie thoracique [CHU Strasbourg], CHU Strasbourg, Service de chirurgie thoracique [Strasbourg], Laboratoire d'Economie de Dauphine (LEDa), Université Paris Dauphine-PSL, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), Laboratoire d'Economie et de Gestion des Organisations de Santé (Legos), and Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Université de Franche-Comté (UFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)
Subjects: Adult, Male, medicine.medical_specialty, Lung Neoplasms, Stereotactic body radiotherapy, Cost-Benefit Analysis, medicine.medical_treatment, 030204 cardiovascular system & hematology, Radiosurgery, 03 medical and health sciences, 0302 clinical medicine, Carcinoma, Non-Small-Cell Lung, Humans, Medicine, Radiology, Nuclear Medicine and imaging, Stage (cooking), Lung cancer, Aged, Neoplasm Staging, Aged, 80 and over, [QFIN]Quantitative Finance [q-fin], business.industry, Cost-effectiveness analysis, Incidence (epidemiology), Hematology, Middle Aged, medicine.disease, Markov Chains, JEL: I - Health, Education, and Welfare/I.I1 - Health/I.I1.I12 - Health Behavior, 3. Good health, Surgery, JEL: I - Health, Education, and Welfare/I.I1 - Health/I.I1.I11 - Analysis of Health Care Markets, Oncology, 030220 oncology & carcinogenesis, Video-assisted thoracoscopic surgery, Lobectomy, Non small cell lung cancer, Female, Non small cell, business, Lung cancer screening
Abstract: Background Projections estimate an increase of 50% of the incidence of lung cancer by 2030. Early-stage non-small cell lung cancer represented 19% of NSCLC cases diagnosed in the US between 2005 and 2011. There is rising evidence in favour of lung cancer screening, which will reduce the occurrence of later-stage lung cancers while raising the incidence of early-stage NSCLC. Current guidelines state that for early-stage NSCLC, surgical resection should be performed, and stereotactic body radiotherapy (SBRT) is an option for patients who are non-medically operable. In this study, we compared the cost-effectiveness of SBRT with lobectomy in medically operable patients. Methods We developed a Markov model based on the survival results of two randomized studies comparing SBRT and video assisted thoracoscopic surgery (VATS) lobectomy in early-stage NSCLC, to describe survival and treatment related complications of patients treated for early-stage NSCLC. This analysis was conducted from the French payer perspective on a lifetime perspective. Utility values, recurrence risks, and costs were adapted from the literature. Deterministic (DSA) and probabilistic (PSA) sensitivity analyses were performed to assess the influence of the assumptions made. Results The Markov model developed was consistent with survival data reported in the pool analysis of the randomized studies. SBRT and lobectomy total costs were 9,234.15€ and 10,726.98€, respectively, and the quality-adjusted life expectancies were 16.35 and 15.80 QALYs, respectively. The DSA, run on every assumption made, revealed that the incremental cost-effectiveness ratio was mainly sensitive to the decrement of utility caused by treatment related complications and initial cost of both surgery and SBRT. The PSA showed that SBRT had the highest probability of cost-effectiveness compared to lobectomy. Conclusions This is the first medico-economic study evaluating SBRT and lobectomy in stage I NSCLC based on randomized studies, and our analyses suggest that SBRT is dominant over lobectomy in operable early-stage NSCLC treatment. Deterministic and probabilistic sensitivity analyses confirmed that this result was robust and that it was not modified by the assumptions made in the Markov model building.
Published: 2018

36. Novel diagnostic tool for prediction of variant spliceogenicity derived from a set of 395 combined in silico/in vitro studies: an international collaborative effort

Author: Gérald Le Gac, Alexandra Martins, Pascaline Gaildrat, Florence Coulet, Françoise Revillon, Antoine Rousselin, Sandrine M. Caputo, Marine Guillaud-Bataille, Chandran Ka, Mélanie Léoné, Nadia Boutry-Kryza, Virginie Caux-Moncoutier, Claude Férec, Capucine Delnatte, Danielle Muller, Grégoire Davy, Amanda B. Spurdle, Maria Rossing, Raphaël Leman, Yann Fichou, Michael T. Parsons, Barbara Wappenschmidt, Violaine Bourdon, Joanna Sokolowska, Nicolas Sevenet, Claude Houdayer, M.-P. Audrézet, Brigitte Bressac-de Paillerets, Françoise Bonnet-Dorion, Sylvie Mazoyer, Gaia Castelain, Sophie Krieger, Laurent Castera, Etienne Rouleau, Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), 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), Génétique, génomique fonctionnelle et biotechnologies (UMR 1078) (GGB), EFS-Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), 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), Université Paris Descartes - Paris 5 (UPD5), Université Sorbonne Paris Cité (USPC), Institut Curie [Paris], Unité Mixte de Génétique Constitutionnelle des Cancers Fréquents, Centre Léon Bérard [Lyon]-Hospices Civils de Lyon (HCL), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Validation et identification de nouvelles cibles en oncologie (VINCO), Institut Bergonié [Bordeaux], UNICANCER-UNICANCER-Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Génétique (Biologie pathologie), Département de biologie et pathologie médicales [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), University Hospital of Cologne [Cologne], IT University of Copenhagen (ITU), Centre Paul Strauss, CRLCC Paul Strauss, Laboratoire d'oncogénétique moléculaire, Unite d'Oncogenese Virale, Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER-Université de Lille-UNICANCER, QIMR Berghofer Medical Research Institute, Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Service de Génétique Clinique [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Génétique épidémiologique et moléculaire des pathologies cardiovasculaires, Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR14-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Génétique médicale [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 hospitalier universitaire de Nantes (CHU Nantes), Etablissement Français du Sang Bretagne, EFS, Laboratoire de Génétique Moléculaire et d'Histocompatibilité [Brest], Hôpital Morvan [Brest]-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), COMBE, Isabelle, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), UNICANCER, 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), IT University of Copenhagen, Institut Gustave Roussy (IGR), Service d'Oncologie Génétique, de Prévention et Dépistage, Laboratoire d'Oncologie Moléculaire Humaine, Université Lille Nord de France (COMUE)-UNICANCER-Université Lille Nord de France (COMUE)-UNICANCER, CHU Pontchaillou [Rennes], Université de Caen Normandie - UFR Santé (UNICAEN Santé), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Centre René Gauducheau, and CRLCC René Gauducheau
Subjects: 0301 basic medicine, International Cooperation, RNA Splicing, In silico, Spice, Breast Neoplasms, Computational biology, Biology, Sensitivity and Specificity, Set (abstract data type), 03 medical and health sciences, Exon, 0302 clinical medicine, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Genetics, Consensus sequence, RNA and RNA-protein complexes, Humans, Computer Simulation, 030304 developmental biology, BRCA2 Protein, Ovarian Neoplasms, Internet, 0303 health sciences, [SDV.BIBS] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], BRCA1 Protein, Intron, Computational Biology, Genetic Variation, Reproducibility of Results, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], In vitro, 030104 developmental biology, 030220 oncology & carcinogenesis, RNA splicing, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Female, RNA Splice Sites, RNA characterisation and manipulation, Corrigendum, Computational Methods, Optimal decision
Abstract: Variant interpretation is the key issue in molecular diagnosis. Spliceogenic variants exemplify this issue as each nucleotide variant can be deleterious via disruption or creation of splice site consensus sequences. Consequently, reliable in silico prediction of variant spliceogenicity would be a major improvement. Thanks to an international effort, a set of 395 variants studied at the mRNA level and occurring in 5′ and 3′ consensus regions (defined as the 11 and 14 bases surrounding the exon/intron junction, respectively) was collected for 11 different genes, including BRCA1, BRCA2, CFTR and RHD, and used to train and validate a new prediction protocol named Splicing Prediction in Consensus Elements (SPiCE). SPiCE combines in silico predictions from SpliceSiteFinder-like and MaxEntScan and uses logistic regression to define optimal decision thresholds. It revealed an unprecedented sensitivity and specificity of 99.5 and 95.2%, respectively, and the impact on splicing was correctly predicted for 98.8% of variants. We therefore propose SPiCE as the new tool for predicting variant spliceogenicity. It could be easily implemented in any diagnostic laboratory as a routine decision making tool to help geneticists to face the deluge of variants in the next-generation sequencing era. SPiCE is accessible at (https://sourceforge.net/projects/spicev2-1/).
Published: 2018

37. Advanced chordoma treated by first-line molecular targeted therapies: Outcomes and prognostic factors. A retrospective study of the French Sarcoma Group (GSF/GETO) and the Association des Neuro-Oncologues d'Expression Française (ANOCEF)

Author: Nicolas Penel, Bruno Chauffert, Elodie Vauleon, Alice Bonneville-Levard, Jean-Yves Blay, Christine Chevreau, Didier Cupissol, Olivier Mir, Esma Saada-Bouzid, Axel Le Cesne, Jacques-Olivier Bay, Loïc Feuvret, Florence Duffaud, Georges Noël, François Bertucci, Loïc Lebellec, Michel Fabbro, Emmanuelle Bompas, Armelle Vinceneux, CHU Amiens-Picardie, 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 de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR), Institut Claudius Regaud, CRLCC René Gauducheau, 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 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 Recherche sur le Cancer et le Vieillissement (IRCAN), 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)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Medical Oncology Unit, S. Camillo-Forlanini Hospital, Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière (CRICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Role of intra-Clonal Heterogeneity and Leukemic environment in ThErapy Resistance of chronic leukemias (CHELTER), Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), CRLCC Eugène Marquis (CRLCC), Centre Paul Strauss, CRLCC Paul Strauss, Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER, Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Equipe 11, Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Université Nice Sophia Antipolis (... - 2019) (UNS), and Université Lille Nord de France (COMUE)-UNICANCER
Subjects: Male, Oncology, Cancer Research, Indoles, 0302 clinical medicine, Sunitinib, Molecular Targeted Therapy, Child, ComputingMilieux_MISCELLANEOUS, Aged, 80 and over, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Middle Aged, Sorafenib, Temsirolimus, 3. Good health, Treatment Outcome, 030220 oncology & carcinogenesis, Imatinib Mesylate, Female, France, Erlotinib, medicine.drug, Adult, Niacinamide, medicine.medical_specialty, Adolescent, Antineoplastic Agents, Skull Base Neoplasms, Erlotinib Hydrochloride, Young Adult, 03 medical and health sciences, Internal medicine, Chordoma, medicine, Humans, Pyrroles, Aged, Retrospective Studies, Sirolimus, business.industry, Phenylurea Compounds, Neurooncology, Retrospective cohort study, medicine.disease, Surgery, business, 030217 neurology & neurosurgery, Progressive disease
Abstract: To assess the role of first-line Molecular Targeted Therapies (MTTs) in Advanced chordoma (AC) patients.Retrospective study of 80 patients treated between January 2004 and December 2015 at 15 major French Sarcoma or Neurooncology Centres.The sex ratio M/F was 46/34. The median age was 59 (6-86) years. The primary sites were the sacrum (50, 62.5%), mobile spine (12, 15.0%), and skull base (18, 22.5%). Metastases were present in 28 patients (36.0%). The first line of MTTs consisted of imatinib (62, 77.5%), sorafenib (11, 13.7%), erlotinib (5, 6.3%), sunitinib (1, 1.2%) and temsirolimus (1, 1.2%). The reported responses were: partial response (5, 6.3%), stable disease (58, 72.5%), or progressive disease (10, 12.5%). Symptomatic improvement was seen in 28/66 assessable patients (42.4%) and was associated with an objective response occurrence (p = 0.005), imatinib (p = 0.020) or erlotinib use (p = 0.028). The median progression-free survival (PFS) was 9.4°months (95% CI, [6.8-16.1]). Two independent factors of poor prognosis for PFS were identified: a skull-based primary location (HR = 2.5, p = 0.019), and the interval between diagnosis and MTT of52months (HR = 2.8, p 0.001). The median overall survival (OS) was 4.4°years (95% CI, [3.8-5.6]). Four independent factors of poor prognosis for OS were identified: the presence of liver metastases (HR = 13.2, p 0.001), pain requiring opioids (HR = 2.9, p = 0.012), skull-based primary location (HR = 19.7, p 0.001), and prior radiotherapy (photon alone) (HR = 2.5, p = 0.024). The PFS and OS did not significantly differ between the MTT.The prognostic factors identified require validation in an independent database but are potently useful to guide treatment decisions and design further clinical trials.
Published: 2017

38. Radiation-induced lung toxicity predictors: Retrospective analysis of 90 patients treated with stereotactic body radiation therapy for stage I non-small-cell lung carcinoma

Author: Georges Noël, P. Truntzer, Delphine Antoni, A. Labani, C. Mazzara, I. Menoux, A. Charloux, E. Quoix, Pierre Emmanuel Falcoz, Centre Paul Strauss, CRLCC Paul Strauss, Institut Pluridisciplinaire Hubert Curien (IPHC), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), and CHU Strasbourg
Subjects: Male, medicine.medical_specialty, Lung Neoplasms, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Pulmonary Fibrosis, Angiotensin-Converting Enzyme Inhibitors, Radiosurgery, Asymptomatic, 03 medical and health sciences, Angiotensin Receptor Antagonists, Pulmonary Disease, Chronic Obstructive, 0302 clinical medicine, Carcinoma, Non-Small-Cell Lung, Carcinoma, Medicine, Humans, Radiology, Nuclear Medicine and imaging, Lung volumes, Lung, Aged, Retrospective Studies, Aged, 80 and over, Analysis of Variance, business.industry, Smoking, Middle Aged, Models, Theoretical, medicine.disease, Acute toxicity, Radiation therapy, Radiation Pneumonitis, medicine.anatomical_structure, Oncology, 030220 oncology & carcinogenesis, Toxicity, Female, Radiology, Radiotherapy, Intensity-Modulated, medicine.symptom, Complication, business
Abstract: Background The main complication after hypofractionated radiotherapy for lung carcinoma is radiation-induced lung toxicity, which can be divided into radiation pneumonitis (acute toxicity, occurring within 6 months) and lung fibrosis (late toxicity, occurring after 6 months). The literature describes several predictive factors related to the patient, to the tumor (volume, central location), to the dosimetry and to biological factors. Materials and methods This study is a retrospective analysis of 90 patients treated with stereotactic body irradiation for stage I non-small-cell lung carcinoma between December 2010 and May 2015. Results Radiation pneumonitis was observed in 61.5% of the patients who were mainly asymptomatic (34%). Chronic obstructive pulmonary disease was not predictive of radiation pneumonitis, whereas active smoking was protective. Centrally located tumors were not more likely to result in this complication if the radiation schedule utilized adapted fractionation. In our study, no predictive factor was identified. Whereas the mean lung dose was a predictive factor in 3D radiotherapy, the lung volume irradiated at high doses seemed to be involved in the pathogenesis after hypofractionated radiotherapy. Conclusion The discovery of predictive factors for radiation pneumonitis is difficult due to the rarity of this complication, especially with an 8 × 7.5 Gy schedule. Radiation pneumonitis seems to be correlated with the volume irradiated at high doses, which is in contrast to the known knowledge about the organs in parallel. This finding leads us to raise the hypothesis that vessel damage, organs in series, occurring during hypofractionated radiotherapy could be responsible for this toxicity.
Published: 2019

39. Conformity to Clinical Practice Guidelines at Initial Management in Adult Soft Tissue and Visceral Tumors since the Implementation of the NetSarc Network in Eastern France

Author: Jean-Pierre Ghnassia, Jérémie Jégu, D. Brinkert, Jean-Baptiste Delhorme, Justine Gantzer, Antonio Di Marco, Thibaut Fabacher, Jean-Emmanuel Kurtz, Guillaume Bierry, Noëlle Weingertner, Les Hôpitaux Universitaires de Strasbourg (HUS), Centre Paul Strauss, CRLCC Paul Strauss, and univOAK, Archive ouverte
Subjects: Adult, Male, Cancer Research, medicine.medical_specialty, Multivariate analysis, Adolescent, media_common.quotation_subject, Soft Tissue Neoplasms, [SDV.CAN]Life Sciences [q-bio]/Cancer, Cancer Care Facilities, Conformity, 03 medical and health sciences, Young Adult, Soft tissue tumors, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Biopsy, medicine, Humans, National level, 030212 general & internal medicine, media_common, Aged, Retrospective Studies, Tumor imaging, Aged, 80 and over, Diagnostic management, medicine.diagnostic_test, business.industry, Sarcomas, Soft tissue, Disease Management, Sarcoma, Middle Aged, medicine.disease, Clinical Practice, Oncology, 030220 oncology & carcinogenesis, Practice Guidelines as Topic, Conformity to clinical guidelines, Female, Radiology, France, Guideline Adherence, business
Abstract: Background Soft tissue sarcomas are rare and heterogenous tumors that are hard to diagnose. The aim of this study was to evaluate local practices and conformity to clinical practice guidelines (CPGs) for their initial diagnostic management. Materials and Methods Patients were carriers of a soft tissue or visceral tumor, presented at a sarcoma tumor board (STB) between 2010 and 2016. Conformity to CPGs was evaluated using ten criteria designed for this purpose. Associations between different factors and conformity to composite criteria, reflecting the three main diagnostic steps (imaging, biopsy and histological report) were analyzed. Results A total of 643 patients were included. A preoperative tumor imaging assessment and a biopsy were performed according to CPGs in 80.8% and 36.8% of the cases, respectively. When done, the first surgical resection was R0 in 30.3% of cases, R1 in 28.6%, and R2 in 10.9%. The rest of the operated patients with sarcoma had a second surgical excision (11.4%), an intraoperative fragmentation (4.3%), or margins were unknown (14.4%). Six of the ten quality criteria presented a conformity rate higher than 70%. Two criteria with a conformity rate lower than 20% were the most controversial: presentation at a STB before biopsy and freezing of a tumor fragment. A multivariate analysis revealed that the common predictor of nonconformity to composite criteria was the initial management in a nonexpert center. Conclusion Initial diagnostic management requires improvement, especially outside of specialized centers.
Published: 2019

40. Dose distribution of the brain tissue associated with cognitive functions in high-grade glioma patients

Author: Dimitri Psimaras, Delphine Antoni, Khê Hoang-Xuan, D. Ricard, C. Jenny, Antoine F. Carpentier, J. Jacob, M.A. Benadjaoud, M.O. Bernier, Monica Ribeiro, Loïc Feuvret, E. Clausse, Philippe Maingon, Jean-Jacques Mazeron, Cognition and Action Group (COGNAC-G - UMR 8257), Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPC), Service d'Oncologie Radiothérapie [CHU Pitié Salpétrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université (SU), Service de Médecine Physique et de Réadaptation [CHU Pitié-Salpêtrière] (MPR), Laboratoire de radiobiologie des expositions médicales‎ (LRMed), Institut de Radioprotection et de Sûreté Nucléaire (IRSN)-Sorbonne Université (SU)-Université Paris-Saclay, Service de neurologie 2 [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Paul Strauss, CRLCC Paul Strauss, Les Hôptaux universitaires de Strasbourg (HUS), CHU Strasbourg, PSE-SANTE/SESANE/LEPID, Institut de Radioprotection et de Sûreté Nucléaire (IRSN), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de Neurochirurgie [CHU Pitié-Salpêtrière], Hôpital d'instruction des Armées Percy, Service de Santé des Armées, Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), PSE-SANTE/SERAMED, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Adult, Male, Organs at Risk, Cerebellum, Intensity-modulated radiation therapy, medicine.medical_treatment, Fonctions cognitives, [SDV.CAN]Life Sciences [q-bio]/Cancer, Brain tissue, Dose distribution, [SDV.IB.MN]Life Sciences [q-bio]/Bioengineering/Nuclear medicine, Corpus callosum, Tomotherapy, 03 medical and health sciences, 0302 clinical medicine, Glioma, medicine, Humans, Radiology, Nuclear Medicine and imaging, Prospective Studies, High-Grade Glioma, Aged, business.industry, Brain Neoplasms, Brain, Cognition, Radiotherapy Dosage, Middle Aged, medicine.disease, Gliome, Cognitive functions, medicine.anatomical_structure, Oncology, Radiothérapie conformationnelle par modulation d’intensité, 030220 oncology & carcinogenesis, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Female, Radiotherapy, Intensity-Modulated, business, Nuclear medicine, Glioblastoma, Organ Sparing Treatments
Abstract: International audience; Purpose: The purpose of this prospective dosimetric study was to assess the dose distribution regarding the brain areas implied in cognitive functions using two approaches: volumetric modulated arc therapy (VMAT) and helical tomotherapy (HT).Patients and methods: Thirty-seven patients were treated using a dual-arc VMAT approach for supratentorial glioblastoma between 2016 and 2018. The total dose of 60 Gy in 30 daily fractions was administered to the planning target volume (PTV). The brain structures that play an important role in cognitive physiology, such as the hippocampi, corpus callosum, cerebellum, subventricular zones (SVZ), were delineated. For each patient, a new treatment plan in HT was determined by a second medical physicist in a blindly fashion according to the same dose constraints and priorities. Statistical analyses were performed using the Wilcoxon-signed rank test.Results: Conformity indexes remained similar with both techniques. The mean values were 0.96 (0.19–1.00) for VMAT and 0.98 (range, 0.84–1.00) for HT, respectively (P = 0.73). Significant D50% reductions were observed with VMAT compared to HT: 14.6 Gy (3.8–28.0) versus 17.4 Gy (12.1–25.0) for the normal brain (P = 0.014); 32.5 Gy (10.3–60.0) versus 35.6 Gy (17.1–58.0) for the corpus callosum (P = 0.038); 8.1 Gy (0.4–34.0) versus 12.8 Gy (0.8–27.0) for the cerebellum (P < 0.001), respectively.Conclusion: The VMAT approach seemed to improve the sparing of the key brain areas implied in cognitive functions without jeopardizing PTV coverage.; Objectif: L’objectif de cette étude prospective dosimétrique était d’évaluer la distribution de dose en regard des aires cérébrales impliquées dans les fonctions cognitives selon deux techniques : arcthérapie volumétrique modulée (VMAT) et tomothérapie hélicoïdale (HT).Patients et méthodes: Trente-sept patients ont été pris en charge pour un glioblastome sus-tentoriel par une VMAT à base de deux arcs entre 2016 et 2018. Une dose totale de 60 Gy en 30 fractions quotidiennes a été administrée au volume cible prévisionnel (PTV). Les structures cérébrales occupant une place importante dans la physiologie cognitive, comme les hippocampes, le corps calleux, le cervelet, les zones péri-ventriculaires (ZPV), ont été délinées. Pour chaque patient, un nouveau plan de HT a été déterminé en aveugle par une seconde physicienne médicale selon les mêmes contraintes de dose et priorités. Les analyses statistiques ont été menées à l’aide du test des rangs signés de Wilcoxon.Résultats: Les indices de conformité étaient similaires entre les deux techniques. Les valeurs moyennes étaient de 0,96 (0,19–1,00) respectivement en VMAT et de 0,98 (0,84–1,00) en tomothérapie hélicoïdale (p = 0,73). Des réductions significatives de la D50 % (dose reçue dans 50 % du volume) ont été observées en VMAT, comparativement à la HT : respectivement 14,6 Gy (3,8–28,0) contre 17,4 Gy (12,1–25,0) pour l’encéphale sain (p = 0,014), 32,5 Gy (10,3–60,0) contre 35,6 Gy (17,1–58,0) pour le corps calleux (p = 0,038), 8,1 Gy (0,4–34,0) contre 12,8 Gy (0,8–27,0) pour le cervelet (p < 0,001).Conclusion: La VMAT semblait améliorer la protection des principales régions cérébrales impliquées dans les fonctions cognitives sans compromettre la couverture du PTV.
Published: 2019

41. Surgery in reference centers improves survival of sarcoma patients: a nationwide study

Author: A. Giraud, P. Soibinet, Sébastien Carrère, E. Stoeckle, G. Vaz, J. Guiramand, J.-C. Ruzic, A. Dufresne, Jean-Yves Blay, F. Gouin, A. Rochwerger, F. Duffaud, A. Le Cesne, Francis Guillemin, J.-P. Spano, M. Rios, P. Meeus, Isabelle Ray-Coquard, A. Di Marco, G. Ferron, François Bertucci, François Sirveaux, N. Firmin, F. Fiorenza, O. Collard, S. Bonvalot, Emmanuelle Bompas, S. Causeret, P. Anract, M. Jafari, D. Pérol, J.-C. Machiavello, O. Marco, F. Ducimetière, C. Honore, A. Italiano, A. Michot, M. Karanian-Philippe, Nicolas Penel, P. Gimbergues, Mickaël Ropars, M. Toulmonde, F. Marchal, M. Brahmi, C. Le Pechoux, L.R. Le Nail, C. Perrin, F. Le Loarer, C. Chevreau, A. Dupré, J.-M. Guilloit, L. Chaigneau, F. Dujardin, Department of Medical Oncology [Lyon], Centre Léon Bérard [Lyon], Institut de Cancérologie Lucien Neuwirth, Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Département de Chirurgie cancérologique, Institut Gustave Roussy (IGR), Département d'oncologie médicale, Institut Bergonié [Bordeaux], UNICANCER-UNICANCER, Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER, Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), 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), Service d’Oncologie Médicale [Hôpital de la Timone - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), CHU Pontchaillou [Rennes], Centre Eugène Marquis (CRLCC), 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 Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), Centre Paul Strauss, CRLCC Paul Strauss, Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de chirurgie [Centre Georges-François Leclerc], Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), Department of Surgical Oncology, Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), Service d'Oncologie médicale [CHU Limoges], CHU Limoges, 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), 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), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Claudius Regaud, Oncogenesis Stress Signaling (OSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC), 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 de radiothérapie [Gustave Roussy], Centre de Recherches sur les Macromolécules Végétales (CERMAV ), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Laboratoire Interdisciplinaire de Recherche Impliquant la Géologie et la Mécanique, Université Joseph Fourier - Grenoble 1 (UJF), Institut Curie [Paris], NetSARC, INCa & DGOS, RREPS, RESOS (INCa & DGOS) and LYRICAN, Association DAM’s, Ensemble contre Le GIST, FP7-278742, Eurosarc, ANR-10-LABX-0061, la Fondation ARC, Infosarcome, Ligue de L’Ain contre le Cancer, La Ligue contre le Cancer, EC 739521, EURACAN, ANR-10-LABX-0061,DEVWECAN,Development Cancer and Targeted Therapies(2010), CHU Saint-Etienne, 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 de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CRLCC Eugène Marquis (CRLCC), Laboratoire des Mécanismes et Transfert en Géologie (LMTG), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Observatoire Midi-Pyrénées (OMP), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Centre National de la Recherche Scientifique (CNRS), Université Lille Nord de France (COMUE)-UNICANCER, Hôpital de la Timone [CHU - APHM] (TIMONE)-Assistance Publique - Hôpitaux de Marseille (APHM), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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), Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Centre National de la Recherche Scientifique (CNRS), CHU Lille, Université de Lille, Université Claude Bernard Lyon 1 [UCBL], METRICS : Evaluation des technologies de santé et des pratiques médicales - ULR 2694, Institut Gustave Roussy [IGR], Centre Hospitalier Régional Universitaire [Lille] [CHRU Lille], Hôpital Cochin [AP-HP], Hôpital de la Timone [CHU - APHM] [TIMONE], Institut de Recherche en Cancérologie de Montpellier [IRCM - U1194 Inserm - UM], Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] [UNICANCER/ICL], CHU Strasbourg, Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] [UNICANCER/CRLCC-CGFL], Centre Jean Perrin [Clermont-Ferrand] [UNICANCER/CJP], Centre Hospitalier Régional Universitaire de Besançon [CHRU Besançon], CRLCC Jean Godinot, Centre Régional de Lutte contre le Cancer François Baclesse [Caen] [UNICANCER/CRLC], Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen [CLCC Henri Becquerel], Centre Hospitalier Universitaire de La Réunion [CHU La Réunion], and Evaluation des technologies de santé et des pratiques médicales - ULR 2694 [METRICS]
Subjects: 0301 basic medicine, Male, Multivariate analysis, sarcoma, medicine.medical_treatment, [SDV]Life Sciences [q-bio], surgery, 0302 clinical medicine, Prospective Studies, Registries, resection, Referral and Consultation, Aged, 80 and over, relapse, Hazard ratio, Hematology, Middle Aged, Prognosis, Corrigenda, 3. Good health, Survival Rate, Oncology, 030220 oncology & carcinogenesis, Surgical Procedures, Operative, Female, Sarcoma, France, Adult, medicine.medical_specialty, Adolescent, [SDV.CAN]Life Sciences [q-bio]/Cancer, reference center, Relapse free survival, survival, 03 medical and health sciences, Young Adult, medicine, Humans, Neurofibromatosis, Pathological, Aged, business.industry, Cancer, Original Articles, medicine.disease, Surgery, Radiation therapy, Editor's Choice, 030104 developmental biology, Neoplasm Recurrence, Local, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Follow-Up Studies
Abstract: International audience; BackgroundNETSARC (netsarc.org) is a network of 26 sarcoma reference centers with specialized multidisciplinary tumor boards (MDTB) aiming to improve the outcome of sarcoma patients. Since 2010, presentation to an MDTB and expert pathological review are mandatory for sarcoma patients nationwide. In the present work, the impact of surgery in a reference center on the survival of sarcoma patients investigated using this national NETSARC registry.Patients and methodsPatients’ characteristics and follow-up are prospectively collected and data monitored. Descriptive, uni- and multivariate analysis of prognostic factors were conducted in the entire series (N = 35 784) and in the subgroup of incident patient population (N = 29 497).ResultsAmong the 35 784 patients, 155 different histological subtypes were reported. 4310 (11.6%) patients were metastatic at diagnosis. Previous cancer, previous radiotherapy, neurofibromatosis type 1 (NF1), and Li–Fraumeni syndrome were reported in 12.5%, 3.6%, 0.7%, and 0.1% of patients respectively. Among the 29 497 incident patients, 25 851 (87.6%) patients had surgical removal of the sarcoma, including 9949 (33.7%) operated in a NETSARC center. Location, grade, age, size, depth, histotypes, gender, NF1, and surgery outside a NETSARC center all correlated to overall survival (OS), local relapse free survival (LRFS), and event-free survival (EFS) in the incident patient population. NF1 history was one of the strongest adverse prognostic factors for LRFS, EFS, and OS. Presentation to an MDTB was associated with an improved LRFS and EFS, but was an adverse prognostic factor for OS if surgery was not carried out in a reference center. In multivariate analysis, surgery in a NETSARC center was positively correlated with LRFS, EFS, and OS [P
Published: 2019

42. Preferential Response of Basal-Like Head and Neck Squamous Cell Carcinoma Cell Lines to EGFR-Targeted Therapy Depending on EREG-Driven Oncogenic Addiction

Author: Alain C. Jung, Sylvie Job, Laurent Brino, Eric Guérin, Aurélien de Reyniès, Nelly Etienne-Selloum, Bohdan Wasylyk, Cyril Bour, Betty Heller, Christian Gaiddon, Christine Macabre, Christine Wasylyk, Amélie Weiss, Sonia Ledrappier, Gaiddon, Christian, (le programme) Cartes d'identité des tumeurs (CIT), Ligue Nationales Contre le Cancer (LNCC), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Interface de Recherche Fondamentale et Appliquée en Cancérologie (IRFAC - Inserm U1113), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Paul Strauss : Centre Régional de Lutte contre le Cancer (CRLCC)-Fédération de Médecine Translationelle de Strasbourg (FMTS), Laboratoire de Biochimie et de Biologie Moléculaire, CHU Strasbourg-Hôpital de Hautepierre [Strasbourg], Centre Paul Strauss, CRLCC Paul Strauss, Laboratoire de Bioimagerie et Pathologies (LBP), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), and Financial support for this study was provided by the Ligue Nationale Contre le Cancer, the Centre National de la Recherche Scientifique (CNRS), the Institut National de la Santé Et de la Recherche Médicale (INSERM), the Paul Strauss Cancer Center, the Université de Strasbourg and the LabEx INRT.
Subjects: 0301 basic medicine, Cancer Research, cancer subgroups, [SDV]Life Sciences [q-bio], Afatinib, EGFR, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, head and neck squamous cell carcinoma, lcsh:RC254-282, Article, Epiregulin, 03 medical and health sciences, 0302 clinical medicine, Gefitinib, [SDV.CAN] Life Sciences [q-bio]/Cancer, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, medicine, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Epidermal growth factor receptor, drug sensitivity, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, PI3K/AKT/mTOR pathway, Cetuximab, biology, business.industry, EREG, medicine.disease, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Head and neck squamous-cell carcinoma, 3. Good health, [SDV] Life Sciences [q-bio], 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, Cancer research, biology.protein, treatment combinations, business, Tyrosine kinase, medicine.drug
Abstract: The management of locally advanced head and neck squamous cell carcinoma (HNSCC) with Cetuximab, a monoclonal antibody targeting the epidermal growth factor receptor (EGFR), achieves only moderate response rates, and clinical trials that evaluated EGFR-blockade with tyrosine kinase inhibitors (TKI) yielded disappointing results. Inter-tumor heterogeneity may hinder the therapeutic efficiency of anti-EGFR treatments. HNSCC heterogeneity was addressed in several studies, which all converged towards the definition of molecular subgroups. They include the basal subgroup, defined by the deregulated expression of factors involved in the EGFR signaling pathway, including the epiregulin EGFR ligand encoded by the EREG gene. These observations indicate that basal tumors could be more sensitive to anti-EGFR treatments. To test this hypothesis, we performed a screen of a representative collection of basal versus non-basal HNSCC cell lines for their sensitivity to several anti-EGFR drugs (Cetuximab, Afatinib, and Gefitinib), tested as monotherapy or in combination with drugs that target closely-linked pathways [Mitogen-activated protein kinase kinase/ extracellular signal&ndash, regulated kinases (MEK), mammalian Target of Rapamycine (mTOR) or Human Epidermal growth factor Receptor 2 (HER2)]. Basal-like cell lines were found to be more sensitive to EGFR blockade alone or in combination with treatments that target MEK, mTOR, or HER2. Strikingly, the basal-like status was found to be a better predictor of cell response to EGFR blockade than clinically relevant mutations [e.g., cyclin-dependent kinase Inhibitor 2A (CDKN2A)]. Interestingly, we show that EGFR blockade inhibits EREG expression, and that EREG knock-down decreases basal cell clonogenic survival, suggesting that EREG expression could be a predictive functional marker of sensitivity to EGFR blockade in basal-like HNSCC.
Published: 2019

43. Long-term survival in patients with recurrent glioblastoma treated with bevacizumab: a multicentric retrospective study

Author: Georges Noël, D Bello-Roufai, Veronique Lorgis, Luc Taillandier, M C Morisse, Alberto Duran-Peña, Guido Ahle, Marie Blonski, Bruno Chauffert, Mathieu Boone, Nelly Etienne-Selloum, CHU Amiens-Picardie, Laboratoire de Bioimagerie et Pathologies (LBP), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Institut Curie [Paris], Centre de Recherche en Automatique de Nancy (CRAN), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, CRLCC Paul Strauss, Service de Neurologie [Hôpitaux Civils de Colmar], Hôpitaux Civils Colmar, CHU Pitié-Salpêtrière [AP-HP], and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: Oncology, Adult, Male, Cancer Research, medicine.medical_specialty, Multivariate analysis, Bevacizumab, medicine.drug_class, medicine.medical_treatment, [SDV.CAN]Life Sciences [q-bio]/Cancer, Angiogenesis Inhibitors, [SPI.AUTO]Engineering Sciences [physics]/Automatic, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Internal medicine, medicine, Humans, Survivors, Aged, Retrospective Studies, Aged, 80 and over, Temozolomide, business.industry, Brain Neoplasms, Medical record, Retrospective cohort study, Middle Aged, Prognosis, 3. Good health, Survival Rate, Neurology, 030220 oncology & carcinogenesis, Concomitant, Corticosteroid, Female, Neurology (clinical), Neoplasm Recurrence, Local, business, Glioblastoma, Adjuvant, 030217 neurology & neurosurgery, medicine.drug, Follow-Up Studies
Abstract: International audience; Purpose: Recurrence of glioblastoma (GB) occurs in most patients after standard concomitant temozolomide-based radiochemotherapy (CTRC). Bevacizumab (BV), an anti-VEGF antibody, has an effect on progression-free survival (PFS) but not on overall survival (OS). However, a small part of the patients experience a survival, longer than expected. This retrospective study aims to characterize long responder (LR) patients treated with BV for a first or second GBM recurrence.Methods: Medical records from patients (814) who received BV for a first or second recurrence of primary glioblastoma between September 2010 and September 2015, and initially treated by CTRC were analyzed. Patients, who had at least a stable disease according to RANO criteria at 12 months from the start of BV, were included. Patients who had, a secondary GB, or received BV in neoadjuvant or adjuvant setting were excluded.Results: We focused on 65 LR patients without progression 12 months after the first injection of BV (8%). Median PFS was 21.7 months [95% CI (19.3; 27.2)] and median OS was 31.1 months [95% CI (24.3; 37.5)] from the start of BV. No prognostic factor was associated with OS in multivariate analysis. Karnofsky performance status, neurological status and corticosteroid dose were stable at 12 months.Conclusions: Our results highlight that among patients receiving bevacizumab in first or second recurrence, one patient out of twelve could be classified as LR. A median OS of 31.1 months from the start of BV could be expected in this subpopulation. These findings reinforce the potential benefit of the use of BV in the situation of recurrence.
Published: 2019

44. Gemcitabine and Oxaliplatin Chemotherapy or Surveillance in Resected Biliary Tract Cancer (PRODIGE 12-ACCORD 18-UNICANCER GI): A Randomized Phase III Study

Author: Jean-Paul Joly, Eric Assenat, Veronique Guerin-Meyer, Aurélie Bertaut, Jean-Louis Jouve, Jérôme Watelet, Christelle De La Fouchardiere, Catherine Lombard-Bohas, Trevor Stanbury, Karim Boudjema, Eveline Boucher, Laetitia Fartoux, Jean-Marc Phelip, Pascal Hammel, Jean-François Seitz, Karine Bouhier-Leporrier, Jean-Emmanuel Kurtz, M. Benabdelghani, Isabelle Baumgaertner, David Malka, David Tougeron, Roger Faroux, Julien Edeline, Christophe Louvet, Centre Eugène Marquis (CRLCC), Centre Paul Strauss, CRLCC Paul Strauss, Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, Service d'Hépato-gastro-entérologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Hôpital Beaujon, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Amiens-Picardie, CHU Pontchaillou [Rennes], Service d'Oncologie Médicale [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), Hôpital Côte de Nacre [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Hôpital du Bocage, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), CHU Strasbourg, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service d'oncologie digestive et hépato-gastro-entérologie [Hôpital de la Timone - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Service d'Oncologie médicale [CHU Henri Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Henri Mondor, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Centre Léon Bérard [Lyon], Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), UNICANCER [Paris], Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Institut Mutualiste de Montsouris (IMM), Institut Gustave Roussy (IGR), Département de médecine oncologique [Gustave Roussy], Service de gastroentérologie [CHU Saint-Etienne], and Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne)
Subjects: Adult, Male, Cancer Research, medicine.medical_specialty, Time Factors, medicine.medical_treatment, [SDV.CAN]Life Sciences [q-bio]/Cancer, Gastroenterology, MESH: Antineoplastic Combinated Chemotherapy Protocol / therapeutic uses, Biliary Tract Neoplasms / drug therapy, Biliary Tract Neoplasms / surgery, Deoxycytidine / analogs & derivatives, Oxaliplatin / administration & dosage, Watchful waiting, Deoxycytidine, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Progression-free survival, Watchful Waiting, Aged, Aged, 80 and over, Chemotherapy, Biliary tract cancer, business.industry, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, Middle Aged, Gemcitabine, Progression-Free Survival, 3. Good health, Oxaliplatin, Clinical trial, Biliary Tract Surgical Procedures, Biliary Tract Neoplasms, Oncology, Chemotherapy, Adjuvant, 030220 oncology & carcinogenesis, Quality of Life, 030211 gastroenterology & hepatology, Female, France, business, Adjuvant, medicine.drug
Abstract: PURPOSE No standard adjuvant treatment currently is recommended in localized biliary tract cancer (BTC) after surgical resection. We aimed to assess whether gemcitabine and oxaliplatin chemotherapy (GEMOX) would increase relapse-free survival (RFS) while maintaining health-related quality of life (HRQOL) in patients who undergo resection. PATIENTS AND METHODS We performed a multicenter, open-label, randomized phase III trial in 33 centers. Patients were randomly assigned (1:1) within 3 months after R0 or R1 resection of a localized BTC to receive either GEMOX (gemcitabine 1,000 mg/m2 on day 1 and oxaliplatin 85 mg/m2 infused on day 2 of a 2-week cycle) for 12 cycles (experimental arm A) or surveillance (standard arm B). Primary end points were RFS and HRQOL. RESULTS Between July 2009 and February 2014, 196 patients were included. Baseline characteristics were balanced between the two arms. After a median follow-up of 46.5 months (95% CI, 42.6 to 49.3 months), 126 RFS events and 82 deaths were recorded. There was no significant difference in RFS between the two arms (median, 30.4 months in arm A v 18.5 months in arm B; hazard ratio [HR], 0.88; 95% CI, 0.62 to 1.25; P = .48). There was no difference in time to definitive deterioration of global HRQOL (median, 31.8 months in arm A v 32.1 months in arm B; HR, 1.28; 95% CI, 0.73 to 2.26; log-rank P = .39). Overall survival was not different (median, 75.8 months in arm A v 50.8 months in arm B; HR, 1.08; 95% CI, 0.70 to 1.66; log-rank P = .74). Maximal adverse events were grade 3 in 62% (arm A) versus 18% (arm B) and grade 4 in 11% versus 3% ( P < .001). CONCLUSION There was no benefit of adjuvant GEMOX in resected BTC despite adequate tolerance and delivery of the regimen.
Published: 2019

45. Dichloroacetate restores colorectal cancer chemosensitivity through the p53/miR-149-3p/PDK2-mediated glucose metabolic pathway

Author: Yingying Wang, Mengfei Yao, Isabelle Gross, Linjing Li, Yue Li, Huimin Zou, Yu Liang, Liming Zhu, Xiaoling Weng, Yichao Hou, Danxi Zhu, Lei Li, Christian Gaiddon, Yan Gu, Xin Huang, Yu Wang, Lidan Hou, Xiangjun Meng, Tianqi Wu, Jianhua Wang, Meng Luo, Gaiddon, Christian, Department of Gastroenterology [Shanghai, China], Shanghai Jiao Tong University School of Medicine-Shanghai Ninth People's Hospital [China], Department of General Surgery [Shanghai, China], Shanghai Jiao Tong University School of Medicine-Shanghai Ninth People’s Hospital [China], Cancer Institute [Shanghai, China], Fudan University [Shanghai]-Fudan University Shanghai Cancer Center [China], Ningbo Aitagene Technology Co. LTD [Shanghai, China], Department of Biochemistry and Molecular & Cell Biology [Shanghai, China], Shanghai Jiao Tong University School of Medicine, Pathology Center [Shanghai, China], Shanghai Jiao Tong University School of Medicine-Shanghai First People’s Hospital [China], Interface de Recherche Fondamentale et Appliquée en Cancérologie (IRFAC - Inserm U1113), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Paul Strauss : Centre Régional de Lutte contre le Cancer (CRLCC)-Fédération de Médecine Translationelle de Strasbourg (FMTS), Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA), CRLCC Paul Strauss, This work was supported by the National Natural Science Foundation of China (81272745, 81872419, and 81272404) and the Program for Professor of Special Appointment (Eastern Scholar to JW) at Shanghai Institutions of Higher Learning., and Fudan University Shanghai Cancer Center [China]-Fudan University [Shanghai]
Subjects: 0301 basic medicine, Male, Cancer Research, Microarray, Colorectal cancer, [SDV]Life Sciences [q-bio], Apoptosis, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Carbohydrate metabolism, Biology, Article, Non-coding RNAs, 03 medical and health sciences, Mice, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, In vivo, Genetics, medicine, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Animals, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Molecular Biology, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, Gene knockdown, Base Sequence, Dichloroacetic Acid, Pyruvate Dehydrogenase Acetyl-Transferring Kinase, medicine.disease, HCT116 Cells, 3. Good health, [SDV] Life Sciences [q-bio], MicroRNAs, 030104 developmental biology, Glucose, Fluorouracil, Drug Resistance, Neoplasm, 030220 oncology & carcinogenesis, Cancer research, Signal transduction, Tumor Suppressor Protein p53, Colorectal Neoplasms, medicine.drug
Abstract: The development of chemoresistance remains a major challenge that accounts for colorectal cancer (CRC) lethality. Dichloroacetate (DCA) was originally used as a metabolic regulator in the treatment of metabolic diseases; here, DCA was assayed to identify the mechanisms underlying the chemoresistance of CRC. We found that DCA markedly enhanced chemosensitivity of CRC cells to fluorouracil (5-FU), and reduced the colony formation due to high levels of apoptosis. Using the microarray assay, we noted that miR-149-3p was involved in the chemoresistance of CRC, which was modulated by wild-type p53 after DCA treatment. In addition, PDK2 was identified as a direct target of miR-149-3p. Mechanistic analyses showed that overexpression of miR-149-3p enhanced 5-FU-induced apoptosis and reduced glucose metabolism, similar to the effects of PDK2 knockdown. In addition, overexpression of PDK2 partially reversed the inhibitory effect of miR-149-3p on glucose metabolism. Finally, both DCA treatment and miR-149-3p overexpression in 5-FU-resistant CRC cells were found to markedly sensitize the chemotherapeutic effect of 5-FU in vivo, and this effect was also validated in a small retrospective cohort of CRC patients. Taken together, we determined that the p53/miR-149-3p/PDK2 signaling pathway can potentially be targeted with DCA treatment to overcome chemoresistant CRC.
Published: 2019

46. RILA blood biomarker as a predictor of radiation-induced sarcoma in a matched cohort study

Author: S. Renard-Oldrini, Georges Noël, Jean-Léon Lagrange, Paul Sargos, Marc-André Mahé, Julien Domont, F. Bonnetain, C. Chevreau, F. Collin, Isabelle Ray-Coquard, J. Thariat, Gilles Truc, Aurélie Bertaut, Jean-Louis Merlin, X. Liem, Céline Mirjolet, Philippe Maingon, Département d'oncologie médicale [Centre Georges-François Leclerc], Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER, Centre de Recherche en Automatique de Nancy (CRAN), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), UNICANCER, Centre Paul Strauss, CRLCC Paul Strauss, Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), 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], Institut Gustave Roussy (IGR), Institut Bergonié [Bordeaux], Centre Léon Bérard [Lyon], Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER, 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), Service d'Oncologie médicale [CHU Henri Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Henri Mondor [Créteil], CRLCC René Gauducheau, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU), Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Université Lille Nord de France (COMUE)-UNICANCER, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Henri Mondor, Service de Radiothérapie [CHU Pitié-Salpêtrière], 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), 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), Service d'Oncologie Radiothérapie [CHU Pitié Salpétrière], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Adult, Male, 0301 basic medicine, Oncology, medicine.medical_specialty, Neoplasms, Radiation-Induced, Research paper, medicine.medical_treatment, Breast Neoplasms, Apoptosis, [SDV.CAN]Life Sciences [q-bio]/Cancer, CD8-Positive T-Lymphocytes, General Biochemistry, Genetics and Molecular Biology, Cohort Studies, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, Matched cohort, Internal medicine, Biomarkers, Tumor, Humans, Medicine, Prospective Studies, Adverse effect, Aged, Aged, 80 and over, business.industry, Cancer, Sarcoma, General Medicine, Middle Aged, medicine.disease, Primary tumor, 3. Good health, Radiation therapy, Predictive biomarker, 030104 developmental biology, ROC Curve, Area Under Curve, Case-Control Studies, 030220 oncology & carcinogenesis, Radio-induced sarcoma, Biomarker (medicine), Female, Lymphocyte, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business
Abstract: International audience; Purpose: Radiation-induced sarcoma (RIS) is a rare but serious event. Its occurrence has been discussed during the implementation of new radiation techniques and justified appropriate radioprotection requirements. New approaches targeting intrinsic radio-sensitivity have been described, such as radiation-induced CD8 T-lymphocyte apoptosis (RILA) able to predict late radio-induced toxicities. We studied the role of RILA as a predisposing factor for RIS as a late adverse event following radiation therapy (RT).Patients and methods: In this prospective biological study, a total of 120 patients diagnosed with RIS were matched with 240 control patients with cancer other than sarcoma, for age, sex, primary tumor location and delay after radiation. RILA was prospectively assessed from blood samples using flow cytometry.Results: Three hundred and forty-seven patients were analyzed (118 RIS patients and 229 matched control patients). A majority (74%) were initially treated by RT for breast cancer. The mean RT dose was comparable with a similar mean (± standard deviation) for RIS (53.7 ± 16.0 Gy) and control patients (57.1 ± 15.1 Gy) (p = .053). Median RILA values were significantly lower in RIS than in control patients with respectively 18.5% [5.5–55.7] and 22.3% [3.8–52.2] (p = .0008). Thus, patients with a RILA >21.3% are less likely to develop RIS (p
Published: 2019

47. A GATE/Geant4 Monte Carlo toolkit for surface dose calculation in VMAT breast cancer radiotherapy

Author: Nicolas Arbor, Jean Gasteuil, Philippe Meyer, C. Noblet, Matthieu Moreau, Institut Pluridisciplinaire Hubert Curien (IPHC), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), CRLCC Paul Strauss, and Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Surface (mathematics), Dose calculation, Computer science, medicine.medical_treatment, Monte Carlo method, Biophysics, General Physics and Astronomy, Breast Neoplasms, VMAT, [SDV.IB.MN]Life Sciences [q-bio]/Bioengineering/Nuclear medicine, Radiation Dosage, Breast cancer radiotherapy, radiation therapy, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, Software, breast cancer, medicine, Humans, Radiology, Nuclear Medicine and imaging, Simulation, Varian Eclipse, business.industry, Radiotherapy Planning, Computer-Assisted, Radiotherapy Dosage, General Medicine, Monte Carlo dosimetry, Radiation therapy, 030220 oncology & carcinogenesis, [PHYS.PHYS.PHYS-MED-PH]Physics [physics]/Physics [physics]/Medical Physics [physics.med-ph], Radiotherapy, Intensity-Modulated, business, Monte Carlo Method, Bolus (radiation therapy)
Abstract: International audience; The accuracy of superficial dose calculations for breast cancer treatments with Volumetric Modulated Arc Therapy (VMAT) is of major importance. For target volumes close to the surface, the inverse dosimetric planning can lead to very high fluences in the build-up region to properly cover the volume to be treated. Various radiotherapy modalities are currently used in parallel with additional protocols to enable a better control on the dose delivery (bolus, target volume margins). One of the difficulties currently facing medical physicists is the lack of available tools to test the impact of these different solutions on the superficial dose distribution. We present a new open source toolkit to assist medical physicists in evaluating the 3D distributions of superficial dose in VMAT breast cancer treatments. This tool is based on the GATE Monte Carlo software, a Geant4 application dedicated to medical physics. A set of macros has been developed to simulate in an easy way a full VMAT plan from the information available in the DICOM-RT files (image, plan, structure and dose). The toolkit has been tested on a 6 MV Varian NovalisTx TM accelerator. The paper presents a precise comparison of 3D surface dose distributions from experimental measurements (EBT3 films), TPS (Varian Eclipse) and Monte Carlo simulation (GATE). The comparison made it possible to highlight both the TPS biases for the surface dose calculation and the good performances of the developed toolkit. The simulation of surface dose distributions on a real patient has also been performed to illustrate the potential clinical applications.
Published: 2019

48. FOLFIRINOX or Gemcitabine as Adjuvant Therapy for Pancreatic Cancer

Author: Conroy, Thierry, Hammel, Pascal, Hebbar, Mohamed, Ben Abdelghani, Meher, Wei, Alice, Raoul, Jean-Luc, Choné, Laurence, Francois, Eric, Artru, Pascal, Biagi, James, Lecomte, Thierry, Assenat, Eric, Faroux, Roger, Ychou, Marc, Volet, Julien, Sauvanet, Alain, Breysacher, Gilles, Di Fiore, Frédéric, Cripps, Christine, Kavan, Petr, Texereau, Patrick, Bouhier-Leporrier, Karine, Khemissa-Akouz, Faiza, Legoux, Jean-Louis, Juzyna, Beata, Gourgou, Sophie, O'Callaghan, Christopher, Jouffroy-Zeller, Claire, Rat, Patrick, Malka, David, Castan, Florence, Bachet, Jean-Baptiste, Trials Group, Canadian Cancer, Group, Unicancer-GI–PRODIGE, Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), UNICANCER, Hôpital Beaujon, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Claude Huriez [Lille], CHU Lille, CRLCC Paul Strauss, Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Service d'Hépato-gastro-entérologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Hôpital privé Jean Mermoz, CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut de Génétique Moléculaire de Montpellier (IGMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon, Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre Hospitalier Universitaire de Reims (CHU Reims), Service de chirurgie hepato-pancreato-biliaire, Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Hôpital Louis Pasteur [Colmar] (CH Colmar), CHU Rouen, Normandie Université (NU), CHU Mont de Marsan, Hôpital Côte de Nacre [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre Hospitalier Saint Jean de Perpignan, Centre Hospitalier Régional d'Orléans (CHRO), R&D UNICANCER, Fédération Nationale des Centres de Lutte Contre le Cancer (FNCLCL/UNICANCER), UNICANCER-UNICANCER, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Oncologie digestive, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Service d'Hépato-Gastro-Entérologie [CHU Pitié-Salpêtrière], 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), Institut de Cancérologie de Lorraine - Alexis Vautrin (ICL), Hôpital Beaujon-Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Hôpital Claude Huriez, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CRLCC Antoine Lacassagne, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon, Centre Hospitalier Régional d'Orléans (CHR), Service de Gastroentérologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Adult, Male, medicine.medical_specialty, FOLFIRINOX, Leucovorin, [SDV.CAN]Life Sciences [q-bio]/Cancer, Irinotecan, Deoxycytidine, Gastroenterology, Disease-Free Survival, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Pancreatic cancer, Antineoplastic Combined Chemotherapy Protocols, Organometallic Compounds, medicine, Adjuvant therapy, Humans, Prospective Studies, Survival rate, Aged, Proportional Hazards Models, Aged, 80 and over, business.industry, Combination chemotherapy, General Medicine, Middle Aged, medicine.disease, Gemcitabine, 3. Good health, Oxaliplatin, Pancreatic Neoplasms, Drug Combinations, Chemotherapy, Adjuvant, 030220 oncology & carcinogenesis, Female, 030211 gastroenterology & hepatology, Fluorouracil, Folfirinox Regimen, Lung Diseases, Interstitial, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, medicine.drug
Abstract: International audience; BACKGROUND:Among patients with metastatic pancreatic cancer, combination chemotherapy with fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) leads to longer overall survival than gemcitabine therapy. We compared the efficacy and safety of a modified FOLFIRINOX regimen with gemcitabine as adjuvant therapy in patients with resected pancreatic cancer.METHODS:We randomly assigned 493 patients with resected pancreatic ductal adenocarcinoma to receive a modified FOLFIRINOX regimen (oxaliplatin [85 mg per square meter of body-surface area], irinotecan [180 mg per square meter, reduced to 150 mg per square meter after a protocol-specified safety analysis], leucovorin [400 mg per square meter], and fluorouracil [2400 mg per square meter] every 2 weeks) or gemcitabine (1000 mg per square meter on days 1, 8, and 15 every 4 weeks) for 24 weeks. The primary end point was disease-free survival. Secondary end points included overall survival and safety.RESULTS:At a median follow-up of 33.6 months, the median disease-free survival was 21.6 months in the modified-FOLFIRINOX group and 12.8 months in the gemcitabine group (stratified hazard ratio for cancer-related event, second cancer, or death, 0.58; 95% confidence interval [CI], 0.46 to 0.73; P
Published: 2018

49. Do perfusion and diffusion MRI predict glioblastoma relapse sites following chemoradiation?

Author: Jean Albert Lotterie, Corinne Johnson, Jonathan Khalifa, Marie Pierre Sunyach, Anne Laprie, Elizabeth Cohen-Jonathan Moyal, Georges Noël, Léonor Chaltiel, Gilles Truc, F. Tensaouti, Alexandra Benouaich-Amiel, Isabelle Berry, M. Charissoux, I. Catalaa, Patrice Péran, Carlos Gomez-Roca, Toulouse Neuro Imaging Center (ToNIC), 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)-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Dept Radiat Oncol, Institut Claudius Regaud, Institut Claudius Regaud, CHU Rangueil, Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), 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 Paul Strauss, CRLCC Paul Strauss, 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 Nucléaire [Toulouse], CHU Toulouse [Toulouse], Centre Léon Bérard [Lyon], Département de radiothérapie, CRLCC Val d'Aurelle - Paul Lamarque, and Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Adult, Male, Cancer Research, Fluid-attenuated inversion recovery, computer.software_genre, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, Voxel, Image Processing, Computer-Assisted, medicine, Humans, Effective diffusion coefficient, Prospective cohort study, ComputingMilieux_MISCELLANEOUS, Aged, Aged, 80 and over, Brain Mapping, Temozolomide, Brain Neoplasms, business.industry, [SCCO.NEUR]Cognitive science/Neuroscience, Chemoradiotherapy, Middle Aged, Hyperintensity, 3. Good health, Diffusion Magnetic Resonance Imaging, nervous system, Neurology, Oncology, 030220 oncology & carcinogenesis, Concomitant, Female, Neurology (clinical), Neoplasm Recurrence, Local, Glioblastoma, Nuclear medicine, business, computer, Magnetic Resonance Angiography, Diffusion MRI, medicine.drug
Abstract: To assess the value of T2* dynamic-susceptibility contrast MRI (DSC-MRI) and diffusion-weighted imaging (DWI) to predict the glioblastoma relapse sites after chemoradiation. From a cohort of 44 patients, primarily treated with radiotherapy (60 Gy) and concomitant temozolomide for glioblastoma, who were included in the reference arm of a prospective clinical trial (NCT01507506), 15 patients relapsed and their imaging data were analyzed. All patients underwent anatomical MRI, DSC-MRI and DWI before radiotherapy and every 2 months thereafter until relapse. Voxels within the sites of relapse were correlated with their perfusion and/or diffusion abnormality (PDA) pretreatment status after rigid co-registration. The relative cerebral blood volume (rCBV) and apparent diffusion coefficient (ADC) were used as biomarkers. Several PDA areas were thresholded: hyperperfused voxels using a 1.75 fixed rCBV threshold (HPt); hypoperfused (hPg) and hyperperfused (HPg) voxels using a histogram-based Gaussian method; diffusion-restricted voxels (DRg); and HPg voxels with diffusion restriction (HPg&DRg). Two sets of voxels (2,459,483 and 2,073,880) were analyzed according to these thresholding methods. Positive predictive values (PPV) of PDA voxels were low (between 9.5 and 31.9 %). The best PPV was obtained with HPg&DRg voxels within the FLAIR hyperintensity, as 18.3 % of voxels without initial PDA were within relapse sites, versus 31.9 % with initial PDA (p
Published: 2016

50. Toxicity and efficacy of cetuximab associated with several modalities of IMRT for locally advanced head and neck cancer

Author: Michel Rives, Pascal Pommier, P. Boisselier, Enrique Chajon, David Pérol, Philippe Giraud, Lionel Perrier, Marc Alfonsi, M. Morelle, Olivier Gallocher, Etienne Bardet, Sophie Dussart, Valentin Calugaru, Georges Noël, Bernard Coche-Dequeant, J.-E. Bibault, Hinda Mecellem, 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), Université Paris Descartes - Paris 5 (UPD5), Centre Léon Bérard [Lyon], Groupe d'analyse et de théorie économique (GATE Lyon Saint-Étienne), École normale supérieure - Lyon (ENS Lyon)-Université Lumière - Lyon 2 (UL2)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Centre National de la Recherche Scientifique (CNRS), 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, Clinique Pasteur, Clinique Pasteur [Toulouse], Institut Sainte Catherine [Avignon], Centre de Lutte Contre le Cancer Nantes Atlantique 'René Gauducheau' (CLCC), Institut Claudius Regaud, Institut Curie [Paris], CRLCC Eugène Marquis (CRLCC), Centre Paul Strauss, CRLCC Paul Strauss, Centre Alexis Vautrin (CAV), Unité de Biostatistique et d'Evaluation des Thérapeutiques (UBET), Centre National de la Recherche Scientifique (CNRS)-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université Lumière - Lyon 2 (UL2)-École normale supérieure - Lyon (ENS Lyon), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Centre Régional de Lutte Contre le Cancer Oscar Lambret, CRLCC Institut Claudius Regaud, Institut Curie, Groupe d'Analyse et de Théorie Economique Lyon - Saint-Etienne (GATE Lyon Saint-Étienne), École normale supérieure de Lyon (ENS de Lyon)-Université Lumière - Lyon 2 (UL2)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Centre National de la Recherche Scientifique (CNRS), Université de Lille-UNICANCER, Hôpital Européen Georges Pompidou [APHP] ( HEGP ), Université Paris Descartes - Paris 5 ( UPD5 ), Groupe d'analyse et de théorie économique ( GATE Lyon Saint-Étienne ), École normale supérieure - Lyon ( ENS Lyon ) -Université Lumière - Lyon 2 ( UL2 ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] ( UJM ) -Centre National de la Recherche Scientifique ( CNRS ), 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 ), CRLCC Eugène Marquis ( CRLCC ), Centre Alexis Vautrin ( CAV ), and Unité de Biostatistique et d'Evaluation des Thérapeutiques ( UBET )
Subjects: Male, 0301 basic medicine, Oncology, medicine.medical_treatment, Contrôle local, Cetuximab, VMAT, Carcinome tête et cou, 0302 clinical medicine, [ SHS.ECO ] Humanities and Social Sciences/Economies and finances, Prospective Studies, Head and neck cancer, Middle Aged, [SHS.ECO]Humanities and Social Sciences/Economics and Finance, 3. Good health, Survie globale, Epidermoid carcinoma, Chemotherapy, Adjuvant, Head and Neck Neoplasms, 030220 oncology & carcinogenesis, Carcinoma, Squamous Cell, Female, Cétuximab, Drug Eruptions, medicine.drug, Mucositis, Intensity-modulated radiation therapy, medicine.medical_specialty, Efficacy, Antineoplastic Agents, Radiothérapie conformationnelle avec modulation d’intensité, Tomotherapy, 03 medical and health sciences, Toxicité, Internal medicine, otorhinolaryngologic diseases, medicine, Humans, Radiology, Nuclear Medicine and imaging, Propensity Score, neoplasms, Volumetric-modulated arc therapy, Toxicity, business.industry, medicine.disease, digestive system diseases, Acute toxicity, Surgery, Radiation therapy, 030104 developmental biology, Nasopharyngeal carcinoma, Radiotherapy, Intensity-Modulated, Neoplasm Recurrence, Local, Tomothérapie, business, RapidArc
Abstract: Purpose Intensity-modulated radiation therapy (IMRT) has shown its interest for head and neck cancer treatment. In parallel, cetuximab has demonstrated its superiority against exclusive radiotherapy. The objective of this study was to assess the acute toxicity, local control and overall survival of cetuximab associated with different IMRT modalities compared to platinum-based chemotherapy and IMRT in the ARTORL study ( NCT02024035 ). Patients and method This prospective, multicenter study included patients with epidermoid or undifferentiated nasopharyngeal carcinoma, epidermoid carcinoma of oropharynx and oral cavity (T1–T4, M0, N0–N3). Acute toxicity, local control and overall survival were compared between groups (patients receiving cetuximab or not). Propensity score analysis at the ratio 1:1 was undertaken in an effort to adjust for potential bias between groups due to non-randomization. Results From the 180 patients included in the ARTORL study, 29 patients receiving cetuximab and 29 patients treated without cetuximab were matched for the analysis. Ten patients (34.5%) reported acute dermal toxicity of grade 3 in the cetuximab group versus three (10.3%) in the non-cetuximab group obtained after matching ( P = 0.0275). Cetuximab was not significantly associated with more grade 3 mucositis ( P = 0.2563). There were no significant differences in cutaneous or oral toxicity for patients treated with cetuximab between the different IMRT modalities ( P = 1.000 and P = 0.5731, respectively). There was no significant difference in local relapse-free survival ( P = 0.0920) or overall survival ( P = 0.4575) between patients treated with or without cetuximab. Conclusion Patients treated with cetuximab had more cutaneous toxicities, but oral toxicity was similar between groups. The different IMRT modalities did not induce different toxicity profiles.
Published: 2016

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