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1. Potassium iodide (KI) prophylaxis in the case of a nuclear accident: A new marketing authorization in France

Author: Marc Benderitter, Francois Caire-Maurisier, Caroline Crambes, Thierry Pourcher, Jean-Charles Martin, Jacques Darcourt, Maâmar Souidi, Pôle Santé Environnement - Direction Santé (IRSN/PSE-SANTE), Institut de Radioprotection et de Sûreté Nucléaire (IRSN), Pharmacie Centrale des Armées (PCA), Direction des Approvisionnements en produits de Santé des Armées, Fleury-les-Aubrais, 45404, France (PCA), Transporteurs et Imagerie, Radiothérapie en Oncologie et Mécanismes biologiques des Altérations du Tissu Osseux (TIRO-MATOs - UMR E4320), Service Hospitalier Frédéric Joliot (SHFJ), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-UMR E4320 (TIRO-MATOs), 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)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Côte d'Azur (UCA)-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)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Côte d'Azur (UCA), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Département de Médecine Nucléaire [Nice] (CHU-Nice), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA)-UNICANCER-Université Côte d'Azur (UCA)-Centre Hospitalier Universitaire de Nice (CHU Nice), Laboratoire de radiotoxicologie et radiobiologie expérimentale (IRSN/PSE-SANTE/SESANE/LRTOX), Service de recherche sur les effets biologiques et Sanitaires des rayonnements ionisants (IRSN/PSE-SANTE/SESANE), Institut de Radioprotection et de Sûreté Nucléaire (IRSN)-Institut de Radioprotection et de Sûreté Nucléaire (IRSN), and ANR-11-RSNR-0019,PRIODAC,Prophylaxie répétée par l'iode stable et contre-mesures innovantes en situation accidentelle(2011)
Subjects: Thyroid, Global and Planetary Change, Potassium iodide, Potassium iodide Thyroid Nuclear accident Iodine thyroid blocking, Environmental Chemistry, Iodine thyroid blocking, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Environmental Science (miscellaneous), Nuclear accident
Abstract: International audience; Prophylaxis by “KI 65 mg, breakable tablet” is a pharmacological countermeasure of radiological protection adapted for the prevention of thyroid cancer after exposure to radioactive iodine. A first modification of the marketing authorization of “KI 65 mg, breakable tablet” for repeated prophylaxis for adults and children above 12 years old was obtained in France in 2020. At this point in time it is recommended to exclude the repeated intake of “KI- 65 mg, breakable tablet” by pregnant and breastfeeding women and children below 12 years old, who should consequently be subjected to a priority evacuation from the contaminated zone. Regulatory toxicology studies are underway in order to support an upcoming proposal of modification of the marketing authorization of “KI- 65 mg, breakable tablet” for repeated prophylaxis for pregnant women and children below 12 years old.
Published: 2022

2. Métabolomique et imagerie TEP-FDG des cancers du sein

Author: Caroline Bailleux, J. Gal, Thierry Pourcher, Jacques Darcourt, Laurent Arnould, David Chardin, Olivier Humbert, Jean-Marie Guigonis, Pôle d'Imagerie Médecine Nucléaire, Centre Antoine-Lacassagne, Université Côte d'Azur, Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA)-UNICANCER-Université Côte d'Azur (UCA), UMR E4320 (TIRO-MATOs), 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)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Côte d'Azur (UCA), Recherche, Innovation et Statistiques [Nice] (Centre de Cancérologie Antoine-Lacassagne), Service d'oncologie médicale [Centre Antoine Lacassagne, Nice], Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), and UNICANCER
Subjects: 03 medical and health sciences, Breast cancer, 0302 clinical medicine, Radiological and Ultrasound Technology, FDG, [SDV]Life Sciences [q-bio], Biophysics, Metabolomics, Radiology, Nuclear Medicine and imaging, 030218 nuclear medicine & medical imaging
Abstract: Resume Le metabolisme tumoral est etroitement lie a la tumorogenese et varie selon le phenotype tumoral. Les techniques de metabolomique peuvent fournir des donnees quantitatives concernant un grand nombre de metabolites et permettent l’analyse de nombreuses voies metaboliques intriquees. La tomographie par emission (TEP) de positons au 18F-fluorodeoxyglucose (FDG) permet une mesure in vivo de l’avidite cellulaire en glucose. L’objectif de ce travail etait de rechercher et comprendre les correlations existantes entre donnees de metabolomique et intensite de captation du FDG dans le cadre du cancer du sein. Soixante-dix echantillons tumoraux provenant de patientes presentant un cancer du sein et pour lesquelles les resultats d’une TEP-FDG pretherapeutique etaient disponibles ont ete analyses selon un protocole de metabolomique, non ciblee par chromatographie liquide et couplee a une spectrometrie de masse. Les echantillons ont ete separes en deux groupes selon l’intensite de fixation tumorale du FDG en prenant la valeur mediane de la SUVmax pour dichotomiser. Huit cent cinquante-quatre metabolites ont ete identifies. Une analyse discriminante des moindres carres partiels et une analyse de classification supervisee ont permis de creer un modele permettant de predire l’avidite en FDG a partir des donnees de metabolomique avec une precision de 0,73 a 0,77. Les metabolites correles a l’intensite de fixation du FDG etaient, entre autres, la glutathione, des acides amines tels que le glutamate, la proline ou la tyrosine, l’acetyl-carnitine, des metabolites de la voie de la kynurenine et des polyamines telles que la N1,N12-diacetylspermine. Ces metabolites ont deja ete rapportes comme marqueurs de l’agressivite tumorale. Une correlation directe entre avidite en FDG et glycolyse n’a pas pu etre mise en evidence, cependant de nombreux signes indirects montraient une plus forte activite glycolytique dans les tumeurs avides en FDG. L’analyse de metabolites inconnus, mise en evidence par cette approche, pourrait permettre l’identification de nouveaux biomarqueurs d’interet.
Published: 2021

3. A double-blind placebo-controlled randomized phase II trial assessing the activity and safety of regorafenib in non-adipocytic sarcoma patients previously treated with both chemotherapy and pazopanib

Author: Sébastien Salas, Jennifer Wallet, Emilie Decoupigny, Thomas Brodowicz, Jean-Yves Blay, Christine Chevreau, Marie-Cécile Le Deley, Marie Vanseymortier, Olivier Mir, Axel Le Cesne, Loic Chaigneau, Lucie Laroche, François Bertucci, Esma Saada-Bouzid, Isabelle Ray-Coquard, Nicolas Penel, Sophie Taïeb, Corinne Delcambre, Emmanuelle Bompas, Antoine Italiano, Université de Lille, Institut Gustave Roussy (IGR), Service de Biostatistiques [CHRU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Léon Bérard [Lyon], Département de médecine oncologique [Gustave Roussy], Université de Bordeaux (UB), Hôpital de la Timone [CHU - APHM] (TIMONE), 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 l'Ouest [Angers/Nantes] (UNICANCER/ICO), 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), Medical Oncology Department [Nice], Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA)-UNICANCER-Université Côte d'Azur (UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), 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 Claudius Regaud, Medizinische Universität Wien = Medical University of Vienna, Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER, Direction de la recherche clinique et de l'innovation [CHU Amiens], CHU Amiens-Picardie, Centre de recherche en épidémiologie et santé des populations (CESP), and Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay
Subjects: Male, 0301 basic medicine, Cancer Research, Pyridines, medicine.medical_treatment, Soft Tissue Neoplasms, Kaplan-Meier Estimate, Gastroenterology, chemistry.chemical_compound, 0302 clinical medicine, Antineoplastic Combined Chemotherapy Protocols, ComputingMilieux_MISCELLANEOUS, Sulfonamides, Cross-Over Studies, Soft tissue sarcoma, Hazard ratio, Anemia, Sarcoma, Middle Aged, Treatment Outcome, Oncology, 030220 oncology & carcinogenesis, Disease Progression, Female, medicine.drug, Adult, Diarrhea, Chest Pain, medicine.medical_specialty, Indazoles, [SDV.CAN]Life Sciences [q-bio]/Cancer, Placebo, Pazopanib, 03 medical and health sciences, Double-Blind Method, Regorafenib, Internal medicine, medicine, Humans, Adverse effect, Aged, Chemotherapy, business.industry, Phenylurea Compounds, Leukopenia, medicine.disease, Confidence interval, Pyrimidines, 030104 developmental biology, chemistry, business
Abstract: Background Metastatic soft tissue sarcomas (STSs) management remains an unmet medical need. We assessed the activity and safety of regorafenib in patients with metastatic non-adipocytic STS who were previously treated with both chemotherapy and pazopanib. Patients and methods This double-blind, placebo-controlled, multicenter comparative randomized phase II trial included patients with histologically proven advanced and inoperable STS. Patients receiving placebo were offered optional cross-over for centrally confirmed disease progression. Primary end-point was centrally reviewed Response Evaluation Criteria in Solid Tumours–based progression-free survival (PFS), analysed on the intent-to-treat data set. In total, 24 events were required for 90% power, hazard ratio (HR) = 0.33 (median PFS, 3.6 versus 1.2 months), and 1-sided α = 0.1 ( ClinicalTrials.gov , NCT01900743 ). Results From December 2015 to October 2017, 37 patients were randomized; 18 to regorafenib and 19 to placebo. Thirteen patients assigned to placebo switched to regorafenib after progression. Median follow-up was 27.2 months (95% confidence interval [CI]: 24.4–not reached). We observed a significant PFS benefit of regorafenib compared with placebo (adjusted HR = 0.33; 95% CI: 0.15–0.74; p = 0.0007 median PFS = 2.1 versus 1.1 months, respectively), and a large and nearly significant overall survival (OS) benefit despite the cross-over (adjusted HR = 0.49; 95% CI: 0.23–1.06; p = 0.007; median OS = 17.8 versus 8.2 months). Before cross-over, the most common grade III or higher adverse events were lymphopenia (5 versus 1, respectively), diarrhoea (4 versus 0), dyspnoea (3 versus 1), skin toxicity (3 versus 0), arterial hypertension (2 versus 0), and increased transaminases (2 versus 0). Conclusion The present study demonstrated a meaningful clinical anti-tumour activity with regorafenib in heavily pre-treated patients with non-adipocytic STS.
Published: 2020

4. Deep Learning Facilitates Distinguishing Histologic Subtypes of Pulmonary Neuroendocrine Tumors on Digital Whole-Slide Images

Author: Marius Ilié, Jonathan Benzaquen, Paul Tourniaire, Simon Heeke, Nicholas Ayache, Hervé Delingette, Elodie Long-Mira, Sandra Lassalle, Marame Hamila, Julien Fayada, Josiane Otto, Charlotte Cohen, Abel Gomez-Caro, Jean-Philippe Berthet, Charles-Hugo Marquette, Véronique Hofman, Christophe Bontoux, Paul Hofman, FHU OncoAge - Pathologies liées à l’âge [CHU Nice] (OncoAge), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Pharmacologie Moléculaire et Cellulaire [UNIV Côte d'Azur] (UPMC)-Université Côte d'Azur (UCA), 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), Université Côte d'Azur (UCA), Laboratoire de Pathologie Clinique et Expérimentale. Hôpital Pasteur [Nice], Hôpital Pasteur [Nice] (CHU), Département Oncologie Médicale [Nice], Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA)-UNICANCER-Université Côte d'Azur (UCA), E-Patient : Images, données & mOdèles pour la médeciNe numériquE (EPIONE), 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), The University of Texas M.D. Anderson Cancer Center [Houston], UNICANCER-Université Côte d'Azur (UCA), Centre Hospitalier Universitaire de Nice (CHU Nice), ANR-19-P3IA-0002,3IA@cote d'azur,3IA Côte d'Azur(2019), and ANR-15-IDEX-0001,UCA JEDI,Idex UCA JEDI(2015)
Subjects: Cancer Research, HALO-AI, lung, neuroendocrine carcinoma, deep learning, CNN, Oncology, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], [SDV.CAN]Life Sciences [q-bio]/Cancer, [INFO.INFO-AI]Computer Science [cs]/Artificial Intelligence [cs.AI], respiratory tract diseases
Abstract: International audience; The histological distinction of lung neuroendocrine carcinoma, including small cell lung carcinoma (SCLC), large cell neuroendocrine carcinoma (LCNEC) and atypical carcinoid (AC), can be challenging in some cases, while bearing prognostic and therapeutic significance. To assist pathologists with the differentiation of histologic subtyping, we applied a deep learning classifier equipped with a convolutional neural network (CNN) to recognize lung neuroendocrine neoplasms. Slides of primary lung SCLC, LCNEC and AC were obtained from the Laboratory of Clinical and Experimental Pathology (University Hospital Nice, France). Three thoracic pathologists blindly established gold standard diagnoses. The HALO-AI module (Indica Labs, UK) trained with 18,752 image tiles extracted from 60 slides (SCLC = 20, LCNEC = 20, AC = 20 cases) was then tested on 90 slides (SCLC = 26, LCNEC = 22, AC = 13 and combined SCLC with LCNEC = 4 cases; NSCLC = 25 cases) by F1-score and accuracy. A HALO-AI correct area distribution (AD) cutoff of 50% or more was required to credit the CNN with the correct diagnosis. The tumor maps were false colored and displayed side by side to original hematoxylin and eosin slides with superimposed pathologist annotations. The trained HALO-AI yielded a mean F1-score of 0.99 (95% CI, 0.939–0.999) on the testing set. Our CNN model, providing further larger validation, has the potential to work side by side with the pathologist to accurately differentiate between the different lung neuroendocrine carcinoma in challenging cases.
Published: 2022

5. CyberSec4Europe D3.21 - Framework to design and implement adaptive security systems

Author: Alzubair Hassan, Dimitri Van Landuyt, Liliana Pasquale, Manuel Cheminod, Marko Kompara, Panayiotis Kotzanikolaou, Romain Laborde, Susana Gonzalez, Laborde, Romain, Cyber Security for Europe - CyberSec4Europe - 830929 - INCOMING, University College Dublin [Dublin] (UCD), John Paul II Catholic University of Lublin (KUL), National Research Council of Italy | Consiglio Nazionale delle Ricerche (CNR), University of Maribor, Unité de Pharmacogénétique et Radiogénétique des Cancers (UPRC), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA)-UNICANCER-Université Côte d'Azur (UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), Service IntEgration and netwoRk Administration (IRIT-SIERA), Institut de recherche en informatique de Toulouse (IRIT), Université Toulouse Capitole (UT Capitole), Université de Toulouse (UT)-Université de Toulouse (UT)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Toulouse Mind & Brain Institut (TMBI), Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université Toulouse Capitole (UT Capitole), Université de Toulouse (UT), Atos Spain, University college Dublin, KU Leuven, Consiglio Nazionale delle Ricerche, University of Piraeus Research Centre, IRIT - Institut de Recherche en Informatique de Toulouse, ATOS, and European Project: 830929,CyberSec4Europe
Subjects: [INFO.INFO-CR]Computer Science [cs]/Cryptography and Security [cs.CR], [INFO.INFO-NI]Computer Science [cs]/Networking and Internet Architecture [cs.NI], [INFO.INFO-NI] Computer Science [cs]/Networking and Internet Architecture [cs.NI], [INFO.INFO-CR] Computer Science [cs]/Cryptography and Security [cs.CR]
Abstract: The research results presented in this document represent the deliverable D3.21: “Framework to design and implement adaptive security systems” and are the continuation of the deliverable D3.4: “Analysis of key research challenges for adaptive security”. In this deliverable we aim to validate the challenges elicited in D3.4 with practitioners from industry. We also aim to understand how the assets developed by each partner in task T3.5 could be used to engineer an adaptive security system. In this deliverable, we present the results of a survey conducted with security practitioners from industry. The objective of the survey is to acquire the practitioners’ perspective on the application of adaptive security technologies and identify the research challenges that practitioners perceive to be the most critical in adaptive security. We use a reference architecture of an adaptive security system to identify the contributions of the assets provided by each partner. We showcase how the joint contributions of each asset can support some of the maritime transport use case scenarios elicited in task T5.5 Maritime Transport.
Published: 2022

6. Cabozantinib-nivolumab sequence in metastatic renal cell carcinoma: The CABIR study

Author: Yann‐Alexandre Vano, Letuan Phan, Gwenaelle Gravis, Iphigénie Korakis, Friederike Schlürmann, Denis Maillet, Mostefa Bennamoun, Nadine Houede, Delphine Topart, Delphine Borchiellini, Philippe Barthelemy, Raffaele Ratta, Thomas Ryckewaert, Ali Hasbini, Sophie Hans, Sheik Emambux, Sandra Cournier, Elena Braychenko, Réza‐Thierry Elaidi, Stéphane Oudard, Cancer Research and Personalized Medicine - CARPEM [Paris], Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'Oncologie Médicale [Centre hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Institut Mutualiste de Montsouris (IMM), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), ChemBioPharm, Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER, Département de Radio-Oncologie [Brest] (Clinique Pasteur), Clinique Pasteur [Brest], Département de radiologie, Institut Gustave Roussy (IGR), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), 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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), 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), 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), Service d'Oncologie Médicale [Montsouris], Institut de Cancérologie du GARD ICG - CHU Nîmes (Instit Cancéro - GARD), 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), Pôle de Chirurgie Oncologique générale, Gynécologique et Mammaire [Centre Antoine-Lacassagne], UNICANCER-Université Côte d'Azur (UCA)-UNICANCER-Université Côte d'Azur (UCA), 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), Institut de Cancérologie de Strasbourg Europe (ICANS), Hôpital Foch [Suresnes], Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), and PSEN Pharm
Subjects: Cancer Research, Pyridines, [SDV]Life Sciences [q-bio], Tyrosine kinase inhibitor, Antineoplastic Agents, [SDV.CAN]Life Sciences [q-bio]/Cancer, MESH: Anilides, Humans, MESH: Protein Kinase Inhibitors, Anilides, Carcinoma, Renal Cell, Protein Kinase Inhibitors, Retrospective Studies, MESH: Humans, MESH: Pyridines, Cabozantinib, MESH: Retrospective Studies, MESH: Carcinoma, Renal Cell, Kidney Neoplasms, Renal cell carcinoma, Nivolumab, Oncology, Matching-adjusted study, MESH: Antineoplastic Agents, MESH: Nivolumab, Immunotherapy, MESH: Kidney Neoplasms
Abstract: International audience; Nivolumab and cabozantinib are approved agents in mRCC patients after sunitinib/pazopanib (TKI) failure. However, the optimal sequence, cabozantinib then nivolumab (CN) or nivolumab then cabozantinib (NC), is still unknown. The CABIR study aimed to identify the optimal sequence between CN and NC after frontline VEGFR-TKI. In this multicenter retrospective study, we collected data from mRCC pts receiving CN or NC, after frontline VEGFR-TKI. A propensity score (PrS) was calculated to manage bias selection, and sequence comparisons were carried out with a cox model on a matched sample 1:1. The primary endpoint was progression-free survival (PFS) from the start of second line to progression in third line (PFS2-3 ). Key secondary endpoints included overall survival from second line (OS2 ). Out of 139 included mRCC patients, 38 (27%) and 101 (73%) received CN and NC, respectively. Overlap in PrS allowed 1:1 matching for each CN pts, with characteristics well balanced. For both PFS2-3 and OS2 , NC sequence was superior to CN (PFS2-3 : HR = 0.58 [0.34-0.98], P = .043; OS2 : 0.66 [0.42-1.05], P = .080). Superior PFS2-3 was in patients treated between 6 and 18 months with prior VEGFR-TKI (P = .019) and was driven by a higher PFSL3 with cabozantinib when given after nivolumab (P
Published: 2022

7. TAXOMET : A French prospective multicentric randomized controlled phase II study comparing docetaxel plus metformin versus docetaxel plus placebo in mCRPC

Author: Pujalte Martin, Marc, Borchiellini, Delphine, Thamphya, Brice, Guillot, Aline, Paoli, Jean-Baptiste, Besson, Dominique, Hilgers, Werner, Priou, Frank, El Kouri, Claude, Hoch, Benjamin, Deville, Jean-Laurent, Schiappa, Renaud, Cheli, Sandrine, Milano, Gérard, Tanti, Jean-François, Bost, Frédéric, Ferrero, Jean-Marc, Pôle de Chirurgie Oncologique générale, Gynécologique et Mammaire [Centre Antoine-Lacassagne], Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA)-UNICANCER-Université Côte d'Azur (UCA), UNICANCER-Université Côte d'Azur (UCA), Institut de Cancérologie Lucien Neuwirth, CHU Saint-Etienne, Hôpital Privé Clairval [Marseille], Hôpital Privé des Côtes d'Armor (HPCA), Institut Sainte Catherine [Avignon], CHD Vendee (La Roche Sur Yon), Centre Catherine-de-Sienne [Nantes] (CCS), Centre Azuréen de Cancérologie [Mougins, France], Hôpital de la Timone [CHU - APHM] (TIMONE), Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon (CHD Vendée), Université Nice Sophia Antipolis (1965 - 2019) (UNS), and Tanti, Jean-François
Subjects: [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Prostate cancer, Docetaxel, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Metformin, Metastatic castration-resistant prostate cancer
Abstract: International audience; Background: Docetaxel (DOCE) is a standard of care in metastatic castration-resistant prostate cancer (mCRPC). Several retrospective studies suggested a decrease in Prostate Cancer incidence and mortality with metformin (MET). MET has also demonstrated anti-tumor activity in Prostate Cancer preclinical models, with increased apoptosis when added to DOCE. We aimed at exploring the role of MET in combination with DOCE in mCRPC.Patients and methods: Non-diabetic mCRPC patients were randomly assigned to receive DOCE 75 mg/m2 every 21 days + prednisone (5 mg. BID) with either MET 850 mg BID (D+M) or placebo (D+P) up to 10 cycles. Prostate-Specific Antigen (PSA) response ≥50% from baseline was the primary end point. Secondary end points included objective response rate (ORR), progression-free survival (PFS), overall survival (OS), toxicity and quality of life (QoL).Results: Out of 99 patients were randomized (D+M = 50; D+P = 49) in 10 French centers. The median follow-up was 86 (IQR 73-88) months. The PSA-response rate reached 66% in the D+M arm, but was not different from that observed in the D+P arm (63%, P = 0,94). In the D+M and D+P arms, the ORR was 28% and 24%, the median PFS was 7.8 and 6.0 months and the median OS was 27 and 20 months (ns), respectively. Diarrhea grade I to II was more frequent in the MET arm (66% vs. 43%). No impairment of QoL was observed.Conclusion: MET addition failed to improve the standard DOCE regimen in mCRPC. Further research targeting tumor cell metabolism should be performed.
Published: 2021

8. Leptomeningeal enhancement on post-contrast FLAIR images for early diagnosis of Susac syndrome

Author: François Cotton, Damien Biotti, Margaux Roques, Mahmoud Charif, Christophe Cognard, Francoise Durand Dubief, Jean Darcourt, Jérôme De Seze, Thomas Tourdias, Vincent Larrue, Gilles Adam, Fanny Varenne, Guillaume Bellanger, Stéphane Kremer, Alain Viguier, Nicolas Menjot de Champfleur, Pierre Labauge, Fabrice Bonneville, Fleur Lerebours, Jonathan Ciron, Julien Savatovsky, Michael Obadia, Sofia Patsoura, Cécile Dulau, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Pôle d'Imagerie Médecine Nucléaire, Centre Antoine-Lacassagne, Université Côte d'Azur, Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA)-UNICANCER-Université Côte d'Azur (UCA), Laboratoire de psychologie clinique, de psychopathologie et de psychanalyse (LPCPP), Aix Marseille Université (AMU), Ingénierie des Matériaux Polymères (IMP), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Département de neurologie [Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [CHU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université de Montpellier (UM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université de Montpellier (UM), Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), RMN et optique : De la mesure au biomarqueur, Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), CHU Bordeaux [Bordeaux], Wageningen University and Research [Wageningen] (WUR), CIC Strasbourg (Centre d’Investigation Clinique Plurithématique (CIC - P) ), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Nouvel Hôpital Civil de Strasbourg-Hôpital de Hautepierre [Strasbourg], i-SEP (i-SEP), CRLCC René Huguenin, Institut Curie [Paris], Unité de recherche Pharmacologie-Toxicologie (UPT), and Institut National de la Recherche Agronomique (INRA)
Subjects: medicine.medical_specialty, Susac Syndrome, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, media_common.quotation_subject, Contrast Media, Fluid-attenuated inversion recovery, post-contrast FLAIR, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, leptomeningeal enhancement, medicine, Contrast (vision), Humans, media_common, Retrospective Studies, business.industry, Multiple sclerosis, medicine.disease, Magnetic Resonance Imaging, Multiples sclerosis, Early Diagnosis, Neurology, Feature (computer vision), Neurology (clinical), Radiology, business, 030217 neurology & neurosurgery
Abstract: Background: Leptomeningeal enhancement (LME) is a key feature of Susac syndrome (SuS) but is only occasionally depicted on post-contrast T1-weighted images (T1-WI). Objective: As post-contrast fluid-attenuated inversion recovery (FLAIR) may be more sensitive, our aim was to assess LME in SuS on this sequence. Methods: From 2010 to 2020, 20 patients with definite SuS diagnosis were retrospectively enrolled in this multicentre study. Two radiologists independently assessed the number of LME on post-contrast FLAIR and T1-WI acquisitions performed before any treatment. A chi-square test was used to compare both sequences and the interrater agreement was calculated. Results: Thirty-five magnetic resonance imagings (MRIs) were performed before treatment, including 19 post-contrast FLAIR images in 17 patients and 25 post-contrast T1-WI in 19 patients. In terms of patients, LME was observed on all post-contrast FLAIR, contrary to post-contrast T1-WI (17/17 (100%) vs. 15/19 (79%), p Conclusion: LME was always observed and easily visible on post-contrast FLAIR images prior to SuS treatment. In association with other MRI features, it is highly indicative of SuS.
Published: 2021

9. COVID-19 vaccine race: watch your step for cancer patients

Author: Raphaelle Fanciullino, Joseph Ciccolini, Gérard Milano, Simulation and Modeling of Adaptive Response for Therapeutics in Cancer (SMARTc), Centre de Recherche en Cancérologie de Marseille (CRCM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU)-Centre 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), Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), 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), Unité de Pharmacogénétique et Radiogénétique des Cancers (UPRC), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA)-UNICANCER-Université Côte d'Azur (UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), UNICANCER-Université Côte d'Azur (UCA), 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, and 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)
Subjects: Oncology, Cancer Research, medicine.medical_specialty, COVID-19 Vaccines, Time Factors, Coronavirus disease 2019 (COVID-19), [SDV]Life Sciences [q-bio], Acceleration, Population, Cancer immunotherapy, Vaccines Administered, 03 medical and health sciences, 0302 clinical medicine, Neoplasms, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, Humans, Medicine, RNA, Messenger, Dosing, education, Pandemics, 030304 developmental biology, Drug Carriers, 0303 health sciences, Liposome, education.field_of_study, Frailty, Immunization Programs, SARS-CoV-2, business.industry, Vaccination, Comment, Significant part, COVID-19, Cancer, medicine.disease, Health policy, 3. Good health, 030220 oncology & carcinogenesis, Liposomes, business
Abstract: SummaryPatients with cancer should benefit from COVID-19 vaccination. Some of the most advanced vaccine candidates are mRNAs encapsulated into lipid carriers, and small liposomes are expected to accumulate in tumour tissues through the enhanced and permeation retention effect. However, to what extent solid tumours could take up a significant part of the vaccine dose as well remains unknown. This calls for a careful evaluation of the efficacy of these promising mRNA COVID-19 vaccines administered as lipid carriers for patients with solid tumours, including a possible re-appraisal of the dosing for optimal protection of this specific and frail population.
Published: 2021

10. The association between adverse events and outcome under checkpoint inhibitors: Where is the deal?

Author: Federico Innocenti, Joseph Ciccolini, Gérard Milano, Unité de Pharmacogénétique et Radiogénétique des Cancers (UPRC), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA)-UNICANCER-Université Côte d'Azur (UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), UNICANCER-Université Côte d'Azur (UCA), University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC), Simulation and Modeling of Adaptive Response for Therapeutics in Cancer (SMARTc), Centre de Recherche en Cancérologie de Marseille (CRCM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU)-Centre 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), 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, and 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)
Subjects: 0301 basic medicine, Cancer Research, medicine.medical_specialty, Immune checkpoint inhibitors, [SDV]Life Sciences [q-bio], Treatment outcome, Immunogenetics, lcsh:RC254-282, Outcome (game theory), 03 medical and health sciences, Review article, 0302 clinical medicine, Immune-related adverse events, polycyclic compounds, Medicine, Adverse effect, Association (psychology), Intensive care medicine, business.industry, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Treatment efficacy, 3. Good health, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, Immunotherapy, business, hormones, hormone substitutes, and hormone antagonists, Checkpoint inhibitors
Abstract: Highlights • A review which lays out different potential contributions which can help to understand the IRAEs-outcome link. • There is a possibility to compute a multifactorial index to characterise patients as ICI sensitive or ICI unsensitive. • Prospective trails with ICIs are now fesaible to shape patient care beyond high -dose steroids., Recent reports have put into evidence the possibility of a link between immune-related adverse events (IRAEs) and treatment outcome, patients drawing a benefit from treatment being also exposed to the risk to develop toxicity. A still unanswered question remains the biological origin(s) which can sustain and explain such a relationship. The purpose of this review paper is to lay out different potential contributions which can help to understand the IRAEs-outcome link and to propose clinical perspectives taking advantage of this association. In this respect, pharmacokinetics aspects, immunological and immunogenetics implications have been taken into consideration., Graphical abstract Image, graphical abstract
Published: 2021

11. Subcutaneous Rituximab-MiniCHOP Compared With Subcutaneous Rituximab-MiniCHOP Plus Lenalidomide in Diffuse Large B-Cell Lymphoma for Patients Age 80 Years or Older

Author: Corinne Haioun, Hassan Farhat, Christophe Bonnet, René-Olivier Casasnovas, Peggy Dartigues-Cuillères, Fontanet Bijou, Gilles Salles, Hervé Maisonneuve, Julie Abraham, Ronan Le Calloch, Pierre Feugier, Mathieu Puyade, Jerome Paget, Gianmatteo Pica, Bettina Fabiani, Philippe Ruminy, Gandhi Damaj, Fabrice Jardin, Frederic Peyrade, Elodie Gat, Lucie Oberic, Agathe Waultier-Rascalou, Sandra Malak, Catherine Thieblemont, Hervé Tilly, 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), Pôle de Chirurgie Oncologique générale, Gynécologique et Mammaire [Centre Antoine-Lacassagne], Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA)-UNICANCER-Université Côte d'Azur (UCA), 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), Biomarqueurs et essais cliniques en Cancérologie et Onco-Hématologie (BECCOH), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Saclay, Unité de neurophysiologie [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), 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), Hôpital Dupuytren [CHU Limoges], Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Hospices Civils de Lyon (HCL), Institut Bergonié [Bordeaux], UNICANCER, Centre Hospitalier Métropole Savoie [Chambéry], Laboratoire d'Hématologie Biologique [CHU Caen], 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), CHU Henri Mondor, CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Hospitalier de Versailles André Mignot (CHV), Université de Bretagne Occidentale - UFR Médecine et Sciences de la Santé (UBO UFR MSS), Université de Brest (UBO), Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Hôpital René HUGUENIN (Saint-Cloud), and The Lymphoma Academic Research Organisation [Lyon] (LYSARC)
Subjects: Oncology, Cancer Research, medicine.medical_specialty, business.industry, [SDV]Life Sciences [q-bio], medicine.disease, 3. Good health, Lymphoma, 03 medical and health sciences, 0302 clinical medicine, 030220 oncology & carcinogenesis, Internal medicine, hemic and lymphatic diseases, medicine, Rituximab, Doxorubicin, business, Diffuse large B-cell lymphoma, 030215 immunology, medicine.drug, Lenalidomide
Abstract: PURPOSE: The prognosis of elderly patients with diffuse large B-cell lymphoma (DLBCL) is worse than that of young patients. An attenuated dose of chemotherapy—cyclophosphamide, doxorubicin, vincristine, and prednisone plus rituximab (R-miniCHOP)—is a good compromise between efficacy and safety in very elderly patients. In combination with R-CHOP (R2-CHOP), lenalidomide has an acceptable level of toxicity and may mitigate the negative prognosis of the non–germinal center B-cell–like phenotype. The Lymphoma Study association conducted a multicentric, phase III, open-label, randomized trial to compare R-miniCHOP and R2-miniCHOP. PATIENTS AND METHODS: Patients of age 80 years or older with untreated DLBCL were randomly assigned into the R-miniCHOP21 group or the R2-miniCHOP21 group for six cycles and stratified according to CD10 expression and age. The first cycle of rituximab was delivered by IV on D1 after a prephase and then delivered subcutaneously on D1 of cycles 2-6. Lenalidomide was delivered at a dose of 10 mg once daily on D1-D14 of each cycle. The primary end point was overall survival (OS). RESULTS: A total of 249 patients with new DLBCL were randomly assigned (127 R-miniCHOP and 122 R2-miniCHOP). The median age was 83 years (range, 80-96), and 55% of the patients were classified as non-GCB. The delivered dose for each R-miniCHOP compound was similar in both arms. Over a median follow-up of 25.1 months, the intention-to-treat analysis revealed that R2-miniCHOP did not improve OS (2-year OS 66% in R-miniCHOP and 65.7% in R2-miniCHOP arm, P = .98) in the overall population or in the non-GCB population. Grade 3-4 adverse events occurred in 53% of patients with R-miniCHOP and in 81% of patients with R2-miniCHOP. CONCLUSION: The addition of lenalidomide to R-miniCHOP does not improve OS. Rituximab delivered subcutaneously was safe in this population.
Published: 2021

12. How to promote physical activity during pregnancy : A systematic review

Author: R. Morgant, P. Merviel, Y. Guillodo, P. James, M.A. Giroux-Metges, A. Saraux, M. Muller, P.F. Dupré, Service de Rhumatologie, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-Hôpital Michallon, Pôle de Chirurgie Oncologique générale, Gynécologique et Mammaire [Centre Antoine-Lacassagne], Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), and UNICANCER-Université Côte d'Azur (UCA)-UNICANCER-Université Côte d'Azur (UCA)
Subjects: Adult, medicine.medical_specialty, Maternal Health, media_common.quotation_subject, [SDV]Life Sciences [q-bio], Psychological intervention, Physical activity, Health Promotion, Smartphone application, Body Mass Index, law.invention, 03 medical and health sciences, 0302 clinical medicine, Promotion (rank), Randomized controlled trial, Pregnancy, law, Intervention (counseling), medicine, Humans, Exercise, media_common, 030219 obstetrics & reproductive medicine, business.industry, Pregnancy Outcome, Obstetrics and Gynecology, medicine.disease, Comorbidity, 3. Good health, Pregnancy Complications, Diabetes, Gestational, Treatment Outcome, Reproductive Medicine, 030220 oncology & carcinogenesis, Physical therapy, Female, business
Abstract: Introduction Sedentary lifestyles and physical inactivity have been shown to increase during pregnancy and are a cause of obstetric comorbidity. The objective of this study was to conduct a systematic review of interventions aiming to promote physical activity during pregnancy. Material and methods Databases were searched from January 2008 to September 2019. Selection criteria included randomized controlled trials evaluating the efficacy of interventions promoting physical activity during pregnancy. Results In total, 256 articles were extracted from databases. 202 articles were excluded. Finally, 15 articles were included in the study. 5633 patients were included from various populations. Six studies rated physical activity (PA) as the primary outcome. Five studies suggested promoting physical activity through individual interviews which in two studies showed an increase in PA. Three studies evaluated an intervention based on group interviews and one of these reported a significant increase in PA. Two studies evaluated the use of a Smartphone application to promote physical activity but they did not conclude that they were effective because they were designed with low statistical power. Conclusion The practice of regular PA during pregnancy reduces obstetrical comorbidity. However, interventions seem to have a low impact on the promotion of PA during pregnancy. New intervention strategies need to assessed, such as the use of mobile health interventions.
Published: 2020

13. Identifying a reliable radiomic signature from scarce data: illustration for 18F-FDOPA PET images in glioblastoma patients

Author: Orlhac, Fanny, Rollet, Anne-Capucine, Buvat, Irène, Darcourt, Jacques, Bourg, Véronique, Nioche, Christophe, Bouveyron, Charles, Ayache, Nicholas, Humbert, Olivier, Laboratoire d'Imagerie Translationnelle en Oncologie (LITO ), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), E-Patient : Images, données & mOdèles pour la médeciNe numériquE (EPIONE), 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 Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Département de Médecine Nucléaire [Nice] (CHU-Nice), UNICANCER-Université Côte d'Azur (UCA)-UNICANCER-Université Côte d'Azur (UCA)-Centre Hospitalier Universitaire de Nice (CHU Nice), Transporteurs et Imagerie, Radiothérapie en Oncologie et Mécanismes biologiques des Altérations du Tissu Osseux (TIRO-MATOs - UMR E4320), Service Hospitalier Frédéric Joliot (SHFJ), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-UMR E4320 (TIRO-MATOs), 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)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Côte d'Azur (UCA)-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)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Côte d'Azur (UCA), Service de Neurologie [CHU Nice], Hôpital Pasteur [Nice] (CHU)-Centre Hospitalier Universitaire de Nice (CHU Nice), Modèles et algorithmes pour l’intelligence artificielle (MAASAI), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-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)-Laboratoire Jean Alexandre Dieudonné (LJAD), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)-Scalable and Pervasive softwARe and Knowledge Systems (Laboratoire I3S - SPARKS), Laboratoire d'Informatique, Signaux, et Systèmes de Sophia Antipolis (I3S), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)-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)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)-Laboratoire d'Informatique, Signaux, et Systèmes de Sophia Antipolis (I3S), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Orlhac, Fanny, UMR E4320 (TIRO-MATOs), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Côte d'Azur (UCA)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Côte d'Azur (UCA)-Service Hospitalier Frédéric Joliot (SHFJ), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Laboratoire Jean Alexandre Dieudonné (JAD), Université Côte d'Azur (UCA)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS)-Scalable and Pervasive softwARe and Knowledge Systems (Laboratoire I3S - SPARKS), and COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)-Université Nice Sophia Antipolis (... - 2019) (UNS)
Subjects: [SDV.IB] Life Sciences [q-bio]/Bioengineering, [SDV.IB]Life Sciences [q-bio]/Bioengineering
Abstract: International audience; Aim/Introduction: The design and validation of a reliable radiomic signature is challenging when few patients are available because the disease is rare, the imaging protocol is specific and/or the classes are unbalanced. In this context, we propose an approach to identify a signature and estimate its reliability. Materials and Methods: 84 patients with a clinical and MRI suspicion of recurrent glioblastoma were retrospectively included. Each patient underwent a 18F-FDOPA PET-CT scan. For each patient, the suspicious lesion was segmented and 49 radiomic features were calculated using LIFEx [1]. Our goal was to distinguish between tumor recurrence and radiation-induced necrosis as confirmed on pathological data, or on a 3-month clinical/imaging follow-up. A screening procedure was developed to identify a signature using leave-one-out (LOO) cross-validation. The procedure involved: 1) selection of all features with a p-value of univariate Wilcoxon test lower than alpha varying from 0.005 to 0.10 for (N-1) learning patients, 2) based on these features, selection of only one feature among correlated features using a Pearson correlation cutoff R varying from 0.95 to 0.50, 3) building of a radiomic signature involving the resulting features using a linear discriminant analysis, 4) test of the model on the Nth patient, 5) characterization of the model performance using the Youden Index (Y=sensitivity+specificity-1). The final model selection was based on the consistency of Y values as a function of alpha and R, on the consistency of selected features between the different models, and favored models involving a low number of features. To test the reliability of the selected signature, we repeated the process by excluding one patient using a jackknife procedure (ie, 84 LOO of 83 patients each). We compared the results with those obtained with the same alpha and R when randomly assigning a label to each patient (sham task). Results: 61 patients had tumor recurrence and 23 had radiation necrosis. Visual interpretation yielded Y equal to 0.35 (Lizarraga scale, Se=100%, Sp=35%). Using LOO, 10/28 radiomic models had Y>0.35. The largest Y (Y=0.49, Se=62%, Sp=87%) were obtained with 4 features on average, reflecting the volume, sphericity and heterogeneity (GLCM_Correlation, GLCM_Contrast) of the lesion uptake. Using the jackknife procedure, Y was 0.47±0.06 (range: [0.32;0.56]), significantly higher (Wilcoxon p < 0.05) than for the sham task (Y=0.06±0.18, range: [-0.52;0.47]). Conclusion: The proposed systematic screening procedure enabled the identification of a parsimonious radiomic signature from scarce data. References: [1] Nioche et al. Cancer Res 2018.
Published: 2020

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

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

15. Intrathecal liposomal cytarabine plus systemic therapy versus systemic chemotherapy alone for newly diagnosed leptomeningeal metastasis from breast cancer

Author: Thomas Boulanger, Jérôme Barrière, Audrey Mailliez, Michael Weller, Emilie Le Rhun, Isabelle Rodrigues, Veronique Lorgis, Yves Marie Robin, Jacques Bonneterre, Marie-Cécile Le Deley, Jennifer Wallet, Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U 1192 (PRISM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER, University hospital of Zurich [Zurich], Universität Zürich [Zürich] = University of Zurich (UZH), Service de neuro-oncologie, de neurochirurgie générale et stéréotaxique [CHRU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de Biostatistiques [CHRU Lille], Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Département d'Imagerie [Lille] (Cancer Oscar Lambret ), Cancer Oscar Lambret [Lille], 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 Oncologie Médicale [Nice], Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA)-UNICANCER-Université Côte d'Azur (UCA), Service de pathologie [CHU Lille], Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Université Lille Nord de France (COMUE)-UNICANCER, Service de biostatistiques [CHU Lille] (Centre Oscar Lambret), Université Côte d'Azur (UCA)-UNICANCER-Université Côte d'Azur (UCA)-UNICANCER, University of Zurich, and SALZET, Michel
Subjects: Cancer Research, medicine.medical_specialty, medicine.medical_treatment, brain, [SDV]Life Sciences [q-bio], Population, Clinical Investigations, 610 Medicine & health, Breast Neoplasms, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, Internal medicine, depocyte, medicine, Clinical endpoint, Humans, cerebrospinal, Progression-free survival, education, 030304 developmental biology, 0303 health sciences, education.field_of_study, business.industry, Hazard ratio, Cytarabine, meningitis, neoplastic, medicine.disease, Chemotherapy regimen, 10040 Clinic for Neurology, 3. Good health, [SDV] Life Sciences [q-bio], Radiation therapy, Oncology, 030220 oncology & carcinogenesis, Drug Therapy, Combination, Neurology (clinical), business, medicine.drug
Abstract: Background DEPOSEIN (NCT01645839) was a randomized open-label phase III study to explore the role of intrathecal chemotherapy in patients with newly diagnosed leptomeningeal metastasis (LM), a common manifestation of breast cancer. Methods Patients with newly diagnosed LM defined by tumor cells in the cerebrospinal fluid or combination of clinical and neuroimaging signs of LM were randomized to receive systemic therapy alone (control group) or systemic therapy plus intrathecal liposomal cytarabine (experimental group). Progression-free survival related to LM (LM-PFS) was the primary endpoint. Results Thirty-seven and 36 patients were assigned to the control and the experimental groups. Median number of liposomal cytarabine injections in the experimental group was 5 (range 1–20). Focal radiotherapy was performed in 6 (16%) and 3 (8%) patients in the control and experimental groups. In the intent-to-treat population, median LM-PFS was 2.2 months (95% CI: 1.3–3.1) in the control versus 3.8 months (95% CI: 2.3–6.8) in the experimental group (hazard ratio 0.61, 95% CI: 0.38–0.98) (P = 0.04). Seventy-one patients have died. Median overall survival was 4.0 months (95% CI: 2.2–6.3) in the control versus 7.3 months (95% CI: 3.9–9.6) in the experimental group (hazard ratio 0.85, 95% CI: 0.53–1.36) (P = 0.51). Serious adverse events were reported in 22 and 30 patients, respectively. Quality of life until progression did not differ between groups. Conclusion The addition of intrathecal liposomal cytarabine to systemic treatment improves LM-related PFS. Confirmatory trials with optimized patient selection criteria and more active drugs may be required to demonstrate a survival benefit from intrathecal pharmacotherapy.
Published: 2020

16. Hyperprogression under Immune Checkpoint Inhibitor: a potential role for germinal immunogenetics

Author: Frederic Peyrade, Gérard Milano, Patrick Brest, Jocelyn Gal, Sadal Refae, Joël Guigay, Nathalie Ebran, Delphine Borchiellini, Damien Giacchero, Esma Saada-Bouzid, Bodescot, Myriam, Oncopharmacology Unit [Nice], Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA)-UNICANCER-Université Côte d'Azur (UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), Epidemiology and Biostatistics Department [Nice], Pathologies liées à l’âge [Nice] (FHU OncoAge), UNICANCER-Université Côte d'Azur (UCA)-UNICANCER-Université Côte d'Azur (UCA)-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)-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), Medical Oncology Department [Nice], The authors acknowledge support from Centre Antoine Lacassagne, Oncopharmacology unit team, University Côte d’Azur, France., COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA)-UNICANCER-Université Côte d'Azur (UCA), Université Nice Sophia Antipolis (... - 2019) (UNS), and 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)-Université Nice Sophia Antipolis (... - 2019) (UNS)
Subjects: Male, Candidate gene, medicine.medical_treatment, Programmed Cell Death 1 Receptor, lcsh:Medicine, Immunogenetics, B7-H1 Antigen, 0302 clinical medicine, Neoplasms, lcsh:Science, Immune Checkpoint Inhibitors, Aged, 80 and over, 0303 health sciences, Univariate analysis, Multidisciplinary, Middle Aged, 3. Good health, 030220 oncology & carcinogenesis, Toxicity, Disease Progression, Female, [SDV.IMM.IMM] Life Sciences [q-bio]/Immunology/Immunotherapy, Adult, Antineoplastic Agents, [SDV.CAN]Life Sciences [q-bio]/Cancer, Single-nucleotide polymorphism, Predictive markers, Polymorphism, Single Nucleotide, Article, 03 medical and health sciences, Immune system, [SDV.CAN] Life Sciences [q-bio]/Cancer, Cancer epigenetics, medicine, Humans, Author Correction, Aged, Cell Proliferation, 030304 developmental biology, business.industry, lcsh:R, Cancer, [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy, Immunotherapy, medicine.disease, Vascular Endothelial Growth Factor Receptor-2, Cancer research, lcsh:Q, business
Abstract: Hyperprogressive disease (HPD), an unexpected acceleration of tumor growth kinetics, is described in cancer patients treated with anti-PD-1/anti-PD-L1 agents. Here, our aim was to take into consideration the host and explore whether single nucleotide polymorphisms (SNPs) in key genes involved in immune response might predispose to HPD. DNA was extracted from blood-samples from 98 patients treated under CPI monotherapy. Four candidate genes (PD-1, PD-L1, IDO1 and VEGFR2) and 15 potential SNPs were selected. The TGKR (ratio of the slope of tumor growth before treatment and the slope of tumor growth on treatment) was calculated. Hyperprogression was defined as a TGKR≥2. TGKR calculation was feasible for 80 patients (82%). HPD was observed for 11 patients (14%) and was associated with shorter overall survival (P = 0.003). In univariate analysis, HPD was significantly associated with age ≥70 y (P = 0.025), immune-related toxicity (P = 0.016), VEGFR2 rs1870377 A/T or A/A (P = 0.005), PD-L1 rs2282055 G/T or G/G (P = 0.024) and PD-L1 rs2227981 G/A or A/A (P = 0.024). Multivariate analysis confirmed the correlation between HPD and age ≥70 y (P = 0.006), VEGFR2 rs1870377 A/T or A/A (P = 0.007) and PD-L1 rs2282055 G/T or G/G (P = 0.018). Immunogenetics could become integral predictive factors for CPI-based immunotherapy.
Published: 2020

17. Germinal Immunogenetics predict treatment outcome for PD-1/PD-L1 checkpoint inhibitors

Author: Jocelyn Gal, Patrick Brest, Gérard Milano, Emmanuel Chamorey, Frederic Peyrade, Sadal Refae, Delphine Borchiellini, Josiane Otto, Nathalie Ebran, Esma Saada-Bouzid, Oncopharmacology Unit [Nice], Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA)-UNICANCER-Université Côte d'Azur (UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), UNICANCER-Université Côte d'Azur (UCA), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), Laboratory of Solid Tumors Genetics, Nice University Hospital, Infection bactérienne, inflammation, et carcinogenèse digestive, Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-IFR50-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Institut de Recherche sur le Cancer et le Vieillissement (IRCAN), 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), Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS), Département de pharmacogénomique, and UNICANCER-Université Côte d'Azur (UCA)-UNICANCER-Université Côte d'Azur (UCA)
Subjects: 0301 basic medicine, Oncology, Adult, Male, medicine.medical_specialty, In silico, [SDV]Life Sciences [q-bio], Programmed Cell Death 1 Receptor, Single-nucleotide polymorphism, [SDV.CAN]Life Sciences [q-bio]/Cancer, Immunogenetics, B7-H1 Antigen, 03 medical and health sciences, 0302 clinical medicine, Antineoplastic Agents, Immunological, Internal medicine, PD-L1, Neoplasms, Gene expression, medicine, Biomarkers, Tumor, Humans, Pharmacology (medical), Adverse effect, Gene, Germ-Line Mutation, ComputingMilieux_MISCELLANEOUS, Aged, Retrospective Studies, Pharmacology, Aged, 80 and over, biology, business.industry, Middle Aged, Prognosis, 3. Good health, Pharmacogenomic Testing, Survival Rate, 030104 developmental biology, 030220 oncology & carcinogenesis, Expression quantitative trait loci, biology.protein, Female, Immunotherapy, business, Follow-Up Studies
Abstract: Background Checkpoint inhibitors bring marked benefits but only in a minority of patients and may also be associated with severe adverse events. Treatment outcome still cannot be faithfully predicted. The following study hypothesized that host genetics could be applied as predictive biomarkers for checkpoint inhibitor response and immune-related adverse events. We conducted a study based on germinal polymorphisms from genes coding for proteins involved in immune regulation. Methods Germinal DNA was obtained from advanced cancer patients treated with anti-PD-1/PD-L1 checkpoint inhibitors. DNA was genotyped using a custom panel of 166 single nucleotide polymorphisms covering 86 preselected immunogenetic-related genes. Computational analysis using a GTEX portal was made to determine potential expression Quantitative Trait Loci in tissues. Results Ninety-four consecutive patients were included. Objective response rate (complete or partial response) was significantly correlated to tumor microenvironment-related SNPs concerning CCL2, NOS3, IL1RN, IL12B, CXCR3 and IL6R genes. Toxicity were linked to target-related gene SNPs including UNG, IFNW1, CTLA4, PD-L1 and IFNL4 genes. The Area Under the ROC curve (AUC) was 0.81 (95% CI: 0.72–0.9) for response and 0.89 (95% CI: 0.76–1.00) for toxicity. In silico functionality exploring pointed rs4845618 (IL6R), rs10964859 (IFNW1) and rs3087243 (CTLA4) as potentially impacting gene expression. Conclusion These results strongly support a role for distinct immunogenetic-related gene SNPs able to predict efficacy and safety of anti-PD1/PD-L1 therapies. The results highlight the existence of patient-specific, germinal biomarkers able predict response to checkpoint inhibitor efficacy and, possibly, to predict treatment-related adverse events.
Published: 2020

18. 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

19. Imaging issues specific to hadrontherapy (proton, carbon, helium therapy and other charged particles) for radiotherapy planning, setup, dose monitoring and tissue response assessment

Author: Thariat, J., Herault, J., Beddok, A., Feuvret, L., Dauvergne, D., Gérard, M., Balosso, J., Noël, G., Valable, S., Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), ARCHADE (Advanced Resource Centre for HADrontherapy in Europe), Laboratoire de physique corpusculaire de Caen (LPCC), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Département Oncologie Médicale [Nice], Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA)-UNICANCER-Université Côte d'Azur (UCA), Département de radiothérapie oncologique [Paris], Institut Curie [Paris], 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), Laboratoire de Physique Subatomique et de Cosmologie (LPSC), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Université Grenoble Alpes (UGA), Centre Paul Strauss, CRLCC Paul Strauss, Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales (ISTCT), and Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Carbone, Planification, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, Hadronthérapie, Particle therapy, Response, Protonthérapie, Parcours, Réponse, [SDV.IB.MN]Life Sciences [q-bio]/Bioengineering/Nuclear medicine, Range, Proton therapy, Carbon, Imaging, Planning, Imagerie, Hadrontherapy
Abstract: CERVOXY; International audience; Imaging is critical to each step of precision radiation therapy, i.e. planning, setup, delivery and assessment of response. Hadrontherapy can be considered to deliver more precise dose distribution that may better spare normal tissues from intermediate low doses of radiation. In addition, hadrontherapy using high linear energy transfer ions may also be used for dose escalation on biological target volumes defined by functional imaging. However, the physical characteristics of hadrontherapy also make it more demanding in terms of imaging accuracy and image-based dose calculation. Some of the developments needed in imaging are specific to hadrontherapy. The current review addresses current status of imaging in proton therapy and the drawbacks of photon-based imaging for hadrons. It also addresses requirements in hadrontherapy planning with respect to multimodal imaging for proper target and organ at risk definition as well as to target putative radioresistant areas such as hypoxic ones, and with respect to dose calculation using dual energy CT, MR-proton therapy, proton radiography. Imaging modalities, such as those used in photon-based radiotherapy (intensity modulated and stereotactic radiotherapy), are somewhat already implemented or should be reaching “routine” hadrontherapy (at least proton therapy) practice in planning, repositioning and response evaluation optimizable within the next five years. Online monitoring imaging by PET, as currently developed for hadrontherapy, is already available. Its spatiotemporal limits restrict its use but similar to prompt gamma detection, represents an area of active research for the next 5 to 10 years. Because of the more demanding and specific dose deposit characteristics, developments image-guided hadrontherapy, such as specific proton imaging using tomography or ionoacoustics, as well as delivery with MR-proton therapy, may take another 10 years to reach the clinics in specific applications. Other aspects are briefly described such as range monitoring. Finally, the potential of imaging normal tissue changes and challenges to assess tumour response are discussed.; L’imagerie est essentielle à chaque étape de la radiothérapie de précision, et en particulier la planification, la vérification du repositionnement en salle, la vérification de la dose et l’évaluation de la réponse. Certains des développements nécessaires en imagerie sont spécifiques à l’hadronthérapie du fait des caractéristiques du dépôt de dose et des interactions dans la matière. Cette brève revue porte sur l’état actuel de l’imagerie en protonthérapie et sur les inconvénients de l’utilisation d’une imagerie X pour les hadrons. Elle décrit les exigences de la planification de l’hadronthérapie en ce qui concerne l’imagerie multimodale pour la définition de la cible et des organes à risque, ainsi que les pistes actuellement identifiées pour cibler spatialement et temporellement l’hypoxie tumorale. Le calcul de la dose par tomodensitométrie à double énergie, la protonthérapie-IRM et la radiographie par protons sont des voies de recherche actuelles en imagerie pour réduire les incertitudes liées à l’imagerie X dans le calcul de la dose. Les modalités d’imagerie utilisées en radiothérapie classique par photons en planification, repositionnement et évaluation de la réponse sont globalement toutes transposables ou déjà présentes et optimisables en hadronthérapie dans un horizon de 5 ans. L’imagerie de contrôle en ligne, actuellement spécifique à l’hadronthérapie, par TEP est déjà disponible. Ses limites spatiotemporelles restreignent son usage mais sont une voie de recherche active, comme la détection de gamma prompts, pour les 5-10 années à venir. Les problématiques de radiothérapie guidée par l’image spécifiques à l’hadronthérapie, plus requérante du fait du dépôt de dose “fini”, telles que la tomographie par protons ou la ionoacoustique, le seront probablement dans un horizon de 10 ans dans des applications particulières. Les aspects de vérification du parcours des hadrons sont brièvement décrits. Enfin, le potentiel de l’imagerie pour analyser des effets infracliniques dans les tissus normaux et les défis liés à l’évaluation de la réponse tumorale sont discutés.
Published: 2020

20. Oncologic outcomes, prognostic factor analysis and therapeutic algorithm evaluation of head and neck mucosal melanomas in France

Author: A. Moya-Plana, A. Aupérin, R. Obongo, A. Baglin, F.R. Ferrand, B. Baujat, N. Saroul, O. Casiraghi, S. Vergez, P. Herman, F. Janot, J. Thariat, B. Vérillaud, L. de Gabory, S. Albert, G. Andry, E. Babin, C. Bach, J.-M. Badet, C. Badoual, A.C. Baglin, A. Banal, B. Barry, E. Baudin, R.J. Bensadoun, C. Bertolus, J.-P. Bessède, D. Blanchard, C. Borel, A. Bozorg-Grayeli, R. Breheret, P. Breton, L. Brugel, G. Calais, E. Cassagnau, L. Castillo, P. Ceruse, F. Chabolle, D. Chevalier, J.C. Chobaut, O. Choussy, A. Cosmidis, A. Coste, V. Costes, L. Crampette, V. Darrouzet, P. Demez, P. Dessi, B. Devauchelle, L. Digue, G. Dolivet, F. Dubrulle, S. Duflo, X. Dufour, C. Even, S. Faivre, N. Fakhry, C. Ferron, F. Floret, R. Garrel, L. Geoffrois, L. Gilain, A. Giovanni, A. Girod, B. Guerrier, S. Hans, P. Hofman, M. Housset, R. Jankowski, F. Jegoux, M. Juliéron, M.-C. Kaminsky, F. Kolb, J. Lacau St Guily, L. Laccoureye, B. Lallemant, P. Lang, E. Lartigau, J.-P. Lavieille, M. Lefevre, X. Leroy, O. Malard, F. Massip, O. Mauvais, J.-C. Merol, J. Michel, T. Mom, S. Morinière, E. de Monès, G. Moulin, G. Noel, G. Poissonnet, J.-M. Prades, D. de Raucourt, E. Reyt, C. Righini, Y. Marie Robin, F. Rolland, B. Ruhin, N. Sarroul, P. Schultz, E. Serrano, O. Sterkers, V. Strunski, A. Sudaka, M. Tassart, S. Testelin, A. Timochenko, B. Toussaint, E. Uro Coste, G. Valette, T. Van den Abbeele, A. Varoquaux, F. Veillon, M. Wassef, Institut Gustave Roussy (IGR), Service de biostatistique et d'épidémiologie (SBE), Direction de la recherche clinique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Département de cancérologie cervico-faciale [Gustave Roussy] (CCF), Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Clermont-Ferrand, Laboratorium für Physikalische Chemie (ETH-LPC), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), French Rare Head and Neck Cancer Expert Network (REFCOR), Service d'Oto-Rhino-Laryngologie (O.R.L.) et de Chirurgie Cervico-Faciale [CHU Caen], 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), French Rare Head and Neck Cancer Expert Network. (REFCOR), Laboratoire d'études spatiales et d'instrumentation en astrophysique (LESIA), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Service d'ORL et de Chirurgie Cervico-Faciale (PARIS - BICHAT - ORL et CCF), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Médecine nucléaire, Département d'imagerie médicale [Gustave Roussy], Service d’ORL et de chirurgie cervico-faciale [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Paul Strauss de Lutte contre le Cancer (Strasbourg), Génétique, immunothérapie, chimie et cancer (GICC), UMR 6239 CNRS [2008-2011] (GICC UMR 6239 CNRS), Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL), Chambre Régionale d'Agriculture des Pays de la Loire, Service de chirurgie, Hôpital Charles Nicolle [Rouen]-CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Service d’Otorhinolaryngologie [Centre Hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université de Montpellier (UM), Service d'ORL, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Anthropologie bio-culturelle, Droit, Ethique et Santé (ADES), Aix Marseille Université (AMU)-EFS ALPES MEDITERRANEE-Centre National de la Recherche Scientifique (CNRS), Département de chirurgie maxillofaciale et stomatologie [CHU d'Amiens-Picardie], CHU Amiens-Picardie, Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), UNICANCER, Service de Radiologie (LILLE - Radio), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de médecine gériatrique, CHU de Saint-Etienne, Université Paris 13 (UP13), Hôpital Pellegrin, Service d'ORL et chirurgie cervico-faciale, Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service d'ORL et Chirurgie Cervico-Facial, Hôpital de la Timone [CHU - APHM] (TIMONE), Fluides, automatique, systèmes thermiques (FAST), Université Paris-Sud - Paris 11 (UP11)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Géomatériaux (DGCB-LGM), École Nationale des Travaux Publics de l'État (ENTPE)-Centre National de la Recherche Scientifique (CNRS), Neurobiologie des réseaux sensorimoteurs (NRS (U7060)), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS), Centre méditérannéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Oto-Rhino-Laryngologie et de Chirurgie Cervico-Faciale [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), CHU Pontchaillou [Rennes], Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), University of St Andrews [Scotland], Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université Lille Nord de France (COMUE)-UNICANCER, Centre hospitalier universitaire de Nantes (CHU Nantes), Statistique en grande dimension pour la génomique, Département PEGASE [LBBE] (PEGASE), Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Reims (CHU Reims), Institut d'Electronique du Solide et des Systèmes (InESS), Centre National de la Recherche Scientifique (CNRS), Service d'ORL et de Chirurgie Cervico-Faciale (TOURS - ORL et CCF), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Université de Rennes (UNIV-RENNES), Service de chirurgie oncologique cervico-faciale [centre Antoine Lacassagne, Nice], Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA)-UNICANCER-Université Côte d'Azur (UCA), Department of Otolaryngology and Head and Neck Surgery, University Hospital of Grenoble, BP 217, 38043, Grenoble Cedex 09, France, Université Joseph Fourier - Grenoble 1 (UJF), Institut d'oncologie/développement Albert Bonniot de Grenoble (INSERM U823), Institut National de la Santé et de la Recherche Médicale (INSERM)-EFS-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF), CRLCC René Gauducheau, CHU Strasbourg-Hôpital de Hautepierre [Strasbourg], Réhabilitation Chirurgicale mini-Invasive et Robotisée de l'Audition, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Centre de résonance magnétique biologique et médicale (CRMBM), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de cristallographie et sciences des matériaux (CRISMAT), École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Institut de Chimie du CNRS (INC), Department of Head and Neck Surgery, Hôpital Larrey [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Service d'oto-rhino-laryngologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Biomécanique et génie biomédical (BIM), Réseau d’Expertise Français sur les Cancers ORL Rares - French Network of Rare Head and Neck Tumors (REFCOR), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Groupe innovation et ciblage cellulaire (GICC), EA 7501 [2018-...] (GICC EA 7501), Université de Tours (UT), Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Université Nice Sophia Antipolis (1965 - 2019) (UNS), Université de Lille-UNICANCER, Université de Rennes (UR), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Normandie Université (NU)-Normandie Université (NU)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche sur les Matériaux Avancés (IRMA), Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Rouen Normandie (UNIROUEN), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), Les Hôpitaux Universitaires de Strasbourg (HUS), Service Chirurgie maxillo-faciale et plastique de la face [CHU Toulouse], Pôle Céphalique [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Tours-Centre National de la Recherche Scientifique (CNRS), and Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Oncology, Male, Cancer Research, Multivariate analysis, medicine.medical_treatment, 0302 clinical medicine, Paranasal Sinuses, Medicine, Prospective Studies, Stage (cooking), Head and neck, Lymph node, Melanoma, Aged, 80 and over, Mucosal melanoma, Middle Aged, Prognosis, Progression-Free Survival, 3. Good health, Tumor Burden, Survival Rate, medicine.anatomical_structure, Head and Neck Neoplasms, 030220 oncology & carcinogenesis, Female, Mouth Neoplasms, France, Algorithms, Paranasal Sinus Neoplasms, Adult, medicine.medical_specialty, Nose Neoplasms, [SDV.CAN]Life Sciences [q-bio]/Cancer, 03 medical and health sciences, Young Adult, Internal medicine, Humans, Sinonasal, Aged, Neoplasm Staging, Radiotherapy, business.industry, Head and neck cancer, Mouth Mucosa, medicine.disease, Otorhinolaryngologic Surgical Procedures, Oral cavity, Radiation therapy, Nasal Mucosa, 030104 developmental biology, Oral Cavity Mucosal Melanoma, Radiotherapy, Adjuvant, business
Abstract: International audience; BACKGROUND:Head and neck mucosal melanoma (HNMM) is aggressive and rare, with a poor prognosis because of its high metastatic potential. The two main subtypes are sinonasal (sinonasal mucosal melanoma [SNMM]) and oral cavity (oral cavity mucosal melanoma [OCMM]). Consensual therapeutic guidelines considering the primary tumour site and tumour-node-metastasis (TNM) stage are not well established.MATERIAL & METHODS:Patients with HNMM from the prospective national French Rare Head and Neck Cancer Expert Network database between 2000 and 2017 were included. Clinical characteristics, treatment modalities, outcomes and prognostic factors were analysed.RESULTS:In total, 314 patients were included. The 5-year overall survival (OS) and progression-free survival (PFS) rates were 49.4% and 24.7%, respectively, in the surgery group; no long-term survivors were observed when surgery was not feasible. Moreover, even after surgery, a high recurrence rate was reported with a median PFS of 22 months. In multivariate analysis, Union for International Cancer Control (UICC) stage and tumour site correlated with PFS and OS. Postoperative radiotherapy (PORT) improved the PFS but not OS in patients with small (T3) SNMM and OCMM tumours. Nodal involvement was more frequent in patients with OCMM (p < 10-4), although, as in SNMM, it was not a significant prognostic predictor.CONCLUSION:Even early HNMM was associated with poor oncologic outcomes due to distant metastases despite surgical resection with clear margins. Lymph node metastases had no impact on the prognosis, suggesting treatment de-escalation in cervical node management. PORT might be useful for local control.
Published: 2019

21. Proton Energy Loss in GaN: Proton Energy Loss in GaN

Author: Jean-Claude Grini, Julie Zucchi, Sébastien Chenot, Maxime Hugues, Jean-Yves Duboz, J Hérault, Eric Frayssinet, Centre de recherche sur l'hétéroepitaxie et ses applications (CRHEA), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Pôle d'Imagerie Médecine Nucléaire, Centre Antoine-Lacassagne, Université Côte d'Azur, Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), and UNICANCER-Université Côte d'Azur (UCA)-UNICANCER-Université Côte d'Azur (UCA)
Subjects: [PHYS]Physics [physics], Materials science, Nuclear Theory, 02 engineering and technology, 021001 nanoscience & nanotechnology, Condensed Matter Physics, Proton energy, 01 natural sciences, 010305 fluids & plasmas, Electronic, Optical and Magnetic Materials, proton GaN, Condensed Matter::Materials Science, 0103 physical sciences, Physics::Accelerator Physics, Atomic physics, Nuclear Experiment, 0210 nano-technology, MESH: proton GaN
Abstract: International audience; We investigate the proton energy loss in GaN in an energy range between 0 and 65 MeV. The energy of protons generated by a cyclotron at about 65 MeV is varied by inserting an energy- absorbing medium of varying thickness. The precise modeling of the GaN Schottky diode response as a function of the absorbing medium thickness allows us to demonstrate that the energy absorption loss in GaN precisely follows the Bethe theory. In addition, we can identify the region of the detector contributing to its response to a proton beam, which is of prime importance for proton detector optimization.
Published: 2021

22. Germinal immunogenetics as a predictive factor for immunotherapy

Author: Patrick Brest, Jocelyn Gal, Gérard Milano, Sadal Refae, Oncopharmacology Unit [Nice], Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA)-UNICANCER-Université Côte d'Azur (UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), UNICANCER-Université Côte d'Azur (UCA), Institut de Recherche sur le Cancer et le Vieillissement (IRCAN), Université Nice Sophia Antipolis (... - 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), Département de pharmacogénomique, and UNICANCER-Université Côte d'Azur (UCA)-UNICANCER-Université Côte d'Azur (UCA)
Subjects: 0301 basic medicine, Oncology, medicine.medical_specialty, medicine.medical_treatment, [SDV]Life Sciences [q-bio], DNA Mutational Analysis, Single-nucleotide polymorphism, [SDV.CAN]Life Sciences [q-bio]/Cancer, Immunogenetics, Germline, 03 medical and health sciences, 0302 clinical medicine, Neoplasms, Internal medicine, Tumor Microenvironment, Humans, Immunologic Factors, Medicine, Allele frequency, Germ-Line Mutation, ComputingMilieux_MISCELLANEOUS, Tumor microenvironment, [SDV.GEN]Life Sciences [q-bio]/Genetics, business.industry, Hematology, Immunotherapy, Prognosis, Pharmacogenomic Testing, 3. Good health, Treatment Outcome, 030104 developmental biology, Clinical research, Drug Resistance, Neoplasm, Sample size determination, 030220 oncology & carcinogenesis, [SDV.IMM]Life Sciences [q-bio]/Immunology, business
Abstract: Clinical response to checkpoint inhibitors-based (CPIs) therapies can vary among tumor types and between patients. This led to a significant amount of pre-clinical and clinical research into biomarker identification. Biomarkers have been found to cover both the tumor itself and the tumor microenvironment. Entering host-related parameters into the equation should provide a valuable strategy for identifying not only factors predictive of treatment efficacy but also of treatment-related toxicity. It is clear that germline variants can offer efficient and easily-assessable indicators (blood DNA) to enlarge the spectrum of predictive markers for CPI-based treatment. A major issue concerns the real functional significance of the reported single-nucleotide polymorphisms (SNPs) linked to CPI-treatment outcome. Powered calculations should lead to an optimal trade-off between sample size and allele frequency. New molecular technologies and new analytical methods should provide opportunities to bridge the knowledge gap between SNP-CPI treatment associations and the functional impact of these SNPs.
Published: 2019

23. [Dihydropyrimidine dehydrogenase deficiency screening for management of patients receiving a fluoropyrimidine: Results of two national practice surveys addressed to clinicians and biologists]

Author: Loriot, Marie-Anne, Masskouri, Fadil, Carni, Paolo, Le Malicot, Karine, Seitz, Jean-François, Michel, Pierre, Legoux, Jean-Louis, Bouche, Olivier, André, Thierry, Faroux, Roger, Delaloge, Suzette, Malka, David, Guigay, Joël, Thariat, Juliette, Thomas, Fabienne, Barin-Le-Guellec, Chantal, Ciccolini, Joseph, Boyer, Jean-Christophe, Etienne-Grimaldi, Marie-Christine, Médecine Personnalisée, Pharmacogénomique, Optimisation Thérapeutique (MEPPOT - U1147), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Fédération Francophone de la Cancérologie Digestive, FFCD, 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), F2ME, PSA Peugeot - Citroën (PSA), PSA Peugeot Citroën (PSA)-PSA Peugeot Citroën (PSA)-Laboratoire Pluridisciplinaire de Recherche en Ingénierie des Systèmes, Mécanique et Energétique (PRISME), Ecole Nationale Supérieure d'Ingénieurs de Bourges (ENSI Bourges)-Université d'Orléans (UO)-Ecole Nationale Supérieure d'Ingénieurs de Bourges (ENSI Bourges)-Université d'Orléans (UO), Regional Hospital of Orleans, Centre Hospitalier Universitaire de Reims (CHU Reims), Centre de Recherche Saint-Antoine (UMRS893), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHD Vendée - Hôpital Les Oudairies [La Roche sur Yon], Institut Gustave Roussy (IGR), Onco-génétique, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Medical Oncology Department [Nice], COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA)-UNICANCER-Université Côte d'Azur (UCA), Institute of Developmental Biology and Cancer (IBDC), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Centre de Recherche en Cancérologie de Marseille (CRCM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Laboratoire de biochimie et biologie moléculaire, Université d'Orléans (UO)-Ecole Nationale Supérieure d'Ingénieurs de Bourges (ENSI Bourges)-Université d'Orléans (UO)-Ecole Nationale Supérieure d'Ingénieurs de Bourges (ENSI Bourges), Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon (CHD Vendée), UNICANCER-Université Côte d'Azur (UCA)-UNICANCER-Université Côte d'Azur (UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), Université Nice Sophia Antipolis (1965 - 2019) (UNS), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, and 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)
Subjects: Biomedical Research, Dihydropyrimidine Dehydrogenase Deficiency, MESH: Pharmacovigilance, [SDV]Life Sciences [q-bio], Surveys, MESH: Health Care Surveys, Digestive System Neoplasms, MESH: Genotype, Pharmacovigilance, MESH: Practice Guidelines as Topic, Antineoplastic Combined Chemotherapy Protocols, MESH: Otorhinolaryngologic Neoplasms, Oncologists, MESH: Antimetabolites, Antineoplastic, Enquête, DPD, MESH: Antineoplastic Combined Chemotherapy Protocols, Practice Guidelines as Topic, Screening, Female, Fluorouracil, France, Dihydropyrimidine dehydrogenase, Fluoropyrimidine, Antimetabolites, Antineoplastic, Genotype, Breast Neoplasms, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Dihydropyrimidine déshydrogénase, Reimbursement Mechanisms, Toxicité, MESH: Reimbursement Mechanisms, MESH: Biology, Humans, Biology, Capecitabine, MESH: Humans, Toxicity, MESH: Digestive System Neoplasms, MESH: Biomedical Research, MESH: Oncologists, MESH: Capecitabine, MESH: France, Otorhinolaryngologic Neoplasms, Pyrimidines, Dépistage, Health Care Surveys, MESH: Pyrimidines, MESH: Dihydropyrimidine Dehydrogenase Deficiency, MESH: Female, MESH: Fluorouracil, MESH: Breast Neoplasms
Abstract: International audience; Dihydropyrimidine dehydrogenase (DPD) deficiency is the main cause of early severe toxicities induced by fluoropyrimidines (FP). The French Group of Clinical Oncopharmacology (GPCO)-Unicancer and the French Pharmacogenetics Network (RNPGx) initiated two surveys, one addressed to oncologists, the other to biologists, in order to evaluate routine practices regarding DPD deficiency screening at national level, as well as compliance, motivations and obstacles for implementation of these tests. These anonymized online surveys were performed with the logistic assistance of the Francophone Federation of Digestive Oncology (FFCD) and the support of numerous medical and biological societies. The surveys were conducted in 2016-2017 before the creation of the French INCa/HAS expert panel, which contributed to the drafting of rules and recommendations for DPD deficiency screening published in December 2018. In all, 554 questionnaires from clinicians were analyzed (23% participation) and 35 from biologists. The main arguments raised by clinicians for justifying the limited practice of DPD deficiency screening were: the lack of recommendations from medical societies or Health Authorities, delays in obtaining results, and the lack of adequate reimbursement by the health insurance system. The goal of these surveys was to provide the French Health Authorities with an overview on nationwide DPD-deficiency screening practices and thus help to design recommendations for the standardization and improvement of the management and safety of cancer patients receiving FP-based chemotherapy.
Published: 2019

24. Sarcomas in patients over 90: Natural history and treatment—A nationwide study over 6 years

Author: Basse, Clémence, Italiano, Antoine, Penel, Nicolas, Mir, Olivier, Chemin, Claire, Toulmonde, Maud, Duffaud, Florence, Le Cesne, Axel, Chevreau, Christine, Maynou, Carlos, Anract, Philippe, Gouin, François, Rios, Maria, Firmin, Nelly, Kurtz, Jean-Emmanuel, Kerbrat, Pierre, Piperno-Neumann, Sophie, Bertucci, Francois, Rosset, Philippe, Isambert, Nicolas, Bompas, Emmanuelle, Dubray-Longeras, Pascale, Fiorenza, Fabrice, Le Maignan, Christine, Chaigneau, Loic, Thyss, Antoine, Bouché, Olivier, Eymard, Jean-Christophe, Delcambre Lair, Corinne, Adam, Julien, Karanian, Marie, Lebbé, Céleste, Dupré, Aurélien, Méeus, Pierre, Brahmi, Mehdi, Dufresne, Armelle, Ducimetière, Françoise, Ray-Coquard, Isabelle, Blay, Jean-Yves, Kurtz, Jean‐emmanuel, Piperno‐neumann, Sophie, Dubray‐longeras, Pascale, Eymard, Jean‐christophe, Ray‐coquard, Isabelle, Blay, Jean‐yves, Institut Bergonié [Bordeaux], UNICANCER, 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), AGROCAMPUS OUEST, Hôpital de la Timone [CHU - APHM] (TIMONE), Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR), Institut Claudius Regaud, Physiopathologie des Adaptations Nutritionnelles (PhAN), Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN), Centre Alexis Vautrin (CAV), Département d'oncologie Médicale, CRLCC Val d'Aurelle - Paul Lamarque, Les Hôpitaux Universitaires de Strasbourg (HUS), Service d'Oncologie Médicale [Rennes], CRLCC Eugène Marquis (CRLCC), Département d'Oncologie Médicale [Institut Curie, Paris], Institut Curie [Paris], 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), STeRéO, Institut des Sciences Moléculaires de Marseille (ISM2), Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), CRLCC René Gauducheau, Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), Service d'hématologie A [CHU HEGP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Service 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), Service d'Hématologie, Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA)-UNICANCER-Université Côte d'Azur (UCA), Centre Hospitalier Universitaire de Reims (CHU Reims), Institut Jean Godinot [Reims], 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), 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), Immunologie, dermatologie, oncologie, Oncodermatologie, immunologie et cellules souches cutanées (IDO (U976 / UMR_S 976)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Oncologie Chirurgicale [Lyon], Centre Léon Bérard [Lyon], Département d'Oncologie Médicale, Service d'Oncologie Médicale, Université Lille Nord de France (COMUE)-UNICANCER, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, and Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU)
Subjects: Male, Cancer Research, Databases, Factual, [SDV]Life Sciences [q-bio], Soft Tissue Neoplasms, registry, 0302 clinical medicine, Medicine, Registries, Cancer Therapy and Prevention, Child, sarcomas, Aged, 80 and over, relapse, education.field_of_study, Incidence (epidemiology), Sarcoma, Middle Aged, 3. Good health, Natural history, Oncology, 030220 oncology & carcinogenesis, Child, Preschool, Cohort, Female, France, Adult, medicine.medical_specialty, Adolescent, Population, [SDV.CAN]Life Sciences [q-bio]/Cancer, elderly patients, survival, Disease-Free Survival, 03 medical and health sciences, Young Adult, Internal medicine, Humans, education, Pathological, Aged, business.industry, Infant, Newborn, Cancer, Infant, medicine.disease, NETSARC, Clinical trial, progression, Neoplasm Recurrence, Local, business, oncogeriatry, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Soft tissue sarcomas (STS) are rare tumors accounting for less than 1% of human cancers. While the highest incidence of sarcomas is observed in elderly, this population is often excluded or poorly represented in clinical trials. The present study reports on clinicopathological presentation, and outcome of sarcoma patients over 90 recorded in the Netsarc.org French national database. NETSARC (netsarc.org) is a network of 26 reference sarcoma centers with specialized multidisciplinary tumor board (MDTB), funded by the French National Cancer Institute to improve the outcome of sarcoma patients. Since 2010, presentation to an MDTB, second pathological review, and collection of sarcoma patient characteristics and follow‐up are collected in a database Information of patients registered from January 1, 2010, to December 31, 2016, in NETSARC were collected, analyzed and compared to the younger population. Patients with sarcomas aged >90 have almost exclusively sarcomas with complex genomics (92.0% vs. 66.3%), are less frequently metastatic (5.3% vs. 14·7%) at diagnosis, have more often superficial tumors (39.8% vs. 14.7%), as well as limbs and head and neck sites (75.2% vs. 38.7%) (all p, What's new? While the highest incidence of soft‐tissue sarcoma (STS) is observed in the elderly, this population is often excluded or poorly represented in clinical trials. Therefore, little is known about the characteristics, treatment, and outcomes of STS in these patients. In this study, the authors analyzed numerous clinical characteristics of patients with sarcoma diagnosed at age 91 or older. They conclude that standard STS management and clinical practice guidelines should be followed for these patients if possible.
Published: 2019

25. [Does orbital exenteration still has a place in 2019?]

Author: Martel, A., Hamedani, M., Lagier, J., Bertolotto, C., Gastaud, L., Poissonnet, G., BERTOLOTTO-BALLOTTI, BERTOLOTTO-BALLOTTI, Service d'Ophtalmologie [CHU Nice], Centre Hospitalier Universitaire de Nice (CHU Nice), Département d'oculoplastie [Lausanne, Suisse], Fondation Asile des aveugles - Hôpital Ophtalmique Jules-Gonin [Lausanne], Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Service d'oncologie médicale [Centre Antoine Lacassagne, Nice], Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA)-UNICANCER-Université Côte d'Azur (UCA), and Service de chirurgie oncologique cervico-faciale [centre Antoine Lacassagne, Nice]
Subjects: Immunothérapie, Eye Neoplasms, [SDV.CAN]Life Sciences [q-bio]/Cancer, Plastic Surgery Procedures, Eyelid Neoplasms, Prognosis, History, 21st Century, Survival Analysis, eye diseases, Episthesis, Targeted therapy, Life Expectancy, Treatment Outcome, Survie globale, [SDV.CAN] Life Sciences [q-bio]/Cancer, Épithèse, Exentération orbitaire, Humans, Orbital Neoplasms, Orbital exenteration, Overall survival, Immunotherapy, Orbit Evisceration, Thérapie ciblée
Abstract: International audience; INTRODUCTION:Orbital exenteration is a radical anatomically and psychologically disfiguring procedure. It is mostly performed for management of orbital cancers or cancers with orbital involvement. The lack of benefit in terms of overall survival and the development of new molecular therapies (targeted therapies, immunotherapy) in recent years leads us to question its use. The goal of our review is to answer to the following question: is orbital exenteration a viable procedure in 2019?MATERIALS AND METHODS:A literature review was performed using the PUBMED and MEDLINE databases. The following terms were used then crossed with each other: "orbital exenteration", "exenterated socket", "overall survival", "life expectancy", "orbital reconstruction", "socket reconstruction". Oncology articles from the past 15 years were included and separated into those in the oculoplastic literature and those in the ENT literature.RESULTS:Nineteen articles were included in this review. Eyelid tumours represent the main etiology of orbital exenteration. Basal cell carcinoma is the most frequently incriminated tumor, while sebaceous carcinoma and conjunctival squamous cell carcinoma are the most frequently encountered in Asian series. Non-conservative orbital exenteration is the most prevalent surgery performed. Orbital reconstruction depends on the surgeon's speciality: healing by secondary intention and split thickness skin grafts are mostly performed by oculoplastic surgeons, whereas regional or free flaps are mostly performed by ENT surgeons. Cerebrospinal fluid leakage is the most common intraoperative complication, encountered in 0 to 13 % of cases. The most common postoperative complications are ethmoid fistula and infection of the operative site, encountered in 0 to 50 % and 0 to 43 % of cases respectively. Orbital exenteration allows surgical resection of R0 tumors in 42.5 % to 97 % of cases. Overall survival following orbital exenteration is 83 % (50.5-97) and 65 % (37-92) at 1 and 5 years respectively. Identified risk factors for poor overall survival are: age, tumor histology (worse prognosis with choroidal melanoma, better prognosis with basal cell carcinoma), non-R0 surgical resection, locally advanced tumors (size>20mm, BCVA
Published: 2019

26. GAPDH Expression Predicts the Response to R-CHOP, the Tumor Metabolic Status, and the Response of DLBCL Patients to Metabolic Inhibitors

Author: Vincent Delwail, Jean-Ehrland Ricci, Isabelle Peyrottes, Celine Delpech-Debiais, Sandrine Marchetti, Julie Reverso-Meinietti, Jacqueline Lehmann-Che, Gabriel Brisou, Jozef P. Bossowski, Manuel Grima-Reyes, Christiane Copie-Bergman, Camila Rubio-Patiño, Konstantina Fragaki, Eric de Kerviler, Véronique Paquis-Flucklinger, Thierry Jo Molina, Frederic Peyrade, Annabelle Mouchotte, Tony Petrella, Emma Proïcs, Bertrand Nadel, Els Verhoeyen, Bruno Taillan, Richard Delarue, Catherine Thieblemont, Laetitia Shintu, Agnès Paquet, Rana Mhaidly, Johanna Chiche, Elodie Villa, Georges Garnier, Pascal Barbry, Josette Brière, Damien Ambrosetti, Nicolas Mounier, André Bosly, Jean-François Michiels, COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), Université Nice Sophia Antipolis - Faculté de Médecine (UNS UFR Médecine), 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), Centre méditerranéen de médecine moléculaire (C3M), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Institut de pharmacologie moléculaire et cellulaire (IPMC), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Institut de Recherche sur le Cancer et le Vieillissement (IRCAN), 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), Service d'anatomo-pathologie [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Pasteur [Nice] (CHU), Hôpital Hôtel Dieu, INSERM U955, équipe 9, Département de pathologie [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-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), Pathologie cellulaire : aspects moléculaires et viraux / Pathologie et Virologie Moléculaire, Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS), Department of Pathology, Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA)-UNICANCER-Université Côte d'Azur (UCA), UNICANCER-Université Côte d'Azur (UCA), Hôpital Princesse Grace [Monaco], Institut National de la Santé et de la Recherche Médicale (INSERM), Institut des Sciences Moléculaires de Marseille (ISM2), Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), 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), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Service d'immuno-hématologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Cliniques universitaires UCL de Mont-Godinne 5530 Yvoir, Centre de pathologie [Dijon], Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS), Service hématologie Nice, Centre Hospitalier Universitaire de Nice (CHU Nice), Service d'onco-hématologie [AP-HP Hôpital Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Physiopathologie de la survie et de la mort cellulaire et infection virale, COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-IFR50-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Université Nice Sophia Antipolis (... - 2019) (UNS), Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de pathologie, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Université Côte d'Azur (UCA), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Nice Sophia Antipolis (... - 2019) (UNS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut Mondor de Recherche Biomédicale (IMRB), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), CRLCC Antoine Lacassagne, Centre Antoine Lacassagne, Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR50-Université Nice Sophia Antipolis (... - 2019) (UNS), UCL - (MGD) Service d'hématologie, UCL - SSS/IREC/MIRO - Pôle d'imagerie moléculaire, radiothérapie et oncologie, and UCL - SSS/IREC/MONT - Pôle Mont Godinne
Subjects: 0301 basic medicine, Male, Physiology, Phenformin, Cohort Studies, chemistry.chemical_compound, Mice, 0302 clinical medicine, immune system diseases, hemic and lymphatic diseases, Antineoplastic Combined Chemotherapy Protocols, Glyceraldehyde 3-phosphate dehydrogenase, Cells, Cultured, Aged, 80 and over, Predictive marker, biology, GAPDH, Glyceraldehyde-3-Phosphate Dehydrogenases, OxPhos, Middle Aged, glycolysis, Prognosis, 3. Good health, Metformin, Gene Expression Regulation, Neoplastic, medicine.anatomical_structure, Treatment Outcome, Vincristine, R-CHOP, mTOR, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Lymphoma, Large B-Cell, Diffuse, Rituximab, predictive marker, medicine.drug, Adult, Antimetabolites, Antineoplastic, Mice, Transgenic, Gene Expression Regulation, Enzymologic, 03 medical and health sciences, Young Adult, stomatognathic system, medicine, Animals, Humans, Molecular Biology, Cyclophosphamide, PI3K/AKT/mTOR pathway, B cell, Aged, Retrospective Studies, Glutaminolysis, business.industry, Cell Biology, medicine.disease, L-asparaginase, Mice, Inbred C57BL, 030104 developmental biology, HEK293 Cells, chemistry, Doxorubicin, DLBCL, biology.protein, Cancer research, Prednisone, business, Diffuse large B-cell lymphoma, 030217 neurology & neurosurgery
Abstract: International audience; Diffuse large B cell lymphoma (DLBCL) is a heterogeneous disease treated with anti-CD20-based immuno-chemotherapy (R-CHOP). We identified that low levels of GAPDH predict a poor response to R-CHOP treatment. Importantly, we demonstrated that GAPDH(low) lymphomas use OxPhos metabolism and rely on mTORC1 signaling and glutaminolysis. Consistently, disruptors of OxPhos metabolism(phenformin) or glutaminolysis (L-asparaginase) induce cytotoxic responses in GAPDH(low) B cells and improve GAPDH(low) B cell-lymphoma-bearing mice survival, while they are low or not efficient on GAPDH(high) B cell lymphomas. Ultimately, we selected four GAPDH(low) DLBCL patients, who were refractory to all anti-CD20-based therapies, and targeted DLBCL metabolism-using L-asparaginase (K), mTOR inhibitor (T), and metformin (M) (called KTM therapy). Three out of the four patients presented a complete response upon one cycle of KTM. These findings establish that the GAPDH expression level predicts DLBCL patients' response to R-CHOP treatment and their sensitivity to specific metabolic inhibitors.
Published: 2019

27. In-House Implementation of Tumor Mutational Burden Testing to Predict Durable Clinical Benefit in Non-Small Cell Lung Cancer and Melanoma Patients

Author: Benoît Audelan, Henri Montaudié, Jonathan Benzaquen, Simon Heeke, Hervé Delingette, Charles-Hugo Marquette, Olivier Bordone, Marius Ilie, Salomé Lalvée, Michel Poudenx, Elodie Long-Mira, Véronique Hofman, Albrecht Stenzinger, Olivier Humbert, Pierre-Michel Dugourd, Katia Zahaf, Thierry Passeron, Paul Hofman, Madleen Chassang, Virginie Lespinet, COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), Institute of research on Cancer and Aging (IRCAN), Laboratoire de Pathologie Clinique et Expérimentale. Hôpital Pasteur [Nice], Hôpital Pasteur [Nice] (CHU), FHU OncoAge - Pathologies liées à l’âge [CHU Nice] (OncoAge), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Pharmacologie Moléculaire et Cellulaire [UNIV Côte d'Azur] (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Department of Pulmonology and Thoracic Oncology, Centre Hospitalier Universitaire de Nice, Centre Hospitalier Universitaire de Nice (CHU Nice), E-Patient : Images, données & mOdèles pour la médeciNe numériquE (EPIONE), 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), Department of Oncology, Antoine Lacassagne Comprehensive Cancer Center, Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA)-UNICANCER-Université Côte d'Azur (UCA), Department of Nuclear Medicine, Antoine Lacassagne Comprehensive Cancer Center, Department of Dermatology, Archet II Hospital, Centre Hospitalier Universitaire de Nice, Centre Hospitalier Universitaire de Nice (CHU de Nice), Department of Radiology, Archet 2 Hospital, Centre Hospitalier Universitaire de Nice, Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Institute of Pathology, University Hospital Heidelberg, University Hospital Heidelberg, Center for Personalized Oncology (DKFZ-HIPO), Deutsches Krebsforschungszentrum (DKFZ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Pharmacologie Moléculaire et Cellulaire [UNIV Côte d'Azur] (UPMC)-Université Côte d'Azur (UCA), Université Nice Sophia Antipolis (1965 - 2019) (UNS), and Audelan, Benoît
Subjects: 0301 basic medicine, Oncology, Cancer Research, medicine.medical_specialty, tumor mutational burden, medicine.medical_treatment, [SDV.CAN]Life Sciences [q-bio]/Cancer, lcsh:RC254-282, Article, Oncomine TML assay, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, FoundationOne assay, Internal medicine, medicine, melanoma, Lung cancer, neoplasms, business.industry, Melanoma, Immunotherapy, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, 3. Good health, lung cancer, 030104 developmental biology, 030220 oncology & carcinogenesis, Potential biomarkers, Cohort, Immunohistochemistry, Non small cell, immunotherapy, business, Progressive disease
Abstract: Tumor mutational burden (TMB) has emerged as an important potential biomarker for prediction of response to immune-checkpoint inhibitors (ICIs), notably in non-small cell lung cancer (NSCLC). However, its in-house assessment in routine clinical practice is currently challenging and validation is urgently needed. We have analyzed sixty NSCLC and thirty-six melanoma patients with ICI treatment, using the FoundationOne test (FO) in addition to in-house testing using the Oncomine TML (OTML) panel and evaluated the durable clinical benefit (DCB), defined by &gt, 6 months without progressive disease. Comparison of TMB values obtained by both tests demonstrated a high correlation in NSCLC (R2 = 0.73) and melanoma (R2 = 0.94). The association of TMB with DCB was comparable between OTML (area-under the curve (AUC) = 0.67) and FO (AUC = 0.71) in NSCLC. Median TMB was higher in the DCB cohort and progression-free survival (PFS) was prolonged in patients with high TMB (OTML HR = 0.35, FO HR = 0.45). In contrast, we detected no differences in PFS and median TMB in our melanoma cohort. Combining TMB with PD-L1 and CD8-expression by immunohistochemistry improved the predictive value. We conclude that in our cohort both approaches are equally able to assess TMB and to predict DCB in NSCLC.
Published: 2019

28. Impact of HPV-associated p16-expression and other clinical factors on therapeutic decision-making in patients with oropharyngeal cancer: A GETTEC multicentric study

Author: Anne Sudaka, Emmanuel Chamorey, Nicolas Fakhry, Julien Viotti, Agnès Dupret-Bories, Renaud Schiappa, Sébastien Vergez, Olivier Dassonville, Françoise Chapel, Renaud Garrel, Florence Jourdan-Soulier, Alexandre Bozec, D. Culié, Karen Benezery, Benjamin Lallemant, Frederic Peyrade, Gilles Poissonnet, Bruno Guelfucci, José Santini, Service d'ORL, Hôpital Gui de Chauliac (CHRU de Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), CNRS UMR7284, INSERM U1081, Institute for Research on Cancer and Aging, Nice (IRCAN), Centre Antoine Lacassagne, Université Côte d'Azur (UCA), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), ORL et Chirurgie cervico-faciale pédiatrique - [Hôpitaux Timone et Nord - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)- Hôpital Nord [CHU - APHM], Laboratoire Parole et Langage (LPL), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Institut de mécanique des fluides de Toulouse (IMFT), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées, Biomatériaux et Bioingénierie (BB), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-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), Service d'ORL, UNICANCER-Université Côte d'Azur (UCA)-UNICANCER-Université Côte d'Azur (UCA), Service ORL [Hôpital Gui de Chauliac] (CHRU de Montpellier), Hôpital Gui de Chauliac [CHU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Matériaux et Nanosciences Grand-Est (MNGE), and 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)
Subjects: Male, medicine.medical_specialty, Multivariate analysis, Decision Making, [SDV.CAN]Life Sciences [q-bio]/Cancer, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Tumor stage, Biomarkers, Tumor, medicine, [SDV.MHEP.AHA]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Humans, In patient, Oropharyngeal squamous cell carcinoma, 030223 otorhinolaryngology, ComputingMilieux_MISCELLANEOUS, Neoplasm Staging, Retrospective Studies, Human papillomavirus 16, business.industry, Cancer, Retrospective cohort study, General Medicine, Therapeutic decision making, Middle Aged, medicine.disease, 3. Good health, Oropharyngeal Neoplasms, Oropharyngeal Neoplasm, Oncology, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, 030220 oncology & carcinogenesis, Carcinoma, Squamous Cell, Female, Surgery, France, business
Abstract: To analyze the impact of tumor p16 status and other clinical factors on the therapeutic decision-making process in patients with oropharyngeal squamous cell carcinoma (OPSCC).We conducted a multicenter retrospective study (GETTEC collaborative study group) enrolling all OPSCC patients with a determined p16-status considered eligible for surgery between 2009 and 2014. The impact of p16-status and other clinical factors on the therapeutic decision was evaluated in multivariate analysis.A total of 476 patients were enrolled in the study, including 244 cases (51%) of p16-positive OPSCC. Overall, 223 (47%) patients underwent primary surgery, and 184 (83%) of them received postoperative radiotherapy ± chemotherapy. More patients with p16-positive OPSCC tended to undergo non-surgical treatment than did patients with p16-negative OPSCC (p = 0.10). Multivariate analysis showed that 5 factors significantly influenced therapeutic management of the patients: T-stage ≥ 3 (towards a non-surgical strategy; p 0.001), N-stage ≥ 2a (non-surgical strategy; p = 0.02), tumor involvement of the glosso-tonsillar sulcus (surgical strategy; p = 0.002), tumor extension to the oral cavity (surgical strategy; p 0.009) and the center of care (p 0.001). The rate of patients directed towards a surgical strategy varied between 9% and 74% depending on the center.There was a non-significant trend to recommend patients with p16-positive OPSCC for non-surgical treatment. Center of care, tumor stage and tumor anatomical subsite and extensions were the main determinants of the treatment choice.
Published: 2018

29. Target volume delineation for radiotherapy of meningiomas: an ANOCEF consensus guideline

Author: Martz, Nicolas, Salleron, Julia, Dhermain, Frédéric, Vogin, Guillaume, Daisne, Jean-François, Mouttet-Audouard, Raphaelle, Tanguy, Ronan, Noel, Georges, Peyre, Matthieu, Lecouillard, Isabelle, Jacob, Julian, Attal, Justine, Charissoux, Marie, Veresezan, Ovidiu, Hanzen, Chantal, Huchet, Aymeri, Latorzeff, Igor, Coutte, Alexandre, Doyen, Jérôme, Stefan, Dinu, Feuvret, Loic, Garcia, Gabriel, Royer, Philippe, Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), UNICANCER, Institut Gustave Roussy (IGR), Luxembourg Institute of Health (LIH), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER, Centre Léon Bérard [Lyon], CRLCC Paul Strauss, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU), CRLCC Eugène Marquis (CRLCC), 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 Claudius Regaud, UNICANCER - Institut régional du Cancer Montpellier Val d'Aurelle (ICM), CRLCC Val d'Aurelle - Paul Lamarque, Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), CHU Bordeaux [Bordeaux], Clinique Pasteur [Toulouse], 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), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Université Côte d'Azur (UCA), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), and Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)
Subjects: Radiotherapy, [SDV.CAN]Life Sciences [q-bio]/Cancer, Delineation, Target volume, Meningiomas, Consensus guidelines
Abstract: International audience; Purpose Radiotherapy is, with surgery, one of the main therapeutic treatment strategies for meningiomas. No prospective study has defined a consensus for the delineation of target volumes for meningioma radiotherapy. Therefore, target volume definition is mainly based on information from retrospective studies that include heterogeneous patient populations. The aim is to describe delineation guidelines for meningioma radiotherapy as an adjuvant or definitive treatment with intensity-modulated radiation therapy and stereotactic radiation therapy techniques. This guideline is based on a consensus endorsed by a multidisciplinary group of brain tumor experts, members of the Association of French-speaking Neuro-oncologists (ANOCEF). Materials and methods A 3-step procedure was used. First, the steering group carried out a comprehensive review to identify divergent issues on meningiomas target volume delineation. Second, an 84-item web-questionnaire has been developed to precisely define meningioma target volume delineation in the most common clinical situations. Third, experts members of the ANOCEF were requested to answer. The first two rounds were completed online. A third round was carried out by videoconference to allow experts to debate and discuss the remaining uncertain questions. All questions remained in a consensus. Results Limits of the target volume were defined using visible landmarks on computed tomography and magnetic resonance imaging, considering the pathways of tumor extension. The purpose was to develop clear and precise recommendations on meningiomas target volumes. Conclusion New recommendations for meningiomas delineation based on simple anatomic boundaries are proposed by the ANOCEF. Improvement in uniformity in target volume definition is expected.
Published: 2023

30. Plasminogen Activator System and Breast Cancer: Potential Role in Therapy Decision Making and Precision Medicine

Author: Sadek Benharkat, Aoulia Dekaken, Arifa Aissaoui, Gérard Milano, Joseph Ciccolini, Nihad Laabed, Khalid El Bairi, Mohamed Chefrour, Adel Gouri, Laboratoire de biochimie, Université Badji Mokhtar - Annaba [Annaba] (UBMA), Département de médecine interne, Hôpital El Hakim Okbi, Université Mohamed 1 Oujda MAROC, SMARTc, Centre de Recherches en Oncologie biologique et Oncopharmacologie (CRO2), Institut National de la Santé et de la Recherche Médicale (INSERM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Aix Marseille Université (AMU), Département de pharmacogénomique, Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA)-UNICANCER-Université Côte d'Azur (UCA), Université Badji Mokhtar Annaba (UBMA), Simulation & Modelling : Adaptive Response for Therapeutics in Cancer (SMARTc unit), Aix Marseille Université (AMU)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), and ciccolini, joseph
Subjects: 0301 basic medicine, Oncology, medicine.medical_specialty, precision medicine, [SDV.CAN]Life Sciences [q-bio]/Cancer, Disease, Review, Bioinformatics, Metastasis, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, breast cancer, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, medicine, Adjuvant therapy, urokinase plasminogen activator, Pharmacology, lcsh:R5-920, business.industry, Biochemistry (medical), Cancer, Precision medicine, medicine.disease, 3. Good health, Urokinase receptor, 030104 developmental biology, 030220 oncology & carcinogenesis, Molecular Medicine, therapy decision, business, lcsh:Medicine (General), Plasminogen activator
Abstract: International audience; Shifting from the historical TNM paradigm to the determination of molecular and genetic subtypes of tumors has been a major improvement to better picture cancerous diseases. The sharper the picture is, the better will be the possibility to develop subsequent strategies, thus achieving higher efficacy and prolonged survival eventually. Recent studies suggest that urokinase-type plasminogen activator (uPA), uPA receptor (uPAR), and plasmino-gen activator inhibitor-1 (PAI-1) may play a critical role in cancer invasion and metastasis. Consistent with their role in cancer dissemination, high levels of uPA, PAI-1, and uPAR in multiple cancer types correlate with dismal prognosis. In this respect, upfront determination of uPA and PAI-1 as invasion markers has further opened up the possibilities for individualized therapy of breast cancer. Indeed, uPA and PAI-1 could help to classify patients on their risk for metastatic spreading and subsequent relapse, thus helping clinicians in their decision-making process to propose, or not propose, adjuvant therapy. This review covers the implications for cancer diagnosis, prognosis, and therapy of uPA and PAI-1, and therefore how they could be major actors in the development of a precision medicine in breast cancer.
Published: 2016

31. MicroRNA-375/SEC23A as biomarkers of the in vitro efficacy of vandetanib

Author: Patrick Brest, Pascal Barbry, Marius Ilie, Paul Hofman, Sandra Lassalle, Elodie Long, Frédérique Tissier, Joséphine Zangari, Philippe Vielh, Géraldine Lemaire, Imène Sarah Henaoui, Catherine Butori, Alexandra Popa, Olivier Blanck, Christelle Bonnetaud, Hélène Trouette, Nicolas Guevara, Olivier Bordone, Alexandre Bozec, Bernard Mari, Geneviève Belléannée, J.-L. Sadoul, José Santini, Isabelle Peyrottes, Bogdan Catargi, Véronique Hofman, Martine Patey, 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), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), An algorithmic view on genomes, cells, and environments (BAMBOO), Inria Grenoble - Rhône-Alpes, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-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), Institut de la physique de la matière condensée (IPMC), Université Joseph Fourier - Grenoble 1 (UJF)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National Polytechnique de Grenoble (INPG)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Nice (CHU Nice), Laboratory of Clinical and Experimental Pathology, Laboratoire d’anatomie et cytologie pathologique, Hôpital Robert Debré, CHU de Reims, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Bordeaux [Bordeaux], Department of Pathology, Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA)-UNICANCER-Université Côte d'Azur (UCA), UNICANCER-Université Côte d'Azur (UCA), Service d'Endocrinologie (NICE - Endocrino), Hôpital Pasteur [Nice] (CHU), Institut de pharmacologie moléculaire et cellulaire (IPMC), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), 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), Bayer Cropscience, Pathologie morphologique, Département de biologie et pathologie médicales [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS), Infection bactérienne, inflammation, et carcinogenèse digestive, COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-IFR50-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), FHU OncoAge - Pathologies liées à l’âge [CHU Nice] (OncoAge), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Pharmacologie Moléculaire et Cellulaire [UNIV Côte d'Azur] (UPMC)-Université Côte d'Azur (UCA), Université Nice Sophia Antipolis (... - 2019) (UNS), Service de pathologie [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 National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)-Institut de Pharmacologie Moléculaire et Cellulaire [UNIV Côte d'Azur] (UPMC), Service d'Anatomie et cytologie pathologiques = Service de Pathologie [CHU Pitié-Salpêtrière] (ACP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Brest, Patrick
Subjects: Male, 0301 basic medicine, [SDV]Life Sciences [q-bio], Vesicular Transport Proteins, [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Vandetanib, 0302 clinical medicine, Piperidines, RNA interference, medullary thyroid carcinoma, ComputingMilieux_MISCELLANEOUS, Aged, 80 and over, microRNA, treatment, Thyroid, Middle Aged, 3. Good health, [SDV] Life Sciences [q-bio], Gene Expression Regulation, Neoplastic, medicine.anatomical_structure, Oncology, 030220 oncology & carcinogenesis, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Immunohistochemistry, Female, RNA Interference, Research Paper, medicine.drug, Adult, vandetanib, microRNA-375, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Cell Line, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, Cell Line, Tumor, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Biomarkers, Tumor, medicine, Humans, Gene silencing, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Thyroid Neoplasms, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, Aged, Cell Proliferation, business.industry, Cell growth, Gene Expression Profiling, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Carcinoma, Neuroendocrine, Gene expression profiling, MicroRNAs, 030104 developmental biology, Quinazolines, Cancer research, business
Abstract: In this study, we performed microRNA (miRNA) expression profiling on a large series of sporadic and hereditary forms of medullary thyroid carcinomas (MTC). More than 60 miRNAs were significantly deregulated in tumor vs adjacent non-tumor tissues, partially overlapping with results of previous studies. We focused our attention on the strongest up-regulated miRNA in MTC samples, miR-375, the deregulation of which has been previously observed in a variety of human malignancies including MTC. We identified miR-375 targets by combining gene expression signatures from human MTC (TT) and normal follicular (Nthy-ori 3-1) cell lines transfected with an antagomiR-375 inhibitor or a miR-375 mimic, respectively, and from an in silico analysis of thyroid cell lines of Cancer Cell Line Encyclopedia datasets. This approach identified SEC23A as a bona fide miR-375 target, which we validated by immunoblotting and immunohistochemistry of non-tumor and pathological thyroid tissue. Furthermore, we observed that miR-375 overexpression was associated with decreased cell proliferation and synergistically increased sensitivity to vandetanib, the clinically relevant treatment of metastatic MTC. We found that miR-375 increased PARP cleavage and decreased AKT phosphorylation, affecting both cell proliferation and viability. We confirmed these results through SEC23A direct silencing in combination with vandetanib, highlighting the importance of SEC23A in the miR-375-associated increased sensitivity to vandetanib. Since the combination of increased expression of miR-375 and decreased expression of SEC23A point to sensitivity to vandetanib, we question if the expression levels of miR-375 and SEC23A should be evaluated as an indicator of eligibility for treatment of MTC patients with vandetanib.
Published: 2016

32. Standardization of 18F-FDG PET/CT According to Deauville Criteria for MRD Evaluation in Newly Diagnosed Transplant Eligible Multiple Myeloma Patients: Joined Analysis of Two Prospective Randomized Phase III Trials

Author: Elena Zamagni, Cristina Nanni, Luca Dozza, Thomas Carlier, Paola Tacchetti, Annibale Versari, Stephane Chauvie, Andrea Gallamini, Michel Attal, Barbara Gamberi, Denis Caillot, Francesca Patriarca, Margaret Macro, Mario Boccadoro, Laurent Garderet, Stefano Fanti, Aurore Perrot, Francesca Gay, Pieter Sonneveld, Lionel Karlin, Michele Cavo, Caroline Bodet-Milin, Philippe Moreau, Francoise Kraeber-Bodere, The Institute of Hematology and Oncology L. and A. Seràgnoli [Bologna, Italy], Alma Mater Studiorum Università di Bologna [Bologna] (UNIBO), Nuclear Medicine Unit [Bologna, Italy], Sant'Orsola-Malpighi Hospital [Bologna, Italy], Nuclear Oncology (CRCINA-ÉQUIPE 13), 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), S.C. Medicina Nucleare - Centro PET [Reggio Emilia, Italy], A.O. Arcispedale S. Maria Nuova [Reggio Emilia, Italy], Medical Physics Unit [Cuneo, Italy], Santa Croce e Carle Hospital [Cuneo, Italy], Recherche, Innovation et Statistiques [Nice] (Centre de Cancérologie Antoine-Lacassagne), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA)-UNICANCER-Université Côte d'Azur (UCA), 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), Arcispedale Santa Maria Nuova [Reggio Emilia, Italy], Service d'Hématologie Clinique (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Hematology and Bone Marrow Transplant Unit [Udine, Italy], Università degli Studi di Udine - University of Udine [Italie], Laboratoire d'Hématologie Biologique [CHU Caen], 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), Department of Molecular Biotechnologies and Health Sciences [Torino, Italy] (Hematology Division), Università degli studi di Torino (UNITO), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Cibles thérapeutiques, formulation et expertise pré-clinique du médicament (CITHEFOR), Université de Lorraine (UL), Myeloma Unit [Torino, Italy] (Division of Hematology), Depatment of Hematology [Rotterdam, Netherlands], Erasmus University Medical Center [Rotterdam] (Erasmus MC), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Centre hospitalier universitaire de Nantes (CHU Nantes), Bernardo, Elizabeth, 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), 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), and Università degli studi di Torino = University of Turin (UNITO)
Subjects: medicine.medical_specialty, Phase iii trials, Immunology, Computed tomography, [SDV.CAN]Life Sciences [q-bio]/Cancer, Newly diagnosed, Biochemistry, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, medicine, Multiple myeloma, ComputingMilieux_MISCELLANEOUS, medicine.diagnostic_test, business.industry, Cell Biology, Hematology, medicine.disease, Standard technique, 3. Good health, Transplantation, Homogeneous, 030220 oncology & carcinogenesis, Family medicine, Fdg pet ct, business, 030215 immunology
Abstract: F-18-fluorodeoxyglucose positron emission tomography integrated with computed tomography (FDG-PET/CT) is actually considered as the standard technique to assess and monitor the metabolic response to therapy and to define minimal residual disease (MRD) status outside the bone marrow (BM) in multiple myeloma (MM) patients. In this regard, standardization of image criteria and definition of cut-offs for positivity/negativity is of highly importance. Aim of the present study was to prospectively evaluate FDG-PET/CT at diagnosis and prior to maintenance therapy in a joined analysis of a sub-group of patients with newly diagnosed transplant-eligible MM, enrolled in 2 independent European randomized phase III trials (EMN02/HO95 and IFM2009) (Cavo M et al, Blood 2017 abs; Attal M et al, NEJM 2017). The primary end-point was to standardize PET/CT evaluation by centralized imaging and revision and to define criteria for PET negativity after therapy (MRD definition). 236 patients (102 and 134 from the EMN02 and IFM2009 trial, respectively) were enrolled in the PET/CT imaging sub-studies and followed for a median of 62.9 (IQR: 44.9-67.9) months. By study design, PET/CT scans were performed locally at baseline (B) and prior to the start of maintenance (PM), uploaded in a central website and re-interpreted a-posteriori in a blinded independent central review process, by a panel of expert nuclear medicine physicians. According to the IMPeTUs criteria (Nanni C et al, EJNM 2017), the five-point Deauville scores (between 1 and 5) were applied to the following parameters: bone marrow (BM), focal lesions (FLs), extramedullary disease (EMD). The impact of each parameter on outcomes was evaluated by landmark analyses at PM; the univariate and multivariate analyses were stratified by trial to smooth out differences between the 2 studies. Baseline characteristics of the patients were generally homogeneous between the 2 trials and as follows: median age 59 years, ISS and R-ISS stage III 15.8% and 11.5%, respectively, high-risk cytogenetics (t(4;14) ± del(17p) ± t(14;16) detected by FISH) 14%. Fifty seven percent of the patients were randomized in the transplant arm, and 43% in the bortezomib-intensification arm, with a higher percentage in the IFM2009 vs EMN02 trial (54% vs 24%, respectively). At baseline, 80% of the patients had FLs, with a median maximum standardized uptake value (SUVmax) of 5. Median BM SUVmax was 3. Both median FLs and BM SUVmax were slightly higher in the IFM2009 vs the EMN02 trial (5.7 vs 4.2 and 3.7 vs 2.68, respectively), while reference SUVmean (mediastinal blood pool and liver) did not differ between the 2 studies. FLs Deauville score (FS) and BM Deauville score (BMS) > 3 (higher than the liver) were present in 79.8% and 35.5% of the patients, respectively, with no difference between the 2 trials. EMD was present in 11% of the patients. Prior to maintenance therapy, median FLs and BM SUVmax were 3.6 and 2.3, respectively, with 53.5% and 71.2% of the patients obtaining a FS and BMS ≤ 2 and 79% and 91.4% ≤ 3, respectively. In univariate analysis, at Landmark time prior to maintenance, attaining a FS and BMS ≤ 3 was the strongest predictor for prolonged PFS (FS≤ 3 vs >3: median 40 vs 26.6 months, HR 0.6, CI 0.39-0.98, P= 0.0019; BMS≤ 3 vs >3: median 39.8 vs 26.6 months, HR 0.47, CI 0.24-0.91, P= 0.024, respectively) and OS (FS≤ 3 vs >3: estimate at 63 months 73% vs 63.6% months, HR 0.51, CI 0.26-0.98, P= 0.028; BMS≤ 3 vs >3: estimate at 75.5% vs 49.7%, HR 0.28, CI 0.12-0.64, P= 0.002, respectively) and could be identified as the most representative cut-off values for PET negativity after therapy. Of the two PM scores, only FS ≤ 3 retained prognostic relevance in the subgroup of patients not receiving transplant, in terms of PFS. In Cox multivariable analysis, FS and BMS ≤ 3 at PM were independent predictors of prolonged PFS (FS: HR 0.58, CI 0.35-0.96, P= 0.036; BMS HR 0.41, CI 0.20-0.84, P= 0.014) and OS (FS: HR 0.36, CI 0.17-0.74, P= 0.005; BMS HR 0.24, CI 0.09-0.63, P= 0.004). In conclusion, FDG PET/CT was confirmed to be a reliable predictor of outcomes in newly diagnosed MM, regardless of treatment. Reduction of FDG uptake lower than the liver after therapy, both in the FLs and in the BM (FS and BMS), was an independent predictor for improved PFS and OS. Findings from this analysis could be proposed as standardized criteria to define PET negativity after therapy, confirming the value of Deauville scores in MM. Disclosures Zamagni: Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees. Tacchetti:Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria; Janssen: Honoraria; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Honoraria. Gallamini:Takeda: Consultancy, Speakers Bureau. Patriarca:Jazz: Other: Travel, accommodations, expenses; Medac: Other: Travel, accommodations, expenses; Celgene: Other: Advisory Role; Travel, accommodations, expenses; Janssen: Other: Advisory role; MSD Italy: Other: Advisory Role. Macro:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Financial support for congress; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Financial support for congress; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Financial support for congress; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Financial support for congress. Boccadoro:Bristol-Myers Squibb: Honoraria, Research Funding; AbbVie: Honoraria; Novartis: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Amgen: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Sanofi: Honoraria, Research Funding; Mundipharma: Research Funding. Garderet:Takeda: Consultancy; Amgen: Consultancy; Celgene: Consultancy. Perrot:Takeda: Honoraria; Sanofi: Honoraria; Amgen: Honoraria; Janssen: Honoraria; Celgene: Honoraria. Sonneveld:Amgen: Honoraria, Research Funding; BMS: Honoraria, Research Funding; Karyopharm: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Celgene: Honoraria, Research Funding. Karlin:Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel support; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel support. Cavo:Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Adaptive Biotechnologies: Honoraria, Membership on an entity's Board of Directors or advisory committees. Moreau:Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees.
Published: 2018

33. Docetaxel, cisplatin, and fluorouracil chemotherapy for metastatic or unresectable locally recurrent anal squamous cell carcinoma (Epitopes-HPV02): a multicentre, single-arm, phase 2 study

Author: Stefano Kim, Nabil Baba-Hamed, Denis Smith, Dewi Vernerey, Marine Jary, Aurélia Meurisse, Olivier Adotevi, Olivier Bouché, Nicolas Badet, Thierry André, Amélie Anota, François Ghiringhelli, Julien Taieb, Eric Francois, Emmanuelle Samalin, Aurélie Parzy, Mélanie Deberne, Laurie Spehner, Véronique Vendrely, Christelle De La Fouchardiere, Simon Pernot, Jérôme Desramé, Mustapha Zoubir, Bruno Buecher, Marie-Christine Kaminsky, Christophe Borg, Farid El Hajbi, 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 d'Investigation Clinique de Besançon (Inserm CIC 1431), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), 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]), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Fédération Francophone de la Cancérologie Digestive, FFCD, Service d'oncologie médicale (Centre Antoine Lacassagne, Nice), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA)-UNICANCER-Université Côte d'Azur (UCA), 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), CRLC Val d'Aurelle-Paul Lamarque, CRLCC Val d'Aurelle - Paul Lamarque, UNICANCER - Institut régional du Cancer Montpellier Val d'Aurelle (ICM), Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université Lille Nord de France (COMUE)-UNICANCER, Groupe Hospitalier Paris Saint Joseph, 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), Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), UNICANCER, Département d'oncologie médicale (CHU Robert Debré, Reims), Centre Hospitalier Universitaire de Reims (CHU Reims), Center Jean Mermoz, Hôpital privé des Peupliers (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, Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Centre Léon Bérard [Lyon], Département d'Oncologie [CHU Bordeaux] (Cancérologie/Oncologie/Digestive), GH Sud Haut-Lévêque [CHU Hôpitaux de Bordeaux] (Centre médico chirurgical Magellan)-Hôpital Saint-André [CHU de Bordeaux], Service d'Oncologie Médicale [Centre hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Clinique Saint Vincent [Besançon], Plateforme Qualité de vie et cancer, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Département d'Oncologie Médicale [Institut Curie, Paris], Institut Curie [Paris], Cooperator Multidisciplinary Oncology Group (GERCOR), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC), Université de Lille-UNICANCER, Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), and Hôpital Haut-Lévêque - CHU de Bordeaux (Centre médico chirurgical Magellan)-Hôpital Saint-André [CHU de Bordeaux]
Subjects: Male, 0301 basic medicine, medicine.medical_specialty, Population, [SDV.CAN]Life Sciences [q-bio]/Cancer, Docetaxel, Neutropenia, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Squamous cell carcinoma, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Progression-free survival, Neoplasm Metastasis, education, Aged, education.field_of_study, Performance status, business.industry, Anal Squamous Cell Carcinoma, Middle Aged, Anus Neoplasms, medicine.disease, Progression-Free Survival, 3. Good health, 030104 developmental biology, Oncology, Fluorouracil, 030220 oncology & carcinogenesis, Carcinoma, Squamous Cell, Female, Cisplatin, Neoplasm Recurrence, Local, business, Febrile neutropenia, medicine.drug
Abstract: Summary Background The incidence of anal squamous cell carcinoma has been increasing markedly in the past few decades. Currently, there is no validated treatment for advanced-stage anal squamous cell carcinoma. Therefore, we aimed to validate the clinical activity and safety of docetaxel, cisplatin, and fluorouracil (DCF) chemotherapy in patients with metastatic or unresectable locally recurrent anal squamous cell carcinoma. Methods We did a multicentre, single-arm, phase 2 study. We recruited patients from 25 academic hospitals, cancer research centres, and community hospitals in France who were aged 18 years or older with histologically confirmed anal squamous cell carcinoma, with metastatic disease or with unresectable local recurrence; an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1; and with at least one evaluable lesion according to the Response Evaluation Criteria in Solid Tumors (version 1.1). Chemotherapy-naive patients received either six cycles of standard DCF (75 mg/m 2 docetaxel and 75 mg/m 2 cisplatin on day 1 and 750 mg/m 2 per day of fluorouracil for 5 days, every 3 weeks) or eight cycles of modified DCF (40 mg/m 2 docetaxel and 40 mg/m 2 cisplatin on day 1 and 1200 mg/m 2 per day of fluorouracil for 2 days, every 2 weeks), which were administered intravenously. The choice between the standard versus modified regimens was recommended based on, but not limited to, age (≤75 years vs >75 years) and ECOG performance status (0 vs 1). The primary endpoint was investigator-assessed progression-free survival at 12 months from the first DCF cycle; for the primary endpoint to be met, at least 11 (17%) of 66 enrolled patients had to be alive without disease progression at 12 months. Efficacy and safety analyses were done in a modified intention-to-treat population, defined as all patients who were evaluable for progression at 12 months who received at least one cycle of DCF. This trial is registered at ClinicalTrials.gov, number NCT02402842, and the final results are presented here. Findings Between Sept 17, 2014, and Dec 7, 2016, we enrolled 69 patients. Of these patients, three did not receive DCF. Of the 66 patients who received treatment, 36 received the standard DCF regimen and 30 received modified DCF. The primary endpoint was met: 31 (47%) of 66 patients were alive and progression free at 12 months. 22 (61%) of 36 patients who received the standard DCF regimen and 18 (60%) of 30 patients who received the modified DCF regimen had disease progression at data cutoff. 46 (70%) of 66 patients had at least one grade 3–4 adverse event (30 [83%] of 36 in the standard DCF regimen and 16 [53%] of 30 in the modified DCF regimen). The most common grade 3–4 adverse events were neutropenia (15 [23%]; eight [22%] for standard DCF vs seven [23%] for modified DCF), diarrhoea (12 [18%]; nine [25%] vs three [10%]), asthenia (ten [15%]; eight [22%] vs two [7%]), anaemia (ten [15%]; six [17%] vs four [13%]), lymphopenia (eight [12%]; three [8%] vs five [17%]), mucositis (seven [11%]; seven [19%] vs none), and vomiting (seven [11%]; five [14%] vs two [7%]). No grade 4 non-haematological adverse events and febrile neutropenia were observed with modified DCF, whereas three (8%) grade 4 non-haematological adverse events and five (14%) cases of febrile neutropenia were reported with standard DCF. 97 serious adverse events were reported (69 in patients who received the standard DCF regimen [61 drug-related] and 28 in those given the modified DCF regimen [14 drug-related]). No treatment-related deaths were recorded. Interpretation Compared with standard DCF, modified DCF provided long-lasting response with good tolerability in patients with metastatic or unresectable locally recurrent anal squamous cell carcinoma with ECOG performance status of 0–1 in the first-line setting, and therefore could be considered as a new standard of care for these patients. Regarding the elevated risk of high-grade and serious adverse events and febrile neutropenia, standard DCF cannot be recommended in this situation. Funding Besancon University Hospital and Ligue contre le cancer Grand-Est.
Published: 2018

34. Towards holistic building optimization using a computing environment that enable interoperability between numerical tools

Author: Fraisse, G., Souyri, B., Wurtz, F., Brunotte, X., Enciu, P., Peuportier, B., Robillart, M., Mohamed El Mankibi, Stathopoulos, N., Truchet, S., François, E., Shyam, Laboratoire Optimisation de la Conception et Ingénierie de l'Environnement (LOCIE), Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Génie Electrique de Grenoble (G2ELab), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Cedrat, CEDRAT, Centre Efficacité Énergétique des Systèmes (CES), MINES ParisTech - École nationale supérieure des mines de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), Laboratoire de Tribologie et Dynamique des Systèmes (LTDS), École Centrale de Lyon (ECL), Université de Lyon-Université de Lyon-École Nationale des Travaux Publics de l'État (ENTPE)-Ecole Nationale d'Ingénieurs de Saint Etienne-Centre National de la Recherche Scientifique (CNRS), Service d'oncologie médicale (Centre Antoine Lacassagne, Nice), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), and UNICANCER-Université Côte d'Azur (UCA)-UNICANCER-Université Côte d'Azur (UCA)
Subjects: [SPI]Engineering Sciences [physics], Life cycle Analysis, Building, Global optimization, Interoperability, Surrogate model
Abstract: International audience; Performance optimization has become a standard approach for the design and control of energy systems. The building sector doesn't escape this trend with very dynamic research activity on the subject. This allows designing more and more efficient buildings that contributes to limit the climate change's effects. Design of buildings is usually based on a sequential approach: reduction of demand improvement of energy efficiency and finally use of renewable energies. A holistic building design approach is more efficient since the optimum of a system can be different from the one obtained by separating its components. It is thus necessary to optimize the design by considering the building as a whole (envelope, system, occupants, and environment) and over its lifetime, particularly in the perspective of the climate change. In this context, there are significant difficulties linked to calculation time, dynamic simulations of the building (envelope and systems), taking into account the climate change, combinatorial explosion related to the decision parameters during the optimization, and inclusion of uncertainties ... It is therefore necessary to use specific methodologies such as the use of surrogate models or parallel computing. The optimization is obviously multi-criteria and the overall optimum must be obtained with a reasonable computing time for an engineering office for example. The performance functions (environment, financial, comfort, reliability ...) can be evaluated with different tools that must be interoperable. In this context, we present a methodology and an environment for the holistic optimization of buildings. This environment allows the interoperability of numerical tools used by engineering offices. Finally, two optimized multi-criteria design case studies (2 test functions and the real building "Les Roches Blanche" in Chambéry) are presented to illustrate the approach and the developed environment.
Published: 2018

35. Long-term quality of life and psycho-social outcomes after oropharyngeal cancer surgery and radial forearm free-flap reconstruction: A GETTEC prospective multicentric study

Author: Gilles Poissonnet, Jean-Claude Merol, Esteban Brenet, Frederic Peyrade, José Santini, Maria Lesnik, Pierre Demez, Jocelyn Gal, Pierre Ransy, E. Berta, Emmanuel Babin, Alexandre Bozec, Emmanuel Chamorey, Marie-Yolande Louis, Olivier Dassonville, Karen Benezery, D. Blanchard, Dominique De Raucourt, Institut Universitaire de la Face et du Cou [Nice], Department of Otorhinolaryngology and Head and Neck Surgery, University Hospital of Liege, Belgium, Département Recherche Clinique Innovation et Statistiques/Unité d'Epidémiologie et Biostatistiques (Centre Antoine Lacassagne), FNCLL, 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), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Department of Maxillo-facial and Head and Neck Surgery, Centre François-Baclesse, Caen, Centre Hospitalier Universitaire de Reims (CHU Reims), Department of Otorhinolaryngology and Head and Neck Surgery, University Hospital of Reims, Service d'ORL, UNICANCER-Université Côte d'Azur (UCA)-UNICANCER-Université Côte d'Azur (UCA), Service d’Otorhino-laryngologie et de chirurgie cervicofaciale [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Department of Otorhinolaryngology and Head and Neck Surgery, Hospital of Annecy, Centre d'étude et de recherche sur les risques et les vulnérabilités (CERREV), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Service d'Oto-Rhino-Laryngologie (O.R.L.) et de Chirurgie Cervico-Faciale [CHU Caen], Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Unité de recherche interdisciplinaire pour la prévention et le traitement des cancers (ANTICIPE), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Université de Caen Normandie (UNICAEN), 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), and UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER
Subjects: Adult, Male, Quality of life, Oropharynx cancer, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Anxiety, Hospital Anxiety and Depression Scale, Surgical Flaps, 03 medical and health sciences, 0302 clinical medicine, Swallowing, Psychosocial outcomes, Surveys and Questionnaires, medicine, Humans, Prospective Studies, Voice Handicap Index, 030223 otorhinolaryngology, Prospective cohort study, Head and neck cancer, Aged, Aged, 80 and over, business.industry, Depression, Middle Aged, Plastic Surgery Procedures, medicine.disease, Prognosis, Dysphagia, humanities, 3. Good health, Survival Rate, Forearm, Oropharyngeal Neoplasms, Oncology, 030220 oncology & carcinogenesis, Physical therapy, Carcinoma, Squamous Cell, Female, Surgery, medicine.symptom, business, Follow-Up Studies
Abstract: International audience; ObjectiveTo assess long-term quality of life (QoL) and psycho-social outcomes, and to determine their predictive factors after oropharyngeal cancer (OPC) surgery and radial forearm free-flap (RFFF) reconstruction.MethodsPatients who had undergone OPC surgery and RFFF reconstruction who were still alive and disease-free at least 1 year after surgery were enrolled in this prospective multicentric study. Patients completed the European Organization for Research and Treatment of Cancer (EORTC) Core (QLQ-C30) and Head and Neck Cancer (QLQ-H&N35) QoL questionnaires, the Voice Handicap Index (VHI-10) questionnaire and the Hospital Anxiety and Depression Scale (HADS). The level of dysphagia was evaluated using the Dysphagia Handicap Index (DHI) and the Dysphagia Outcomes and Severity Scale (DOSS). Predictive factors of these clinical outcomes were determined in univariate and multivariate analysis.ResultsA total of 58 patients were included in this study. Long-term QoL and functioning scales scores were well-preserved (all superior to 70%). Main persistent symptoms were fatigue, reduced sexuality and oral function-related disorders (swallowing, teeth, salivary and mouth-opening problems). HADS anxiety and depression scores were 7.2 and 5.4, respectively. Twenty-one (36%) patients presented an anxiodepressive disorder (HADS global score ≥ 15). Among the 21 patients who were still working before surgery, 11 (52%) had returned to work at the time of our study. The HADS global score (p < 0.001) was the main predictor of QoL, VHI-10 and DOSS scores.ConclusionsPsychological distress is the main determinant of long-term QoL and is therefore of critical importance in the multidisciplinary management of OPC patients.
Published: 2018

36. Dépistage du déficit en dihydropyrimidine déshydrogénase (DPD) et sécurisation des chimiothérapies à base de fluoropyrimidines:mise au point et recommandations nationales du GPCO-Unicancer et du RNPGx

Author: Xavier Fonrose, Bernard Royer, Sylvie Quaranta, Anne-Sophie Wozny, Nicolas Picard, Vianney Poinsignon, Fadil Masskouri, Antonin Schmitt, Jean-Christophe Boyer, Franck Broly, Fabienne Thomas, Gérard Milano, Céline Narjoz, Claire Lafay-Chebassier, Joseph Ciccolini, Céline Verstuyft, Angelo Paci, Christine Bobin-Dubigeon, Alexandre Harlé, Marie-Christine Etienne-Grimaldi, Alexandre Evrard, Benjamin Hennart, Laurent Becquemont, Marie-Anne Loriot, Chantal Barin-Le-Guellec, CHU Lille, Institut Pasteur de Lille, Université de Lille, Toxicologie et Génopathies [CHRU Lille], 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), Simulation & Modelling : Adaptive Response for Therapeutics in Cancer (SMARTc unit), Centre de Recherches en Oncologie biologique et Oncopharmacologie (CRO2), Institut National de la Santé et de la Recherche Médicale (INSERM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Aix Marseille Université (AMU), Institut Claudius Regaud, Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Département de pharmacogénomique, Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA)-UNICANCER-Université Côte d'Azur (UCA), Département Micro-Ondes (MO), Université européenne de Bretagne - European University of Brittany (UEB)-Télécom Bretagne-Institut Mines-Télécom [Paris] (IMT), Service de génétique moléculaire, pharmacogénétique et hormonologie, Hôpital Bicêtre-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Bases moléculaires de la réponse aux xénobiotiques (U775 (IFR95)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre d'épidémiologie des populations (CEP), Université de Bourgogne (UB)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER, Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Centre de Recherche en Automatique de Nancy (CRAN), Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL), Pharmacologie, Département de biologie et pathologie médicales [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Laboratoire de Biochimie [CHRU Nîmes], Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), 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), Laboratoire de Toxicologie, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Ciblage thérapeutique en Oncologie (EA3738), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, UNICANCER-Université Côte d'Azur (UCA), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Aix Marseille Université (AMU)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), Individualisation des traitements des cancers ovariens (ITCO), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut Universitaire du Cancer Toulouse - Oncopôle (IUCT), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (HOTE GREFFON), Université de Franche-Comté (UFC)-Etablissement français du sang [Bourgogne-France-Comté] (EFS [Bourgogne-France-Comté])-Institut National de la Santé et de la Recherche Médicale (INSERM), CRLCC Antoine Lacassagne, Institut Mines-Télécom [Paris] (IMT)-Télécom Bretagne-Université européenne de Bretagne - European University of Brittany (UEB), Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Bicêtre, Université de Bourgogne (UB)-Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc (CRLCC - CGFL), Institut de cancérologie de l'Ouest - Nantes (ICO Nantes), CRLCC Paul Papin-CRLCC René Gauducheau, Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire de Nîmes (CHRU Nîmes), Centre Antoine Lacassagne, Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre
Subjects: 03 medical and health sciences, Cancer Research, 0302 clinical medicine, Oncology, 030220 oncology & carcinogenesis, Radiology, Nuclear Medicine and imaging, [SDV.CAN]Life Sciences [q-bio]/Cancer, Hematology, General Medicine, Fluoropyrimidine, 5-Fluorouracile, Capécitabine, Dihydropyrimidine déshydrogénase, DPYD, Dépistage, Toxicité, Recommandation, Pharmacogénétique, 030226 pharmacology & pharmacy, 5Fluorouracil, Capecitabine, Dihydropyrimidine dehydrogenase, Screening, Toxicity, Recommendation, Pharmacogenetics, 3. Good health
Abstract: Les fluoropyrimidines restent les molécules anticancéreuses les plus prescrites dans le traitement des tumeurs solides. Elles induisent des toxicités sévères chez 10–40 % des patients et des toxicités létales chez 0,2–0,8 % des patients. Une abondante littérature a établi le lien entre un déficit enzymatique en dihydropyrimidine déshydrogénase (DPD, enzyme qui dégrade le 5-FU) et la survenue d’une toxicité sévère sous fluoropyrimidine. Si les déficits complets en DPD sont rares (0,1–0,5 %), les déficits partiels sont retrouvés chez 3–15 % des patients. La recherche du déficit en DPD peut être réalisée par phénotypage (mesure directe ou indirecte de l’activité enzymatique) ou par génotypage (recherche des principaux polymorphismes fonctionnels du gène DPYD). Actuellement, il n’existe pas d’obligation réglementaire pour le dépistage du déficit en DPD avant l’administration de fluoropyrimidines. Sur la base des niveaux de preuve issus de la littérature, et des pratiques actuelles, le Groupe de Pharmacologie Clinique Oncologique (GPCO)-UNICANCER et le Réseau National de Pharmacogénétique hospitalière (RNPGx) recommandent : (1) de rechercher un déficit en DPD avant la mise en route de tout traitement à base de 5-FU ou capécitabine ; (2) de réaliser ce dépistage par phénotypage en dosant en première intention l’uracile plasmatique (U) (éventuellement complété par le rapport dihydrouracil/U) et en y associant le génotypage des variants *2A, *13, p.D949V et HapB3 ; (3) de réduire si nécessaire la posologie en fonction du statut DPD dès la première cure et d’envisager une augmentation de dose aux cures suivantes en fonction de la tolérance. Actuellement en France, 17 laboratoires hospitaliers réalisent en routine la recherche du déficit en DPD. Fluoropyrimidines (FU) are still the most prescribed anticancer drugs for the treatment of solid cancers. However, fluoropyrimidines cause severe toxicities in 10 to 40% of patients and toxic deaths in 0.2 to 0.8% of patients, resulting in a real public health problem. The main origin of FU-related toxicities is a deficiency of dihydropyrimidine dehydrogenase (DPD), the rate-limiting enzyme of 5-FU catabolism. DPD deficiency may be identified through pharmacogenetics testing including phenotyping (direct or indirect measurement of enzyme activity) or genotyping (detection of inactivating polymorphisms on the DPYD gene). Approximately 3 to 15% of patients exhibit a partial deficiency and 0.1 to 0.5% a complete DPD deficiency. Currently, there is no regulatory obligation for DPD deficiency screening in patients scheduled to receive a fluoropyrimidine-based chemotherapy. Based on the levels of evidence from the literature data and considering current French practices, the Group of Clinical Pharmacology in Oncology (GPCO)-UNICANCER and the French Network of Pharmacogenetics (RNPGx) recommend the following: (1) to screen DPD deficiency before initiating any chemotherapy containing 5-FU or capecitabine; (2) to perform DPD phenotyping by measuring plasma uracil (U) concentrations (possibly associated with dihydrouracil/U ratio), and DPYD genotyping (variants *2A, *13, p.D949V, HapB3); (3) to reduce the initial FU dose (first cycle) according to DPD status, if needed, and further, to consider increasing the dose at subsequent cycles according to treatment tolerance. In France, 17 public laboratories currently undertake routine screening of DPD deficiency. 105;4
Published: 2018

37. SUV calculation in breast cancer

Author: Humbert, Olivier, Riedinger, Jean Marc, David, Chardin, Desmoulins, Isabelle, Brunotte, François, Cochet, Alexandre, Pôle d'Imagerie Médecine Nucléaire, Centre Antoine-Lacassagne, Université Côte d'Azur, Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA)-UNICANCER-Université Côte d'Azur (UCA), Transporteurs et Imagerie, Radiothérapie en Oncologie et Mécanismes biologiques des Altérations du Tissu Osseux (TIRO-MATOs - UMR E4320), UMR E4320 (TIRO-MATOs), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Côte d'Azur (UCA)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Côte d'Azur (UCA)-Service Hospitalier Frédéric Joliot (SHFJ), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Service de Médecine Nucléaire, Centre Georges-François Leclerc [Dijon] (CGFL), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER, Département de Biologie et pathologie des tumeurs [Centre Georges-François Leclerc], Département de Médecine nucléaire, Centre Antoine Lacassagne, Département d'oncologie médicale [Centre Georges-François Leclerc], Service de radiologie et d'Imagerie médicale diagnostique et thérapeutique (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Laboratoire d'Electronique, d'Informatique et d'Image [EA 7508] (Le2i), Université de Technologie de Belfort-Montbeliard (UTBM)-Université de Bourgogne (UB)-École Nationale Supérieure d'Arts et Métiers (ENSAM), Arts et Métiers Sciences et Technologies, HESAM Université (HESAM)-HESAM Université (HESAM)-Arts et Métiers Sciences et Technologies, HESAM Université (HESAM)-HESAM Université (HESAM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), Service Hospitalier Frédéric Joliot (SHFJ), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-UMR E4320 (TIRO-MATOs), 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)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Côte d'Azur (UCA)-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)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Côte d'Azur (UCA), 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)-Arts et Métiers Sciences et Technologies, and HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: [SDV.CAN]Life Sciences [q-bio]/Cancer
Abstract: International audience; BACKGROUND:When using 18F-FDG PET, glucose metabolism quantification is affected by various factors. We aimed to investigate the benefit of different SUV normalizations to improve the accuracy of 18F-FDG uptake to predict breast cancer aggressiveness and response to treatment.METHODS:Two hundred fifty-two women with locally advanced breast cancer treated with neoadjuvant chemotherapy (NAC) were included. Women underwent 18F-FDG PET before and after the first course of NAC. Glucose serum levels, patient heights and weights were recorded at the time of each PET exam. Four different procedures for SUV normalization of the primary tumor were used: by body weight (SUVBW by blood glucose level ( SUVG, by lean body mass (SUL) and then corrected for both lean body mass and blood glucose level ( SULG).RESULTS:At baseline, SUL was significantly lower than SUVBW (5.9±4.0 and 9.5±6.5, respectively; p0.95; p
Published: 2018

38. Ca2+ protein alpha 1D of CaV1.3 regulates intracellular calcium concentration and migration of colon cancer cells through a non-canonical activity

Author: Fourbon, Yann, Guéguinou, Maxime, Félix, Romain, Constantin, Bruno, Uguen, Arnaud, Fromont, Gaëlle, Lajoie, Laurie, Magaud, Christophe, Lecomte, Thierry, Chamorey, Emmanuel, Chatelier, Aurélien, Mignen, Olivier, Potier-Cartereau, Marie, Chantôme, Aurélie, Bois, Patrick, Vandier, Christophe, Nutrition, croissance et cancer (U 1069) (N2C), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Signalisation et Transports Ioniques Membranaires (STIM), Université de Poitiers-Université de Tours-Centre National de la Recherche Scientifique (CNRS), Université de Bordeaux (UB), Laboratoire d'Anatomo-Pathologie, CHU de Poiters, Unite Mixte de Recherche 7292, Centre National de la Recherche Scientifique (CNRS), Génétique, immunothérapie, chimie et cancer (GICC), UMR 7292 CNRS [2012-2017] (GICC UMR 7292 CNRS), Université de Tours-Centre National de la Recherche Scientifique (CNRS), Dept. of Statistics, Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA)-UNICANCER-Université Côte d'Azur (UCA), Lymphocyte B et Auto-immunité (LBAI), 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), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Network 'Ion channels and Cancer-Canceropole Grand Ouest' [Nantes] (IC-CGO), Cancéropôle Grand-Ouest [Bretagne-Centre-Pays de Loire], Penn State Health Milton S. Hershey Medical Center, Pennsylvania Commonwealth System of Higher Education (PCSHE)-Penn State System, Université de Poitiers-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), 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), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), UNICANCER-Université Côte d'Azur (UCA), Lymphocytes B, Autoimmunité et Immunothérapies (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-LabEX IGO Immunothérapie Grand Ouest, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Institut Brestois Santé Agro Matière (IBSAM), This work was funded by the ARC fund of 'University of Tours and University of Poitiers', 'INSERM', the 'Région Centre' of France (LIPIDS project of ARD2020 Biomédicaments), the 'Ligue Nationale Contre le Cancer' (committees of Charente, Indre et Loire, Mayenne and Morbihan), the Association 'CANCEN' and Tours’ Hospital oncology association ACORT.' Yann Fourbon and Maxime Guéguinou held fellowship from the 'Région Centre'. We thank the « Local tumor tissue biobank BB-0033-00037 ('CRB Santé/Tumorothèque de Brest') » and the UTTIL platform of Tours (Unité Technologique Transversale Innovante des Laboratoires)., Constantin, Bruno, Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), and Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Calcium Channels, L-Type, [SDV.MHEP.PHY] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], [SDV]Life Sciences [q-bio], Active Transport, Cell Nucleus, Intracellular Space, lcsh:Medicine, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, [SDV.BC.IC] Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], Endoplasmic Reticulum, Article, Sodium-Calcium Exchanger, Cytosol, [SDV.CAN] Life Sciences [q-bio]/Cancer, Cell Movement, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Humans, lcsh:Science, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, Cell Nucleus, Cell Membrane, lcsh:R, HCT116 Cells, Electrophysiological Phenomena, Gene Expression Regulation, Neoplastic, [SDV] Life Sciences [q-bio], Colonic Neoplasms, Calcium, lcsh:Q
Abstract: International audience; It is generally accepted that voltage-gated Ca2+ channels, CaV, regulate Ca2+ homeostasis in excitable cells following plasma membrane depolarization. Here, we show that the Ca2+ protein α1D of CaV1.3 channel is overexpressed in colorectal cancer biopsies compared to normal tissues. Gene silencing experiments targeting α1D reduced the migration and the basal cytosolic Ca2+ concentration of HCT116 colon cancer cell line and modified the cytosolic Ca2+ oscillations induced by the sodium/calcium exchanger NCX1/3 working in its reverse mode. Interestingly, NCX1/3 regulated membrane potential of HCT116 cells only when α1D was silenced, and blocking NCX1/3 increased cytosolic Ca2+ concentration and cell migration. However, membrane depolarization did not induce an increase in intracellular Ca2+. Patch-clamp experiments clearly showed that the inward Ca2+ current was absent. Finally, flow cytometry and immunofluorescence studies showed that α1D protein was localized at the plasma membrane, in cytosol and cell nuclei. Altogether, we uncover a novel signaling pathway showing that α1D is involved in the regulation of Ca2+ homeostasis and cell migration by a mechanism independent of its plasma membrane canonical function but that involved plasma membrane Na+/Ca2+ exchanger.
Published: 2017

39. Bevacizumab (Bev) or cetuximab (Cet) plus chemotherapy after progression with bevacizumab plus chemotherapy in patients with wild-type (WT) KRAS metastatic colorectal cancer (mCRC): Final analysis of a French randomized, multicenter, phase II study (PRODIGE 18)

Author: G. Des Guetz, O. Bouche, Trevor Stanbury, S. Charpentier, F. Ghiringhelli, E. Francois, Marc G. Denis, Antoine Adenis, Pascal Artru, J. Bennouna, Sandrine Hiret, Christophe Borg, Gael Deplanque, T. Conroy, J.F. Seitz, Aurélie Bertaut, Service d'hépato-gastro-entérologie, cancérologie digestive et assistance nutritionnelle [CHU de Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Service d'Oncologie Médicale [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Service Biostatistiques et Informatique Médicale (CHU de Dijon) (DIM), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Hospitalier Universitaire de Reims (CHU Reims), Service d'oncologie médicale (Centre Antoine Lacassagne, Nice), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA)-UNICANCER-Université Côte d'Azur (UCA), Département d’Oncologie Médicale [Vandoeuvre Les Nancy], Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), UNICANCER-UNICANCER, Département d'oncologie médicale [Centre Georges-François Leclerc], Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), Service d'Oncologie médicale [CHU Limoges], CHU Limoges, Service d'hépatologie et de gastroentérologie [Hôpital Saint-Joseph - Marseille], Aix Marseille Université (AMU)-Hôpital Saint-Joseph [Marseille], Clinique Jean-Mermoz, Hôpital privé Jean Mermoz, R&D UNICANCER, Fédération Nationale des Centres de Lutte Contre le Cancer (FNCLCL/UNICANCER), AGROCAMPUS OUEST, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Service de génétique médicale - Unité de génétique clinique [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université Lille Nord de France (COMUE)-UNICANCER, and Université de Lille-UNICANCER
Subjects: 0301 basic medicine, Oncology, medicine.medical_specialty, Bevacizumab, Colorectal cancer, medicine.medical_treatment, Phases of clinical research, [SDV.CAN]Life Sciences [q-bio]/Cancer, bevacizumab, medicine.disease_cause, phase 2 clinical trials, kras2 gene, chemotherapy regimen, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, cetuximab, medicine, Chemotherapy, Cetuximab, business.industry, Wild type, Hematology, medicine.disease, Chemotherapy regimen, 3. Good health, k-ras oncogene, 030104 developmental biology, 030220 oncology & carcinogenesis, colorectal cancer metastatic, KRAS, business, medicine.drug
Abstract: IF 11.855; International audience
Published: 2017

40. Predictive factors for early progression during induction chemotherapy (IC) and chemotherapy-free interval (CFI): Analysis from PRODIGE 9 trial

Author: E. Francois, Oana Cojocarasu, Joëlle Egreteau, Côme Lepage, Julien Taieb, K. Le Malicot, Thomas Aparicio, Veronique Guerin-Meyer, François Ghiringhelli, O. Bouche, Jaafar Bennouna, J-B. Bachet, Laetitia Dahan, M-C. Kaminsky-Forrett, Christian Borel, J.M. Phelip, Roger Faroux, Mohamed Gasmi, J.-M. Gornet, Valérie Boige, Service d'hépato-gastro-entérologie, cancérologie digestive et assistance nutritionnelle [CHU de Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), 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), Service d'Hépato-Gastro Entérologie et Oncologie Digestive, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), département d'oncologie médicale (CHU Robert Debré, Reims), Centre Hospitalier Universitaire de Reims (CHU Reims), Service d'oncologie médicale (Centre Antoine Lacassagne, Nice), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA)-UNICANCER-Université Côte d'Azur (UCA), Service de gastroentérologie [CHU Saint-Etienne], Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Centre Paul Strauss de Lutte contre le Cancer (Strasbourg), Service de gastroentérologie (CHD Vendee - Hopital Les Oudairies, La Roche Sur Yon), CHD Vendee (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), Service d'Oncologie médicale [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), Service d'oncologie medicale (CH Bretagne Sud, Lorient), CH Bretagne Sud, Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), UNICANCER, Service d'Hémato-oncologie [CHU Saint-Louis], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'hémato-oncologie (CH du Mans), Centre Hospitalier du Mans, Service d'hépatologie et de gastroentérologie [Hôpital Saint-Joseph - Marseille], Aix Marseille Université (AMU)-Hôpital Saint-Joseph [Marseille], Service d'Oncologie Médicale [Angers], Centre Paul Papin, 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 d'hépato-gastroentérologie et cancérologie digestive (CHU de Dijon), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre hospitalier universitaire de Nantes ( CHU Nantes ), Service Biostatistiques et Informatique Médicale (CHU de Dijon) ( DIM ), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Européen Georges Pompidou [APHP] ( HEGP ), Centre Hospitalier Universitaire de Reims ( CHU Reims ), Centre Antoine Lacassagne de Nice, Centre Hospitalier Universitaire de Saint-Etienne ( CHU de Saint-Etienne ), Assistance Publique - Hôpitaux de Marseille ( APHM ) - Hôpital de la Timone [CHU - APHM] ( TIMONE ), Service d'oncologie médicale [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], Institut de Cancérologie de Lorraine - Alexis Vautrin ( ICL ), Aix Marseille Université ( AMU ) -Hôpital Saint-Joseph [Marseille], Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc ( CRLCC - CGFL ), Lipides - Nutrition - Cancer [Dijon - U1231] ( LNC ), Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service de Gastro-entérologie et Hépatologie [CHU Saint-Etienne], Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon (CHD Vendée), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and 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
Subjects: Oncology, 0303 health sciences, Chemotherapy, medicine.medical_specialty, business.industry, medicine.medical_treatment, Induction chemotherapy, [SDV.CAN]Life Sciences [q-bio]/Cancer, Hematology, 3. Good health, Free interval, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, 03 medical and health sciences, 0302 clinical medicine, 030220 oncology & carcinogenesis, Internal medicine, medicine, Predictor variable, business, 030304 developmental biology
Abstract: IF 11.855; International audience
Published: 2017

41. Expanded repertoire of RASGRP2 variants responsible for platelet dysfunction and severe bleeding

Author: Emilse Bermejo, Michele P. Lambert, Chris Van Geet, Samya Obaji, Marie-Christine Alessi, Sofia Papadia, Matthias Canault, Shoshana Revel-Vilk, Daniel Greene, Andrew D Mumford, Ernest Turro, Salih Tuna, Sarah K Westbury, Kate Downes, Willem H. Ouwehand, Carolyn M. Millar, Christopher Watt, Kathleen Freson, Katharine Hanlon, Paquita Nurden, Michael Laffan, 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), Biostatistics Unit, Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA)-UNICANCER-Université Côte d'Azur (UCA), Hematological Research Institute, National Academy of Medicine, Department of Haematology [Glasgow Royal Infirmary], University of Glasgow-Glasgow Royal Infirmary, Institut Parisien de Recherche Architecture Urbanistique Société (IPRAUS), Architecture Urbanisme Société : Savoir Enseignement Recherche (UMR AUSser), Centre National de la Recherche Scientifique (CNRS)-Ministère de la Culture et de la Communication (MCC)-École nationale supérieure d'architecture de Paris-Belleville (ENSA PB)-École nationale supérieure d'architecture de Paris-La Villette (ENSAPLV)-École nationale supérieure d'architecture de Paris-Malaquais (ENSAPM)-École Nationale Supérieure d'Architecture de la Ville et des Territoires à Marne-la-Vallée (éavt&t)-Centre National de la Recherche Scientifique (CNRS)-Ministère de la Culture et de la Communication (MCC)-École nationale supérieure d'architecture de Paris-Belleville (ENSA PB)-École nationale supérieure d'architecture de Paris-La Villette (ENSAPLV)-École nationale supérieure d'architecture de Paris-Malaquais (ENSAPM)-École Nationale Supérieure d'Architecture de la Ville et des Territoires à Marne-la-Vallée (éavt&t), IHU-LIRYC, CHU Bordeaux [Bordeaux]-Université Bordeaux Segalen - Bordeaux 2, Pediatric Hematology/Oncology Department, Hadassah Hebrew University Medical Center [Jerusalem], Department of Cardiovascular Sciences, Center for Molecular and Vascular Biology, Université Catholique de Louvain = Catholic University of Louvain (UCL), NIHR BioResource - Rare Diseases, Cambridge University Hospitals (CUH), Department of Haematology, Queens Elizabeth Hospital [Birmingham], NHS Blood and Transplant, Center for Molecular and Vascular Biology, Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), University of Cambridge [UK] (CAM), The Wellcome Trust Sanger Institute [Cambridge], 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 ), CRLCC Antoine Lacassagne, Institut Parisien de Recherche Architecture Urbanistique Société ( IPRAUS ), Architecture Urbanisme Société : Savoir Enseignement Recherche ( UMR AUSser ), École nationale supérieure d'architecture de Paris-La Villette ( ENSAPLV ) -École nationale supérieure d'architecture de Paris-Belleville ( ENSA PB ) -Ministère de la Culture et de la Communication ( MCC ) -École nationale supérieure d'architecture de Paris-Malaquais ( ENSAPM ) -Centre National de la Recherche Scientifique ( CNRS ) -École nationale supérieure d'architecture de Paris-La Villette ( ENSAPLV ) -École nationale supérieure d'architecture de Paris-Belleville ( ENSA PB ) -Ministère de la Culture et de la Communication ( MCC ) -École nationale supérieure d'architecture de Paris-Malaquais ( ENSAPM ) -Centre National de la Recherche Scientifique ( CNRS ), Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux], Université Catholique de Louvain, Cambridge University Hospitals ( CUH ), Queen Elizabeth Hospital, Catholic University of Leuven ( KU Leuven ), University of Cambridge [UK] ( CAM ), Medical Research Council (MRC), Downes, Kate [0000-0003-0366-1579], Papadia, Sofia [0000-0002-9222-3812], Tuna, Salih [0000-0003-3606-4367], Ouwehand, Willem [0000-0002-7744-1790], Turro Bassols, Ernest [0000-0002-1820-6563], Apollo - University of Cambridge Repository, École nationale supérieure d'architecture de Paris-La Villette (ENSAPLV), 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)-École nationale supérieure d'architecture de Paris-Belleville (ENSA PB)-Ministère de la Culture et de la Communication (MCC)-École nationale supérieure d'architecture de Paris-Malaquais (ENSAPM)-Centre National de la Recherche Scientifique (CNRS)-École Nationale Supérieure d'Architecture de la Ville et des Territoires à Marne-la-Vallée (éavt&t)-École nationale supérieure d'architecture de Paris-La Villette (ENSAPLV), and 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)-École nationale supérieure d'architecture de Paris-Belleville (ENSA PB)-Ministère de la Culture et de la Communication (MCC)-École nationale supérieure d'architecture de Paris-Malaquais (ENSAPM)-Centre National de la Recherche Scientifique (CNRS)-École Nationale Supérieure d'Architecture de la Ville et des Territoires à Marne-la-Vallée (éavt&t)
Subjects: Male, 0301 basic medicine, genetic disorde, 030204 cardiovascular system & hematology, Bioinformatics, Biochemistry, ACTIVATION, 0302 clinical medicine, ISTH, GENETIC-VARIANTS, [SDV.IDA]Life Sciences [q-bio]/Food engineering, 1114 Paediatrics And Reproductive Medicine, Guanine Nucleotide Exchange Factors, Missense mutation, Platelet, WORLDWIDE SURVEY, [ SDV.GEN.GH ] Life Sciences [q-bio]/Genetics/Human genetics, ComputingMilieux_MISCELLANEOUS, Blood Platelet Disorders, Hematology, [ SDV.IDA ] Life Sciences [q-bio]/Food engineering, DEFECTS, Phenotype, trouble génétiq, Pedigree, 3. Good health, phénotype, thrombocytopath, Female, Life Sciences & Biomedicine, Blood Platelets, medicine.medical_specialty, DISORDERS, NIHR BioResource–Rare Diseases Consortium, Platelet disorder, Immunology, Hemorrhage, DIAGNOSIS, 1102 Cardiovascular Medicine And Haematology, 03 medical and health sciences, Internal medicine, Journal Article, medicine, Humans, Alleles, Science & Technology, Base Sequence, MUTATIONS, business.industry, Genetic heterogeneity, THROMBOCYTOPENIA, séquençage à ha, 1103 Clinical Sciences, Cell Biology, activation plaq, 030104 developmental biology, Platelet transfusion, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Mutation, CALDAG-GEFI, business
Abstract: International audience; Heritable platelet function disorders (PFDs) are genetically heterogeneous and poorly characterised. Pathogenic variants in RASGRP2, which encodes calcium and diacylglycerol-regulated guanine exchange factor I (CalDAG-GEFI), have been reported previously in three pedigrees with bleeding and reduced platelet aggregation responses. To better define the phenotype associated with pathogenic RASGRP2 variants, we compared high-throughput sequencing and phenotype data from 2,042 cases in pedigrees with unexplained bleeding or platelet disorders to data from 5,422 controls. Eleven cases harboured 11 different, previously unreported RASGRP2 variants that were biallelic and likely pathogenic. The variants included five high-impact variants predicted to prevent CalDAG-GEFI expression and six missense variants affecting the CalDAG-GEFI CDC25 domain, which mediates Rap1 activation during platelet inside-out αIIbβ3 signalling. Cases with biallelic RASGRP2 variants had abnormal mucocutaneous, surgical and dental bleeding from childhood, requiring at least one blood or platelet transfusion in 78% of cases. Platelets displayed reduced aggregation in response to ADP and epinephrine, but variable aggregation defects with other agonists. There were no other consistent clinical or laboratory features. These data enable definition of human CalDAG-GEFI deficiency as a non-syndromic, recessive PFD associated with a moderate or severe bleeding phenotype and complex defects in platelet aggregation.
Published: 2017

42. The SigmaR1 chaperone drives breast and colorectal cancer cell migration by tuning SK3-dependent Ca2+ homeostasis

Author: Y Fourbon, Gaëlle Fromont, Lucie Clarysse, R Schiappa, Aurélie Chantôme, Marie Potier-Cartereau, Raphael Rapetti-Mauss, Maxime Guéguinou, Pierre-Marie Martin, Christophe Vandier, Arnaud Uguen, E Chamorey, B Pellissier, D Crottès, Pascal Jézéquel, Franck Borgese, Olivier Mignen, Alban Girault, Olivier Soriani, Catherine Guérin-Charbonnel, Nutrition, croissance et cancer (U 1069) (N2C), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Laboratoire des technologies de la microélectronique (LTM ), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Dept. of Statistics, Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA)-UNICANCER-Université Côte d'Azur (UCA), Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Institute of Developmental Biology and Cancer (IBDC), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Lymphocytes B, Autoimmunité et Immunothérapies (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-LabEX IGO Immunothérapie Grand Ouest, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Université Nice Sophia Antipolis (1965 - 2019) (UNS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Tours, and Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS)
Subjects: 0301 basic medicine, Cancer Research, medicine.medical_specialty, Colorectal cancer, [SDV]Life Sciences [q-bio], chemistry.chemical_element, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Calcium, Biology, Molecular oncology, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Genetics, medicine, Molecular Biology, ComputingMilieux_MISCELLANEOUS, Calcium signaling, Calcium metabolism, ORAI1, Calcium channel, Bone metastasis, medicine.disease, 3. Good health, 030104 developmental biology, Endocrinology, chemistry, 030220 oncology & carcinogenesis, Cancer research
Abstract: The remodeling of calcium homeostasis contributes to the cancer hallmarks and the molecular mechanisms involved in calcium channel regulation in tumors remain to be characterized. Here, we report that SigmaR1, a stress-activated chaperone, is required to increase calcium influx by triggering the coupling between SK3, a Ca2+-activated K+ channel (KCNN3) and the voltage-independent calcium channel Orai1. We show that SigmaR1 physically binds SK3 in BC cells. Inhibition of SigmaR1 activity, either by molecular silencing or by the use of sigma ligand (igmesine), decreased SK3 current and Ca2+ entry in breast cancer (BC) and colorectal cancer (CRC) cells. Interestingly, SigmaR1 inhibition diminished SK3 and/or Orai1 levels in lipid nanodomains isolated from BC cells. Analyses of tissue microarray from CRC patients showed higher SigmaR1 expression levels in cancer samples and a correlation with tumor grade. Moreover, the exploration of a cohort of 4937 BC patients indicated that high expression of SigmaR1 and Orai1 channels was significantly correlated to a lower overall survival. As the SK3/Orai1 tandem drives invasive process in CRC and bone metastasis progression in BC, our results may inaugurate innovative therapeutic approaches targeting SigmaR1 to control the remodeling of Ca2+ homeostasis in epithelial cancers.
Published: 2017

43. Evaluation and Selection of Quality Indicators for the Management of Endometrial Cancer

Author: Xavier Deffieux, Pierre Collinet, Lobna Ouldamer, Jean Luc Brun, Cyrille Huchon, Emmanuel Barranger, Tristan Gautier, Laure Chenoz, François Golfier, Juliette Phelippeau, Charles Coutant, Roman Rouzier, Nicolas Bourdel, Elisabeth Chereau, Martin Koskas, Emile Daraï, Pôle de Chirurgie Oncologique générale, Gynécologique et Mammaire [Centre Antoine-Lacassagne], Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA)-UNICANCER-Université Côte d'Azur (UCA), Institut Pascal (IP), SIGMA Clermont (SIGMA Clermont)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Service de Gynécologie-Obstétrique, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de gynécologie-obstétrique, médecine de la reproduction [Béclère], Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Antoine Béclère [Clamart], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de gynécologie et obstétrique [CHI Poissy-Saint Germain], CHI Poissy-Saint-Germain, Nutrition, croissance et cancer (U 1069) (N2C), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'obstétrique, gynécologie et médecine reproductive, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], SIGMA Clermont (SIGMA Clermont)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), 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), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: Adult, Oncology, medicine.medical_specialty, media_common.quotation_subject, Population, MEDLINE, [SDV.MHEP.GEO]Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, 03 medical and health sciences, 0302 clinical medicine, Uterine cancer, Multiple correspondence analysis, Internal medicine, Health care, medicine, Humans, Quality (business), education, ComputingMilieux_MISCELLANEOUS, Aged, Neoplasm Staging, Quality Indicators, Health Care, media_common, Aged, 80 and over, education.field_of_study, 030219 obstetrics & reproductive medicine, business.industry, Endometrial cancer, Obstetrics and Gynecology, Perioperative, Middle Aged, medicine.disease, Endometrial Neoplasms, 3. Good health, 030220 oncology & carcinogenesis, Family medicine, Female, France, business
Abstract: Objective The aim of this study was to evaluate 36 quality indicators (QIs) for monitoring the quality of care of uterine cancer to be implemented in the EFFECT (effectiveness of endometrial cancer treatment) project. Methods The 36 QIs were evaluated in the first 10 patients diagnosed with endometrial cancer and managed in 14 French hospitals in 2011. To assess the status of each QI, a questionnaire detailing the 36 QIs was sent to each hospital, and the information was cross-checked with information from the multidisciplinary staff meeting, surgical reports, and pathological reports. The QIs were evaluated in terms of measurability and improvability. The remaining QIs were evaluated with a multiple correspondence analysis to highlight the interrelationships between qualitative variables describing a population. Results Thirteen of the 14 institutions responded to the survey for a total of 130 patients. Twenty-five of the 36 QIs affected less than 80% of the patients. Thirteen QIs were found not to be improvable because they reached more than 95% of the theoretical target. Finally, 5 QIs concerning more than 80% of the patients were found to be improvable. The multiple correspondence analysis finally identified 3 dimensions—outcome, safety, and perioperative management—that included the 5 QIs. Conclusions In the present study, 5 of the 36 QIs suggested by the EFFECT project seem to be sufficient to report on the quality of endometrial cancer management. Further studies are needed to correlate the information provided by those 5 questions and the relevant outcomes reflecting quality of care in endometrial cancer.
Published: 2017

44. 3D Silicon Coincidence Avalanche Detector (3D-SiCAD) for Hadrontherapy and Proton Tomography : Preliminary Results on Charged Particle Detection

Author: VIGNETTI, M., Calmon, F., Pittet, P., PARES, G., Cellier, R., Quiquerez, L., Chaves de Albuquerque, T., Bechetoille, E., Testa, E., Lopez, J.-P., Dauvergne, D., Hérault, J., Savoy-Navarro, A., INL - Dispositifs Electroniques (INL - DE), Institut des Nanotechnologies de Lyon (INL), École Centrale de Lyon (ECL), Université de Lyon-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-École supérieure de Chimie Physique Electronique de Lyon (CPE)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-École Centrale de Lyon (ECL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), INL - Conception de Systèmes Hétérogènes (INL - CSH), Laboratoire d'Electronique et des Technologies de l'Information (CEA-LETI), Université Grenoble Alpes (UGA)-Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut de Physique Nucléaire de Lyon (IPNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Physique Subatomique et de Cosmologie (LPSC), Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Institut Polytechnique de Grenoble - Grenoble Institute of Technology-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Unité de Radiothérapie, Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Centre Antoine Lacassagne de Nice-Centre de Lutte contre le Cancer, APC - Astrophysique des Hautes Energies (APC - AHE), AstroParticule et Cosmologie (APC (UMR_7164)), Observatoire de Paris, PSL Research University (PSL)-PSL Research University (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Observatoire de Paris, PSL Research University (PSL)-PSL Research University (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Dipartimento di Astronomia, Universita degli Studi di Bologna, Università di Bologna [Bologna] (UNIBO)-Università di Bologna [Bologna] (UNIBO), APC - Cosmologie, Physique Corpusculaire et Cosmologie - Collège de France (PCC), Collège de France (CdF)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Collège de France (CdF)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-AstroParticule et Cosmologie (APC (UMR_7164)), PSL Research University (PSL)-PSL Research University (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), European Project: 317446,EC:FP7:PEOPLE,FP7-PEOPLE-2012-ITN,INFIERI(2013), Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-École Centrale de Lyon (ECL), Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-École supérieure de Chimie Physique Electronique de Lyon (CPE)-Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-École supérieure de Chimie Physique Electronique de Lyon (CPE), Commissariat à l'énergie atomique et aux énergies alternatives - Laboratoire d'Electronique et de Technologie de l'Information (CEA-LETI), Direction de Recherche Technologique (CEA) (DRT (CEA)), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), Université Côte d'Azur (UCA)-UNICANCER-Université Côte d'Azur (UCA)-UNICANCER-Centre de Lutte contre le Cancer, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Observatoire de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Dipartimento di Astronomia, Universita degli Studi di Bologna, Alma Mater Studiorum Università di Bologna [Bologna] (UNIBO)-Alma Mater Studiorum Università di Bologna [Bologna] (UNIBO), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3), Université de Lyon-École Supérieure de Chimie Physique Électronique de Lyon (CPE)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université Nice Sophia Antipolis (1965 - 2019) (UNS), UNICANCER-Université Côte d'Azur (UCA)-UNICANCER-Université Côte d'Azur (UCA)-Centre de Lutte contre le Cancer, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Observatoire de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Observatoire de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS)-Alma Mater Studiorum Università di Bologna [Bologna] (UNIBO), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Rayet, Béatrice, INtelligent Fast Interconnected and Efficient Devices for Frontier Exploitation in Research and Industry - INFIERI - - EC:FP7:PEOPLE2013-02-01 - 2017-01-31 - 317446 - VALID, Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-École supérieure de Chimie Physique Electronique de Lyon (CPE)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-École Centrale de Lyon (ECL), Université de Lyon, Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Observatoire de Paris, PSL Research University (PSL)-PSL Research University (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Observatoire de Paris, PSL Research University (PSL)-PSL Research University (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Dipartimento di Astronomia, Universita degli Studi di Bologna, PSL Research University (PSL)-PSL Research University (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Observatoire de Paris, and PSL Research University (PSL)-PSL Research University (PSL)-Université Paris Diderot - Paris 7 (UPD7)
Subjects: SPAD, [PHYS.PHYS.PHYS-MED-PH] Physics [physics]/Physics [physics]/Medical Physics [physics.med-ph], [PHYS.PHYS.PHYS-INS-DET] Physics [physics]/Physics [physics]/Instrumentation and Detectors [physics.ins-det], hadrontherapy, charged particle detector, [PHYS.PHYS.PHYS-MED-PH]Physics [physics]/Physics [physics]/Medical Physics [physics.med-ph], proton tomography, [PHYS.PHYS.PHYS-INS-DET]Physics [physics]/Physics [physics]/Instrumentation and Detectors [physics.ins-det]
Abstract: National audience; Ce travail vise à démontrer les capacités d’un nouveau type de détecteur de particules chargées, bénéficiant des progrès récents en intégration microélectronique 3D, pour des applications médicales avancées telles que l’hadronthérapie (ex. réduction des incertitudes dans la fluence pour délivrer la bonne dose, étiquetage précis d'un temps d'arrivée des ions pour la sélection en temps de vol des rayons gamma prompts) et la radiographie - tomographie proton (ex. filtrage des neutrons et des rayons gamma, amélioration potentielle de la résolution spatiale).Ce détecteur intégré en technologie CMOS est appelé 3D-SiCAD (3D Silicon Coincidence Avalanche Detector).Il met en oeuvre un mode de coïncidence interne innovant, objet d’une forte activité R&D au niveau international, basé sur un empilement vertical de pixels de type SPAD -Single Photon Avalanche Diode (mode Geiger) permettant d’améliorer significativement la discrimination entre les évènements liés au passage de particules (déclenchement simultané de deux pixels) et le bruit intrinsèque. L’originalité de notre démarche consiste en l’application de ce concept innovateur aux applications médicales.Les étapes de conception du premier prototype ainsi que les principaux résultats obtenus seront présentés avec notamment :i) les performances de la diode SPAD seule réalisée en technologie CMOS 0.35μm avec par exemple un taux de comptage dans l’obscurité moyen de 70Hz/μm²,ii) la démonstration expérimentale de la diminution du bruit apparent (taux de comptage de faux événements) grâce à la détection en coïncidence dans une courte fenêtre temporelle. En pratique, le taux de réjection du bruit peut atteindre un facteur x103 dans les conditions optimales,iii) la mise en oeuvre de cette solution technologique pour la mesure de l’activité d’une source de strontium.Finalement les performances actuelles, les pistes d’amélioration possibles ainsi qu’une revue des travaux en cours et futurs seront brièvement discutés.
Published: 2017

45. Multicenter prospective micro-costing study evaluating mandibular free-flap reconstruction

Author: Jocelyn Gal, Yann Château, Renaud Schiappa, Morbize Julieron, Marie-Helene Orlanducci, Emmanuel Chamorey, Bernard Devauchelle, Olivier Dassonville, Jérôme Sarini, Jacques Yachouh, Gilles Poissonnet, Yann Mallet, Marie-Yolande Louis, Alexandre Bozec, Gilles Dolivet, Emile Reyt, Pierre Breton, Service d'ORL, Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA)-UNICANCER-Université Côte d'Azur (UCA), UNICANCER-Université Côte d'Azur (UCA), Service d'ORL et de chirurgie cervicale, CHU Grenoble, Département de chirurgie maxillofaciale et stomatologie [CHU d'Amiens-Picardie], CHU Amiens-Picardie, Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université Lille Nord de France (COMUE)-UNICANCER, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut Claudius Regaud, Université de Lorraine (UL), CHU Nice [Cimiez], Hôpital Cimiez [Nice] (CHU), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), and Université de Lille-UNICANCER
Subjects: Adult, Male, Reoperation, medicine.medical_specialty, Adolescent, Hospital bed, Total cost, [SDV]Life Sciences [q-bio], Young Adult, 03 medical and health sciences, 0302 clinical medicine, Mandibular reconstruction, medicine, Cost analysis, Humans, Hospital Costs, 030223 otorhinolaryngology, Intensive care medicine, Prospective cohort study, health care economics and organizations, Aged, business.industry, General Medicine, Middle Aged, Multicenter study, 3. Good health, Hospitalization, Otorhinolaryngology, Free tissue flaps, 030220 oncology & carcinogenesis, Micro costing, Emergency medicine, Free flap reconstruction, Female, France, Neurosurgery, business, Prospective studies
Abstract: International audience; Free-flap mandibular reconstruction is a highly specialized procedure associated with severe complications necessitating re-interventions and re-hospitalizations. This surgery is expensive in terms of health workers' time, equipment, medical devices and drugs. Our main objective was to assess the direct hospital cost generated by osseocutaneous free-flap surgery in a multicentric prospective micro-costing study. Direct medical costs evaluated from a hospital perspective were assessed using a micro-costing method from the first consultation with the surgeon until the patient returns home, thus confirming the success or failure of the free-flap procedure. The mean total cost for free-flap intervention was 34,009€ (5151-119,604€), the most expensive item being the duration of hospital bed occupation, representing 30-90% of the total cost. In the event of complications, the mean cost increased by 77.3%, due primarily to hospitalization in ICU and the conventional unit. This surgery is effective and provides good results but remains highly complex and costly.
Published: 2017

46. A cost-effective monitoring technique in particle therapy via uncollimated prompt gamma peak integration

Author: Joel Herault, Marco Pinto, H. Mathez, J. Krimmer, Denis Dauvergne, Jean Michel Létang, Nicolas Freud, G. Angellier, Y. Zoccarato, Etienne Testa, L. Balleyguier, Institut de Physique Nucléaire de Lyon (IPNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), PRISME (PRISME), Institut de Physique des 2 Infinis de Lyon (IP2I Lyon), Université de Lyon-Université de Lyon-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Unité de Radiothérapie, Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Centre Antoine Lacassagne de Nice-Centre de Lutte contre le Cancer, Laboratoire de Physique Subatomique et de Cosmologie (LPSC), Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Institut Polytechnique de Grenoble - Grenoble Institute of Technology-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Centre Léon Bérard [Lyon], Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Imagerie Tomographique et Radiothérapie, Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), Université Côte d'Azur (UCA)-UNICANCER-Université Côte d'Azur (UCA)-UNICANCER-Centre de Lutte contre le Cancer, Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Université Nice Sophia Antipolis (1965 - 2019) (UNS), UNICANCER-Université Côte d'Azur (UCA)-UNICANCER-Université Côte d'Azur (UCA)-Centre de Lutte contre le Cancer, Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), and Rayet, Béatrice
Subjects: Physics and Astronomy (miscellaneous), Proton, medicine.medical_treatment, Astrophysics::High Energy Astrophysical Phenomena, Cyclotron, [SDV.IB.MN]Life Sciences [q-bio]/Bioengineering/Nuclear medicine, Modulators, Position sensitive detectors, 030218 nuclear medicine & medical imaging, law.invention, [SDV.IB.MN] Life Sciences [q-bio]/Bioengineering/Nuclear medicine, 03 medical and health sciences, 0302 clinical medicine, Optics, law, medicine, [PHYS.PHYS.PHYS-INS-DET]Physics [physics]/Physics [physics]/Instrumentation and Detectors [physics.ins-det], Particle beam detectors, Physics, Range (particle radiation), Particle therapy, [PHYS.PHYS.PHYS-MED-PH] Physics [physics]/Physics [physics]/Medical Physics [physics.med-ph], business.industry, Detector, Gamma rays, Gamma ray, Solid angle, 3. Good health, Beamline, [PHYS.PHYS.PHYS-INS-DET] Physics [physics]/Physics [physics]/Instrumentation and Detectors [physics.ins-det], 030220 oncology & carcinogenesis, [PHYS.PHYS.PHYS-MED-PH]Physics [physics]/Physics [physics]/Medical Physics [physics.med-ph], Protons, business
Abstract: International audience; For the purpose of detecting deviations from the prescribed treatment during particle therapy, the integrals of uncollimated prompt gamma-ray timing distributions are investigated. The intention is to provide information, with a simple and cost-effective setup, independent from monitoring devices of the beamline. Measurements have been performed with 65 MeV protons at a clinical cyclotron. Prompt gamma-rays emitted from the target are identified by means of time-of-flight. The proton range inside the PMMA target has been varied via a modulator wheel. The measured variation of the prompt gamma peak integrals as a function of the modulator position is consistent with simulations. With detectors covering a solid angle of 25 msr (corresponding to a diameter of 3–4 in. at a distance of 50 cm from the beam axis) and 108 incident protons, deviations of a few per cent in the prompt gamma-ray count rate can be detected. For the present configuration, this change in the count rate corresponds to a 3 mm change in the proton range in a PMMA target. Furthermore, simulation studies show that a combination of the signals from multiple detectors may be used to detect a misplacement of the target. A different combination of these signals results in a precise number of the detected prompt gamma rays, which is independent on the actual target position.
Published: 2017

47. Combination of phosphotidylinositol-3-kinase targeting with cetuximab and irradiation: A preclinical study on an orthotopic xenograft model of head and neck cancer

Author: Bozec, Alexandre, Ebran, Nathalie, Radosevic-Robin, Nina, Chamorey, Emmanuel, Yahia, Hedi Ben, Marcie, Serge, Gautier, Mathieu, Penault-Llorca, Frédérique, Milano, Gérard, Institut Universitaire de la Face et du Cou [Nice], Laboratory of Solid Tumors Genetics, Nice University Hospital, Equipe de recherche sur les traitements individualisés des cancers (ERTICa), Université d'Auvergne - Clermont-Ferrand I (UdA), Dept. of Statistics, Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA)-UNICANCER-Université Côte d'Azur (UCA), UNICANCER-Université Côte d'Azur (UCA), Laboratoire Simulation Interactive (LSI), Département Intelligence Ambiante et Systèmes Interactifs (DIASI), Laboratoire d'Intégration des Systèmes et des Technologies (LIST (CEA)), Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Laboratoire d'Intégration des Systèmes et des Technologies (LIST (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), 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]), Unité de ciblage pharmacologique dans les cancers ORL, 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), Laboratoire d'Intégration des Systèmes et des Technologies (LIST), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Laboratoire d'Intégration des Systèmes et des Technologies (LIST), and Université Nice Sophia Antipolis (... - 2019) (UNS)
Subjects: Squamous Cell Carcinoma of Head and Neck, Morpholines, [SDV]Life Sciences [q-bio], Aminopyridines, Cetuximab, Mice, Nude, [SDV.CAN]Life Sciences [q-bio]/Cancer, targeted therapy, Combined Modality Therapy, Xenograft Model Antitumor Assays, epidermal growth factor receptor (EGFR), Disease Models, Animal, Mice, stomatognathic diseases, Antineoplastic Agents, Immunological, phosphatidylinositol 3-kinase (PIK3CA), Head and Neck Neoplasms, Carcinoma, Squamous Cell, Animals, Female, head and neck cancer, neoplasms, radiotherapy, Phosphoinositide-3 Kinase Inhibitors
Abstract: The purpose of this study was to investigate the effects of combining the phosphotidylinositol-3-kinase (PI3K) inhibitor buparlisib (BKM)120 with the anti-epidermal growth factor receptor (EGFR) agent cetuximab and radiotherapy (RT) on an orthotopic model of head and neck squamous cell carcinoma (HNSCC).We evaluated the antitumor efficacy of BKM120, cetuximab, and RT, administered alone or in combination, using the human PIK3CA-mutated HNSCC cell line, CAL33, injected into the floor of the mouth of nude mice.Compared with control, the BKM120-cetuximab and the BKM120-cetuximab-RT combinations led to the highest tumor inhibition (p.001). The highest inhibitory effect of treatments on cell proliferation, mitogen-activated protein kinase (MAPK) and PI3K/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathways were found with the BKM120-cetuximab association. The association of BKM120 and cetuximab with RT inhibited RT-induced activation of the MAPK pathway.These results can serve as a preclinical rationale for innovative treatments combining PI3K inhibition with anti-EGFR therapies and irradiation in patients with HNSCC. © 2016 Wiley Periodicals, Inc. Head Neck 39: 151-159, 2017.
Published: 2017

48. Assessment of the prognostic role of a 94-single nucleotide polymorphisms risk score in early breast cancer in the SIGNAL/PHARE prospective cohort: no correlation with clinico-pathological characteristics and outcomes

Author: Carole Tarpin, Sophie Paget-Bailly, Xavier Pivot, David Assouline, Maria Rios, Isabelle Tennevet, Gilles Romieu, Jean-Marc Ferrero, Céline Faure-Mercier, Pierre Fumoleau, Jean-François Deleuze, David G. Cox, Hélène Blanché, Marie-Christine Mathieu, Thierry Petit, Christelle Jouannaud, Hugues Bourgeois, Oana Cojocarasu, Thomas Bachelot, Elsa Curtit, Jérôme Meunier, Ariane Darut-Jouve, Delphine Bacq, Jean-Yves Pierga, Sandrine Lavau-Denes, Iris Pauporté, Valérie Delecroix, Christelle Levy, Patrick Soulié, Pierre Kerbrat, Véronique Trillet-Lenoir, Anne Boland, Hervé Bonnefoi, Mourad Sahbatou, Gilles Thomas, Jean-Philippe Jacquin, Julie Henriques, Céline Besse, 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 [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), Unité de Méthodologie et de Qualité de Vie en Cancérologie (UMQVC), Institut Régional Fédératif du Cancer (IRFC)-Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (EA 3181) (CEF2P / CARCINO), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-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)-Pôle cancérologie (CHRU Besançon), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), 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 d’Oncologie Médicale [Vandoeuvre Les Nancy], Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), Département d'oncologie médicale, Institut Bergonié [Bordeaux], Département de Cancérologie Médicale [Lyon], Centre Léon Bérard : Centre Régional de Lutte Contre le Cancer Lyon Rhône-Alpes, Service Oncologie Médicale [Angers], Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), Service Oncologie Médicale [Reims], Institut Jean Godinot [Reims], Centre Jean Bernard [Institut Inter-régional de Cancérologie - Le Mans], Service d’Oncologie Médicale [Strasbourg], Centre Paul Strauss : Centre Régional de Lutte contre le Cancer (CRLCC), Département d'oncologie médicale [Rouen], Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Service Oncologie Médicale [Grenoble], Institut Daniel Hollard [Grenoble], Pathologie mammaire, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Service Oncologie Médicale [Saint Priest en Jarez], Institut de Cancérologie Lucien Neuwirth [Saint Priest en Jarez], Service d'Oncologie médicale [CHU Limoges], CHU Limoges, Centre d'oncologie et de radiothérapie du parc [Dijon], Département Oncologie Médicale [Nice], Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA)-UNICANCER-Université Côte d'Azur (UCA), Département d’Oncologie Médicale [Marseille], Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Service d'Oncologie Médicale [Caen], Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Service Oncologie Médicale [Saint-Nazaire] (Pôle Mutualiste), Centre Etienne Dolet [Saint-Nazaire], Service d’Oncologie Médicale [CHU Lyon Sud], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Service d’Onco-Hématologie et Médecine interne [Le Mans], Centre Hospitalier Le Mans (CH Le Mans), Service d’Oncologie médicale [Orleans], Centre Hospitalier Régional d'Orléans (CHRO), Département d'Oncologie Médicale [Paris], Institut Curie [Paris], Service d'Oncologie Médicale [Rennes], CRLCC Eugène Marquis (CRLCC), Direction de la Recherche [Boulogne-Billancourt], Institut National du Cancer [Boulogne Billancourt] (INC), Centre de Ressources Biologiques [Paris], Fondation Jean Dausset - Centre d’Etudes du Polymorphisme Humain [Paris] (CEPH), Centre de Ressources Biologiques [Evry], Centre National du Génotypage [Evry], Synergie Lyon Cancer [Lyon], 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 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), This work has fully been funded by the sponsor of the study, l’Institut National du Cancer, France (INCa)., Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC ( HOTE GREFFON ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Etablissement français du sang [Bourgogne-France-Comté] ( EFS [Bourgogne-France-Comté] ) -Université de Franche-Comté ( UFC ), Service d'Oncologie Médicale [Besançon], Centre Hospitalier Régional Universitaire Hôpital Jean Minjoz [Besançon], Unité de Méthodologie et de Qualité de Vie en Cancérologie ( UMQVC ), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC ( CEF2P / CARCINO ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Université Bourgogne Franche-Comté ( UBFC ) -Université de Franche-Comté ( UFC ) -Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Université Bourgogne Franche-Comté ( UBFC ) -Université de Franche-Comté ( UFC ) -Pôle cancérologie (CHU Besançon), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Institut Régional Fédératif du Cancer ( IRFC ), Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc ( CRLCC - CGFL ), Institut de Cancérologie de Lorraine - Alexis Vautrin ( ICL ), Institut Bergonié - CRLCC Bordeaux, UNICANCER - Institut de cancérologie de l'Ouest - Paul Papin [Angers], Centre Jean Bernard [Le Mans], Clinique Victor Hugo [Le Mans], Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen ( CLCC Henri Becquerel ), Institut Gustave Roussy ( IGR ) -Institut Gustave Roussy ( IGR ), Centre d’oncologie et de radiothérapie du Parc [Dijon], Clinique Drévon [Dijon], UNICANCER - Centre Antoine Lacassagne [Nice], Institut Paoli-Calmettes [Marseille], Centre Régional de Lutte contre le Cancer François Baclesse ( CRLC François Baclesse ), Service Oncologie Médicale [Saint-Nazaire] ( Pôle Mutualiste ), Centre Hospitalier Lyon Sud [CHU - HCL] ( CHLS ), Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ), Centre Hospitalier Le Mans, Centre Hospitalier Régional d'Orléans ( CHR ), Institut Curie (Paris), CRLCC Eugène Marquis ( CRLCC ), Institut National du Cancer [Boulogne Billancourt] ( INC ), Centre d’Etudes du Polymorphisme Humain [Paris], Institut de recherche en cancérologie de Montpellier ( IRCM ), Université Montpellier 1 ( UM1 ) -CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Montpellier ( UM ), Centre de Recherche en Cancérologie de Lyon ( CRCL ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), 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), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (UR 3181) (CEF2P / CARCINO), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Institut Régional Fédératif du Cancer (IRFC), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), BMC, BMC, Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (EA 3181) (CEF2P / CARCINO), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Institut Régional Fédératif du Cancer (IRFC), Polyclinique du Parc - Clinique Drevon [Dijon], Université Côte d'Azur (UCA)-UNICANCER-Université Côte d'Azur (UCA)-UNICANCER, and UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)
Subjects: 0301 basic medicine, Oncology, [SDV]Life Sciences [q-bio], Metastasis, Cohort Studies, 0302 clinical medicine, Breast cancer, Neoplasm Metastasis, Prospective cohort study, Estrogen Receptor Status, Genetic variant, Randomized Controlled Trials as Topic, Aged, 80 and over, Framingham Risk Score, Middle Aged, Prognosis, Tumor Burden, 3. Good health, [SDV] Life Sciences [q-bio], 030220 oncology & carcinogenesis, Cohort, Female, Research Article, Adult, medicine.medical_specialty, Genotype, Breast Neoplasms, Single-nucleotide polymorphism, Polymorphism, Single Nucleotide, Young Adult, 03 medical and health sciences, Internal medicine, Biomarkers, Tumor, medicine, Humans, Genetic Predisposition to Disease, Alleles, Genetic Association Studies, Aged, Neoplasm Staging, [ SDV ] Life Sciences [q-bio], business.industry, Cancer, medicine.disease, Survival Analysis, Single nucleotide polymorphism, 030104 developmental biology, Clinical Trials, Phase III as Topic, Risk score, Neoplasm Grading, business
Abstract: Background Genome-wide association studies (GWAS) have to date identified 94 genetic variants (single nucleotide polymorphisms (SNPs)) associated with risk of developing breast cancer. A score based on the combined effect of the 94 risk alleles can be calculated to measure the global risk of breast cancer. We aimed to test the hypothesis that the 94-SNP-based risk score is associated with clinico-pathological characteristics, breast cancer subtypes and outcomes in early breast cancer. Methods A 94-SNP risk score was calculated in 8703 patients in the PHARE and SIGNAL prospective case cohorts. This score is the total number of inherited risk alleles based on 94 selected SNPs. Clinical data and outcomes were prospectively registered. Genotyping was obtained from a GWAS. Results The median 94-SNP risk score in 8703 patients with early breast cancer was 77.5 (range: 58.1–97.6). The risk score was not associated with usual prognostic and predictive factors (age; tumor, node, metastasis (TNM) status; Scarff-Bloom-Richardson grade; inflammatory features; estrogen receptor status; progesterone receptor status; human epidermal growth factor receptor 2 (HER2) status) and did not correlate with breast cancer subtypes. The 94-SNP risk score did not predict outcomes represented by overall survival or disease-free survival. Conclusions In a prospective case cohort of 8703 patients, a risk score based on 94 SNPs was not associated with breast cancer characteristics, cancer subtypes, or patients’ outcomes. If we hypothesize that prognosis and subtypes of breast cancer are determined by constitutional genetic factors, our results suggest that a score based on breast cancer risk-associated SNPs is not associated with prognosis. Trial registration PHARE cohort: NCT00381901, Sept. 26, 2006 – SIGNAL cohort: INCa RECF1098, Jan. 28, 2009 Electronic supplementary material The online version of this article (doi:10.1186/s13058-017-0888-4) contains supplementary material, which is available to authorized users.
Published: 2016

49. The ongoing French metastatic breast cancer (MBC) cohort: the example-based methodology of the Epidemiological Strategy and Medical Economics (ESME)

Author: Monia Ezzalfani, Sophie Gourgou, Bernard Asselain, Simone Mathoulin-Pélissier, Michel Velten, Loïc Campion, Christian Cailliot, Marie-Ange Mouret-Reynier, Gaëtane Simon, Anne-Valérie Guizard, Matthieu Carton, Geneviève Perrocheau, Stéphanie Delaine-Clisant, Agnes Loeb, Mathias Breton, Delphine Berchery, M. Mons, Mathieu Robain, Emmanuel Chamorey, Carine Laurent, Damien Parent, Patrick Arveux, David Pérol, Véronique Diéras, Lilian Laborde, Department of Biostatistics, Centre Léon Bérard [Lyon], FRANCIM, Réseau des registres français du cancer, Plateforme de génétique moléculaire des cancers d'Aquitaine, Institut Bergonié [Bordeaux], UNICANCER-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), Dept. of Statistics, Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), Université Côte d'Azur (UCA)-UNICANCER-Université Côte d'Azur (UCA)-UNICANCER, Cancer et génome: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, MINES ParisTech - 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 Médical, Institut Claudius Regaud, 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, Institut Gustave Roussy (IGR), Institute Curie, Institut Curie [Paris], Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), EDF (EDF), Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER, Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER - Institut régional du Cancer Montpellier Val d'Aurelle (ICM), CRLCC Val d'Aurelle - Paul Lamarque, UNICANCER-Université Côte d'Azur (UCA)-UNICANCER-Université Côte d'Azur (UCA), Mines Paris - PSL (École nationale supérieure des mines de Paris), Université de Lille-UNICANCER, and Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)
Subjects: Male, medicine.medical_specialty, Breast Neoplasms, [SDV.CAN]Life Sciences [q-bio]/Cancer, Disease, patient medical record, 03 medical and health sciences, 0302 clinical medicine, Medical economics, Epidemiology, Health care, medicine, Humans, Longitudinal Studies, Registries, 030212 general & internal medicine, Neoplasm Metastasis, quality control, Reimbursement, Aged, Retrospective Studies, Cohort Profile, real-world data, business.industry, Cancer, General Medicine, Middle Aged, medicine.disease, Metastatic breast cancer, 3. Good health, Oncology, Research Design, 030220 oncology & carcinogenesis, Family medicine, Cohort, Disease Progression, Female, epidemiology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, France, metastatic breast cancer, data platform, business
Abstract: PurposeThe currently ongoing Epidemiological Strategy and Medical Economics (ESME) research programme aims at centralising real-life data on oncology care for epidemiological research purposes. We draw on results from the metastatic breast cancer (MBC) cohort to illustrate the methodology used for data collection in the ESME research programme.ParticipantsAll consecutive ≥18 years patients with MBC treatment initiated between 2008 and 2014 in one of the 18 French Comprehensive Cancer Centres were selected. Diagnostic, therapeutic and follow-up data (demographics, primary tumour, metastatic disease, treatment patterns and vital status) were collected through the course of the disease. Data collection is updated annually.Finding to dateWith a recruitment target of 30 000 patients with MBC by 2019, we currently screened a total of 45 329 patients, and >16 700 patients with a metastatic disease treatment initiated after 2008 have been selected. 20.7% of patients had an hormone receptor (HR)-negative MBC, 73.7% had a HER2-negative MBC and 13.9% were classified as triple-negative BC (ie, HER2 and HR status both negative). Median follow-up duration from MBC diagnosis was 48.55 months for the whole cohort.Future plansThese real-world data will help standardise the management of MBC and improve patient care. A dozen of ancillary research projects have been conducted and some of them are already accepted for publication or ready to be issued. The ESME research programme is expanding to ovarian cancer and advanced/metastatic lung cancer. Our ultimate goal is to achieve a continuous link to the data of the cohort to the French national Health Data System for centralising data on healthcare reimbursement (drugs, medical procedures), inpatient/outpatient stays and visits in primary/secondary care settings.Trial registration numberNCT03275311; Pre-results.
Published: 2019

50. Weekly Adaptive Radiotherapy vs Standard Intensity-Modulated Radiotherapy for Improving Salivary Function in Patients With Head and Neck Cancer

Author: Castelli, Joël, Thariat, Juliette, Benezery, Karen, Hasbini, Ali, Gery, Bernard, Berger, Antoine, Liem, Xavier, Guihard, Sébastien, Chapet, Sophie, Thureau, Sébastien, Auberdiac, Pierre, Pommier, Pascal, Ruffier, Amandine, Perrier, Lionel, Devillers, Anne, Campillo-Gimenez, Boris, de Crevoisier, Renaud, CRLCC Eugène Marquis (CRLCC), Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-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), Laboratoire de physique corpusculaire de Caen (LPCC), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Clinique Pasteur-Lanroze (FRANCE), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER, Institut de Cancérologie de Strasbourg Europe (ICANS), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Clinique Claude Bernard - ELSAN [Albi] (CCBE), Centre Léon Bérard [Lyon], Université de Lyon, and This study was sponsored by the Cancer Institute Eugène Marquis, Rennes, France, and grant PAIR VADS 2011 (Prof de Crevoisier) from the French National Cancer Institute.
Subjects: [SDV.IB]Life Sciences [q-bio]/Bioengineering, [SDV.CAN]Life Sciences [q-bio]/Cancer
Abstract: International audience; Importance: Xerostomia is a major toxic effect associated with intensity-modulated radiotherapy (IMRT) for oropharyngeal cancers.Objective: To assess whether adaptive radiotherapy (ART) improves salivary function compared with IMRT in patients with head and neck cancer.Design, setting, and participants: This phase 3 randomized clinical trial was conducted in 11 French centers. Patients aged 18 to 75 years with stage III-IVB squamous cell oropharyngeal cancer treated with chemoradiotherapy were enrolled between July 5, 2013, and October 1, 2018. Data were analyzed from November 2021 to May 2022.Interventions: The patients were randomly assigned (1:1) to receive standard IMRT (without replanning) or ART (systematic weekly replanning).Main outcomes and measures: The primary end point was the frequency of xerostomia, measured by stimulating salivary flow with paraffin. Secondary end points included salivary gland excretory function measured using technetium-99m pertechnetate scintigraphy, patient-reported outcomes (Eisbruch xerostomia-specific questionnaire and the MD Anderson Symptom Inventory for Head and Neck Cancer questionnaire), early and late toxic effects, disease control, and overall and cancer-specific survival.Results: A total of 132 patients were randomized, and after 1 exclusion in the ART arm, 131 were analyzed: 66 in the ART arm (mean [SD] age at inclusion, 60 [8] years; 57 [86.4%] male) and 65 in the standard IMRT arm (mean [SD] age at inclusion, 60 [8] years; 57 [87.7%] male). The median follow-up was 26.4 months (IQR, 1.2-31.3 months). The mean (SD) salivary flow (paraffin) at 12 months was 630 (450) mg/min in the ART arm and 584 (464) mg/min in the standard arm (P = .64). The mean (SD) excretory function of the parotid gland at 12 months, measured by scintigraphy, improved in the ART arm (48% [17%]) compared with the standard arm (41% [17%]) (P = .02). The 2-year-overall survival was 76.9% (95% CI, 64.7%-85.4%) in both arms.Conclusions and relevance: This randomized clinical trial did not demonstrate a benefit of ART in decreasing xerostomia compared with standard IMRT. No significant differences were found in secondary end points except for parotid gland excretory function, as assessed by scintigraphy, or in survival rates.Trial registration: ClinicalTrials.gov Identifier: NCT01874587.
Published: 2023

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