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198 results on '"Centre Eugène Marquis (CRLCC)"'

1. Cost-Effectiveness Analysis of Sequential Treatment Strategies for Advanced Melanoma in Real Life in France

Author: Marguerite Kandel, Aurélie Bardet, Stéphane Dalle, Clara Allayous, Laurent Mortier, Bernard Guillot, Caroline Dutriaux, Marie-Thérèse Leccia, Sophie Dalac, Henri Montaudie, Philippe Saiag, Delphine Legoupil, Florence Brunet-Possenti, Jean-Philippe Arnault, Julie De Quatrebarbes, Marie Beylot-Barry, Eve Maubec, Thierry Lesimple, François Aubin, Jean-Jacques Grob, Florence Granel-Brocard, Pierre-Emmanuel Stoebner, Alain Dupuy, Brigitte Dreno, Stefan Michiels, Céleste Lebbe, Isabelle Borget, Institut Gustave Roussy [IGR], Oncostat [U1018 (Équipe 2)], Centre Léon Bérard [Lyon], Immunologie humaine, physiopathologie & immunothérapie [HIPI (UMR_S_976 / U976)], Thérapies Laser Assistées par l'Image pour l'Oncologie - U 1189 [ONCO-THAI], Centre Hospitalier Régional Universitaire [Lille] [CHRU Lille], Centre Hospitalier Universitaire de Bordeaux [CHU de Bordeaux], Centre Hospitalier Universitaire [Grenoble] [CHU], Service de Dermatologie (CHU de Dijon), Centre Hospitalier Universitaire de Nice [CHU Nice], Hôpital Ambroise Paré [AP-HP], Centre Hospitalier Régional Universitaire de Brest [CHRU Brest], AP-HP - Hôpital Bichat - Claude Bernard [Paris], CHU Amiens-Picardie, Hôpital Avicenne [AP-HP], Centre Eugène Marquis [CRLCC], Centre Hospitalier Régional Universitaire de Besançon [CHRU Besançon], Hôpital de la Timone [CHU - APHM] [TIMONE], Service de Dermatologie et Allergologie [CHRU Nancy], Hôpital Universitaire Carémeau [Nîmes] [CHU Nîmes], Institut de Recherche en Cancérologie de Montpellier [IRCM - U1194 Inserm - UM], CHU Pontchaillou [Rennes], Centre hospitalier universitaire de Nantes [CHU Nantes], Groupe de Recherche et d'Accueil en Droit et Economie de la Santé [GRADES], Institut Gustave Roussy (IGR), Oncostat (U1018 (Équipe 2)), Institut Gustave Roussy (IGR)-Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Service de biostatistique et d'épidémiologie (SBE), Direction de la recherche clinique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), 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 de Dermatologie [AP-HP Hôpital Saint-Louis], Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Immunologie humaine, physiopathologie & immunothérapie (HIPI (UMR_S_976 / U976)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Thérapies Laser Assistées par l'Image pour l'Oncologie - U 1189 (ONCO-THAI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université de Montpellier (UM), Centre Hospitalier Universitaire de Bordeaux (CHU de Bordeaux), Centre Hospitalier Universitaire [Grenoble] (CHU), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Hospitalier Universitaire de Nice (CHU Nice), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Centre Eugène Marquis (CRLCC), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Hôpital de la Timone [CHU - APHM] (TIMONE), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Hôpital Universitaire Carémeau [Nîmes] (CHU 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), Centre hospitalier universitaire de Nantes (CHU Nantes), Groupe de Recherche et d'Accueil en Droit et Economie de la Santé (GRADES), Université Paris-Saclay, and This research was funded by the French Institute National of Cancer (DOC 16-009).
Subjects: Proto-Oncogene Proteins B-raf, MESH: Melanoma, Cost-Benefit Analysis, Cost-Effectiveness Analysis, [SDV.CAN]Life Sciences [q-bio]/Cancer, JEL: I - Health, Education, and Welfare/I.I1 - Health/I.I1.I18 - Government Policy • Regulation • Public Health, Targeted therapy, Advanced melanoma, Cost-effectiveness analysis, Immunotherapy, Real-life clinical practice, Humans, Prospective Studies, Melanoma, MESH: Proto-Oncogene Proteins B-raf, MESH: Humans, MESH: Cost-Effectiveness Analysis, [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy, [SHS.ECO]Humanities and Social Sciences/Economics and Finance, MESH: Prospective Studies, MESH: France, cost-effectiveness analysis, advanced melanoma, real-life clinical practice, immunotherapy, targeted therapy, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, France, [SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology, MESH: Cost-Benefit Analysis
Abstract: International audience; Nine drugs have been marketed for 10 years for the treatment of advanced melanoma (AM). With half of patients reaching a second line, the optimal sequence of treatments remains unclear. To inform policy-makers about their efficiency, we performed a cost-effectiveness analysis of sequential strategies in clinical practice in France, for BRAF-mutated and wild-type patients. A multistate model was developed to describe treatment sequences, associated costs, and health outcomes over 10 years. Sequences, clinical outcomes, utility scores, and economic data were extracted from the prospective Melbase cohort, collecting individual data in 1518 patients since 2013, from their AM diagnosis until their death. To adjust the differences in patients’ characteristics among sequences, weighting by inverse probability was used. In the BRAF-mutated population, the MONO-targeted therapies (TT)-anti-PD1 sequence was the less expensive, whereas the anti-PD1-BI-TT sequence had an incremental cost-effectiveness ratio (ICER) of 180,441 EUR/QALY. Regarding the BRAF wild-type population, the three sequences constituted the cost-effective frontier, with ICERs ranging from 116 to 806,000 EUR/QALY. For BRAF-mutated patients, the sequence anti-PD1-BI-TT appeared to be the most efficient one in BRAF-mutated AM patients until 2018. Regarding the BRAF wild-type population until 2018, the sequence starting with IPI+NIVO appeared inefficient compared to anti-PD1, considering the extra cost for the QALY gained.
Published: 2022

2. Adaptive radiotherapy in head and neck cancer is required to avoid tumor underdose

Author: Caroline Lafond, Franck Jegoux, B. Rigaud, R. de Crevoisier, O. Henry, K. Benezery, Enrique Chajon, Joël Castelli, Antoine Simon, Juliette Thariat, Elodie Vauleon, Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Eugène Marquis (CRLCC), CHU Pontchaillou [Rennes], Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire Traitement du Signal et de l'Image ( LTSI ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), and Centre Eugène Marquis ( CRLCC )
Subjects: medicine.medical_specialty, medicine.medical_treatment, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, Planned Dose, medicine, Humans, Radiology, Nuclear Medicine and imaging, [ SDV.IB ] Life Sciences [q-bio]/Bioengineering, Precision Medicine, Adaptive radiotherapy, ComputingMilieux_MISCELLANEOUS, business.industry, Radiotherapy Planning, Computer-Assisted, Head and neck cancer, Dose-Response Relationship, Radiation, Radiotherapy Dosage, Hematology, General Medicine, medicine.disease, Tumor Burden, 3. Good health, Radiation therapy, Oropharyngeal Neoplasms, Oncology, Head and Neck Neoplasms, 030220 oncology & carcinogenesis, Carcinoma, Squamous Cell, [SDV.IB]Life Sciences [q-bio]/Bioengineering, Radiotherapy, Intensity-Modulated, Radiology, business, Radiotherapy, Image-Guided
Abstract: During the course of intensity-modulated radiotherapy (IMRT) for head and neck cancer (HNC), the delivered dose may differ from the planned dose due to significant anatomical variations. Several st...
Published: 2018

3. Retrieving the vital status of patients with cancer using online obituaries

Author: Sylvestre , E., Bouzillé , G., Breton , M., Cuggia , M., Campillo-Gimenez , B., Laboratoire Traitement du Signal et de l'Image ( LTSI ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre d'Investigation Clinique [Rennes] ( CIC ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre Eugène Marquis ( CRLCC ), Klein G.O.Karlsson D.Moen A.Ugon A. (eds), Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Eugène Marquis (CRLCC), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Web mining, Digital epidemiology, [SDV.IB]Life Sciences [q-bio]/Bioengineering, Vital status, Medical Record Linkage, [ SDV.IB ] Life Sciences [q-bio]/Bioengineering
Abstract: International audience; The aim of this study was to develop a methodology to link mortality data from Internet sources with administrative data from electronic health records and to assess the performance of different record linkage methods. We extracted the electronic health records of all adult patients hospitalized at Rennes comprehensive cancer center between January 1, 2010 and December 31, 2015 and separated them in two groups (training and test set). We also extracted all available online obituaries from the most exhaustive French funeral home website using web scraping techniques. We used and evaluated three different algorithms (deterministic, approximate deterministic and probabilistic) to link the patients' records with online obituaries. We optimized the algorithms using the training set and then evaluated them in the test set. The overall precision was between 98 and 100%. The three classification algorithms performed better for men than women. The probabilistic classification decreased the number of manual reviews, but slightly increased the number of false negatives. To address the problem of long delays in the publication or sharing of mortality data, online obituary data could be considered for real-time surveillance of mortality in patients with cancer because they are easily available and time-efficient. © 2018 European Federation for Medical Informatics (EFMI) and IOS Press.
Published: 2018

4. Emerging and Evolving Concepts in Cancer Immunotherapy Imaging

Author: Laurent Dercle, Shawn Sun, Romain-David Seban, Ahmed Mekki, Roger Sun, Lambros Tselikas, Sophie Hans, Alice Bernard-Tessier, Fadila Mihoubi Bouvier, Nicolas Aide, Laetitia Vercellino, Alexia Rivas, Antoine Girard, Fatima-Zohra Mokrane, Guillaume Manson, Roch Houot, Egesta Lopci, Randy Yeh, Samy Ammari, Lawrence H. Schwartz, Columbia University Medical Center (CUMC), Columbia University [New York], Institut Curie [Paris], Hôpital Raymond Poincaré [AP-HP], Radiothérapie Moléculaire et Innovation Thérapeutique (RaMo-IT), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, TheraPanacea [Paris], Institut Gustave Roussy (IGR), Département d'imagerie médicale [Gustave Roussy], CHU Henri Mondor [Créteil], Département d’Innovation Thérapeutique et essais précoces [Gustave Roussy] (DITEP), AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Unité de recherche interdisciplinaire pour la prévention et le traitement des cancers (ANTICIPE), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)-Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM), Hopital Saint-Louis [AP-HP] (AP-HP), Centre Eugène Marquis (CRLCC), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Microenvironment and B-cells: Immunopathology,Cell Differentiation, and Cancer (MOBIDIC), Université de Rennes (UR)-Etablissement français du sang [Rennes] (EFS Bretagne)-Institut National de la Santé et de la Recherche Médicale (INSERM), Humanitas Clinical and Research Center [Rozzano, Milan, Italy], Memorial Sloan Kettering Cancer Center (MSKCC), Fondation ARC pour la recherche médicale (international mobility grant and grant SIGN’IC20161236437), INSERM, and Fondation Bettencourt Schueller, pending U.S. patent (no. 16630031), and Fondazione AIRC
Subjects: [SDV]Life Sciences [q-bio], CLINICAL BENEFIT, NIVOLUMAB, MELANOMA, ASSOCIATION, HYPERPROGRESSIVE DISEASE, GUIDELINES, Neoplasms, Positron-Emission Tomography, Disease Progression, Humans, Immunologic Factors, CRITERIA, Radiology, Nuclear Medicine and imaging, Immunotherapy, IMMUNE-RELATED RESPONSE, ADVERSE EVENTS, INHIBITORS
Abstract: International audience; Criteria based on measurements of lesion diameter at CT have guided treatment with historical therapies due to the strong association between tumor size and survival. Clinical experience with immune checkpoint modulators shows that editing immune system function can be effective in various solid tumors. Equally, novel immune-related phenomena accompany this novel therapeutic paradigm. These effects of immunotherapy challenge the association of tumor size with response or progression and include risks and adverse events that present new demands for imaging to guide treatment decisions. Emerging and evolving approaches to immunotherapy highlight further key issues for imaging evaluation, such as dissociated response following local administration of immune checkpoint modulators, pseudoprogression due to immune infiltration in the tumor environment, and premature death due to hyperprogression. Research that may offer tools for radiologists to meet these challenges is reviewed. Different modalities are discussed, including immuno-PET, as well as new applications of CT, MRI, and fluorodeoxyglucose PET, such as radiomics and imaging of hematopoietic tissues or anthropometric characteristics. Multilevel integration of imaging and other biomarkers may improve clinical guidance for immunotherapies and provide theranostic opportunities.
Published: 2023

5. 18F-FDOPA PET/CT of Paraganglioma in the Spermatic Cord

Author: Goujon, Anna, Pop, Gabriel, Hissier, Julien, Moreau, Benjamin, Palard-Novello, Xavier, CHU Pontchaillou [Rennes], Centre Eugène Marquis (CRLCC), Laboratoire Traitement du Signal et de l'Image (LTSI), and Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: paraganglioma, F-18-FDOPA PET, [SDV]Life Sciences [q-bio], spermatic cord, Radiology, Nuclear Medicine and imaging, General Medicine, CT
Abstract: International audience; A 53-year-old man with chronic kidney failure was referred to perform an F-18-FDOPA PET/CT to characterize a mass located on the right spermatic cord. Previously, the pathological analysis of CT-guided biopsies suggested paraganglioma or metastatic lesion of pheochromocytoma. Serum normetanephrine and serum metanephrine values were respectively 2- and 1.5-fold greater than the normal upper limit, which could be explained by the chronic kidney failure. PET/CT images revealed intense F-18-FDOPA uptake of the mass without any other pathological findings, suggesting the diagnosis of paraganglioma. Pathological examination of surgical specimen confirmed the diagnosis of paraganglioma of the spermatic cord, which is exceptional.
Published: 2023

6. Real-Time Detection of ESR1 Mutation in Blood by Droplet Digital PCR in the PADA-1 Trial: Feasibility and Cross-Validation with NGS

Author: Celine Callens, Francois-Clement Bidard, Anaïs Curto-Taribo, Olfa Trabelsi-Grati, Samia Melaabi, Suzette Delaloge, Anne-Claire Hardy-Bessard, Thomas Bachelot, Florian Clatot, Thibault De La Motte Rouge, Jean-Luc Canon, Laurent Arnould, Fabrice Andre, Sandrine Marques, Marc-Henri Stern, Jean-Yves Pierga, Anne Vincent-Salomon, Camille Benoist, Emmanuelle Jeannot, Frederique Berger, Ivan Bieche, Anne Pradines, Immunité et cancer (U932), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Centre d'Investigation Clinique en Biotherapie des cancers (CIC 1428 , CBT 507 ), Institut Gustave Roussy (IGR)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR), Centre Armoricain de Radiothérapie, d'Imagerie médicale et d'Oncologie [Plérin, Saint-Brieuc] (CARIO), Centre Léon Bérard [Lyon], Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Centre Eugène Marquis (CRLCC), Département de Biologie et pathologie des tumeurs [Centre Georges-François Leclerc], Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER, UNICANCER, Unité de génétique et biologie des cancers (U830), Université Paris Cité - UFR Médecine Paris Centre [Santé] (UPC Médecine Paris Centre), Université Paris Cité (UPC), Institut Curie [Paris], Centre de Recherches en Cancérologie de Toulouse (CRCT), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Claudius Regaud, Pfizer, AstraZeneca, Roche, Ministère des Affaires Sociales et de la Santé, Institut National Du Cancer, INCa: PRT-K19-110, Institut Curie: INCa-DGOS-INSERM_12554, The authors declare the following competing financial interest(s): F.-C.B.: Grants from Pfizer during the conduct of the study, grants, personal fees, and nonfinancial support from Pfizer and Novartis personal fees from Lilly, Amgen, Sanofi, and Radius personal fees and nonfinancial support from Roche and AstraZeneca, grants and personal fees from Seagen, and grants from Prolynx outside the submitted work, and a pending patent on ctDNA detection by ddPCR. F.-C.B., M.-H.S., and E.J. are coholders of a patent related to ESR1 mutation detection (PCT/EP2019/056445). S.D.: Consulting Fees (e.g., advisory boards), Author, AstraZeneca, Besins, Rappta. Contracted Research, Pfizer, MSD, BMS, AstraZeneca, Orion, Sanofi, Novartis, Puma, Roche, Lilly, Daich. A.-C.H.-B.: Personal fees from AstraZeneca, Daiichi, Clovis, GSK, MSD, Novartis, Pfizer, and Roche outside the submitted work. T.B.: Consulting Fees (e.g., advisory boards), AstraZeneca, SeaGen, Roche, Novartis, Pfizer. Contracted Research, Roche, AstraZeneca, Pfizer, SeaGen. T.D.L.M.R.: Consulting Fees (e.g., advisory boards), AstraZeneca, Clovis Oncology, Eisai, MSD, Novartis, Pfizer, Roche, Sanofi, Tesaro. Contracted Research, Novartis, Pfizer, AstraZeneca. Other, AstraZeneca, MSD, Roche, Pfizer. F.A.: Grants from Roche, AstraZeneca, Daiichi Sankyo, Pfizer, Novartis, and Lilly outside the submitted work. M.S.: Receipt of Intellectual Property Rights/Patent Holder, patent on ESR1 ddPCR. J.P.: Consulting Fees (e.g., advisory boards), Exact Sciences, AstraZeneca, Daiichi, Sankyo, Lilly, Novartis, Pfizer, Pierre Fabre, Oncology, Roche, SeaGen. Fees for Non-CME Services Received Directly from Commercial Interest or their Agents (e.g., speaker bureaus), Amgen, MSD, Novartis, Pfizer, SeaGen. Contracted Research, Servier, Roche. F.J.: Receipt of Intellectual Property Rights/Patent Holder, patent on ESR1 ddPCR. Acknowledgments, and This study was supported by a grant from the French Ministry of Health and the French National Cancer Institute (Grant PRT-K19-110) and Pfizer. The PADA-1 trial was funded by Pfizer through a grant to Unicancer. The initial development of the bESR1 assay used in the trial was supported by the Institut Curie SIRIC2 program (Grant INCa-DGOS-INSERM_12554). mut
Subjects: [CHIM.ANAL]Chemical Sciences/Analytical chemistry, Mutation, Feasibility Studies, High-Throughput Nucleotide Sequencing, Humans, Polymerase Chain Reaction, Circulating Tumor DNA, Analytical Chemistry
Abstract: International audience; The clinical actionability of circulating tumor DNA requires sensitive detection methods with a short turnaround time. In the PADA-1 phase 3 trial (NCT03079011), metastatic breast cancer patients treated with an aromatase inhibitor and palbociclib were screened every 2 months for activating ESR1 mutations in blood (bESR1mut). We report the feasibility of the droplet digital polymerase chain reaction (ddPCR) and cross-validation with next-generation sequencing (NGS). bESR1mut testing was centralized in two platforms using the same ddPCR assay. Results were reported as copies/mL of plasma and mutant allele frequency (MAF). We analyzed 200 positive ddPCR samples with an NGS assay (0.5-1% sensitivity). Overall, 12,552 blood samples were collected from 1017 patients from 83 centers. Among the 12,525 available samples with ddPCR results, 11,533 (92%) were bESR1mut-negative. A total of 267 patients newly displayed bESR1mut (26% patients/2% samples) with a median copy number of 14/mL (range: 4-1225) and a median MAF of 0.83% (0.11-35), 648 samples (20% patients/5% samples) displayed persistent bESR1mut, and 77 (
Published: 2022

7. Compréhension/acceptation de la radiothérapie : un dilemme éthique résolu par une éthique de la considération et de la sollicitude

Author: de Crevoisier, Renaud, Leseur, Julie, Bouvet, C., Huguet, Florence, Lagrange, J. L., Haaser, Thibaud, Pasquier, David, Créhange, Gilles, Supiot, Stéphane, Pommier, Pascal, Roy, Amit, Berna, A., Blanchard, Pierre, Marcucci, L., Centre 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), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Université Bordeaux Montaigne (UBM), Hôpital Pellegrin, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Centre de Recherche en Informatique, Signal et Automatique de Lille - UMR 9189 (CRIStAL), Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Institut Curie [Paris], Laboratoire d'Imagerie Translationnelle en Oncologie (LITO ), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Curie Centre de Protonthérapie d'Orsay, Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Centre Léon Bérard [Lyon], Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Institut Gustave Roussy (IGR), Centre Atlantique de Philosophie (CAPHI), Université de Rennes (UR)-Université de Brest (UBO)-Institut Brestois des Sciences de l'Homme et de la Société (IBSHS), Université de Brest (UBO)-Nantes Université - UFR Lettres et Langages (Nantes Univ - UFR LL), Nantes Université - pôle Humanités, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Humanités, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Université de Rennes - Faculté des sciences pharmaceutiques et biologiques (UR Pharmacie), and Université de Rennes (UR)
Subjects: Ethics, Oncology, Radiotherapy, [SDV]Life Sciences [q-bio], Beneficence, Consideration, Radiology, Nuclear Medicine and imaging, [SDV.CAN]Life Sciences [q-bio]/Cancer, Autonomy
Abstract: International audience; Purpose: Ethical questions are poorly investigated specifically in radiation oncology. The objective of the study was to identify and understand the main ethical issue in radiation oncology. Materials and methods: A quantitative analysis was based on the answers to a questionnaire of 200 professionals from 22 radiation oncology departments. The questionnaire mainly aimed to characterize the main ethical issue. A monocentric qualitative analysis was based on semi-structured interviews focused on the main identified ethical issue, carried out with eight technologists, and 20 patients undergoing radiotherapy. Results: The main ethical issue was the understanding and/or acceptance of the treatment by the patients (71 %), which frequently arises (more than once a month) (52 %), and corresponds to an ethical tension between the principles of respect for autonomy and beneficence (the good as viewed by the patient) as defined by Beauchamp and Childress. The technologists, wish the patient to be fully involved in his treatment, with the even possibility of refusing it. However, excluding paternalism and autonomic relentlessness, the technologists have the feeling of acting for the good of the patients by treating them with radiation, even if the patients are not always aware of it, because they are within a situation of vulnerability. If the hierarchy of principles is a compromise alternative, this problem is finally well resolved by the effective implementation of an ethic of consideration and solicitude, restoring the patient capabilities, i.e. the maximum development of his potentialities in his situation of vulnerability. Beyond the legal dimension, patient information is crucial and must consider the specific temporality of the patient. Conclusion: The main ethical issue in radiation oncology is the understanding and/or acceptance of the treatment involving the development of an ethic of consideration and solicitude.
Published: 2023

8. Skin photoaging around the site of occurrence of primary melanoma as a clinical predictive biomarker of response to PD-1 inhibitors

Author: Russo, David, Poizeau, Florence, Dinulescu, Monica, Baggio, Raphaelle, Orion, Camille, Soethoudt, Camille, Saillard, Clémence, Law Ping Man, Sarah, Lesimple, Thierry, Pracht, Dr Marc, Dupuy, Alain, Boussemart, Lise, CHU Pontchaillou [Rennes], Recherche en Pharmaco-épidémiologie et Recours aux Soins (REPERES), Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP), Centre Eugène Marquis (CRLCC), Immunology and New Concepts in ImmunoTherapy (INCIT), Université d'Angers (UA)-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)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, and Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)
Subjects: Immunothérapie, [SDV]Life Sciences [q-bio], Mutation, Charge tumorale, [SDV.CAN]Life Sciences [q-bio]/Cancer, Immunotherapy, Tumor burden, Melanoma, Mélanome
Abstract: International audience
Published: 2023

9. The Association Between Antibiotic Use and Outcome Among Metastatic Melanoma Patients Receiving Immunotherapy

Author: Florence Poizeau, Sandrine Kerbrat, Frédéric Balusson, Pierre Tattevin, Matthieu Revest, Vincent Cattoir, David Luque-Paz, Thierry Lesimple, Marc Pracht, Monica Dinulescu, David Russo, Emmanuel Oger, Alain Dupuy, Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), École des Hautes Études en Santé Publique [EHESP] (EHESP), Recherche en Pharmaco-épidémiologie et Recours aux Soins (REPERES), Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP), CHU Pontchaillou [Rennes], ARN régulateurs bactériens et médecine (BRM), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre Eugène Marquis (CRLCC), This work was supported by the Ligue Contre le Cancer ([French] League Against Cancer) (PhD grant to FP)., and Chard-Hutchinson, Xavier
Subjects: Cancer Research, [SDV]Life Sciences [q-bio], Neoplasms, Second Primary, [SDV.CAN]Life Sciences [q-bio]/Cancer, Articles, Anti-Bacterial Agents, [SDV] Life Sciences [q-bio], [SDV.CAN] Life Sciences [q-bio]/Cancer, Oncology, Dysbiosis, Humans, Immunologic Factors, Immunotherapy, Immune Checkpoint Inhibitors, Melanoma, Retrospective Studies
Abstract: Background Several observational studies have reported a decreased response to immune checkpoint inhibitors (ICI) following antibiotic use. ICI activity has been hypothesized to be impaired by antibiotic-induced gut dysbiosis. Methods Patients with advanced melanoma receiving an anti-PD-1 antibody as a first-line therapy between 2015 and 2017 in France were selected using the French Health Insurance database. We compared overall survival and time-to-treatment discontinuation according to antibiotic exposure in the 3 months prior to the initiation of anti-PD-1 antibody. To disentangle a causal effect of antibiotics from a confounding bias, we balanced characteristics of patients exposed and nonexposed to antibiotics using an overlap weighting method based on a propensity score. We also evaluated a control cohort of patients with advanced melanoma receiving first-line targeted therapy, as there is no rationale for decreased efficacy of targeted therapy following antibiotic treatment. Results The anti-PD-1 antibody cohort comprised 2605 individuals. Antibiotic exposure in the 3 months prior to anti-PD-1 antibody initiation was not associated with shorter overall survival (weighted hazard ratio = 1.01, 95% confidence interval = 0.88 to 1.17) or time-to-treatment discontinuation (weighted hazard ratio = 1.00, 95% confidence interval = 0.89 to 1.11). Consistent results were observed when the time frame of antibiotics was narrowed to 1 month prior to anti-PD-1 initiation or when exposure was restricted to antibiotics leading to more profound gut dysbiosis. Similar results were observed in the targeted therapy cohort. Conclusions In a large cohort of advanced melanoma patients, we showed that antibiotic use preceding anti-PD-1 antibody was not associated with worse outcome. Physicians should not delay immunotherapy for patients who have recently received antibiotics.
Published: 2022

10. Automatic segmentation for plan-of-the-day selection in CBCT-guided adaptive radiation therapy of cervical cancer

Author: Chen Zhang, Caroline Lafond, Anaïs Barateau, Julie Leseur, Bastien Rigaud, Diane Barbara Chan Sock Line, Guanyu Yang, Huazhong Shu, Jean-Louis Dillenseger, Renaud de Crevoisier, Antoine Simon, Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratory of Image Science and Technology [Nanjing] (LIST), Southeast University [Jiangsu]-School of Computer Science and Engineering, CRLCC Eugène Marquis (CRLCC), Centre Eugène Marquis (CRLCC), Southeast University, Centre de Recherche en Information Biomédicale sino-français (CRIBS), Université de Rennes (UR)-Southeast University [Jiangsu]-Institut National de la Santé et de la Recherche Médicale (INSERM), projet DELPEL de ITMO Cancer AVIESAN, plan cancer de la 'Ligue contre le Cancer' et 'La Vannetaise, Ambassade de France en Chine, and ANR-11-LABX-0004,CAMI,Gestes Médico-Chirurgicaux Assistés par Ordinateur(2011)
Subjects: Radiological and Ultrasound Technology, cervical cancer, CBCT segmentation, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, Radiology, Nuclear Medicine and imaging, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.IB.MN]Life Sciences [q-bio]/Bioengineering/Nuclear medicine, plan-of-the-day, [SDV.MHEP.GEO]Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, adaptive radiation therapy
Abstract: Objective. Plan-of-the-day (PoD) adaptive radiation therapy (ART) is based on a library of treatment plans, among which, at each treatment fraction, the PoD is selected using daily images. However, this strategy is limited by PoD selection uncertainties. This work aimed to propose and evaluate a workflow to automatically and quantitatively identify the PoD for cervix cancer ART based on daily CBCT images. Approach. The quantification was based on the segmentation of the main structures of interest in the CBCT images (clinical target volume [CTV], rectum, bladder, and bowel bag) using a deep learning model. Then, the PoD was selected from the treatment plan library according to the geometrical coverage of the CTV. For the evaluation, the resulting PoD was compared to the one obtained considering reference CBCT delineations. Main results. In experiments on a database of 23 patients with 272 CBCT images, the proposed method obtained an agreement between the reference PoD and the automatically identified PoD for 91.5% of treatment fractions (99.6% when considering a 5% margin on CTV coverage). Significance. The proposed automatic workflow automatically selected PoD for ART using deep-learning methods. The results showed the ability of the proposed process to identify the optimal PoD in a treatment plan library.
Published: 2022

11. Les inégalités socio-territoriales de prise en charge des patient.e.s atteint.e.s de cancer en France (Métropole / Outre-mer): Le terrain des Outre-mer – perspective comparative. Des difficultés rencontrées par les soignés aux recherches-actions mises en place (partie 1). La « démocratie sanitaire » en question en Métropole. Des « migrants » au presque « tout venant » ? (partie 2)

Author: Vega, Anne, Poveda Avila, Juan Diego, Solignat, Blandine, Pracht, Dr Marc, Ludet, Louise, Rousseau, Estelle, Dramé, Zoé, Chaze, Milhan, Sociologie, philosophie et anthropologie politiques (SOPHIAPOL), Université Paris Nanterre (UPN), Médecins du Monde [Paris] (MDM), Université de Guyane (UG), Centre Eugène Marquis (CRLCC), Centre hospitalier universitaire de Nantes (CHU Nantes), Nantes Université - UFR Sociologie (Nantes Univ - UFR S), Nantes Université - pôle Sociétés, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Université Clermont Auvergne (UCA), MSH-PN, CENS, EHESP, Sophiapol, and Anne Vega, avec Norbert Amsellem et Ibtissem Ben Dridi
Subjects: Études qualitatives et quantitatives, Métropole, Actes de colloque, Cancers, MSH-PN, Outre-mer, [SHS]Humanities and Social Sciences
Abstract: National audience; Le colloque sur « Les inégalités socio-territoriales de prise en charge des patient.e.s atteint.e.s de cancer en France (Métropole / Outre-mer) » a permis des échanges fructueux entre les intervenants, les modérateurs et le public, issus de diverses disciplines (anthropologie, sociologie, géographie de la santé, sciences politiques, sciences infirmières, etc.). La plupart des problématiques présentées ont trouvé une résonance avec l’étude au long cours Corsac, ayant motivé l’organisation de ce colloque. En outre, l’ensemble des communications présente des continuités, dépassant à la fois la prise en charge exclusive du cancer et la simple opposition Métropole/Outre-mer. Dans le contexte actuel d’augmentation des inégalités sociales et de détérioration des services publics (notamment de santé), il s’agit ici de valoriser en particulier les communications d’associations humanitaires et de jeunes chercheurs, y compris professionnels de santé ultramarins (1ère journée du colloque : Le terrain des Outre-mer, perspective comparative et politique. Des difficultés rencontrées par les soignés aux recherches-actions). Des diapositives, des supports illustrés et cartographiques, ainsi que des notes de bas de page permettent de mieux contextualiser et comprendre des actions localisées et des études en cours à Mayotte, en Guyane, ainsi qu’à La Réunion. Les travaux d’autres jeunes chercheurs en métropole sont présentés dans une seconde partie (2ème journée du colloque : La démocratie sanitaire en question). Certaines communications, présentées uniquement ici sous forme de diaporama, feront l’objet de publications plus développées (revues, ouvrage collectif). Nous remercions la MSH-PN, l’EHESP, le Sophiapol et le Cens pour leurs soutiens financiers; Norbert Amsellem pour la relecture de communications, et Blandine Solignat pour son aide technique.
Published: 2022

12. Immune checkpoint inhibitors in patients aged 80 or older with advanced non-small cell lung cancer or melanoma: a real-life multicentre study

Author: Soraya Benguerfi, Thierry Lesimple, Roch Houot, Charles Ricordel, Delphine Legoupil, Corinne Alleaume, Régine Lamy, Delphine Deniel Lagadec, Romain Corre, CHU Pontchaillou [Rennes], Centre Eugène Marquis (CRLCC), Microenvironment and B-cells: Immunopathology,Cell Differentiation, and Cancer (MOBIDIC), Université de Rennes (UR)-Etablissement français du sang [Rennes] (EFS Bretagne)-Institut National de la Santé et de la Recherche Médicale (INSERM), Oncogenesis, Stress, Signaling (OSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), CHU de Saint-Brieuc, Groupe Hospitalier Bretagne Sud (GHBS), and Centre Hospitalier Intercommunal de Cornouaille (CHIC)
Subjects: safety, Aged, 80 and over, Lung Neoplasms, efficacy, [SDV.CAN]Life Sciences [q-bio]/Cancer, Hematology, General Medicine, elderly, Oncology, Carcinoma, Non-Small-Cell Lung, Humans, Radiology, Nuclear Medicine and imaging, Immune Checkpoint Inhibitors, Melanoma, non-small cell lung cancer, Aged, Retrospective Studies
Abstract: International audience; Background Data regarding characteristics, safety and survival outcomes of patients aged 80 or older treated with immune checkpoint inhibitors (ICI) in routine oncology practice are limited. Materials and methods We retrospectively collected data of patients aged 80 and older with advanced non-small cell lung cancer (NSCLC) or melanoma treated with anti-PD1, anti-PD-L1 or anti-CTLA-4 regardless of the treatment line, in 14 institutions, between January 2014 and June 2017. Progression-free survival (PFS) and overall survival (OS) were estimated with the Kaplan Meier method. Toxicity was assessed according to CTCAE 5.0. Multivariate analyses were performed with the Cox model. Results Eighty-two patients were included (36 with NSCLC, 45 with melanoma). Their median age was 82 years (range 80-93). Nivolumab and pembrolizumab were mainly used. In the NSCLC group, median PFS and OS were 2.3 months (95%CI 1.8-6.1) and 8.8 months (95%CI 5.5-18.1), respectively. In the melanoma group, median PFS and OS were 10.2 months (95%CI 4.5-20.0) and 24.5 months (95%CI 14.1-NR), respectively. The albumin level was found to be independently associated with a better OS in both groups. Grade 3-4 toxicities occurred in 15 patients (18.5%). One patient died from ICI-induced pulmonary toxicity. Conclusion Our study findings suggest that treatment with ICI in elderly patients with NSCLC and melanoma has a risk-benefit ratio that supports its use. However, we report in this cohort that one in five patients has a grade 3-4 IRAEs leading to treatment discontinuation. Geriatric assessment prior to initiation of therapy and during therapy should be routine in patients aged 80 years and older.
Published: 2022

13. Study of radiolabeled hepatotropic peptide derivatives for the diagnosis and treatment of hepatocellular carcinoma

Author: Hanadi Nahas, Clarisse Brossard, Elise Vène, Stébastien Gouard, Michel Chérel, Mickaël Bourgeois, Pascal Loyer, Nicolas Lepareur, Sandrine Cammas-Marion, Nutrition, Métabolismes et Cancer (NuMeCan), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut des Sciences Chimiques de Rennes (ISCR), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), GIP ARRONAX [Nantes], Université de Nantes (UN), and Centre Eugène Marquis (CRLCC)
Subjects: Cancer Research, Molecular Medicine, [CHIM]Chemical Sciences, Radiology, Nuclear Medicine and imaging
Abstract: International audience; Meeting Abstract P-19
Published: 2022

14. Recommendations for planning and delivery of radical radiotherapy for localized urothelial carcinoma of the bladder

Author: Renaud de Crevoisier, David Azria, Christophe Hennequin, Jonathan Khalifa, Pierre Graff-Cailleaud, Igor Latorzeff, Gilles Créhange, Pierre Blanchard, Arnaud Mejean, Nicolas Magné, Morgane Cabaillé, Olivier Riou, Morgan Rouprêt, Géraldine Pignot, S. Belhomme, Olivier Chapet, Paul Sargos, Stéphane Culine, David Pasquier, Stéphane Supiot, 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), Endothelium Radiobiology and Targeting (CRCINA-ÉQUIPE 14), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Gustave Roussy (IGR), Department of Radiotherapy, Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER, Institut de Cancérologie Lucien Neuwirth, Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), 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 Eugène Marquis (CRLCC), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut du Cancer de Montpellier (ICM), Institut Bergonié [Bordeaux], UNICANCER, Clinique Pasteur [Toulouse], Equipe IFTIM [ImViA - EA7535], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER-Imagerie et Vision Artificielle [Dijon] (ImViA), Université de Bourgogne (UB)-Université de Bourgogne (UB), Centre pour l'innovation en cancérologie de Lyon (CICLY), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Européen Georges Pompidou [APHP] (HEGP), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)
Subjects: medicine.medical_specialty, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, medicine.medical_treatment, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.IB.MN]Life Sciences [q-bio]/Bioengineering/Nuclear medicine, Guidelines, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, Radiology, Nuclear Medicine and imaging, Medical physics, Adaptive radiotherapy, Adaptative radiotherapy, Urothelial carcinoma, Image-guided radiation therapy, Carcinoma, Transitional Cell, Bladder cancer, Image guided radiation therapy, Radiotherapy, business.industry, Radiotherapy Planning, Computer-Assisted, Standard treatment, Radiotherapy Dosage, Radical radiotherapy, Hematology, medicine.disease, Clinical trial, Radiation therapy, Urinary Bladder Neoplasms, Oncology, 030220 oncology & carcinogenesis, Radiotherapy, Intensity-Modulated, Trimodal therapy, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Radiotherapy, Image-Guided
Abstract: International audience; Purpose: Curative radio-chemotherapy is recognized as a standard treatment option for muscle-invasive bladder cancer (MIBC). Nevertheless, the technical aspects for MIBC radiotherapy are heterogeneous with a lack of practical recommendations.Methods and materials: In 2018, a workshop identified the need for two cooperative groups to develop consistent, evidence-based guidelines for irradiation technique in the delivery of curative radiotherapy. Two radiation oncologists performed a review of the literature addressing several topics relative to radical bladder radiotherapy: planning computed tomography acquisition, target volume delineation, radiation schedules (total dose and fractionation) and dose delivery (including radiotherapy techniques, image-guided radiotherapy (IGRT) and adaptive treatment modalities). Searches for original and review articles in the PubMed and Google Scholar databases were conducted from January 1990 until March 2020. During a meeting conducted in October 2020, results on 32 topics were presented and discussed with a working group involving 15 radiation oncologists, 3 urologists and one medical oncologist. We applied the American Urological Association guideline development's method to define a consensus strategy.Results: A consensus was obtained for all 34 except 4 items. The group did not obtain an agreement on CT enhancement added value for planning, PTV margins definition for empty bladder and full bladder protocols, and for pelvic lymph-nodes irradiation. High quality evidence was shown in 6 items; 8 items were considered as low quality of evidence.Conclusion: The current recommendations propose a homogenized modality of treatment both for routine clinical practice and for future clinical trials, following the best evidence to date, analyzed with a robust methodology. The XXX group formulates practical guidelines for the implementation of innovative techniques such as adaptive radiotherapy.
Published: 2021

15. Safety and efficacy of nivolumab, an anti-PD1 immunotherapy, in patients with advanced basal cell carcinoma, after failure or intolerance to sonic Hedgehog inhibitors: UNICANCER AcSé NIVOLUMAB trial

Author: Marie Véron, Sylvie Chevret, Jean-Jacques Grob, Marie Beylot-Barry, Philippe Saiag, Aude Fléchon, Benoit You, Eve Maubec, Thomas Jouary, Elise Toulemonde, Philippe Jamme, Laëtitia Gambotti, Assia Lamrani-Ghaouti, Alain Dupuy, Céleste Lebbe, Nicole Basset Seguin, Nadine Houede, Marie-Thérèse Leccia, Fanny Le Du, Michel de Pontville, Caroline Gaudy-Marquestre, Bernard Guillot, Clotilde Simon, Aurélien Marabelle, Laurent Mortier, Hôpital Claude Huriez [Lille], CHU Lille, Faculté de Médecine Henri Warembourg - Université de Lille, Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de dermatologie, vénéreologie et cancérologie cutanée [Hôpital de la Timone - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), 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 de dermatologie [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], BoRdeaux Institute in onCology (Inserm U1312 - BRIC), Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Ambroise Paré [AP-HP], Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Centre Léon Bérard [Lyon], Hospices Civils de Lyon (HCL), Ciblage thérapeutique en Oncologie (EA3738), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Hôpital Avicenne [AP-HP], Centre hospitalier de Pau, Institut national du cancer [Boulogne] (INCA), UNICANCER, CHU Pontchaillou [Rennes], CIC Saint Louis (CIC-1427), 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), Immunologie humaine, physiopathologie & immunothérapie (HIPI (UMR_S_976 / U976)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Centre Hospitalier Universitaire [Grenoble] (CHU), Centre Eugène Marquis (CRLCC), Service de Dermatologie [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), Hôpital de la Timone [CHU - APHM] (TIMONE), Hôpital Saint Eloi (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Département d’Innovation Thérapeutique et essais précoces [Gustave Roussy] (DITEP), Institut Gustave Roussy (IGR), and Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)
Subjects: Cancer Research, Skin Neoplasms, MESH: Immunotherapy, PD1 blocker, [SDV.CAN]Life Sciences [q-bio]/Cancer, Antineoplastic Agents, MESH: Carcinoma, Basal Cell, Humans, Hedgehog Proteins, Cancer, MESH: Humans, MESH: Skin Neoplasms, Metastatic basal cell carcinoma, MESH: Hedgehog Proteins, Nivolumab, Oncology, Carcinoma, Basal Cell, Basal cell carcinoma, MESH: Antineoplastic Agents, MESH: Nivolumab, Immune checkpoint, Immunotherapy, Neoplasm Recurrence, Local, Locally advanced basal cell carcinoma, MESH: Neoplasm Recurrence, Local, [SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology
Abstract: International audience; Basal cell carcinoma (BCC) is the most common human malignancy. In most cases, BCC has slow progression and can be definitively cured by surgery or radiotherapy. However, in rare cases, it can become locally advanced or, even more rarely, metastatic. The alternative recommended treatments are Sonic Hedgehog pathway inhibitors; however, the response is often short-lived.Methods: This was a phase 2 basket study (NCT03012581) evaluating the efficacy and safety of nivolumab in a cohort of 32 advanced BCC patients, enrolled after failure of Sonic Hedgehog inhibitors, including 29 laBCC (91%) and 3 mBCC (9%).Results: Compared to previously published studies, our population consisted of severe patients with a poor prognosis because they had already received multiple lines of treatment: all patients received previous Sonic Hedgehog inhibitors, 53% of patients already had chemotherapy and 75% radiotherapy. At 12 weeks, we reported 3.1% of complete responses, 18.8% of partial responses, and 43.8% of stable diseases. The best response rate to nivolumab reached 12.5% of complete responses (four patients), 18.8% of partial responses (three patients), and 43.8% of stable diseases (14 patients). Adverse events (AE) were mostly grade 2 or 3, slightly different to the adverse events observed in the treatment of metastatic melanoma (higher rate of diabetes, no thyroid dysfunction).Conclusion: Nivolumab is a relevant therapeutic option for patients with advanced relapsing/refractory BCC.
Published: 2022

16. Efficacy and safety of bevacizumab-based combination regimens in patients with previously untreated metastatic colorectal cancer: Final results from a randomised phase ii study of bevacizumab plus 5-fluorouracil, leucovorin plus irinotecan versus bevacizumab plus capecitabine plus irinotecan

Author: C. Montoto-Grillot, T. Conroy, E. Francois, J.P. Pignon, J-Y Pierga, E. Boucher, Bruno Chauffert, Antoine Adenis, Michel Ducreux, J.L. Ichante, M. Ychou, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR), CRLCC Oscar Lambret, Service de biostatistique et d'épidémiologie (SBE), Direction de la recherche clinique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Centre Antoine Lacassagne, CRLCC Antoine Lacassagne, Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc (CRLCC - CGFL), Centre Eugène Marquis (CRLCC), Centre Régional de Lutte contre le Cancer Val d'Aurelle, Institut Curie, UNICANCER [Paris], Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Maladies chroniques, santé perçue, et processus d'adaptation (APEMAC), Université Paris Descartes - Paris 5 (UPD5)-Université de Lorraine (UL), Institut de Cancérologie de Lorraine - Alexis Vautrin (ICL), Institut Gustave Roussy ( IGR ), Service de biostatistique et d'épidémiologie ( SBE ), Institut Gustave Roussy ( IGR ) -Institut Gustave Roussy ( IGR ), Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc ( CRLCC - CGFL ), Centre Eugène Marquis ( CRLCC ), Maladies chroniques, santé perçue, et processus d'adaptation. Approches épidémiologiques et psychologiques. ( APEMAC - EA 4360 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Université de Lorraine ( UL ), Institut de Cancérologie de Lorraine - Alexis Vautrin ( ICL ), Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER, Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, Institut Curie [Paris], Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), and Université Lille Nord de France (COMUE)-UNICANCER
Subjects: Oncology, MESH: Fatigue, Cancer Research, Time Factors, genetic structures, Colorectal cancer, MESH : Antineoplastic Combined Chemotherapy Protocols, Leucovorin, Phases of clinical research, MESH : Camptothecin, MESH : Diarrhea, MESH : Leucovorin, Gastroenterology, Deoxycytidine, 0302 clinical medicine, Antineoplastic Combined Chemotherapy Protocols, Neoplasm Metastasis, Fatigue, MESH: Treatment Outcome, Venous Thrombosis, 0303 health sciences, [ SDV.SPEE ] Life Sciences [q-bio]/Santé publique et épidémiologie, MESH: Follow-Up Studies, MESH : Venous Thrombosis, 3. Good health, Bevacizumab, MESH : Fatigue, MESH: Antineoplastic Combined Chemotherapy Protocols, MESH: Diarrhea, Treatment Outcome, Fluorouracil, 030220 oncology & carcinogenesis, MESH : Neoplasm Metastasis, FOLFIRI, MESH : Fluorouracil, MESH: Camptothecin, MESH : Disease-Free Survival, MESH : Colorectal Neoplasms, Colorectal Neoplasms, medicine.drug, MESH : Time Factors, Diarrhea, medicine.medical_specialty, Neutropenia, MESH: Neutropenia, MESH : Drug Administration Schedule, MESH : Neutropenia, MESH : Treatment Outcome, MESH: Drug Administration Schedule, Antibodies, Monoclonal, Humanized, Irinotecan, MESH : Capecitabine, Disease-Free Survival, Drug Administration Schedule, MESH : Antibodies, Monoclonal, Humanized, Capecitabine, 03 medical and health sciences, MESH : Deoxycytidine, MESH: Bevacizumab, Internal medicine, medicine, Humans, MESH : Bevacizumab, 030304 developmental biology, XELIRI, MESH: Humans, business.industry, MESH : Humans, MESH: Time Factors, MESH: Deoxycytidine, MESH: Capecitabine, MESH: Quality of Life, MESH : Follow-Up Studies, MESH : Quality of Life, medicine.disease, MESH: Neoplasm Metastasis, eye diseases, digestive system diseases, MESH: Antibodies, Monoclonal, Humanized, MESH: Venous Thrombosis, MESH: Disease-Free Survival, Quality of Life, Camptothecin, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, sense organs, business, MESH: Leucovorin, MESH: Fluorouracil, MESH: Colorectal Neoplasms, Follow-Up Studies
Abstract: International audience; BACKGROUND:The combination of bevacizumab and bolus 5-fluorouracil, leucovorin and irinotecan is highly effective in patients with metastatic colorectal cancer (mCRC). This randomised, multicenter, non-comparative phase II trial assessed the efficacy and safety of bevacizumab plus oral capecitabine plus irinotecan (XELIRI) or infusional 5-fluorouracil, leucovorin plus irinotecan (FOLFIRI) as first-line therapy for patients with mCRC.PATIENTS AND METHODS:Patients received bevacizumab 7.5mg/kg on day 1 plus XELIRI (irinotecan 200mg/m(2) on day 1 and oral capecitabine 1,000 mg/m(2) bid on days 1-14) every 3 weeks or bevacizumab 5mg/kg on day 1 plus FOLFIRI (5-fluorouracil 400mg/m(2) on day 1 plus 2,400 mg/m(2) as a 46-h infusion, leucovorin 400mg/m(2) on day 1, and irinotecan 180 mg/m(2) on day 1) every 2 weeks. Patients aged ≥ 65 years received a lower dose of capecitabine (800 mg/m(2) twice daily). The primary endpoint was 6-month progression-free survival (PFS) rate.RESULTS:A total of 145 patients were enrolled (bevacizumab-XELIRI, n=72; bevacizumab-FOLFIRI, n=73). The 6-month PFS rate was 82% (95% confidence intervals (CI) 71-90%) in the bevacizumab-XELIRI arm and 85% (95% CI 75-92%) in the bevacizumab-FOLFIRI arm. In both the bevacizumab-XELIRI and bevacizumab-FOLFIRI arms, median PFS and overall survival (OS) were 9 and 23 months, respectively. The most frequent toxicities were grade 3/4 neutropenia (bevacizumab-XELIRI 18%; bevacizumab-FOLFIRI 26%) and grade 3 diarrhoea (12% and 5%, respectively).CONCLUSIONS:This randomised non-comparative study demonstrates that bevacizumab-XELIRI and bevacizumab-FOLFIRI are effective regimens for the first-line treatment of patients with mCRC with manageable toxicity profiles.
Published: 2013

17. Efficacy and safety of regorafenib in patients with metastatic or locally advanced chondrosarcoma: Results of a non-comparative, randomised, double-blind, placebo controlled, multicentre phase II study

Author: Loic Chaigneau, Mathilde Cancel, Corinne Delcambre, Corinne Bouvier, Emannuelle Bompas, Olivier Collard, Antoine Italiano, Christine Chevreau, Alice Hervieu, Pascaline Boudou-Rouquette, Vincent Vidal, Sylvie Chabaud, Olivier Mir, Esma Saada-Bouzid, Nicolas Penel, Maria Rios, Florence Duffaud, Camille Schiffler, Jean-Yves Blay, Christophe Perrin, Sophie Piperno-Neumann, Laure Monard, François Bertucci, Hôpital de la Timone [CHU - APHM] (TIMONE), Institut Bergonié [Bordeaux], UNICANCER, Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), University of Lille, Institut Gustave Roussy (IGR), Département interdisciplinaire d’organisation des parcours patients (DIOPP), Department of Medical Oncology, Institut Curie, Paris 75248, France, Institut Claudius Regaud, Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), 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), 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), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Eugène Marquis (CRLCC), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Centre Léon Bérard [Lyon], Hôpital JeanMinjoz, Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), Institut de Cancérologie de la Loire Lucien Neuwirth, and Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)
Subjects: 0301 basic medicine, Cancer Research, medicine.medical_specialty, business.industry, Phases of clinical research, [SDV.CAN]Life Sciences [q-bio]/Cancer, Placebo, medicine.disease, Clinical trial, 03 medical and health sciences, chemistry.chemical_compound, 030104 developmental biology, 0302 clinical medicine, Oncology, chemistry, 030220 oncology & carcinogenesis, Regorafenib, Internal medicine, Cohort, Clinical endpoint, medicine, business, Adverse effect, ComputingMilieux_MISCELLANEOUS, Progressive disease
Abstract: Background This multi-cohort trial explored the efficacy and safety of regorafenib for patients with advanced sarcomas of bone origin; this report details the cohort of patients with metastatic or locally advanced chondrosarcoma (CS), progressing after prior chemotherapy. Patients and methods Patients with CS, progressing despite prior standard therapy, were randomised (2:1) to receive regorafenib or placebo. Patients on placebo could crossover to receive regorafenib after centrally confirmed progressive disease. The primary endpoint was progression-free rate (PFR) at 12 weeks. With one-sided α of 0.05, and 80% power, at least 16/24 progression-free patients at 12 weeks were needed for success (P0 = 50%, P1 = 75%). Results From September 2014 to February 2019, 46 patients were included in the CS cohort, and 40 patients were evaluable for efficacy: 16 on placebo and 24 on regorafenib. Thirteen patients (54.2%; 95% CI [35.8%-[) were non-progressive at 12 weeks on regorafenib versus 5 (31.3%; 95% CI [13.2%-[);) on placebo. Median PFS was 19.9 weeks on regorafenib, and 8.0 on placebo. Fourteen placebo patients crossed over to regorafenib after progression. The most common grade ≥3 treatment-related adverse events on regorafenib included hypertension (12%), asthenia (8%), thrombocytopenia (8%) and diarrhoea (8%). One episode of fatal liver dysfunction occurred on regorafenib. Conclusion Although the primary endpoint was not met statistically in this small randomised cohort, there is modest evidence to suggest that regorafenib might slow disease progression in patients with metastatic CS after the failure of prior chemotherapy. Clinical trial registration The trial is registered at ClinicalTrials.gov ( NCT02389244 ).
Published: 2021

18. Optimal timing of interval debulking surgery for advanced epithelial ovarian cancer: A retrospective study from the ESME national cohort

Author: Quentin Dominique Thomas, Amal Boussere, Jean-Marc Classe, Christophe Pomel, Hélène Costaz, Manuel Rodrigues, Isabelle Ray-Coquard, Laurence Gladieff, Roman Rouzier, Thibault De La Motte Rouge, Sébastien Gouy, Emmanuel Barranger, Renaud Sabatier, Anne Floquet, Frédéric Marchal, Cécile Guillemet, Valentine Polivka, Anne-Laure Martin, Pierre-Emmanuel Colombo, Frédéric Fiteni, Institut du Cancer de Montpellier (ICM), CRLCC René Gauducheau, Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA), Service de chirurgie [Centre Georges-François Leclerc], Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER, Institut Curie [Paris], Centre Léon Bérard [Lyon], Institut Claudius Regaud, Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Centre Eugène Marquis (CRLCC), Institut Gustave Roussy (IGR), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Institut Bergonié [Bordeaux], UNICANCER, Service d'oncogénétique [Vandoeuvre-Lès-Nancy] (Institut de Cancérologie de Lorraine - CLCC Alexis Vautrin), Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Institut Desbrest de santé publique (IDESP), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)
Subjects: Ovarian Neoplasms, Survival, Propensity score, Obstetrics and Gynecology, [SDV.CAN]Life Sciences [q-bio]/Cancer, Cytoreduction Surgical Procedures, Carcinoma, Ovarian Epithelial, Prognosis, Neoadjuvant Therapy, Cytoreduction, Oncology, Chemotherapy, Adjuvant, Humans, Female, Neoadjuvant, Neoplasm Staging, Retrospective Studies
Abstract: International audience; Objective. Interval debulking surgery is recommended after 3–4 cycles (standard IDS) of neoadjuvant chemotherapy (NACT) for epithelial ovarian cancer (EOC) not able to received upfront complete debulking surgery. However, real world practices frequently report performing IDS after ≥5 NAC cycles (delayed IDS). The aim of this work was to evaluate the impact on survival of the number of NACT cycles before IDS.Methods. We identified from a French national database, women with newly diagnosed EOC who underwent IDS from January 2011 to December 2016. Progression free survival (PFS) and overall survival (OS) were compared using Cox model with adjustments for confounding factors provided by two propensity score methods: inverse probability of treatment weighting (IPTW) and matched-pair analysis.Results. 928 patients treated by IDS for which our propensity score could be applied were identified. After a median follow-up of 49.0 months (95% CI [46.0;52.9]); from the IPTW analysis, median PFS was 17.6 months and 11.5 months (HR = 1.42; CI 95% [1.22–1.67]; p < 0.0001); median OS was 51.2 months and 44.3 months (HR = 1.29; CI 95% [1.06–1.56]; p = 0.0095) for the standard and delayed IDS groups. From the matched-pair analysis (comparing 352 patients for each group), standard IDS was associated with better PFS (HR = 0,77; CI 95% [0.65–0.90]; p = 0.018) but not significantly associated with better OS (HR = 0,84; CI 95% [0.68–1,03]; p = 0.0947).Conclusions. Carrying IDS after ≥5 NACT cycles seems to have a negative effect on patients survival. The goal of IDS surgery is complete resection and should not be performed after >3–4 NACT cycles.
Published: 2022

19. Switch to fulvestrant and palbociclib versus no switch in advanced breast cancer with rising ESR1 mutation during aromatase inhibitor and palbociclib therapy (PADA-1): a randomised, open-label, multicentre, phase 3 trial

Author: François-Clément Bidard, Anne-Claire Hardy-Bessard, Florence Dalenc, Thomas Bachelot, Jean-Yves Pierga, Thibault de la Motte Rouge, Renaud Sabatier, Coraline Dubot, Jean-Sébastien Frenel, Jean Marc Ferrero, Sylvain Ladoire, Christelle Levy, Marie-Ange Mouret-Reynier, Alain Lortholary, Julien Grenier, Camille Chakiba, Laetitia Stefani, Jérôme Edouard Plaza, Florian Clatot, Luis Teixeira, Véronique D'Hondt, Hélène Vegas, Olfa Derbel, Claire Garnier-Tixidre, Jean-Luc Canon, Barbara Pistilli, Fabrice André, Laurent Arnould, Anne Pradines, Ivan Bièche, Céline Callens, Jérôme Lemonnier, Frédérique Berger, Suzette Delaloge, Francois-Clement BIDARD, Barbara PISTILLI, Florence DALENC, Thomas BACHELOT, Thibault DE LA MOTTE ROUGE, Renaud SABATIER, Coraline DUBOT, Jean-Sébastien FRENEL, Jean-Marc FERRERO, Sylvain LADOIRE, Christelle LEVY, Marie-Ange MOURET-REYNIER, Anne-Claire HARDY-BESSARD, Alain LORTHOLARY, Julien GRENIER, Camille CHAKIBA, Laetitia STEFANI, Patrick SOULIE, Jean-Philippe JACQUIN, Jérôme Edouard PLAZA, Florian CLATOT, Luis TEIXEIRA, Véronique D'HONDT, Hélène VEGAS, Olfa DERBEL, Claire GARNIER TIXIDRE, Catherine DELBALDO, Lionel MOREAU, Caroline CHENEAU, Jean-François PAITEL, Chantal BERNARD-MARTY, Dominique SPAETH, Dominique GENET, Isabelle MOULLET, Nathalie BONICHON-LAMICHHANE, Laura DEIANA, Charlotte GREILSAMER, Laurence VENAT-BOUVET, Valérie DELECROIX, Adrien MELIS, Hubert ORFEUVRE, Suzanne NGUYEN, Eric LEGOUFFE, Alain ZANNETTI, Romuald LE SCODAN, Nadine DOHOLLOU, Philippe DALIVOUST, Olivier ARSENE, Nathalie MARQUES, Thierry PETIT, Delphine MOLLON, Jérôme DAUBA, Nathalie BONNIN, François MORVAN, Miriam GARDNER, Adina MARTI, Charles-Briac LEVACHE, Emma LACHAIER, Mihaela ACHILLE, Christophe VALMAR, Ryan BOUAITA, Jacques MEDIONI, Cyril FOA, Francesco DEL PIANO, Michel GOZY, Anne ESCANDE, Nicolas LEDUC, Brigitte LUCAS, Dominique MILLE, Hanifa AMMARGUELLAT, Abeer NAJEM, Fanny TROUBOUL, Philippe BARTHELEMY, Hervé DESCLOS, Didier MAYEUR, Fabrice LORCHEL, François GUINET, Anne-Pascale LAURENTY, Axelle BOUDRANT, Olivier GISSEROT, Corinne ALLEAUME, Aimery DE GRAMONT, Institut Curie [Paris], Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Centre Armoricain de Radiothérapie, d'Imagerie médicale et d'Oncologie [Plérin, Saint-Brieuc] (CARIO), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département cancer environnement (Centre Léon Bérard - Lyon), Centre Léon Bérard [Lyon], Centre Eugène Marquis (CRLCC), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Service d'oncogénétique [Centre georges-François Leclerc], Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER, Radiothérapie [Centre François Baclesse], Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA), Hôpital privé du Confluent [Nantes], Institut Sainte Catherine [Avignon], Institut Bergonié [Bordeaux], Centre Hospitalier Annecy-Genevois [Saint-Julien-en-Genevois], Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut du Cancer de Montpellier (ICM), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Hôpital privé Jean Mermoz [Lyon], Institut Gustave Roussy (IGR), Département de médecine oncologique [Gustave Roussy], Université Paris Dauphine-PSL, Université Paris sciences et lettres (PSL), and Pfizer
Subjects: Adult, Neutropenia, Adolescent, Aromatase Inhibitors, Receptor, ErbB-2, [SDV]Life Sciences [q-bio], Breast Neoplasms, Disease-Free Survival, Oncology, Receptors, Estrogen, Lymphopenia, Antineoplastic Combined Chemotherapy Protocols, Mutation, Humans, Female, Prospective Studies, Fulvestrant
Abstract: In advanced oestrogen receptor-positive, HER2-negative breast cancer, acquired resistance to aromatase inhibitors frequently stems from ESR1-mutated subclones, which might be sensitive to fulvestrant. The PADA-1 trial aimed to show the efficacy of an early change in therapy on the basis of a rising ESR1 mutation in blood (bESR1We did a randomised, open-label, phase 3 trial in 83 hospitals in France. Women aged at least 18 years with oestrogen receptor-positive, HER2-negative advanced breast cancer and an Eastern Cooperative Oncology Group performance status of 0-2 were recruited and monitored for rising bESR1From March 22, 2017, to Jan 31, 2019, 1017 patients were included, of whom 279 (27%) developed a rising bESR1PADA-1 is the first prospective randomised trial showing that the early therapeutic targeting of bESR1Pfizer.
Published: 2022

20. Gallium-68 and Copper-64 radiolabelling of hepatotropic GBVA10-9 or CPB peptide derivatives for hepatocellular carcinoma imaging

Author: Clarisse Brossard, Mickaël Bourgeois, Stébastien Gouard, Christelle Bouvry, Elise Vène, Hanadi Nahas, Michel Chérel, Pascal Loyer, Sandrine Cammas-Marion, Nicolas Lepareur, Institut des Sciences Chimiques de Rennes (ISCR), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), GIP ARRONAX [Nantes], Université de Nantes (UN), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Eugène Marquis (CRLCC), Institut National de la Santé et de la Recherche Médicale (INSERM), and Meeting Abstract P-190
Subjects: Cancer Research, Molecular Medicine, [CHIM]Chemical Sciences, Radiology, Nuclear Medicine and imaging
Abstract: International audience
Published: 2022

21. Feelings of cancer patients in exclusive palliative care: Towards a general practitioner, oncologist pairing?

Author: Peinoit, Alexandre, Robert, Guillaume, Lassus, Isabelle, Evin, Adrien, Morel, Vincent, Centre Eugène Marquis (CRLCC), CHU Pontchaillou [Rennes], Université de Rennes (UR), Centre hospitalier universitaire de Nantes (CHU Nantes), Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)
Subjects: Oncologists, Patient’s disappointment, Emotions, [SDV.CAN]Life Sciences [q-bio]/Cancer, Ressenti du patient, General Practitioners, General practitioner-oncologist pairing, Patient’s feelings, Neoplasms, Binôme médecin généraliste-cancérologue, Palliative care, Soins palliatifs, Humans, Déception du patient, Qualitative study, Étude qualitative, Qualitative Research
Abstract: National audience; INTRODUCTION: In palliative care, cancer patients’ thoughts about support given by their general practitioner are poorly described in the literature. General practitioners are involved in the management of cancer patients in palliative care, but when contact with the oncologist become less frequent, the place of the patient’s different doctors becomes difficult to define. The objective of our work is to analyze the patient’s perception of the place and role of the general practitioner. METHODS: Qualitative study by individual semi-directed interviews, with voluntary patients with solid cancer in palliative care. Patients were selected by palliative care physicians. A thematic analysis was performed on the basis of the patients’ verbatim transcripts. RESULTS: Seventeen patients were interviewed and four main themes were highlighted: a perception of abandonment, a resignation to call the general practitioner, an omnipresence of the oncologist who seems not to leave the place to the general practitioner and a search for global support. The general practitioner did not appear to be empathetic nor supportive enough and was not available enough. DISCUSSION: Patients are looking for empathy and for their doctors to listen. Our work shows a certain disappointment of the patients regarding the place and role of their general practitioner. This disappointment reflects the insufficient coordination between hospital and community care setting. While the early integration of palliative care is becoming a standard of care, the patients’ testimony commits us to improve the articulation between the oncologist and the general practitioner.
Published: 2022

22. Nivolumab, nivolumab–ipilimumab, and VEGFR-tyrosine kinase inhibitors as first-line treatment for metastatic clear-cell renal cell carcinoma (BIONIKK): a biomarker-driven, open-label, non-comparative, randomised, phase 2 trial

Author: Yann-Alexandre Vano, Réza Elaidi, Mostefa Bennamoun, Christine Chevreau, Delphine Borchiellini, Diane Pannier, Denis Maillet, Marine Gross-Goupil, Christophe Tournigand, Brigitte Laguerre, Philippe Barthélémy, Elodie Coquan, Gwenaëlle Gravis, Nadine Houede, Mathilde Cancel, Olivier Huillard, Philippe Beuzeboc, Laure Fournier, Arnaud Méjean, Xavier Cathelineau, Nicolas Doumerc, Philippe Paparel, Jean-Christophe Bernhard, Alexandre de la Taille, Karim Bensalah, Thibault Tricard, Thibaut Waeckel, Géraldine Pignot, Elena Braychenko, Stefano Caruso, Cheng-Ming Sun, Virginie Verkarre, Guillaume Lacroix, Marco Moreira, Maxime Meylan, Antoine Bougouïn, Letuan Phan, Christelle Thibault-Carpentier, Jessica Zucman-Rossi, Wolf Herman Fridman, Catherine Sautès-Fridman, 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), Association pour la Recherche de Thérapeutiques Innovantes en Cancérologie [Paris] (ARTIC), Institut Mutualiste de Montsouris (IMM), 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 Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER, 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), Hôpital Saint-André, Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre Eugène Marquis (CRLCC), Institut de Cancérologie de Strasbourg Europe (ICANS), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), 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), Institut de Cancérologie du GARD ICG - CHU Nîmes (Instit Cancéro - GARD), Clinique d'Oncologie et de Radiothérapie [Tours] (CORAD), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Hôpital Foch [Suresnes], Service des Explorations Fonctionnelles Physiologiques [CHU Toulouse], Pôle Urologie - Néphrologie - Dialyse - Transplantations - Brûlés - Chirurgie plastique - Explorations fonctionnelles et physiologiques [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Hospices Civils de Lyon (HCL), Nouvel Hôpital Civil de Strasbourg, Service de Néphrologie-Dialyse-Transplantation rénale [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), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Institut 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), Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), and 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)
Subjects: MESH: Humans, MESH: Carcinoma, Renal Cell / drug therapy, MESH: Angiogenesis Inhibitors / adverse effects, [SDV.CAN]Life Sciences [q-bio]/Cancer, MESH: Neoplasm Staging, MESH: Male, MESH: Prospective Studies, MESH: Ipilimumab, MESH: Lipase, Oncology, MESH: Tumor Microenvironment, MESH: Sunitinib, MESH: Biomarkers, MESH: Antineoplastic Combined Chemotherapy Protocols / adverse effects, MESH: Female, MESH: Nivolumab / adverse effects, MESH: Protein Kinase Inhibitors / adverse effects
Abstract: International audience; Background: We previously reported a 35-gene expression classifier identifying four clear-cell renal cell carcinoma groups (ccrcc1 to ccrcc4) with different tumour microenvironments and sensitivities to sunitinib in metastatic clear-cell renal cell carcinoma. Efficacy profiles might differ with nivolumab and nivolumab-ipilimumab. We therefore aimed to evaluate treatment efficacy and tolerability of nivolumab, nivolumab-ipilimumab, and VEGFR-tyrosine kinase inhibitors (VEGFR-TKIs) in patients according to tumour molecular groups.Methods: This biomarker-driven, open-label, non-comparative, randomised, phase 2 trial included patients from 15 university hospitals or expert cancer centres in France. Eligible patients were aged 18 years or older, had an Eastern Cooperative Oncology Group performance status of 0-2, and had previously untreated metastatic clear-cell renal cell carcinoma. Patients were randomly assigned (1:1) using permuted blocks of varying sizes to receive either nivolumab or nivolumab-ipilimumab (ccrcc1 and ccrcc4 groups), or either a VEGFR-TKI or nivolumab-ipilimumab (ccrcc2 and ccrcc3 groups). Patients assigned to nivolumab-ipilimumab received intravenous nivolumab 3 mg/kg plus ipilimumab 1 mg/kg every 3 weeks for four doses followed by intravenous nivolumab 240 mg every 2 weeks. Patients assigned to nivolumab received intravenous nivolumab 240 mg every 2 weeks. Patients assigned to VEGFR-TKIs received oral sunitinib (50 mg/day for 4 weeks every 6 weeks) or oral pazopanib (800 mg daily continuously). The primary endpoint was the objective response rate by investigator assessment per Response Evaluation Criteria in Solid Tumors version 1.1. The primary endpoint and safety were assessed in the population who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, NCT02960906, and with the EU Clinical Trials Register, EudraCT 2016-003099-28, and is closed to enrolment.Findings: Between June 28, 2017, and July 18, 2019, 303 patients were screened for eligibility, 202 of whom were randomly assigned to treatment (61 to nivolumab, 101 to nivolumab-ipilimumab, 40 to a VEGFR-TKI). In the nivolumab group, two patients were excluded due to a serious adverse event before the first study dose and one patient was excluded from analyses due to incorrect diagnosis. Median follow-up was 18·0 months (IQR 17·6-18·4). In the ccrcc1 group, objective responses were seen in 12 (29%; 95% CI 16-45) of 42 patients with nivolumab and 16 (39%; 24-55) of 41 patients with nivolumab-ipilimumab (odds ratio [OR] 0·63 [95% CI 0·25-1·56]). In the ccrcc4 group, objective responses were seen in seven (44%; 95% CI 20-70) of 16 patients with nivolumab and nine (50% 26-74) of 18 patients with nivolumab-ipilimumab (OR 0·78 [95% CI 0·20-3·01]). In the ccrcc2 group, objective responses were seen in 18 (50%; 95% CI 33-67) of 36 patients with a VEGFR-TKI and 19 (51%; 34-68) of 37 patients with nivolumab-ipilimumab (OR 0·95 [95% CI 0·38-2·37]). In the ccrcc3 group, no objective responses were seen in the four patients who received a VEGFR-TKI, and in one (20%; 95% CI 1-72) of five patients who received nivolumab-ipilimumab. The most common treatment-related grade 3-4 adverse events were hepatic failure and lipase increase (two [3%] of 58 for both) with nivolumab, lipase increase and hepatobiliary disorders (six [6%] of 101 for both) with nivolumab-ipilimumab, and hypertension (six [15%] of 40) with a VEGFR-TKI. Serious treatment-related adverse events occurred in two (3%) patients in the nivolumab group, 38 (38%) in the nivolumab-ipilimumab group, and ten (25%) patients in the VEGFR-TKI group. Three deaths were treatment-related: one due to fulminant hepatitis with nivolumab-ipilimumab, one death from heart failure with sunitinib, and one due to thrombotic microangiopathy with sunitinib.Interpretation: We demonstrate the feasibility and positive effect of a prospective patient selection based on tumour molecular phenotype to choose the most efficacious treatment between nivolumab with or without ipilimumab and a VEGFR-TKI in the first-line treatment of metastatic clear-cell renal cell carcinoma.
Published: 2022

23. Adjustment of young women with breast cancer after chemotherapy: A mediation model of emotional competence via emotional distress

Author: Anne‐Sophie Baudry, Sonya Yakimova, Anne Congard, Aurélie Untas, Séverine Guiu, Claudia Lefeuvre‐Plesse, Catherine Loustalot, Cécile Guillemet, Carine Segura‐Djezzar, Aude‐Marie Savoye, Florence Coussy, Jean‐Sébastien Frenel, Laurence Vanlemmens, Véronique Christophe, Centre de Recherche en Psychologie de la Connaissance, du Langage et de l'Émotion (PsyCLÉ), Aix Marseille Université (AMU), Laboratoire de Psychologie des Pays de la Loire (LPPL), Université d'Angers (UA)-Nantes Université - UFR Lettres et Langages (Nantes Univ - UFR LL), Nantes Université - pôle Humanités, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Humanités, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Laboratoire de Psychopathologie et Processus de Santé (LPPS (URP_4057)), Université Paris Cité (UPCité), 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), UNICANCER - Institut régional du Cancer Montpellier Val d'Aurelle (ICM), CRLCC Val d'Aurelle - Paul Lamarque, Centre Eugène Marquis (CRLCC), Centre hospitalier d'Auxerre (CHA), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Residual Tumor & Response to Treatment Laboratory [Paris] (RT2Lab), Translational Research Department [Paris], Immunité et cancer (U932), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Immunité et cancer (U932), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Département d'Oncologie Médicale [Institut Curie, Paris], Institut Curie [Paris], Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER, Laboratoire Sciences Cognitives et Sciences Affectives - UMR 9193 (SCALab), and Université de Lille-Centre National de la Recherche Scientifique (CNRS)
Subjects: Psychiatry and Mental health, Oncology, Depression, [SCCO.PSYC]Cognitive science/Psychology, Quality of Life, Humans, Breast Neoplasms, Female, Experimental and Cognitive Psychology, Anxiety, Child, Psychological Distress
Abstract: Emotional competence (EC) is considered a substantial resource in the adjustment of cancer patients, especially via its effect on anxiety and depression symptoms. This research aimed at assessing the impact of intrapersonal EC in young women (≤45 years) with breast cancer (YWBC) on their specific quality of life (i.e. subjective experience related to daily difficulties and perceived repercussions of the disease and treatments) related to chemotherapy, via anxiety and depression symptoms.Two hundred fifty YWBC from 24 French centers completed a self-reported questionnaire after diagnosis (T1) and after the chemotherapy phase (T2), comprising the Young Women Breast Cancer Inventory, the Profile of EC and the Hospital Anxiety and Depression Scale. The indirect effect of EC (T1) on subjective experience (T2) via anxiety and depression symptoms (T2) was tested using regressions and the Macro PROCESS.Emotional competence predicted fewer anxiety and depression symptoms at T1 and T2, and a better subjective experience at T2 via fewer anxiety and depression symptoms. Depression symptoms appeared to be a stronger mediator than anxiety symptoms on four dimensions (Support from close relatives, feeling of couple cohesion, body image and sexuality, management of children and everyday life), whereas anxiety symptoms appeared to be a stronger mediator on two dimensions (negative affectivity and apprehension about the future, deterioration of relationships).These results support the importance of developing psycho-affective interventions to reinforce the EC of YWBC during chemotherapy in order to facilitate the cognitive and emotional processes necessary for a better adjustment and subjective experience.
Published: 2022

24. Efficacy of trastuzumab emtansine (T-DM1) and lapatinib after dual HER2 inhibition with trastuzumab and pertuzumab in patient with metastatic breast cancer: Retrospective data from a French multicenter real-life cohort

Author: Fabien Moinard-Butot, Caroline Saint-Martin, Carole Pflumio, Matthieu Carton, William Jacot, Paul-Henri Cottu, Véronique Diéras, Florence Dalenc, Anthony Goncalves, Marc Debled, Anne Patsouris, Marie-Ange Mouret-Reynier, Laurence Vanlemmens, Marianne Leheurteur, George Emile, Jean-Marc Ferrero, Isabelle Desmoulins, Lionel Uwer, Jean-Christophe Eymard, Bianca Cheaib, Coralie Courtinard, Thomas Bachelot, Michaël Chevrot, Thierry Petit, Institut de Cancérologie de Strasbourg Europe (ICANS), Institut Curie [Paris], Institut du Cancer de Montpellier (ICM), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre Eugène Marquis (CRLCC), Institut Claudius Regaud, 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), Institut Bergonié [Bordeaux], UNICANCER, Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER, Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Institut de Cancérologie de Bourgogne, Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), Institut Jean Godinot [Reims], Institut Gustave Roussy (IGR), Département de médecine oncologique [Gustave Roussy], 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), Centre Léon Bérard [Lyon], Roche, Pfizer, AstraZeneca, Eisai, Daiichi-Sankyo, and Admin, Oskar
Subjects: Adult, Adolescent, Receptor, ErbB-2, T-DM1, Breast Neoplasms, [SDV.CAN]Life Sciences [q-bio]/Cancer, Ado-Trastuzumab Emtansine, Antibodies, Monoclonal, Humanized, [SDV.CAN] Life Sciences [q-bio]/Cancer, Antineoplastic Combined Chemotherapy Protocols, Humans, Overall survival, skin and connective tissue diseases, neoplasms, Capecitabine, Retrospective Studies, Progression-free survival, Lapatinib, General Medicine, Trastuzumab, Metastatic breast cancer, Dual HER2 blockade, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Female, Taxoids, Surgery, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie
Abstract: International audience; PURPOSE: Trastuzumab-emtansine (T-DM1), as well as lapatinib plus capecitabine were proven effective in two Phase III studies, following first-line trastuzumab plus a taxane. The introduction of dual HER2 blockade by trastuzumab and pertuzumab as first-line has positioned T-DM1 into second-line, and lapatinib plus capecitabine beyond, without formal evaluation of these strategies.METHODS: ESME Data Platform (NCT03275311) included individual data from all patients aged ≥18 years, in whom first-line treatment for metastatic breast cancer (MBC) was initiated between January 1, 2008 and December 31, 2016 in one of the 18 French Comprehensive Cancer Centers. The efficacy of T-DM1 and lapatinib plus capecitabine combination, following double blockade associating trastuzumab and pertuzumab were evaluated in this national real-life database. Eligibility criteria were: female, MBC, HER2+ tumor, first-line taxane-based chemotherapy and dual HER2-blockage by trastuzumab plus pertuzumab. Cohort A received second-line T-DM1, and Cohort B second-line T-DM1 and third or fourth-line lapatinib plus capecitabine.RESULTS: Cohort A comprised 233 patients, and Cohort B 47 patients. Median progression-free survival (PFS) was 7.1 months in Cohort A and 4.6 months in Cohort B. Median overall survival were 36.7 months and 12.9 months, respectively. PFS was significantly dependent on the preceding treatment line's duration. In cohort A, HER2 expression status was a significant predictive factor of PFS.CONCLUSION: First-line trastuzumab plus pertuzumab do not markedly diminish T-DM1's efficacy in second-line. Similarly, sequential treatment with trastuzumab plus pertuzumab then T-DM1 does not noticeably modify the efficacy of lapatinib plus capecitabine.
Published: 2022

25. 18F-FDG PET/CT-Based Prognostic Survival Model After Surgery for Head and Neck Cancer

Author: Gwenaelle Creff, Franck Jegoux, Xavier Palard, Adrien Depeursinge, Ronan Abgral, Remi Marianowski, Jean-Christophe Leclere, Thomas Eugene, Olivier Malard, Renaud De Crevoisier, Anne Devillers, Joel Castelli, Jonchère, Laurent, CHU Pontchaillou [Rennes], Département de médecine nucléaire [Rennes], CRLCC Eugène Marquis (CRLCC), Centre Eugène Marquis (CRLCC), Haute Ecole Spécialisée de Suisse Occidentale (HES-SO), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Centre hospitalier universitaire de Nantes (CHU Nantes), Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), LTSI, INSERM, U1099 (Rennes, France), and Cancer Institute (Rennes, France)
Subjects: [SDV.IB] Life Sciences [q-bio]/Bioengineering, overall sur-vival, 030218 nuclear medicine & medical imaging, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, PET, distant metastasis, 030220 oncology & carcinogenesis, Radiology, Nuclear Medicine and imaging, head and neck cancer, [SDV.IB]Life Sciences [q-bio]/Bioengineering, Clinical Investigation, prognosis, CT
Abstract: International audience; The aims of this multicenter study were to identify clinical and preop-erative PET/CT parameters predicting overall survival (OS) and distant metastasis???free survival (DMFS) in a cohort of head and neck squa-mous cell carcinoma patients treated with surgery, to generate a prog-nostic model of OS and DMFS, and to validate this prognostic model with an independent cohort. Methods: A total of 382 consecutive patients with head and neck squamous cell carcinoma, divided into training (n = 318) and validation (n = 64) cohorts, were retrospectively included. The following PET/CT parameters were analyzed: clinical parameters, SUVmax, SUVmean, metabolic tumor volume (MTV), total lesion glycolysis, and distance parameters for the primary tumor and lymph nodes defined by 2 segmentation methods (relative SUVmax threshold and absolute SUV threshold). Cox analyses were performed for OS and DMFS in the training cohort. The concordance index (c-index) was used to identify highly prognostic parameters. These prognostic parameters were externally tested in the validation cohort. Results: In multivariable analysis, the significant parameters for OS were T stage and nodal MTV, with a c-index of 0.64 (P < 0.001). For DMFS, the significant parameters were T stage, nodal MTV, and maxi-mal tumor???node distance, with a c-index of 0.76 (P < 0.001). These combinations of parameters were externally validated, with c-indices of 0.63 (P < 0.001) and 0.71 (P < 0.001) for OS and DMFS, respec-tively. Conclusion: The nodal MTV associated with the maximal tumor???node distance was significantly correlated with the risk of DMFS. Moreover, this parameter, in addition to clinical parameters, was associated with a higher risk of death. These prognostic factors may be used to tailor individualized treatment. Superscript/Subscript Available
Published: 2022

26. Tumoural thrombosis extended into the right atrium revealed by 18F-flurodeoxyglucose positron emission tomography/computed tomography

Author: Antoine Girard, Christophe Perrin, Vincent Lavoué, Erwan Donal, Xavier Palard-Novello, Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Eugène Marquis (CRLCC), CHU Pontchaillou [Rennes], and Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Thrombosis, General Medicine, 030204 cardiovascular system & hematology, 030218 nuclear medicine & medical imaging, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, Fluorodeoxyglucose F18, Positron Emission Tomography Computed Tomography, Positron-Emission Tomography, Humans, Radiology, Nuclear Medicine and imaging, [SDV.IB]Life Sciences [q-bio]/Bioengineering, Heart Atria, Radiopharmaceuticals, Cardiology and Cardiovascular Medicine, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2022

27. Immunotherapy in MSI/dMMR tumors in the perioperative setting: The IMHOTEP trial

Author: Clélia Coutzac, Frederic Bibeau, Meher Ben Abdelghani, Thomas Aparicio, Romain Cohen, Elodie Coquan, Olivier Dubreuil, Ludovic Evesque, François Ghiringhelli, Stefano Kim, Samuel Lesourd, Cindy Neuzillet, Jean-Marc Phelip, Guillaume Piessen, Philippe Rochigneux, Emmanuelle Samalin, Emilie Soularue, Yann Touchefeu, David Tougeron, Aziz Zaanan, Christelle de la Fouchardière, Département cancer environnement (Centre Léon Bérard - Lyon), Centre Léon Bérard [Lyon], Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'Anatomie pathologique [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre Paul Strauss, CRLCC Paul Strauss, Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Groupe Hospitalier Diaconesses Croix Saint-Simon, Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Service d'oncogénétique [Centre georges-François Leclerc], Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER, Centre Eugène Marquis (CRLCC), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Hôpital Claude Huriez [Lille], CHU Lille, Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Institut du Cancer de Montpellier (ICM), Institut Mutualiste de Montsouris (IMM), Nantes Université (Nantes Univ), Centre hospitalier universitaire de Poitiers (CHU Poitiers), 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), Amgen, Bristol-Myers Squibb, BMS, Pfizer, AstraZeneca, Bayer, Roche, Sanofi, Meso Scale Diagnostics, MSD, Les Laboratories Pierre Fabre, MSD France, Ministère des Affaires Sociales et de la Santé, Institut National Du Cancer, INCa: PHRC-K 2019 Inca-DGOS_14333, PRT-K 2020–15324, Servier, Institut Servier, CC declares a consulting and advisory board for Amgen, Servier, and received honoria from Servier, Amgen. TA received honoraria from Servier, Pierre fabre, Amgen, AstraZeneca and declares consulting for Bioven, Servier, SIRTEC, MSD. RC received honoraria from MSD Oncology, Pierre Fabre, and Bristol-Myers Squibb, declares consulting from Exeliom Biosciences, Enterome Bioscience and received research funding from Servier Institute. OD received honoraria from Amgen, Sanofi, Merck Serono, MSD, Servier, Ipsen, Keocyt and declares consulting for Merck Serono, Sanofi, MSD, AstraZeneca, Novartis. LE declares consulting for BMS and Servier. FG declares research grant from Roche, AstraZeneca and consulting for Astrazenca, Roche, Sanofi, BMS, MSD, Merck-Serono, Amgen. EL declares consulting for Roche, Servier, Ipsen, Bayer, BTG, MSD. CN received honoraria from Amgen, AstraZeneca, Baxter, Bristol-Myers Squibb, Fresenius Kabi, Incyte Biosciences, Merck, MSD, Mylan, Novartis, Nutricia, Pierre Fabre, Roche, Sanofi, Servier and research funding from Roche. ES received honoraria from Servier, Amgen, Merck Serono, MSD, Pierre Fabre Oncology BMS, Sanofi, Research funding from Bayer, and declares consulting for Pierre Fabre Oncology. YT declares honoraria from MSD, Astra Zeneca, Bayer, Amgen, Servier, Ipsen, Pierre Fabre, AAA and consulting for Merck. DT received honoraria from Amgen, Roche, Sanofi, Bristol-Myers Squibb, Merck Serono, MSD, Bristol-Myers Squibb, Servier/Pfizer, Ipsen, research funding from AstraZeneca, SERVIER, Roche, MSD, BTG, and declares consulting for Sanofi, MSD, Pierre Fabre, and AstraZeneca. A.Z. declares consulting and/or advisory boards for Amgen, Lilly, Merck, Roche, Sanofi, Servier, Baxter, MSD, Pierre Fabre, Havas Life, Alira Health, Zymeworks, and Daiichi. CDLF received honoraria from Amgen, Astra- Zeneca, Bayer, Bristol-Myers Squibb, Eisai, Incyte Biosciences, Ipsen, Lilly, Merck Serono, MSD, Pierre Fabre Oncologie, Pfizer, Roche, Sanofi-Aventis, Servier. FB, MBZ, SK, EC, PR and ES declares no conflicts of interests., and This study is supported by a grant from the French Ministry of Health and the French National Cancer Institute (PHRC-K 2019 Inca-DGOS_14333 and PRT-K 2020–15324). It is also carried out with the support of MSD France. The opinions expressed in this article are those of the authors and do not necessarily reflect those of MSD France.
Subjects: Hepatology, MSI/dMMR, [SDV]Life Sciences [q-bio], Gastroenterology, Immune checkpoint inhibitor, DNA Mismatch Repair, Colorectal cancer, Perioperative immunotherapy, Antineoplastic Agents, Immunological, Endometrial cancer, Neoplasms, Humans, Immunologic Factors, Microsatellite Instability, Immunotherapy, Prospective Studies, Colorectal Neoplasms, Gastric cancer, Immune Checkpoint Inhibitors
Abstract: International audience; Background: Immune checkpoint inhibitors (ICI) targeting Programmed death-1 (PD-1) have shown their efficacy in advanced MSI/dMMR (microsatellite instability/deficient mismatch repair) tumors. The MSI/dMMR status predicts clinical response to ICI. The promising results evaluating ICI in localized MSI/dMMR tumors in neoadjuvant setting need to be confirmed in MSI/dMMR solid tumors. The aim of the IMHOTEP trial is to assess the efficacy of neoadjuvant anti-PD-1 treatment in MSI/dMMR tumors regarding the pathological complete response rate. Methods: This study is a prospective, multicenter, phase II study including 120 patients with localized MSI/dMMR carcinomas suitable for curative surgery. A single dose of pembrolizumab will be administered before the surgery planned 6 weeks later. Primary objective is to evaluate the efficacy of neoadjuvant pembrolizumab according to pathological complete tumor response. Secondary objectives are to assess safety, recurrence-free survival and overall survival. Ancillary studies will assess molecular and immunological biomarkers predicting response/resistance to ICI. First patient was enrolled in December 2021. Discussion: The IMHOTEP trial will be one of the first clinical trial investigating perioperative ICI in localized MSI/dMMR in a tumor agnostic setting. Assessing neoadjuvant anti-PD-1 is mandatory to improve MSI/dMMR patient's outcomes. The translational program will explore potential biomarker to improve our understanding of immune escape and response in this ICI neoadjuvant setting.
Published: 2022

28. Correlation between radiation dose and myocardial remodeling after stereotactic radiation therapy for ventricular tachycardia: First assessment of dose-effect relationship in human

Author: Karim Benali, Louis Rigal, Antoine Simon, Julien Bellec, Pierre Jaïs, Tsukasa Kamakura, Clifford G. Robinson, Phillip Cuculich, Renaud De Crevoisier, Raphaël P. Martins, Jonchère, Laurent, CHU Saint-Etienne, 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 Eugène Marquis (CRLCC), CHU Bordeaux [Bordeaux], Washington University School of Medicine in St. Louis, Washington University in Saint Louis (WUSTL), CHU Pontchaillou [Rennes], and Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)
Subjects: Anti-arrhythmic effects, [SDV.IB] Life Sciences [q-bio]/Bioengineering, Myocardium, Radiation dose, Cardiac SBRT, Arrhythmias, Cardiac, Ventricular tachycardia, Arrhythmias, Radiation Dosage, Radiosurgery, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Radiation therapy, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Physiology (medical), Tachycardia, Ventricular, Humans, [SDV.IB]Life Sciences [q-bio]/Bioengineering, Cardiology and Cardiovascular Medicine, Anti-Arrhythmia Agents, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2022

29. Concurrent cisplatin and dose escalation with intensity-modulated radiotherapy (IMRT) versus conventional radiotherapy for locally advanced head and neck squamous cell carcinomas (HNSCC): GORTEC 2004-01 randomized phase III trial

Author: Stéphanie Wong Hee Kam, Michel Rives, P. Boisselier, Yungan Tao, Yoann Pointreau, S. Heymann, Marc Alfonsi, Julian Biau, Ovidiu Veresezan, X. Sun, Cedrik Lafond, Pierre Blanchard, A. Cornely, Sophie Renard-Oldrini, Anne Auperin, Juliette Thariat, Odile Casiraghi, Pierre Graff, Jean Bourhis, Joël Castelli, Michel Lapeyre, 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 radiothérapie [Gustave Roussy], Institut Sainte Catherine [Avignon], Hôpital Nord Franche-Comté [Hôpital de Trévenans] (HNFC), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Institut Claudius Regaud, Centre Jean Bernard [Institut Inter-régional de Cancérologie - Le Mans], Centre Eugène Marquis (CRLCC), Centre Alexis Vautrin (CAV), Hôpital de la Timone [CHU - APHM] (TIMONE), 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)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), UNICANCER, Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), 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), Centre Jean Bernard [Le Mans], service de radiothérapie, UNICANCER-UNICANCER, Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Radiation Oncology Service, Normandie Université (NU)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), and COLO, Mouniati
Subjects: medicine.medical_specialty, Intensity-modulated radiotherapy, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Cell, Locally advanced, [SDV.CAN]Life Sciences [q-bio]/Cancer, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, otorhinolaryngologic diseases, medicine, Clinical endpoint, Humans, Radiology, Nuclear Medicine and imaging, IMRT, Stage (cooking), Head and neck cancer, Cisplatin, Dose escalation, Squamous Cell Carcinoma of Head and Neck, business.industry, Radiotherapy Dosage, Chemoradiotherapy, Hematology, medicine.disease, Concurrent chemoradiotherapy, 3. Good health, [SDV] Life Sciences [q-bio], Radiation therapy, stomatognathic diseases, medicine.anatomical_structure, Oncology, Head and Neck Neoplasms, 030220 oncology & carcinogenesis, Concomitant, Radiotherapy, Intensity-Modulated, Radiology, business, medicine.drug
Abstract: International audience; Background: Concurrent chemoradiotherapy (CRT) is the standard of care (SoC) in locally advanced (LA) head and neck squamous cell carcinomas (HNSCC). This trial was designed to test whether dose-escalated IMRT and cisplatin could improve locoregional control without increasing complications over 3D-radiotherapy.Methods: Patients were randomized between 70 Gy/35F in 7 weeks with 3D-RT (Arm A) versus 75 Gy/35F with IMRT (Arm B). Both arms received 50 Gy in 25 fractions followed by a sequential boost of 20 Gy/10F in Arm A and 25 Gy/10F to gross tumor volume in Arm B, as well as 3 cycles of cisplatin at 100 mg/m2 during RT. The primary endpoint was locoregional progression (LRP).Results: 188 patients were randomized: 85% oropharynx and 73% stage IVa. P16 status was documented for 137 oropharyngeal tumors with P16+ in 53 (39%) patients; and 90% were smokers. Median follow-up was 60.5 months. Xerostomia was markedly decreased in arm B (p < 0.0001). The 1-year grade ≥2 xerostomia (RTOG criteria) was 63% vs 23% and 3-year 45% vs 11% in arms A and B, respectively. Xerostomia LENT-SOMA scale was also reduced in arm B. Dose-escalated IMRT did not reduce LRP with an adjusted HR of 1.13 [95%CI = 0.64-1.98] (p = 0.68). Survival was not different (adjusted HR: 1.19 [95%CI = 0.78-1.81], p = 0.42). No interaction between p16 and treatment effect was found.Conclusion: Dose-escalated IMRT did not improve LRC in LA-HNSCC patients treated with concomitant CRT over standard 3D-RT. This trial reinforces the evidence showing IMRT reduces xerostomia in LA-HNSCC treated with radiotherapy. Clinicaltrial.gov: NCT00158678.
Published: 2020

30. Management of adjuvant settings for Stage III melanoma patients in France prior to checkpoint inhibitors: epidemiological data from the RIC-Mel database

Author: Jean-Michel Nguyen, S. Dalac-Rat, P. Celerier, Laurent Mortier, Céleste Lebbé, E. Varey, Brigitte Dréno, Alain Dupuy, C. Lesage, Amir Khammari, Stéphane Dalle, Caroline Dutriaux, Henri Montaudié, Nicolas Meyer, François Skowron, Marie-Thérèse Leccia, Hospices Civils de Lyon (HCL), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Eugène Marquis (CRLCC), Hôpital l'Archet, Hôpital Saint Eloi (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Thérapies Laser Assistées par l'Image pour l'Oncologie - U 1189 (ONCO-THAI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Lille, CHU Grenoble, Centre Hospitalier de Valence (CH DE VALENCE), Centre hospitalier de Valence, CH La Rochelle, Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), CHU Bordeaux [Bordeaux], CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Immunologie humaine, physiopathologie & immunothérapie (HIPI (UMR_S_976 / U976)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Malbec, Odile, and 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)
Subjects: Male, Oncology, Skin Neoplasms, Databases, Factual, [SDV]Life Sciences [q-bio], medicine.medical_treatment, sentinel lymph node, Antineoplastic Agents, Immunological, 0302 clinical medicine, Medicine, 030212 general & internal medicine, Age of Onset, Stage (cooking), Immune Checkpoint Inhibitors, Melanoma, education.field_of_study, medicine.diagnostic_test, Middle Aged, [SDV] Life Sciences [q-bio], targeted treatment, Chemotherapy, Adjuvant, 030220 oncology & carcinogenesis, Female, immunotherapy, France, Adjuvant, Adult, Proto-Oncogene Proteins B-raf, medicine.medical_specialty, Population, Sentinel lymph node, adjuvant treatment, Dermatology, BRAF, 03 medical and health sciences, Internal medicine, Biopsy, Humans, Stage IIIC, education, Aged, Neoplasm Staging, Sentinel Lymph Node Biopsy, business.industry, Interferon-alpha, medicine.disease, Survival Analysis, Superficial spreading melanoma, Mutation, Lymph Node Excision, business
Abstract: International audience; Background: Targeted therapies such as BRAF and MEK inhibitors and immunotherapies have been made available to treat melanoma.Objectives: To provide an overview of the management of the French Stage III melanoma population after complete lymph node resection prior to new adjuvant therapies.Materials and methods: A subgroup data analysis.Results: Data from 1,835 patients were analysed (15.58% Stage IIIA, 39.24% Stage IIIB, 43.92% Stage IIIC and 1.25% Stage IIID). Superficial spreading melanoma was the most frequent (70.98% in Stage IIIA for whom mutation analysis was performed; BRAF mutation was identified in up to 62% Stage IIIA patients). Sentinel lymph node biopsy was performed in 88.46% of Stage IIIA patients, 42.36% of Stage IIIB, 53.97% of Stage IIIC and 34.78% of Stage IIID. Up to 80% of Stage IIIA patients had no adjuvant treatment follow-up. Ulceration (p = 0.004; RR: 2.98; 95% CI: 1.4-6.3) and age at diagnosis (p = 0.0002; RR: 1.04; 95% CI: 1.02-1.06) were significant predictive factors for survival. Adjuvant interferon-α was administered in up to 13.04% of Stage IIID patients.Conclusion: Only a small number of Stage III melanoma patients were treated with interferon-α in adjuvant settings. New adjuvant therapies are currently having an effect on clinical practice in France, increasing survival and decreasing cost.
Published: 2020

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

Author: Frank, Sophie, Carton, Matthieu, Dubot, Coraline, Campone, Mario, Pistilli, Barbara, Dalenc, Florence, Mailliez, Audrey, Lévy, Christelle, D'Hondt, Veronique, Debled, Marc, Vermeulin, Thomas, Coudert, Benoit, Perrin, Christophe, Gonçalves, Anthony, Uwer, Lionel, Ferrero, Jean-Marc, Eymard, Jean-Christophe, Petit, Thierry, Mouret-Reynier, Marie-Ange, Patsouris, Anne, Guesmia, Tahar, Bachelot, Thomas, Robain, Mathieu, Cottu, Paul, D’Hondt, Véronique, Institut Curie [Paris], Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Hôpital Guillaume-et-René-Laennec [Saint-Herblain], Institut Gustave Roussy (IGR), Département de médecine oncologique [Gustave Roussy], Institut Claudius Regaud, Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER, Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Institut du Cancer de Montpellier (ICM), Institut Bergonié [Bordeaux], Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), Centre Eugène Marquis (CRLCC), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Institut Jean Godinot [Reims], Centre Paul Strauss, CRLCC Paul Strauss, Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), Centre Léon Bérard [Lyon], Institut Curie [Saint-Cloud], French Breast Cancer Intergroup - UCBG [Paris] (R&D UNICANCER), R&D Unicancer [Paris], Cohortes épidémiologiques en population (CONSTANCES), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université de Paris (UP), Département d'Oncologie Médicale [Institut Curie, Paris], Centre de Lutte Contre le Cancer Nantes Atlantique 'René Gauducheau' (CLCC), Université Lille Nord de France (COMUE)-UNICANCER, Service d'Oncologie médicale [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Université Catholique de Louvain = Catholic University of Louvain (UCL), Service d'Oncologie Médicale, UNICANCER-UNICANCER, Hôpital Charles Nicolle [Tunis], Département d'oncologie médicale [Rennes], CRLCC Eugène Marquis (CRLCC), Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), Senescence Escape and Soluble Markers of Cancer Progression (CRCINA-ÉQUIPE 12), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Oncogénèse et progression tumorale, Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de recherche translationnelle, Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université Paris Cité (UPC), Université Côte d'Azur (UCA)-UNICANCER, and Centre hospitalier universitaire de Nantes (CHU Nantes)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes (UN)-Université d'Angers (UA)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes (UN)-Université d'Angers (UA)
Subjects: Adult, Oncology, medicine.medical_specialty, Receptor, ErbB-2, [SDV]Life Sciences [q-bio], Age at diagnosis, Breast Neoplasms, Triple Negative Breast Neoplasms, [SDV.CAN]Life Sciences [q-bio]/Cancer, lcsh:RC254-282, Cohort Studies, Metastatic disease, 03 medical and health sciences, Age Distribution, Breast cancer, Age, 0302 clinical medicine, Internal medicine, Overall survival, Humans, Medicine, 030212 general & internal medicine, Stage (cooking), skin and connective tissue diseases, Early Detection of Cancer, Retrospective Studies, business.industry, Cancer, General Medicine, Middle Aged, Prognosis, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, Survival Analysis, Metastatic breast cancer, Real-world data, 3. Good health, Young age, 030220 oncology & carcinogenesis, Cohort, Original Article, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Surgery, France, business
Abstract: Background Young age is a poor prognostic factor in early stage breast cancer (BC) but its value is less established in metastatic BC (MBC). We evaluated the impact of age at MBC diagnosis on overall survival (OS) across three age groups ( 60 years(y)). Methods ESME MBC database is a national cohort, collecting retrospective data from 18 participating French cancer centers between January 01, 2008 and December 31, 2014. Results Among 14 403 women included, 1077 (7.5%), 6436 (44.7%) and 6890 (47.8%) pts were 60 y respectively. Pts 60y) and triple negative subtypes (27.4 vs 14.6% in >60y), and more frequent visceral involvement (36.3 vs 29.8% in >60y). At a median follow-up of 48 months, median OS differed across age groups: 38.8, 38.4 and 35.6 months for pts 60y, respectively (p 60y, respectively (p, Highlights • Young age is a poor prognosis factor in early stage breast cancer. • Young age is associated with an aggressive presentation in metastatic breast cancer. • Young age had no impact on overall survivall in metastatic breast cancer. • Oppositely, older women (>60y) had a stightly poorer prognosis at the metastatic stage.
Published: 2020

32. Resensitization to Nivolumab after Intratumoral Chemotherapy in Recurrent Head and Neck Squamous Cell Cancer: A Report of 2 Cases

Author: Antoine Galmiche, Claude Krzisch, Jérèmie Bettoni, Bruno Chauffert, Alexandre Coutte, Aurélie Moreira, Marine Schoonaker, Aurélie Biet, Aline Houessinon, Chloé Sauzay, Université de Picardie Jules Verne (UPJV), CHirurgie, IMagerie et REgénération tissulaire de l’extrémité céphalique - Caractérisation morphologique et fonctionnelle - UR UPJV 7516 (CHIMERE), CHU Amiens-Picardie, Jonchère, Laurent, Service de Stomatologie et Chirurgie Maxillo-facial [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université - Faculté de médecine [CHU Pitié Salpétrière], Centre Eugène Marquis (CRLCC), Chemistry, Oncogenesis, Stress and Signaling (COSS), Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: 0301 basic medicine, Oncology, medicine.medical_specialty, medicine.medical_treatment, [SDV]Life Sciences [q-bio], intratumoral chemotherapy, Case Report, Intratumoral chemotherapy, lcsh:RC254-282, abscopal-like effect, 03 medical and health sciences, 0302 clinical medicine, Refractory, Internal medicine, medicine, Head and neck, nivolumab, Cetuximab, business.industry, Head and neck cancer, Immunotherapy, medicine.disease, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Head and neck squamous-cell carcinoma, [SDV] Life Sciences [q-bio], 030104 developmental biology, 030220 oncology & carcinogenesis, head and neck cancer, Nivolumab, business, medicine.drug
Abstract: International audience; The survival of patients with head and neck squamous cancer with locoregional recurrence is short if salvage surgery or radiation cannot be performed. Systemic chemotherapy based on platinum salts and cetuximab produces only partial and transient responses. Immune checkpoint inhibitors (i.e., nivolumab) lead to a low complete response rate of only about 10%, but in some cases the effects can be long-lasting. Intratumoral chemotherapy (ITC) has been proposed for patients with local recurrence of head and neck squamous cell carcinoma with an objective response rate of 27-50%. However, it often leads to peritumoral tissue necrosis, and the duration of local control is limited. Here, we present 2 patients with head and neck squamous cell cancer whose local recurrences were refractory to intravenous chemotherapy and nivolumab. ITC using nonnecrotizing molecules, associated with nivolumab, led to complete stable local and distant response. ITC seems to trigger tumor resensitization to previously ineffective immunotherapy. This combination deserves an evaluation in the framework of a prospective trial.
Published: 2020

33. Implementation of a molecular tumor board at a regional level to improve access to targeted therapy

Author: Jean-Philippe Metges, Thierry Lesimple, Solène-Florence Kammerer-Jacquet, Alexandra Lespagnol, Florent Denoual, Lise Boussemart, Julien Edeline, Edouard Le Gall, Boris Campillo-Gimenez, Ingrid Felten-Vinot, Cédric le Marechal, Héloïse Bourien, Romain Corre, Marie de Tayrac, Jean Mosser, Marie-Dominique Galibert, Centre Eugène Marquis (CRLCC), CHU Pontchaillou [Rennes], Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Institut de Génétique et Développement de Rennes (IGDR), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Service de Pathologie [Rennes] = Pathology [Rennes], and Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )
Subjects: Adult, Male, 0301 basic medicine, Oncology, medicine.medical_specialty, Adolescent, medicine.medical_treatment, [SDV.CAN]Life Sciences [q-bio]/Cancer, Molecular Targeted Therapies, Molecular tumor board, Medical Oncology, Health Services Accessibility, Targeted therapy, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Surgical oncology, Next generation sequencing, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Neoplasms, Internal medicine, medicine, Drug approval, Humans, Tumor board, Molecular Targeted Therapy, Precision Medicine, Medical prescription, Child, Aged, Retrospective Studies, Aged, 80 and over, business.industry, High-Throughput Nucleotide Sequencing, Hematology, General Medicine, Middle Aged, 3. Good health, Clinical trial, Treatment Outcome, 030104 developmental biology, Drug Resistance, Neoplasm, 030220 oncology & carcinogenesis, Female, Surgery, Personalized medicine, business
Abstract: International audience; Background With the development of precision oncology, Molecular Tumor Boards (MTB) are developing in many institutions. However, the implementation of MTB in routine clinical practice has still not been thoroughly studied. Material and methods Since the first drugs approved for targeted therapies, patient tumor samples were centralized to genomic testing platforms. In our institution, all tumor samples have been analyzed since 2014 by Next Generation Sequencing (NGS). In 2015, we established a regional MTB to discuss patient cases with 1 or more alterations identified by NGS, in genes different from those related to drug approval. We conducted a retrospective comparative analysis to study whether our MTB increased the prescriptions of Molecular Targeted Therapies (MTT) and the inclusions of patients in clinical trials with MTT, in comparison with patients with available NGS data but no MTB discussion. Results In 2014, 86 patients had UGA, but the results were not available to clinicians and not discussed in MTB. During the years 2015 and 2016, 113 patients with an UGA (unreferenced genomic alteration) were discussed in MTB. No patients with an UGA were included in 2014 in a clinical trial, versus 2 (2%) in 2015-2016. 13 patients with an UGA (12%) were treated in 2015-2016 with a MTT whereas in 2014, no patient (p = 0.001). Conclusions In this retrospective analysis, we showed that the association of large-scale genomic testing and MTB was feasible, and could increase the prescription of MTT. However, in routine clinical practice, the majority of patients with UGA still do not have access to MTT.
Published: 2020

34. Loss of SMARCB1 expression in colon carcinoma

Author: Julien Taieb, Jean-François Emile, S. Melloul, P. Laurent Puig, D. Dansette, J. Masliah-Planchon, K. Le Malicot, Julien Edeline, O. Delattre, J.-F. Mosnier, J.-M. Gornet, Côme Lepage, Patrick Texereau, Hôpital Ambroise Paré [AP-HP], Hôpital Hôtel-Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Unité de génétique et biologie des cancers (U830), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'hépato-gastroentérologie et cancérologie digestive (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Hôpital Cochin [AP-HP], Centre Eugène Marquis (CRLCC), Nutrition, Métabolismes et Cancer (NuMeCan), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), CHU Mont de Marsan, Médecine Personnalisée, Pharmacogénomique, Optimisation Thérapeutique (MEPPOT - U1147), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris-Saclay, Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Biomarqueurs et essais cliniques en Cancérologie et Onco-Hématologie (BECCOH), and Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Saclay
Subjects: Adult, Male, Cancer Research, Pathology, medicine.medical_specialty, Medullary cavity, Tumor suppressor gene, SMARCB1, [SDV.CAN]Life Sciences [q-bio]/Cancer, colon carcinoma, Young Adult, Genetics, medicine, Humans, 0501 psychology and cognitive sciences, Stage (cooking), Aged, Neoplasm Staging, 0505 law, Tissue microarray, BRAF V600E, mismatch repair deficiency, business.industry, 05 social sciences, Histology, SMARCB1 Protein, General Medicine, Middle Aged, medicine.disease, Immunohistochemistry, 3. Good health, Oncology, Medullary carcinoma, Colonic Neoplasms, 050501 criminology, Female, business, 050104 developmental & child psychology
Abstract: International audience; SMARCB1 is a tumor suppressor gene, which is part of SWI/SNF complex involved in transcriptional regulation. Recently, loss of SMARCB1 expression has been reported in gastrointestinal carcinomas. Our purpose was to evaluate the incidence and prognostic value of SMARCB1 loss in colon carcinoma (CC). Patients with stage III CC (n = 1695), and a second cohort of 23 patients with poorly differentiated CC were analyzed. Immunohistochemistry for SMARCB1 was performed on tissue microarrays, and cases with loss of expression were controlled on whole sections. Loss of SMARCB1 was compared with the clinico-pathological and molecular characteristics, and the prognostic value was evaluated. Loss of SMARCB1 was identified in 12 of 1695 (0.7%) patients with stage III CC. Whole section controls showed a complete loss in only one of these cases, corresponding to a medullary carcinoma. SMARCB1 loss was not associated with histological grade, tumor size nor survival. In the cohort of poorly differentiated CC, we detected 2/23 (8.7%) cases with loss of SMARCB1; one was rhabdoid while the other had medullary and mucinous histology. These 2 cases were deficient for MisMatched Repair (dMMR) and mutated for BRAF. SMARCB1 loss is rare in stage III CC, but appears more frequent in poorly differentiated CC.
Published: 2020

35. Recommandations françaises de stratégies thérapeutiques pour la prévention et le traitement de l’ostéoporose induite par les traitements adjuvants du cancer du sein

Author: Eric Lespessailles, Julien Paccou, Rose-Marie Javier, Didier Mayeur, Catherine Cormier, Bernard Cortet, Cyrille B. Confavreux, Karine Briot, A. Lesur, Jean-Michel Hannoun-Levi, Françoise Debiais, Béatrice Bouvard, Christophe Hennequin, Pierre Kerbrat, Marie-Hélène Vieillard, Florence Trémollières, Jacques Bonneterre, Université d'Angers (UA), Service de rhumatologie, Centre Hospitalier Universitaire de Nice (CHU Nice)-Hôpital l'Archet, Service de radiothérapie, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre Eugène Marquis (CRLCC), Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), UNICANCER, and Centre hospitalier universitaire de Poitiers (CHU Poitiers)
Subjects: 030203 arthritis & rheumatology, 03 medical and health sciences, 0302 clinical medicine, Rheumatology, [SDV]Life Sciences [q-bio], 030212 general & internal medicine, 3. Good health
Abstract: Resume Les traitements adjuvants standards du cancer du sein comme la chimiotherapie et les hormonotherapies par inhibiteurs de l’aromatase et/ou analogues de la LH-RH sont associes a un gain significatif de survie des patientes mais sont responsables d’une perte osseuse parfois importante surtout en debut de traitement. Cette perte osseuse est due a la carence estrogenique supplementaire induite par ces traitements et s’observe quel que soit le niveau densitometrique initial des patientes. L’objectif de ces recommandations est de proposer, a la suite d’une revue de la litterature, une attitude consensuelle pratique pour la prevention et le traitement de l’osteoporose chez ces patientes, entre les differentes societes savantes qui ont participe a ce travail : Societe francaise de rhumatologie (SFR), Groupe de recherche et d’Information sur les osteoporoses (GRIO), Groupe europeen d’etudes des metastases osseuses (GEMO), Association francophone pour les soins oncologiques de Support (AFSOS), Societe francaise de senologie et de pathologie mammaire (SFSPM), Societe francaise de radiotherapie oncologique (SFRO), en tenant compte des modalites de prescription et de remboursement des traitements en France. Ces recommandations concernent les femmes menopausees recevant un traitement systemique par chimiotherapie et/ou inhibiteur d’aromatase, les femmes non menopausees recevant un agoniste de LH-RH et les femmes non-menopausees presentant une amenorrhee persistante 1 an apres l’arret de la chimiotherapie. Il est recommande que toutes ces femmes aient une evaluation osseuse et une prevention des facteurs de risque de perte osseuse. Il est recommande que les patientes aux antecedents de fracture osteoporotique severe et/ou ayant un T-score −1. Ces recommandations n’abordent pas l’action anti-tumorale des bisphosphonates ou du denosumab.
Published: 2019

36. Personnalisation de la dose et du fractionnement de la radiothérapie des cancers de la tête et du cou

Author: F. Nguyen, Joël Castelli, Julian Biau, Pierre Graff, Yungan Tao, Pierre Blanchard, Département de radiothérapie [Gustave Roussy], Institut Gustave Roussy (IGR), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, 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 (UCA), 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 Eugène Marquis (CRLCC), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), CCSD, Accord Elsevier, Méthodologie et épidémiologie clinique en oncologie moléculaire (U1018 (Équipe 2)), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut Gustave Roussy (IGR), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), and 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)
Subjects: medicine.medical_specialty, medicine.medical_treatment, Planning target volume, Meta analyse, 03 medical and health sciences, 0302 clinical medicine, chimiothérapie, medicine, Radiology, Nuclear Medicine and imaging, Fractionation, Human papillomavirus, Head and neck, Radiothérapie, Nasopharyngeal cancer, [SDV.IB] Life Sciences [q-bio]/Bioengineering, Gynecology, Virus d’Epstein-Barr, Cancer des voies aérodigestives supérieures, business.industry, Head and neck cancer, Cancer du nasopharynx, medicine.disease, Altered fractionation, 3. Good health, Radiation therapy, Fractionnement, Oncology, Méta-analyse, 030220 oncology & carcinogenesis, [SDV.IB]Life Sciences [q-bio]/Bioengineering, business
Abstract: National audience; Head and neck cancers comprise a variety of tumours depending on the sub-site, for which target volumes and the prescribed doses need to be individualized according to each patient's history and presentation. This article aims at describing the main factors involved in decision-making regarding dose and volume, as well as ongoing research. Contouring and treatment guidelines, use of altered fractionation, major prognostic factors, the role of Human papillomavirus and of functional imaging will be presented and discussed.
Published: 2019

37. Apathy in depression: An arterial spin labeling perfusion MRI study

Author: Batail, Jean-Marie, Corouge, Isabelle, Combès, Benoit, Conan, Camille, Guillery-Sollier, Muriel, Vérin, Marc, Sauleau, Paul, Le Jeune, Florence, Gauvrit, Jean-Yves, Gauvrit, Jen-Yves, Robert, Gabriel, Barillot, Christian, Ferré, Jean-Christophe, Drapier, Dominique, Centre Hospitalier Guillaume Régnier [Rennes], Neuroimagerie: méthodes et applications (EMPENN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Inria Rennes – Bretagne Atlantique, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-SIGNAL, IMAGE ET LANGAGE (IRISA-D6), Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), Comportement et noyaux gris centraux = Behavior and Basal Ganglia [Rennes], Université de Rennes (UR)-Université européenne de Bretagne - European University of Brittany (UEB)-CHU Pontchaillou [Rennes]-Institut des Neurosciences Cliniques de Rennes (INCR), Laboratoire de Psychologie : Cognition, Comportement, Communication (LP3C - EA1285), Université de Bretagne Sud (UBS)-Université de Brest (UBO)-Université de Rennes 2 (UR2)-Institut Brestois des Sciences de l'Homme et de la Société (IBSHS), Université de Brest (UBO), CHU Pontchaillou [Rennes], Centre Hospitalier Universitaire [Rennes], Centre 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), Département de Neuroradiology [Rennes], MRI data acquisition was supported by the Neurinfo MRI research facility from the University of Rennes I. Neurinfo is granted by the European Union (FEDER), the French State, the Brittany Council, Rennes Metropole, Inria, Inserm and the University Hospital of Rennes. This work has been funded by Institut des Neurosciences Cliniques de Rennes (INCR). The authors thank Mr Stéphane Brousse and Mr Jacques Soulabaille for their involvement in the conduct of the study., Corouge, Isabelle, Comportement et noyaux gris centraux - EA 4712, and Université de Rennes (UR)-Institut des Neurosciences Cliniques de Rennes = Institute of Clinical Neurosciences of Rennes (INCR)
Subjects: Psychiatry and Mental health, Depressive disorder, Arterial spin labeling, [SCCO.NEUR]Cognitive science/Neuroscience, Apathy, [SCCO.NEUR] Cognitive science/Neuroscience, Perfusion MRI, Neuroimaging, Biological Psychiatry
Abstract: International audience; IntroductionApathy, as defined as a deficit in goal-directed behaviors, is a critical clinical dimension in depression associated with chronic impairment. Little is known about its cerebral perfusion specificities in depression. To explore neurovascular mechanisms underpinning apathy in depression by pseudo-continuous arterial spin labeling (pCASL) magnetic resonance imaging (MRI).MethodsPerfusion imaging analysis was performed on 90 depressed patients included in a prospective study between November 2014 and February 2017. Imaging data included anatomical 3D T1-weighted and perfusion pCASL sequences. A multiple regression analysis relating the quantified cerebral blood flow (CBF) in different regions of interest defined from the FreeSurfer atlas, to the Apathy Evaluation Scale (AES) total score was conducted.ResultsAfter confound adjustment (demographics, disease and clinical characteristics) and correction for multiple comparisons, we observed a strong negative relationship between the CBF in the left anterior cingulate cortex (ACC) and the AES score (standardized beta = −0.74, corrected p value = 0.0008).ConclusionOur results emphasized the left ACC as a key region involved in apathy severity in a population of depressed participants. Perfusion correlates of apathy in depression evidenced in this study may contribute to characterize different phenotypes of depression.
Published: 2021

38. Gestion des doses liées à l’imagerie de positionnement en radiothérapie

Author: G, Delpon, D, Lazaro, R, de Crevoisier, Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Laboratoire Modélisation et Simulation de Systèmes (LM2S), Département Métrologie Instrumentation & Information (DM2I), 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, and Centre Eugène Marquis (CRLCC)
Subjects: Organs at Risk, Positioning imaging, dosimetry, irradiation, medical imaging, Cone-Beam Computed Tomography, [PHYS.NEXP]Physics [physics]/Nuclear Experiment [nucl-ex], Radiation Dosage, dose measurement, Patient Positioning, Terminology as Topic, radioactivity, [PHYS.PHYS.PHYS-MED-PH]Physics [physics]/Physics [physics]/Medical Physics [physics.med-ph], Humans, cancer, [PHYS.PHYS.PHYS-INS-DET]Physics [physics]/Physics [physics]/Instrumentation and Detectors [physics.ins-det], treatment planning system, ionizing radiation, Image-guided radiotherapy (IGRT), Monte Carlo Method, radiotherapy, Radiotherapy, Image-Guided
Abstract: International audience; Image-guided radiotherapy (IGRT) has become a standard irradiation technique to improve the clinical outcome of patients in terms of toxicity and local control due to better targeting of radiation during the irradiation fraction. Positioning imaging systems, whether embedded or not, such as kV for 2 x 2D acquisitions and especially kVCBCT for 3D acquisitions are however irradiating in a large volume including the target volume but also healthy tissue, with a theoretical risk of increased toxicity and second cancer. It therefore appears very important both to optimize the absorbed dose due to IGRT practice but also to report it, especially in case of kVCBCT. The AAPM report published in 2018 (<< Image guidance doses delivered duringradiotherapy: Quantification, management, and reduction >>) proposes a management of image guidance doses delivered during radiotherapy. This report is the basis of this focus article that aims at giving orders of magnitude and proposing a management of image guidance doses delivered during radiotherapy inclinical practice. The dose delivered per kVCBCT is about 0.5 to 2 cGy at isocenter according to treatment site. As long as the calculation algorithms are not available in the treatment planning systems, it seems appropriate to use at least the published dose orders of magnitude. This estimate should ultimately allow the clinician to decide on the therapeutic strategy in the event of accumulation of positioning imaging sessions. (c) 2020 Societe francaise de radiotherapie oncologique (SFRO).; La radiothérapie guidée par l’image est devenue une technique standard d’irradiation permettant d’améliorer le devenir clinique des patients en termes de toxicité et de contrôle local du fait d’un meilleur ciblage du rayonnement lors de la séance d’irradiation. Les systèmes d’imagerie de positionnement, embarqués ou non, tels que les kV pour les acquisitions bidimensionnelles et surtout les tomographies coniques de basse énergie pour les acquisitions tridimensionnelles sont cependant irradiants dans un large volume comprenant le volume cible mais aussi du tissu sain, avec un risque théorique de majoration de toxicité et de second cancer. Il apparaît donc très important à la fois d’optimiser la dose délivrée par l’imagerie de contrôle de type tomographies coniques de basse énergie mais aussi de rapporter cette dose. Le rapport de l’AAPM (Association of Physicists in Medicine) publié en 2018 (« Image guidance doses delivered during radiotherapy : Quantification, management, and reduction ») propose une démarche d’optimisation et de gestion de ces doses. Ce rapport constitue la base de cette mise au point dont les objectifs sont de donner les ordres de grandeur des doses délivrées par l’imagerie de positionnement et de proposer une méthodologie de gestion de ces doses dans la pratique clinique. Une tomographie conique de basse énergie délivre approximativement 0,5 à 2 cGy à l’isocentre selon la localisation anatomique. Tant que les algorithmes de calcul ne sont pas disponibles dans les systèmes de planimétrie pour les faisceaux de positionnement, il semble adapté d’utiliser au moins les ordres de grandeur publiés. Cette estimation doit permettre au clinicien de décider de la stratégie thérapeutique en cas d’accumulation de sessions d’imagerie de positionnement.
Published: 2021

39. Intracavernous Schwannoma Characterized With 18F-FDG, 68Ga-DOTATOC, and 18F-Choline PET

Author: Isabelle Lecouillard, Julien Farce, Antoine Girard, Maxime Bretonnier, Beatrice Carsin Nicol, Centre Eugène Marquis (CRLCC), CHU Pontchaillou [Rennes], CRLCC Eugène Marquis (CRLCC), Laboratoire Traitement du Signal et de l'Image (LTSI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Male, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Schwannoma, 18F-choline, Malignancy, Octreotide, 030218 nuclear medicine & medical imaging, Choline, 68ga dotatoc, Lesion, 03 medical and health sciences, Prostate cancer, 0302 clinical medicine, Fluorodeoxyglucose F18, Positron Emission Tomography Computed Tomography, Biopsy, medicine, Organometallic Compounds, Humans, Radiology, Nuclear Medicine and imaging, Aged, Diplopia, medicine.diagnostic_test, business.industry, General Medicine, medicine.disease, 3. Good health, Radiology, medicine.symptom, business, 030217 neurology & neurosurgery, Neurilemmoma
Abstract: International audience; We report the case of a 75-year-old man with history of prostate cancer whose left intracavernous lesion was successfully characterized by 3 PETs performed successively with different tracers. This poorly characterized tumor was initially discovered on an MRI conducted to investigate an acute diplopia and slowly growing during follow-up. On 18F-FDG PET, the lesion showed no significant uptake, and no extracranial lesion was found nor did it have increased 68Ga-DOTATOC uptake. Finally, this tumor displayed a high 18F-choline uptake, and no extracranial lesion was revealed with this tracer. The diagnosis of schwannoma without malignancy criterion was proven by biopsy.
Published: 2021

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

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

41. Cardiac stereotactic ablative radiotherapy for refractory ventricular arrhythmias: A radical alternative? A narrative review of rationale and cardiological aspects

Author: Karim Benali, Antoine Da Costa, Louis Rigal, Renaud de Crevoisier, Vincent Galand, Raphaël P. Martins, Nefissa Hammache, Antoine Simon, N. Jaksic, J. Bellec, Pierre Caille, CHU Saint-Etienne, Centre 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), Imagerie Adaptative Diagnostique et Interventionnelle (IADI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), CRLCC Eugène Marquis (CRLCC), CHU Pontchaillou [Rennes], Jonchère, Laurent, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)
Subjects: medicine.medical_specialty, cardiac radioablation, medicine.medical_treatment, Catheter ablation, 030204 cardiovascular system & hematology, Radiosurgery, 03 medical and health sciences, cardiac SBRT, 0302 clinical medicine, Refractory, Ablative case, catheter ablation, medicine, Humans, Radiology, Nuclear Medicine and imaging, 030212 general & internal medicine, cardiovascular diseases, Cardiac disorders, Intensive care medicine, [SDV.IB] Life Sciences [q-bio]/Bioengineering, Radiological and Ultrasound Technology, business.industry, ventricular arrhythmias, Arrhythmias, Cardiac, Heart, refractory ventricular tachycardia, 3. Good health, Radiation therapy, cardiovascular system, Narrative review, [SDV.IB]Life Sciences [q-bio]/Bioengineering, business, cardiac sterteotactic radiotherapy
Abstract: International audience; Ventricular arrhythmias are serious life-threatening cardiac disorders. Despite many technological improvements, a non-negligible number of patients present refractory ventricular tachycardias, resistant to a catheter ablation procedure, placing these patients in a therapeutic impasse. Recently, a cardiac stereotactic radioablative technique has been developed to treat patients with refractory ventricular arrhythmias, as a bail out strategy. This new therapeutic option historically brings together two fields of expertise unknown to each other, pointing out the necessity of an optimal partnership between cardiologists and radiation oncologists. As described in this narrative review, the understanding of cardiological aspects of the technique for radiation oncologists and treatment technical aspects comprehension for cardiologists represent a major challenge for the application and the future development of this promising treatment.
Published: 2021

42. Development of multiplex digital PCR assays for the detection of PIK3CA mutations in the plasma of metastatic breast cancer patients

Author: Fanny Le Du, Florence Godey, Thibault De La Motte Rouge, Christophe Perrin, Héloïse Bourien, Angélique Brunot, Julien Corné, Véronique Diéras, Véronique Quillien, Laurence Crouzet, C. Lefeuvre-Plesse, Lucie Robert, Centre Eugène Marquis (CRLCC), Chemistry, Oncogenesis, Stress and Signaling (COSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), This work was supported by the association ‘La Vannetaise’, a French association for the prevention and awareness of cancer in women., Jonchère, Laurent, Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Molecular biology, medicine.disease_cause, Polymerase Chain Reaction, chemistry.chemical_compound, 0302 clinical medicine, Medicine, Multiplex, Digital polymerase chain reaction, Child, Cancer, 0303 health sciences, Mutation, Multidisciplinary, Screening assay, Metastatic breast cancer, 3. Good health, Oncology, Child, Preschool, 030220 oncology & carcinogenesis, Clinical validity, Female, Cell-Free Nucleic Acids, Adolescent, Class I Phosphatidylinositol 3-Kinases, Science, Breast Neoplasms, [SDV.CAN]Life Sciences [q-bio]/Cancer, Article, Young Adult, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, Biomarkers, Tumor, Genetics, Humans, neoplasms, 030304 developmental biology, Base Sequence, business.industry, Infant, Newborn, Infant, Reproducibility of Results, medicine.disease, Circulating free DNA, chemistry, Cancer research, business, Biomarkers, DNA
Abstract: With the approval of new therapies targeting the PI3K pathway, the detection of PIK3CA mutations has become a key factor in treatment management for HR+/HER2− metastatic breast cancer (MBC). We developed multiplex digital PCR (dPCR) assays to detect and quantify PIK3CA mutations. A first screening assay allows the detection of 21 mutations, with a drop-off system targeting the 542–546 hotspot mutations combined with the simultaneous detection of N345K, C420R, H1047L and H1047R mutations. In the case of a positive result, a sequential strategy based on other assays that we have developped allows for precise mutation identification. Clinical validity was determined by analyzing plasma circulating free DNA (cfDNA) from 213 HR+/HER2− MBC samples, as well as DNA extracted from 97 available matched tumors from 89 patients. Our assays have shown reliable specificity, accuracy and reproducibility, with limits of blank of three and four droplets for the screening assay. Sixty-eight patients (32%) had at least one PIK3CA mutation detectable in their plasma, and we obtained 83.1% agreement between the cfDNA analysis and the corresponding tumors. The high sensitivity and robustness of these new dPCR assays make them well-suited for rapid and cost-effective detection of PIK3CA mutations in the plasma of MBC patients.
Published: 2021

43. A new software tool for planning interventional procedures in liver cancer

Author: Antoine Petit, Yan Rolland, Chloé Rousseau, Lucas Royer, Anne Landreau, Ondine Delache, Florent Lalys, Centre Eugène Marquis (CRLCC), Therenva SAS, CHU Pontchaillou [Rennes], Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: medicine.medical_specialty, Carcinoma, Hepatocellular, Left gastric artery, medicine.medical_treatment, [SDV]Life Sciences [q-bio], 030218 nuclear medicine & medical imaging, Gastroduodenal artery, 03 medical and health sciences, 0302 clinical medicine, Hepatic Artery, medicine.artery, interventional radiology, medicine, Humans, Superior mesenteric artery, Catheter interventions, Chemoembolization, Therapeutic, liver surgery, Computed tomography angiography, medicine.diagnostic_test, business.industry, Selective internal radiation therapy, Liver Neoplasms, minimally invasive procedures, Interventional radiology, computed tomography, 3. Good health, Radiation therapy, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Surgery, Radiology, business, Software, Artery
Abstract: Introduction Intra-arterial therapy is an effective way of performing chemotherapy or radiation therapy in patients with primary liver cancer (i.e. hepatocellular carcinoma). Although this minimally invasive approach is now an established treatment option, support tools for pre-operative planning and intra-operative assistance might be helpful. Material and methods We developed an approach for semi-automatic segmentation of computed tomography angiography images of the main arterial branches (required for access path to the treatment site), automatic segmentation of the liver, arterial and venous tree, and interactive segmentation of the tumors (required for procedure-specific planning). This approach was then integrated into a liver-specific workflow within EndoSize® solution, a planning software for endovascular procedures. The main branches extraction approach was qualitatively evaluated inside the software, while the automatic segmentation methods were quantitatively assessed. Results Main branches extraction provides a success rate of 85% (i.e. all arteries correctly extracted) in a dataset of 172 patients. On public databases, a mean DICE of 0.91, 0.47 and 0.92 was obtained for liver, venous and arterial trees segmentation, respectively. Conclusions This pipeline is suitable for directly accessing the treatment site, giving anatomic measurements, and visualizing the hepatic trees, liver, and surrounding arteries during the pre-operative planning. Abbreviations HCC: hepatocellular carcinoma; TACE: transarterial chemoembolization; SIRT: selective internal radiation therapy; CT: computed tomography; CTA: computed tomography angiography; AMS: superior mesenteric artery; LGA: left gastric artery; RHA: right hepatic artery; LHA: left hepatic artery; rbHA: right branch of the hepatic artery; lbHA: left branch of the hepatic artery; GDA: gastroduodenal artery; VOI: volume of interest; SD: standard deviation; MICCAI: medical image computing and computer assisted interventions; MR: magnetic resonance.
Published: 2021

44. Impact of systematic whole-body 18F-fluorodeoxyglucose PET/CT on the management of patients suspected of infective endocarditis: the prospective multicenter TEPvENDO study

Author: Xavier, Duval, Vincent, Le Moing, Sarah, Tubiana, Marina, Esposito-Farèse, Emila, Ilic-Habensus, Florence, Leclercq, Aurélie, Bourdon, François, Goehringer, Christine, Selton-Suty, Elodie, Chevalier, David, Boutoille, Nicolas, Piriou, Thierry, Le Tourneau, Catherine, Chirouze, Marie-France, Seronde, Olivier, Morel, Lionel, Piroth, Jean-Christophe, Eicher, Olivier, Humbert, Matthieu, Revest, Elise, Thébault, Anne, Devillers, François, Delahaye, André, Boibieux, Bastien, Grégoire, Bruno, Hoen, Cédric, Laouenan, Bernard, Iung, François, Rouzet, Ophélie, Rogier, CIC - CHU Bichat, Institut National de la Santé et de la Recherche Médicale (INSERM), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Université Sorbonne Paris Nord, Université de Montpellier (UM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service de Cardiologie [CHRU Nancy], Centre hospitalier universitaire de Nantes (CHU Nantes), Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Marqueurs pronostiques et facteurs de régulations des pathologies cardiaques et vasculaires - UFC ( EA 3920) (PCVP / CARDIO), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Centre d'Investigation Clinique 1432 (Dijon) - Module Plurithématique : Périnatalité Cancérologie Handicap et Ophtalmologie (CIC-P803), Institut National de la Santé et de la Recherche Médicale (INSERM)-Direction Générale de l'Organisation des Soins (DGOS)-Université de Bourgogne (UB), Centre de génétique - Centre de référence des maladies rares, anomalies du développement et syndromes malformatifs (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), CHU Dijon, CHU Pontchaillou [Rennes], ARN régulateurs bactériens et médecine (BRM), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Eugène Marquis (CRLCC), Hospices Civils de Lyon (HCL), Service de Maladies Infectieuses et Tropicales [Hôpital de la Croix-Rousse - HCL], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), 13549-P130938, French Ministry of Health, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Unité de recherche de l'institut du thorax (ITX-lab), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Laboratoire Chrono-environnement (UMR 6249) (LCE), Marqueurs pronostiques et facteurs de régulations des pathologies cardiaques et vasculaires - UFC ( UR 3920) (PCVP / CARDIO), Université de Bourgogne (UB)-Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), and Jonchère, Laurent
Subjects: Microbiology (medical), medicine.medical_specialty, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, 18F-FDG-PET/CT, 030204 cardiovascular system & hematology, Tertiary care, Duke criteria, Fluorodeoxyglucose PET, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Fluorodeoxyglucose F18, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Positron Emission Tomography Computed Tomography, diagnostic impact, medicine, Humans, 030212 general & internal medicine, Prospective Studies, patient management, Prosthetic valve, Endocarditis, business.industry, infective endocarditis, medicine.disease, Diagnostic classification, 3. Good health, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Infectious Diseases, [SDV.IB.IMA] Life Sciences [q-bio]/Bioengineering/Imaging, Native valve, Infective endocarditis, Heart Valve Prosthesis, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Radiology, Radiopharmaceuticals, Whole body, business
Abstract: BackgroundDiagnostic and patients’ management modifications induced by whole-body 18F-FDG-PET/CT had not been evaluated so far in prosthetic valve (PV) or native valve (NV) infective endocarditis (IE)-suspected patients.MethodsIn sum, 140 consecutive patients in 8 tertiary care hospitals underwent 18F-FDG-PET/CT. ESC-2015-modified Duke criteria and patients’ management plan were established jointly by 2 experts before 18F-FDG-PET/CT. The same experts reestablished Duke classification and patients’ management plan immediately after qualitative interpretation of 18F-FDG-PET/CT. A 6-month final Duke classification was established.ResultsAmong the 70 PV and 70 NV patients, 34 and 46 were classified as definite IE before 18F-FDG-PET/CT. Abnormal perivalvular 18F-FDG uptake was recorded in 67.2% PV and 24.3% NV patients respectively (P < .001) and extracardiac uptake in 44.3% PV and 51.4% NV patients. IE classification was modified in 24.3% and 5.7% patients (P = .005) (net reclassification index 20% and 4.3%). Patients’ managements were modified in 21.4% PV and 31.4% NV patients (P = .25). It was mainly due to perivalvular uptake in PV patients and to extra-cardiac uptake in NV patients and consisted in surgery plan modifications in 7 patients, antibiotic plan modifications in 22 patients and both in 5 patients. Altogether, 18F-FDG-PET/CT modified classification and/or care in 40% of the patients (95% confidence interval: 32–48), which was most likely to occur in those with a noncontributing echocardiography (P < .001) or IE classified as possible at baseline (P = .04), while there was no difference between NV and PV.ConclusionsSystematic 18F-FDG-PET/CT did significantly and appropriately impact diagnostic classification and/or IE management in PV and NV-IE suspected patients.Clinical Trials RegistrationNCT02287792.
Published: 2021

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

Author: Celine Garrec, Monique Mozelle-Nivoix, Jérôme Lemonnier, Etienne Rouleau, Tan Dat Nguyen, Dominique Vaur, Elodie Lacaze, Sarah Bonnet-Boissinot, Sophie Nambot, Jean Chiesa, Sophie Giraud, Dominique Stoppa-Lyonnet, Michel Longy, Alain Lortholary, Jean-Marc Rey, Olivier Caron, Christine Lasset, Claude Houdayer, Christine Maugard, Virginie Bubien, Véronique Mari, Marie-Emmanuelle Morin-Meschin, Nadine Andrieu, Nancy Uhrhammer, Louise Crivelli, Hélène Dreyfus, Vincent Goussot, Stephanie Chieze-Valéro, Nicolas Sevenet, Lisa Golmard, Séverine Eon-Marchais, Mathilde Martinez, Isabelle Coupier, Marie-Gabrielle Dondon, Odile Béra, Paul Vilquin, Capucine Delnatte, Odile Cohen-Haguenauer, Cornel Popovici, Christine Toulas, Laurence Gladieff, Marie-Agnès Collonge-Rame, Chrystelle Colas, Paul Gesta, Catherine Noguès, Fanny Brayotel, Audrey Mailliez, Fabienne Lesueur, Julie Tinat, Marie Bidart, Yves-Jean Bignon, Florence Coulet, Nadia Boutry-Kryza, Fabienne Prieur, Juana Beauvallet, Philippe Denizeau, Cancer et génome: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, Institut Curie [Paris]-MINES ParisTech - École nationale supérieure des mines de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Curie [Paris], Institut Gustave Roussy (IGR), Génétique (Biologie pathologie), Département de biologie et pathologie médicales [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Hôtel-Dieu de Nantes, CHU Rouen, Normandie Université (NU), Institut Claudius Regaud, Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Jean Godinot [Reims], UNICANCER, Centre Eugène Marquis (CRLCC), Institut de Cancérologie de Strasbourg Europe (ICANS), Centre Paul Strauss, CRLCC Paul Strauss, Institut Bergonié [Bordeaux], Actions for OnCogenesis understanding and Target Identification in ONcology (ACTION), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Bordeaux Segalen - Bordeaux 2-Institut Bergonié [Bordeaux], UNICANCER-UNICANCER, Centre Hospitalier Georges Renon [Niort] (CH Georges Renon Niort), Genetic and Immunology Medical Institute (GIMI), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), CHU de Saint-Étienne Hôpital Nord [Saint Etienne], Hôpital Nord (Saint Etienne), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), CHU Bordeaux [Bordeaux], Centre Catherine-de-Sienne [Nantes] (CCS), Hôpital privé du Confluent [Nantes], Institut Sainte Catherine [Avignon], hôpital couple-enfant [CHU Grenoble Alpes], Centre Hospitalier Universitaire [Grenoble] (CHU), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre Hospitalier de Troyes, Hospices Civils de Lyon (HCL), Groupement Hospitalier Lyon-Est (GHE), Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Hôpital Sud [CHU Rennes], CHU Pontchaillou [Rennes], Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA), Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), Immunologie humaine, physiopathologie & immunothérapie (HIPI (UMR_S_976 / U976)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université Lille Nord de France (COMUE)-UNICANCER, Hôpital Arnaud de Villeneuve [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut de recherche en cancérologie de Montpellier (IRCM - U896 Inserm - UM1), Université Montpellier 1 (UM1)-CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Groupe Hospitalier du Havre, CHU de la Martinique [Fort de France], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CRLCC René Gauducheau, Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Centre Léon Bérard [Lyon], Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de génétique et biologie des cancers (U830), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Centre médical de Bligny, Onco-génétique, Département de médecine oncologique [Gustave Roussy], COLO, Mouniati, Mines Paris - PSL (École nationale supérieure des mines de Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), UNICANCER-UNICANCER-Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de médecine génomique et d’immunothérapie (Genomic and Immunotherapy Medical Institute) (institut GIMI), UNICANCER-UNICANCER-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-FHU TRANSLAD (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Université de Lille-UNICANCER, Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), UNICANCER-UNICANCER-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-FHU TRANSLAD (CHU de Dijon), and Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)
Subjects: 0301 basic medicine, Cancer Research, medicine.medical_specialty, Sequencing data, [SDV.CAN]Life Sciences [q-bio]/Cancer, Context (language use), [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, [SDV.MHEP.GEO]Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, 030105 genetics & heredity, Article, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Care plan, Internal medicine, Epidemiology, medicine, RC254-282, Genetic testing, medicine.diagnostic_test, business.industry, Cancer, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, 3. Good health, genetic predisposition to breast and ovarian cancer, [SDV.MHEP.GEO] Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Oncology, 030220 oncology & carcinogenesis, multigene panels, Cancer risk, Ovarian cancer, business, cancer risk estimate, penetrance of pathogenic variants
Abstract: Simple Summary TUMOSPEC was designed for estimating the risk of cancer for carriers of a predicted pathogenic variant (PPV) in a gene usually tested in a hereditary breast and ovarian cancer context. Index cases are enrolled consecutively among patients who undergo genetic testing as part of their care plan in France. First- and second-degree relatives and cousins of PPV carriers are invited to participate whether they are affected by cancer or not, and are tested for the familial PPV. Genetic, clinical, family and epidemiological data are centralized at the coordinating centre. The three-year feasibility study included 4431 prospective index cases, with 19.1% of them carrying a PPV. This showed that the study logistics are well adapted to clinical and laboratory constraints, and collaboration between partners (clinicians, biologists, coordinating centre and participants) is smooth. Hence, TUMOSPEC is being pursued, with the aim of optimizing clinical management guidelines specific to each gene. Abstract Assessment of age-dependent cancer risk for carriers of a predicted pathogenic variant (PPV) is often hampered by biases in data collection, with a frequent under-representation of cancer-free PPV carriers. TUMOSPEC was designed to estimate the cumulative risk of cancer for carriers of a PPV in a gene that is usually tested in a hereditary breast and ovarian cancer context. Index cases are enrolled consecutively among patients who undergo genetic testing as part of their care plan in France. First- and second-degree relatives and cousins of PPV carriers are invited to participate whether they are affected by cancer or not, and genotyped for the familial PPV. Clinical, family and epidemiological data are collected, and all data including sequencing data are centralized at the coordinating centre. The three-year feasibility study included 4431 prospective index cases, with 19.1% of them carrying a PPV. When invited by the coordinating centre, 65.3% of the relatives of index cases (5.7 relatives per family, on average) accepted the invitation to participate. The study logistics were well adapted to clinical and laboratory constraints, and collaboration between partners (clinicians, biologists, coordinating centre and participants) was smooth. Hence, TUMOSPEC is being pursued, with the aim of optimizing clinical management guidelines specific to each gene.
Published: 2021

46. Dual-time point brain FDG PET to differentiate tumor progression from radionecrosis after stereotactic radiotherapy for brain metastases

Author: M. Bilal Chawki, J. Farce, A. Girard, D. Mariano Goulart, Florent Cachin, F. Lejeune, M. Chanchou, H. Otman, Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER, Département de médecine nucléaire [Rennes], CRLCC Eugène Marquis (CRLCC), Service de Médecine Nucléaire [Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA), Université Clermont Auvergne (UCA), Hôpital Lapeyronie [Montpellier] (CHU), Centre Eugène Marquis (CRLCC), and Service de Médecine Nucléaire [CHRU Nancy]
Subjects: Radiological and Ultrasound Technology, business.industry, Significant difference, Biophysics, [SDV.IB.MN]Life Sciences [q-bio]/Bioengineering/Nuclear medicine, Visual scale, 030218 nuclear medicine & medical imaging, Cochran's Q test, Lesion, Stereotactic radiotherapy, 03 medical and health sciences, 0302 clinical medicine, Tumor progression, 030220 oncology & carcinogenesis, medicine, Radiology, Nuclear Medicine and imaging, Medical diagnosis, medicine.symptom, Nuclear medicine, business, ComputingMilieux_MISCELLANEOUS, Dual time point
Abstract: Introduction Dual phase 18[F]-FDG brain PET (dual-PET) is useful to distinguish tumor recurrence (TR) from radionecrosis (RN) after stereotaxic radiosurgery (SRS) of brain metastases, when contrast-enhanced MRI is inconclusive. We aimed to compare six different visual and quantitative interpretation criteria to enhance diagnostic performances. Materials and methods In this retrospective french multicentric study (Clermont-Ferrand, Montpellier, Rennes), we evaluated 45 patients previously treated with SRS for BM, addressed for a dual-PET by the local neuro-oncological committees for an evolving lesion on MRI inconclusive between TR and RN, at least 3 months after the last SRS session. Dual-PET included both an “early” and a “delayed” acquisition, respectively 30 to 60 minutes and 4 to 5 hours after 18[F]-FDG injection. After measuring SUVmax values of both lesion (L) and mirror contralateral grey matter (GM) at early (1) and delayed (2) acquisitions, three quantitative metrics were calculated: ratios of L SUVmax to GM SUVmax at “early” (L1/GM1) and “delayed” (L2/GM2) acquisitions and the retention index which is the variation over time of the standardized SUVmax ratio (RI = [(Delayed-Early)/Early]). Visual analysis was also conducted using a subjective 6 points visual scale of the lesion uptake at both acquisitions. The five interpretation criteria were compared according to their area under the ROC curve (AUC), and to their diagnostic accuracy applying the best cut off value (maximizing the Youden's index) by the Cochran Q test. The final diagnosis was based on pathology, or by default radiological and clinical follow-up criteria after at least 6 months. Results Final diagnoses were TR for 24 patients and RN for 21 patients. There was no statistically significant difference regarding AUC between the different interpretation methods. AUC ranged from 0,78 [95 %CI 0,63; 0,89] with the L1/GM1 Ratio, to 0.85 [95 %CI 0.72; 0.94] with the L2/GM2 ratio. Visual analyses AUC were excellent at both early (0.835 [95 %CI 0.7; 0.93]) and delayed acquisitions (0.83 [95 %CI 0.69; 0.92]). There was no statistically significant difference between accuracies (p = 0.87) ranging from 0.71 with the RI ratio to 0.80 with both the “delayed” visual and quantitative analyses. Conclusion Dual-PET protocol distinguishes RN and TR after SRS with robust diagnostic performances in case of doubtful MR, with an accuracy up to 80 %.
Published: 2021

47. Analysis of Mesencephalic Astrocyte-derived Neurotrophic Factor in Multiple Myeloma

Author: Antoine Galmiche, Christophe Louandre, Yves-Edouard Herpe, Chloé Sauzay, Amandine Dernoncourt, Cathy Gomila, Pierre Duhaut, Jean Schmidt, V. Salle, Zuzana Saidak, CHU Amiens-Picardie, Centre Eugène Marquis (CRLCC), Chemistry, Oncogenesis, Stress and Signaling (COSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Médecine Interne [CHU Amiens-Picardie], Réseau d'Epidémiologie Clinique International Francophone [Amiens] (RECIF Amiens), Université de Picardie Jules Verne (UPJV)-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), HEMATIM - Hématopoïèse et immunologie - UR UPJV 4666 (HEMATIM), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de dermatologie [CHU d'Amiens-Picardie], Mécanismes physiopathologiques et conséquences des calcifications vasculaires - UR UPJV 7517 (MP3CV), and Biobanque de Picardie [CHU Amiens - Hôpital Sud]
Subjects: Adult, Cancer Research, [SDV]Life Sciences [q-bio], Monoclonal Gammopathy of Undetermined Significance, Pathogenesis, Young Adult, Downregulation and upregulation, Neurotrophic factors, Cell Line, Tumor, Medicine, cancer, Humans, Computer Simulation, Nerve Growth Factors, Multiple myeloma, Aged, Retrospective Studies, Aged, 80 and over, business.industry, General Medicine, unfolded protein response, Middle Aged, medicine.disease, Up-Regulation, Gene Expression Regulation, Neoplastic, mesencephalic astrocyte-derived neurotrophic factor, medicine.anatomical_structure, Oncology, Cell culture, Case-Control Studies, Cancer research, Biomarker (medicine), biomarker, business, Multiple Myeloma, Monoclonal gammopathy of undetermined significance, Astrocyte
Abstract: International audience; Background/Aim: Multiple myeloma (MM) is characterized by high production of immunoglobulins resulting in a constant source of endoplasmic reticulum (ER)-stress. Mesencephalic astrocyte-derived neurotrophic factor (MANF) was identified as a possible circulating biomarker that could help in monitoring ER-stress mediated diseases. Materials and Methods: To assess the relevance of MANF in MM, we performed in silico and in vitro analysis in malignant cell lines including the myeloma cell line RPMI 8226. Serum MANF concentration was compared between healthy subjects (n=60), patients with MM (n=68), or those with monoclonal gammopathy of undetermined significance (MGUS) (n=73). Results: MANF mRNA expression was upregulated in the RPMI 8226 cell line, and higher secretion of MANF was measured in RPMI 8226 supernatant. Serum MANF levels were not significantly different between MM or MGUS patients and those in age-and sex-matched healthy controls. Conclusion: MANF was not validated as a biomarker of interest in MM patients. Its potential implication in myeloma pathogenesis should be investigated.
Published: 2021

48. Alpelisib and fulvestrant efficacy in HR-positive HER2-negative PIK3CA -mutant advanced breast cancer: Data from the French early access program

Author: Bertucci, F., Bello, Diana, Bertucci, Alexandre, de La Motte Rouge, Thibault, Blonz, Cyriac, Akla, Sarra, Grenier, Julien, Bailleux, Caroline, Benderra, Marc Antoine, Simon, Helene, Desmoulins, Isabelle, Tharin, Zoé, Renaud, Emmanuelle, Delaloge, Suzette, Bertho, Marion, Cottu, Paul, Goncalves, Anthony, Bidard, François-Clément, Lerebours, Florence, 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), Centre Eugène Marquis (CRLCC), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Université Paris Cité (UPCité), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), Département d'oncologie médicale [Centre Georges-François Leclerc], UNICANCER-UNICANCER, Institut Gustave Roussy (IGR), Pathologie mammaire, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), and Institut Curie [Paris]
Subjects: Oncology, Cancer Research, medicine.medical_specialty, Fulvestrant, business.industry, Advanced breast, Mutant, HER2 negative, [SDV.CAN]Life Sciences [q-bio]/Cancer, Cancer data, Internal medicine, medicine, business, medicine.drug
Abstract: 1064 Background: In 11.2018, the PIK3CA-inhibitor alpelisib was made available in France through an early access program (EAP), in combination with fulvestrant in pre-treated PIK3CA-mutant, HR-positive, HER2-negative advanced breast cancer (ABC) patients. Patients had to received two or more prior systemic treatments for ABC, including an aromatase inhibitor and a CDK4/6 inhibitor in the absence of contraindications. This retrospective real-life, EAP-based study aimed to assess the efficacy and safety of alpelisib/fulvestrant combination in the post CDK4/6 inhibitor setting. Methods: The IRB-approved protocol and call for data were sent on 10.2020 to the cancer centers which participated the most in the EAP prospective registry. Eligible patients were women who started alpelisib/fulvestrant between 11. 2018 and 10.2020 as part of the EAP (which excluded patients with visceral crisis or inflammatory BC). Alpelisib and fulvestrant were used at standard doses. Primary endpoint was PFS by local investigators using RECIST1.1. Secondary endpoints included objective response rate and safety (NCI CTCAE v5.0). Results: 10 centers provided individual data regarding 209 consecutive patients. Patients had received a median number of 4 (1-14) previous systemic treatments for ABC, including CDK4/6 inhibitors, chemotherapy, fulvestrant (alone or in combination) and everolimus for 206 (98.8%), 159 (76.1%), 163 (78%) and 123 (58.8%) patients, respectively. With a median FU of 7.0 months, median PFS was 4.0 months (95%CI [3.5;5.0]) and 35.4% of 164 evaluable patients had an objective response. After stratification on the number of prior lines of treatment, prior exposure to everolimus had no impact on PFS (mPFS in the 123 patients pretreated with everolimus: 4.0m, 95%CI [3.5-5.5]). Of note, this population was enriched in patients who had a long disease control by everolimus (median time spent on everolimus: 7.0m, range (6.5-9.0)). In multivariable analysis, characteristics significantly associated with longer PFS were PS < 3 (HR = 0.03, 95%CI [0.02-0.29]) and prior treatment with fulvestrant (HR = 0.53, 95%CI [0.32-0.89]). N = 81(38.8%) patients discontinued alpelisib due to adverse events (AEs). Most frequent grade 3/4 AEs were hyperglycemia, skin rash, diarrhea and fatigue occurring in 13.4, 8.1, 4.8 and 1.9 % of patients, respectively. Conclusions: Despite heavy pre-treatments, alpelisib +fulvestrant had a clinically relevant efficacy in the French EAP population. Interestingly, prior treatment with either everolimus or fulvestrant did not overtly impair alpelisib-fulvestrant efficacy. The best treatment sequence for PI3KCA/mTOR inhibitors could be examined in future trials in PIK3CA-mutant ER+/HER2- ABC patients.
Published: 2021

49. Impact of Neck Dissection in Head and Neck Squamous Cell Carcinomas of Unknown Primary

Author: Jessica Miroir, Yungan Tao, M. Doré, Shakeel Sumodhee, Nicolas Blanchard, A. Beddok, Alexandre Coutte, Matthieu Caubet, C. Pflumio, Julia Salleron, Jean-Christophe Faivre, Juliette Thariat, S. Servagi-Vernat, Valentin Calugaru, Joël Castelli, X. Sun, I. Troussier, Paul Giraud, Vincent Roth, Bruno Toussaint, Marco Krengli, J. Khalifa, Duc Trung Nguyen, Claire Petit, Florent Carsuzaa, Yazan Abu-Shama, Lionel Geoffrois, Edouard Romano, Charles Dupin, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), UNICANCER, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre Hospitalier Universitaire de Nice (CHU Nice), Institut Gustave Roussy (IGR), Département de radiothérapie [Gustave Roussy], Institut Curie [Paris], Institut Jean Godinot [Reims], Centre Eugène Marquis (CRLCC), Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), Università degli Studi del Piemonte Orientale - Amedeo Avogadro (UPO), Service d'oncologie-radiothérapie [CHU Tenon], CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), Clinique des Dentellières [Valenciennes, France], CHU Amiens-Picardie, CHU Bordeaux [Bordeaux], Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Easy Global Market [Sophia-Antipolis], Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), and UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)
Subjects: Cancer Research, medicine.medical_specialty, medicine.medical_treatment, Urology, [SDV.CAN]Life Sciences [q-bio]/Cancer, Article, Chemoradiotherapy, Head and neck, Neck dissection, Neoplasms/cancers/carcinomas, Prognosis, Unknown primary, chemoradiotherapy, head and neck, 03 medical and health sciences, 0302 clinical medicine, neoplasms/cancers/carcinomas, medicine, Stage (cooking), 030223 otorhinolaryngology, neck dissection, RC254-282, Chemotherapy, business.industry, Incidence (epidemiology), Neoplasms. Tumors. Oncology. Including cancer and carcinogens, 3. Good health, Radiation therapy, Oncology, 030220 oncology & carcinogenesis, unknown primary, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Lymphadenectomy, prognosis, business, Adenectomy
Abstract: International audience; Simple Summary: A retrospective multicentric study of 322 patients with head and neck cancers of unknown primary (HNCUP) was performed testing the impact of neck dissection (ND) extent on nodal relapse, progression-free survival and survival. After 5 years, the incidence of nodal relapse was 13.4%, and progression-free survival (PFS) was 59.1%. In multivariate analysis after adjusting for nodal stage, the risk of nodal relapse or progression was reduced with lymphadenectomy, selective ND or radical/modified ND but survival rates were similar. Patients undergoing lymphadenectomy or ND had significantly better PFS and a lower nodal relapse incidence in the N1 + N2a group, but the improvement was not significant for the N2b or N2 + N3c patients. Severe toxicity rates exceeded 40% with radical ND. In HNCUP, ND improves PFS regardless of nodal stage but fails to improve survival. The magnitude of the benefit of ND did not appear to depend on ND extent and decreased with a more advanced nodal stage.Abstract: Purpose: Management of head and neck cancers of unknown primary (HNCUP) combines neck dissection (ND) and radiotherapy, with or without chemotherapy. The prognostic value of ND has hardly been studied in HNCUP.Methods: A retrospective multicentric study assessed the impact of ND extent (adenectomy, selective ND, radical/radical-modified ND) on nodal relapse, progression-free survival (PFS) or survival, taking into account nodal stage. Results: 53 patients (16.5%) had no ND, 33 (10.2%) had lymphadenectomy, 116 (36.0%) underwent selective ND and 120 underwent radical/radical-modified ND (37.3%), 15 of which received radical ND (4.7%). With a 34-month median follow-up, the 3-year incidence of nodal relapse was 12.5% and progression-free survival (PFS) 69.1%. In multivariate analysis after adjusting for nodal stage, the risk of nodal relapse or progression was reduced with lymphadenectomy, selective or radical/modified ND, but survival rates were similar. Patients undergoing lymphadenectomy or ND had a better PFS and lowered nodal relapse incidence in the N1 + N2a group, but the improvement was not significant for the N2b or N2 + N3c patients. Severe toxicity rates exceeded 40% with radical ND. Conclusion: In HNCUP, ND improves PFS, regardless of nodal stage. The magnitude of the benefit of ND does not appear to depend on ND extent and decreases with a more advanced nodal stage
Published: 2021
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50. Trifluridine/tipiracil in combination with oxaliplatin and either bevacizumab or nivolumab in metastatic colorectal cancer: a dose-expansion, phase I study

Author: Ronan Fougeray, Mark P Saunders, Catherine Leger, Antoine Hollebecque, Laetitia Dahan, Gerald W. Prager, Julien Edeline, Alexander Stein, Gábor Rubovszky, Alessandra Auriemma, Zsuzsanna Papai, Roberto Bordonaro, Aitana Calvo, Antonio Cubillo, Guillem Argiles, V. Cattan, Thierry André, Nadia Amellal, Josep Tabernero, ARNAS 'Garibaldi, S. Luigi-Currò, Ascoli-Tomaselli', Hospital General Universitario 'Gregorio Marañón' [Madrid], University of Verona (UNIVR), Département d’Innovation Thérapeutique et essais précoces [Gustave Roussy] (DITEP), Institut Gustave Roussy (IGR), National Institute of Oncology [Budapest, Hungary], The Christie NHS Foundation Trust [Manchester, Royaume-Uni], Medizinische Universität Wien = Medical University of Vienna, Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), 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), Vall d'Hebron Institute of Oncology [Barcelone] (VHIO), Vall d'Hebron University Hospital [Barcelona], Hospital Universitario HM Sanchinarro [Madrid, Spain], 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 Eugène Marquis (CRLCC), Institut de Recherches Internationales Servier [Suresnes] (IRIS), Università degli studi di Verona = University of Verona (UNIVR), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), 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), Gestionnaire, HAL Sorbonne Université 5, Service d'Oncologie Médicale [CHU Saint-Antoine], 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 Català de la Salut, [Bordonaro R] Azienda Ospedaliera ARNAS Garibaldi, Catania, Italy. [Calvo A] Gregorio Marañon University General Hospital, Madrid, Spain. [Auriemma A] Azienda Ospedaliera Universitaria Integrat, University of Verona, Verona, Italy. [Hollebecque A] Drug Development Department, Gustave Roussy Cancer Campus, Villejuif, France. [Rubovszky G] Department of Medical Oncology and Clinical Pharmacology, National Institute of Oncology Hungary, Budapest, Hungary. [Saunders MP] Christie NHS Foundation Trust, Manchester, UK. [Argilés G] Vall d'Hebron Hospital Universitari, Barcelona, Spain. Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Tabernero J] Vall d'Hebron Hospital Universitari, Barcelona, Spain. Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain. UVic-UCC, IOB-Quiron, Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus
Subjects: Cancer Research, Pyrrolidines, Colorectal cancer, Other subheadings::Other subheadings::/drug therapy [Other subheadings], Otros calificadores::Otros calificadores::/efectos adversos [Otros calificadores], Gastroenterology, Trifluridine, trifluridine/tipiracil, Còlon - Càncer - Tractament, chemistry.chemical_compound, 0302 clinical medicine, Antineoplastic Combined Chemotherapy Protocols, Original Research, metastatic colorectal cancer, terapéutica::terapéutica::farmacoterapia::protocolos antineoplásicos::terapéutica::farmacoterapia::protocolos de quimioterapia antineoplásica combinada [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, neoplasias::neoplasias por localización::neoplasias del sistema digestivo::neoplasias gastrointestinales::neoplasias intestinales::neoplasias colorrectales [ENFERMEDADES], 3. Good health, [SDV.SP] Life Sciences [q-bio]/Pharmaceutical sciences, Bevacizumab, Nivolumab, Oncology, 030220 oncology & carcinogenesis, Cohort, medicine.symptom, Colorectal Neoplasms, medicine.drug, medicine.medical_specialty, Nausea, Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores], [SDV.CAN]Life Sciences [q-bio]/Cancer, Neutropenia, fluoropyrimidines, Quimioteràpia combinada, 03 medical and health sciences, Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Gastrointestinal Neoplasms::Intestinal Neoplasms::Colorectal Neoplasms [DISEASES], [SDV.CAN] Life Sciences [q-bio]/Cancer, Therapeutics::Therapeutics::Drug Therapy::Antineoplastic Protocols::Therapeutics::Drug Therapy::Antineoplastic Combined Chemotherapy Protocols [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], Internal medicine, Recte - Càncer - Tractament, Other subheadings::Other subheadings::/adverse effects [Other subheadings], medicine, Humans, Tipiracil, business.industry, oxaliplatin, medicine.disease, Oxaliplatin, chemistry, business, Thymine, 030215 immunology
Abstract: Background In preclinical studies trifluridine/tipiracil (FTD/TPI) plus oxaliplatin (Industriestrasse, Holzkirchen, Germany) sensitised microsatellite stable (MSS) metastatic colorectal cancer (mCRC) to anti-programmed cell death protein-1; the addition of oxaliplatin or bevacizumab (F Hoffmann- la ROCHE AG, Kaiseraugst, Switzerland) enhanced the antitumour effects of FTD/TPI. This study aimed to investigate the safety and efficacy of FTD/TPI plus oxaliplatin and either bevacizumab or nivolumab (Uxbridge business Park, Uxbridge, United Kingdom) in patients with mCRC who had progressed after at least one prior line of treatment. Patients and methods In 14-day cycles, patients received FTD/TPI 35 mg/m2 (twice daily, days 1-5) plus oxaliplatin 85 mg/m2 (day 1), and, on day 1, either bevacizumab 5 mg/kg (cohort A) or nivolumab 3 mg/kg (cohort B). Patients in Cohort B had confirmed MSS status. Results In total, 54 patients were enrolled: 37 in cohort A and 17 in cohort B. Recruitment in cohort B was stopped early due to the low response rate (RR) observed at interim analyses of efficacy. The most common adverse events (AEs) in cohort A were neutropenia/decreased neutrophils (75.7%), nausea (59.5%), vomiting (40.5%), diarrhoea (37.8%), peripheral sensory neuropathy (37.8%), fatigue (35.1%) and decreased appetite (35.1%). In cohort B, the most common AEs were neutropenia/decreased neutrophils (70.6%), diarrhoea (58.8%), nausea (47.1%), vomiting (47.1%), fatigue (47.1%), asthenia (41.2%), paraesthesia (41.2%), thrombocytopenia/decreased platelets (35.3%) and decreased appetite (35.3%). Confirmed objective RR was 17.1% in cohort A and 7.1% in cohort B; the corresponding values for median progression-free survival in the two cohorts were 6.3 and 6.0 months. Conclusion FTD/TPI plus oxaliplatin and bevacizumab or nivolumab had an acceptable safety profile and demonstrated antitumour activity in previously treated patients with mCRC., Highlights • This study evaluated the safety and efficacy of FTD/TPI plus oxaliplatin and either bevacizumab or nivolumab in mCRC patients. • FTD/TPI plus oxaliplatin in combination with bevacizumab or nivolumab had an acceptable and manageable safety profile. • Antitumour activity was observed following treatment with FTD/TPI plus oxaliplatin and bevacizumab. • Despite a modest RR with the addition of nivolumab, survival data were promising in these poor-prognosis patients.
Published: 2021

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