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1. Constitutive or Induced HIF-2 Addiction is Involved in Resistance to Anti-EGFR Treatment and Radiation Therapy in HNSCC

Author: Coliat, Pierre, Ramolu, Ludivine, Jégu, Jérémie, Gaiddon, Christian, Jung, Alain, Pencreach, Erwan, Equipe 2 'Réponse au Stress Cellulaire & Thérapies Innovantes' / 'Stress Response & Innovative Therapies' (STREINTH - Inserm U1113), Interface de Recherche Fondamentale et Appliquée en Cancérologie (IRFAC - Inserm U1113), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Paul Strauss : Centre Régional de Lutte contre le Cancer (CRLCC)-Fédération de Médecine Translationelle de Strasbourg (FMTS)-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Paul Strauss : Centre Régional de Lutte contre le Cancer (CRLCC)-Fédération de Médecine Translationelle de Strasbourg (FMTS), CRLCC Paul Strauss, Service de Pharmacie [Strasbourg] (CRLCC Paul Strauss), Épidémiologie et Santé Publique [Strasbourg] (UNISTRA), Université de Strasbourg (UNISTRA), Service de Santé Publique [Strasbourg] (HUS), Les Hôpitaux Universitaires de Strasbourg (HUS), Laboratoire de Biochimie et Biologie Moléculaire [Strasbourg] (HUS), This work was financially supported by the French Académie de Pharmacie/SFPO, the Conférence de Coordination Interrégionale du Grand Est de la Ligue Contre le Cancer, and Merck/Serono (Bourse oncologie)., and Gaiddon, Christian
Subjects: anti-EGFR targeted therapy, [SDV]Life Sciences [q-bio], HIF-2α, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, head and neck squamous cell carcinoma, lcsh:RC254-282, Article, [SDV] Life Sciences [q-bio], resistance, [SDV.CAN] Life Sciences [q-bio]/Cancer, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, oncogenic addiction, [SDV.BC] Life Sciences [q-bio]/Cellular Biology
Abstract: Background: management of head and neck squamous cell carcinomas (HNSCC) include anti-Epidermal Growth Factor Receptor (EGFR) antibodies and radiotherapy, but resistance emerges in most patients. RAS mutations lead to primary resistance to EGFR blockade in metastatic colorectal cancer but are infrequent in HNSCC, suggesting that other mechanisms are implicated. Since hypoxia and Hypoxia Inducible Factor-1 (HIF-1) have been associated with treatment failure and tumor progression, we hypothesized that EGFR/mammalian Target of Rapamycin (mTOR)/HIF-1 axis inhibition could radiosensitize HNSCC. Methods: We treated the radiosensitive Cal27 used as control, and radioresistant SQ20B and UD-SCC1 cells, in vivo and in vitro, with rapamycin and cetuximab before irradiation and evaluated tumor progression and clonogenic survival. Results: Rapamycin and cetuximab inhibited the mTOR/HIF-1α axis, and sensitized the SQ20B cell line to EGFR-inhibition. However, concomitant delivery of radiation to SQ20B xenografts increased tumor relapse frequency, despite effective HIF-1 inhibition. Treatment failure was associated with the induction of HIF-2α expression by cetuximab and radiotherapy. Strikingly, SQ20B and UD-SCC1 cells clonogenic survival dropped
Published: 2019

2. Incidental thyroid papillary microcarcinoma: survival and follow-up

Author: Gorostis, Sophie, Raguin, Thibaut, Schneegans, Olivier, Takeda, Catherine, Debry, Christian, Dupret Bories, Agnès, CHU Strasbourg, CRLCC Paul Strauss, Groupe Hospitalier Saint-Vincent, Institut Claudius Regaud, Centre Hospitalier Universitaire de Strasbourg - CHU Strasbourg (FRANCE), CRLCC Paul Strauss (FRANCE), Groupe Hospitalier Saint-Vincent - GHSV (FRANCE), and Institut Claudius Regaud - ICR (FRANCE)
Subjects: Thyroid lobo‐isthmectomy, Survival, Endocrinologie et métabolisme, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Total thyroidectomy, Thyroid papillary microcarcinoma
Abstract: International audience; Objectives/Hypothesis : The aim was to study the survival of incidental thyroid papillary microcarcinoma patients treated with surgery for benign thyroid disease to validate absence of oncological follow‐up and reduce unnecessary health expenses. Study Design :Retrospective cohort study. Methods : We analyzed patient's files and interviewed 252 patients by telephone whose cases were submitted to the multidisciplinary meeting of thyroid pathology in Strasbourg, France, for incidental thyroid papillary microcarcinoma without clinical lymph node involvement, between January 1996 and December 2012. Results : Thirteen patients (5.8%) died while the data were being collected; however, none of the deaths were due to the thyroid pathology, and no patients showed signs of relapse of the thyroidectomy or cervical lymph node level. Conclusions : Our retrospective study shows that patients with incidental localized thyroid papillary microcarcinoma who underwent surgery without radioactive iodine treatment have an identical survival compared to the general population at the same age to validate absence of oncological follow‐up and reduce unnecessary health expenses.
Published: 2019

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

Author: Martz, Nicolas, Salleron, Julia, Dhermain, Frédéric, Vogin, Guillaume, Daisne, Jean-François, Mouttet-Audouard, Raphaelle, Tanguy, Ronan, Noel, Georges, Peyre, Matthieu, Lecouillard, Isabelle, Jacob, Julian, Attal, Justine, Charissoux, Marie, Veresezan, Ovidiu, Hanzen, Chantal, Huchet, Aymeri, Latorzeff, Igor, Coutte, Alexandre, Doyen, Jérôme, Stefan, Dinu, Feuvret, Loic, Garcia, Gabriel, Royer, Philippe, Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), UNICANCER, Institut Gustave Roussy (IGR), Luxembourg Institute of Health (LIH), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER, Centre Léon Bérard [Lyon], CRLCC Paul Strauss, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU), CRLCC Eugène Marquis (CRLCC), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Claudius Regaud, UNICANCER - Institut régional du Cancer Montpellier Val d'Aurelle (ICM), CRLCC Val d'Aurelle - Paul Lamarque, Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), CHU Bordeaux [Bordeaux], Clinique Pasteur [Toulouse], CHU Amiens-Picardie, CHirurgie, IMagerie et REgénération tissulaire de l’extrémité céphalique - Caractérisation morphologique et fonctionnelle - UR UPJV 7516 (CHIMERE), Université de Picardie Jules Verne (UPJV), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Université Côte d'Azur (UCA), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), and Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)
Subjects: Radiotherapy, [SDV.CAN]Life Sciences [q-bio]/Cancer, Delineation, Target volume, Meningiomas, Consensus guidelines
Abstract: International audience; Purpose Radiotherapy is, with surgery, one of the main therapeutic treatment strategies for meningiomas. No prospective study has defined a consensus for the delineation of target volumes for meningioma radiotherapy. Therefore, target volume definition is mainly based on information from retrospective studies that include heterogeneous patient populations. The aim is to describe delineation guidelines for meningioma radiotherapy as an adjuvant or definitive treatment with intensity-modulated radiation therapy and stereotactic radiation therapy techniques. This guideline is based on a consensus endorsed by a multidisciplinary group of brain tumor experts, members of the Association of French-speaking Neuro-oncologists (ANOCEF). Materials and methods A 3-step procedure was used. First, the steering group carried out a comprehensive review to identify divergent issues on meningiomas target volume delineation. Second, an 84-item web-questionnaire has been developed to precisely define meningioma target volume delineation in the most common clinical situations. Third, experts members of the ANOCEF were requested to answer. The first two rounds were completed online. A third round was carried out by videoconference to allow experts to debate and discuss the remaining uncertain questions. All questions remained in a consensus. Results Limits of the target volume were defined using visible landmarks on computed tomography and magnetic resonance imaging, considering the pathways of tumor extension. The purpose was to develop clear and precise recommendations on meningiomas target volumes. Conclusion New recommendations for meningiomas delineation based on simple anatomic boundaries are proposed by the ANOCEF. Improvement in uniformity in target volume definition is expected.
Published: 2023

4. Panitumumab in combination with chemoradiotherapy for the treatment of locally-advanced anal canal carcinoma: Results of the FFCD 0904 phase II trial

Author: Vendrely, Véronique, Ronchin, Philippe, Minsat, Mathieu, Le Malicot, Karine, Lemanski, Claire, Mirabel, Xavier, Etienne, Pierre-Luc, Lièvre, Astrid, Darut-Jouve, Ariane, de la Fouchardière, Christelle, Giraud, Nicolas, Breysacher, Gilles, Argo-Leignel, Delphine, Thimonnier, Elsa, Magné, Nicolas, Abdelghani, Meher Ben, Lepage, Côme, Aparicio, Thomas, BoRdeaux Institute in onCology (Inserm U1312 - BRIC), Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Agro Dijon, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Institut du Cancer de Montpellier (ICM), Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER, Oncogenesis, Stress, Signaling (OSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Cancérologie de Bourgogne, Centre Léon Bérard [Lyon], Institut de Cancérologie Lucien Neuwirth, Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), CRLCC Paul Strauss, CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Hopital Saint-Louis [AP-HP] (AP-HP), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: Epidermal growth factor receptor, Panitumumab, Squamous cell carcinoma, [SDV.CAN]Life Sciences [q-bio]/Cancer, Chemoradiotherapy, Immunotherapy, Anal cancer
Abstract: Background and purpose: Standard treatment of squamous cell carcinoma of the anus (SCCA)is 5-fluorouracil (5FU) and mitomycin C (MMC) based chemoradiotherapy (CRT). This phase II study (EudraCT: 2011-005436-26) assessed the tolerance and complete response (CR) rate at 8 weeks of panitumumab (Pmab) combined with MMC-5FU-based CRT.Methods: Patients with locally advanced tumors without metastases (T2 > 3 cm, T3-T4, or N + whatever T stage) were treated with IMRT up to 65 Gy and concomitant CT according to the doses defined by a previous phase I study (MMC: 10 mg/m2; 5FU: 400 mg/m2; Pmab: 3 mg/kg). The expected CR rate was 80%.Results: Forty-five patients (male: 9, female: 36; median age: 60.1 [41.5-81]) were enrolled in 15 French centers. The most common related grade 3-4 toxicities observed were digestive (51.1%), hematologic (lymphopenia: 73.4%; neutropenia: 11.1%), radiation dermatitis (13.3%), and asthenia (11.1%) with RT interruption in 14 patients. One patient died because of mesenteric ischemia during the CRT, possibly related to treatment. In ITT analysis, the CR rate at 8 weeks after CRT was 66.7% [90%CI: 53.4-78.2]. Median follow-up was 43.6 months [IC 95%: 38.61-47.01]. Overall survival, recurrence-free and colostomy-free survival at 3 years were 80% [95%CI: 65.1-89], 62.2% [IC95%: 46.5-74.6] and 68.8 % [IC95%: 53.1-80.2] respectively.Conclusion: Panitumumab in combination with CRT for locally advanced SCCA failed to meet the expected CR rate and exhibited a poor tolerance. Furthermore, late RFS, CFS, and OS did not suggest any outcome improvement to justify further clinical trials.Clinicaltrials: gov identifier: NCT01581840.
Published: 2023

5. Trends in incidence of invasive vaginal cancer in France from 1990 to 2018 and survival of recently diagnosed women – A population-based study

Author: Brigitte Trétarre, Emmanuelle Dantony, Gaëlle Coureau, Gautier Defossez, Anne-Valérie Guizard, Patricia Delafosse, Laetitia Daubisse, Michel Velten, null Karima Hammas, Simona Barra, Bénédicte Lapotre, Sandrine Plouvier, Tania d'Almeida, Florence Molinié, Anne-Sophie Woronoff, Registre des Tumeurs de l'Hérault, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), 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), Hospices Civils de Lyon (HCL), 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), CIC - Poitiers, Université de Poitiers-Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Registre Général des Tumeurs du Calvados, CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-UNICANCER, Unité de recherche interdisciplinaire pour la prévention et le traitement des cancers (ANTICIPE), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)-Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM), FRANCIM, Réseau des registres français du cancer, Registre des cancers de l’Isère [CHU de Grenoble], Centre Hospitalier Universitaire [Grenoble] (CHU)-Université Grenoble Alpes (UGA), Registre général des cancers du Tarn, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), CRLCC Paul Strauss, CHU Amiens-Picardie, CHirurgie, IMagerie et REgénération tissulaire de l’extrémité céphalique - Caractérisation morphologique et fonctionnelle - UR UPJV 7516 (CHIMERE), Université de Picardie Jules Verne (UPJV), Registre général des cancers de Lille et de sa région (GCS-C2RC), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Hôpital Albert Calmette [Lille], Université Sorbonne Paris Nord, Centre hospitalier universitaire de Nantes (CHU Nantes), Registre des tumeurs du Doubs et du Territoire de Belfort [CHRU Besançon], Pôle cancérologie (CHRU Besançon), and Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)
Subjects: Vaginal cancer, Reproductive Medicine, Survival, Epidemiology, Incidence, Obstetrics and Gynecology, [SDV.CAN]Life Sciences [q-bio]/Cancer
Abstract: Objective: The aim of this study was to analyze trends in the incidence of vaginal cancer in France over a 28-year period and to present survival for recently-diagnosed women.Methods: French cancer registries provided data on invasive vaginal cancers diagnosed from 1990 to 2015 and followed up through June 2018. Trends in incidence were analyzed using a Poisson model with a bidimensional penalized spline of age and year at diagnosis. Net survival analysis was restricted to recently-diagnosed cases (2010-2015) and used a novel approach based on a bidimensional penalized spline of age and time-since-diagnosis to model excess mortality hazard.Results: With 162 new cases estimated in France in 2018, vaginal cancer represented 0.9 % of genital cancers in French women. In 2018, the world population age-standardized incidence rate was 0.2 per 100,000 person-years, median age at diagnosis was 75 years. The standardized incidence rate decreased significantly by 3 % per year (95 % CI, -3.8; -2.2) between 1990 and 2018 (0.4 cases per 100,000 person-year in 1990, vs 0.2 in 2018). Age-standardized net survival at 1 and 5 years after diagnosis was respectively 74 % and 45 %.Conclusions: This study confirms that vaginal cancer is still a rare malignancy in France with 5-year net survival that remains low. We observed a consistent decrease in the incidence rate between 1990 and 2018. It may be too early to attribute these trends to a positive impact of vaccination campaigns against hrHPV infection, since vaginal cancer mainly affects older women and HPV vaccination has only been available since the early 2000s, and only targets young girls.
Published: 2023

6. 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

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

Author: Michel Longy, Christine Maugard, Elisabeth Luporsi, Capucine Delnatte, Séverine Eon-Marchais, Marion Gauthier-Villars, Juana Beauvallet, Noura Mebirouk, Muriel Belotti, Alain Lortholary, Sophie Lejeune-Dumoulin, Christine Lasset, Isabelle Mortemousque, Yves-Jean Bignon, François Eisinger, Sylvie Mazoyer, Valérie Bonadona, Jean-Marc Limacher, Anne Tardivon, Paul Gesta, Sandra Fert-Ferrer, Fabienne Lesueur, Dorothée Le Gal, Jean Chiesa, Florent Soubrier, Pascaline Berthet, Laurence Faivre, Bruno Buecher, Nadine Andrieu, Juliette Coignard, Julie Tinat, Thierry Frebourg, Isabelle Coupier, Sophie Giraud, Laure Barjhoux, Catherine Noguès, Séverine Audebert-Bellanger, Claude Adenis-Lavignasse, Chrystelle Colas, Maximiliano Ribeiro Guerra, Laurence Venat-Bouvet, Eve Cavaciuti, Anne Floquet, Pascal Pujol, Francesca Damiola, Anne Fajac, Jean-Pierre Fricker, Hélène Dreyfus, Dominique Stoppa-Lyonnet, Marie-Gabrielle Dondon, Laurence Gladieff, Olivier Caron, Cancer et génome: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, Mines Paris - PSL (École nationale supérieure des mines de Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Curie [Paris], Université Paris sciences et lettres (PSL), Federal University of Juiz de Fora (UFIJ), Institut Gustave Roussy (IGR), AP-HP. Université Paris Saclay, Hôpital Arnaud de Villeneuve [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre Catherine-de-Sienne [Nantes] (CCS), Centre Paul Strauss, CRLCC Paul Strauss, Centre Hospitalier Georges Renon [Niort] (CH Georges Renon Niort), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Centre hospitalier régional Metz-Thionville (CHR Metz-Thionville), Hôpital de Mercy, Centre René Gauducheau, CRLCC René Gauducheau, Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Centre Léon Bérard [Lyon], Les Hôpitaux Universitaires de Strasbourg (HUS), Institut Bergonié [Bordeaux], Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA), Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), Ramsay Générale de Santé - Hôpital Privé La Louvière, Hôpital Dupuytren [CHU Limoges], Institut Sainte Catherine [Avignon], hôpital couple-enfant [CHU Grenoble Alpes], Institut Claudius Regaud, Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Bretonneau, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Hôpital Morvan [Brest], CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hospices Civils de Lyon (HCL), Groupement Hospitalier Lyon-Est (GHE), Clinique de Génétique médicale Guy Fontaine [CHRU LIlle], Hôpital pasteur [Colmar], Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), CHU de Bordeaux Pellegrin [Bordeaux], Centre Hospitalier Métropole Savoie [Chambéry], Hôpital René HUGUENIN (Saint-Cloud), CHU Rouen, Normandie Université (NU), Hôpital Edouard Herriot [CHU - HCL], Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Unité de génétique et biologie des cancers (U830), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5), MINES ParisTech - École nationale supérieure des mines de Paris, Institut de recherche en cancérologie de Montpellier (IRCM - U896 Inserm - UM1), CRLCC Val d'Aurelle - Paul Lamarque-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 1 (UM1), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de recherche en neurosciences de Lyon (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), COLO, Mouniati, Institut Curie [Paris]-MINES ParisTech - École nationale supérieure des mines de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université Montpellier 1 (UM1)-CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)
Subjects: Adult, Risk, Oncology, medicine.medical_specialty, DNA Repair, DNA repair, [SDV]Life Sciences [q-bio], Genes, BRCA2, Genes, BRCA1, Breast Neoplasms, X-ray exposure, Logistic regression, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, Risk Factors, Surgical oncology, Internal medicine, medicine, Genetic predisposition, Humans, Genetic Predisposition to Disease, 030212 general & internal medicine, Risk factor, RC254-282, High-risk population, Pregnancy, DNA repair genes, business.industry, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Cancer, Middle Aged, medicine.disease, 3. Good health, Radiography, [SDV] Life Sciences [q-bio], Low dose, 030220 oncology & carcinogenesis, Mutation, Female, business, Research Article
Abstract: Background Diagnostic ionizing radiation is a risk factor for breast cancer (BC). BC risk increases with increased dose to the chest and decreases with increased age at exposure, with possible effect modification related to familial or genetic predisposition. While chest X-rays increase the BC risk of BRCA1/2 mutation carriers compared to non-carriers, little is known for women with a hereditary predisposition to BC but who tested negative for a BRCA1 or BRCA2 (BRCA1/2) mutation. Methods We evaluated the effect of chest X-rays from diagnostic medical procedures in a dataset composed of 1552 BC cases identified through French family cancer clinics and 1363 unrelated controls. Participants reported their history of X-ray exposures in a detailed questionnaire and were tested for 113 DNA repair genes. Logistic regression and multinomial logistic regression models were used to assess the association with BC. Results Chest X-ray exposure doubled BC risk. A 3% increased BC risk per additional exposure was observed. Being 20 years old or younger at first exposure or being exposed before first full-term pregnancy did not seem to modify this risk. Birth after 1960 or carrying a rare likely deleterious coding variant in a DNA repair gene other than BRCA1/2 modified the effect of chest X-ray exposure. Conclusion Ever/never chest X-ray exposure increases BC risk 2-fold regardless of age at first exposure and, by up to 5-fold when carrying 3 or more rare variants in a DNA repair gene. Further studies are needed to evaluate other DNA repair genes or variants to identify those which could modify radiation sensitivity. Identification of subpopulations that are more or less susceptible to ionizing radiation is important and potentially clinically relevant.
Published: 2021

8. 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

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

Author: Gilles Robinet, Christos Chouaid, Radj Gervais, Roland Schott, Florian Guisier, Chantal Decroisette, Jean-Bernard Auliac, Olivier Bylicki, Charles Ricordel, Laurent Greillier, Maurice Pérol, Benjamin Besse, Renaud Descourt, Hôpital Morvan - CHRU de Brest (CHU - BREST ), Service de Pneumologie [CHI Créteil], CHI Créteil, IMRB - CEPIA/'Clinical Epidemiology And Ageing : Geriatrics, Primary Care and Public Health' [Créteil] (U955 Inserm - UPEC), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre Léon Bérard [Lyon], Institut Gustave Roussy (IGR), Université Paris-Saclay, Département de médecine oncologique [Gustave Roussy], Méthodes computationnelles pour la prise en charge thérapeutique en oncologie : Optimisation des stratégies par modélisation mécaniste et statistique (COMPO), Inria Sophia Antipolis - Méditerranée (CRISAM), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'oncologie multidisciplinaire innovations thérapeutiques [Hôpital Nord - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital Nord [CHU - APHM], Hôpital d'Instruction des Armées Sainte Anne, Service de Santé des Armées, CHU Pontchaillou [Rennes], Centre d'Investigation Clinique [CHU Rouen] (CIC Rouen), Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Centre Paul Strauss, CRLCC Paul Strauss, Centre Hospitalier Annecy-Genevois [Saint-Julien-en-Genevois], and Hôpital Charles Nicolle [Rouen]-CHU Rouen
Subjects: Adult, Male, Oncology, Cancer Research, medicine.medical_specialty, Lung Neoplasms, First line, medicine.medical_treatment, [SDV.CAN]Life Sciences [q-bio]/Cancer, Pembrolizumab, Antibodies, Monoclonal, Humanized, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, B7-H1 Antigen, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Carcinoma, Non-Small-Cell Lung, PD-L1, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, Humans, Multicenter Studies as Topic, Medicine, Prospective Studies, 030212 general & internal medicine, Lung cancer, Lung, Response Evaluation Criteria in Solid Tumors, Randomized Controlled Trials as Topic, Chemotherapy, biology, business.industry, General Medicine, Middle Aged, medicine.disease, Progression-Free Survival, Clinical trial, Clinical Trials, Phase III as Topic, 030220 oncology & carcinogenesis, Disease Progression, biology.protein, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Pd l1 expression, business, Follow-Up Studies
Abstract: Pembrolizumab plus chemotherapy is currently used in the first-line treatment of advanced non-small-cell lung cancer withoutLay abstract Non-small-cell lung cancer (NSCLC) is the most frequent type of lung cancer. Most NSCLC patients are diagnosed with advanced disease and only 10–15% of them are alive after 5 years. In the absence of specific tumor mutations, the currently recommended treatment is a combination of chemotherapy and immunotherapy with the monoclonal antibody pembrolizumab. The goal of immunotherapy is to prevent cancer from evading the immune system by interacting with molecules expressed at the surface of tumor cells (PD-L1) or immune cells (PD-1). A study comparing chemotherapy plus pembrolizumab versus pembrolizumab alone has never been performed in patients with a high level of PD-L1 expression on tumor cells. Therefore we designed the PERSEE study to compare these treatments in advanced-stage NSCLC patients with PD-L1 expression on ≥50% of tumor cells.
Published: 2021

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

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

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

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

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

Author: Audrey Mailliez, Khalil Saleh, Thierry Petit, Christelle Jouannaud, Etienne Brain, Matthieu Carton, Jean Marc Ferrero, Pierre-Etienne Heudel, Elise Deluche, Marc Debled, Anne Patsouris, Anthony Gonçalves, Lionel Uwer, George Emile, Alexia Savignoni, Florence Dalenc, Marianne Leheurteur, C. Courtinard, Lucie Veron, Marie-Ange Mouret-Reynier, Paul Cottu, Véronique Diéras, Véronique D'Hondt, Suzette Delaloge, Sylvain Ladoire, Mathieu Robain, Institut Gustave Roussy (IGR), Oncologie gynécologique, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Institut Curie [Paris], Centre Eugène Marquis (CRLCC), Centre Léon Bérard [Lyon], Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université Lille Nord de France (COMUE)-UNICANCER, Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), Université Côte d'Azur (UCA)-UNICANCER, Centre Paul Strauss, CRLCC Paul Strauss, Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), Institut Bergonié [Bordeaux], Institut Claudius Regaud, Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Jean Godinot [Reims], Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), UNICANCER [Paris], CHU Limoges, Université de Lille-UNICANCER, UNICANCER-Université Côte d'Azur (UCA), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), COLO, Mouniati, Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), and UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)
Subjects: MBC, metastatic breast cancer, BMI, body mass index, [SDV]Life Sciences [q-bio], ESME, Epidemio-Strategy-Medical-Economical, Overweight, Body Mass Index, 0302 clinical medicine, Risk Factors, Medicine, Overall survival, 030212 general & internal medicine, Underweight, TNBC, triple negative breast cancer, ComputingMilieux_MISCELLANEOUS, 2. Zero hunger, General Medicine, Prognosis, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Metastatic breast cancer, 3. Good health, [SDV] Life Sciences [q-bio], 030220 oncology & carcinogenesis, Cohort, Original Article, Female, medicine.symptom, medicine.medical_specialty, BC, breast cancer, Breast Neoplasms, lcsh:RC254-282, OS, overall survival, 03 medical and health sciences, BMI, Breast cancer, Internal medicine, Humans, Obesity, Risk factor, Retrospective Studies, business.industry, HR, hormone receptor, Cancer, nutritional and metabolic diseases, medicine.disease, Surgery, business, Body mass index, PFS, progression free-survival
Abstract: Background High Body mass index (BMI) is a risk factor for breast cancer among postmenopausal women and an adverse prognostic factor in early-stage. Little is known about its impact on clinical outcomes in patients with metastatic breast cancer (MBC). Methods The National ESME-MBC observational cohort includes all consecutive patients newly diagnosed with MBC between Jan 2008 and Dec 2016 in the 18 French comprehensive cancer centers. Results Of 22 463 patients in ESME-MBC, 12 999 women had BMI data available at MBC diagnosis. Median BMI was 24.9 kg/m2 (range 12.1–66.5); 20% of women were obese and 5% underweight. Obesity was associated with more de novo MBC, while underweight patients had more aggressive cancer features. Median overall survival (OS) of the BMI cohort was 47.4 months (95% CI [46.2–48.5]) (median follow-up: 48.6 months). Underweight was independently associated with a worse OS (median OS 33 months; HR 1.14, 95%CI, 1.02–1.27) and first line progression-free survival (HR, 1.11; 95%CI, 1.01; 1.22), while overweight or obesity had no effect. Conclusion Overweight and obesity are not associated with poorer outcomes in women with metastatic disease, while underweight appears as an independent adverse prognostic factor., Highlights • This is the first large multicenter cohort reporting BMI’s effect on outcomes among patients with metastatic breast cancer. • Overweight or obese status does not negatively influence outcome of metastatic breast cancer patients, whatever the subtype. • Underweight is a strong negative independent prognostic factor on outcomes, whatever the subtype.
Published: 2021

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

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

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

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

15. Long-term outcomes in patients with PET-predicted poor-responsive HER2-positive breast cancer treated with neoadjuvant bevacizumab added to trastuzumab and docetaxel: 5-year follow-up of the randomised Avataxher study

Author: Jean-Yves Pierga, Alina Berriolo-Riedinger, Thierry Petit, Laurent Arnould, David Coeffic, Abdennour Ferhat, Gilles Paintaud, Jean-Briac Prevost, Pierre-Francois Dupre, Fanny Le Du, Thomas Bachelot, Marie-Pierre Chauvet, Jean-Marc Ferrero, Gilles Thibault, Kaldoun Kerrou, Philippe Gabelle, Catherine Barbe, Julien Dupin, Bruno Coudert, Marie-Ange Mouret-Reynier, Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, Institut Curie [Paris], Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Centre Paul Strauss, CRLCC Paul Strauss, Centre Eugène Marquis (CRLCC), Hôpital Morvan - CHRU de Brest (CHU - BREST ), Centre Léon Bérard [Lyon], Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université Lille Nord de France (COMUE)-UNICANCER, Hôpital Bretonneau, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Roche France, Département d'information médicale [Centre Georges-François Leclerc] (DIM), UNICANCER-UNICANCER, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Université de Lille-UNICANCER
Subjects: Oncology, medicine.medical_specialty, Positron emission tomography, Early pet assessment, Bevacizumab, medicine.medical_treatment, [SDV]Life Sciences [q-bio], 01 natural sciences, Group B, 03 medical and health sciences, Her-2 positive breast cancer, 0302 clinical medicine, Breast cancer, Trastuzumab, Internal medicine, medicine, Adjuvant therapy, 030212 general & internal medicine, 0101 mathematics, Adverse effect, Long-term follow-up, Neoadjuvant therapy, lcsh:R5-920, business.industry, 010102 general mathematics, General Medicine, medicine.disease, 3. Good health, Docetaxel, pathological complete response, Δsuvmax, Neoadjuvant, lcsh:Medicine (General), business, Research Paper, medicine.drug
Abstract: Background: The open-label, randomised Phase 2 AVATAXHER study (NCT01142778) demonstrated that early PET assessment identified HER2-positive breast cancer patients who responded poorly to neoadjuvant docetaxel plus trastuzumab. Adding neoadjuvant bevacizumab for PET-predicted poor-responders improved pathological complete response (pCR) rates (43.8% vs 24.0%). We investigated long-term study outcomes. Methods: Patients were treated in three groups. All patients initially received two cycles of standard neoadjuvant therapy with [¹⁸F]-FDG PET conducted before each cycle. Those with ≥70% change in the maximum standardised uptake value (∆SUVmax) received four further cycles of standard neoadjuvant therapy (PET responders). PET-predicted poor-responders (∆SUVmax
Published: 2020

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

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

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

Author: Marie-Ange Mouret-Reynier, Véronique D'Hondt, Audrey Mailliez, Gaëtane Simon, Damien Parent, Silvia Ilie, N. Madranges, Christelle Levy, David Pérol, Gaëlle Chenuc, Pierre Heudel, Thomas Vermeulin, Lionel Uwer, Paule Augereau, Thierry Petit, Suzette Delaloge, Florence Dalenc, Christophe Perrin, Etienne Brain, Jean-Sebastien Frenel, Anthony Gonçalves, Jean-Christophe Eymard, Jean-Marc Ferrero, Mathieu Robain, Marie-Paule Sablin, Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER, Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Paul Strauss, and CRLCC Paul Strauss
Subjects: Adult, Male, Oncology, Cancer Research, medicine.medical_specialty, Databases, Factual, Combination therapy, [SDV]Life Sciences [q-bio], Population, Administration, Oral, Breast Neoplasms, Vinorelbine, Breast Neoplasms, Male, Capecitabine, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Neoplasm Metastasis, education, ComputingMilieux_MISCELLANEOUS, Aged, Retrospective Studies, 030304 developmental biology, 0303 health sciences, education.field_of_study, business.industry, Cancer, Retrospective cohort study, General Medicine, Middle Aged, medicine.disease, Metastatic breast cancer, Progression-Free Survival, 3. Good health, Clinical trial, 030220 oncology & carcinogenesis, Female, business, medicine.drug
Abstract: Background/aim Vinorelbine is indicated for use in the treatment of MBC as a single agent or in combination but there is little real world data on this molecule and even less on its oral form. We exploited the Unicancer Epidemiology Strategy Medical-Economics (ESME) metastatic breast cancer (MBC) database to investigate current patterns of use of oral vinorelbine (OV), as well as outcomes of patients receiving this drug. Patients and methods Data were collected retrospectively from women and men treated for MBC between 2008 and 2014 at one of 18 French Comprehensive Cancer Centres. The efficacy of OV was evaluated in terms of progression-free (PFS) and overall survival (OS) and treatment duration. The population and patterns of OV usage were also described. Results A total of 1806 patients (11% of the ESME MBC database) were included in this analysis. OV was prescribed as monotherapy (46%) or in combination (29%), especially with capecitabine. mainly in later treatment lines. Median PFS was 3.3 months: 2.9 months for single agent, 3.6 months for combination therapy. Median OS was 40.9 months. Conclusion Real-world data offer complementary results to the data from traditional clinical trials, but they concern a much larger population. In this ESME MBC cohort, OV was only prescribed to a small subset of MBC patients. OV was mainly given as single agent to patients with heavily pre-treated MBC; less commonly, it was co-administered with capecitabine or anti-HER2, in earlier lines of therapy. PFS was modest but in line with previous reports.
Published: 2020

18. COVID-19 and people followed for breast cancer: French guidelines for clinical practice of Nice-St Paul de Vence, in collaboration with the Collège Nationale des Gynécologues et Obstétriciens Français (CNGOF), the Société d’Imagerie de la Femme (SIFEM), the Société Française de Chirurgie Oncologique (SFCO), the Société Française de Sénologie et Pathologie Mammaire (SFSPM) and the French Breast Cancer Intergroup-UNICANCER (UCBG)

Author: Gligorov, Joseph, Bachelot, Thomas, Pierga, Jean-Yves, Antoine, Eric-Charles, Balleyguier, Corinne, Barranger, Émmanuel, Belkacemi, Yazid, Bonnefoi, Hervé, Bidard, François-Clément, Ceugnart, Luc, Classe, Jean-Marc, Cottu, Paul, Coutant, Charles, Cutuli, Bruno, Dalenc, Florence, Darai, Émile, Dieras, Veronique, Dohollou, Nadine, Giacchetti, Sylvie, Gonçalves, Anthony, Hardy-Bessard, Anne-Claire, Houvenaeghel, Gilles, Jacquin, Jean-Philippe, Jacot, William, Levy, Christelle, Mathelin, Carole, Nisand, Israël, Petit, Thierry, Poncelet, Edouard, Rivera, Sofia, Rouzier, Roman, Salmon, Remy, Scotté, Florian, Spano, Jean-Philippe, Uzan, Catherine, Zelek, Laurent, Spielmann, Marc, Penault-Llorca, Frédérique, Namer, Moïse, Delaloge, Suzette, Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Léon Bérard [Lyon], Institut Curie [Paris], Institut Gustave Roussy (IGR), Département d'imagerie médicale [Gustave Roussy], Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), CHU Henri Mondor [Créteil], Institut Bergonié [Bordeaux], UNICANCER, Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER, Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), Institut Claudius Regaud, Centre Eugène Marquis (CRLCC), Hopital Saint-Louis [AP-HP] (AP-HP), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Institut de Cancérologie de la Loire Lucien Neuwirth, Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Institut du Cancer de Montpellier (ICM), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), CHU Strasbourg, Centre Paul Strauss, CRLCC Paul Strauss, Centre hospitalier [Valenciennes, Nord], Clinique Saint Jean de Dieu, Département interdisciplinaire d’organisation des parcours patients (DIOPP), Hôpital Avicenne [AP-HP], Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Pathologie mammaire, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), CHU Henri Mondor, Université Lille Nord de France (COMUE)-UNICANCER, Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), and UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)
Subjects: Breast cancer, Recommandation, SARS-CoV-2, [SDV]Life Sciences [q-bio], Guidelines, Covid-19, Cancer du sein, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Nous sommes confrontés à la pandémie COVID-19 qui est certes sans conséquences graves chez près de 85 % de la population générale mais qui peut engager le pronostic vital, plus particulièrement dans une population fragile. Le taux de mortalité estimé du COVID-19 est de 1 à 3 % soit entre 10 et 30 fois plus que le virus saisonnier de la grippe, et ceci sous réserve de données épidémiologiques imparfaites liées au fait que la recherche de SARS-CoV-2 n’est pas systématique dans une population asymptomatique, voire même symptomatique sans critères de gravité.
Published: 2020

19. Radiation therapy to the primary tumor for de novo metastatic breast cancer and overall survival in a retrospective multicenter cohort analysis

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

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

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

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

Author: jacob, j, Clausse, E, Benadjaoud, M A, Jenny, C, Ribeiro, M, Feuvret, L, Mazeron, J-J, Antoni, D, Bernier, M-O, Hoang-Xuan, K, Psimaras, D, Carpentier, A, Ricard, D, Maingon, P, Cognition and Action Group (COGNAC-G - UMR 8257), Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Service d'Oncologie Radiothérapie [CHU Pitié Salpétrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU), Service de médecine physique et de réadaptation [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), PSE-SANTE/SERAMED, Institut de Radioprotection et de Sûreté Nucléaire (IRSN), Service de neurologie 2 [CHU Pitié-Salpêtrière], Centre Paul Strauss, CRLCC Paul Strauss, Les Hôptaux universitaires de Strasbourg (HUS), CHU Strasbourg, PSE-SANTE/SESANE/LEPID, Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de Neurochirurgie [CHU Pitié-Salpêtrière], Hôpital d'instruction des Armées Percy, and Service de Santé des Armées
Subjects: Intensity-modulated radiation therapy, Radiothérapie conformationnelle par modulation d’intensité, Fonctions cognitives, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], [SDV.CAN]Life Sciences [q-bio]/Cancer, Glioma, [SDV.IB.MN]Life Sciences [q-bio]/Bioengineering/Nuclear medicine, Gliome, Cognitive functions
Abstract: International audience; Purpose: The purpose of this prospective dosimetric study was to assess the dose distribution regarding the brain areas implied in cognitive functions using two approaches: volumetric modulated arc therapy (VMAT) and helical tomotherapy (HT).Patients and methods: Thirty-seven patients were treated using a dual-arc VMAT approach for supratentorial glioblastoma between 2016 and 2018. The total dose of 60 Gy in 30 daily fractions was administered to the planning target volume (PTV). The brain structures that play an important role in cognitive physiology, such as the hippocampi, corpus callosum, cerebellum, subventricular zones (SVZ), were delineated. For each patient, a new treatment plan in HT was determined by a second medical physicist in a blindly fashion according to the same dose constraints and priorities. Statistical analyses were performed using the Wilcoxon-signed rank test.Results: Conformity indexes remained similar with both techniques. The mean values were 0.96 (0.19–1.00) for VMAT and 0.98 (range, 0.84–1.00) for HT, respectively (P = 0.73). Significant D50% reductions were observed with VMAT compared to HT: 14.6 Gy (3.8–28.0) versus 17.4 Gy (12.1–25.0) for the normal brain (P = 0.014); 32.5 Gy (10.3–60.0) versus 35.6 Gy (17.1–58.0) for the corpus callosum (P = 0.038); 8.1 Gy (0.4–34.0) versus 12.8 Gy (0.8–27.0) for the cerebellum (P < 0.001), respectively.Conclusion: The VMAT approach seemed to improve the sparing of the key brain areas implied in cognitive functions without jeopardizing PTV coverage.; Objectif: L’objectif de cette étude prospective dosimétrique était d’évaluer la distribution de dose en regard des aires cérébrales impliquées dans les fonctions cognitives selon deux techniques : arcthérapie volumétrique modulée (VMAT) et tomothérapie hélicoïdale (HT).Patients et méthodes: Trente-sept patients ont été pris en charge pour un glioblastome sus-tentoriel par une VMAT à base de deux arcs entre 2016 et 2018. Une dose totale de 60 Gy en 30 fractions quotidiennes a été administrée au volume cible prévisionnel (PTV). Les structures cérébrales occupant une place importante dans la physiologie cognitive, comme les hippocampes, le corps calleux, le cervelet, les zones péri-ventriculaires (ZPV), ont été délinées. Pour chaque patient, un nouveau plan de HT a été déterminé en aveugle par une seconde physicienne médicale selon les mêmes contraintes de dose et priorités. Les analyses statistiques ont été menées à l’aide du test des rangs signés de Wilcoxon.Résultats: Les indices de conformité étaient similaires entre les deux techniques. Les valeurs moyennes étaient de 0,96 (0,19–1,00) respectivement en VMAT et de 0,98 (0,84–1,00) en tomothérapie hélicoïdale (p = 0,73). Des réductions significatives de la D50 % (dose reçue dans 50 % du volume) ont été observées en VMAT, comparativement à la HT : respectivement 14,6 Gy (3,8–28,0) contre 17,4 Gy (12,1–25,0) pour l’encéphale sain (p = 0,014), 32,5 Gy (10,3–60,0) contre 35,6 Gy (17,1–58,0) pour le corps calleux (p = 0,038), 8,1 Gy (0,4–34,0) contre 12,8 Gy (0,8–27,0) pour le cervelet (p < 0,001).Conclusion: La VMAT semblait améliorer la protection des principales régions cérébrales impliquées dans les fonctions cognitives sans compromettre la couverture du PTV.
Published: 2020

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

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

23. Leveraging Immunotherapy with Nanomedicine

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

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

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

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

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

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

Author: Christelle Jouannaud, David Pasquier, Guillaume Louvel, Jean Marc Ferrero, William Jacot, Jean Sébastien Fresnel, Paule Augereau, Thierry Petit, Marianne Leheurteur, Thomas Bachelot, Jean-David Fumet, Julien Geffrelot, Florence Dalenc, Elise Deluche, Anthony Gonçalves, Paul Cottu, Véronique Diéras, Raphaëlle Mouttet-Audouard, Marie Ange Mouret-Reynier, Julien Fraisse, C. Courtinard, Lionel Uwer, I. Lecouillard, Amélie Darlix, Adeline Petit, Mathieu Robain, Etienne Brain, Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER, Centre de Recherche en Informatique, Signal et Automatique de Lille - UMR 9189 (CRIStAL), Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), CRLCC Eugène Marquis (CRLCC), Unité de biostatistiques, CRLCC Val d'Aurelle - Paul Lamarque, Department of Medical Oncology [Saint-Cloud], Institut Curie [Saint-Cloud], Département de radiothérapie [Bordeaux], Institut Bergonié [Bordeaux], UNICANCER-UNICANCER, Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER, Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Institut Claudius Regaud, CHU Limoges, Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Département d'oncologie médicale [Centre Georges-François Leclerc], Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), Service de radiothérapie, Département de Recherche Translationnelle, Institut Curie [Paris], Centre Paul Strauss, CRLCC Paul Strauss, Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), CRLCC Jean Godinot, Service d'Oncologie Médicale, CRLCC Haute Normandie-Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Medical Oncology Department, Salah Azaiz Institute, Oncogénèse et progression tumorale, Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Lille Nord de France (COMUE)-UNICANCER, Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), and Département de recherche translationnelle
Subjects: 0301 basic medicine, Cancer Research, medicine.medical_specialty, medicine.medical_treatment, Neurological progression-free survival, [SDV]Life Sciences [q-bio], Breast Neoplasms, [SDV.CAN]Life Sciences [q-bio]/Cancer, Stereotactic radiation therapy, Central Nervous System Neoplasms, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, Internal medicine, Epidemiology, medicine, Humans, skin and connective tissue diseases, Retrospective Studies, Proportional hazards model, business.industry, Retrospective cohort study, Brain metastases, Middle Aged, medicine.disease, Metastatic breast cancer, Progression-Free Survival, 3. Good health, Radiation therapy, Treatment Outcome, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, Cohort, Female, business
Abstract: The aims of the present study were to describe treatment patterns and survival outcomes in patients with central nervous system metastases (CNSM) selected among metastatic breast cancer (MBC) patients included in a retrospective study from the Epidemiological Strategy and Medical Economics (ESME) MBC cohort.Neurological progression-free survival (NPFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Signiﬁcant contributors to NPFS were determined using a multivariate Cox proportional hazards model.After a median follow-up of 42.8 months, of 16 701 patients included in the ESME MBC database, CNSM were diagnosed in 24.6% of patients. The most frequent treatments after diagnosis of CNSM were whole-brain radiotherapy (WBRT) (45.2%) and systemic treatment (59.3%). Median OS and NPFS were 7.9 months (95% CI: 7.2-8.4) and 5.5 months (95% CI: 5.2-5.8), respectively. In multivariate analysis, age70 years (vs50 years; HR = 1.40; 95% CI: 1.24-1.57), triple-negative tumours (vs HER2-/HR+; HR = 1.87; 95% CI: 1.71-2.06), HER2+/HR-tumours (vs HER2-/HR+; HR = 1.14; 95% CI: 1.02-1.27), ≥3 metastatic sites (vs 3; HR = 1.32; 95% CI: 1.21-1.43) and ≥3 previous treatment lines (vs 3; HR = 1.75; 95% CI: 1.56-1.96) were detrimental for NPFS. A time interval between selection and CNSM diagnosis superior to 18 months (vs9 months; HR = 0.88; 95% CI: 0.78-0.98) was associated with longer NPFS.This study describes current treatment patterns of MBC patients in a "real life" setting. Despite advances in stereotactic radiation therapy, most of the patients still received WBRT. More research is warranted to identify patient subsets for tailored treatment strategies.
Published: 2020

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

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

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

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

29. Radiotherapy of T4M0 prostate cancer : A multicentric retrospective analysis

Author: Goupy, F., Meyer, E., Pommier, P., Magne, N., Sargos, P., David Pasquier, Noel, G., Schick, U., Hasbini, A., Supiot, S., Bossi, A., Latorzeff, I., Riverain, J., Duverge, L., Benna, M., Benziane, N., Le Roy, T., Bigot, C., Rehn, M., Vaugier, L., Le Proust, B., Barateau, A., Campillo-Gimenez, B., Castelli, J., Crevoisier, R., CRLCC Eugène Marquis (CRLCC), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Centre Léon Bérard [Lyon], Institut de Cancérologie Lucien Neuwirth, CHU Saint-Etienne, Institut Bergonié [Bordeaux], UNICANCER, Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université Lille Nord de France (COMUE)-UNICANCER, CRLCC Paul Strauss, Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Institut Gustave Roussy (IGR), Département de radiothérapie [Gustave Roussy], Clinique Pasteur [Toulouse], 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), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Université de Lille-UNICANCER, and Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: [SDV.IB]Life Sciences [q-bio]/Bioengineering, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2020

30. Gene alterations in epigenetic modifiers and JAK-STAT signaling are frequent in breast implant-associated ALCL

Author: Luc Xerri, Alina Nicolae, Reda Bouabdallah, Joan Somja, Marie-Pierre Chenard, François-Xavier Frenois, Fabien Reyal, Catherine Chassagne-Clément, Lénaïg Mescam, Marie-Hélène Delfau-Larue, Frédéric Escudié, Anne Moreau, Corinne Haioun, Philippe Gaulard, Lucie Oberic, Nadia Amara, Asma Beldi-Ferchiou, Laetitia Lacroix, Alexandra Traverse-Glehen, François Lemonnier, Jean-Marc Schiano, Bruno Tesson, Virginie Fataccioli, Marie Bannier, Daniel Birnbaum, Cécile Laurent, Nadine Martin, P. Brousset, Fabien Le Bras, José Adélaïde, Marc André, Naïs Prade, Camille Laurent, Arnaud Guille, Anne-Sophie Hamy, 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), Bidaut, Ghislain, Laboratoire Jacques-Louis Lions (LJLL), Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Rt2 Lab, Institut Curie [Paris], CHU Henri Mondor, Service d'hématologie clinique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Islamic University of Gaza (IUG - IU Gaza), 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 Carnot Lymphome (CALYM), 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 Générale, CHU Strasbourg-Hôpital de Hautepierre [Strasbourg], Centre hospitalier universitaire de Nantes (CHU Nantes), Département d'anatomopathologie, biopathologie, Centre Léon Bérard [Lyon], Groupe de Recherche d'Histoire (GRHis), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut de Recherche Interdisciplinaire Homme et Société (IRIHS), Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Centre d'Études des Phénomènes Aléatoires et Géophysiques (CEPHAG), École Nationale Supérieure d'Ingénieurs Électriciens de Grenoble (ENSIEG)-Centre National de la Recherche Scientifique (CNRS), 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)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Centre des maladies du sein, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Surgery Department, CRLCC Paul Strauss, Service Hématologie - IUCT-Oncopole [CHU Toulouse], Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle IUCT [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Hôpital Henri Mondor, Service d'Hématologie, 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), IUCT Oncopole - Institut Universitaire du Cancer de Toulouse, UCL - (MGD) Service d'hématologie, UCL - SSS/IREC/MIRO - Pôle d'imagerie moléculaire, radiothérapie et oncologie, Service d'Hématologie [CHU Toulouse], CHU Toulouse [Toulouse], Laboratoire d'Hématologie [Purpan], CHU Henri Mondor [Créteil], École Pratique des Hautes Études (EPHE), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Institut Carnot CALYM [Pierre-Benite], Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Hématologie [IUCT Toulouse], Université Fédérale Toulouse Midi-Pyrénées-Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse]
Subjects: Adult, 0301 basic medicine, DNA Copy Number Variations, Breast Implants, [SDV]Life Sciences [q-bio], Immunology, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, medicine.disease_cause, Biochemistry, Germline, Epigenesis, Genetic, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, Epigenetics, SOCS3, STAT3, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, Anaplastic large-cell lymphoma, PI3K/AKT/mTOR pathway, ComputingMilieux_MISCELLANEOUS, Aged, Janus Kinases, Aged, 80 and over, Mutation, Lymphoid Neoplasia, Genome, Human, JAK-STAT signaling pathway, Cell Biology, Hematology, Middle Aged, medicine.disease, [SDV] Life Sciences [q-bio], STAT Transcription Factors, 030104 developmental biology, Cancer research, biology.protein, Lymphoma, Large-Cell, Anaplastic, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Signal Transduction, 030215 immunology
Abstract: The oncogenic events involved in breast implant-associated anaplastic large cell lymphoma (BI-ALCL) remain elusive. To clarify this point, we have characterized the genomic landscape of 34 BI-ALCLs (15 tumor and 19 in situ subtypes) collected from 54 BI-ALCL patients diagnosed through the French Lymphopath network. Whole-exome sequencing (n = 22, with paired tumor/germline DNA) and/or targeted deep sequencing (n = 24) showed recurrent mutations of epigenetic modifiers in 74% of cases, involving notably KMT2C (26%), KMT2D (9%), CHD2 (15%), and CREBBP (15%). KMT2D and KMT2C mutations correlated with a loss of H3K4 mono- and trimethylation by immunohistochemistry. Twenty cases (59%) showed mutations in ≥1 member of the JAK/STAT pathway, including STAT3 (38%), JAK1 (18%), and STAT5B (3%), and in negative regulators, including SOCS3 (6%), SOCS1 (3%), and PTPN1 (3%). These mutations were more frequent in tumor-type samples than in situ samples (P = .038). All BI-ALCLs expressed pSTAT3, regardless of the mutational status of genes in the JAK/STAT pathway. Mutations in the EOMES gene (12%) involved in lymphocyte development, PI3K-AKT/mTOR (6%), and loss-of-function mutations in TP53 (12%) were also identified. Copy-number aberration (CNA) analysis identified recurrent alterations, including gains on chromosomes 2, 9p, 12p, and 21 and losses on 4q, 8p, 15, 16, and 20. Regions of CNA encompassed genes involved in the JAK/STAT pathway and epigenetic regulators. Our results show that the BI-ALCL genomic landscape is characterized by not only JAK/STAT activating mutations but also loss-of-function alterations of epigenetic modifiers.
Published: 2019

31. Antibody-targeting of ultra-small nanoparticles enhances imaging sensitivity and enables longitudinal tracking of multiple myeloma

Author: Fred C. Lam, Irene M. Ghobrial, Clelia Mathieu, Alexandre Detappe, Peter Harvey, Andrea Protti, Thibaud P. Coroller, Jeremiah A. Johnson, Petr Jarolim, Quang-Dé Nguyen, Yannick Crémillieux, Yingjie Yu, Mairead Reidy, Hung V.-T. Nguyen, Olivier Tillement, P. Peter Ghoroghchian, Dana-Farber Cancer Institute [Boston], Harvard Medical School [Boston] (HMS), David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology (MIT), Centre Paul Strauss, CRLCC Paul Strauss, McMaster University [Hamilton, Ontario], Brigham and Women's Hospital [Boston], Dana-Farber Cancer Institute and Harvard Medical School, Institut des Sciences Moléculaires (ISM), Université Montesquieu - Bordeaux 4-Université Sciences et Technologies - Bordeaux 1-École Nationale Supérieure de Chimie et de Physique de Bordeaux (ENSCPB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut Lumière Matière [Villeurbanne] (ILM), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon
Subjects: Neoplasm, Residual, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, Plasma Cells, Contrast Media, Gadolinium, 02 engineering and technology, Mice, SCID, Plasma cell, Signal-To-Noise Ratio, 010402 general chemistry, 01 natural sciences, Antibodies, Mice, Bone Marrow, Signaling Lymphocytic Activation Molecule Family, Biopsy, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, Medicine, Animals, Humans, General Materials Science, Tissue Distribution, B-Cell Maturation Antigen, Multiple myeloma, Early Detection of Cancer, ComputingMilieux_MISCELLANEOUS, Tumor microenvironment, medicine.diagnostic_test, business.industry, Magnetic resonance imaging, 021001 nanoscience & nanotechnology, medicine.disease, Minimal residual disease, Magnetic Resonance Imaging, 0104 chemical sciences, 3. Good health, Bone marrow examination, Disease Models, Animal, medicine.anatomical_structure, Microscopy, Fluorescence, Cancer research, Nanoparticles, [SDV.IB]Life Sciences [q-bio]/Bioengineering, Bone marrow, 0210 nano-technology, business, Multiple Myeloma
Abstract: International audience; Monitoring malignant progression and disease recurrence post-therapy are central challenges to improving the outcomes of patients with multiple myeloma (MM). Whereas current detection methods that rely upon bone marrow examination allow for precise monitoring of minimal residual disease and can help to elucidate clonal evolution, they do not take into account the spatial heterogeneity of the tumor microenvironment. As such, they are uninformative as to the localization of malignant plasma cells and may lead to false negative results. With respect to the latter challenge, clinically-available imaging agents are neither sufficiently sensitive nor specific enough to detect minute plasma cell populations. Here, we sought to explore methods by which to improve detection of MM cells within their natural bone marrow environment, using whole-animal magnetic resonance imaging to longitudinally monitor early-stage disease as well as to enhance tumor detection after systemic therapy. We conducted a proof-of-concept study to demonstrate that ultra-small (
Published: 2019

32. High LET Radiation Overcomes In Vitro Resistance to X-Rays of Chondrosarcoma Cell Lines

Author: Chevalier, François, Hamdi, Dounia Houria, Lepleux, Charlotte, Temelie, Mihaela, Nicol, Anaïs, Austry, Jean Baptiste, Lesueur, Paul, Vares, Guillaume, Savu, Diana, Nakajima, Tetsuo, Saintigny, Yannick, Laboratoire d'Accueil et de Recherche avec les Ions Accélérés (LARIA), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Centre Paul Strauss, CRLCC Paul Strauss, Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), National Institute of Radiobiological Sciences, Department of Life and Environmental Physics [Magurele, Roumanie], Horia Hulubei National Institute of Physics and Nuclear Engineering [Magurele, Roumanie], and UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)
Subjects: musculoskeletal diseases, colony size distributions, analysis of variance, sarcoma, 5-ethynyl-2 0 -deoxyuridine, Cell Survival, DNA damage response Abbreviations ANOVA, Grand Accelérateur National d'Ions Lourds, Chondrosarcoma, RBE, Apoptosis, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.IB.MN]Life Sciences [q-bio]/Bioengineering/Nuclear medicine, DNA damage response, poly-methyl methacrylate, relative biological effectiveness, Cell Line, Tumor, Radiation, Ionizing, 2D culture, Humans, CSDs, GANIL, Heavy Ion Medical Accelerator in Chiba, PBS, phosphate buffered saline, HIMAC, linear energy transfer, X-Rays, MEM, Dose-Response Relationship, Radiation, C-ions, EdU, PMMA, Radiography, radiation-resistance, LET, minimum essential medium Eagle, Original Article, DNA Damage
Abstract: International audience; Chondrosarcomas are malignant tumors of the cartilage that are chemoresistant and radioresistant to X-rays. This restricts the treatment options essential to surgery. In this study, we investigated the sensitivity of chondrosarcoma to X-rays and C-ions in vitro. The sensitivity of 4 chondrosarcoma cell lines (SW1353, CH2879, OUMS27, and L835) was determined by clonogenic survival assays and cell cycle progression. In addition, biomarkers of DNA damage responses were analyzed in the SW1353 cell line. Chondrosarcoma cells showed a heterogeneous sensitivity toward irradiation. Chondrosarcoma cell lines were more sensitive to C-ions exposure compared to X-rays. Using D10 values, the relative biological effectiveness of C-ions was higher (relative biological effectiveness ¼ 5.5) with cells resistant to X-rays (CH2879) and lower (relative biological effectiveness ¼ 3.7) with sensitive cells (L835). C-ions induced more G2 phase blockage and micronuclei in SW1353 cells as compared to X-rays with the same doses. Persistent unrepaired DNA damage was also higher following C-ions irradiation. These results indicate that chondrosarcoma cell lines displayed a heterogeneous response to conventional radiation treatment; however, treatment with C-ions irradiation was more efficient in killing chondrosarcoma cells, compared to X-rays.
Published: 2019

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

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

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

Author: A. Giraud, P. Soibinet, Sébastien Carrère, E. Stoeckle, G. Vaz, J. Guiramand, J.-C. Ruzic, A. Dufresne, Jean-Yves Blay, F. Gouin, A. Rochwerger, F. Duffaud, A. Le Cesne, Francis Guillemin, J.-P. Spano, M. Rios, P. Meeus, Isabelle Ray-Coquard, A. Di Marco, G. Ferron, François Bertucci, François Sirveaux, N. Firmin, F. Fiorenza, O. Collard, S. Bonvalot, Emmanuelle Bompas, S. Causeret, P. Anract, M. Jafari, D. Pérol, J.-C. Machiavello, O. Marco, F. Ducimetière, C. Honore, A. Italiano, A. Michot, M. Karanian-Philippe, Nicolas Penel, P. Gimbergues, Mickaël Ropars, M. Toulmonde, F. Marchal, M. Brahmi, C. Le Pechoux, L.R. Le Nail, C. Perrin, F. Le Loarer, C. Chevreau, A. Dupré, J.-M. Guilloit, L. Chaigneau, F. Dujardin, Department of Medical Oncology [Lyon], Centre Léon Bérard [Lyon], Institut de Cancérologie Lucien Neuwirth, Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Département de Chirurgie cancérologique, Institut Gustave Roussy (IGR), Département d'oncologie médicale, Institut Bergonié [Bordeaux], UNICANCER-UNICANCER, Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER, Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d’Oncologie Médicale [Hôpital de la Timone - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), CHU Pontchaillou [Rennes], Centre Eugène Marquis (CRLCC), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), Centre Paul Strauss, CRLCC Paul Strauss, Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de chirurgie [Centre Georges-François Leclerc], Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), Department of Surgical Oncology, Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), Service d'Oncologie médicale [CHU Limoges], CHU Limoges, Service d'Oncologie Médicale [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Institut Jean Godinot [Reims], Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Claudius Regaud, Oncogenesis Stress Signaling (OSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC), Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Département de radiothérapie [Gustave Roussy], Centre de Recherches sur les Macromolécules Végétales (CERMAV ), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Laboratoire Interdisciplinaire de Recherche Impliquant la Géologie et la Mécanique, Université Joseph Fourier - Grenoble 1 (UJF), Institut Curie [Paris], NetSARC, INCa & DGOS, RREPS, RESOS (INCa & DGOS) and LYRICAN, Association DAM’s, Ensemble contre Le GIST, FP7-278742, Eurosarc, ANR-10-LABX-0061, la Fondation ARC, Infosarcome, Ligue de L’Ain contre le Cancer, La Ligue contre le Cancer, EC 739521, EURACAN, ANR-10-LABX-0061,DEVWECAN,Development Cancer and Targeted Therapies(2010), CHU Saint-Etienne, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CRLCC Eugène Marquis (CRLCC), Laboratoire des Mécanismes et Transfert en Géologie (LMTG), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Observatoire Midi-Pyrénées (OMP), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Centre National de la Recherche Scientifique (CNRS), Université Lille Nord de France (COMUE)-UNICANCER, Hôpital de la Timone [CHU - APHM] (TIMONE)-Assistance Publique - Hôpitaux de Marseille (APHM), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Centre National de la Recherche Scientifique (CNRS), CHU Lille, Université de Lille, Université Claude Bernard Lyon 1 [UCBL], METRICS : Evaluation des technologies de santé et des pratiques médicales - ULR 2694, Institut Gustave Roussy [IGR], Centre Hospitalier Régional Universitaire [Lille] [CHRU Lille], Hôpital Cochin [AP-HP], Hôpital de la Timone [CHU - APHM] [TIMONE], Institut de Recherche en Cancérologie de Montpellier [IRCM - U1194 Inserm - UM], Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] [UNICANCER/ICL], CHU Strasbourg, Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] [UNICANCER/CRLCC-CGFL], Centre Jean Perrin [Clermont-Ferrand] [UNICANCER/CJP], Centre Hospitalier Régional Universitaire de Besançon [CHRU Besançon], CRLCC Jean Godinot, Centre Régional de Lutte contre le Cancer François Baclesse [Caen] [UNICANCER/CRLC], Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen [CLCC Henri Becquerel], Centre Hospitalier Universitaire de La Réunion [CHU La Réunion], and Evaluation des technologies de santé et des pratiques médicales - ULR 2694 [METRICS]
Subjects: 0301 basic medicine, Male, Multivariate analysis, sarcoma, medicine.medical_treatment, [SDV]Life Sciences [q-bio], surgery, 0302 clinical medicine, Prospective Studies, Registries, resection, Referral and Consultation, Aged, 80 and over, relapse, Hazard ratio, Hematology, Middle Aged, Prognosis, Corrigenda, 3. Good health, Survival Rate, Oncology, 030220 oncology & carcinogenesis, Surgical Procedures, Operative, Female, Sarcoma, France, Adult, medicine.medical_specialty, Adolescent, [SDV.CAN]Life Sciences [q-bio]/Cancer, reference center, Relapse free survival, survival, 03 medical and health sciences, Young Adult, medicine, Humans, Neurofibromatosis, Pathological, Aged, business.industry, Cancer, Original Articles, medicine.disease, Surgery, Radiation therapy, Editor's Choice, 030104 developmental biology, Neoplasm Recurrence, Local, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Follow-Up Studies
Abstract: International audience; BackgroundNETSARC (netsarc.org) is a network of 26 sarcoma reference centers with specialized multidisciplinary tumor boards (MDTB) aiming to improve the outcome of sarcoma patients. Since 2010, presentation to an MDTB and expert pathological review are mandatory for sarcoma patients nationwide. In the present work, the impact of surgery in a reference center on the survival of sarcoma patients investigated using this national NETSARC registry.Patients and methodsPatients’ characteristics and follow-up are prospectively collected and data monitored. Descriptive, uni- and multivariate analysis of prognostic factors were conducted in the entire series (N = 35 784) and in the subgroup of incident patient population (N = 29 497).ResultsAmong the 35 784 patients, 155 different histological subtypes were reported. 4310 (11.6%) patients were metastatic at diagnosis. Previous cancer, previous radiotherapy, neurofibromatosis type 1 (NF1), and Li–Fraumeni syndrome were reported in 12.5%, 3.6%, 0.7%, and 0.1% of patients respectively. Among the 29 497 incident patients, 25 851 (87.6%) patients had surgical removal of the sarcoma, including 9949 (33.7%) operated in a NETSARC center. Location, grade, age, size, depth, histotypes, gender, NF1, and surgery outside a NETSARC center all correlated to overall survival (OS), local relapse free survival (LRFS), and event-free survival (EFS) in the incident patient population. NF1 history was one of the strongest adverse prognostic factors for LRFS, EFS, and OS. Presentation to an MDTB was associated with an improved LRFS and EFS, but was an adverse prognostic factor for OS if surgery was not carried out in a reference center. In multivariate analysis, surgery in a NETSARC center was positively correlated with LRFS, EFS, and OS [P
Published: 2019

35. High LET Radiation Overcomes in vitro Resistance to X-rays of Chondrosarcoma Cell Lines

Author: Hamdi, Dounia Houria, Lepleux, Charlotte, NICOLLE, Agnès, Varès, Guillaume, Lesueur, Paul, Chevalier, François, Accueil et Recherche en Radiobiologie des Ions Accélérés (ARIA), Centre de recherche sur les Ions, les MAtériaux et la Photonique (CIMAP - UMR 6252), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Centre Paul Strauss, CRLCC Paul Strauss, Cell Signal Unit [Onna, Okinawa, Japon], Okinawa Institute of Science and Technology Graduate University (OIST), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche sur les Matériaux Avancés (IRMA), Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Rouen Normandie (UNIROUEN), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Université de Caen Normandie (UNICAEN), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), and Chevalier, Francois
Subjects: [SDV.CAN] Life Sciences [q-bio]/Cancer, [PHYS.PHYS.PHYS-BIO-PH] Physics [physics]/Physics [physics]/Biological Physics [physics.bio-ph], [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], [PHYS.PHYS.PHYS-BIO-PH]Physics [physics]/Physics [physics]/Biological Physics [physics.bio-ph], [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2019

36. 6 months versus 12 months of adjuvant trastuzumab in early breast cancer (PHARE): final analysis of a multicentre, open-label, phase 3 randomised trial

Author: Pivot, Xavier, Romieu, Gilles, Debled, Marc, Pierga, Jean-Yves, Kerbrat, Pierre, Bachelot, Thomas, Lortholary, Alain, Espié, Marc, Fumoleau, Pierre, Serin, Daniel, Jacquin, Jean-Philippe, Jouannaud, Christelle, Rios, Maria, Abadie-Lacourtoisie, Sophie, Venat-Bouvet, Laurence, Cany, Laurent, Catala, Stéphanie, Khayat, David, Gambotti, Laetitia, Pauporté, Iris, Faure-Mercier, Céline, Paget-Bailly, Sophie, Henriques, Julie, Grouin, Jean Marie, Centre Paul Strauss, CRLCC Paul Strauss, CRLCC Val d'Aurelle - Paul Lamarque, Institut Bergonié [Bordeaux], UNICANCER, Institut Curie [Paris], Université Paris Descartes - Paris 5 (UPD5), CRLCC Eugène Marquis (CRLCC), Centre Léon Bérard [Lyon], Centre Catherine-de-Sienne [Nantes] (CCS), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Sainte Catherine [Avignon], Institut de Cancérologie Lucien Neuwirth, CHU Saint-Etienne, CRLCC Jean Godinot, Institut Jean Godinot [Reims], Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), CHU Limoges, Clinique Francheville [Périgueux], CHU Saint-Pierre, Clinique Bizet [Pais], Institut national du cancer [Boulogne] (INCA), Ligue Nationale Contre le Cancer - Paris, Ligue Nationale Contre le Cancer (LNCC), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Unité de biostatistiques [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), The French National Cancer Institute, PHARE trial investigators: C Piprot, L Cals, L Chaigneau, F Demarchi, T N'Guyen, U Stein, C Villanueva, J L Bréau, A K Chouahnia, P Saintigny, F Boué, P deSaint-Hilaire, I Guimont, N Grossat, B Valenza, E Lévy, J Médioni, C Delbaldo, J Grenier, D Pouessel, S Lavau-Denès, C Falandry, C Fournel-Fédérico, G Freyer, S Tartas, V Trillet-Lenoir, F Bons, G Auclerc, S Chièze, N Raban, C Tournigand, S Trager-Maury, G Bousquet, C Cuvier, S Giacchetti, A Hocini, C LeMaignan, J L Misset, D Avenin, C Beerblock, J Gligorov, P Rivera, H Roché, P Bougnoux, N Hajjaji, O Capitain, R Delva, P Maillart, P Soulié, H Bonnefoi, M Durand, N Madranges, L Mauriac, P Chollet, A F Dillies, X Durando, J P Ferrière, C Mouret-Reynier, J M Nabholtz, I Van Praagh, P Cottu, V Diéras, A Durieux, M Galotte, V Girre, S Henry, I Iurisci, M Jouve, V Laurence, L Mignot, S Piperno-Neumann, P Tresca, B Coudert, E Ferrant, F Mayer, A C Vanneuville, J Bonneterre, V Servent, L Vanlemmens, P Vennin, J P Guastalla, P Biron, L Dupuy-Brousseau, L Lancry, I Ray-Coquard, P Rebattu, O Trédan, J M Extra, F Rousseau, C Tarpin, M Fabbro, E Luporsi, L Uwer, B Weber, D Berton-Rigaud, E Bourbouloux, M Campone, J M Ferrero, P Follana, R Largillier, V Mari, B Costa, H Curé, J C Eymard, N Jovenin, D Lebrun, J Meunier, G Yazbek, D Gedoin, B Laguerre, C Lefeuvre, E Vauléon, A Chevrier, C Guillemet, M Leheurteur, O Rigal, I Tennevet, C Veyret, E Brain, M Guiterrez, F Mefti-Lacheraf, T Petit, F Dalenc, L Gladieff, H Roché, F André, S Delaloge, J Domont, J Ezenfis, M Spielmann, P Guillet, V Boulanger, J Provençal, L Stefani, C Alliot, D Ré, C Bellaiche-Miccio, G Boutan-Laroze, R Vanica, P Dion, A Hocini, G Sadki-Benaoudia, A Marti, A L Villing, B Slama, J L Dutel, S Nguyen, R Saad, O Arsène, Z Merad-Boudia, H Orfeuvre, J Egreteau, M J Goudier, R Lamy, B Leduc, C Sarda, B Salles, C Agostini, I Cauvin, A Dufresne, M Mangold, S Lebouvier-Sadot, B Audhuy, J C Barats, S Cluet-Dennetière, D Zylberait, G Netter, L Gautier-Felizot, I Cojean-Zelek, A Plantade, S Vignot, E Guardiola, P Marti, I deHartingh, R Diab, A Dietmann, S Ruck, C Portois, E Guardiola, S Oddou-Lagranière, F Campos-Gazeau, A Bourcier, F Priou, J F Geay, D Mayeur, P Gabez, R ElAmarti, M Combe, J Ezenfis, P Raichon-Patru, P Amsalhem, J Dauba, D Paraiso, F Guinet, B Duvert, M Litor, F Kara-Slimane, A Bichoffe, N Denizon, J Meunier, P Soyer, F Morvan, S Van-Hulst, L Vincent, C Alleaume, P Ibanez-Martin, A Youssef, Z Tadrist, E Carola, C Pourny, J F Toccanier, N Al-Aukla, K Mahour-Bacha, J Salvat, L Cals, P Nouyrigat, S Clippe, M C Gouttebel, L Vedrine, G Clavreul, O Collard, D Mille, Y Goubely, J Grenier, R Hervé, S Kirscher, F Plat, V Delecroix, V Ligeza-Poisson, D Coeffic, L Dupuy-Brousseau, D Fric, C Garnier, C Leyronnas, T Kreitman, R Largillier, E Teissier, P Martin, S Rohart deCordoue, C ElKouri, J F Ramée, C Laporte, O Bernard, T Altwegg, A Darut-Jouve, J P Dujols, F Darloy, C Giraud, V Pottier-Kyndt, N Achour, S Drony, M Moriceau, C Sarrazin, J C Legueul, J Mandet, D Besson, A C Hardy-Bessard, J Cretin, P Houyau, E Achille, D Genêt, H Thévenot, A Moran-Ribon, J M Pavlovitch, P Ardisson, I Moullet, B Couderc, V Fichet, F Burki, A Auliard, C B Levaché, G Auclerc, P Cailleux, F Schaeffer, N Albin, D Sévin-Robiche, J Domas, S Ellis, P Montcuquet, G A Baumont, M Bégue, S Gréget, J L Ratoanina, A Vanoli, C Bielsa, M Bonichon-Lamichhane, D Jaubert, H Laharie-Mineur, L Alcaraz, J Cretin, E Legouffe, H Bourgeois, G Cartron, F Denis, O Dupuis, G Ganem, S Roche-Forestier, L Delzenne, E Chirat, J L Baticle, E Béguier, S Jacquot, E Janssen, H Lauché, A LeRol, J P Chantelard, G A L'Helgoualc'h, E C Antoine, A Kanoui, J F Llory, J M Vannetzel, J Vignoud, C Bruna, T Facchini, K Moutel-Corviole, A Voloch, A Ghoul, D Loiseau, K Mahour-Bacha, N Barbet, N Dohollou, K Yakendji, CCSD, Accord Elsevier, and Ligue Nationnale Contre le Cancer
Subjects: [SDV.CAN] Life Sciences [q-bio]/Cancer, [SDV.CAN]Life Sciences [q-bio]/Cancer, skin and connective tissue diseases
Abstract: International audience; Background: In 2013, the interim analysis of the Protocol for Herceptin as Adjuvant therapy with Reduced Exposure (PHARE) trial could not show that 6 months of adjuvant trastuzumab was non-inferior to 12 months. Here, we report the planned final analysis based on the prespecified number of occurring events.Methods: PHARE is an open-label, phase 3, non-inferiority randomised trial of patients with HER2-positive early breast cancer comparing 6 months versus 12 months of trastuzumab treatment concomitant with or following standard neoadjuvant or adjuvant chemotherapy. The study was undertaken in 156 centres in France. Eligible patients were women aged 18 years or older with non-metastatic, operable, histologically confirmed adenocarcinoma of the breast and either positive axillary nodes or negative axillary nodes but a tumour of at least 10 mm. Participants must have received at least four cycles of a chemotherapy for this breast cancer and have started receiving adjuvant trastuzumab-treatment. Eligible patients were randomly assigned to either 6 months or 12 months of trastuzumab therapy duration between the third and sixth months of adjuvant trastuzumab. The randomisation was stratified by concomitant or sequential treatment with chemotherapy, oestrogen receptor status, and centre. The primary objective was non-inferiority in the intention-to-treat population in the 6-month group in terms of disease-free survival with a prespecified hazard margin of 1·15. This trial is registered with ClinicalTrials.gov, number NCT00381901.Findings: 3384 patients were enrolled and randomly assigned to either 12 months (n=1691) or 6 months (n=1693) of adjuvant trastuzumab. One patient in the 12-month group and three patients in the 6-month group were excluded, so 1690 patients in each group were included in the intention-to-treat analysis. At a median follow-up of 7·5 years (IQR 5·3-8·8), 704 events relevant to disease-free survival were observed (345 [20·4%] in the 12-month group and 359 [21·2%] in the 6-month group). The adjusted hazard ratio for disease-free survival in the 12-month group versus the 6-month group was 1·08 (95% CI 0·93-1·25; p=0·39). The non-inferiority margin was included in the 95% CI. No differences in effects pertaining to trastuzumab duration were found in any of the subgroups. After the completion of trastuzumab treatment, rare adverse events occurred over time and the safety analysis remained similar to the previously published report. In particular, we found no change in the cardiac safety comparison, and only three additional cases in which the left ventricular ejection fraction decreased to less than 50% have been reported in the 12-month group.Interpretation: The PHARE study did not show the non-inferiority of 6 months versus 12 months of adjuvant trastuzumab. Hence, adjuvant trastuzumab standard duration should remain 12 months.
Published: 2019

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

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

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

Author: S. Renard-Oldrini, Georges Noël, Jean-Léon Lagrange, Paul Sargos, Marc-André Mahé, Julien Domont, F. Bonnetain, C. Chevreau, F. Collin, Isabelle Ray-Coquard, J. Thariat, Gilles Truc, Aurélie Bertaut, Jean-Louis Merlin, X. Liem, Céline Mirjolet, Philippe Maingon, Département d'oncologie médicale [Centre Georges-François Leclerc], Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER, Centre de Recherche en Automatique de Nancy (CRAN), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), UNICANCER, Centre Paul Strauss, CRLCC Paul Strauss, Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR), Institut Bergonié [Bordeaux], Centre Léon Bérard [Lyon], Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER, Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Oncologie médicale [CHU Henri Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Henri Mondor [Créteil], CRLCC René Gauducheau, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU), Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Université Lille Nord de France (COMUE)-UNICANCER, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Henri Mondor, Service de Radiothérapie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Oncologie Radiothérapie [CHU Pitié Salpétrière], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Adult, Male, 0301 basic medicine, Oncology, medicine.medical_specialty, Neoplasms, Radiation-Induced, Research paper, medicine.medical_treatment, Breast Neoplasms, Apoptosis, [SDV.CAN]Life Sciences [q-bio]/Cancer, CD8-Positive T-Lymphocytes, General Biochemistry, Genetics and Molecular Biology, Cohort Studies, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, Matched cohort, Internal medicine, Biomarkers, Tumor, Humans, Medicine, Prospective Studies, Adverse effect, Aged, Aged, 80 and over, business.industry, Cancer, Sarcoma, General Medicine, Middle Aged, medicine.disease, Primary tumor, 3. Good health, Radiation therapy, Predictive biomarker, 030104 developmental biology, ROC Curve, Area Under Curve, Case-Control Studies, 030220 oncology & carcinogenesis, Radio-induced sarcoma, Biomarker (medicine), Female, Lymphocyte, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business
Abstract: International audience; Purpose: Radiation-induced sarcoma (RIS) is a rare but serious event. Its occurrence has been discussed during the implementation of new radiation techniques and justified appropriate radioprotection requirements. New approaches targeting intrinsic radio-sensitivity have been described, such as radiation-induced CD8 T-lymphocyte apoptosis (RILA) able to predict late radio-induced toxicities. We studied the role of RILA as a predisposing factor for RIS as a late adverse event following radiation therapy (RT).Patients and methods: In this prospective biological study, a total of 120 patients diagnosed with RIS were matched with 240 control patients with cancer other than sarcoma, for age, sex, primary tumor location and delay after radiation. RILA was prospectively assessed from blood samples using flow cytometry.Results: Three hundred and forty-seven patients were analyzed (118 RIS patients and 229 matched control patients). A majority (74%) were initially treated by RT for breast cancer. The mean RT dose was comparable with a similar mean (± standard deviation) for RIS (53.7 ± 16.0 Gy) and control patients (57.1 ± 15.1 Gy) (p = .053). Median RILA values were significantly lower in RIS than in control patients with respectively 18.5% [5.5–55.7] and 22.3% [3.8–52.2] (p = .0008). Thus, patients with a RILA >21.3% are less likely to develop RIS (p
Published: 2019

39. An integrated genomic and metabolomic approach for defining survival time in adult oligodendrogliomas patients

Author: Mariana Guergova-Kuras, François Proust, Roland Schott, Nassim Dali-Youcef, Benoit Lhermitte, A. Ercument Cicek, Izzie Jacques Namer, Natacha Entz-Werle, Pilar Schneider, Rémy Heller, Martial Piotto, Caroline Bund, Georges Noël, Marie-Pierre Chenard, François-Marie Moussallieh, Hôpital de Hautepierre [Strasbourg], Les Hôpitaux Universitaires de Strasbourg (HUS), Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie (ICube), École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Université de Strasbourg (UNISTRA)-Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Les Hôpitaux Universitaires de Strasbourg (HUS)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Ariana Pharmaceuticals (ARIANA), Ariana Pharmaceuticals, Carnegie Mellon University [Pittsburgh] (CMU), Bilkent University [Ankara], 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), Nouvel Hôpital Civil de Strasbourg, Bruker BioSpin, GmbH, Hôpitaux Civils de Colmar, Centre Paul Strauss, CRLCC Paul Strauss, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA), Çiçek, A. Ercüment, Bruker BioSpin [Wissembourg], and DALI-YOUCEF, Nassim
Subjects: Adult, IDH, PTEN, Magnetic Resonance Spectroscopy, Time Factors, IDH1, Methyltransferase, [SDV]Life Sciences [q-bio], Endocrinology, Diabetes and Metabolism, Clinical Biochemistry, Oligodendroglioma, Biology, Severity of Illness Index, 01 natural sciences, Biochemistry, 03 medical and health sciences, chemistry.chemical_compound, medicine, Humans, Tensin, Metabolomics, Overall survival, neoplasms, Tumor metabolome, 030304 developmental biology, Phosphocholine, 0303 health sciences, 010401 analytical chemistry, Methylation, medicine.disease, Survival Analysis, HRMAS-NMR spectroscopy, 0104 chemical sciences, [SDV] Life Sciences [q-bio], chemistry, Cancer research, biology.protein, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]
Abstract: International audience; Introduction: The identification of frequent acquired mutations shows that patients with oligodendrogliomas have divergent biology with differing prognoses regardless of histological classification. A better understanding of molecular features as well as their metabolic pathways is essential.Objectives: The aim of this study was to examine the relationship between the tumor metabolome, six genomic aberrations (isocitrate dehydrogenase1 [IDH1] mutation, 1p/19q codeletion, tumor protein p53 [TP53] mutation, O6-methylguanin-DNA methyltransferase [MGMT] promoter methylation, epidermal growth factor receptor [EGFR] amplification, phosphate and tensin homolog [PTEN] methylation), and the patients' survival time.Methods: We applied 1H high-resolution magic-angle spinning (HRMAS) nuclear magnetic resonance (NMR) spectroscopy to 72 resected oligodendrogliomas.Results: The presence of IDH1, TP53, 1p19q codeletion, MGMT promoter methylation reduced the relative risk of death, whereas PTEN methylation and EGFR amplification were associated with poor prognosis. Increased concentration of 2-hydroxyglutarate (2HG), N-acetyl-aspartate (NAA), myo-inositol and the glycerophosphocholine/phosphocholine (GPC/PC) ratio were good prognostic factors. Increasing the concentration of serine, glycine, glutamate and alanine led to an increased relative risk of death.Conclusion: HRMAS NMR spectroscopy provides accurate information on the metabolomics of oligodendrogliomas, making it possible to find new biomarkers indicative of survival. It enables rapid characterization of intact tissue and could be used as an intraoperative method.
Published: 2019

40. Continuation of Bevacizumab vs Cetuximab Plus Chemotherapy After First Progression in KRAS Wild-Type Metastatic Colorectal Cancer

Author: Bennouna, Jaafar, Hiret, Sandrine, Bertaut, Aurélie, Bouche, Olivier, Deplanque, Gaël, Borel, Christian, François, Eric, Conroy, Thierry, Ghiringhelli, François, Des Guetz, Gaëtan, Seitz, Jean-François, Artru, Pascal, Hebbar, Mohamed, Stanbury, Trevor, Denis, Marc, Adenis, Antoine, Borg, Christophe, Centre hospitalier universitaire de Nantes (CHU Nantes), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Département d'oncologie médicale [Centre Georges-François Leclerc], Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER, Centre Hospitalier Universitaire de Reims (CHU Reims), Hôpital Saint-Joseph [Marseille], CRLCC Paul Strauss, Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'oncologie digestive et hépato-gastro-entérologie [Hôpital de la Timone - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Hôpital privé Jean Mermoz, Service d'oncologie médicale (CHRU Lille), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), R&D Unicancer [Paris], Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université Lille Nord de France (COMUE)-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), Service d'Oncologie Médicale [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Université de Lille-UNICANCER, and Herrada, Anthony
Subjects: [SDV.CAN] Life Sciences [q-bio]/Cancer, [SDV.CAN]Life Sciences [q-bio]/Cancer
Abstract: International audience; Importance:Second-line treatment with chemotherapy plus bevacizumab or cetuximab is a valid option for metastatic colorectal cancer.Objective:To evaluate the progression-free survival (PFS) rate at 4 months with chemotherapy plus bevacizumab vs cetuximab for patients with progression of metastatic colorectal cancer after bevacizumab plus chemotherapy.Design, Setting, and Participants:A prospective, open-label, multicenter, randomized phase 2 trial was conducted from December 14, 2010, to May 5, 2015. The main eligibility criterion was disease progression after bevacizumab plus fluorouracil with irinotecan or oxaliplatin in patients with wild-type KRAS exon 2 metastatic colorectal cancer. All analyses were performed on the modified intent-to-treat population.Interventions:Patients were randomized to arm A (FOLFIRI [fluorouracil and folinic acid combined with irinotecan] or modified FOLFOX6 [fluorouracil and folinic acid combined with oxaliplatin] plus bevacizumab) or arm B (FOLFIRI or modified FOLFOX6 plus cetuximab); the second-line chemotherapy regimen was chosen according to first-line treatment (crossover).Main Outcomes and Measures:The primary end point was the 4-month PFS rate. Secondary end points included safety, objective response rate, overall survival, and PFS.Results:A total of 132 patients (47 women and 85 men; median age, 63.0 years [range, 33.0-84.0 years]; 74 patients with an Eastern Cooperative Oncology Group performance status of 0, 54 patients with a performance status of 1, and 4 patients with unknown performance status) were included at 25 sites. The 4-month PFS rate was 80.3% (95% CI, 68.0%-88.3%) in arm A and 66.7% (95% CI, 53.6%-76.8%) in arm B. The median PFS was 7.1 months (95% CI, 5.7-8.2 months) in arm A and 5.6 months (95% CI, 4.2-6.5 months) in arm B (hazard ratio, 0.71; 95% CI, 0.50-1.02; P = .06), and the median overall survival was 15.8 months (95% CI, 9.5-22.3 months) in arm A and 10.4 months (95% CI, 7.0-16.2 months) in arm B (hazard ratio, 0.69; 95% CI, 0.46-1.04; P = .08). A central analysis of KRAS (exons 2, 3, and 4), NRAS (exons 2, 3, and 4), and BRAF (V600) was performed for 95 tumor samples. Eighty-one patients had wild-type KRAS and wild-type NRAS tumors.Conclusions and Relevance:The results of the PRODIGE18 (Partenariat de Recherche en Oncologie DIGEstive) study showed a nonsignificant difference but favored continuation of bevacizumab with chemotherapy crossover for patients with wild-type RAS metastatic colorectal cancer that progressed with first-line bevacizumab plus chemotherapy.Trial Registration:ClinicalTrials.gov identifier: NCT01442649 and clinicaltrialsregister.eu identifier: EUDRACT 2009-012942-22.
Published: 2019

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

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

42. FOLFIRINOX or Gemcitabine as Adjuvant Therapy for Pancreatic Cancer

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

43. Merkel cell carcinoma in France: a registries-based, comprehensive epidemiological survey

Author: E. Marrer, Bénédicte Lapôtre-Ledoux, Simona Bara, M. Fondain, Zoé Uhry, Michel Velten, Pascale Grosclaude, Florence Molinié, Marc Colonna, B. Tretarre, Olivier Dereure, Bernard Guillot, A.V. Guizard, A. S. Woronoff, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Pathogénèse et contrôle des infections chroniques (PCCI), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), CHU Montpellier, Cancer Registry of Isère, Département d'Ingénierie des Systèmes (ex SIS) (DIS), Institut de Recherches sur les lois Fondamentales de l'Univers (IRFU), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Laboratoire de Physique des Composants à Semiconducteurs (LPCS), École Nationale Supérieure d'Électronique et de Radioélectricité de Grenoble (ENSERG)-Centre National de la Recherche Scientifique (CNRS), Registre des cancers du Bas-Rhin, CRLCC Paul Strauss, Registre général des cancers du Tarn, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Registre des Tumeurs de l'Hérault, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre Hospitalier Universitaire de Montpellier (CHU Montpellier ), Registre des cancers du Tarn, and Association humanitaire (entraide, action sociale) - Albi
Subjects: Adult, Male, medicine.medical_specialty, Pediatrics, Skin Neoplasms, Adolescent, Dermatology, 030207 dermatology & venereal diseases, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Sex Factors, Epidemiology, Carcinoma, medicine, Humans, Registries, Young adult, Child, Survival rate, ComputingMilieux_MISCELLANEOUS, Aged, Retrospective Studies, Aged, 80 and over, Relative survival, Merkel cell carcinoma, business.industry, Incidence (epidemiology), Incidence, Age Factors, Infant, Newborn, food and beverages, Infant, Retrospective cohort study, Middle Aged, medicine.disease, 3. Good health, Carcinoma, Merkel Cell, Survival Rate, Epidemiologic Studies, Infectious Diseases, 030220 oncology & carcinogenesis, Child, Preschool, Female, France, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Background Merkel cell carcinoma (MCC) is a rare primary cutaneous neuroendocrine carcinoma. Owing to its low incidence, epidemiological data are scarce and have never been analysed in France to identify the main epidemiological trends. Methods Data from MCC patients diagnosed between 1998 and 2010 were obtained from 11 French cancer registries in the FRANCIM network. The main epidemiological characteristics of MCC were investigated between 2006 and 2010 because comprehensive data were only available for this period. The main focus was tumour incidence and mortality over time. Results Between 1998 and 2010, 562 cases of MCC were reported in the registries. From 2006 to 2010 (290 cases), European- and world-standardized incidence rates were 0.26 and 0.43 per 100,000 person-years in men and 0.24 and 0.38 per 100,000 person-years in women. MCC is more frequent in females in France (56.9%) with male/female ratio 1.1. Relative survival rates were 84%, 56% and 42% at one, three and 5 years, respectively. Conclusions The incidence of MCC clearly increased over time in all areas under focus. The standardized incidence in France was comparable to the incidence observed in other countries for the same period, but French data are too recent to conclude on an increase in MCC incidence. Prognosis remains poor in all countries in which data are available.
Published: 2018

44. Efficacy of anthracycline/taxane-based neo-adjuvant chemotherapy on triple-negative breast cancer in BRCA1 / BRCA2 mutation carriers

Author: Véronique Mari, Catherine Noguès, Paul Gesta, Laurence Faivre, Thierry Petit, Jean-Pierre Fricker, Christine Lasset, Michel Velten, Emmanuelle Mouret-Fourme, Lucie Bignon, Alain Lortholary, Akila Hamimi, Laurence Gladieff, Olivier Caron, Dominique Stoppa-Lyonnet, Département de médecine oncologique, CRLCC Paul Strauss, CRLCC René Huguenin, Département de Biologie des Tumeurs, Institut Curie [Paris], Unité de génétique et biologie des cancers (U830), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5), Université Sorbonne Paris Cité (USPC), Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR), Centre Catherine-de-Sienne [Nantes] (CCS), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, 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), Centre Léon Bérard [Lyon], Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Centre Hospitalier Georges Renon [Niort] (CH Georges Renon Niort), Institut Claudius Regaud, Hôpital René HUGUENIN (Saint-Cloud), Département d'Oncologie et Hématologie [Strasbourg], Les Hôpitaux Universitaires de Strasbourg (HUS), Progression tumorale et microenvironnement. Approches translationnelles et épidémiologie, Université de Strasbourg (UNISTRA)-CHU Strasbourg-Les Hôpitaux Universitaires de Strasbourg (HUS)-Institut Régional du Cancer-Centre Paul Strauss : Centre Régional de Lutte contre le Cancer (CRLCC), université de Bourgogne, LNC, Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), Institut Curie, Université Paris Descartes - Paris 5 (UPD5)-Institut Curie-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc (CRLCC - CGFL), Centre Antoine Lacassagne, CRLCC Antoine Lacassagne, and CRLCC Institut Claudius Regaud
Subjects: 0301 basic medicine, Oncology, medicine.medical_treatment, neo-adjuvant chemotherapy, BRCA2 mutation, Triple Negative Breast Neoplasms, Docetaxel, 0302 clinical medicine, Antineoplastic Combined Chemotherapy Protocols, Anthracyclines, skin and connective tissue diseases, Triple-negative breast cancer, BRCA1 Protein, Middle Aged, Neoadjuvant Therapy, 3. Good health, prognostic significance, Treatment Outcome, 030220 oncology & carcinogenesis, Mutation (genetic algorithm), triple-negative breast cancer, Female, Adult, Heterozygote, medicine.medical_specialty, Paclitaxel, Anthracycline, [SDV.CAN]Life Sciences [q-bio]/Cancer, Disease-Free Survival, 03 medical and health sciences, pathologic complete response, Breast cancer, BRCA1 mutation, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, Internal Medicine, medicine, Humans, Neo adjuvant chemotherapy, Brca1 gene, BRCA2 Protein, Chemotherapy, Taxane, business.industry, medicine.disease, 030104 developmental biology, Mutation, Surgery, business
Abstract: IF 2.424; International audience; This study aims to estimate the pathologic complete response (pCR) rate after neo-adjuvant chemotherapy and to compare disease-free survival (DFS) and overall survival (OS) between pCR and non-pCR groups of patients with triple-negative breast cancer (TNBC) and deleterious BRCA1 or BRCA2 mutation. We carried out a retrospective analysis of 53 patients including 46 BRCA1, 6 BRCA2, and 1 combined BRCA1 and BRCA2 mutation. All patients had been diagnosed with triple-negative breast cancer (TNBC) between 1997 and 2014. Neo-adjuvant therapy consisted of regimens that were based on anthracycline or an anthracycline-taxane doublet. DFS included any relapse or second cancer. The Kaplan-Meier method and the log-rank test were used to compare pCR and non-pCR groups. A pCR was observed in 23 (42.6% [95% CI, 29.2%-56.8%]) of the TNBC included. The pCR rate was 38.3% [95% CI, 26%-55%] among BRCA1 mutation carriers, and 66% among the 6 BRCA2 mutation carriers. Median follow-up was 4.4 years (range 0.62-16.2 years) and did not differ between the groups (P = .25). Fifteen relapses and six second cancers were recorded during the follow-up period. Eleven deaths occurred, all of which were in the non-pCR group. DFS (P
Published: 2018

45. Prognostic factors for survival in adult patients with recurrent glioblastoma: a decision-tree-based model

Author: Edouard Dezamis, Phong Dam Hieu, Johan Pallud, Luc Bauchet, Renata Ursu, J. Duntze, Olivier Langlois, Jean-Luc Barat, Alexandre Roux, Georges Noël, Marc Zanello, Elodie Sorbets, Jimmy Voirin, Jacques Guyotat, Antoine Petit, Philippe Menei, Robert Corns, Evelyne Emery, Johann Peltier, Fabien Litre, Nicolas Desse, Adeline Riondel, Sonia Zouaoui, François Caire, Pierre-Jean Le Reste, Pascale Fabbro-Peray, Jean-Rodolphe Vignes, Philippe Metellus, Antoine F. Carpentier, Anaïs Chivet, Etienne Audureau, Thierry Faillot, Emmanuelle Lechapt-Zalcman, Service de santé publique [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Laboratoire d'Investigation Clinique (LIC), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre Hospitalier Sainte Anne [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Descartes - Paris 5 (UPD5), Hôpital Avicenne [AP-HP], Hôpital Privé Clairval [Marseille], Centre de Recherches en Oncologie biologique et Oncopharmacologie (CRO2), Aix Marseille Université (AMU)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Paul Strauss, CRLCC Paul Strauss, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA), Service de Neurochirurgie [Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-CHU Gui de Chauliac [Montpellier], Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], Hospices Civils de Lyon (HCL), Service de neurochirurgie [Rennes] = Neurosurgery [Rennes], CHU Pontchaillou [Rennes], Service de neurochirurgie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon [AP-HP], Hôpital Maison Blanche, Centre Hospitalier Universitaire de Reims (CHU Reims), Hôpital d'Instruction des Armées Sainte Anne, Service de Santé des Armées, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Service de Neurochirurgie [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), Département de Pathologie [CHU Caen], CHU Amiens-Picardie, Hôpital pasteur [Colmar], Département de neurochirurgie [Angers], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Service de Neurochirurgie [CHU Limoges], CHU Limoges, Service de neurochirurgie [Brest], Hôpital de la Cavale Blanche - CHRU Brest (CHU - BREST ), Service de neurochirurgie [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Hôpital Pellegrin, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, BESPIM, Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Aide à la Décision pour une Médecine Personnalisé - Laboratoire de Biostatistique, Epidémiologie et Recherche Clinique - EA 2415 (AIDMP), Université Montpellier 1 (UM1)-Université de Montpellier (UM), Institut de psychiatrie et neurosciences (U894 / UMS 1266), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut des Neurosciences de Montpellier - Déficits sensoriels et moteurs (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Service de neurochirurgie [Rennes], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Hôpital Jean Minjoz, Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Université de Caen Normandie (UNICAEN), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital avicenne, Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Avicenne, Hôpital Beaujon-Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Service de neurochirurgie [Rouen], Centre Hospitalier Régional Universitaire de Nîmes (CHRU Nîmes), Institut des Neurosciences de Montpellier (INM), Service de Neurochirurgie [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [CHU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), and Centre de Psychiatrie et Neurosciences (U894)
Subjects: Oncology, Male, Cancer Research, medicine.medical_specialty, Neurology, Prognostic models, medicine.medical_treatment, Conditional random forest, Recursive partitioning, [SDV.CAN]Life Sciences [q-bio]/Cancer, Karnofsky performance status, 03 medical and health sciences, 0302 clinical medicine, Recurrence, Internal medicine, Decision tree, Medicine, Humans, Overall survival, ComputingMilieux_MISCELLANEOUS, Aged, Retrospective Studies, Chemotherapy, Adult patients, business.industry, Proportional hazards model, Brain Neoplasms, Decision Trees, Random survival forest, Retrospective cohort study, Middle Aged, Prognosis, 3. Good health, 030220 oncology & carcinogenesis, Cox model, Disease Progression, Female, Surgery, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neurology (clinical), Recursive partitioning analysis, business, Glioblastoma, 030217 neurology & neurosurgery, Chemoradiotherapy, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: We assessed prognostic factors in relation to OS from progression in recurrent glioblastomas. Retrospective multicentric study enrolling 407 (training set) and 370 (external validation set) adult patients with a recurrent supratentorial glioblastoma treated by surgical resection and standard combined chemoradiotherapy as first-line treatment. Four complementary multivariate prognostic models were evaluated: Cox proportional hazards regression modeling, single-tree recursive partitioning, random survival forest, conditional random forest. Median overall survival from progression was 7.6 months (mean, 10.1; range, 0-86) and 8.0 months (mean, 8.5; range, 0-56) in the training and validation sets, respectively (p = 0.900). Using the Cox model in the training set, independent predictors of poorer overall survival from progression included increasing age at histopathological diagnosis (aHR, 1.47; 95% CI [1.03-2.08]; p = 0.032), RTOG-RPA V-VI classes (aHR, 1.38; 95% CI [1.11-1.73]; p = 0.004), decreasing KPS at progression (aHR, 3.46; 95% CI [2.10-5.72]; p
Published: 2018

46. Thoracic skeletal anomalies following surgical treatment of esophageal atresia. Lessons from a national cohort

Author: Nicoleta Panait, E. Habonimana, Philine De Vries, F. Lefebvre, Hubert Lardy, Olivier Jaby, Christian Piolat, Frédéric Auber, Julia Boubnova, Sabine Irtan, Guillaume Podevin, Thierry Lamireau, François Bastard, Aurélie Le Mandat, Aline Ranke-Chrétien, L. Fourcade, Jean-Luc Michel, Jean François Lecompte, Laurent Michaud, Arnaud Bonnard, Françoise Schmitt, Benoit Delorme, Marc Margaryan, Josephine Borgnon, François Becmeur, Anne Dariel, Virginie Fouquet, J. Gaudin, Corinne Borderon, H. Allal, Thomas Gelas, V. Rousseau, Cecilia Tolg, P. Buisson, T. Petit, Unité Pédiatrique [Jeanne de Flandre], Hôpital Jeanne de Flandre [Lille], Service de neurochirurgie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de chirurgie pédiatrique [CHU Grenoble], Centre Hospitalier Universitaire [Grenoble] (CHU), Service de chirurgie pédiatrique [CHU Strasbourg], Les Hôpitaux Universitaires de Strasbourg (HUS), Unité de Recherche Oenologie [Villenave d'Ornon], Institut National de la Recherche Agronomique (INRA)-Université de Bordeaux (UB)-Institut des Sciences de la Vigne et du Vin (ISVV), Hôpital des Enfants, CHU Toulouse [Toulouse], Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), CRLCC Paul Strauss, Hôpital Bicètre, Service de chirurgie pédiatrique, Hôpital Bicêtre, Chirurgie orthopédique et pédiatrique [Hôpital de la Timone - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), CHU Pontchaillou [Rennes], Laboratoire de recherche sur la gouvernance publique, territoire et communication (LARGOTEC/CECCOPOP), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre Hospitalier Régional Universitaire de Tours (CHRU de Tours), Service de chirurgie viscérale pédiatrique [CHU Trousseau], CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Clermont-Ferrand, Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Biomolécules Thérapies anti-tumorales (EA4021), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503), Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Unité de Recherche Oenologie [Villenave d'Ornon] (OENO), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Male, medicine.medical_specialty, medicine.medical_treatment, Thoracic, [SDV]Life Sciences [q-bio], Scoliosis, 03 medical and health sciences, 0302 clinical medicine, Thoracic Diseases, 030225 pediatrics, medicine, Operative report, Thoracoscopy, Humans, Thoracotomy, Child, Esophageal Atresia, Digestive System Surgical Procedures, Retrospective Studies, Rib cage, medicine.diagnostic_test, business.industry, Retrospective cohort study, General Medicine, medicine.disease, 3. Good health, Surgery, Musculoskeletal Abnormalities, Radiography, medicine.anatomical_structure, Treatment Outcome, Atresia, Pediatrics, Perinatology and Child Health, Radiography, Thoracic, 030211 gastroenterology & hepatology, Female, business, Thoracic wall
Abstract: International audience; INTRODUCTION: Thoracotomy as surgical approach for esophageal atresia treatment entails the risk of deformation of the rib cage and consequently secondary thoracogenic scoliosis. The aim of our study was to assess these thoracic wall anomalies on a large national cohort and search for factors influencing this morbidity.MATERIALS AND METHODS: Pediatric surgery departments from our national network were asked to send recent thoracic X-ray and operative reports for patients born between 2008 and 2010 with esophageal atresia. The X-rays were read in a double-blind manner to detect costal and vertebral anomalies.RESULTS: Among 322 inclusions from 32 centers, 110 (34.2%) X-rays were normal and 25 (7.7%) displayed thoracic malformations, including 14 hemivertebrae. We found 187 (58.1%) sequelae of surgery, including 85 costal hypoplasia, 47 other types of costal anomalies, 46 intercostal space anomalies, 21 costal fusions and 12 scoliosis, with some patients suffering from several lesions. The rate of patients with these sequelae was not influenced by age at intervention, weight at birth, type of atresia, number of thoracotomy or size of the center. The rate of sequelae was higher following a classical thoracotomy (59.1%), whatever the way that thoracotomy was performed, compared to nonconverted thoracoscopy (22.2%; p=0.04).CONCLUSION: About 60 % of the patients suffered from a thoracic wall morbidity caused by the thoracotomy performed as part of surgical treatment of esophageal atresia. Minimally invasive techniques reduced thoracic wall morbidity. Further studies should be carried out to assess the potential benefit of minimally invasive approaches to patient pulmonary functions and on the occurrence of thoracogenic scoliosis in adulthood.LEVELS OF EVIDENCE: Level III retrospective comparative treatment study.
Published: 2018

47. Combined irradiation and targeted therapy or immune checkpoint blockade in brain metastases: toxicities and efficacy

Author: Youlia M. Kirova, Georges Noël, F. Dhermain, E. Le Rhun, Agnès Tallet, Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Institut Gustave Roussy (IGR), Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U 1192 (PRISM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER, Centre Paul Strauss, CRLCC Paul Strauss, Institut Curie [Paris], Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Université Lille Nord de France (COMUE)-UNICANCER, and SALZET, Michel
Subjects: 0301 basic medicine, Oncology, medicine.medical_specialty, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Stereotactic radiation therapy, Pharmacology, Systemic therapy, radiation therapy, Radiosurgery, Targeted therapy, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Humans, Medicine, Molecular Targeted Therapy, combination, Brain Neoplasms, business.industry, radiosurgery, Antibodies, Monoclonal, toxicity, Hematology, Immunotherapy, Combined Modality Therapy, Immune checkpoint, 3. Good health, [SDV] Life Sciences [q-bio], Radiation therapy, 030104 developmental biology, 030220 oncology & carcinogenesis, Concomitant, cerebral, immunotherapy, Cranial Irradiation, business
Abstract: International audience; Background: Targeted therapies (TT) and immune checkpoint inhibitors (ICI) are currently modifying the landscape of metastatic cancer management and are increasingly used over the course of many cancers treatment. They allow long-term survival with controlled extra-cerebral disease, contributing to the increasing incidence of brain metastases (BMs). Radiation therapy remains the cornerstone of BMs treatment (either whole brain irradiation or stereotactic radiosurgery), and investigating the safety profile of radiation therapy combined with TT or ICI is of high interest. Discontinuing an efficient systemic therapy, when BMs irradiation is considered, might allow systemic disease progression and, on the other hand, the mechanisms of action of these two therapeutic modalities might lead to unexpected toxicities and/or greater efficacy, when combined.Patients and methods: We carried out a systematic literature review focusing on the safety profile and the efficacy of BMs radiation therapy combined with targeted agents or ICI, emphasizing on the role (if any) of the sequence of combination scheme (drug given before, during, and/or after radiation therapy).Results: Whereas no relevant toxicity has been noticed with most of these drugs, the concomitant use of some other drugs with brain irradiation requires caution.Conclusion: Most of available studies appear to advocate for TT or ICI combination with radiation therapy, without altering the clinical safety profiles, allowing the maintenance of systemic treatments when stereotactic radiation therapy is considered. Cognitive functions, health-related quality of life and radiation necrosis risk remain to be assessed. The results of prospective studies are awaited in order to complete and validate the above discussed retrospective data.
Published: 2017

48. Minimal clinically important difference for the EORTC QLQ-C30 and QLQ-BN20 questionnaires in glioblastoma patients using several distribution and anchor-based methods

Author: Ousmen, Ahmad, Anota, Amelie, Chauffert, Bruno, Feuvret, Loic, Taillandier, Luc, Frappaz, Didier, Taillia, Herve, Schott, Roland, Ducray, Francois, Fabbro, Michel, Tennevet, Isabelle, Ghiringhelli, Francois, Guillamo, Jean-Sebastien, Durando, Xavier, Castera, Daniel, Frenay, Marc, Campello, Chantal, Skrzypski, Jerome, Chinot, Olivier, Bonnetain, Franck, Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Cancéropôle du Grand Est, CHU Amiens-Picardie, CHirurgie, IMagerie et REgénération tissulaire de l’extrémité céphalique - Caractérisation morphologique et fonctionnelle - UR UPJV 7516 (CHIMERE), Université de Picardie Jules Verne (UPJV), Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière (CRICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Automatique de Nancy (CRAN), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Service de neurologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Société française du cancer de l'enfant [Rennes] (SFCE), Centre Léon Bérard [Lyon], Groupe onco-hématologie adolescents jeunes adultes [Paris] (GO-AJA), Association des neuro-oncologues d'expression française [Nancy] (ANOCEF), Service d'Oncologie (HIA VAL DE GRACE - Oncologie), HIA VAL DE GRACE, Centre Paul Strauss, CRLCC Paul Strauss, 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), UNICANCER - Institut régional du Cancer Montpellier Val d'Aurelle (ICM), CRLCC Val d'Aurelle - Paul Lamarque, Département d'oncologie médicale [Rouen], Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), 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, CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Hypoxie, physiopathologies cérébrovasculaire et tumorale (CERVOxy), Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales (ISTCT), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER, Clinique Saint Pierre, Perpignan, Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), Département de neurooncologie, Hôpital de la Timone [CHU - APHM] (TIMONE), Unité de Méthodologie et de Qualité de Vie en Cancérologie (UMQVC), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (UR 3181) (CEF2P / CARCINO), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Pôle cancérologie (CHRU Besançon), and Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Institut Régional Fédératif du Cancer (IRFC)
Subjects: [SDV]Life Sciences [q-bio], humanities
Abstract: published in Quality of Life Research, 26(Suppl 1):134:135, 2017; International audience; Many researches have been conducted in the last decades on the determination of the minimal clinically important difference(MCID) for health-related quality of life (HRQOL) scores. Several methods have been proposed, generally classified in distribution oranchor-based methods. A joint use of both distribution and anchorbased approaches, using several distributions and anchors, should be recommended to study the consistency and reliability of the results. Our objective was to explore and to compare sevenapproaches from the distribution and anchor based methods of the MCID in EORTC questionnaires using a small sample size, tohighlight the advantages and disadvantages of each of them and the consistency of the results. Methods: Data from a randomized phase II clinical trial in unresectable glioblastoma patients were used. Patients completed the EORTC QLQ-C30 questionnaire and the QLQ-BN20 brain cancer module at baseline and during the treatment. Four distribution-based approaches were applied usingbaseline scores: 0.2 standard deviation (SD), 0.3 SD, 0.5 SD and the standard error of measurement. Three anchors were used: the patient rating of change (PRC), global HRQOL change (GHC) using item 30 of the QLQ-C30 and the Karnofsky performance status (PS). Correlation between HRQOL and the anchors were checked. Results: Among the 134 patients involved in this study,102 patients (76 %) had at least one HRQOL score available at baseline and were included in the analysis based on the distribution.For the distributions, the minimal and maximal MCID were (4–18) and (2–16) for the QLQ-C30 and QLQ-BN20 questionnairesrespectively. Regarding the anchor, the role functioning dimension of the QLQ-C30 questionnaire was correlated with both PS andGHC anchors (r[0.30). The MCID calculated for this dimension was 5 points for deterioration and 2 points for improvement.Conclusions: The strength of our study is the diversity of anchors explored in order to estimate the MCID (evaluated by the patienthimself and one evaluated by the clinicians), but the sample size is challenging in this context of poor prognostic disease using anchor based approaches. These results will be compared to other published results for brain cancer tumor with QLQ-BN20.
Published: 2017

49. Contraintes de dose en radiothérapie conformationnelle fractionnée et en radiothérapie stéréotaxique dans les hippocampes, le tronc cérébral et l’encéphale : limites et perspectives

Author: Julian Biau, J. Horion, Raphael Jumeau, B. Pichon, G. Noël, M. Gérard, E. Blais, Laboratoire de Cosmologie, Astrophysique Stellaire & Solaire, de Planétologie et de Mécanique des Fluides (CASSIOPEE), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire de la Côte d'Azur, Université Côte d'Azur (UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Centre Paul Strauss, and CRLCC Paul Strauss
Subjects: Gynecology, medicine.medical_specialty, business.industry, medicine.medical_treatment, Stereotactic radiation therapy, Dose constraints, 3. Good health, 03 medical and health sciences, Conformational radiotherapy, 0302 clinical medicine, Oncology, 030220 oncology & carcinogenesis, Organ at risk, medicine, Radiology, Nuclear Medicine and imaging, business, 030217 neurology & neurosurgery, ComputingMilieux_MISCELLANEOUS, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Resume La toxicite cerebrale de la radiotherapie n’est pas rare. L’epargne de cet organe a risque constitue un enjeu pour la preservation cognitive, en particulier en cas de longue survie. Le diagnostic clinique, physiopathologique et radiologique de la radionecrose reste difficile. Les contraintes de doses utilisees en radiotherapie conformationnelle avec modulation d’intensite (RCMI), en radiochirurgie et en radiotherapie stereotaxique sont critiquables. Elles ont ete elaborees a partir d’etudes retrospectives clinicodosimetriques anciennes. Le rapport α/β et l’architecture — en serie ou en parallele — des organes a risque sont discutables. Ils peuvent conduire a mesestimer les doses equivalentes (BED) par le modele lineaire-quadratique ou la dose equivalente a une irradiation de 2 Gy par fraction (EQD2), en particulier en cas d’hypofractionnement. Les modeles mathematiques se heurtent a l’heterogeneite spatiale de la relation dose-reponse, aux differents fractionnements et etalements ainsi qu’a l’irradiation partielle des organes a risque induites par les forts gradients de doses. Ces limites doivent etre connues en pratique clinique courante. A partir d’une revue de la litterature, notre article propose une mise au point sur le tronc cerebral, les hippocampes et l’encephale. La pertinence des valeurs rapportees fait l’objet de discussions et de pistes de reflexions.
Published: 2017

50. Implication du pharmacien dans l’accompagnement des patients sous anticancéreux oraux : état des lieux dans les centres de lutte contre le cancer (CLCC)

Author: Occhipinti, Sandrine, Petit-Jean, Emilie, Pinguet, Frédéric, Beaupin, Cécile, Daouphars, Mikaël, Parent, Damien, Donamaria, Catherine, Bertrand, Claude, Divanon, Fabienne, Benard-Thiery, Isabelle, Chevrier, Régine, Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER, Centre Paul Strauss, CRLCC Paul Strauss, CRLCC Val d'Aurelle - Paul Lamarque, Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Institut Jean Godinot [Reims], Institut Bergonié [Bordeaux], Centre Eugène Marquis (CRLCC), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), and UNICANCER-Université Côte d'Azur (UCA)
Subjects: Hospital-to-community coordination, Pharmaceutical consultation, Multidisciplinary management, MESH: Administration, oral, Antineoplastic agents, Health Education/methods, Neoplasms/drug therapy, Pharmacists, Professionnal Role, Prospective Studies, [SDV.CAN]Life Sciences [q-bio]/Cancer, Oral chemotherapy
Abstract: International audience; INTRODUCTION:The increasing prescription of oral anticancer therapies has significantly changed inpatient care to outpatient care. This transformation requires an excellent coordination between different professionals to ensure healthcare channel security.METHOD:We performed a prospective study in 18 French cancer centers from March to April 2016. The aim of this study was to identify resources deployed to support patients receiving oral anticancer therapies and to assess pharmacist's involvement.RESULTS:More than half of the centers have developed patient education program and/or practice pharmaceutical consultations. In total, 54.5% have deployed an oral anticancer drugs program and the pharmacist is involved in multidisciplinary teams. In total, 44.4% of the centers have developed hospital-to-community coordination actions but all of them highlight the time-consuming character of those programs.DISCUSSION:Administrative burdens are seriously hindering patient education program's development. Multidisciplinary consultations can offer an attractive alternative because of easy implementation modalities. Finally, hospital-to-community coordination actions seem hard to implement and require harmonization of communication practices, and need more technical and financial means.
Published: 2017

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