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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. Genomic Instability and Protumoral Inflammation Are Associated with Primary Resistance to Anti–PD-1 + Antiangiogenesis in Malignant Pleural Mesothelioma

Author: François-Xavier Danlos, Matthieu Texier, Bastien Job, Severine Mouraud, Lydie Cassard, Capucine Baldini, Andrea Varga, Andrey A. Yurchenko, Audrey Rabeau, Stéphane Champiat, Diane Letourneur, Delphine Bredel, Sandrine Susini, Yuna Blum, Aurelien Parpaleix, Cedric Parlavecchio, Lambros Tselikas, Jean-Eudes Fahrner, Anne-Gaelle Goubet, Mathieu Rouanne, Saloomeh Rafie, Alae Abbassi, Ines Kasraoui, Marie Breckler, Siham Farhane, Samy Ammari, Salim Laghouati, Anas Gazzah, Ludovic Lacroix, Benjamin Besse, Nathalie Droin, Marc Deloger, Sophie Cotteret, Julien Adam, Laurence Zitvogel, Sergey I. Nikolaev, Nathalie Chaput, Christophe Massard, Jean-Charles Soria, Carlos Gomez-Roca, Gerard Zalcman, David Planchard, Aurelien Marabelle, Institut Gustave Roussy (IGR), Immunologie anti-tumorale et immunothérapie des cancers (ITIC), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, École normale supérieure de Lyon (ENS de Lyon), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Département d'imagerie médicale [Gustave Roussy], Département de biologie et pathologie médicales [Gustave Roussy], Département de médecine oncologique, CRLCC Paul Strauss, Dynamique moléculaire de la transformation hématopoïétique (Dynamo), Département de médecine oncologique [Gustave Roussy], Prédicteurs moléculaires et nouvelles cibles en oncologie (PMNCO), Analyse moléculaire, modélisation et imagerie de la maladie cancéreuse (AMMICa), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Département d’Innovation Thérapeutique et essais précoces [Gustave Roussy] (DITEP), and Institut Claudius Regaud
Subjects: Oncology, [SDV.CAN]Life Sciences [q-bio]/Cancer
Abstract: Cancer immunotherapy combinations have recently been shown to improve the overall survival of advanced mesotheliomas, especially for patients responding to those treatments. We aimed to characterize the biological correlates of malignant pleural mesotheliomas’ primary resistance to immunotherapy and antiangiogenics by testing the combination of pembrolizumab, an anti–PD-1 antibody, and nintedanib, a pan-antiangiogenic tyrosine kinase inhibitor, in the multicenter PEMBIB trial (NCT02856425). Thirty patients with advanced malignant pleural mesothelioma were treated and explored. Unexpectedly, we found that refractory patients were actively recruiting CD3+CD8+ cytotoxic T cells in their tumors through CXCL9 tumor release upon treatment. However, these patients displayed high levels of somatic copy-number alterations in their tumors that correlated with high blood and tumor levels of IL6 and CXCL8. Those proinflammatory cytokines resulted in higher tumor secretion of VEGF and tumor enrichment in regulatory T cells. Advanced mesothelioma should further benefit from stratified combination therapies adapted to their tumor biology. Significance: Sequential explorations of fresh tumor biopsies demonstrated that mesothelioma resistance to anti–PD-1 + antiangiogenics is not due to a lack of tumor T-cell infiltration but rather due to adaptive immunosuppressive pathways by tumors, involving molecules (e.g., IL6, CXCL8, VEGF, and CTLA4) that are amenable to targeted therapies. This article is highlighted in the In This Issue feature, p. 799
Published: 2023

5. Chemotherapy in advanced pancreatic adenosquamous carcinoma: A retrospective multicenter AGEO study

Author: Marie Auvray Kuentz, Vincent Hautefeuille, Louis de Mestier, Clélia Coutzac, Thierry Lecomte, Victor Nardon, Pascal Artru, Anthony Turpin, Antoine Drouillard, David Malka, My‐Linh Tran‐Minh, Isabelle Trouilloud, Astrid Lièvre, Nicolas Williet, Simon Pernot, Yann Touchefeu, Julien Taieb, Pascal Hammel, Aziz Zaanan, 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), CHU Amiens-Picardie, Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Léon Bérard [Lyon], Nutrition, croissance et cancer (U 1069) (N2C), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Cancérologie de Strasbourg Europe (ICANS), Hôpital privé Jean Mermoz [Lyon], CHU Lille, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Institut Gustave Roussy (IGR), Département de médecine oncologique, CRLCC Paul Strauss, Hopital Saint-Louis [AP-HP] (AP-HP), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Pontchaillou [Rennes], Oncogenesis, Stress, Signaling (OSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Institut Bergonié [Bordeaux], UNICANCER, Centre hospitalier universitaire de Nantes (CHU Nantes), Cancer Research and Personalized Medicine - CARPEM [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Necker - Enfants Malades [AP-HP], and None
Subjects: Cancer Research, Oncology, adenosquamous carcinoma, advanced disease, pancreatic cancer, [SDV.CAN]Life Sciences [q-bio]/Cancer, chemotherapy
Abstract: International audience; Pancreatic adenosquamous carcinoma (PASC) account for < 5% of pancreatic malignancies. The efficacy of modern chemotherapy regimens in patients with advanced PASC is unknown. Patients with advanced PASC from 2008 to 2021 were consecutively included in this retrospective multicenter study. Overall survival (OS) and progression-free survival (PFS) were evaluated by Kaplan-Meier method. Ninety-four PASC from 16 French centers were included (median age, 67.3 years; males, 56.4%; metastatic disease, 85.1%). The first-line treatment was chemotherapy for 79 patients (84.0%) (37 FOLFIRINOX (FX), 7 Gemcitabine-nab paclitaxel (GN) and 35 for all other regimen) or best supportive care (BSC) alone for 15 patients (16.0%). No significant difference was observed between FX and GN in terms of PFS (P = .67) or OS (P = .5). Modern regimens pooled together (FX and GN) as compared to all others chemotherapy regimens showed an improvement of overall response rate (39.5% and 9.7%, P = .002), PFS (median, 7.8 vs 4.7 months, P = .02) and OS (median, 12.7 vs 9.2 months, P = .35). This large study evaluating first-line treatment regimens in advanced PASC suggests that modern regimens as FX or GN may be preferable to all other chemotherapy regimens. These results deserve confirmation in prospective studies.
Published: 2023

6. 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

7. Contour‐guided deep learning based deformable image registration for dose monitoring during CBCT‐guided radiotherapy of prostate cancer

Author: Cédric Hemon, Bastien Rigaud, Anais Barateau, Florian Tilquin, Vincent Noblet, David Sarrut, Philippe Meyer, Julien Bert, Renaud De Crevoisier, Antoine Simon, Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), CRLCC Eugène Marquis (CRLCC), 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), Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Paul Strauss, CRLCC Paul Strauss, Laboratoire de Traitement de l'Information Medicale (LaTIM), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), This work was partly funded by the French National Research Association (ANR) as part of the Investissement d'Avenir program (Labex CAMI) under reference ANR- 11-LABX-0004, by France Life Imaging (grant ANR-11-INBS-0006), and by the DELPEL project with financial support from ITMO Cancer AVIESAN (National Alliance for Life Sciences & Health) within the framework of the Cancer Plan., ANR-11-LABX-0004,CAMI,Gestes Médico-Chirurgicaux Assistés par Ordinateur(2011), and ANR-11-INBS-0006,FLI,France Life Imaging(2011)
Subjects: prostate, Radiation, [INFO.INFO-TI]Computer Science [cs]/Image Processing [eess.IV], CBCT, [SDV.IB]Life Sciences [q-bio]/Bioengineering, Radiology, Nuclear Medicine and imaging, deformable registration, Instrumentation, dose monitoring
Abstract: Purpose: To evaluate deep learning (DL)-based deformable image registration (DIR) for dose accumulation during radiotherapy of prostate cancer patients.Methods and materials: Data including 341 CBCTs (209 daily, 132 weekly) and 23 planning CTs from 23 patients was retrospectively analyzed. Anatomical deformation during treatment was estimated using free-form deformation (FFD) method from Elastix and DL-based VoxelMorph approaches. The VoxelMorph method was investigated using anatomical scans (VMorph_Sc) or label images (VMorph_Msk), or the combination of both (VMorph_Sc_Msk). Accumulated doses were compared with the planning dose.Results: The DSC ranges, averaged for prostate, rectum and bladder, were 0.60-0.71, 0.67-0.79, 0.93-0.98, and 0.89-0.96 for the FFD, VMorph_Sc, VMorph_Msk, and VMorph_Sc_Msk methods, respectively. When including both anatomical and label images, VoxelMorph estimated more complex deformations resulting in heterogeneous determinant of Jacobian and higher percentage of deformation vector field (DVF) folding (up to a mean value of 1.90% in the prostate). Large differences were observed between DL-based methods regarding estimation of the accumulated dose, showing systematic overdosage and underdosage of the bladder and rectum, respectively. The difference between planned mean dose and accumulated mean dose with VMorph_Sc_Msk reached a median value of +6.3 Gy for the bladder and -5.1 Gy for the rectum.Conclusion: The estimation of the deformations using DL-based approach is feasible for male pelvic anatomy but requires the inclusion of anatomical contours to improve organ correspondence. High variability in the estimation of the accumulated dose depending on the deformable strategy suggests further investigation of DL-based techniques before clinical deployment.
Published: 2023

8. 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

9. 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

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

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

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

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

12. 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

13. 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

14. 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

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

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

16. Oral contraceptive use and ovarian cancer risk for BRCA1/2 mutation carriers: an international cohort study

Author: Lieske H. Schrijver, Antonis C. Antoniou, Håkan Olsson, Thea M. Mooij, Marie-José Roos-Blom, Leyla Azarang, Julian Adlard, Munaza Ahmed, Daniel Barrowdale, Rosemarie Davidson, Alan Donaldson, Ros Eeles, D. Gareth Evans, Debra Frost, Alex Henderson, Louise Izatt, Kai-Ren Ong, Valérie Bonadona, Isabelle Coupier, Laurence Faivre, Jean-Pierre Fricker, Paul Gesta, Klaartje van Engelen, Agnes Jager, Fred H. Menko, Marian J.E. Mourits, Christian F. Singer, Yen Y. Tan, Lenka Foretova, Marie Navratilova, Rita K. Schmutzler, Carolina Ellberg, Anne-Marie Gerdes, Trinidad Caldes, Jacques Simard, Edith Olah, Anna Jakubowska, Johanna Rantala, Ana Osorio, John L. Hopper, Kelly-Anne Phillips, Roger L. Milne, Mary Beth Terry, Catherine Noguès, Christoph Engel, Karin Kast, David E. Goldgar, Flora E. van Leeuwen, Douglas F. Easton, Nadine Andrieu, Matti A. Rookus, Lilian Laborde, Pauline Pontois, Emanuelle Breysse, Margot Berline, Dominique Stoppa-Lyonnet, Marion Gauthier-Villars, Bruno Buecher, Chrystelle Colas, Olivier Caron, Emmanuelle Mouret-Fourme, Claire Saule, Christine Lasset, Sophie Dussard, Pascaline Berthet, Elisabeth Luporsi, Véronique Mari, Laurence Gladieff, Stéphanie Chieze-Valéro, Jessica Moretta, Hagay Sobol, François Eisinger, Cornel Popovici, Michel Longy, Louise Grivelli, Florent Soubrier, Patrick Benusiglio, Pascal Pujol, Carole Corsini, Marie-Emmanuelle Morin-Meschin, Alain Lortholary, Claude Adenis, Audrey Maillez, Tan Dat Nguyen, Capucine Delnatte, Caroline Abadie, Julie Tinat, Isabelle Tennevet, Christine Maugard, Yves-Jean Bignon, Mathilde Gay Bellile, Clotilde Penet, Hélène Dreyfus, Odile Cohen-Haguenauer, Brigitte Gilbert, Laurence Venat-Bouvet, Dominique Leroux, Clémentine Legrand, Hélène Zattara-Cannoni, Valérie Layet, Elodie Lacaze, Sandra Fert-Ferrer, Odile Bera, Brigitte Gilbert-Dussardier, David Tougeron, Hakima Lallaoui, M.A. Rookus, F.B.L. Hogervorst, F.E. van Leeuwen, M.A. Adank, M.K. Schmidt, D.J. Jenner, J.M. Collée, A.M.W. van den Ouweland, M.J. Hooning, I.A. Boere, C.J. van Asperen, P. Devilee, R.B. van der Luijt, T.C.T.E.F. van Cronenburg, M.R. Wevers, A.R. Mensenkamp, M.G.E.M. Ausems, M.J. Koudijs, I. van de Beek, K. van Engelen, J.J.P. Gille, E.B. Gómez García, M.J. Blok, M. de Boer, L.P.V. Berger, A.H. van der Hout, M.J.E. Mourits, G.H. de Bock, S. Siesling, J. Verloop, E.C. van den Broek, Damage and Repair in Cancer Development and Cancer Treatment (DARE), Targeted Gynaecologic Oncology (TARGON), Human genetics, Epidemiology and Data Science, Cancer Center Amsterdam, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Hôpital Arnaud de Villeneuve [CHRU Montpellier], Institut National de la Santé et de la Recherche Médicale (INSERM), UNICANCER - Institut régional du Cancer Montpellier Val d'Aurelle (ICM), CRLCC Val d'Aurelle - Paul Lamarque, 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 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), Aix Marseille Université (AMU), Institut Curie [Paris], Mines Paris - PSL (École nationale supérieure des mines de Paris), Université Paris sciences et lettres (PSL), Human Genetics, APH - Methodology, APH - Quality of Care, Antoniou, Antonis [0000-0001-9223-3116], Easton, Douglas [0000-0003-2444-3247], Apollo - University of Cambridge Repository, RS: GROW - R4 - Reproductive and Perinatal Medicine, MUMC+: DA KG Polikliniek (9), Klinische Genetica, MUMC+: DA KG Lab Centraal Lab (9), Michel-Avella, Amandine, Medical Oncology, and Clinical Genetics
Subjects: endocrine system diseases, [SDV]Life Sciences [q-bio], MESH: Proportional Hazards Models, Cohort Studies, fetal growth restriction, small for gestational age, MESH: BRCA2 Protein, EPITHELIAL OVARIAN-CANCER, Medicine, pharma-ceutical treatment, MESH: Cohort Studies, Original Research, oral contraceptives, risk, Ovarian Neoplasms, education.field_of_study, Women's cancers Radboud Institute for Molecular Life Sciences [Radboudumc 17], MESH: Middle Aged, obstetrics, Obstetrics, BRCA1 Protein, Hazard ratio, MESH: Genetic Predisposition to Disease, Obstetrics and Gynecology, Oral/administration & dosage, Contraceptives, pregnancy complica-tions, MESH: Follow-Up Studies, Contraceptives, Oral/administration & dosage, Middle Aged, BRCA2 Protein/genetics, drug therapy, [SDV] Life Sciences [q-bio], Europe, MESH: Ovarian Neoplasms, ovarian cancer, SURVIVAL, Female, epidemiology, Ovarian Neoplasms/epidemiology, pregnancy, MESH: Contraceptives, Oral, preterm delivery, legislative framework, Rare cancers Radboud Institute for Health Sciences [Radboudumc 9], Cohort study, HORMONAL FACTORS, Adult, preterm labor, medicine.medical_specialty, preterm premature rupture of membranes, MESH: Mutation, Population, REPRODUCTIVE RISK-FACTORS, retrospective, clinical trials with pregnant women, MUTATION CARRIERS, BREAST, Europe/epidemiology, research and development, preeclampsia, Breast cancer, multivariate, SDG 3 - Good Health and Well-being, Humans, Genetic Predisposition to Disease, observational, education, MESH: BRCA1 Protein, Proportional Hazards Models, Retrospective Studies, BRCA2 Protein, MESH: Humans, survival bias, treatment during pregnancy, Proportional hazards model, business.industry, Retrospective cohort study, MESH: Adult, MESH: Retrospective Studies, medicine.disease, BRCA1, BRCA2, drug development, Confidence interval, placental transfer, Gynecology, obstetrical syndromes, Mutation, BRCA1 Protein/genetics, MESH: Europe, business, Ovarian cancer, MESH: Female, Contraceptives, Oral, Follow-Up Studies
Abstract: Contains fulltext : 237895.pdf (Publisher’s version ) (Open Access) BACKGROUND: Ovarian cancer risk in BRCA1 and BRCA2 mutation carriers has been shown to decrease with longer duration of oral contraceptive use. Although the effects of using oral contraceptives in the general population are well established (approximately 50% risk reduction in ovarian cancer), the estimated risk reduction in mutation carriers is much less precise because of potential bias and small sample sizes. In addition, only a few studies on oral contraceptive use have examined the associations of duration of use, time since last use, starting age, and calendar year of start with risk of ovarian cancer. OBJECTIVE: This study aimed to investigate in more detail the associations of various characteristics of oral contraceptive use and risk of ovarian cancer, to provide healthcare providers and carriers with better risk estimates. STUDY DESIGN: In this international retrospective study, ovarian cancer risk associations were assessed using oral contraceptives data on 3989 BRCA1 and 2445 BRCA2 mutation carriers. Age-dependent-weighted Cox regression analyses were stratified by study and birth cohort and included breast cancer diagnosis as a covariate. To minimize survival bias, analyses were left truncated at 5 years before baseline questionnaire. Separate analyses were conducted for each aspect of oral contraceptive use and in a multivariate analysis, including all these aspects. In addition, the analysis of duration of oral contraceptive use was stratified by recency of use. RESULTS: Oral contraceptives were less often used by mutation carriers who were diagnosed with ovarian cancer (ever use: 58.6% for BRCA1 and 53.5% BRCA2) than by unaffected carriers (ever use: 88.9% for BRCA1 and 80.7% for BRCA2). The median duration of use was 7 years for both BRCA1 and BRCA2 carriers who developed ovarian cancer and 9 and 8 years for unaffected BRCA1 and BRCA2 carriers with ovarian cancer, respectively. For BRCA1 mutation carriers, univariate analyses have shown that both a longer duration of oral contraceptive use and more recent oral contraceptive use were associated with a reduction in the risk of ovarian cancer. However, in multivariate analyses, including duration of use, age at first use, and time since last use, duration of oral contraceptive use proved to be the prominent protective factor (compared with 10 years [hazard ratio, 0.37; 95% confidence interval, 0.19-0.73]; P(trend)=.008). The inverse association between duration of use and ovarian cancer risk persisted for more than 15 years (duration of ≥10 years; BRCA1 15 years since last use [hazard ratio, 0.56; 95% confidence interval, 0.18-0.59]). Univariate results for BRCA2 mutation carriers were similar but were inconclusive because of limited sample size. CONCLUSION: For BRCA1 mutation carriers, longer duration of oral contraceptive use is associated with a greater reduction in ovarian cancer risk, and the protection is long term.
Published: 2021

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

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

Author: Flora Nguyen Van Long, Audrey Lardy-Cleaud, Dimitri Carène, Caroline Rossoni, Frédéric Catez, Paul Rollet, Nathalie Pion, Déborah Monchiet, Agathe Dolbeau, Marjorie Martin, Valentin Simioni, Susan Bray, Doris Le Beherec, Fernanda Mosele, Ibrahim Bouakka, Amélie Colombe-Vermorel, Laetitia Odeyer, Alexandra Diot, Lee B. Jordan, Alastair M. Thompson, Françoise Jamen, Thierry Dubois, Sylvie Chabaud, Stefan Michiels, Isabelle Treilleux, Jean-Christophe Bourdon, David Pérol, Alain Puisieux, Fabrice André, Jean-Jacques Diaz, Virginie Marcel, Malbec, Odile, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Léon Bérard [Lyon], Développement Cancer et Thérapies Ciblées [Lyon] (LabEx DEVweCAN), Université de Lyon, Biomarqueurs prédictifs et nouvelles stratégies moléculaires en thérapeutique anticancéreuse (U981), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Gustave Roussy (IGR), Ninewells Hospital and Medical School [Dundee], Analyse moléculaire, modélisation et imagerie de la maladie cancéreuse (AMMICa), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), University of Dundee, Baylor College of Medicine (BCM), Baylor University, Complexité, Innovation, Activités Motrices et Sportives (CIAMS), Université d'Orléans (UO)-Université Paris-Saclay, Département de Recherche Translationnelle, Institut Curie [Paris], Service de biostatistique et d'épidémiologie (SBE), Direction de la recherche clinique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Oncostat (U1018 (Équipe 2)), Institut Gustave Roussy (IGR)-Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Direction de la recherche [Gustave Roussy], Département de médecine oncologique, and CRLCC Paul Strauss
Subjects: Cancer Research, rRNA 2’O-ribose methylation complex, Chromosomal Proteins, Non-Histone, [SDV]Life Sciences [q-bio], Breast Neoplasms, AgNOR, [SDV] Life Sciences [q-bio], Breast cancer, Fibrillarin, Oncology, Ribosome biogenesis, Genetics, Humans, Female, RNA, Messenger, Ribosomes, Biomarkers
Abstract: Background A current critical need remains in the identification of prognostic and predictive markers in early breast cancer. It appears that a distinctive trait of cancer cells is their addiction to hyperactivation of ribosome biogenesis. Thus, ribosome biogenesis might be an innovative source of biomarkers that remains to be evaluated. Methods Here, fibrillarin (FBL) was used as a surrogate marker of ribosome biogenesis due to its essential role in the early steps of ribosome biogenesis and its association with poor prognosis in breast cancer when overexpressed. Using 3,275 non-metastatic primary breast tumors, we analysed FBL mRNA expression levels and protein nucleolar organisation. Usage of TCGA dataset allowed transcriptomic comparison between the different FBL expression levels-related breast tumours. Results We unexpectedly discovered that in addition to breast tumours expressing high level of FBL, about 10% of the breast tumors express low level of FBL. A correlation between low FBL mRNA level and lack of FBL detection at protein level using immunohistochemistry was observed. Interestingly, multivariate analyses revealed that these low FBL tumors displayed poor outcome compared to current clinical gold standards. Transcriptomic data revealed that FBL expression is proportionally associated with distinct amount of ribosomes, low FBL level being associated with low amount of ribosomes. Moreover, the molecular programs supported by low and high FBL expressing tumors were distinct. Conclusion Altogether, we identified FBL as a powerful ribosome biogenesis-related independent marker of breast cancer outcome. Surprisingly we unveil a dual association of the ribosome biogenesis FBL factor with prognosis. These data suggest that hyper- but also hypo-activation of ribosome biogenesis are molecular traits of distinct tumors.
Published: 2021

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

Author: Eric Guérin, Hélène Burckel, Georges Noël, Benoit Lhermitte, Quentin Fuchs, David Castel, Marie Pierre Chenard, Olivier Poch, Eric Van Dyck, Laetitia Poidevin, Laurence Choulier, Monique Dontenwill, Petr V. Nazarov, Natacha Entz-Werle, Laboratoire de Bioimagerie et Pathologies (LBP), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), CHU Strasbourg, Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie (ICube), Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Réseau nanophotonique et optique, Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Matériaux et nanosciences d'Alsace (FMNGE), Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CRBS - Centre de Recherche en Biomédecine de Strasbourg (Inserm UMS38/UNISTRA), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Luxembourg Institute of Health (LIH), Institut de Cancérologie de Strasbourg Europe (ICANS), Université de Strasbourg (UNISTRA), UNICANCER, CRLCC Paul Strauss, Biomarqueurs prédictifs et nouvelles stratégies moléculaires en thérapeutique anticancéreuse (U981), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Vectorologie et thérapeutiques anti-cancéreuses [Villejuif] (UMR 8203), Centre National de la Recherche Scientifique (CNRS)-Institut Gustave Roussy (IGR)-Université Paris-Sud - Paris 11 (UP11), École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Université de Strasbourg (UNISTRA)-Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Les Hôpitaux Universitaires de Strasbourg (HUS)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Biomédecine de Strasbourg (CRBS), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Centre National de la Recherche Scientifique (CNRS), and univOAK, Archive ouverte
Subjects: [INFO.INFO-AI] Computer Science [cs]/Artificial Intelligence [cs.AI], 0301 basic medicine, Cancer Research, pediatric high-grade gliomas, DNA damage repair, prognostic clustering, PARP1, XRCC1, DNA repair, DNA damage, Biology, Article, [INFO.INFO-AI]Computer Science [cs]/Artificial Intelligence [cs.AI], Transcriptome, 03 medical and health sciences, 0302 clinical medicine, Radioresistance, Gene expression, RC254-282, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Cell cycle, Cell Cycle Gene, 3. Good health, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, Cancer research
Abstract: Simple Summary Pediatric high-grade gliomas are incurable brain tumors for which there is a critical need for new therapeutic strategies as well as treatment-predictive biomarkers. This study examined the expression of DNA repair and cell cycle genes in pediatric high-grade gliomas with distinct driving mutations. The aim is to propose a novel classification of these tumors based on sub-groups exposing therapeutic vulnerabilities. Several DNA repair factors were identified that might become new diagnostic markers. Abstract Background: Pediatric high-grade gliomas (pHGGs) are the leading cause of mortality in pediatric neuro-oncology, displaying frequent resistance to standard therapies. Profiling DNA repair and cell cycle gene expression has recently been proposed as a strategy to classify adult glioblastomas. To improve our understanding of the DNA damage response pathways that operate in pHGGs and the vulnerabilities that these pathways might expose, we sought to identify and characterize a specific DNA repair and cell-cycle gene expression signature of pHGGs. Methods: Transcriptomic analyses were performed to identify a DNA repair and cell-cycle gene expression signature able to discriminate pHGGs (n = 6) from low-grade gliomas (n = 10). This signature was compared to related signatures already established. We used the pHGG signature to explore already transcriptomic datasets of DIPGs and sus-tentorial pHGGs. Finally, we examined the expression of key proteins of the pHGG signature in 21 pHGG diagnostic samples and nine paired relapses. Functional inhibition of one DNA repair factor was carried out in four patients who derived H3.3 K27M mutant cell lines. Results: We identified a 28-gene expression signature of DNA repair and cell cycle that clustered pHGGs cohorts, in particular sus-tentorial locations, in two groups. Differential protein expression levels of PARP1 and XRCC1 were associated to TP53 mutations and TOP2A amplification and linked significantly to the more radioresistant pHGGs displaying the worst outcome. Using patient-derived cell lines, we showed that the PARP-1/XRCC1 expression balance might be correlated with resistance to PARP1 inhibition. Conclusion: We provide evidence that PARP1 overexpression, associated to XRCC1 expression, TP53 mutations, and TOP2A amplification, is a new theranostic and potential therapeutic target.
Published: 2021

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

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

21. 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

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

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

23. Real‐life activity of eribulin mesylate among metastatic breast cancer patients in the multicenter national observational ESME program

Author: Audrey Mailliez, Jean-Marc Ferrero, Marie Chaix, Julien Fraisse, Mathieu Robain, Sophie Gourgou, Paul Cottu, Anthony Gonçalves, Claudia Lefeuvre, Marc Debled, Séverine Guiu, Jean-Christophe Eymard, Christelle Levy, C. Courtinard, Mario Campone, Marianne Leheurteur, Pierre-Etienne Heudel, William Jacot, Lionel Uwer, Barbara Pistilli, Florence Dalenc, Thierry Petit, Marie-Ange Mouret-Reynier, Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Institut du Cancer de Montpellier (ICM), CRLC Val d'Aurelle-Paul Lamarque, CRLCC Val d'Aurelle - Paul Lamarque, Centre Léon Bérard [Lyon], Université de Montpellier (UM), Institut Claudius Regaud, Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Gustave Roussy (IGR), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Institut Bergonié [Bordeaux], Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), CRLCC Eugène Marquis (CRLCC), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Institut Jean Godinot [Reims], Centre Paul Strauss, CRLCC Paul Strauss, Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), Institut Curie [Paris], Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), and Université Lille Nord de France (COMUE)-UNICANCER
Subjects: Oncology, Cancer Research, medicine.medical_specialty, Receptor, ErbB-2, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Population, Antineoplastic Agents, Breast Neoplasms, Disease-Free Survival, law.invention, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Breast cancer, real-life cohort, Randomized controlled trial, law, Internal medicine, Humans, Medicine, Furans, education, eribulin, Aged, Retrospective Studies, Chemotherapy, education.field_of_study, business.industry, Ketones, Middle Aged, medicine.disease, Metastatic breast cancer, Progression-Free Survival, 3. Good health, chemistry, 030220 oncology & carcinogenesis, Concomitant, Cohort, Female, metastatic breast cancer, business, Eribulin
Abstract: International audience; Eribulin mesylate (EM) was recently approved for metastatic breast cancer (MBC) chemotherapy (CT) in late lines by the FDA, with debated results in second line. We evaluated outcomes in breast cancer patients receiving EM as second, third and fourth line in a national real-life cohort of 16,703 consecutive MBC patients initiating their first metastatic therapeutic line between 2008 and 2014. Primary and secondary objectives were overall survival (OS) and progression-free survival (PFS). An imbalance was seen for HER2+ tumors and concomitant anti-HER2 targeted therapies use, we thus performed a subanalysis in HER2- patients. PFS and OS were significantly better in EM patients in third and fourth lines, compared to "Other chemotherapies" patients (PFS: 4.14 vs. 3.02 months, p = 0.0010; 3.61 vs. 2.53 months, p = 0.0102, third and fourth-line; OS: 11.27 vs. 7.65 months, p = 0.0001; 10.91 vs. 5.95 months, p
Published: 2019

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

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

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

Author: Richard Iggo, Jean-Michel Picquenot, Denis Larsimont, Véronique Becette, Jonas Bergh, Gaëtan MacGrogan, Jeremy Thomas, Olivier Kerdraon, Leen Slaets, David Cameron, Fanny Pommeret, C. Poncet, Jean-Christophe Tille, Frédéric Bibeau, Hervé Bonnefoi, Alexandre Bodmer, Jean-Pierre Ghnassia, Thomas Grellety, Donnat, Martin, Validation et identification de nouvelles cibles en oncologie (VINCO), Institut Bergonié [Bordeaux], UNICANCER-UNICANCER-Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), CIC Bordeaux, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de pathologie, UNICANCER-UNICANCER, UNICANCER, European Organisation for Research and Treatment of Cancer [Bruxelles] (EORTC), European Cancer Organisation [Bruxelles] (ECCO), Actions for OnCogenesis understanding and Target Identification in ONcology (ACTION), Institut Jules Bordet [Bruxelles], Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Hôpital René HUGUENIN (Saint-Cloud), Centre René Gauducheau, CRLCC René Gauducheau, Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre Paul Strauss, CRLCC Paul Strauss, Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Cancer Research UK Edinburgh Centre [Edinburgh, UK], University of Edinburgh-MRC Institute of Genetics and Molecular Medicine [Edinburgh] (IGMM), University of Edinburgh-Medical Research Council-Medical Research Council, Hôpitaux Universitaires de Genève (HUG), Department of Oncology-Pathology [Karolinska Institutet], Karolinska Institutet [Stockholm], Bordeaux PharmacoEpi, Inserm CIC1401, Université de Bordeaux, Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Bergonié [Bordeaux], UNICANCER-UNICANCER-Université Bordeaux Segalen - Bordeaux 2, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Bordeaux Segalen - Bordeaux 2-Institut Bergonié [Bordeaux], and Swiss Group for Clinical Cancer Research (SAKK)
Subjects: Oncology, Cancer Research, medicine.medical_specialty, Receptor, ErbB-2, Concordance, medicine.medical_treatment, Breast Neoplasms, [SDV.CAN]Life Sciences [q-bio]/Cancer, ddc:616.07, Disease-Free Survival, Article, 03 medical and health sciences, Breast cancer, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Survival rate, Chemotherapy, business.industry, Gene Expression Profiling, Apocrine, medicine.disease, Immunohistochemistry, Subtyping, 3. Good health, Cancérologie, ErbB Receptors, Survival Rate, Clinical trial, Biological sciences, Treatment Outcome, Receptors, Estrogen, Chemotherapy, Adjuvant, Receptors, Androgen, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, 030220 oncology & carcinogenesis, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Female, Receptors, Progesterone, business
Abstract: Background: We explored, within the EORTC10994 study, the outcomes for patients with molecular apocrine (MA) breast cancer, and defined immunohistochemistry (IHC) as androgen-receptor (AR) positive, oestrogen (ER) and progesterone (PR) negative. We also assessed the concordance between IHC and gene expression arrays (GEA) in the identification of MA cancers. Methods: Centrally assessed biopsies for AR, ER, PR, HER2 and Ki67 by IHC were classified into six subtypes: MA, triple-negative (TN) basal-like, luminal A, luminal B HER2 negative, luminal B HER2 positive and “other”. The two main objectives were the pCR rates and survival outcomes in the overall MA subtype (and further divided by HER2 status) and the remaining five subtypes. Results: IHC subtyping was obtained in 846 eligible patients. Ninety-three (11%) tumours were classified as the MA subtype. Both IHC and GEA data were available for 64 patients. In this subset, IHC concordance was 88.3% in identifying MA tumours compared with GEA. Within the MA subtype, pCR was observed in 33.3% of the patients (95% CI: 29.4–43.9) and the 5-year recurrence-free interval was 59.2% (95% CI: 48.2–68.6). Patients with MA and TN basal-like tumours have lower survival outcomes. Conclusions: Irrespective of their HER2 status, the prognosis for MA tumours remains poor and adjuvant trials evaluating anti-androgens should be considered., SCOPUS: ar.j, info:eu-repo/semantics/published
Published: 2019

26. The carbon substrate in RST Si ribbon technology for solar cells

Author: E. Jolivet, C. Bigot, R. Varrot, J. Chancolon, M. Monville, C. Belouet, Sylvie Bonnamy, Institut de Recherches Subatomiques (IReS), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Cancéropôle du Grand Est-Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique (CNRS), CRLCC Paul Strauss, Institut de génétique et microbiologie [Orsay] (IGM), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Interfaces, Confinement, Matériaux et Nanostructures ( ICMN), and Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Materials science, Fabrication, Silicon, Composite number, chemistry.chemical_element, 02 engineering and technology, engineering.material, 010402 general chemistry, 7. Clean energy, 01 natural sciences, Coating, Ribbon, [CHIM]Chemical Sciences, General Materials Science, Lamellar structure, Composite material, ComputingMilieux_MISCELLANEOUS, Deposition (law), [PHYS]Physics [physics], General Chemistry, 021001 nanoscience & nanotechnology, 0104 chemical sciences, chemistry, engineering, 0210 nano-technology, Carbon
Abstract: The carbon substrate used in the RST (silicon Ribbon growth on a Sacrificial carbon Template) process, a silicon ribbon growth technology aimed at the fabrication of silicon solar cells, is a composite made of a compressed expanded natural graphite (CENG) ribbon coated by a protective rough lamellar high-temperature (RLHT) pyrocarbon. It is shown that the reactivity of RLHT pyrocarbon with molten silicon is stimulated by the presence of topological defects of the CENG ribbon. This reactivity generates a contamination of the silicon melt by carbon and its metallic impurities and, in turn, adversely affects the performances of solar cells made from RST silicon films. Reactivity with molten silicon can be drastically reduced by the control of the deposition conditions of pyrocarbon and of the roughness of the CENG ribbon. A new model is proposed to explain the mechanism of the intrinsic reactivity of RLHT pyrocarbon with molten silicon. Based on this model the reactivity problem can virtually be eliminated by the deposition of a SiC coating about 0.3 μm on the RLHT pyrocarbon. Improvements of the carbon ribbon, described in this study, especially its pyrocarbon coating, should lead to flexible silicon solar cells 70–80 μm thick with conversion efficiency above 18%.
Published: 2019

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

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

28. 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

29. 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

30. 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

31. 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

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

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

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

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

34. 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

35. 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

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

Author: Thomas Bachelot, Lionel Uwer, Marianne Leheurteur, Anne Patsouris, Florence Dalenc, Virginie Perotin, Laurence Vanlemmens, Jean S Frenel, Camille Sabathe, Carole Bouleuc, Marie Ange Mouret-Reynier, Suzette Delaloge, C. Courtinard, Anne Jaffre, Anthony Gonçalves, Jean Marc Ferrero, Isabelle Desmoulins, Matthieu Frasca, Jean C Eymard, Thierry Petit, Simone Mathoulin-Pélissier, Angéline Galvin, Christelle Levy, Véronique Diéras, Michaël Chevrot, Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER, Centre Paul Strauss, and CRLCC Paul Strauss
Subjects: 0301 basic medicine, Cancer Research, medicine.medical_specialty, Palliative care, [SDV]Life Sciences [q-bio], Psychological intervention, Breast Neoplasms, [SDV.CAN]Life Sciences [q-bio]/Cancer, History, 21st Century, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Older patients, Internal medicine, parasitic diseases, medicine, Humans, cardiovascular diseases, Neoplasm Metastasis, ComputingMilieux_MISCELLANEOUS, Aged, Inpatient care, business.industry, Palliative Care, Age Factors, Cancer, EPICENE, medicine.disease, Metastatic breast cancer, Confidence interval, 3. Good health, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, Cohort, Female, business
Abstract: Patients with metastatic breast cancer (MBC) often require inpatient palliative care (IPC). However, mounting evidence suggests age-related disparities in palliative care delivery. This study aimed to assess the cumulative incidence function (CIF) of IPC delivery, as well as the influence of age.The national ESME (Epidemio-Strategy-Medical-Economical)-MBC cohort includes consecutive MBC patients treated in 18 French Comprehensive Cancer Centres. ICD-10 palliative care coding was used for IPC identification.Our analysis included 12,375 patients, 5093 (41.2%) of whom were aged 65 or over. The median follow-up was 41.5 months (95% confidence interval [CI], 40.5-42.5). The CIF of IPC was 10.3% (95% CI, 10.2-10.4) and 24.8% (95% CI, 24.7-24.8) at 2 and 8 years, respectively. At 2 years, among triple-negative patients, young patients (65 yo) had a higher CIF of IPC than older patients after adjusting for cancer characteristics, centre and period (65+/65: β = -0.05; 95% CI, -0.08 to -0.01). Among other tumour sub-types, older patients received short-term IPC more frequently than young patients (65+/65: β = 0.02; 95% CI, 0.01 to 0.03). At 8 years, outside large centres, IPC was delivered less frequently to older patients adjusted to cancer characteristics and period (65+/65: β = -0.03; 95% CI, -0.06 to -0.01).We found a relatively low CIF of IPC and that age influenced IPC delivery. Young triple-negative and older non-triple-negative patients needed more short-term IPCs. Older patients diagnosed outside large centres received less long-term IPC. These findings highlight the need for a wider implementation of IPC facilities and for more age-specific interventions.
Published: 2020

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

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

38. 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

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

Author: Laetitia Daubisse-Marliac, Brigitte Lacour, Tania d'Almeida, Karima Hammas, Olivier Ganry, Alain Monnereau, Emmanuel Desandes, Nicolas Boissel, Brigitte Trétarre, Isabelle Baldi, Anne-Valérie Guizard, Anne Cowppli-Bony, Patricia Delafosse, Thomas Raze, Jacqueline Clavel, G. Coureau, Michel Velten, Sandrine Plouvier, Gautier Defossez, Xavier Troussard, Simona Bara, Véronique Bouvier, Anne-Sophie Woronoff, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Registre National des Tumeurs Solides de l'Enfant (RNTSE), Equipe 7 : EPICEA - Epidémiologie des cancers de l'enfant et de l'adolescent (CRESS - U1153), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Registre National des Cancers de l'Enfant - National Registry of Childhood Cancers [Villejuif & CHU Nancy] (RNCE), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM), French network of cancer registries [Toulouse] (Francim), Registre des cancers de Loire‐Atlantique et Vendée, Imaging and Longitudinal Investigations to Ameliorate Decision-making [Nantes] (ILIAD), Site de Recherche Intégrée sur le Cancer [Nantes] (SIRIC), Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre hospitalier universitaire de Nantes (CHU Nantes), FRANCIM, Réseau des registres français du cancer, Registre des cancers de l’Isère [CHU de Grenoble], Centre Hospitalier Universitaire [Grenoble] (CHU)-Université Grenoble Alpes (UGA), CRLCC Paul Strauss, Registre des Tumeurs de l'Hérault, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), CIC - Poitiers, Université de Poitiers-Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), MethodS in Patients-centered outcomes and HEalth ResEarch (SPHERE), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Université de Nantes (UN)-Université de Nantes (UN), Registre des tumeurs du Doubs et du Territoire de Belfort [CHRU Besançon], Pôle cancérologie (CHRU Besançon), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), CHU Amiens-Picardie, CHirurgie, IMagerie et REgénération tissulaire de l’extrémité céphalique - Caractérisation morphologique et fonctionnelle - UR UPJV 7516 (CHIMERE), Université de Picardie Jules Verne (UPJV), Registre général des cancers de Lille et de sa région (GCS-C2RC), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Hôpital Albert Calmette [Lille], Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Registre Général des Tumeurs du Calvados, CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-UNICANCER, Unité de recherche interdisciplinaire pour la prévention et le traitement des cancers (ANTICIPE), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)-Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM), Registre des cancers de la Manche [CHPC - Site Louis Pasteur], Site Louis Pasteur [CHPC], CH Centre Hospitalier Public du Cotentin (CHPC)-CH Centre Hospitalier Public du Cotentin (CHPC), A&O (Apprentissage et Optimisation) (A&O), Laboratoire Interdisciplinaire des Sciences du Numérique (LISN), Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Science des Données (SDD), Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Algorithmes, Apprentissage et Calcul (AAC), Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Epidémiologie et analyses en santé publique : risques, maladies chroniques et handicaps (LEASP), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Université Sorbonne Paris Nord, Cancer environnement (EPICENE ), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Registre National des Hémopathies malignes de l'Enfant (RNHE), and Institut de Veille Sanitaire (INVS)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Male, Pediatrics, medicine.medical_specialty, Survival, Adolescent, Lymphoma, [SDV]Life Sciences [q-bio], Population, Improved survival, Adolescents, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Neoplasms, Medicine, Humans, 030212 general & internal medicine, Registries, Young adult, education, Melanoma, Cancer, education.field_of_study, business.industry, Incidence (epidemiology), Incidence, Cancer survival, Neoplasms, Germ Cell and Embryonal, medicine.disease, humanities, Young Adults, Survival Rate, Oncology, 030220 oncology & carcinogenesis, Pediatrics, Perinatology and Child Health, Female, France, Trends, business
Abstract: International audience; Purpose: This study was undertaken to determine cancer survival and describe the spectrum of cancers diagnosed among French adolescent and young adult (AYA) population.Methods: All cases of cancer diagnosed in 15-24 years, recorded by all French population-based registries (18% of the French population), over the 2000-2016 period, were included. Age-standardized incidences rates (ASR), conventional annual percentage change (cAPC) of incidence over time, and 5-year overall survival (5yOS) were calculated.Results: We analyzed 2,734 cancer diagnoses in adolescents and 4,199 in young adults. Overall incidence rates were 231.9/106 in 15-19 year olds and 354.0/106 in 20-24 year olds. The most frequently diagnosed cancers in male AYA were malignant gonadal germ-cell tumors (GCT), Hodgkin lymphoma (HL), and malignant melanoma, and were HL, thyroid carcinoma, and malignant melanoma in females. Cancer incidence was stable over time with a cAPC of 0.8% (p=0.72). For all cancers combined, 5yOS was 86.6% (95%CI: 85.8-87.4), greater than 85% for HL, non-Hodgkin lymphomas (NHL), GCT, thyroid carcinomas, and malignant melanomas, and around 60% and lower for osteosarcomas, Ewing tumors, hepatic carcinomas, and rhabdomyosarcomas. The 5yOS has significantly improved from 2000-2007 to 2008-2015 for all cancers pooled, with a substantial gain of 4% for 15-19 year-olds, and 3% for 20-24 year-olds.Conclusion: Notwithstanding the encouraging results for some cancers, and overall, persistent poorer survivals in AYA were shown compared to children for acute lymphoblastic leukemia, osteosarcoma, Ewing tumor, rhabdomyosarcoma and malignant hepatic tumors. These disparities require further investigation to identify and address the causes of these inferior outcomes.
Published: 2020

40. 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

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

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

42. 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

43. 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

44. 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

45. 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

46. 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

47. 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

48. 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

49. 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

50. 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

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