1. Advanced chordoma treated by first-line molecular targeted therapies: Outcomes and prognostic factors. A retrospective study of the French Sarcoma Group (GSF/GETO) and the Association des Neuro-Oncologues d'Expression Française (ANOCEF)
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Nicolas Penel, Bruno Chauffert, Elodie Vauleon, Alice Bonneville-Levard, Jean-Yves Blay, Christine Chevreau, Didier Cupissol, Olivier Mir, Esma Saada-Bouzid, Axel Le Cesne, Jacques-Olivier Bay, Loïc Feuvret, Florence Duffaud, Georges Noël, François Bertucci, Loïc Lebellec, Michel Fabbro, Emmanuelle Bompas, Armelle Vinceneux, CHU Amiens-Picardie, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR), Institut Claudius Regaud, CRLCC René Gauducheau, Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Institut de Recherche sur le Cancer et le Vieillissement (IRCAN), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Medical Oncology Unit, S. Camillo-Forlanini Hospital, Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière (CRICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Role of intra-Clonal Heterogeneity and Leukemic environment in ThErapy Resistance of chronic leukemias (CHELTER), Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), CRLCC Eugène Marquis (CRLCC), Centre Paul Strauss, CRLCC Paul Strauss, Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER, Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Equipe 11, Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), Université Nice Sophia Antipolis (... - 2019) (UNS), and Université Lille Nord de France (COMUE)-UNICANCER
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Male ,Oncology ,Cancer Research ,Indoles ,0302 clinical medicine ,Sunitinib ,Molecular Targeted Therapy ,Child ,ComputingMilieux_MISCELLANEOUS ,Aged, 80 and over ,[SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology ,Middle Aged ,Sorafenib ,Temsirolimus ,3. Good health ,Treatment Outcome ,030220 oncology & carcinogenesis ,Imatinib Mesylate ,Female ,France ,Erlotinib ,medicine.drug ,Adult ,Niacinamide ,medicine.medical_specialty ,Adolescent ,Antineoplastic Agents ,Skull Base Neoplasms ,Erlotinib Hydrochloride ,Young Adult ,03 medical and health sciences ,Internal medicine ,Chordoma ,medicine ,Humans ,Pyrroles ,Aged ,Retrospective Studies ,Sirolimus ,business.industry ,Phenylurea Compounds ,Neurooncology ,Retrospective cohort study ,medicine.disease ,Surgery ,business ,030217 neurology & neurosurgery ,Progressive disease - Abstract
To assess the role of first-line Molecular Targeted Therapies (MTTs) in Advanced chordoma (AC) patients.Retrospective study of 80 patients treated between January 2004 and December 2015 at 15 major French Sarcoma or Neurooncology Centres.The sex ratio M/F was 46/34. The median age was 59 (6-86) years. The primary sites were the sacrum (50, 62.5%), mobile spine (12, 15.0%), and skull base (18, 22.5%). Metastases were present in 28 patients (36.0%). The first line of MTTs consisted of imatinib (62, 77.5%), sorafenib (11, 13.7%), erlotinib (5, 6.3%), sunitinib (1, 1.2%) and temsirolimus (1, 1.2%). The reported responses were: partial response (5, 6.3%), stable disease (58, 72.5%), or progressive disease (10, 12.5%). Symptomatic improvement was seen in 28/66 assessable patients (42.4%) and was associated with an objective response occurrence (p = 0.005), imatinib (p = 0.020) or erlotinib use (p = 0.028). The median progression-free survival (PFS) was 9.4°months (95% CI, [6.8-16.1]). Two independent factors of poor prognosis for PFS were identified: a skull-based primary location (HR = 2.5, p = 0.019), and the interval between diagnosis and MTT of52months (HR = 2.8, p 0.001). The median overall survival (OS) was 4.4°years (95% CI, [3.8-5.6]). Four independent factors of poor prognosis for OS were identified: the presence of liver metastases (HR = 13.2, p 0.001), pain requiring opioids (HR = 2.9, p = 0.012), skull-based primary location (HR = 19.7, p 0.001), and prior radiotherapy (photon alone) (HR = 2.5, p = 0.024). The PFS and OS did not significantly differ between the MTT.The prognostic factors identified require validation in an independent database but are potently useful to guide treatment decisions and design further clinical trials.
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- 2017