Loïc Lebellec1, Bruno Chauffert2, Jean-Yves Blay3, Axel Le Cesne4, Christine Chevreau5, Emmanuelle Bompas6, François Bertucci7, Didier Cupissol8, Michel Fabbro8, Esma Saada-Bouzid9, Florence Duffaud10, Loïc Feuvret11, Alice Bonneville-Levard3, Jacques-Olivier Bay12, Elodie Vauleon13, Armelle Vinceneux14, Georges Noel15, Nicolas Penel16, Olivier Mir4. 1. Department of General Oncology, Centre Oscar Lambret, Lille, France. 2. Department of Medical Oncology, University Hospital (CHU), Amiens, France. 3. Department of Medical Oncology, Centre Léon Bérard, Lyon, France. 4. Department of Medical Oncology, Institut Gustave Roussy, Villejuif, France. 5. Department of Medical Oncology, Institut Claudius Regaud, Toulouse, France. 6. Department of Medical Oncology, Centre René Gauducheau, Nantes, France. 7. Department of Medical Oncology, Institut Paoli-Calmettes, Marseille, France. 8. Department of Medical Oncology, Institut regional du cancer, Montpellier, France. 9. Department of Medical Oncology, Centre Antoine Lacassagne, Nice, France. 10. Department of Medical Oncology, University Hospital La Timone (CHU), Marseille, France. 11. Department of Radiotherapy, University Hospital La Pitié-Salpétrière (CHU) (APHP), Paris, France. 12. Cellular Therapy and Clinic Hematology Unit for Adults, University Hospital (CHU), Clermont-Ferrand, France. 13. Department of Medical Oncology, Eugène Marquis Cancer Institute, Rennes, France. 14. Department of Medical Oncology, University Hospital (CHU) Bretonneau, Tours, France. 15. Department of Radiotherapy, Centre Paul Strauss, Strasbourg, France. 16. Department of General Oncology, Centre Oscar Lambret, Lille, France; Clinical Research and Methodology Platform, SIRIC OncoLille Consortium, Lille, France. Electronic address: n-penel@o-lambret.fr.
Abstract
BACKGROUND: To assess the role of first-line Molecular Targeted Therapies (MTTs) in Advanced chordoma (AC) patients. METHODS: Retrospective study of 80 patients treated between January 2004 and December 2015 at 15 major French Sarcoma or Neurooncology Centres. RESULTS: 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 of <52months (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. CONCLUSIONS: The prognostic factors identified require validation in an independent database but are potently useful to guide treatment decisions and design further clinical trials.
BACKGROUND: To assess the role of first-line Molecular Targeted Therapies (MTTs) in Advanced chordoma (AC) patients. METHODS: Retrospective study of 80 patients treated between January 2004 and December 2015 at 15 major French Sarcoma or Neurooncology Centres. RESULTS: 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 of <52months (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. CONCLUSIONS: The prognostic factors identified require validation in an independent database but are potently useful to guide treatment decisions and design further clinical trials.
Authors: Molly E Heft Neal; Nicole L Michmerhuizen; Kevin J Kovatch; John Henry J Owen; Jingyi Zhai; Hui Jiang; Erin L McKean; Mark E P Prince; J Chad Brenner Journal: J Neurol Surg B Skull Base Date: 2020-10-12
Authors: Stefan Gröschel; Daniel Hübschmann; Francesco Raimondi; Peter Horak; Gregor Warsow; Martina Fröhlich; Barbara Klink; Laura Gieldon; Barbara Hutter; Kortine Kleinheinz; David Bonekamp; Oliver Marschal; Priya Chudasama; Jagoda Mika; Marie Groth; Sebastian Uhrig; Stephen Krämer; Christoph Heining; Christoph E Heilig; Daniela Richter; Eva Reisinger; Katrin Pfütze; Roland Eils; Stephan Wolf; Christof von Kalle; Christian Brandts; Claudia Scholl; Wilko Weichert; Stephan Richter; Sebastian Bauer; Roland Penzel; Evelin Schröck; Albrecht Stenzinger; Richard F Schlenk; Benedikt Brors; Robert B Russell; Hanno Glimm; Matthias Schlesner; Stefan Fröhling Journal: Nat Commun Date: 2019-04-09 Impact factor: 14.919
Authors: Samantha E Hoffman; Sally A Al Abdulmohsen; Saksham Gupta; Blake M Hauser; David M Meredith; Ian F Dunn; Wenya Linda Bi Journal: Front Neurol Date: 2020-07-08 Impact factor: 4.003
Authors: Edward Anderson; Tammy M Havener; Kimberley M Zorn; Daniel H Foil; Thomas R Lane; Stephen J Capuzzi; Dave Morris; Anthony J Hickey; David H Drewry; Sean Ekins Journal: Sci Rep Date: 2020-07-31 Impact factor: 4.379