{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T19:40:40Z","timestamp":1786390840071,"version":"build-2736575974"},"reference-count":62,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T00:00:00Z","timestamp":1781136000000},"content-version":"vor","delay-in-days":10,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Reports"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>This retrospective series reports outcomes and prognostic factors for advanced chordoma (AC) treatment with molecular targeted therapies (MTTs) in different treatment lines.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This is a retrospective series of 57 patients with AC treated between 2004 and 2023 at one of seven participating sarcoma centres. Demographics, previous treatment, treatment details and outcomes were recorded.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      57 patients were treated with 7 different MTTs. Treatment was received in first (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200957), second (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200916), third (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20095) or fourth (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20091) line. The most frequently administered agent in first line was imatinib (84.2%) and in second line imatinib + sirolimus (35.7%). Overall median progression free survival (PFS) and overall survival (OS) in first\u2010line treatment was 6.5 (95% CI 4.0\u20139.0) and 29.5\u2009months (95% CI 24.0\u201340.4) and in second\u2010line 10.0 (95% CI 4.0\u201322.0) and 37.2\u2009months (95% CI 9.4\u201345.9). Partial response according to RECIST 1.1 was seen in 5\/79 treatments (6.3%). Dose reductions and interruptions were reported in 19.0% and 27.8% of treatments.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>PFS and response rates with these MTTs were in line with previous phase II trials and retrospective series. Although the efficacy does not meet the European Society of Medical Oncology (ESMO) Magnitude of Clinical Benefit Scale (MCBS) criteria for single arm studies in orphan diseases, MTTs are frequently used off\u2010label due to the high unmet need and lack of other systemic treatment options. The toxicity profile and limited efficacy rate should be taken into account when counselling patients. Further research is needed to explore other systemic treatment options including (combinations with) immunotherapy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cnr2.70596","type":"journal-article","created":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T12:21:53Z","timestamp":1781180513000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Systemic Treatment of Advanced Chordoma With Molecular Targeted Therapies: A Large Multicentre European Retrospective Case Series"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5400-1138","authenticated-orcid":false,"given":"Astrid","family":"Lipplaa","sequence":"first","affiliation":[{"name":"Department of Medical Oncology Leiden University Medical Center  Leiden the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadia","family":"Hindi","sequence":"additional","affiliation":[{"name":"Department of Oncology Hospital Universitario Virgen del Roc\u00edo  Seville Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pawel","family":"Teterycz","sequence":"additional","affiliation":[{"name":"Department of Soft Tissue\/Bone Sarcoma and Melanoma Maria Sklodowska\u2010Curie Institute \u2010 Oncology Center  Warsaw Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robin J.","family":"Young","sequence":"additional","affiliation":[{"name":"Department of Oncology Weston Park Hospital  Sheffield UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ioannis","family":"Boukonavis","sequence":"additional","affiliation":[{"name":"Department of Oncology Aristotle University of Thessaloniki  Thessaloniki Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josefina","family":"Cruz","sequence":"additional","affiliation":[{"name":"Department of Oncology Hospital Universitario de Canarias  San Crist\u00f3bal de La Laguna Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"Martinez\u2010Trufero","sequence":"additional","affiliation":[{"name":"Department of Oncology Hospital Universitario Miguel Servet  Zaragoza Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Speetjens","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Leiden University Medical Center  Leiden the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wilco","family":"Peul","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Leiden University Medical Center  Leiden the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert J. 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