{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T21:26:50Z","timestamp":1790803610180,"version":"4.1.0"},"reference-count":45,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2024,8,7]],"date-time":"2024-08-07T00:00:00Z","timestamp":1722988800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100004622","name":"Dutch Cancer Society","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100004622","id-type":"DOI","asserted-by":"crossref"}]},{"name":"The Dutch Ministry of Health, Welfare and Sport"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,12,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Diagnosis and treatment of leptomeningeal metastases (LM) in epidermal growth factor receptor mutation-positive (EGFRm +) non-small-cell lung carcinoma (NSCLC) is challenging. We aimed to identify resistance mechanisms (RM) to osimertinib in cerebrospinal fluid (CSF) and plasma.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>EGFRm\u2005+\u2005patients with new or progressive LM during osimertinib were enrolled. NGS Ampliseq was performed on DNA isolated from CSF. Patients were prescribed osimertinib dose escalation (DE, 160 mg QD) following lumbar puncture. Clinical and radiological response was evaluated 4 weeks after osimertinib DE.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Twenty-eight patients were included. The driver mutation was identified in 93% of CSF samples (n\u2005=\u200526). Seven (27%) harbored \u22651 RM. Twenty-five patients (89%) were prescribed osimertinib DE. Four weeks afterwards, symptoms improved in 5 patients, stabilized in 9 and worsened in 11 patients. Twenty-one (84%) patients underwent MR imaging. Four showed radiological improvement, 14 stabilization, and 3 worsening.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In 27% of patients, an RM was found in CSF ctDNA, none of which are targetable at the time of writing, and the clinical efficacy of osimertinib DE seems limited. There is much to gain in diagnostic as well as therapeutic strategies in EGFRm\u2005+\u2005NSCLC LM.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/neuonc\/noae138","type":"journal-article","created":{"date-parts":[[2024,8,2]],"date-time":"2024-08-02T09:44:54Z","timestamp":1722591894000},"page":"2316-2327","source":"Crossref","is-referenced-by-count":12,"title":["Osimertinib-induced DNA resistance mutations in cerebrospinal fluid of epidermal growth factor receptor-mutated non-small-cell lung carcinoma patients developing leptomeningeal metastases: Osimertinib Resistance Analysis-leptomeningeal metastases study"],"prefix":"10.1093","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9128-1930","authenticated-orcid":false,"given":"J W Tijmen","family":"van der Wel","sequence":"first","affiliation":[{"name":"Department of Thoracic Oncology, Netherlands Cancer Institute , Amsterdam ,","place":["The 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Cancer Institute , Amsterdam ,","place":["The Netherlands"]},{"name":"Department of Pulmonary Diseases, Haaglanden Medical Center , The Hague ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1678-2134","authenticated-orcid":false,"given":"Merel J A","family":"Luitse","sequence":"additional","affiliation":[{"name":"Department of Neuro-oncology, Netherlands Cancer Institute , Amsterdam ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9732-2150","authenticated-orcid":false,"given":"Annette","family":"Compter","sequence":"additional","affiliation":[{"name":"Department of Neuro-oncology, Netherlands Cancer Institute , Amsterdam ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robin P B","family":"Boltjes","sequence":"additional","affiliation":[{"name":"Department of Neuro-oncology, Netherlands Cancer Institute , Amsterdam ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1782-1852","authenticated-orcid":false,"given":"Nik","family":"Sol","sequence":"additional","affiliation":[{"name":"Department of Neuro-oncology, Netherlands Cancer Institute , Amsterdam ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8690-3811","authenticated-orcid":false,"given":"Kim","family":"Monkhorst","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Diseases, Haaglanden Medical Center , The Hague ,","place":["The Netherlands"]},{"name":"Department of Pathology, Netherlands Cancer Institute , Amsterdam ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2765-7139","authenticated-orcid":false,"given":"Daan","family":"van den 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