{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T01:37:31Z","timestamp":1771378651707,"version":"3.50.1"},"reference-count":34,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2022,3,10]],"date-time":"2022-03-10T00:00:00Z","timestamp":1646870400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,3,10]],"date-time":"2022-03-10T00:00:00Z","timestamp":1646870400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100014471","name":"mundipharma research limited","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100014471","id-type":"DOI","asserted-by":"publisher"}]},{"name":"University of Innsbruck and Medical University of Innsbruck"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Strahlenther Onkol"],"published-print":{"date-parts":[[2022,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Although there is no proven standard therapy for leptomeningeal metastases (LM), treatment often includes intrathecal chemotherapy combined with whole brain radiation therapy (WBRT). Little is known about the toxicity of such combination therapies. We performed a\u00a0retrospective safety analysis for the combination of intrathecal liposomal cytarabine with WBRT in patients with LM and validated the EANO-ESMO (European Association of Neuro-oncology\u2014European Society for Medical Oncology) classification in this unique cohort.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Treatment toxicities in patients diagnosed with LM between 2004 and 2014 were retrospectively analyzed according to RTOG (Radiation Therapy Oncology Group) toxicity criteria and NCI CTCAE V5.0 (National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0). Diagnostic criteria and treatment response as assessed by EANO-ESMO classification were correlated with survival by Kaplan\u2013Meier analysis and Breslow test.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>In all, 40\u00a0patients with LM who were treated with combined WBRT and intrathecal cytarabine, were identified. Ten patients (25%) experienced adverse events \u2265grade\u00a03 according to RTOG toxicity criteria; in 22\u00a0patients (55%) NCI CTCAE \u2265grade\u00a03 were detected. Median overall survival was 124\u00a0days. Median time to neurological progression was 52\u00a0days. Patients with positive cerebrospinal fluid (CSF) cytology (<jats:italic>n<\/jats:italic>\u202f=\u200926) showed worse prognosis compared to patients with negative CSF cytology (<jats:italic>n<\/jats:italic>\u202f=\u200914; mOS (median overall survival) 84\u00a0days versus 198\u00a0days, <jats:italic>p<\/jats:italic>\u202f=\u20090.006, respectively). The EANO-ESMO response assessment was significantly associated with survival: \u201cstable\u201d (<jats:italic>n<\/jats:italic>\u202f=\u20097) mOS 233\u00a0days, \u201cresponse\u201d (<jats:italic>n<\/jats:italic>\u202f=\u200910) mOS 206\u00a0days, \u201cprogression\u201d (<jats:italic>n<\/jats:italic>\u202f=\u200917) mOS 45\u00a0days, \u201csuspicion of progression\u201d (<jats:italic>n<\/jats:italic>\u202f=\u20096) mOS 133\u00a0days; overall, <jats:italic>p<\/jats:italic>\u202f&lt;\u20090.001.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>In this retrospective analysis, combined treatment of WBRT and intrathecal liposomal cytarabine shows an acceptable safety profile and may indicate a\u00a0trend towards improved efficacy. The EANO-ESMO classification for diagnosis and treatment response predicts survival.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s00066-022-01910-9","type":"journal-article","created":{"date-parts":[[2022,3,10]],"date-time":"2022-03-10T12:03:32Z","timestamp":1646913812000},"page":"475-483","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Whole brain radiotherapy combined with intrathecal liposomal cytarabine for leptomeningeal metastasis\u2014a\u00a0safety analysis and validation of the EANO-ESMO classification"],"prefix":"10.1007","volume":"198","author":[{"given":"Sarah","family":"Iglseder","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8068-315X","authenticated-orcid":false,"given":"Martha","family":"Nowosielski","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriel","family":"Bsteh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Armin","family":"Muigg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johanna","family":"Heugenhauser","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elke","family":"Mayer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Astrid","family":"Grams","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G\u00fcnther","family":"Stockhammer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meinhard","family":"Nevinny-Stickel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2022,3,10]]},"reference":[{"issue":"1","key":"1910_CR1","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1001\/archneur.1997.00550130008003","volume":"54","author":"MC Chamberlain","year":"1997","unstructured":"Chamberlain\u00a0MC (1997) Carcinomatous meningitis. 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