{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T08:39:29Z","timestamp":1792485569734,"version":"4.5.0"},"reference-count":48,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2019,3,8]],"date-time":"2019-03-08T00:00:00Z","timestamp":1552003200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Data on frequency, clinical presentation, and outcome of primary metastatic intracranial ependymoma in children are scarce.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Patients and Methods<\/jats:title>\n                    <jats:p>Prospective data on patients younger than 21\u2009years with metastatic intracranial ependymoma at first diagnosis, registered from 2001 to 2014 in the HIT-2000 trial and the HIT-2000 Interim Registry, were analyzed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Of 453 registered patients with intracranial ependymoma and central neuropathology review, initial staging included spinal magnetic resonance imaging in all patients and lumbar cerebrospinal fluid (CSF) analysis in 402 patients. Ten patients (2.2%) had metastatic disease, including three with microscopic CSF positivity only (M1 metastasis stage, 0.7% of patients with CSF staging). Location of the primary tumor was supratentorial in four patients (all supratentorial RELA-fused ependymoma [ST-EPN-RELA]) and within the posterior fossa in five patients (posterior fossa ependymoma type A [PF-EPN-A], n\u2009=\u20094; posterior fossa ependymoma not further classifiable, n\u2009=\u20091), and multifocal in one patient.<\/jats:p>\n                    <jats:p>All four patients with ST-EPN-RELA were alive in first or second complete remission (CR) 7.5\u201312.3\u2009years after diagnosis. All four patients with macroscopic metastases of posterior fossa or multifocal ependymoma died. Three patients with initial M1 stage (ST-EPN-RELA, n\u2009=\u20091; PF-EPN-A, n\u2009=\u20092) received chemotherapy and local irradiation and were alive in second or third CR 3.0\u20139.7\u2009years after diagnosis. Progression-free and overall survival of the entire cohort at 5\u2009years was 13% (\u00b16%), and 58% (\u00b116%), respectively.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Primary metastatic disease is rare in children with intracranial ependymoma. Prognosis may depend on molecular subgroup and extent of dissemination, and relevance of CSF analysis for initial staging remains to be clarified.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Implications for Practice<\/jats:title>\n                    <jats:p>Childhood ependymoma presenting with metastasis at first diagnosis is very rare with a frequency of 2.4% in this population-based, well-characterized cohort. Detection of microscopic metastases in the cerebrospinal fluid was extremely rare, and impact on prognosis and respective treatment decision on irradiation field remains unclear. Initial metastatic presentation occurs in both supratentorial RELA-fused ependymoma and posterior fossa ependymoma. Prognosis may differ according to extent of metastasis and biological subgroup, with poor prognosis in diffusely spread metastatic posterior fossa ependymoma even after combination therapy with both intensive chemotherapy and craniospinal irradiation, which may help to guide individual therapeutic decisions for future patients.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1634\/theoncologist.2018-0489","type":"journal-article","created":{"date-parts":[[2019,3,8]],"date-time":"2019-03-08T15:14:27Z","timestamp":1552058067000},"page":"e921-e929","source":"Crossref","is-referenced-by-count":35,"title":["Newly Diagnosed Metastatic Intracranial Ependymoma in Children: Frequency, Molecular Characteristics, Treatment, and Outcome in the Prospective HIT Series"],"prefix":"10.1093","volume":"24","author":[{"given":"Martin","family":"Benesch","sequence":"first","affiliation":[{"name":"Division of Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent Medicine, Medical 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