{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T08:48:58Z","timestamp":1791967738978,"version":"4.3.4"},"reference-count":50,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2020,7,2]],"date-time":"2020-07-02T00:00:00Z","timestamp":1593648000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100012869","name":"Morgan Adams Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012869","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001279","name":"Great Ormond Street Hospital Charity","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001279","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Blood &amp; Cancer"],"published-print":{"date-parts":[[2020,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Relapse occurs in 50% of pediatric ependymoma cases and has poor prognosis. Few studies have investigated the clinical progress of relapsed disease, and treatment lacks a standardized approach.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and materials<\/jats:title><jats:p>We analyzed 302 pediatric ependymoma cases. Tumor, demographic, and treatment variables were investigated for association with relapse risk, time to recurrence, and survival after relapse. DNA methylation profiling was performed for 135\/302 cases, and predominant subgroups were EPN_PFA (<jats:italic>n<\/jats:italic>\u00a0=\u00a095) and EPN_RELA (<jats:italic>n<\/jats:italic>\u00a0=\u00a024). Chromosome 1q status was ascertained for 185\/302 cases by fluorescent in\u2010situ hybridization (FISH), multiplex ligation\u2010dependent probe amplification (MLPA), and DNA methylation profiles.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Sixty\u2010two percent of cases relapsed, with a median of two recurrences with no difference between posterior fossa and supratentorial locations (66%\u00a0vs 55% relapse rate). One hundred seventeen (38%) cases relapsed within two years and five (2%) beyond 10 years. The late relapses were clinically heterogeneous. Tumor grade and treatment affected risk and time to relapse variably across subgroups. After relapse, surgery and irradiation delayed disease progression with a minimal impact on survival across the entire cohort. In the EPN_PFA and EPN_RELA groups, 1q gain was independently associated with relapse risk (subhazard ratio [SHR] 4.307, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.027 and SHR 1.982, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.010, respectively) while EPN_PFA had increased relapse risk compared with EPN_RELA (SHR\u00a0=\u00a00.394, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.018).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Recurrent pediatric ependymoma is an aggressive disease with poor outcomes, for which current treatments are inadequate. We report that chromosome 1q gain increases relapse risk in common molecular subgroups in children but a deeper understanding of the underlying biology at relapse and novel therapeutic approaches are urgently needed.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pbc.28426","type":"journal-article","created":{"date-parts":[[2020,7,2]],"date-time":"2020-07-02T10:55:56Z","timestamp":1593687356000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":51,"title":["A retrospective analysis of recurrent pediatric ependymoma reveals extremely poor survival and ineffectiveness of current treatments across central nervous system locations and molecular subgroups"],"prefix":"10.1002","volume":"67","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4438-6588","authenticated-orcid":false,"given":"Timothy A.","family":"Ritzmann","sequence":"first","affiliation":[{"name":"Children's Brain Tumor Research Centre School of Medicine University of Nottingham  Nottingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hazel A.","family":"Rogers","sequence":"additional","affiliation":[{"name":"Children's Brain Tumor Research Centre School of Medicine University of Nottingham  Nottingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon M.L.","family":"Paine","sequence":"additional","affiliation":[{"name":"Department of Neuropathology Nottingham University Hospital  Nottingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa C.D.","family":"Storer","sequence":"additional","affiliation":[{"name":"Children's Brain Tumor Research Centre School of Medicine University of Nottingham  Nottingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas S.","family":"Jacques","sequence":"additional","affiliation":[{"name":"Developmental Biology and Cancer Programme UCL GOS Institute of Child Health and Department of Histopathology Great Ormond Street Hospital for Children NHS Trust  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca J.","family":"Chapman","sequence":"additional","affiliation":[{"name":"Children's Brain Tumor Research Centre School of Medicine University of Nottingham  Nottingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Ellison","sequence":"additional","affiliation":[{"name":"Department of Pathology St Jude Children's Hospital  Memphis Tennessee"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew M.","family":"Donson","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Colorado  Denver Aurora Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas K.","family":"Foreman","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Colorado  Denver Aurora Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard 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