{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T08:43:57Z","timestamp":1769157837611,"version":"3.49.0"},"reference-count":52,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2022,6,10]],"date-time":"2022-06-10T00:00:00Z","timestamp":1654819200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Blood &amp; Cancer"],"published-print":{"date-parts":[[2022,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Purpose<\/jats:title><jats:p>Primary germ cell tumors (GCTs) are the most common central nervous system (CNS) neoplasm in patients with Down syndrome (DS). However, a standard of care has not been established due to paucity of data.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A retrospective multi\u2010institutional analysis was conducted, in addition to a comprehensive review of the literature.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Ten patients from six institutions (five USA, one Brazil) were identified, in addition to 31 patients in the literature from 1975 to 2021. Of the 41 total patients (mean age 9.9\u00a0years; 61% male), 16 (39%) had non\u2010germinomatous germ cell tumors (NGGCTs), 16 (39%) had pure germinomas, and eight (19.5%) had teratomas. Basal ganglia was the most common tumor location (<jats:italic>n<\/jats:italic>\u00a0=\u00a013; 31.7%), followed by posterior fossa (<jats:italic>n<\/jats:italic>\u00a0=\u00a07; 17%). Nine patients (22%) experienced disease relapse or progression, of which four died from tumor progression (one germinoma, three teratomas). Sixteen patients (39%) experienced treatment\u2010related complications, of which eight (50%) died (five germinomas, three NGGCTs). Of the germinoma patients, two died from chemotherapy\u2010related sepsis, one from postsurgery cardiopulmonary failure, one from pneumonia, and one from moyamoya following radiation therapy (RT). Of the NGGCT patients, one died from chemotherapy\u2010related sepsis, one from postsurgical infection, and one from pneumonia following surgery\/chemotherapy\/RT. Three\u2010year overall survival was 66% for all histological types: 62% germinomas, 79% for NGGCTs, and 53% for teratomas.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Patients with DS treated for CNS GCTs are at an increased risk of treatment\u2010related adverse events. A different therapeutic approach may need to be considered to mitigate treatment\u2010related complications and long\u2010term neurocognitive sequelae.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pbc.29830","type":"journal-article","created":{"date-parts":[[2022,6,10]],"date-time":"2022-06-10T12:28:35Z","timestamp":1654864115000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Multi\u2010institutional analysis of central nervous system germ cell tumors in patients with Down syndrome"],"prefix":"10.1002","volume":"69","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9919-5896","authenticated-orcid":false,"given":"Micah K.","family":"Harris","sequence":"first","affiliation":[{"name":"The Ohio State University College of Medicine  Columbus Ohio USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard T.","family":"Graham","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Cincinnati Children's Hospital Medical Center  Cincinnati Ohio USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andr\u00e9a M.","family":"Cappellano","sequence":"additional","affiliation":[{"name":"Pediatric Oncology IOP\u2010GRAACC\/Federal University of S\u00e3o Paulo  S\u00e3o Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ashley S.","family":"Margol","sequence":"additional","affiliation":[{"name":"Division of Hematology, Oncology and Blood &amp; Marrow Transplantation, Children's Center for Cancer and Blood Diseases Children's Hospital Los Angeles  Los Angeles California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"George","family":"Michaiel","sequence":"additional","affiliation":[{"name":"Division of Hematology, Oncology and Blood &amp; Marrow Transplantation, Children's Center for Cancer and Blood Diseases Children's Hospital Los Angeles  Los Angeles California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4100-7001","authenticated-orcid":false,"given":"John R.","family":"Crawford","sequence":"additional","affiliation":[{"name":"Department of Neurology Children's Health Orange County  Orange California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Myrsini","family":"Ioakeim\u2010Ioannidou","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology Massachusetts General Hospital  Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1630-2102","authenticated-orcid":false,"given":"Joseph R.","family":"Stanek","sequence":"additional","affiliation":[{"name":"The Division of Hematology, Oncology, Blood and Marrow Transplant Nationwide Children's Hospital and The Ohio State University  Columbus Ohio USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2071-5137","authenticated-orcid":false,"given":"Kevin X.","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology Massachusetts General Hospital  Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shannon M.","family":"MacDonald","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology Massachusetts General Hospital  Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8262-7469","authenticated-orcid":false,"given":"Mohamed S.","family":"Abdelbaki","sequence":"additional","affiliation":[{"name":"The Division of Hematology and Oncology, St. Louis Children's Hospital, Washington University, School of Medicine in St. Louis Washington University  St. Louis Missouri USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,6,10]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.2008-0037"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.20207"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-8628(19980707)78:3<207::AID-AJMG1>3.0.CO;2-M"},{"key":"e_1_2_10_5_1","unstructured":"SadakataE YoshidaK BabaS FukuK MatsuoT.A case of basal ganglia germ cell tumor associated with Down's syndrome. In: Nervous System in Children;2021.https:\/\/www.jstage.jst.go.jp\/article\/jspn\/46\/3\/46_243\/_article\/-char\/ja\/"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2403188"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000257095.33125.48"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.25917"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.3171\/2011.3.PEDS10500"},{"key":"e_1_2_10_10_1","first-page":"212","article-title":"A case of cerebellar tumor associated with Down's syndrome","volume":"15","author":"Komiya K","year":"1975","journal-title":"Congenit Anom (Kyoto)"},{"issue":"2","key":"e_1_2_10_11_1","first-page":"145","article-title":"[A case of Down's syndrome complicated by teratoma of the third ventricle of the brain]","volume":"34","author":"Nakato H","year":"1982","journal-title":"No to Shinkei"},{"key":"e_1_2_10_12_1","unstructured":"YamasakiS HamasakiY.A infant case of brain tumor associated with Down's syndrome (in Japanese). In. Vol 54.1985.https:\/\/scholar.google.com\/scholar?hl=en&as_sdt=0%2C1&q=A+infant+case+of+a+brain+tumor+associated+with+Down%E2%80%99s+syndrome&btnG= https:\/\/www.karger.com\/Article\/Abstract\/28721 https:\/\/europepmc.org\/article\/med\/8986161"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.2176\/nmc.32.163"},{"issue":"4","key":"e_1_2_10_14_1","first-page":"345","article-title":"[A case of endodermal sinus tumor in the basal ganglia associated with Down's syndrome]","volume":"21","author":"Oshita N","year":"1993","journal-title":"No Shinkei Geka"},{"issue":"1","key":"e_1_2_10_15_1","first-page":"65","article-title":"[A case report of a 6\u2010year\u2010old boy with intracranial yolk sac tumor treated by VAB\u20106 regimen]","volume":"23","author":"Wada H","year":"1995","journal-title":"No Shinkei Geka"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s003810050139"},{"issue":"8","key":"e_1_2_10_17_1","first-page":"3","article-title":"Down syndrome associated with radiosensitive brain tumor","volume":"26","author":"Hokezu Y","year":"1987","journal-title":"Shenkei Naika"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0090-3019(96)00152-8"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1159\/000028721"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1097\/00043426-199903000-00012"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1136\/jcp.2004.016659"},{"issue":"2","key":"e_1_2_10_22_1","first-page":"137","article-title":"[Intracranial germinoma associated with Down syndrome: case report and review of literature]","volume":"40","author":"Satoh S","year":"2012","journal-title":"No Shinkei Geka"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10014-012-0134-9"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.4103\/2152-7806.100198"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s002470050247"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1159\/000282766"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1097\/MPH.0000000000000711"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clineuro.2012.07.023"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00381-017-3690-9"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.wneu.2017.09.024"},{"key":"e_1_2_10_31_1","first-page":"50","article-title":"Basal ganglia germinoma associated with down syndrome in a female patient","volume":"4","author":"Tempaku A","year":"2018","journal-title":"BAOJ Neurol"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.3171\/2018.9.PEDS18181"},{"key":"e_1_2_10_33_1","article-title":"GC\u201008 central nervous system (CNS) germ cell tumors (GCT) and DOWN syndrome: treatment strategies and morbidities","author":"Dagri J","year":"2012","journal-title":"Neuro\u2010oncology"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(20011215)92:12<3155::AID-CNCR10158>3.0.CO;2-C"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11060-006-9282-2"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/nou327"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1159\/000113110"},{"issue":"1","key":"e_1_2_10_38_1","volume":"54","author":"Shibui S","year":"2014","journal-title":"Neurol Med Chir (Tokyo)"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11060-014-1562-7"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00381-016-3167-2"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.3171\/jns.1999.90.2.0258"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00381-017-3632-6"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000261908.36803.ac"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2013.06.024"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11060-009-9951-z"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/noab270"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/noaa222.292"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/nox122"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2014.59.5132"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00381-009-0974-8"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.25338"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/not019"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.1001\/archotol.124.2.171"}],"container-title":["Pediatric Blood &amp; Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pbc.29830","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/pbc.29830","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pbc.29830","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,23]],"date-time":"2023-08-23T11:36:27Z","timestamp":1692790587000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/pbc.29830"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,10]]},"references-count":52,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2022,10]]}},"alternative-id":["10.1002\/pbc.29830"],"URL":"https:\/\/doi.org\/10.1002\/pbc.29830","archive":["Portico"],"relation":{},"ISSN":["1545-5009","1545-5017"],"issn-type":[{"value":"1545-5009","type":"print"},{"value":"1545-5017","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,10]]},"assertion":[{"value":"2022-04-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-05-17","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-06-10","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e29830"}}