153356 20230915094016.0 10.1200/JCO.19.03057 doi 0732-183X ISSN 1527-7755 ISSN altmetric:80563638 altmetric pmid:32330099 pmid DZNE-2020-01353 English 610 Mynarek, Martin 0 Nonmetastatic Medulloblastoma of Early Childhood: Results From the Prospective Clinical Trial HIT-2000 and An Extended Validation Cohort Alexandria, Va. 2020 American Society of Clinical Oncology article DRIVER Output Types/Journal article DataCite Journal Article journal journal PUB:(DE-HGF)16 1624883455_31290 PUB:(DE-HGF) ARTICLE BibTeX JOURNAL_ARTICLE ORCID Journal Article 0 EndNote PURPOSEThe HIT-2000-BIS4 trial aimed to avoid highly detrimental craniospinal irradiation (CSI) in children < 4 years of age with nonmetastatic medulloblastoma by systemic chemotherapy, intraventricular methotrexate, and risk-adapted local radiotherapy.PATIENTS AND METHODSFrom 2001-2011, 87 patients received systemic chemotherapy and intraventricular methotrexate. Until 2006, CSI was reserved for nonresponse or progression. After 2006, local radiotherapy was introduced for nonresponders or patients with classic medulloblastoma (CMB) or large-cell/anaplastic medulloblastoma (LCA). DNA methylation profiles of infantile sonic hedgehog-activated medulloblastoma (SHH-INF) were subdivided into iSHH-I and iSHH-II subtypes in the HIT-2000-BIS4 cohort and a validation cohort (n = 71) from the HIT group and Russia.RESULTSFive years after diagnosis, patients with desmoplastic medulloblastoma (DMB) or medulloblastoma with extensive nodularity (MBEN; n = 42) had 93% progression-free survival (5y-PFS), 100% overall survival (5y-OS), and 93% CSI-free (5y-CSI-free) survival. Patients with CMB/LCA (n = 45) had 37% 5y-PFS, 62% 5y-OS, and 39% 5y-CSI-free survival. Local radiotherapy did not improve survival in patients with CMB/LCA. All DMB/MBEN assessed by DNA methylation profiling belonged to the SHH-INF subgroup. Group 3 patients (5y-PFS, 36%; n = 14) relapsed more frequently than the SHH-INF group (5y-PFS, 93%; n = 28) or group 4 patients (5y-PFS, 83%; n = 6; P < .001). SHH-INF split into iSHH-I and iSHH-II subtypes in HIT-2000-BIS4 and the validation cohort, without prognostic impact (5y-PFS: iSHH-I, 73%, v iSHH-II, 83%; P = .25; n = 99). Intelligence quotient (IQ) was significantly lower in patients after CSI (mean IQ, 90 [no radiotherapy], v 74 [CSI]; P = .012).CONCLUSIONSystemic chemotherapy and intraventricular methotrexate led to favorable survival in both iSHH subtypes of SHH-activated DMB/MBEN with acceptable neurotoxicity. Survival in patients with non-wingless (WNT)/non-SHH disease with CMB/LCA was not improved by local radiotherapy. Patients with group 4 disease had more favorable survival rates than those with group 3 medulloblastoma. 344 - Clinical and Health Care Research (POF3-344) G:(DE-HGF)POF3-344 POF3-344 POF III 0 Dataset connected to CrossRef Cerebellar Neoplasms: drug therapy MeSH Cerebellar Neoplasms: mortality MeSH Cerebellar Neoplasms: radiotherapy MeSH Child, Preschool MeSH Cranial Irradiation: adverse effects MeSH DNA Methylation MeSH Female MeSH Humans MeSH Infant MeSH Male MeSH Medulloblastoma: drug therapy MeSH Medulloblastoma: mortality MeSH Medulloblastoma: radiotherapy MeSH Methotrexate: administration & dosage MeSH Neuropsychological Tests MeSH Prospective Studies MeSH von Hoff, Katja 1 Pietsch, Torsten P:(DE-2719)2812617 2 dzne Ottensmeier, Holger 3 Warmuth-Metz, Monika 4 Bison, Brigitte 5 Pfister, Stefan 6 Korshunov, Andrey 7 Sharma, Tanvi 8 Jaeger, Natalie 9 Ryzhova, Marina 10 Zheludkova, Olga 11 Golanov, Andrey 12 Rushing, Elisabeth Jane 13 Hasselblatt, Martin 14 Koch, Arend 15 Schüller, Ulrich P:(DE-HGF)0 16 von Deimling, Andreas 17 Sahm, Felix 18 Sill, Martin 19 Riemenschneider, Markus J. 20 Dohmen, Hildegard 21 Monoranu, Camelia Maria 22 Sommer, Clemens 23 Staszewski, Ori 24 Mawrin, Christian 25 Schittenhelm, Jens 26 Brück, Wolfgang 27 Filipski, Katharina 28 Hartmann, Christian P:(DE-HGF)0 29 Meinhardt, Matthias 30 Pietschmann, Klaus 31 Haberler, Christine 32 Slavc, Irene 33 Gerber, Nicolas U. 34 Grotzer, Michael 35 Benesch, Martin 36 Schlegel, Paul Gerhardt 37 Deinlein, Frank 38 von Bueren, André O. 39 Friedrich, Carsten 40 Juhnke, Björn-Ole 41 Obrecht, Denise 42 Fleischhack, Gudrun 43 Kwiecien, Robert 44 Faldum, Andreas 45 Kortmann, Rolf Dieter 46 Kool, Marcel 47 Rutkowski, Stefan P:(DE-HGF)0 48 Corresponding author 10.1200/JCO.19.03057 Vol. 38, no. 18, p. 2028 - 2040 PERI:(DE-600)2005181-5 18 2028 - 2040 Journal of clinical oncology 38 2020 1527-7755 VDB oai:pub.dzne.de:153356 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 2 P:(DE-2719)2812617 DE-HGF Gesundheit Erkrankungen des Nervensystems G:(DE-HGF)POF3-340 G:(DE-HGF)POF3-344 G:(DE-HGF)POF3 G:(DE-HGF)POF3-300 G:(DE-HGF)POF Clinical and Health Care Research 0 DE-HGF Programmungebundene Forschung ohne Programm G:(DE-HGF)POF4-890 G:(DE-HGF)POF4-899 G:(DE-HGF)POF4 G:(DE-HGF)POF4-800 G:(DE-HGF)POF ohne Topic 0 2020 DBCoverage StatID:(DE-HGF)0160 StatID Essential Science Indicators 2020-09-04 WoS StatID:(DE-HGF)0113 StatID Science Citation Index Expanded 2020-09-04 Nationallizenz StatID:(DE-HGF)0420 StatID 2022-11-16 ger JCR StatID:(DE-HGF)0100 StatID J CLIN ONCOL : 2021 2022-11-16 DBCoverage StatID:(DE-HGF)0200 StatID SCOPUS 2022-11-16 DBCoverage StatID:(DE-HGF)0300 StatID Medline 2022-11-16 DBCoverage StatID:(DE-HGF)0199 StatID Clarivate Analytics Master Journal List 2022-11-16 DBCoverage StatID:(DE-HGF)0150 StatID Web of Science Core Collection 2022-11-16 DBCoverage StatID:(DE-HGF)1110 StatID Current Contents - Clinical Medicine 2022-11-16 DBCoverage StatID:(DE-HGF)1030 StatID Current Contents - Life Sciences 2022-11-16 IF >= 50 StatID:(DE-HGF)9950 StatID J CLIN ONCOL : 2021 2022-11-16 I:(DE-2719)1011009 Brainbank Unit Bonn Brainbank Unit Bonn 0 journal VDB I:(DE-2719)1011009 UNRESTRICTED