162800 20230915092407.0 10.1093/neuonc/noab136 doi pmid:34077956 pmid pmc:PMC8408859 pmc 1522-8517 ISSN 1523-5866 ISSN altmetric:106956292 altmetric DZNE-2021-01455 English 610 von Hoff, Katja 0000-0002-5669-8546 0 Therapeutic implications of improved molecular diagnostics for rare CNS embryonal tumor entities: results of an international, retrospective study. Oxford 2021 Oxford Univ. Press article DRIVER Output Types/Journal article DataCite Journal Article journal journal PUB:(DE-HGF)16 1637585218_15706 PUB:(DE-HGF) ARTICLE BibTeX JOURNAL_ARTICLE ORCID Journal Article 0 EndNote Only few data are available on treatment-associated behavior of distinct rare CNS embryonal tumor entities previously treated as 'CNS-primitive neuroectodermal tumors' (CNS-PNET). Respective data on specific entities, including CNS neuroblastoma, FOXR2 activated (CNS NB-FOXR2), and embryonal tumors with multilayered rosettes (ETMR) are needed for development of differentiated treatment strategies.Within this retrospective, international study, tumor samples of clinically well-annotated patients with the original diagnosis of CNS-PNET were analyzed using DNA methylation arrays (n = 307). Additional cases (n = 66) with DNA methylation pattern of CNS NB-FOXR2 were included irrespective of initial histological diagnosis. Pooled clinical data (n = 292) were descriptively analyzed.DNA methylation profiling of 'CNS-PNET' classified 58 (19%) cases as ETMR, 57 (19%) as high-grade glioma (HGG), 36 (12%) as CNS NB-FOXR2, and 89(29%) cases were classified into 18 other entities. Sixty-seven (22%) cases did not show DNA methylation patterns similar to established CNS tumor reference classes. Best treatment results were achieved for CNS NB-FOXR2 patients (5-year PFS: 63% ± 7%, OS: 85% ± 5%, n = 63), with 35/42 progression-free survivors after upfront craniospinal irradiation (CSI) and chemotherapy. The worst outcome was seen for ETMR and HGG patients with 5-year PFS of 18% ± 6% and 22% ± 7%, and 5-year OS of 24% ± 6% and 25% ± 7%, respectively.The historically reported poor outcome of CNS-PNET patients becomes highly variable when tumors are molecularly classified based on DNA methylation profiling. Patients with CNS NB-FOXR2 responded well to current treatments and a standard-risk CSI-based regimen may be prospectively evaluated. The poor outcome of ETMR across applied treatment strategies substantiates the necessity for evaluation of novel treatments. 899 - ohne Topic (POF4-899) G:(DE-HGF)POF4-899 POF4-899 POF IV 0 Dataset connected to CrossRef, PubMed, , Journals: pub.dzne.de CNS NB-FOXR2 Other CNS embryonal tumor Other CNS-PNET Other DNA methylation profiling Other ETMR Other FOXR2 protein, human NLM Chemicals Forkhead Transcription Factors NLM Chemicals Brain Neoplasms: diagnosis MeSH Brain Neoplasms: genetics MeSH Brain Neoplasms: therapy MeSH Central Nervous System Neoplasms: diagnosis MeSH Central Nervous System Neoplasms: genetics MeSH Central Nervous System Neoplasms: therapy MeSH Forkhead Transcription Factors MeSH Humans MeSH Neoplasms, Germ Cell and Embryonal: diagnosis MeSH Neoplasms, Germ Cell and Embryonal: genetics MeSH Neoplasms, Germ Cell and Embryonal: therapy MeSH Neuroectodermal Tumors, Primitive: diagnosis MeSH Neuroectodermal Tumors, Primitive: genetics MeSH Neuroectodermal Tumors, Primitive: therapy MeSH Pathology, Molecular MeSH Retrospective Studies MeSH Haberler, Christine 1 Schmitt-Hoffner, Felix 2 Schepke, Elizabeth 3 de Rojas, Teresa 4 Jacobs, Sandra 5 Zapotocky, Michal 6 Sumerauer, David 7 Perek-Polnik, Marta 8 Dufour, Christelle 0000-0001-5993-8077 9 van Vuurden, Dannis 10 Slavc, Irene 11 Gojo, Johannes 12 Pickles, Jessica C 13 Gerber, Nicolas U 14 Massimino, Maura 15 Gil-da-Costa, Maria Joao 16 Garami, Miklos 17 Kumirova, Ella 18 Sehested, Astrid 19 Scheie, David 0000-0002-9772-8828 20 Cruz, Ofelia 21 Moreno, Lucas 22 Cho, Jaeho 23 Zeller, Bernward 24 Bovenschen, Niels 25 Grotzer, Michael 26 Alderete, Daniel 27 Snuderl, Matija 28 Zheludkova, Olga 29 Golanov, Andrey 30 Okonechnikov, Konstantin 31 Mynarek, Martin 32 Juhnke, Björn Ole 33 Rutkowski, Stefan 34 Schüller, Ulrich 35 Pizer, Barry 36 von Zezschwitz, Barbara 37 Kwiecien, Robert 38 Wechsung, Maximilian 39 Konietschke, Frank 40 Hwang, Eugene I 41 Sturm, Dominik 42 Pfister, Stefan M 43 von Deimling, Andreas 44 Rushing, Elisabeth J 45 Ryzhova, Marina 46 Hauser, Peter 47 Łastowska, Maria 48 Wesseling, Pieter 0000-0001-5453-5201 49 Giangaspero, Felice 50 Hawkins, Cynthia 51 Figarella-Branger, Dominique 52 Eberhart, Charles 53 Burger, Peter 54 Gessi, Marco 55 Korshunov, Andrey 56 Jacques, Tom S 57 Capper, David 58 Pietsch, Torsten P:(DE-2719)2812617 59 dzne Kool, Marcel 60 10.1093/neuonc/noab136 Vol. 23, no. 9, p. 1597 - 1611 PERI:(DE-600)2094060-9 9 1597 - 1611 Neuro-Oncology 23 2021 1523-5866 oai:pub.dzne.de:162800 VDB Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 59 P:(DE-2719)2812617 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 2021 DBCoverage StatID:(DE-HGF)0160 StatID Essential Science Indicators 2021-02-03 WoS StatID:(DE-HGF)0113 StatID Science Citation Index Expanded 2021-02-03 Nationallizenz StatID:(DE-HGF)0420 StatID 2022-11-08 ger DBCoverage StatID:(DE-HGF)0300 StatID Medline 2022-11-08 DBCoverage StatID:(DE-HGF)0199 StatID Clarivate Analytics Master Journal List 2022-11-08 DBCoverage StatID:(DE-HGF)0150 StatID Web of Science Core Collection 2022-11-08 DBCoverage StatID:(DE-HGF)1110 StatID Current Contents - Clinical Medicine 2022-11-08 JCR StatID:(DE-HGF)0100 StatID NEURO-ONCOLOGY : 2021 2022-11-08 DBCoverage StatID:(DE-HGF)0200 StatID SCOPUS 2022-11-08 IF >= 10 StatID:(DE-HGF)9910 StatID NEURO-ONCOLOGY : 2021 2022-11-08 I:(DE-2719)1011009 Brainbank Unit Bonn Brainbank Unit Bonn 0 journal VDB I:(DE-2719)1011009 UNRESTRICTED