engvon Hoff, KatjaHaberler, Christinevan Vuurden, DannisSlavc, IreneGojo, JohannesPickles, Jessica CGerber, Nicolas UMassimino, MauraGil-da-Costa, Maria JoaoGarami, MiklosKumirova, EllaSehested, AstridSchmitt-Hoffner, FelixScheie, DavidCruz, OfeliaMoreno, LucasCho, JaehoZeller, BernwardBovenschen, NielsGrotzer, MichaelAlderete, DanielSnuderl, MatijaZheludkova, OlgaSchepke, ElizabethGolanov, AndreyOkonechnikov, KonstantinMynarek, MartinJuhnke, Björn OleRutkowski, StefanSchüller, UlrichPizer, Barryvon Zezschwitz, BarbaraKwiecien, RobertWechsung, Maximiliande Rojas, TeresaKonietschke, FrankHwang, Eugene ISturm, DominikPfister, Stefan Mvon Deimling, AndreasRushing, Elisabeth JRyzhova, MarinaHauser, PeterŁastowska, MariaWesseling, PieterJacobs, SandraGiangaspero, FeliceHawkins, CynthiaFigarella-Branger, DominiqueEberhart, CharlesBurger, PeterGessi, MarcoKorshunov, AndreyJacques, Tom SCapper, DavidPietsch, TorstenZapotocky, MichalKool, MarcelSumerauer, DavidPerek-Polnik, MartaDufour, ChristelleTherapeutic implications of improved molecular diagnostics for rare CNS embryonal tumor entities: results of an international, retrospective study.info:eu-repo/classification/ddc/610Brain Neoplasms: diagnosisBrain Neoplasms: geneticsBrain Neoplasms: therapyCentral Nervous System Neoplasms: diagnosisCentral Nervous System Neoplasms: geneticsCentral Nervous System Neoplasms: therapyForkhead Transcription FactorsHumansNeoplasms, Germ Cell and Embryonal: diagnosisNeoplasms, Germ Cell and Embryonal: geneticsNeoplasms, Germ Cell and Embryonal: therapyNeuroectodermal Tumors, Primitive: diagnosisNeuroectodermal Tumors, Primitive: geneticsNeuroectodermal Tumors, Primitive: therapyPathology, MolecularRetrospective StudiesCNS NB-FOXR2CNS embryonal tumorCNS-PNETDNA methylation profilingETMRFOXR2 protein, humanForkhead Transcription FactorsOnly 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.Neuro-Oncology 23(9), 1597 - 1611 (2021). doi:10.1093/neuonc/noab136info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionOxford Univ. Press2021info:eu-repo/semantics/closedAccessDEhttps://pub.dzne.de/record/162800https://pub.dzne.de/search?p=id:%22DZNE-2021-01455%22Researchersinfo:eu-repo/semantics/altIdentifier/pmid/pmid:34077956info:eu-repo/semantics/altIdentifier/issn/1523-5866info:eu-repo/semantics/altIdentifier/issn/1522-8517info:eu-repo/semantics/altIdentifier/doi/10.1093/neuonc/noab136