Dataset Information

Therapeutic implications of improved molecular diagnostics for rare CNS embryonal tumor entities: results of an international, retrospective study.

ABSTRACT:

Background

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.

Methods

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.

Results

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.

Conclusion

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.

SUBMITTER: von Hoff K

PROVIDER: S-EPMC8408859 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature

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Publications

Therapeutic implications of improved molecular diagnostics for rare CNS embryonal tumor entities: results of an international, retrospective study.

von Hoff Katja K Haberler Christine C Schmitt-Hoffner Felix F Schepke Elizabeth E de Rojas Teresa T Jacobs Sandra S Zapotocky Michal M Sumerauer David D Perek-Polnik Marta M Dufour Christelle C van Vuurden Dannis D Slavc Irene I Gojo Johannes J Pickles Jessica C JC Gerber Nicolas U NU Massimino Maura M Gil-da-Costa Maria Joao MJ Garami Miklos M Kumirova Ella E Sehested Astrid A Scheie David D Cruz Ofelia O Moreno Lucas L Cho Jaeho J Zeller Bernward B Bovenschen Niels N Grotzer Michael M Alderete Daniel D Snuderl Matija M Zheludkova Olga O Golanov Andrey A Okonechnikov Konstantin K Mynarek Martin M Juhnke Björn Ole BO Rutkowski Stefan S Schüller Ulrich U Pizer Barry B von Zezschwitz Barbara B Kwiecien Robert R Wechsung Maximilian M Konietschke Frank F Hwang Eugene I EI Sturm Dominik D Pfister Stefan M SM von Deimling Andreas A Rushing Elisabeth J EJ Ryzhova Marina M Hauser Peter P Łastowska Maria M Wesseling Pieter P Giangaspero Felice F Hawkins Cynthia C Figarella-Branger Dominique D Eberhart Charles C Burger Peter P Gessi Marco M Korshunov Andrey A Jacques Tom S TS Capper David D Pietsch Torsten T Kool Marcel M

Neuro-oncology 20210901 9

<h4>Background</h4>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.<h4>Methods</h4>Within this retrospective, international study, tumor samples of ...[more]

PMID: 34077956

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Dataset Information

Therapeutic implications of improved molecular diagnostics for rare CNS embryonal tumor entities: results of an international, retrospective study.

Background

Methods

Results

Conclusion

Publications

Therapeutic implications of improved molecular diagnostics for rare CNS embryonal tumor entities: results of an international, retrospective study.

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