Therapeutic implications of improved molecular diagnostics for rare CNS-embryonal tumor entities: results of an international, retrospective study
Publication date
2021-09-01
Authors
von Hoff, Katja
Haberler, Christine
Schmitt-Hoffner, Felix
Schepke, Elizabeth
de Rojas, Teresa
Jacobs, Sandra
Zapotocky, Michal
Sumerauer, David
Perek-Polnik, Marta
Dufour, Christelle
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Supervisors
Document Type
Article
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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.
Keywords
CNS embryonal tumor, CNS NB-FOXR2, CNS-PNET, DNA methylation profiling, ETMR, Taverne, Clinical Neurology, Oncology, Cancer Research, Journal Article
Citation
von Hoff, K, Haberler, C, Schmitt-Hoffner, F, Schepke, E, de Rojas, T, Jacobs, S, Zapotocky, M, Sumerauer, D, Perek-Polnik, M, Dufour, C, van Vuurden, D, Slavc, I, Gojo, J, Pickles, J C, Gerber, N U, Massimino, M, Gil-da-Costa, M J, Garami, M, Kumirova, E, Sehested, A, Scheie, D, Cruz, O, Moreno, L, Cho, J, Zeller, B, Bovenschen, N, Grotzer, M, Alderete, D, Snuderl, M, Zheludkova, O, Golanov, A, Okonechnikov, K, Mynarek, M, Juhnke, B O, Rutkowski, S, Schüller, U, Pizer, B, Zezschwitz, B V, Kwiecien, R, Wechsung, M, Konietschke, F, Hwang, E I, Sturm, D, Pfister, S M, von Deimling, A, Rushing, E J, Ryzhova, M, Hauser, P, Łastowska, M, Wesseling, P, Giangaspero, F, Hawkins, C, Figarella-Branger, D, Eberhart, C, Burger, P, Gessi, M, Korshunov, A, Jacques, T S, Capper, D, Pietsch, T & Kool, M 2021, 'Therapeutic implications of improved molecular diagnostics for rare CNS-embryonal tumor entities : results of an international, retrospective study', Neuro-Oncology, vol. 23, no. 9, pp. 1597-1611. https://doi.org/10.1093/neuonc/noab136