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

TY - JOUR

T1 - Therapeutic implications of improved molecular diagnostics for rare CNS-embryonal tumor entities: results of an international, retrospective study

AU - von Hoff, Katja

AU - Haberler, Christine

AU - Schmitt-Hoffner, Felix

AU - Schepke, Elizabeth

AU - de Rojas, Teresa

AU - Jacobs, Sandra

AU - Zapotocky, Michal

AU - Sumerauer, David

AU - Perek-Polnik, Marta

AU - Dufour, Christelle

AU - van Vuurden, Dannis

AU - Slavc, Irene

AU - Gojo, Johannes

AU - Pickles, Jessica C

AU - Gerber, Nicolas U

AU - Massimino, Maura

AU - Gil-da-Costa, Maria Joao

AU - Garami, Miklos

AU - Kumirova, Ella

AU - Sehested, Astrid

AU - Scheie, David

AU - Cruz, Ofelia

AU - Moreno, Lucas

AU - Cho, Jaeho

AU - Zeller, Bernward

AU - Bovenschen, Niels

AU - Grotzer, Michael

AU - Alderete, Daniel

AU - Snuderl, Matija

AU - Zheludkova, Olga

AU - Golanov, Andrey

AU - Okonechnikov, Konstantin

AU - Mynarek, Martin

AU - Juhnke, B Ole

AU - Rutkowski, Stefan

AU - Schüller, Ulrich

AU - Pizer, Barry

AU - Zezschwitz, Barbara V

AU - Kwiecien, Robert

AU - Wechsung, Maximilian

AU - Konietschke, Frank

AU - Hwang, Eugene I

AU - Sturm, Dominik

AU - Pfister, Stefan M

AU - von Deimling, Andreas

AU - Rushing, Elisabeth J

AU - Ryzhova, Marina

AU - Hauser, Peter

AU - Łastowska, Maria

AU - Wesseling, Pieter

AU - Giangaspero, Felice

AU - Hawkins, Cynthia

AU - Figarella-Branger, Dominique

AU - Eberhart, Charles

AU - Burger, Peter

AU - Gessi, Marco

AU - Korshunov, Andrey

AU - Jacques, Tom S

AU - Capper, David

AU - Pietsch, Torsten

AU - Kool, Marcel

N1 - © The Author(s) 2021. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

PY - 2021/9/1

Y1 - 2021/9/1

N2 - 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.

AB - 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.

U2 - 10.1093/neuonc/noab136

DO - 10.1093/neuonc/noab136

M3 - SCORING: Journal article

C2 - 34077956

VL - 23

SP - 1597

EP - 1611

JO - NEURO-ONCOLOGY

JF - NEURO-ONCOLOGY

SN - 1522-8517

IS - 9

ER -