Risk prediction in early childhood sonic hedgehog medulloblastoma treated with radiation-avoiding chemotherapy
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Risk prediction in early childhood sonic hedgehog medulloblastoma treated with radiation-avoiding chemotherapy. / Tonn, Svenja; Korshunov, Andrey; Obrecht, Denise; Sill, Martin; Spohn, Michael; von Hoff, Katja; Milde, Till; Pietsch, Torsten; Goschzik, Tobias; Bison, Brigitte; Juhnke, Björn-Ole; Struve, Nina; Sturm, Dominik; Sahm, Felix; Bockmayr, Michael; Friedrich, Carsten; von Bueren, André O; Gerber, Nicolas U; Benesch, Martin; Jones, David T W; Kool, Marcel; Wefers, Annika K; Schüller, Ulrich; Pfister, Stefan M; Rutkowski, Stefan; Mynarek, Martin.
In: NEURO-ONCOLOGY, Vol. 25, No. 8, 03.08.2023, p. 1518-1529.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Risk prediction in early childhood sonic hedgehog medulloblastoma treated with radiation-avoiding chemotherapy
AU - Tonn, Svenja
AU - Korshunov, Andrey
AU - Obrecht, Denise
AU - Sill, Martin
AU - Spohn, Michael
AU - von Hoff, Katja
AU - Milde, Till
AU - Pietsch, Torsten
AU - Goschzik, Tobias
AU - Bison, Brigitte
AU - Juhnke, Björn-Ole
AU - Struve, Nina
AU - Sturm, Dominik
AU - Sahm, Felix
AU - Bockmayr, Michael
AU - Friedrich, Carsten
AU - von Bueren, André O
AU - Gerber, Nicolas U
AU - Benesch, Martin
AU - Jones, David T W
AU - Kool, Marcel
AU - Wefers, Annika K
AU - Schüller, Ulrich
AU - Pfister, Stefan M
AU - Rutkowski, Stefan
AU - Mynarek, Martin
N1 - © The Author(s) 2023. 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 - 2023/8/3
Y1 - 2023/8/3
N2 - BACKGROUND: The prognostic impact of clinical risk factors and DNA methylation patterns in sonic hedgehog (SHH)-activated early childhood desmoplastic/nodular medulloblastoma (DMB) or medulloblastoma with extensive nodularity (MBEN) were evaluated to better identify patients at risk for relapse.METHODS: One hundred and forty-four patients with DMB (n = 99) or MBEN (n = 45) aged <5 years and treated with radiation-sparing approaches, including intraventricular methotrexate in 132 patients were evaluated.RESULTS: Patients with DMB had less favorable 5-year progression-free survival than MBEN (5y-PFS, 71% [DMB] vs. 93% [MBEN]). Patients aged >3 years were associated with more unfavorable 5y-PFS (47% [>3 years] vs. 85% [<1 year] vs. 84% [1-3 years]). DNA methylation profiles available (n = 78) were reclassified according to the 2021 WHO classification into SHH-1 (n = 39), SHH-2 (n = 38), and SHH-3 (n = 1). Hierarchical clustering delineated 2 subgroups among SHH-2: SHH-2a (n = 19) and SHH-2b (n = 19). Patients with SHH-2b medulloblastoma were older, predominantly displayed DMB histology, and were more often located in the cerebellar hemispheres. Chromosome 9q losses were more frequent in SHH-2b, while few chromosomal alterations were observed in SHH-2a. SHH-2b medulloblastoma carried a significantly increased relapse risk (5y-PFS: 58% [SHH-2b] vs. 83% [SHH-1] vs. 95% [SHH-2a]). Subclassification of SHH-2 with key clinical and cytogenetic characteristics was confirmed using 2 independent cohorts (total n = 188). Gene mutation analysis revealed a correlation of SHH-2a with SMO mutations.CONCLUSIONS: These data suggest further heterogeneity within early childhood SHH-DMB/MBEN: SHH-2 splits into a very low-risk group SHH-2a enriched for MBEN histology and SMO mutations, and SHH-2b comprising older DMB patients with a higher risk of relapse.
AB - BACKGROUND: The prognostic impact of clinical risk factors and DNA methylation patterns in sonic hedgehog (SHH)-activated early childhood desmoplastic/nodular medulloblastoma (DMB) or medulloblastoma with extensive nodularity (MBEN) were evaluated to better identify patients at risk for relapse.METHODS: One hundred and forty-four patients with DMB (n = 99) or MBEN (n = 45) aged <5 years and treated with radiation-sparing approaches, including intraventricular methotrexate in 132 patients were evaluated.RESULTS: Patients with DMB had less favorable 5-year progression-free survival than MBEN (5y-PFS, 71% [DMB] vs. 93% [MBEN]). Patients aged >3 years were associated with more unfavorable 5y-PFS (47% [>3 years] vs. 85% [<1 year] vs. 84% [1-3 years]). DNA methylation profiles available (n = 78) were reclassified according to the 2021 WHO classification into SHH-1 (n = 39), SHH-2 (n = 38), and SHH-3 (n = 1). Hierarchical clustering delineated 2 subgroups among SHH-2: SHH-2a (n = 19) and SHH-2b (n = 19). Patients with SHH-2b medulloblastoma were older, predominantly displayed DMB histology, and were more often located in the cerebellar hemispheres. Chromosome 9q losses were more frequent in SHH-2b, while few chromosomal alterations were observed in SHH-2a. SHH-2b medulloblastoma carried a significantly increased relapse risk (5y-PFS: 58% [SHH-2b] vs. 83% [SHH-1] vs. 95% [SHH-2a]). Subclassification of SHH-2 with key clinical and cytogenetic characteristics was confirmed using 2 independent cohorts (total n = 188). Gene mutation analysis revealed a correlation of SHH-2a with SMO mutations.CONCLUSIONS: These data suggest further heterogeneity within early childhood SHH-DMB/MBEN: SHH-2 splits into a very low-risk group SHH-2a enriched for MBEN histology and SMO mutations, and SHH-2b comprising older DMB patients with a higher risk of relapse.
U2 - 10.1093/neuonc/noad027
DO - 10.1093/neuonc/noad027
M3 - SCORING: Journal article
C2 - 36715306
VL - 25
SP - 1518
EP - 1529
JO - NEURO-ONCOLOGY
JF - NEURO-ONCOLOGY
SN - 1522-8517
IS - 8
ER -