Risk prediction in early childhood sonic hedgehog medulloblastoma treated with radiation-avoiding chemotherapy: Evidence for more than 2 subgroups.

Autor:	Tonn S; Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Korshunov A; Clinical Cooperation Unit Neuropathology (B300), German Cancer Research Center (DKFZ), and German Cancer Consortium (DKTK), Heidelberg, Germany.; Department of Neuropathology, Heidelberg University Hospital, Heidelberg, Germany.; Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany., Obrecht D; Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Sill M; Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.; Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany.; Division of Pediatric Neurooncology (B062), German Cancer Research Center (DKFZ), and German Cancer Consortium (DKTK), Heidelberg, Germany.; Research Institute Children's Cancer Center Hamburg, Hamburg, Germany., Spohn M; Bioinformatics Core Unit, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., von Hoff K; Department of Pediatric Oncology and Hematology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany., Milde T; Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany.; Clinical Cooperation Unit Pediatric Oncology, German Cancer Research Center (DKFZ) and German Consortium for Translational Cancer Research (DKTK), Heidelberg, Germany.; Department of Pediatric Oncology, Hematology and Immunology, Heidelberg University Hospital, Heidelberg, Germany., Pietsch T; Institute of Neuropathology, DGNN Brain Tumor Reference Center, University of Bonn Medical Center, Bonn, Germany., Goschzik T; Institute of Neuropathology, DGNN Brain Tumor Reference Center, University of Bonn Medical Center, Bonn, Germany., Bison B; Diagnostic and interventional Neuroradiology, Faculty of Medicine, University Hospital Augsburg, Augsburg, Germany.; Neuroradiological Reference Center for the pediatric brain tumor (HIT) studies of the German Society of Pediatric Oncology and Hematology, University Hospital Wuerzburg, Wuerzburg, Germany (until 2020).; University Augsburg, Faculty of Medicine, Augsburg, Germany (since 2021), Germany., Juhnke BO; Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Struve N; Department of Radiotherapy, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.; Mildred Scheel Cancer Career Center HaTriCS4, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Sturm D; Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany.; Division of Pediatric Neurooncology (B062), German Cancer Research Center (DKFZ), and German Cancer Consortium (DKTK), Heidelberg, Germany.; Department of Pediatric Oncology, Hematology and Immunology, Heidelberg University Hospital, Heidelberg, Germany., Sahm F; Clinical Cooperation Unit Neuropathology (B300), German Cancer Research Center (DKFZ), and German Cancer Consortium (DKTK), Heidelberg, Germany.; Department of Neuropathology, Heidelberg University Hospital, Heidelberg, Germany.; Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany., Bockmayr M; Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.; Research Institute Children's Cancer Center Hamburg, Hamburg, Germany.; Mildred Scheel Cancer Career Center HaTriCS4, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Friedrich C; Department of Pediatrics and Pediatric Hematology/Oncology, University Children's Hospital, Klinikum Oldenburg AöR, Carl von Ossietzky University, Oldenburg, Germany., von Bueren AO; Division of Pediatric Oncology and Hematology, Department of Pediatrics, Gynecology and Obstetrics, University Hospital of Geneva, Geneva, Switzerland.; CANSEARCH research platform for Pediatric Oncology and Hematology, Faculty of Medicine, Department of Pediatrics, Gynecology and Obstetrics, University of Geneva, Geneva, Switzerland., Gerber NU; Department of Oncology, University Children's Hospital, Zurich, Switzerland., Benesch M; Institute of Pathology, Charité - Universitätsmedizin Berlin, Berlin, Germany.; Division of Pediatric Hematology/Oncology, Department of Pediatrics and Adolescent Medicine, Medical University of Graz, Graz, Austria., Jones DTW; Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany.; Division of Pediatric Glioma Research (B360), German Cancer Research Center (DKFZ), Heidelberg, Germany., Kool M; Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany.; Division of Pediatric Neurooncology (B062), German Cancer Research Center (DKFZ), and German Cancer Consortium (DKTK), Heidelberg, Germany.; Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands., Wefers AK; Mildred Scheel Cancer Career Center HaTriCS4, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.; Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Schüller U; Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.; Research Institute Children's Cancer Center Hamburg, Hamburg, Germany.; Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Pfister SM; Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany.; Division of Pediatric Neurooncology (B062), German Cancer Research Center (DKFZ), and German Cancer Consortium (DKTK), Heidelberg, Germany.; Department of Pediatric Oncology, Hematology and Immunology, Heidelberg University Hospital, Heidelberg, Germany., Rutkowski S; Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Mynarek M; Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.; Mildred Scheel Cancer Career Center HaTriCS4, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Jazyk:	angličtina
Zdroj:	Neuro-oncology [Neuro Oncol] 2023 Aug 03; Vol. 25 (8), pp. 1518-1529.
DOI:	10.1093/neuonc/noad027
Abstrakt:	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. (© 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.)
Databáze:	MEDLINE
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