Clinical implementation of integrated molecular‐morphologic risk prediction for meningioma
Brain Pathology, vol. 33, pp. e13132
Abstract
Risk prediction for meningioma tumors was until recently almost exclusively based on morphological features of the tumor. To improve risk prediction, multiple models have been established that incorporate morphological and molecular features for an integrated risk prediction score. One such model is the integrated molecular-morphologic meningioma integrated score (IntS), which allocates points to the histological grade, epigenetic methylation family and specific copy-number variations. After publication of the IntS, questions arose in the neuropathological community about the practical and clinical implementation of the IntS, specifically regarding the calling of CNVs, the applicability of the newly available version (v12.5) of the brain tumor classifier and the need for incorporation of TERT-promoter and CDKN2A/B status analysis in the IntS calculation. To investigate and validate these questions additional analyses of the discovery (n = 514), retrospective validation (n = 184) and prospective validation (n = 287) cohorts used for IntS discovery and validation were performed. Our findings suggest that any loss over 5% of the chromosomal arm suffices for the calling of a CNV, that input from the v12.5 classifier is as good or better than the dedicated meningioma classifier (v2.4) and that there is most likely no need for additional testing for TERT-promoter mutations and/or homozygous losses of CDKN2A/B when defining the IntS for an individual patient. The findings from this study help facilitate the clinical implementation of IntS-based risk prediction for meningioma patients.
Authors 9
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Affiliation as printed
Department of Biostatistics German Cancer Research Center (DKFZ) Heidelberg Germany
Department of Biostatistics, German Cancer Research Center (DKFZ), Heidelberg, Germany
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Hopp Children's Cancer Center Heidelberg
Affiliation as printed
Hopp Children's Cancer Center Heidelberg (KiTZ) Heidelberg Germany
Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany
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German Cancer Research Center · Heidelberg University · University Hospital Heidelberg · Deutsches Konsortium für Translationale Krebsforschung
Affiliation as printed
Department of Neuropathology, University Hospital Heidelberg and CCU Neuropathology, German Consortium for Translational Cancer Research (DKTK) German Cancer Research Center (DKFZ) Heidelberg Germany
Department of Neuropathology, University Hospital Heidelberg and CCU Neuropathology, German Consortium for Translational Cancer Research (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany
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German Cancer Research Center · Heidelberg University · University Hospital Heidelberg · Deutsches Konsortium für Translationale Krebsforschung
Affiliation as printed
Department of Neuropathology, University Hospital Heidelberg and CCU Neuropathology, German Consortium for Translational Cancer Research (DKTK) German Cancer Research Center (DKFZ) Heidelberg Germany
Department of Neuropathology, University Hospital Heidelberg and CCU Neuropathology, German Consortium for Translational Cancer Research (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany
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National Health Service · University College London Hospitals NHS Foundation Trust · National Hospital for Neurology and Neurosurgery · UCL Queen Square Institute of Neurology · University College London
Affiliation as printed
Department of Neurodegenerative Disease, Queen Square Institute of Neurology University College London London UK
Division of Neuropathology, National Hospital for Neurology and Neurosurgery University College London NHS Foundation Trust London UK
Department of Neurodegenerative Disease, Queen Square Institute of Neurology, University College London, London, UK
Division of Neuropathology, National Hospital for Neurology and Neurosurgery, University College London NHS Foundation Trust, London, UK
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German Cancer Research Center · Hopp Children's Cancer Center Heidelberg
Affiliation as printed
Division of Pediatric Glioma Research German Cancer Research Center (DKFZ) Heidelberg Germany
Hopp Children's Cancer Center Heidelberg (KiTZ) Heidelberg Germany
Division of Pediatric Glioma Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany
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German Cancer Research Center · Heidelberg University · University Hospital Heidelberg · Deutsches Konsortium für Translationale Krebsforschung
Affiliation as printed
Department of Neuropathology, University Hospital Heidelberg and CCU Neuropathology, German Consortium for Translational Cancer Research (DKTK) German Cancer Research Center (DKFZ) Heidelberg Germany
Department of Neuropathology, University Hospital Heidelberg and CCU Neuropathology, German Consortium for Translational Cancer Research (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany
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Felix Sahm corresponding
German Cancer Research Center · Heidelberg University · University Hospital Heidelberg · Deutsches Konsortium für Translationale Krebsforschung
Affiliation as printed
Department of Neuropathology, University Hospital Heidelberg and CCU Neuropathology, German Consortium for Translational Cancer Research (DKTK) German Cancer Research Center (DKFZ) Heidelberg Germany
Department of Neuropathology, University Hospital Heidelberg and CCU Neuropathology, German Consortium for Translational Cancer Research (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany
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Sybren L. N. Maas Aachen Department of Pathology Leiden University Medical Center Leiden The Netherlands Department of Pathology, Leiden University Medical Center
Leiden University Medical Center · Erasmus MC
Affiliation as printed
Department of Pathology Erasmus Medical Center Rotterdam The Netherlands
Department of Pathology Leiden University Medical Center Leiden The Netherlands
Department of Pathology, Erasmus Medical Center, Rotterdam, The Netherlands
Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands
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