Integrated Molecular-Morphologic Meningioma Classification: A Multicenter Retrospective Analysis, Retrospectively and Prospectively Validated.

Autor:	Maas SLN; 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 Pathology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands., Stichel D; Department of Neuropathology, University Hospital Heidelberg and CCU Neuropathology, German Consortium for Translational Cancer Research (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany., Hielscher T; Department of Biostatistics, German Cancer Research Center (DKFZ), Heidelberg, Germany., Sievers P; Department of Neuropathology, University Hospital Heidelberg and CCU Neuropathology, German Consortium for Translational Cancer Research (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany., Berghoff AS; Institute of Neurology, Medical University of Vienna, Vienna, Austria.; Department of Medicine I, Clinical Division of Oncology, Medical University of Vienna, Vienna, Austria., Schrimpf D; Department of Neuropathology, University Hospital Heidelberg and CCU Neuropathology, German Consortium for Translational Cancer Research (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany., Sill M; Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany., Euskirchen P; Department of Neurology, Charité - Universitätsmedizin Berlin, Berlin, Germany., Blume C; Department of Neuropathology, University Hospital Heidelberg and CCU Neuropathology, German Consortium for Translational Cancer Research (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany., Patel A; Department of Neuropathology, University Hospital Heidelberg and CCU Neuropathology, German Consortium for Translational Cancer Research (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany., Dogan H; Department of Neuropathology, University Hospital Heidelberg and CCU Neuropathology, German Consortium for Translational Cancer Research (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany., Reuss D; Department of Neuropathology, University Hospital Heidelberg and CCU Neuropathology, German Consortium for Translational Cancer Research (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany., Dohmen H; Department of Neuropathology, University Hospital Gießen, Giessen, Germany., Stein M; Department of Neuropathology, University Hospital Gießen, Giessen, Germany.; Department of Neurosurgery, University Hospital Gießen, Giessen, Germany., Reinhardt A; Department of Neuropathology, University Hospital Heidelberg and CCU Neuropathology, German Consortium for Translational Cancer Research (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany., Suwala AK; Department of Neuropathology, University Hospital Heidelberg and CCU Neuropathology, German Consortium for Translational Cancer Research (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany., Wefers AK; Department of Neuropathology, University Hospital Heidelberg and CCU Neuropathology, German Consortium for Translational Cancer Research (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany., Baumgarten P; Department of Neurosurgery, University Hospital Frankfurt, Frankfurt, Germany., Ricklefs F; Department of Neurosurgery, University Hospital Hamburg-Eppendorf, Hamburg, Germany., Rushing EJ; Department of Neuropathology, University Hospital Zurich, Zürich, Switzerland., Bewerunge-Hudler M; Genome and Proteome Core Facility, German Cancer Research Center (DKFZ), Heidelberg, Germany., Ketter R; Department of Neurosurgery, University Hospital Homburg, Homburg, Germany., Schittenhelm J; Department of Neuropathology, University Hospital Tübingen, Tübingen, Germany., Jaunmuktane Z; Division of Neuropathology, National Hospital for Neurology and Neurosurgery, University College London NHS Foundation Trust, London, United Kingdom.; Department of Clinical and Movement Neurosciences and Queen Square Brain Bank for Neurological Disorders, Queen Square Institute of Neurology, University College London, London, United Kingdom., Leu S; Department of Neuropathology, University Hospital Basel, Basel, Switzerland., Greenway FEA; Department of Neurosurgery, St George's Hospital, London, United Kingdom., Bridges LR; Department of Cellular Pathology, St George's Hospital, London, United Kingdom., Jones T; Department of Neurosurgery, St George's Hospital, London, United Kingdom., Grady C; Department of Neurosurgery, NYU Langone Hospital, New York, NY., Serrano J; Department of Neurosurgery, NYU Langone Hospital, New York, NY., Golfinos J; Department of Neurosurgery, NYU Langone Hospital, New York, NY., Sen C; Department of Neurosurgery, NYU Langone Hospital, New York, NY., Mawrin C; Department of Neuropathology, University Hospital Magdeburg, Magdeburg, Germany., Jungk C; Department of Neurosurgery, University Hospital Heidelberg, Heidelberg, Germany., Hänggi D; Department of Neurosurgery, University Hospital Düsseldorf, Düsseldorf, Germany., Westphal M; Department of Neurosurgery, University Hospital Hamburg-Eppendorf, Hamburg, Germany., Lamszus K; Department of Neurosurgery, University Hospital Hamburg-Eppendorf, Hamburg, Germany., Etminan N; Department of Neurosurgery, University Medicine Mannheim, Mannheim, Germany., Jungwirth G; Department of Neurosurgery, University Hospital Heidelberg, Heidelberg, Germany., Herold-Mende C; Division of Exp. Neurosurgery, Department of Neurosurgery, University Hospital Heidelberg, Heidelberg, Germany., Unterberg A; Department of Neurosurgery, University Hospital Heidelberg, Heidelberg, Germany., Harter PN; Neurological Institute (Edinger Institute), University Hospital Frankfurt, Frankfurt, Germany.; Frankfurt Cancer Institute (FCI) and German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Heidelberg, Germany., Wirsching HG; Department of Neurology, University Hospital and University of Zurich, Zurich, Switzerland., Neidert MC; Department of Neurosurgery, Kantonsspital St Gallen, St Gallen, Switzerland., Ratliff M; Department of Neurosurgery, University Medicine Mannheim, Mannheim, Germany., Platten M; Department of Neurology, Medical Faculty Mannheim, MCTN, Heidelberg University, Heidelberg, Germany., Snuderl M; Department of Pathology, NYU Grossman School of Medicine, New York, NY., Aldape KD; Laboratory of Pathology, National Cancer Insitute, Bethesda, MD., Brandner S; Division of Neuropathology, National Hospital for Neurology and Neurosurgery, University College London NHS Foundation Trust, London, United Kingdom.; Department of Neurodegenerative Disease, Queen Square Institute of Neurology, University College London, London, United Kingdom., Hench J; Department of Neuropathology, University Hospital Basel, Basel, Switzerland., Frank S; Department of Neuropathology, University Hospital Basel, Basel, Switzerland., Pfister SM; Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany.; Division of Pediatric Neurooncology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.; Department of Pediatric Oncology, Hematology, Immunology and Pulmonology, University Hospital Heidelberg, Heidelberg, Germany., Jones DTW; Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany.; Division of Pediatric Glioma Research, German Cancer Research Center (DKFZ), Heidelberg, Germany., Reifenberger G; Institute of Neuropathology, Heinrich Heine University Medical Faculty, Düsseldorf, Germany.; German Cancer Consortium (DKTK), Partner Site Essen/Düsseldorf, Germany., Acker T; Department of Neuropathology, University Hospital Gießen, Giessen, Germany., Wick W; Clinical Cooperation Unit Neurooncology, German Consortium for Translational Cancer Research (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.; Department of Neurology and Neurooncology Program, National Center for Tumor Diseases, Heidelberg University Hospital, Heidelberg, Germany., Weller M; Department of Neurology, University Hospital and University of Zurich, Zurich, Switzerland., Preusser M; Department of Medicine I, Clinical Division of Oncology, Medical University of Vienna, Vienna, Austria., von Deimling A; Department of Neuropathology, University Hospital Heidelberg and CCU Neuropathology, German Consortium for Translational Cancer Research (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany., Sahm F; Department of Neuropathology, University Hospital Heidelberg and CCU Neuropathology, German Consortium for Translational Cancer Research (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.; Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany.
Jazyk:	angličtina
Zdroj:	Journal of clinical oncology : official journal of the American Society of Clinical Oncology [J Clin Oncol] 2021 Dec 01; Vol. 39 (34), pp. 3839-3852. Date of Electronic Publication: 2021 Oct 07.
DOI:	10.1200/JCO.21.00784
Abstrakt:	Purpose: Meningiomas are the most frequent primary intracranial tumors. Patient outcome varies widely from benign to highly aggressive, ultimately fatal courses. Reliable identification of risk of progression for individual patients is of pivotal importance. However, only biomarkers for highly aggressive tumors are established ( CDKN2A/B and TERT ), whereas no molecularly based stratification exists for the broad spectrum of patients with low- and intermediate-risk meningioma. Methods: DNA methylation data and copy-number information were generated for 3,031 meningiomas (2,868 patients), and mutation data for 858 samples. DNA methylation subgroups, copy-number variations (CNVs), mutations, and WHO grading were analyzed. Prediction power for outcome was assessed in a retrospective cohort of 514 patients, validated on a retrospective cohort of 184, and on a prospective cohort of 287 multicenter cases. Results: Both CNV- and methylation family-based subgrouping independently resulted in increased prediction accuracy of risk of recurrence compared with the WHO classification (c-indexes WHO 2016, CNV, and methylation family 0.699, 0.706, and 0.721, respectively). Merging all risk stratification approaches into an integrated molecular-morphologic score resulted in further substantial increase in accuracy (c-index 0.744). This integrated score consistently provided superior accuracy in all three cohorts, significantly outperforming WHO grading (c-index difference P = .005). Besides the overall stratification advantage, the integrated score separates more precisely for risk of progression at the diagnostically challenging interface of WHO grade 1 and grade 2 tumors (hazard ratio 4.34 [2.48-7.57] and 3.34 [1.28-8.72] retrospective and prospective validation cohorts, respectively). Conclusion: Merging these layers of histologic and molecular data into an integrated, three-tiered score significantly improves the precision in meningioma stratification. Implementation into diagnostic routine informs clinical decision making for patients with meningioma on the basis of robust outcome prediction. Competing Interests: Elisabeth J. RushingConsulting or Advisory Role: Bayer Suisse Stefan M. PfisterResearch Funding: Lilly, Bayer, Roche, PharmaMar, PfizerPatents, Royalties, Other Intellectual Property: patent on using DNA methylation profiling for tumor classification Michael WellerHonoraria: Merck Serono, MSD, Philogen, Nerviano Medical Sciences, Adastra PharmaceuticalsConsulting or Advisory Role: Bristol Myers Squibb, Orbus Therapeutics, Tocagen, Karyopharm Therapeutics, Ymabs Therapeutics Inc, MedacResearch Funding: Merck Serono, Novocure, Merck Sharp & Dohme, Apogenix, Quercegen Pharmaceuticals Matthias PreusserHonoraria: Roche, GlaxoSmithKline, Bayer, Bristol Myers Squibb, Novartis, Gerson Lehrman Group, CMC Contrast, Mundipharma, BMJ Journals, MedMedia, AstraZeneca, AbbVie, Lilly, MEDahead, Daiichi Sankyo, Sanofi, Merck Sharp & Dome, Tocagen, Adastra PharmaceuticalsConsulting or Advisory Role: Roche, Bristol Myers Squibb, Novartis, Gerson Lehrman Group, CMC Contrast, GlaxoSmithKline, Mundipharma, AbbVieResearch Funding: Roche, GlaxoSmithKline, Boehringer Ingelheim, Merck Sharp & Dohme, Bristol Myers Squibb, Daiichi Sankyo, AbbVieTravel, Accommodations, Expenses: Roche, GlaxoSmithKline, Bristol Myers Squibb, MSD, Mundipharma Andreas von DeimlingConsulting or Advisory Role: Bristol Myers SquibbResearch Funding: BayerPatents, Royalties, Other Intellectual Property: Patent for IDH1R132H antibody H09 administered by the German Cancer Center (DKFZ), Patent for BRAFV600E antibody VE1 administered by the German Cancer Center (DKFZ), DNA methylation–based method for classifying tumor species EP16710700Travel, Accommodations, Expenses: Roche Felix SahmHonoraria: Illumina, AbbVie, BayerNo other potential conflicts of interest were reported.
Databáze:	MEDLINE
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