A molecularly integrated grade for meningioma

DOI PDF PDF 3 Citations
  • Joseph Driver
    Department of Neurosurgery, Brigham and Women’s Hospital, Harvard Medical School , Boston, Massachusetts , USA
  • Samantha E Hoffman
    Department of Neurosurgery, Brigham and Women’s Hospital, Harvard Medical School , Boston, Massachusetts , USA
  • Sherwin Tavakol
    Department of Neurosurgery, Brigham and Women’s Hospital, Harvard Medical School , Boston, Massachusetts , USA
  • Eleanor Woodward
    Department of Neurosurgery, Brigham and Women’s Hospital, Harvard Medical School , Boston, Massachusetts , USA
  • Eduardo A Maury
    Department of Neurosurgery, Brigham and Women’s Hospital, Harvard Medical School , Boston, Massachusetts , USA
  • Varun Bhave
    Department of Neurosurgery, Brigham and Women’s Hospital, Harvard Medical School , Boston, Massachusetts , USA
  • Noah F Greenwald
    Cancer Biology Program, Stanford University School of Medicine , Stanford, California , USA
  • Farshad Nassiri
    Department of Neurosurgery, University of Toronto , Toronto, Ontario , Canada
  • Kenneth Aldape
    National Cancer Institute , Bethesda, Maryland , USA
  • Gelareh Zadeh
    Department of Neurosurgery, University of Toronto , Toronto, Ontario , Canada
  • Abrar Choudhury
    Departments of Radiation Oncology and Neurological Surgery, University of California San Francisco , San Francisco, California , USA
  • Harish N Vasudevan
    Departments of Radiation Oncology and Neurological Surgery, University of California San Francisco , San Francisco, California , USA
  • Stephen T Magill
    Departments of Radiation Oncology and Neurological Surgery, University of California San Francisco , San Francisco, California , USA
  • David R Raleigh
    Departments of Radiation Oncology and Neurological Surgery, University of California San Francisco , San Francisco, California , USA
  • Malak Abedalthagafi
    King Fahad Medical City and King Abdulaziz City for Science and Technology , Riyadh , Saudi Arabia
  • Ayal A Aizer
    Department of Radiation Oncology, Brigham and Women’s Hospital, Harvard Medical School , Boston, Massachusetts , USA
  • Brian M Alexander
    Department of Radiation Oncology, Brigham and Women’s Hospital, Harvard Medical School , Boston, Massachusetts , USA
  • Keith L Ligon
    Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School , Boston, Massachusetts , USA
  • David A Reardon
    Center for Neuro-Oncology, Dana-Farber Cancer Institute , Boston, Massachusetts , USA
  • Patrick Y Wen
    Center for Neuro-Oncology, Dana-Farber Cancer Institute , Boston, Massachusetts , USA
  • Ossama Al-Mefty
    Department of Neurosurgery, Brigham and Women’s Hospital, Harvard Medical School , Boston, Massachusetts , USA
  • Azra H Ligon
    Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School , Boston, Massachusetts , USA
  • Adrian M Dubuc
    Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School , Boston, Massachusetts , USA
  • Rameen Beroukhim
    Center for Neuro-Oncology, Dana-Farber Cancer Institute , Boston, Massachusetts , USA
  • Elizabeth B Claus
    Department of Neurosurgery, Brigham and Women’s Hospital, Harvard Medical School , Boston, Massachusetts , USA
  • Ian F Dunn
    Department of Neurosurgery, Oklahoma University Medical Center , Oklahoma City, Oklahoma , USA
  • Sandro Santagata
    Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School , Boston, Massachusetts , USA
  • Wenya Linda Bi
    Department of Neurosurgery, Brigham and Women’s Hospital, Harvard Medical School , Boston, Massachusetts , USA

Abstract

<jats:title>Abstract</jats:title> <jats:sec> <jats:title>Background</jats:title> <jats:p>Meningiomas are the most common primary intracranial tumor in adults. Clinical care is currently guided by the World Health Organization (WHO) grade assigned to meningiomas, a 3-tiered grading system based on histopathology features, as well as extent of surgical resection. Clinical behavior, however, often fails to conform to the WHO grade. Additional prognostic information is needed to optimize patient management.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>We evaluated whether chromosomal copy-number data improved prediction of time-to-recurrence for patients with meningioma who were treated with surgery, relative to the WHO schema. The models were developed using Cox proportional hazards, random survival forest, and gradient boosting in a discovery cohort of 527 meningioma patients and validated in 2 independent cohorts of 172 meningioma patients characterized by orthogonal genomic platforms.</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>We developed a 3-tiered grading scheme (Integrated Grades 1-3), which incorporated mitotic count and loss of chromosome 1p, 3p, 4, 6, 10, 14q, 18, 19, or CDKN2A. 32% of meningiomas reclassified to either a lower-risk or higher-risk Integrated Grade compared to their assigned WHO grade. The Integrated Grade more accurately identified meningioma patients at risk for recurrence, relative to the WHO grade, as determined by time-dependent area under the curve, average precision, and the Brier score.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusion</jats:title> <jats:p>We propose a molecularly integrated grading scheme for meningiomas that significantly improves upon the current WHO grading system in prediction of progression-free survival. This framework can be broadly adopted by clinicians with relative ease using widely available genomic technologies and presents an advance in the care of meningioma patients.</jats:p> </jats:sec>

Journal

  • Neuro-Oncology

    Neuro-Oncology 24 (5), 796-808, 2021-09-11

    Oxford University Press (OUP)

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