Molecular correlates of long survival in IDH-Wildtype glioblastoma cohorts

Kristyn Galbraith, Ashwani Kumar, Kalil G. Abdullah, Jamie M. Walker, Steven H. Adams, Timothy Prior, Ryan Dimentberg, Fraser C. Henderson, Kanish Mirchia, Adwait Amod Sathe, Mariano S. Viapiano, Lawrence S. Chin, Robert J. Corona, Kimmo J. Hatanpaa, Matija Snuderl, Chao Xing, Steven Brem, Timothy E. Richardson

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

IDH-wildtype glioblastoma is a relatively common malignant brain tumor in adults. These patients generally have dismal prognoses, although outliers with long survival have been noted in the literature. Recently, it has been reported that many histologically lower-grade IDH-wildtype astrocytomas have a similar clinical outcome to grade IV tumors, suggesting they may represent early or under-sampled glioblastomas. cIMPACT-NOW 3 guidelines now recommend upgrading IDH-wildtype astrocytomas with certain molecular criteria (EGFR amplifications, chromosome 7 gain/10 loss, and/or TERT promoter mutations), establishing the concept of a “molecular grade IV” astrocytoma. In this report, we apply these cIMPACT-NOW 3 criteria to 2 independent glioblastoma cohorts, totaling 393 public database and institutional glioblastoma cases: 89 cases without any of the cIMPACT-NOW 3 criteria (GBM-C0) and 304 cases with one or more criteria (GBM-C1-3). In the GBM-C0 groups, there was a trend toward longer recurrence-free survival (median 12-17 vs 6-10 months), significantly longer overall survival (median 32-41 vs 15-18 months), younger age at initial diagnosis, and lower overall mutation burden compared to the GBM-C1-3 cohorts. These data suggest that while histologic features may not be ideal indicators of patient survival in IDH-wildtype astrocytomas, these 3 molecular features may also be important prognostic factors in IDH-wildtype glioblastoma.

Original languageEnglish (US)
Pages (from-to)843-854
Number of pages12
JournalJournal of Neuropathology and Experimental Neurology
Volume79
Issue number8
DOIs
StatePublished - Aug 1 2020

Keywords

  • Astrocytoma
  • GBM
  • Glioblastoma
  • IDH1/2
  • Long survival
  • Prognosis
  • TCGA

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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