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Journal of Neuro-Oncology

, Volume 145, Issue 2, pp 321–328 | Cite as

Negative prognostic impact of epidermal growth factor receptor copy number gain in young adults with isocitrate dehydrogenase wild-type glioblastoma

  • Daniel I. Hoffman
  • Kalil G. Abdullah
  • Makayla McCoskey
  • Zev A. Binder
  • Donald M. O’Rourke
  • Arati S. Desai
  • MacLean P. Nasrallah
  • Ashkan Bigdeli
  • Jennifer J. D. Morrissette
  • Steven Brem
  • Stephen J. BagleyEmail author
Clinical Study

Abstract

Purpose

Young adults with isocitrate-dehydrogenase wild-type (IDH-WT) glioblastoma (GBM) represent a rare, understudied population compared to pediatric high-grade glioma, IDH-mutant GBM, or IDH-WT GBM in older patients. We aimed to explore the prognostic impact of epidermal growth factor receptor copy number gain (EGFR CN gain), one of the most common genetic alterations in IDH-WT glioma, in young adults with IDH-WT GBM.

Methods

We performed a retrospective cohort study of patients 18–45 years old with newly diagnosed, IDH-WT GBM whose tumors underwent next-generation sequencing at our institution between 2014 and 2018. The impact of EGFR CN gain on time to tumor progression (TTP) and overall survival (OS) was assessed. A validation cohort of patients 18–45 years old with IDH-WT GBM was analyzed from The Cancer Genome Atlas (TCGA).

Results

Ten of 28 patients (36%) from our institution had EGFR CN gain, which was associated with shorter TTP (median 6.5 vs. 11.9 months; p = 0.06) and OS (median 16.3 vs. 23.5 months; p = 0.047). The negative prognostic impact of EGFR CN gain on OS persisted in a multivariate model (HR 6.40, 95% CI 1.3–31.0, p = 0.02). In the TCGA cohort (N = 43), EGFR CN gain was associated with shorter TTP and worse OS, although these did not reach statistical significance (TTP, median 11.5 vs. 14.4 months, p = 0.18; OS, median 23.6 vs. 27.8 months; p = 0.18).

Conclusions

EGFR CN gain may be associated with inferior outcomes in young adults with newly diagnosed, IDH-WT GBM, suggesting a potential role for targeting EGFR in this population.

Keywords

Glioblastoma Next generation sequencing Epidermal growth factor receptor isocitrate dehydrogenase Survival 

Notes

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Research involving human and animal participants

This article does not contain any studies with human participants or animals performed by any of the authors.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Daniel I. Hoffman
    • 1
  • Kalil G. Abdullah
    • 2
  • Makayla McCoskey
    • 1
  • Zev A. Binder
    • 2
  • Donald M. O’Rourke
    • 2
  • Arati S. Desai
    • 3
  • MacLean P. Nasrallah
    • 4
  • Ashkan Bigdeli
    • 5
  • Jennifer J. D. Morrissette
    • 5
  • Steven Brem
    • 2
  • Stephen J. Bagley
    • 3
    Email author
  1. 1.Perelman School of Medicine at the University of PennsylvaniaPhiladelphiaUSA
  2. 2.Department of NeurosurgeryUniversity of PennsylvaniaPhiladelphiaUSA
  3. 3.Division of Hematology and Oncology, Department of MedicineUniversity of PennsylvaniaPhiladelphiaUSA
  4. 4.Department of Pathology and Laboratory MedicineUniversity of PennsylvaniaPhiladelphiaUSA
  5. 5.Department of Pathology and Laboratory Medicine, Center for Personalized DiagnosticsUniversity of PennsylvaniaPhiladelphiaUSA

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