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

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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.

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Authors and Affiliations

  1. Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA

    Daniel I. Hoffman & Makayla McCoskey

  2. Department of Neurosurgery, University of Pennsylvania, Philadelphia, PA, USA

    Kalil G. Abdullah, Zev A. Binder, Donald M. O’Rourke & Steven Brem

  3. Division of Hematology and Oncology, Department of Medicine, University of Pennsylvania, 10th Floor, South Pavilion, 3400 Civic Center Blvd, Philadelphia, PA, 19104, USA

    Arati S. Desai & Stephen J. Bagley

  4. Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA

    MacLean P. Nasrallah

  5. Department of Pathology and Laboratory Medicine, Center for Personalized Diagnostics, University of Pennsylvania, Philadelphia, PA, USA

    Ashkan Bigdeli & Jennifer J. D. Morrissette

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  1. Daniel I. Hoffman
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Hoffman, D.I., Abdullah, K.G., McCoskey, M. et al. Negative prognostic impact of epidermal growth factor receptor copy number gain in young adults with isocitrate dehydrogenase wild-type glioblastoma. J Neurooncol 145, 321–328 (2019). https://doi.org/10.1007/s11060-019-03298-6

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