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 L.P. Nasrallah, Ashkan Bigdeli, Jennifer J.D. Morrissette, Steven Brem, Stephen J. Bagley

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)321-328
Number of pages8
JournalJournal of Neuro-Oncology
Volume145
Issue number2
DOIs
StatePublished - Nov 1 2019
Externally publishedYes

Fingerprint

Isocitrate Dehydrogenase
Glioblastoma
Epidermal Growth Factor Receptor
Young Adult
Survival
Neoplasms
Atlases
Glioma
Genome
Population
Cohort Studies
Retrospective Studies
Pediatrics

Keywords

  • Epidermal growth factor receptor
  • Glioblastoma
  • isocitrate dehydrogenase
  • Next generation sequencing
  • Survival

ASJC Scopus subject areas

  • Oncology
  • Neurology
  • Clinical Neurology
  • Cancer Research

Cite this

Negative prognostic impact of epidermal growth factor receptor copy number gain in young adults with isocitrate dehydrogenase wild-type glioblastoma. / Hoffman, Daniel I.; Abdullah, Kalil G.; McCoskey, Makayla; Binder, Zev A.; O’Rourke, Donald M.; Desai, Arati S.; Nasrallah, MacLean L.P.; Bigdeli, Ashkan; Morrissette, Jennifer J.D.; Brem, Steven; Bagley, Stephen J.

In: Journal of Neuro-Oncology, Vol. 145, No. 2, 01.11.2019, p. 321-328.

Research output: Contribution to journalArticle

Hoffman, DI, Abdullah, KG, McCoskey, M, Binder, ZA, O’Rourke, DM, Desai, AS, Nasrallah, MLP, Bigdeli, A, Morrissette, JJD, Brem, S & Bagley, SJ 2019, 'Negative prognostic impact of epidermal growth factor receptor copy number gain in young adults with isocitrate dehydrogenase wild-type glioblastoma', Journal of Neuro-Oncology, vol. 145, no. 2, pp. 321-328. https://doi.org/10.1007/s11060-019-03298-6
Hoffman, Daniel I. ; Abdullah, Kalil G. ; McCoskey, Makayla ; Binder, Zev A. ; O’Rourke, Donald M. ; Desai, Arati S. ; Nasrallah, MacLean L.P. ; Bigdeli, Ashkan ; Morrissette, Jennifer J.D. ; Brem, Steven ; Bagley, Stephen J. / Negative prognostic impact of epidermal growth factor receptor copy number gain in young adults with isocitrate dehydrogenase wild-type glioblastoma. In: Journal of Neuro-Oncology. 2019 ; Vol. 145, No. 2. pp. 321-328.
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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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T1 - Negative prognostic impact of epidermal growth factor receptor copy number gain in young adults with isocitrate dehydrogenase wild-type glioblastoma

AU - Hoffman, Daniel I.

AU - Abdullah, Kalil G.

AU - McCoskey, Makayla

AU - Binder, Zev A.

AU - O’Rourke, Donald M.

AU - Desai, Arati S.

AU - Nasrallah, MacLean L.P.

AU - Bigdeli, Ashkan

AU - Morrissette, Jennifer J.D.

AU - Brem, Steven

AU - Bagley, Stephen J.

PY - 2019/11/1

Y1 - 2019/11/1

N2 - 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.

AB - 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.

KW - Epidermal growth factor receptor

KW - Glioblastoma

KW - isocitrate dehydrogenase

KW - Next generation sequencing

KW - Survival

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