Prognostic impact of CDKN2A/B deletion, TERT mutation, and EGFR amplification on histological and molecular IDH-wildtype glioblastoma. Issue 1 (18th September 2020)

• Record Type: Journal Article
• Authors: Ma, Sirui; Rudra, Soumon; Campian, Jian L; Dahiya, Sonika; Dunn, Gavin P; Johanns, Tanner; Goldstein, Michael; Kim, Albert H; Huang, Jiayi
• Is Part Of: Neuro-oncology advances. Volume 2:Issue 1(2020)
• Publication Date: 2020-09-18
• Subjects: CDKN2A/B -- cIMPACT-NOW -- EGFR -- Glioblastoma -- TERT; 616.99481
• DOI: 10.1093/noajnl/vdaa126
• Languages: English
• ISSNs: 2632-2498

Abstract

Abstract: Background: We aimed to evaluate the clinical outcomes of molecular glioblastoma (mGBM) as compared to histological GBM (hGBM) and to determine the prognostic impact of TERT mutation, EGFR amplification, and CDKN2A/B deletion on isocitrate dehydrogenase (IDH)-wildtype GBM. Methods: IDH-wildtype GBM patients treated with radiation therapy (RT) between 2012 and 2019 were retrospectively analyzed. mGBM was defined as grade II-III IDH-wildtype astrocytoma without histological features of GBM but with one of the following molecular alterations: TERT mutation, EGFR amplification, or combination of whole chromosome 7 gain and whole chromosome 10 loss. Overall survival (OS) and progression-free survival (PFS) were calculated from RT and analyzed using the Kaplan–Meier method. Multivariable analysis (MVA) was performed using Cox regression to identify independent predictors of OS and PFS. Results: Of the 367 eligible patients, the median follow-up was 11.7 months. mGBM and hGBM did not have significantly different OS (median: 16.6 vs 13.5 months, respectively, P = .16), nor PFS (median: 11.7 vs 7.3 months, respectively, P = .08). However, mGBM was associated with better OS (hazard ratio [HR] 0.50, 95% CI 0.29–0.88) and PFS (HR 0.43, 95% CI 0.26–0.72) than hGBM after adjusting for known prognostic factors on MVA. CDKN2A/B deletion was associated with worse OS (HR 1.57, 95% CI 1.003–2.46) and PFS (HR 1.57, 95% CI 1.04–2.36) on MVA, but TERT mutation and EGFR amplification were not. Conclusion: Criteria for mGBM may require further refinement and validation. CDKN2A/B deletion, but not TERT mutation or EGFR amplification, may be an independent prognostic biomarker for IDH-wildtype GBM patients.