Prognostic impact of CDKN2A/B deletion, TERT mutation, and EGFR amplification on histological and molecular IDH-wildtype glioblastoma.

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 mutation, amplification, and 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: mutation, 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, = .16), nor PFS (median: 11.7 vs 7.3 months, respectively, = .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. 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 mutation and amplification were not.

CONCLUSION

Criteria for mGBM may require further refinement and validation. deletion, but not mutation or amplification, may be an independent prognostic biomarker for IDH-wildtype GBM patients.