Diffusion and perfusion MRI may predict EGFR amplification and the TERT promoter mutation status of IDH-wildtype lower-grade gliomas

Abstract

Objectives: Epidermal growth factor receptor (EGFR) amplification and telomerase reverse transcriptase promoter (TERTp) mutation status of isocitrate dehydrogenase-wildtype (IDHwt) lower-grade gliomas (LGGs; grade II/III) are crucial for identifying IDHwt LGG with an aggressive clinical course. The purpose of this study was to assess whether parameters from diffusion tensor imaging, dynamic susceptibility contrast (DSC), and diffusion tensor imaging, dynamic contrast-enhanced imaging can predict the EGFR amplification and TERTp mutation status of IDHwt LGGs.

Methods: A total of 49 patients with IDHwt LGGs with either known EGFR amplification (39 non-amplified, 10 amplified) or TERTp mutation (19 wildtype, 21 mutant) statuses underwent MRI. The mean ADC, fractional anisotropy (FA), normalized cerebral blood volume (nCBV), normalized cerebral blood flow (nCBF), volume transfer constant (Ktrans), rate transfer coefficient (Kep), extravascular extracellular volume fraction (Ve), and plasma volume fraction (Vp) values were assessed. Univariate and multivariate logistic regression models were constructed.

Results: EGFR-amplified tumors showed lower mean ADC values than EGFR-non-amplified tumors (p = 0.019). Mean ADC was an independent predictor of EGFR amplification, with an AUC of 0.75. TERTp mutant tumors showed higher mean nCBV (p = 0.020), higher mean nCBF (p = 0.017), and higher mean Vp (p = 0.002) than TERTp wildtype tumors. With multivariate logistic regression, mean Vp was the independent predictor of TERTp mutation status, with an AUC of 0.85.

Conclusion: This exploratory pilot study shows that lower ADC values may be useful for prediction of EGFR amplification, whereas higher Vp values may be useful for prediction of the TERTp mutation status of IDHwt LGGs.

Key points: • EGFR amplification and TERTp mutation are key molecular markers that predict an aggressive clinical course of IDHwt LGGs. • EGFR-amplified tumors showed lower ADC values than EGFR-non-amplified tumors, suggesting higher cellularity. • TERTp mutant tumors showed a higher plasma volume fraction than TERTp wildtype tumors, suggesting higher vascular proliferation and tumor angiogenesis.