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.
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Change history
10 September 2020
A Correction to this paper has been published: https://doi.org/10.1007/s00330-020-07257-y
Abbreviations
- cIMPACT-NOW:
-
Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy
- CBV:
-
Cerebral blood volume
- DCE:
-
Dynamic contast-enhanced
- DSC:
-
Dynamic susceptibility contrast
- DTI:
-
Diffusion tensor imaging
- EGFR:
-
Epidermal growth factor receptor
- FA:
-
Fractional anisotropy
- FLAIR:
-
Fluid-attenuated inversion recovery
- FOV:
-
Field of view
- IDH:
-
Isocitrate dehydrogenase
- IDHwt:
-
IDH-wildtype
- K ep :
-
Rate transfer coefficient
- K trans :
-
Volume transfer constant
- LGG:
-
Lower-grade glioma
- nCBV:
-
Normalized cerebral blood volume
- nCBF:
-
Normalized cerebral blood flow
- TE:
-
Echo time
- TERTp:
-
Telomerase reverse transcriptase promoter
- TR:
-
Repetition time
- V e :
-
Extravascular extracellular volume fraction
- VIF:
-
Variance inflation factor
- V p :
-
Plasma volume fraction
- WHO:
-
World Health Organization
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Funding
This research received funding from the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning (2017R1D1A1B03030440), and from the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2020R1I1A1A0107164811).
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The scientific guarantor of this publication is Professor Seung-Koo Lee, MD, PhD, from Yonsei University College of Medicine (slee@yuhs.ac).
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Park, Y.W., Ahn, S.S., Park, C.J. et al. Diffusion and perfusion MRI may predict EGFR amplification and the TERT promoter mutation status of IDH-wildtype lower-grade gliomas. Eur Radiol 30, 6475–6484 (2020). https://doi.org/10.1007/s00330-020-07090-3
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DOI: https://doi.org/10.1007/s00330-020-07090-3