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

A Correction to this article was published on 10 September 2020

This article has been updated

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

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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Correspondence to Sung Soo Ahn.

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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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The authors of this manuscript declare no relationships with any companies, whose products or services may be related to the subject matter of the article.

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One of the authors has significant statistical expertise (K.H, a biostatistician with 10 years of experience in biostatistics).

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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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Keywords

  • Epidermal growth factor receptor
  • Genomics
  • Glioma
  • Magnetic resonance imaging
  • Telomerase reverse transcriptase