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Non-invasive prediction of IDH-wildtype genotype in gliomas using dynamic 18F-FET PET

  • Franziska Vettermann
  • Bogdana Suchorska
  • Marcus Unterrainer
  • Debie Nelwan
  • Robert Forbrig
  • Viktoria Ruf
  • Vera Wenter
  • Friedrich-Wilhelm Kreth
  • Jochen Herms
  • Peter Bartenstein
  • Jörg-Christian Tonn
  • Nathalie L. AlbertEmail author
Original Article
  • 38 Downloads
Part of the following topical collections:
  1. Oncology – Brain

Abstract

Purpose

According to the updated WHO classification of gliomas with its emphasis on molecular parameters, tumours with an IDH-wildtype status have a dismal prognosis. To ensure timely adjustment of treatment, demand for non-invasive prediction methods is high. 18F-FET PET has been shown to be an important diagnostic tool for glioma management. The aim of this study was to assess the value of dynamic 18F-FET PET for the non-invasive prediction of the IDH-mutation status.

Methods

Newly diagnosed WHO grade II–IV glioma patients with MRI and dynamic 18F-FET PET were included. The 18F-FET PET parameters mean and maximal tumour-to-background ratio (TBRmean, TBRmax) and minimal time-to-peak (TTPmin) were evaluated. The diagnostic power for the prediction of the IDH genotype (positive/negative predictive value) was tested in the overall study group and in the subgroup of non-contrast enhancing gliomas.

Results

Three hundred forty-one patients were evaluated. Molecular analyses revealed 178 IDH-mutant and 163 IDH-wildtype tumours. Overall, 270/341 gliomas were classified as 18F-FET-positive (TBRmax > 1.6), 90.2% of the IDH-wildtype and 69.1% of IDH-mutant gliomas. Median TBRmax was significantly higher in IDH-wildtype compared with IDH-mutant gliomas (2.9 vs. 2.3, p < 0.001); however, ROC-analyses revealed no reliable cutoff due to a high overlap (range 1.0–7.1 vs. 1.1–7.9). Dynamic analysis revealed a significantly shorter TTPmin in IDH-wildtype gliomas; using TTPmin ≤ 12.5 min as indicator for IDH-wildtype gliomas, a positive predictive value of 87% was reached (negative predictive value 72%, AUC = 0.796, p ≤ 0.001). A total of 161/341 gliomas did not show contrast enhancement on MRI; even within this subgroup, TTPmin ≤ 12.5 min remained a good predictor of IDH-wildtype glioma (positive predictive value 83%, negative predictive value 90%; AUC = 0.868, p < 0.001).

Conclusion

A short TTPmin in dynamic 18F-FET PET serves as good predictor of highly aggressive IDH-wildtype status in gliomas. In particular, a high diagnostic power was observed in the subgroup of non-contrast enhancing gliomas, which helps to identify patients with worse prognosis.

Keywords

Glioma 18F-FET PET Non-invasive grading IDH mutation status 

Notes

Funding information

This work was supported by the Collaborative Research Centre SFB-824 of the Deutsche Forschungsgemeinschaft (DFG) and by the Else Kröner-Fresenius-Stiftung.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Research involving human participants

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee (local ethic committee - approval number 604-16) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Supplementary material

259_2019_4477_MOESM1_ESM.docx (22 kb)
ESM 1 (DOCX 22.3 kb)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Franziska Vettermann
    • 1
    • 2
  • Bogdana Suchorska
    • 2
    • 3
  • Marcus Unterrainer
    • 1
    • 2
  • Debie Nelwan
    • 1
  • Robert Forbrig
    • 4
  • Viktoria Ruf
    • 5
  • Vera Wenter
    • 1
  • Friedrich-Wilhelm Kreth
    • 2
    • 3
  • Jochen Herms
    • 5
  • Peter Bartenstein
    • 1
    • 2
  • Jörg-Christian Tonn
    • 2
    • 3
  • Nathalie L. Albert
    • 1
    • 2
    Email author
  1. 1.Department of Nuclear Medicine, University HospitalLudwig Maximilians-University MunichMunichGermany
  2. 2.German Cancer Consortium (DKTK), partner site Munich, German Cancer Research Center (DKFZ)HeidelbergGermany
  3. 3.Department of Neurosurgery, University HospitalLudwig Maximilians-University MunichMunichGermany
  4. 4.Department of Neuroradiology, University HospitalLudwig Maximilians-University MunichMunichGermany
  5. 5.Center for Neuropathology and Prion ResearchLudwig-Maximilians-University MunichMunichGermany

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