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

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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.

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Funding

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

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Author notes

  1. Franziska Vettermann and Bogdana Suchorska contributed equally to this work.

Authors and Affiliations

  1. Department of Nuclear Medicine, University Hospital, Ludwig Maximilians-University Munich, Munich, Germany

    Franziska Vettermann, Marcus Unterrainer, Debie Nelwan, Vera Wenter, Peter Bartenstein & Nathalie L. Albert

  2. German Cancer Consortium (DKTK), partner site Munich, German Cancer Research Center (DKFZ), Heidelberg, Germany

    Franziska Vettermann, Bogdana Suchorska, Marcus Unterrainer, Friedrich-Wilhelm Kreth, Peter Bartenstein, Jörg-Christian Tonn & Nathalie L. Albert

  3. Department of Neurosurgery, University Hospital, Ludwig Maximilians-University Munich, Munich, Germany

    Bogdana Suchorska, Friedrich-Wilhelm Kreth & Jörg-Christian Tonn

  4. Department of Neuroradiology, University Hospital, Ludwig Maximilians-University Munich, Munich, Germany

    Robert Forbrig

  5. Center for Neuropathology and Prion Research, Ludwig-Maximilians-University Munich, Munich, Germany

    Viktoria Ruf & Jochen Herms

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  1. Franziska Vettermann
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Correspondence to Nathalie L. Albert.

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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.

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Vettermann, F., Suchorska, B., Unterrainer, M. et al. Non-invasive prediction of IDH-wildtype genotype in gliomas using dynamic 18F-FET PET. Eur J Nucl Med Mol Imaging 46, 2581–2589 (2019). https://doi.org/10.1007/s00259-019-04477-3

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