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71. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC)
9. Joint Meeting mit der Japanischen Gesellschaft für Neurochirurgie

Deutsche Gesellschaft für Neurochirurgie (DGNC) e. V.

21.06. - 24.06.2020

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IDH mutation prediction in glioma – a multimodal diagnostic approach

Prädiktionder IDH-Mutation in Gliomen – ein multimodales diagnostisches Konzept

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  • presenting/speaker Tareq Juratli - Universitätsklinikum Carl Gustav Carus Dresden, Klinik für Neurochirurgie, Dresden, Deutschland
  • Amir Zolal - Universitätsklinikum Carl Gustav Carus Dresden, Klinik für Neurochirurgie, Dresden, Deutschland
  • Sebastian Stasik - Universitätsklinikum Carl Gustav Carus Dresden, Medizinische Klinik I, Dresden, Deutschland
  • Graeme Eisenhofer - Universitätsklinikum Carl Gustav Carus Dresden, Institut für Klinische Chemie und Laboratoriumsmedizin, Labor Klinische Neurochemie, Dresden, Deutschland
  • Jennifer Linn - Universitätsklinikum Carl Gustav Carus Dresden, Institut und Poliklinik für Diagnostische und Interventionelle Neuroradiologie, Dresden, Deutschland
  • Gabriele Schackert - Universitätsklinikum Carl Gustav Carus Dresden, Klinik für Neurochirurgie, Dresden, Deutschland
  • Christian Thiede - Universitätsklinikum Carl Gustav Carus Dresden, Medizinische Klinik I, Dresden, Deutschland
  • Annett Werner - Universitätsklinikum Carl Gustav Carus Dresden, Institut und Poliklinik für Diagnostische und Interventionelle Neuroradiologie, Dresden, Deutschland
  • Dietmar Krex - Universitätsklinikum Carl Gustav Carus Dresden, Klinik für Neurochirurgie, Dresden, Deutschland

Deutsche Gesellschaft für Neurochirurgie. 71. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), 9. Joint Meeting mit der Japanischen Gesellschaft für Neurochirurgie. sine loco [digital], 21.-24.06.2020. Düsseldorf: German Medical Science GMS Publishing House; 2020. DocV186

doi: 10.3205/20dgnc182, urn:nbn:de:0183-20dgnc1829

Published: June 26, 2020

© 2020 Juratli et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 License. See license information at http://creativecommons.org/licenses/by/4.0/.

Outline

Text

Objective: Non-invasive and accurate diagnostic techniques to detect isocitrate dehydrogenase (IDH) mutant glioma may have great potential in routine clinical practice. With this in mind, we performed a multimodal diagnostic approach to predict the IDH mutation status in newly diagnosed gliomas using: 2-Hydroxyglutarate (2HG) single-voxel spectroscopy (SVS), IDH-mutant cell-free tumor-derived DNA (tDNA) in the CSF, in addition to 2HG (D- and L- forms) concentration measurement in the CSF.

Methods: 2HG MR spectroscopy was obtained in 18 patients with a newly diagnosed IDH-mutant glioma. The IDH1/2 mutation status was determined using next-generation sequencing in the glioma tissue and in the CSF-tDNA (n=55). In addition, in a subset of patients (n=15), 2HG concentrations were measured in the CSF using liquid chromatography-tandem mass spectrometry (LCMS). Ratios of D-and L-2HG were used to evaluate differences in 2HG accumulation in tumors.

Results: IDH mutations were correctly predicted using the 2HG spectroscopy with 93.3% sensitivity (17/18, 95% CI, 85.3-100%) and 100% specificity (18/18, 95% CI, 88.6-100%). The IDH mutation in the CSF-tDNA was successfully detected with 100% specificity (95% CI, 87.6-100%) and 73.3% sensitivity (95% CI, 65.6-88.3%). The range of the IDH mutation variant allele frequency (VAF) in the CSF-tDNA was 1.53- 47.9%. 2HG detection in the CSF revealed higher sensitivity (100%) and specificity (100%) in a small subset of patients (n = 7). The D-2HG/L-2HG ratios in IDH-mutant cases varied between 1.2 – 13.8, compared with 0.1 – 0.5 in IDH wild-type gliomas.

Conclusion: Our findings suggest that 2HG spectroscopy and 2HG detection in the CSF are two reliable methods in IDH mutation prediction in gliomas. On the other hand, the sensitivity of genomic IDH mutation detection in the CSF-tDNA was lower when compared with 2HG detection. Further studies are needed to complement the findings of our exploratory analysis.