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Fluid attenuation in non‐contrast‐enhancing tumor (nCET): an MRI Marker for Isocitrate Dehydrogenase (IDH) mutation in Glioblastoma

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Abstract

Purpose

The WHO 2016 update classifies glioblastomas (WHO grade IV) according to isocitrate dehydrogenase (IDH) gene mutation status. We aimed to determine MRI-based metrics for predicting IDH mutation in glioblastoma.

Methods

This retrospective study included glioblastoma cases (n = 199) with known IDH mutation status and pre-operative MRI (T1WI, T2WI, FLAIR, contrast-enhanced T1W1 at minimum). Two neuroradiologists determined the following MRI metrics: (1) primary lobe of involvement (frontal or non-frontal); (2) presence/absence of contrast-enhancement; (3) presence/absence of necrosis; (4) presence/absence of fluid attenuation in the non-contrast-enhancing tumor (nCET); (5) maximum width of peritumoral edema (cm); (6) presence/absence of multifocal disease. Inter-reader agreement was determined. After resolving discordant measurements, multivariate association between consensus MRI metrics/patient age and IDH mutation status was determined.

Results

Among 199 glioblastomas, 16 were IDH-mutant. Inter-reader agreement was calculated for contrast-enhancement (ĸ = 0.49 [− 0.11–1.00]), necrosis (ĸ = 0.55 [0.34–0.76]), fluid attenuation in nCET (ĸ = 0.83 [0.68–0.99]), multifocal disease (ĸ = 0.55 [0.39–0.70]), and primary lobe (ĸ = 0.85 [0.80–0.91]). Mean difference for peritumoral edema width between readers was 0.3 cm [0.2–0.5], p < 0.001. Multivariate analysis uncovered significant associations between IDH-mutation and fluid attenuation in nCET (OR 82.9 [19.22, ∞], p < 0.001), younger age (OR 0.93 [0.86, 0.98], p = 0.009), frontal lobe location (OR 11.08 [1.14, 352.97], p = 0.037), and less peritumoral edema (OR 0.15 [0, 0.65], p = 0.044).

Conclusions

Conventional MRI metrics and patient age predict IDH-mutation status in glioblastoma. Among MRI markers, fluid attenuation in nCET represents a novel marker with high inter-reader agreement that is strongly associated with Glioblastoma, IDH-mutant.

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Data availability

The authors confirm that the data supporting the findings of this study are available within the article and its supplementary materials. If there are requests for additional data, they can be sent to the corresponding author (S.H.P.).

Abbreviations

WHO:

World Health Organization

IDH:

Isocitrate dehydrogenase

LGG:

Lower grade glioma

nCET:

Non-contrast-enhancing tumor

IHC:

Immunohistochemistry;

PFS:

Progression-free survival

OS:

Overall survival

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Authors and Affiliations

  1. Department of Radiology and Medical Imaging, University of Virginia Health System, PO Box 800170, Charlottesville, VA, 22908, USA

    Sohil H. Patel, Prem P. Batchala, Thomas J. Eluvathingal Muttikkal & Sergio S. Ferrante

  2. Department of Public Health Sciences, University of Virginia Health System, Charlottesville, VA, USA

    James T. Patrie

  3. Division of Neuro-Oncology, Department of Neurology, University of Virginia Health System, Charlottesville, VA, USA

    Camilo E. Fadul & David Schiff

  4. Department of Pathology, Divisions of Neuropathology and Molecular Diagnostics, University of Virginia Health System, Charlottesville, VA, USA

    M. Beatriz Lopes

  5. Department of Radiology, New York University School of Medicine, 550 1st Avenue, New York, NY, 10016, USA

    Rajan Jain

  6. Department of Neurosurgery, New York University School of Medicine, 550 1st Avenue, New York, NY, 10016, USA

    Rajan Jain

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  1. Sohil H. Patel
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Contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by SHP, PPB, TJEM, SSF, and JTP. The first draft of the manuscript was written by SHP and PPB and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Sohil H. Patel.

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Conflict of interest

Sohil H. Patel, Prem P. Batchala, Thomas J. Eluvathingal Muttikkal, Sergio S. Ferrante, James T. Patrie, Camilo E. Fadul, David Schiff, M. Beatriz Lopes, Rajan Jain declare they have no conflicts of interest.

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Institutional Review Board approval was obtained for this retrospective study.

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Patel, S.H., Batchala, P.P., Muttikkal, T.J.E. et al. Fluid attenuation in non‐contrast‐enhancing tumor (nCET): an MRI Marker for Isocitrate Dehydrogenase (IDH) mutation in Glioblastoma. J Neurooncol 152, 523–531 (2021). https://doi.org/10.1007/s11060-021-03720-y

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