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Amide proton transfer imaging might predict survival and IDH mutation status in high-grade glioma

European Radiology volume 29, pages 6643–6652 (2019)Cite this article

Abstract

Objectives

To assess the utility of amide proton transfer (APT) imaging as an imaging biomarker to predict prognosis and molecular marker status in high-grade glioma (HGG, WHO grade III/IV).

Methods

We included 71 patients with pathologically diagnosed HGG who underwent preoperative MRI with APT imaging. Overall survival (OS) and progression-free survival (PFS) according to APT signal, clinical factors, MGMT methylation status, and IDH mutation status were analyzed. Multivariate Cox regression models with and without APT signal data were constructed. Model performance was compared using the integrated AUC (iAUC). Associations between APT signals and molecular markers were assessed using the Mann-Whitney test.

Results

High APT signal was a significant predictor for poor OS (HR = 3.21, 95% CI = 1.62–6.34) and PFS (HR = 2.22, 95% CI = 1.33–3.72) on univariate analysis. On multivariate analysis, high APT signals were an independent predictor of poor OS and PFS when clinical factors alone (OS: HR = 2.89; PFS: HR = 2.13), or in combination with molecular markers (OS: HR = 2.85; PFS: HR = 2.00), were included as covariates. The incremental prognostic value of APT signals was significant for OS and PFS. IDH-wild type was significantly associated with high APT signals (p = 0.001) when compared to IDH-mutant; however, there was no difference based on MGMT methylation status (p = 0.208).

Conclusion

High APT signal was a significant predictor of poor prognosis in HGG. APT data showed significant incremental prognostic value over clinical prognostic factors and molecular markers and may also predict IDH mutation status.

Key Points

• Amide proton transfer (APT) imaging is a promising prognostic marker of high-grade glioma.

• APT signals were significantly higher in IDH-wild type compared to IDH-mutant high-grade glioma.

• APT imaging may be valuable for preoperative screening and treatment guidance.

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Abbreviations

APT:

Amide proton transfer

AUC:

Area under the curve

CCRT:

Concurrent chemoradiation therapy

HGG:

High-grade glioma

iAUC:

Integrated area under the curve

ICC:

Intraclass correlation coefficients

IDH:

Isocitrate dehydrogenase

KPS:

Karnofsky performance status

MGMT:

O6-methylguanine-DNA methyltransferase

MRI:

Magnetic resonance imaging

MTR asym :

Magnetization transfer ratio asymmetry

OS:

Overall survival

PCR:

Polymerase chain reaction

PFS:

Progression free survival

ROI:

Region of interests

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Acknowledgements

The authors thank Ha-Kyu Jeong (Korea Basic Science Institute, Chungcheongbuk-do, Korea) for his help with protocol optimization and for the valuable suggestions.

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 and Future Planning (2014R1A1A1002716, 2017R1D1A1B03030440) and National Institutes of Health (P41 EB015909, R01 CA166171, R01 EB009731).

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Affiliations

  1. Department of Radiology and Research Institute of Radiological Science, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, South Korea

    Bio Joo, Kyunghwa Han, Sung Soo Ahn, Yoon Seong Choi & Seung-Koo Lee

  2. Department of Neurosurgery, Yonsei University College of Medicine, Seoul, South Korea

    Jong Hee Chang & Seok-Gu Kang

  3. Department of Pathology, Yonsei University College of Medicine, Seoul, South Korea

    Se Hoon Kim

  4. Division of MRI Research, Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Jinyuan Zhou

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  1. Bio Joo
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Corresponding author

Correspondence to Sung Soo Ahn.

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Guarantor

The scientific guarantor of this publication is Professor Seung-Koo Lee, MD, PhD, from Yonsei University College of Medicine.

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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.

Statistics and biometry

One of the authors has significant statistical expertise.

Kyunghwa Han, PhD

Department of Radiology and Research Institute of Radiological Science, College of Medicine, Yonsei University College of Medicine, Seoul, Korea.

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The institutional review board waived the requirement to obtain informed patient consent for this retrospective study.

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• retrospective

• diagnostic or prognostic study

• performed at one institution

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Joo, B., Han, K., Ahn, S.S. et al. Amide proton transfer imaging might predict survival and IDH mutation status in high-grade glioma. Eur Radiol 29, 6643–6652 (2019). https://doi.org/10.1007/s00330-019-06203-x

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  • DOI: https://doi.org/10.1007/s00330-019-06203-x

Keywords

  • Glioma
  • Magnetic resonance imaging
  • Isocitrate dehydrogenase
  • Prognosis