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Early biomarkers from dynamic contrast-enhanced magnetic resonance imaging to predict the response to antiangiogenic therapy in high-grade gliomas

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Abstract

Introduction

The aim of this study is to investigate whether early changes in tumor volume and perfusion measurements derived from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) may predict response to antiangiogenic therapy in recurrent high-grade gliomas.

Methods

Twenty-seven patients who received bevacizumab every 3 weeks were enrolled in the study. For each patient, three MRI scans were performed: at baseline, after the first dose, and after the fourth dose of bevacizumab. The entire tumor volume (Vtot), as well as contrast-enhanced and noncontrast-enhanced tumor subvolumes (VCE-T1 and VNON-CE-T1, respectively) were outlined using post-contrast T1-weighted images as a guide for the tumor location. Histogram analysis of normalized IAUGC (nIAUGC) and transfer constant Ktrans maps were performed. Each patient was classified as a responder patient if he/she had a partial response or a stable disease or as a nonresponder patient if he/she had progressive disease.

Results

Responding patients showed a larger reduction in VNON-CE-T1 after a single dose, compared to nonresponding patients. Tumor subvolumes with increased values of nIAUGC and Ktrans, after a single dose, significantly differed between responders and nonresponders. The radiological response was found to be significantly associated to the clinical outcome. After a single dose, Vtot was predictive of overall survival (OS), while VCE-T1 showed a tendency of correlation with OS.

Conclusion

Tumor subvolumes with increased nIAUGC and Ktrans showed the potential for improving the diagnostic accuracy of DCE. Early assessments of the entire tumor volume, including necrotic areas, may provide complementary information of tumor behavior in response to anti-VEGF therapies and is worth further investigation.

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Acknowledgments

The authors are indebted to the GE Advanced Clinical Education Specialist Lorenzo Viarengo for his contribution to the MR sequence optimization and to Gaetano Fetonti and Michele Farella for their continued technical assistance.

Ethical standards and patient consent

We declare that all human and animal studies have been approved by the our Ethics Committee and have therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. We declare that all patients gave informed consent prior to inclusion in this study.

Conflict of interest

We declare that we have no conflict of interest.

Author information

Authors and Affiliations

  1. Radiology and Diagnostic Imaging Department, Regina Elena National Cancer Institute, Rome, Italy

    Francesca Piludu & Antonello Vidiri

  2. Medical Physics Laboratory, Regina Elena National Cancer Institute, Via Elio Chianesi 53, Rome, 00144, Italy

    Simona Marzi

  3. Neurology Division, Regina Elena National Cancer Institute, Rome, Italy

    Andrea Pace & Veronica Villani

  4. Oncology Department, Regina Elena National Cancer Institute, Rome, Italy

    Alessandra Fabi

  5. Oncologic Surgery Department, Regina Elena National Cancer Institute, Rome, Italy

    Carmine Maria Carapella

  6. Biostatistics-Scientific Direction, Regina Elena National Cancer Institute, Rome, Italy

    Irene Terrenato

  7. Clinical Pathology, Regina Elena National Cancer Institute, Rome, Italy

    Anna Antenucci

Authors
  1. Francesca Piludu
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  2. Simona Marzi
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  3. Andrea Pace
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  4. Veronica Villani
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  5. Alessandra Fabi
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  9. Antonello Vidiri
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Corresponding author

Correspondence to Simona Marzi.

Additional information

FP and SM contributed equally to this work.

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Figure 6

Averages of the differential histograms of the normalized initial area under the gadolinium concentration curve (nIAUGC) inside the entire lesion for the patient groups with progressive disease or partial response/stable disease at baseline and after the first and fourth doses of bevacizumab. (GIF 100 kb)

High resolution image (TIFF 2238 kb)

Figure 7

Averages of the differential histograms of the transfer constant (Ktrans) inside the entire lesion for the patient groups with progressive disease or partial response/stable disease at baseline and after the first and fourth doses of bevacizumab. (GIF 89 kb)

High resolution image (TIFF 191 kb)

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Piludu, F., Marzi, S., Pace, A. et al. Early biomarkers from dynamic contrast-enhanced magnetic resonance imaging to predict the response to antiangiogenic therapy in high-grade gliomas. Neuroradiology 57, 1269–1280 (2015). https://doi.org/10.1007/s00234-015-1582-9

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  • DOI: https://doi.org/10.1007/s00234-015-1582-9

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