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Differentiating pseudoprogression from true progression: analysis of radiographic, biologic, and clinical clues in GBM

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Abstract

Introduction

Pseudoprogression (PsP) is a diagnostic dilemma in glioblastoma (GBM) after chemoradiotherapy (CRT). Magnetic resonance imaging (MRI) features may fail to distinguish PsP from early true progression (eTP), however clinical findings may aid in their distinction.

Methods

Sixty-seven patients received CRT for GBM between 2003 and 2016, and had pre- and post-treatment imaging suitable for retrospective evaluation using RANO criteria. Patients with signs of progression within the first 12-weeks post-radiation (P-12) were selected. Lesions that improved or stabilized were defined as PsP, and lesions that progressed were defined as eTP.

Results

The median follow up for all patients was 17.6 months. Signs of progression developed in 35/67 (52.2%) patients within P-12. Of these, 20/35 (57.1%) were subsequently defined as eTP and 15/35 (42.9%) as PsP. MRI demonstrated increased contrast enhancement in 84.2% of eTP and 100% of PsP, and elevated CBV in 73.7% for eTP and 93.3% for PsP. A decrease in FLAIR was not seen in eTP patients, but was seen in 26.7% PsP patients. Patients with eTP were significantly more likely to require increased steroid doses or suffer clinical decline than PsP patients (OR 4.89, 95% CI 1.003–19.27; p = 0.046). KPS declined in 25% with eTP and none of the PsP patients.

Conclusions

MRI imaging did not differentiate eTP from PsP, however, KPS decline or need for increased steroids was significantly more common in eTP versus PsP. Investigation and standardization of clinical assessments in response criteria may help address the diagnostic dilemma of pseudoprogression after frontline treatment for GBM.

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Funding

This research was funded by the intramural research program at the National Cancer Institute (Grant Number ZID BC 010990).

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Authors and Affiliations

  1. Radiation Oncology Branch, National Cancer Institute, 10 Center Drive Magnuson Clinical Center, Room B2-3500, Bethesda, MD, 20892, USA

    Lindsay S. Rowe, Megan Mackey, Theresa Cooley-Zgela, Holly Ning, DeeDee K. Smart, Kevin Camphausen & Andra V. Krauze

  2. Radiology and Imaging Sciences, National Institutes of Health, 10 Center Drive Magnuson Clinical Center, MSC 1182, Bethesda, MD, 20892, USA

    John A. Butman

  3. Clinical Research Center, National Institutes of Health, 10 Center Drive Magnuson Clinical Center, Bethesda, MD, 20892, USA

    Joanna H. Shih

  4. Neuro-Oncology Branch, National Cancer Institute, Building 82, Room 235A, Bethesda, MD, 20892, USA

    Mark R. Gilbert

Authors
  1. Lindsay S. Rowe
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  2. John A. Butman
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  3. Megan Mackey
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  4. Joanna H. Shih
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  5. Theresa Cooley-Zgela
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  6. Holly Ning
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  7. Mark R. Gilbert
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  8. DeeDee K. Smart
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  9. Kevin Camphausen
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  10. Andra V. Krauze
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Corresponding author

Correspondence to Lindsay S. Rowe.

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The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. For this type of study formal consent is not required.

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Informed consent was obtained from all individual participants included in the study.

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Rowe, L.S., Butman, J.A., Mackey, M. et al. Differentiating pseudoprogression from true progression: analysis of radiographic, biologic, and clinical clues in GBM. J Neurooncol 139, 145–152 (2018). https://doi.org/10.1007/s11060-018-2855-z

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  • DOI: https://doi.org/10.1007/s11060-018-2855-z

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