Journal of Neuro-Oncology

, Volume 139, Issue 1, pp 145–152 | Cite as

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

  • Lindsay S. Rowe
  • John A. Butman
  • Megan Mackey
  • Joanna H. Shih
  • Theresa Cooley-Zgela
  • Holly Ning
  • Mark R. Gilbert
  • DeeDee K. Smart
  • Kevin Camphausen
  • Andra V. Krauze
Clinical Study



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.


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.


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.


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.


Pseudoprogression Glioblastoma Karnofsky performance status Response assessment in neuro-oncology Radiation therapy 



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

Compliance with ethical standards

Conflict of interest

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.

Informed consent

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


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Copyright information

© This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2018

Authors and Affiliations

  • Lindsay S. Rowe
    • 1
  • John A. Butman
    • 2
  • Megan Mackey
    • 1
  • Joanna H. Shih
    • 3
  • Theresa Cooley-Zgela
    • 1
  • Holly Ning
    • 1
  • Mark R. Gilbert
    • 4
  • DeeDee K. Smart
    • 1
  • Kevin Camphausen
    • 1
  • Andra V. Krauze
    • 1
  1. 1.Radiation Oncology BranchNational Cancer InstituteBethesdaUSA
  2. 2.Radiology and Imaging SciencesNational Institutes of HealthBethesdaUSA
  3. 3.Clinical Research CenterNational Institutes of HealthBethesdaUSA
  4. 4.Neuro-Oncology BranchNational Cancer InstituteBethesdaUSA

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