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Pseudoprogression

Last Updated: March 27, 2020

Open Table of Contents: Pseudoprogression

Figure 1: This patient’s pre-treatment (top row left) and 2-month post-radiation and temozolomide contrast-enhanced images (top row right) demonstrate a striking change in the region of abnormality. Notice the significant interval increase in size of the heterogeneously enhancing lesion with large amount of hyperintense edema, mass effect and right to left midline shift on post-treatment FLAIR (middle row left). While there are patchy foci of reduced diffusivity within the post-treatment lesion(middle row right, bottom row left), there is a lack of hyperperfusion in the region of known enhancement on the MR perfusion CBV image (bottom row right). The reduced diffusivity may suggest residual neoplasm, but can also be seen in hemorrhage/coagulative necrosis of radiation injury. The significantly increase in abnormal enhancement and FLAIR hyperintense signal and the lack of hyperperfusion suggests pseudoprogression rather than tumor progression, but serial followup imaging will provide this answer more definitively.

Description

  • Chemoradiation-related increase in contrast enhancement mimicking tumor progression
  • Pseudoprogression typically occurs within 3-6 months after conclusion of radiation therapy
  • Most commonly associated with patients receiving Temozolomide

Pathology

  • Vascular and oligodendroglial injury leading to inflammation and increased permeability of blood-brain barrier
  • May result from transiently increased permeability of tumor vasculature from irradiation

Clinical Features

  • Typically asymptomatic unless there is associated mass effect
  • Incidence 30-50%
  • Has been associated with improved survival

Imaging

  • General
    • New enhancement with increased FLAIR signal in treated GBM or other radiated brain tissue at 3-4 months after XRT
    • Followup studies often necessary to accurately diagnose
  • Modality Specific

    • CT
      • Nonspecific
      • May see increased perilesional edema or enhancement
    • MR

      • T1WI
        • Hypointense
        • May have hyperintense areas of hemorrhage
      • T2WI/FLAIR

        • Hyperintense with mass effect
      • DWI

        • Higher ADC values and ratios of the enhancing tissue when compared to tumor
        • Often striking restricted diffusion in the necrotic/hemorrhage nonenhancing center
      • Contrast

        • Demonstrates enhancement, usually peripheral
      • PWI

        • Lower mean rCBV than tumor
        • Often hypoperfusion compared to normal brain parenchyma
      • Spectroscopy

        • Low choline with a Cho:NAA ratio < 1.4.
        • Increased lactate and lipid peaks compared to normal tissue
    • PET

      • Hypometabolic areas compared to normal brain tissue and compared to tumor
      • Often obscured by normally hypermetabolic cortex
      • Not as specific as MR Perfusion
  • Imaging Recommendations

    • MR with contrast and perfusion. Often need a followup examination to accurately diagnose.
  • Mimic

    • Often very difficult to distinguish between radiation necrosis and progression of disease. Perfusion imaging can be very helpful as tumor usually demonstrates increased cerebral blood volume and radiation necrosis most often demonstrates normal or decreased cerebral blood volume.

For more information, please see the corresponding chapter in Radiopaedia.

Contributor: Sean Dodson, MD

DOI: https://doi.org/10.18791/nsatlas.v1.03.02.23

References

Boxerman JL, Ellingson BM. Response Assessment and Magnetic Resonance Imaging Issues for Clinical Trials Involving High-Grade Gliomas. Top Magn Reson Imaging. 2015; 24(3):127-36.

Chu HH, et al. Differentiation of True Pseudoprogression in Glioblastoma Treated with Radiation Therapy and Concomitant Temozolomide: A Comparison Study of Standard and High-b-Value Diffusion-weighted Imaging. Radiology. 2013; 269(3):831-40.

Gahramanov S, et al. Pseudoprogression of Glioblastoma after Chemo- and Radiation Therapy: Diagnosis by Using Dynamic Susceptibility-weighted Contrast-enhanced Perfusion MR Imaging with Ferumoxytol versus Gadoteridol and Correlation with Survival. Radiology. 2013; 266(3):842-52.

Galldiks N, et al. Diagnosis of pseudoprogression in patients with glioblastoma using O-(2-[18F]fluoroethyl)-L-tyrosine PET. Eur J Nucl Med Mol Imaging. 2015; 42(5):685-95.

Hygino da Cruz LC, et al. Pseudoprogression and Pseudoresponse: Imaging Challenges in the Assessment of Posttreatment Glioma. AJNR. 2011; 32:1978-85.

Kebir S, et al. Late Pseudoprogression in Glioblastoma: Diagnostic Value of Dynamic O-(2-[18F]fluoroethyl)-L-Tyrosine PET. Clin Cancer Res. 2015 Dec 16.

Melguizo-Gavilanes I, et al. Characterization of pseudoprogression in patients with glioblastoma: is histology the gold standard? J Neurooncol. 2015; 123(1):141-150.

Radbruch A, et al. Pseudoprogression in patients with glioblastoma: clinical relevance despite low incidence. Neuro-Oncology. 2015; 17(1):151-9.

Shim H, et al. A potential role of MR spectroscopic imaging in the era of pseudoprogression and pseudoresponse in glioblastoma patient management. CNS Oncol. 2013; 2(%):393-96.

Yun TJ, et al. Glioblastoma treated with concurrent radiation therapy and temozolomide chemotherapy: differentiation of true progression from pseudoprogression with quantitative dynamic contrast-enhanced MR imaging. Radiology. 2015; 274(3):830-40.

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