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

Abstract

Purpose:To compare gadoteridol and ferumoxytol for measurement of relative cerebral blood volume (rCBV) in patients with glioblastoma multiforme (GBM) who showed progressive disease at conventional magnetic resonance (MR) imaging after chemo-and radiation therapy (hereafter, chemoradiotherapy) and to correlate rCBV with survival. Materials and Methods:Informed consent was obtained from all participants before enrollment in one of four institutional review board-approved protocols. Contrast agent leakage maps and rCBV were derived from perfusion MR imaging with gadoteridol and ferumoxytol in 19 patients with apparently progressive GBM on conventional MR images after chemoradiotherapy. Patients were classified as having high rCBV (.1.75), indicating tumor, and low rCBV (1.75), indicating pseudoprogression, for each contrast agent separately, and with or without contrast agent leakage correction for imaging with gadoteridol. Statistical analysis was performed by using Kaplan-Meier survival plots with the log-rank test and Cox proportional hazards models. Results:With ferumoxytol, rCBV was low in nine (47%) patients, with median overall survival (mOS) of 591 days, and high rCBV in 10 (53%) patients, with mOS of 163 days. A hazard ratio of 0.098 (P = .004) indicated significantly improved survival. With gadoteridol, rCBV was low in 14 (74%) patients, with mOS of 474 days, and high in five (26%), with mOS of 156 days and a nonsignificant hazard ratio of 0.339 (P = .093). Five patients with mismatched high rCBV with ferumoxytol and low rCBV with gadoteridol had an mOS of 171 days. When leakage correction was applied, rCBV with gadoteridol was significantly associated with survival (hazard ratio, 0.12; P = .003). Conclusion:Ferumoxytol as a blood pool agent facilitates differentiation between tumor progression and pseudoprogression, appears to be a good prognostic biomarker, and unlike gadoteridol, does not require contrast agent leakage correction.q RSNA, 2012

Using iron oxide nanoparticles to diagnose CNS inflammatory diseases and PCNSL

“…24,30 Our preliminary findings of USPIO-enhanced imaging in CNSL require further evaluation in studies involving systemic lymphoma. Importantly, USPIO imaging provides a safe alternative for MRI in patients with renal failure.…”

“…USPIO-based DSC perfusion requires neither expensive leakage correlation software algorithms nor preloading with additional doses of USPIO, as is necessary with GBCA. 24 Our limited number of PWIs in CNSL cases in this series do not allow generalization, but will be a subject of future study.…”

“…Based on our prior work, immediate post-USPIO MRI shows intravascular, not abnormal parenchymal enhancement. [22][23][24] The second day of imaging at 24 hours is a relatively intracellular-weighted (and/or interstitial-weighted) rather than intravascular-weighted MRI given that ferumoxytol has an intravascular halflife of approximately 14 to 20 hours. 25 This proved helpful in one patient in this series who underwent a second diagnostic biopsy in which a different surgical target was selected based on the T2-weighted USPIOenhanced MRI.…”

A comprehensive literatures update of clinical researches of superparamagnetic resonance iron oxide nanoparticles for magnetic resonance imaging

“…Overall survival was significantly longer in participants with pseudoprogression (35.2 months) compared with those who never experienced pseudoprogression (14.3 months). They concluded that ferumoxytol, used as a blood pool agent, facilitates differentiation between tumor progression and pseudoprogression, appears to be a good prognostic biomarker, and, unlike GBCA, does not require contrast agent leakage correction (139,140) (Figure 18) . Bevacizumab (BEV, Avastin, Genentech, Inc.) is an antivascular endothelial growth factor (VEGF) A antibody working as an angiogenesis inhibitor that normalizes tumor vasculature, and decreases contrast-enhancing tumor volume and blood volume in lesions both in animal models and clinically.…”

Tumour progression or pseudoprogression? A review of post-treatment radiological appearances of glioblastoma

“…A pilot study found lesions that enhance on T1WGd and have low rCBV on ferumoxytol-DSC-MRI are more likely to represent pseudoprogression. 52 Gahramanov et al 53 found that ferumoxytol-based measurements of rCBV measurements correlate better with median survival than leak corrected Gd-based measurements. Ferumoxytol also allows the use of steady-state imaging methods, which can produce high-resolution and distortion-free maps of CBV.…”