title: 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: OBJECTIVE
  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.
  
  
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Neurology, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd, L603, Portland, OR 97239-3098, USA.
authors.forename: Seymur
authors.initials: S
authors.lastname: Gahramanov
authors.forename: Leslie L
authors.initials: LL
authors.lastname: Muldoon
authors.forename: Csanad G
authors.initials: CG
authors.lastname: Varallyay
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.forename: Dale F
authors.initials: DF
authors.lastname: Kraemer
authors.forename: Rongwei
authors.initials: R
authors.lastname: Fu
authors.forename: Bronwyn E
authors.initials: BE
authors.lastname: Hamilton
authors.forename: William D
authors.initials: WD
authors.lastname: Rooney
authors.forename: Edward A
authors.initials: EA
authors.lastname: Neuwelt
mesh_terms: D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000175:diagnosis* / Q000401:mortality / Q000628:therapy*; D059248:Chemoradiotherapy; D003287:Contrast Media; D005260:Female; D052203:Ferrosoferric Oxide; D005682:Gadolinium; D006571:Heterocyclic Compounds; D006801:Humans; D018810:Magnetic Resonance Angiography / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009942:Organometallic Compounds; D011379:Prognosis; D015203:Reproducibility of Results; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D013223:Statistics as Topic; D016019:Survival Analysis; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D003287:Contrast Media; D006571:Heterocyclic Compounds; D009942:Organometallic Compounds; C062402:gadoteridol; D005682:Gadolinium; D052203:Ferrosoferric Oxide