title: Evaluation of pseudoprogression in patients with glioblastoma multiforme using dynamic magnetic resonance imaging with ferumoxytol calls RANO criteria into question.
abstract: BACKGROUND
  Diagnosis of pseudoprogression in patients with glioblastoma multiforme (GBM) is limited by Response Assessment in Neuro-Oncology (RANO) criteria to 3 months after chemoradiotherapy (CRT). Frequency of pseudoprogression occurring beyond this time limit was determined. Survival comparison was made between pseudoprogression and true progression patients as determined by using perfusion magnetic resonance imaging with ferumoxytol (p-MRI-Fe).
  
  
  METHODS
  Fifty-six patients with GBM who demonstrated conventional findings concerning for progression of disease post CRT were enrolled in institutional review board-approved MRI protocols. Dynamic susceptibility-weighted contrast-enhanced p-MRI-Fe was used to distinguish true progression from pseudoprogression using relative cerebral blood volume (rCBV) values. rCBV of 1.75 was assigned as the cutoff value. Participants were followed up using RANO criteria, and survival data were analyzed.
  
  
  RESULTS
  Twenty-seven participants (48.2%) experienced pseudoprogression. Pseudoprogression occurred later than 3 months post CRT in 8 (29.6%) of these 27 participants (ie, 8 [14.3%] of the 56 patients meeting the inclusion criteria). Overall survival was significantly longer in participants with pseudoprogression (35.2 months) compared with those who never experienced pseudoprogression (14.3 months; P < .001).
  
  
  CONCLUSIONS
  Pseudoprogression presented after 3 months post CRT in a considerable portion of patients with GBM, which raises doubts about the value of the 3-month time limit of the RANO criteria. Accurate rCBV measurement (eg, p-MRI-Fe) is suggested when there are radiographical concerns about progression of disease in GBM patients, regardless of any time limit. Pseudoprogression correlates with significantly better survival outcomes.
authors: Department of Neurology, Oregon Health & Science University, Portland, Oregon (M.N., S.G., J.P.N., L.L.M., C.V., E.A.N.); Department of Public Health and Preventative Medicine, Oregon Health & Science University, Portland, Oregon (R.F.); Department of Emergency Medicine, Oregon Health & Science University, Portland, Oregon (R.F.); Department of Neuroradiology, Oregon Health & Science University, Portland, Oregon (B.E.H.); Department of Neurosurgery, Oregon Health & Science University, Portland, Oregon (E.A.N.); Department of Veterans Affairs Medical Center, Portland, Oregon (E.A.N.); Department of Neurosurgery, Swedish Neuroscience Institute, Seattle, Washington (S.G.); Department of Neurosurgery, Wayne State University, Detroit, Michigan (M.N.).
authors: Morad
authors: M
authors: Nasseri
authors: Department of Neurology, Oregon Health & Science University, Portland, Oregon (M.N., S.G., J.P.N., L.L.M., C.V., E.A.N.); Department of Public Health and Preventative Medicine, Oregon Health & Science University, Portland, Oregon (R.F.); Department of Emergency Medicine, Oregon Health & Science University, Portland, Oregon (R.F.); Department of Neuroradiology, Oregon Health & Science University, Portland, Oregon (B.E.H.); Department of Neurosurgery, Oregon Health & Science University, Portland, Oregon (E.A.N.); Department of Veterans Affairs Medical Center, Portland, Oregon (E.A.N.); Department of Neurosurgery, Swedish Neuroscience Institute, Seattle, Washington (S.G.); Department of Neurosurgery, Wayne State University, Detroit, Michigan (M.N.).
authors: Seymur
authors: S
authors: Gahramanov
authors: Department of Neurology, Oregon Health & Science University, Portland, Oregon (M.N., S.G., J.P.N., L.L.M., C.V., E.A.N.); Department of Public Health and Preventative Medicine, Oregon Health & Science University, Portland, Oregon (R.F.); Department of Emergency Medicine, Oregon Health & Science University, Portland, Oregon (R.F.); Department of Neuroradiology, Oregon Health & Science University, Portland, Oregon (B.E.H.); Department of Neurosurgery, Oregon Health & Science University, Portland, Oregon (E.A.N.); Department of Veterans Affairs Medical Center, Portland, Oregon (E.A.N.); Department of Neurosurgery, Swedish Neuroscience Institute, Seattle, Washington (S.G.); Department of Neurosurgery, Wayne State University, Detroit, Michigan (M.N.).
authors: Joao Prola
authors: JP
authors: Netto
authors: Department of Neurology, Oregon Health & Science University, Portland, Oregon (M.N., S.G., J.P.N., L.L.M., C.V., E.A.N.); Department of Public Health and Preventative Medicine, Oregon Health & Science University, Portland, Oregon (R.F.); Department of Emergency Medicine, Oregon Health & Science University, Portland, Oregon (R.F.); Department of Neuroradiology, Oregon Health & Science University, Portland, Oregon (B.E.H.); Department of Neurosurgery, Oregon Health & Science University, Portland, Oregon (E.A.N.); Department of Veterans Affairs Medical Center, Portland, Oregon (E.A.N.); Department of Neurosurgery, Swedish Neuroscience Institute, Seattle, Washington (S.G.); Department of Neurosurgery, Wayne State University, Detroit, Michigan (M.N.).
authors: Rongwei
authors: R
authors: Fu
authors: Department of Neurology, Oregon Health & Science University, Portland, Oregon (M.N., S.G., J.P.N., L.L.M., C.V., E.A.N.); Department of Public Health and Preventative Medicine, Oregon Health & Science University, Portland, Oregon (R.F.); Department of Emergency Medicine, Oregon Health & Science University, Portland, Oregon (R.F.); Department of Neuroradiology, Oregon Health & Science University, Portland, Oregon (B.E.H.); Department of Neurosurgery, Oregon Health & Science University, Portland, Oregon (E.A.N.); Department of Veterans Affairs Medical Center, Portland, Oregon (E.A.N.); Department of Neurosurgery, Swedish Neuroscience Institute, Seattle, Washington (S.G.); Department of Neurosurgery, Wayne State University, Detroit, Michigan (M.N.).
authors: Leslie L
authors: LL
authors: Muldoon
authors: Department of Neurology, Oregon Health & Science University, Portland, Oregon (M.N., S.G., J.P.N., L.L.M., C.V., E.A.N.); Department of Public Health and Preventative Medicine, Oregon Health & Science University, Portland, Oregon (R.F.); Department of Emergency Medicine, Oregon Health & Science University, Portland, Oregon (R.F.); Department of Neuroradiology, Oregon Health & Science University, Portland, Oregon (B.E.H.); Department of Neurosurgery, Oregon Health & Science University, Portland, Oregon (E.A.N.); Department of Veterans Affairs Medical Center, Portland, Oregon (E.A.N.); Department of Neurosurgery, Swedish Neuroscience Institute, Seattle, Washington (S.G.); Department of Neurosurgery, Wayne State University, Detroit, Michigan (M.N.).
authors: Csanad
authors: C
authors: Varallyay
authors: Department of Neurology, Oregon Health & Science University, Portland, Oregon (M.N., S.G., J.P.N., L.L.M., C.V., E.A.N.); Department of Public Health and Preventative Medicine, Oregon Health & Science University, Portland, Oregon (R.F.); Department of Emergency Medicine, Oregon Health & Science University, Portland, Oregon (R.F.); Department of Neuroradiology, Oregon Health & Science University, Portland, Oregon (B.E.H.); Department of Neurosurgery, Oregon Health & Science University, Portland, Oregon (E.A.N.); Department of Veterans Affairs Medical Center, Portland, Oregon (E.A.N.); Department of Neurosurgery, Swedish Neuroscience Institute, Seattle, Washington (S.G.); Department of Neurosurgery, Wayne State University, Detroit, Michigan (M.N.).
authors: Bronwyn E
authors: BE
authors: Hamilton
authors: Department of Neurology, Oregon Health & Science University, Portland, Oregon (M.N., S.G., J.P.N., L.L.M., C.V., E.A.N.); Department of Public Health and Preventative Medicine, Oregon Health & Science University, Portland, Oregon (R.F.); Department of Emergency Medicine, Oregon Health & Science University, Portland, Oregon (R.F.); Department of Neuroradiology, Oregon Health & Science University, Portland, Oregon (B.E.H.); Department of Neurosurgery, Oregon Health & Science University, Portland, Oregon (E.A.N.); Department of Veterans Affairs Medical Center, Portland, Oregon (E.A.N.); Department of Neurosurgery, Swedish Neuroscience Institute, Seattle, Washington (S.G.); Department of Neurosurgery, Wayne State University, Detroit, Michigan (M.N.).
authors: Edward A
authors: EA
authors: Neuwelt
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001932:Brain Neoplasms / Q000175:diagnosis* / Q000473:pathology / Q000628:therapy; D059248:Chemoradiotherapy / Q000379:methods; D003131:Combined Modality Therapy / Q000379:methods; D018450:Disease Progression; D005260:Female; D052203:Ferrosoferric Oxide / Q000627:therapeutic use*; D005909:Glioblastoma / Q000175:diagnosis* / Q000473:pathology / Q000628:therapy; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D052203:Ferrosoferric Oxide
keywords: GBM; RANO criteria; ferumoxytol; perfusion-MRI; pseudoprogression