Evaluation of pseudoprogression in patients with glioblastoma multiforme using dynamic magnetic resonance imaging with ferumoxytol calls RANO criteria into question

Morad Nasseri; Seymur Gahramanov; Joao Prola Netto; Rongwei Fu; Leslie L Muldoon; Csanad Varallyay; Bronwyn E Hamilton; Edward A Neuwelt

doi:10.1093/neuonc/not328

Evaluation of pseudoprogression in patients with glioblastoma multiforme using dynamic magnetic resonance imaging with ferumoxytol calls RANO criteria into question

Neuro Oncol. 2014 Aug;16(8):1146-54. doi: 10.1093/neuonc/not328. Epub 2014 Feb 11.

Authors

Morad Nasseri¹, Seymur Gahramanov¹, Joao Prola Netto¹, Rongwei Fu¹, Leslie L Muldoon¹, Csanad Varallyay¹, Bronwyn E Hamilton¹, Edward A Neuwelt¹

Affiliation

¹ 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.).

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.

Keywords: GBM; RANO criteria; ferumoxytol; perfusion-MRI; pseudoprogression.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Aged
Aged, 80 and over
Brain Neoplasms / diagnosis*
Brain Neoplasms / pathology
Brain Neoplasms / therapy
Chemoradiotherapy / methods
Combined Modality Therapy / methods
Disease Progression
Female
Ferrosoferric Oxide / therapeutic use*
Glioblastoma / diagnosis*
Glioblastoma / pathology
Glioblastoma / therapy
Humans
Magnetic Resonance Imaging / methods
Male
Middle Aged
Treatment Outcome
Young Adult

Substances

Ferrosoferric Oxide

Abstract

Publication types

MeSH terms

Substances

Grants and funding