title: Reevaluating the imaging definition of tumor progression: perfusion MRI quantifies recurrent glioblastoma tumor fraction, pseudoprogression, and radiation necrosis to predict survival.
abstract: BACKGROUND
  Contrast-enhanced MRI (CE-MRI) represents the current mainstay for monitoring treatment response in glioblastoma multiforme (GBM), based on the premise that enlarging lesions reflect increasing tumor burden, treatment failure, and poor prognosis. Unfortunately, irradiating such tumors can induce changes in CE-MRI that mimic tumor recurrence, so called post treatment radiation effect (PTRE), and in fact, both PTRE and tumor re-growth can occur together. Because PTRE represents treatment success, the relative histologic fraction of tumor growth versus PTRE affects survival. Studies suggest that Perfusion MRI (pMRI)-based measures of relative cerebral blood volume (rCBV) can noninvasively estimate histologic tumor fraction to predict clinical outcome. There are several proposed pMRI-based analytic methods, although none have been correlated with overall survival (OS). This study compares how well histologic tumor fraction and OS correlate with several pMRI-based metrics.
  
  
  METHODS
  We recruited previously treated patients with GBM undergoing surgical re-resection for suspected tumor recurrence and calculated preoperative pMRI-based metrics within CE-MRI enhancing lesions: rCBV mean, mode, maximum, width, and a new thresholding metric called pMRI-fractional tumor burden (pMRI-FTB). We correlated all pMRI-based metrics with histologic tumor fraction and OS.
  
  
  RESULTS
  Among 25 recurrent patients with GBM, histologic tumor fraction correlated most strongly with pMRI-FTB (r = 0.82; P < .0001), which was the only imaging metric that correlated with OS (P<.02).
  
  
  CONCLUSIONS
  The pMRI-FTB metric reliably estimates histologic tumor fraction (i.e., tumor burden) and correlates with OS in the context of recurrent GBM. This technique may offer a promising biomarker of tumor progression and clinical outcome for future clinical trials.
authors.affiliation: Department of Radiology, Mayo Clinic in Arizona, Phoenix, AZ 85054, USA. hu.leland@mayo.edu
authors.forename: Leland S
authors.initials: LS
authors.lastname: Hu
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Eschbacher
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Heiserman
authors.forename: Amylou C
authors.initials: AC
authors.lastname: Dueck
authors.forename: William R
authors.initials: WR
authors.lastname: Shapiro
authors.forename: Seban
authors.initials: S
authors.lastname: Liu
authors.forename: John P
authors.initials: JP
authors.lastname: Karis
authors.forename: Kris A
authors.initials: KA
authors.lastname: Smith
authors.forename: Stephen W
authors.initials: SW
authors.lastname: Coons
authors.forename: Peter
authors.initials: P
authors.lastname: Nakaji
authors.forename: Robert F
authors.initials: RF
authors.lastname: Spetzler
authors.forename: Burt G
authors.initials: BG
authors.lastname: Feuerstein
authors.forename: Josef
authors.initials: J
authors.lastname: Debbins
authors.forename: Leslie C
authors.initials: LC
authors.lastname: Baxter
mesh_terms: D000328:Adult; D000368:Aged; D001810:Blood Volume; D001932:Brain Neoplasms / Q000401:mortality* / Q000473:pathology* / Q000628:therapy; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D005909:Glioblastoma / Q000401:mortality* / Q000473:pathology* / Q000628:therapy; D006801:Humans; D018810:Magnetic Resonance Angiography; D008297:Male; D008875:Middle Aged; D009336:Necrosis; D009364:Neoplasm Recurrence, Local / Q000401:mortality* / Q000473:pathology* / Q000628:therapy; D009367:Neoplasm Staging; D011379:Prognosis; D011832:Radiation Injuries / Q000175:diagnosis / Q000209:etiology; D015996:Survival Rate; D047368:Tumor Burden