title: Parametric response map as an imaging biomarker to distinguish progression from pseudoprogression in high-grade glioma.
abstract: OBJECTIVE
  To assess whether a new method of quantifying therapy-associated hemodynamic alterations may help to distinguish pseudoprogression from true progression in patients with high-grade glioma.
  
  
  METHODS
  Patients with high-grade glioma received concurrent chemoradiotherapy. Relative cerebral blood volume (rCBV) and blood flow (rCBF) maps were acquired before chemoradiotherapy and at week 3 during treatment on a prospective institutional review board-approved study. Pseudoprogression was defined as imaging changes 1 to 3 months after chemoradiotherapy that mimic tumor progression but stabilized or improved without change in treatment or for which resection revealed radiation effects only. Clinical and conventional magnetic resonance (MR) parameters, including average percent change of rCBV and CBF, were evaluated as potential predictors of pseudoprogression. Parametric response map (PRM), an innovative, voxel-by-voxel method of image analysis, was also performed.
  
  
  RESULTS
  Median radiation dose was 72 Gy (range, 60 to 78 Gy). Of 27 patients, stable disease/partial response was noted in 13 patients and apparent progression was noted in 14 patients. Adjuvant temozolomide was continued in all patients. Pseudoprogression occurred in six patients. Based on PRM analysis, a significantly reduced blood volume (PRM(rCBV)) at week 3 was noted in patients with progressive disease as compared with those with pseudoprogression (P < .01). In contrast, change in average percent rCBV or rCBF, MR tumor volume changes, age, extent of resection, and Radiation Therapy Oncology Group recursive partitioning analysis classification did not distinguish progression from pseudoprogression.
  
  
  CONCLUSIONS
  PRM(rCBV) at week 3 during chemoradiotherapy is a potential early imaging biomarker of response that may be helpful in distinguishing pseudoprogression from true progression in patients with high-grade glioma.
authors.affiliation: Department of Radiation Oncology, University of Michigan Medical Center, 1500 E. Medical Center Dr, Ann Arbor, MI 48109, USA. ctsien@umich.edu
authors.forename: Christina
authors.initials: C
authors.lastname: Tsien
authors.forename: Craig J
authors.initials: CJ
authors.lastname: Galbán
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Chenevert
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Johnson
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Hamstra
authors.forename: Pia C
authors.initials: PC
authors.lastname: Sundgren
authors.forename: Larry
authors.initials: L
authors.lastname: Junck
authors.forename: Charles R
authors.initials: CR
authors.lastname: Meyer
authors.forename: Alnawaz
authors.initials: A
authors.lastname: Rehemtulla
authors.forename: Theodore
authors.initials: T
authors.lastname: Lawrence
authors.forename: Brian D
authors.initials: BD
authors.lastname: Ross
mesh_terms: D000328:Adult; D001706:Biopsy; D001810:Blood Volume; D001932:Brain Neoplasms / Q000098:blood supply / Q000175:diagnosis* / Q000473:pathology / Q000628:therapy*; D002560:Cerebrovascular Circulation; D017024:Chemotherapy, Adjuvant; D016009:Chi-Square Distribution; D003287:Contrast Media; D003937:Diagnosis, Differential; D018450:Disease Progression; D019786:Gadolinium DTPA; D005910:Glioma / Q000098:blood supply / Q000175:diagnosis* / Q000473:pathology / Q000628:therapy*; D006439:Hemodynamics; D006801:Humans; D016013:Likelihood Functions; D016015:Logistic Models; D008279:Magnetic Resonance Imaging; D008875:Middle Aged; D009367:Neoplasm Staging; D009493:Neurosurgery; D011237:Predictive Value of Tests; D011446:Prospective Studies; D011829:Radiation Dosage; D018714:Radiotherapy, Adjuvant; D012039:Regional Blood Flow; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D003287:Contrast Media; D019786:Gadolinium DTPA