title: Evaluation of early imaging response criteria in glioblastoma multiforme.
abstract: BACKGROUND
  Early and accurate prediction of response to cancer treatment through imaging criteria is particularly important in rapidly progressive malignancies such as Glioblastoma Multiforme (GBM). We sought to assess the predictive value of structural imaging response criteria one month after concurrent chemotherapy and radiotherapy (RT) in patients with GBM.
  
  
  METHODS
  Thirty patients were enrolled from 2005 to 2007 (median follow-up 22 months). Tumor volumes were delineated at the boundary of abnormal contrast enhancement on T1-weighted images prior to and 1 month after RT. Clinical Progression [CP] occurred when clinical and/or radiological events led to a change in chemotherapy management. Early Radiologic Progression [ERP] was defined as the qualitative interpretation of radiological progression one month post-RT. Patients with ERP were determined pseudoprogressors if clinically stable for ≥6 months. Receiver-operator characteristics were calculated for RECIST and MacDonald criteria, along with alternative thresholds against 1 year CP-free survival and 2 year overall survival (OS).
  
  
  RESULTS
  13 patients (52%) were found to have ERP, of whom 5 (38.5%) were pseudoprogressors. Patients with ERP had a lower median OS (11.2 mo) than those without (not reached) (p < 0.001). True progressors fared worse than pseudoprogressors (median survival 7.2 mo vs. 19.0 mo, p < 0.001). Volume thresholds performed slightly better compared to area and diameter thresholds in ROC analysis. Responses of > 25% in volume or > 15% in area were most predictive of OS.
  
  
  CONCLUSIONS
  We show that while a subjective interpretation of early radiological progression from baseline is generally associated with poor outcome, true progressors cannot be distinguished from pseudoprogressors. In contrast, the magnitude of early imaging volumetric response may be a predictive and quantitative metric of favorable outcome.
authors.affiliation: Faculty of Medicine, University of Toronto, Toronto, Canada. adam.gladwish@utoronto.ca
authors.forename: Adam
authors.initials: A
authors.lastname: Gladwish
authors.forename: Eng-Siew
authors.initials: ES
authors.lastname: Koh
authors.forename: Jeremy
authors.initials: J
authors.lastname: Hoisak
authors.forename: Gina
authors.initials: G
authors.lastname: Lockwood
authors.forename: Barbara-Ann
authors.initials: BA
authors.lastname: Millar
authors.forename: Warren
authors.initials: W
authors.lastname: Mason
authors.forename: Eugene
authors.initials: E
authors.lastname: Yu
authors.forename: Normand J
authors.initials: NJ
authors.lastname: Laperriere
authors.forename: Cynthia
authors.initials: C
authors.lastname: Ménard
mesh_terms: D000368:Aged; D000465:Algorithms; D001932:Brain Neoplasms / Q000175:diagnosis / Q000628:therapy*; D003952:Diagnostic Imaging / Q000379:methods; D018450:Disease Progression; D005260:Female; D005909:Glioblastoma / Q000175:diagnosis / Q000628:therapy*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012372:ROC Curve; D011878:Radiotherapy / Q000379:methods; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D016896:Treatment Outcome