title: ACRIN 6684: Assessment of Tumor Hypoxia in Newly Diagnosed Glioblastoma Using 18F-FMISO PET and MRI.
abstract: OBJECTIVE
  Structural and functional alterations in tumor vasculature are thought to contribute to tumor hypoxia which is a primary driver of malignancy through its negative impact on the efficacy of radiation, immune surveillance, apoptosis, genomic stability, and accelerated angiogenesis. We performed a prospective, multicenter study to test the hypothesis that abnormal tumor vasculature and hypoxia, as measured with MRI and PET, will negatively impact survival in patients with newly diagnosed glioblastoma.
  
  
  METHODS
  Prior to the start of chemoradiation, patients with glioblastoma underwent MRI scans that included dynamic contrast enhanced and dynamic susceptibility contrast perfusion sequences to quantitate tumor cerebral blood volume/flow (CBV/CBF) and vascular permeability (ktrans) as well as18F-Fluoromisonidazole (18F-FMISO) PET to quantitate tumor hypoxia. ROC analysis and Cox regression models were used to determine the association of imaging variables with progression-free and overall survival.
  
  
  RESULTS
  Fifty patients were enrolled of which 42 had evaluable imaging data. Higher pretreatment18F-FMISO SUVpeak(P = 0.048), mean ktrans(P = 0.024), and median ktrans(P = 0.045) were significantly associated with shorter overall survival. Higher pretreatment median ktrans(P = 0.021), normalized RCBV (P = 0.0096), and nCBF (P = 0.038) were significantly associated with shorter progression-free survival. SUVpeak[AUC = 0.75; 95% confidence interval (CI), 0.59-0.91], nRCBV (AUC = 0.72; 95% CI, 0.56-0.89), and nCBF (AUC = 0.72; 95% CI, 0.56-0.89) were predictive of survival at 1 year.
  
  
  CONCLUSIONS
  Increased tumor perfusion, vascular volume, vascular permeability, and hypoxia are negative prognostic markers in newly diagnosed patients with gioblastoma, and these important physiologic markers can be measured safely and reliably using MRI and18F-FMISO PET. Clin Cancer Res; 22(20); 5079-86. ©2016 AACR.
authors.affiliation: Massachusetts General Hospital Cancer Center, Boston, Massachusetts. Martinos Center for Biomedical Research, Charlestown, Massachusetts. egerstner@mgh.harvard.edu.
authors.forename: Elizabeth R
authors.initials: ER
authors.lastname: Gerstner
authors.affiliation: Brown University, Providence, Rhode Island.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: University of Washington, Seattle, Washington.
authors.forename: James R
authors.initials: JR
authors.lastname: Fink
authors.affiliation: University of Washington, Seattle, Washington.
authors.forename: Mark
authors.initials: M
authors.lastname: Muzi
authors.affiliation: Brown University, Providence, Rhode Island.
authors.forename: Lucy
authors.initials: L
authors.lastname: Hanna
authors.affiliation: Brown University, Providence, Rhode Island.
authors.forename: Erin
authors.initials: E
authors.lastname: Greco
authors.affiliation: Medical College of Wisconsin, Milwaukee, Wisconsin.
authors.forename: Melissa
authors.initials: M
authors.lastname: Prah
authors.affiliation: Medical College of Wisconsin, Milwaukee, Wisconsin.
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Schmainda
authors.affiliation: Wake Forest School of Medicine, Winston-Salem, North Carolina.
authors.forename: Akiva
authors.initials: A
authors.lastname: Mintz
authors.affiliation: Mount Sinai Medical Center, New York, NY.
authors.forename: Lale
authors.initials: L
authors.lastname: Kostakoglu
authors.affiliation: Moffitt Cancer Center, Tampa, Florida.
authors.forename: Edward A
authors.initials: EA
authors.lastname: Eikman
authors.affiliation: UCLA Medical Center, Los Angeles, California.
authors.forename: Benjamin M
authors.initials: BM
authors.lastname: Ellingson
authors.affiliation: Martinos Center for Biomedical Research, Charlestown, Massachusetts. Department of Radiology, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Eva-Maria
authors.initials: EM
authors.lastname: Ratai
authors.affiliation: Siemens Healthcare, Malvern, Pennsylvania.
authors.forename: A Gregory
authors.initials: AG
authors.lastname: Sorensen
authors.affiliation: Duke University Medical Center, Durham, North Carolina.
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Barboriak
authors.affiliation: University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: David A
authors.initials: DA
authors.lastname: Mankoff
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000032:analysis; D001932:Brain Neoplasms / Q000098:blood supply* / Q000401:mortality* / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D005909:Glioblastoma / Q000098:blood supply* / Q000401:mortality* / Q000473:pathology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D008920:Misonidazole / Q000031:analogs & derivatives / Q000494:pharmacology; D009389:Neovascularization, Pathologic / Q000473:pathology*; D049268:Positron-Emission Tomography; D011446:Prospective Studies; D019275:Radiopharmaceuticals / Q000494:pharmacology; D000072258:Tumor Hypoxia / Q000502:physiology*
chemical_list: D015415:Biomarkers; D019275:Radiopharmaceuticals; C031843:fluoromisonidazole; D008920:Misonidazole