title: Early biomarkers from dynamic contrast-enhanced magnetic resonance imaging to predict the response to antiangiogenic therapy in high-grade gliomas.
abstract: BACKGROUND
  The aim of this study is to investigate whether early changes in tumor volume and perfusion measurements derived from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) may predict response to antiangiogenic therapy in recurrent high-grade gliomas.
  
  
  METHODS
  Twenty-seven patients who received bevacizumab every 3 weeks were enrolled in the study. For each patient, three MRI scans were performed: at baseline, after the first dose, and after the fourth dose of bevacizumab. The entire tumor volume (V(tot)), as well as contrast-enhanced and noncontrast-enhanced tumor subvolumes (V(CE-T1) and V(NON-CE-T1), respectively) were outlined using post-contrast T1-weighted images as a guide for the tumor location. Histogram analysis of normalized IAUGC (nIAUGC) and transfer constant K(trans) maps were performed. Each patient was classified as a responder patient if he/she had a partial response or a stable disease or as a nonresponder patient if he/she had progressive disease.
  
  
  RESULTS
  Responding patients showed a larger reduction in V(NON-CE-T1) after a single dose, compared to nonresponding patients. Tumor subvolumes with increased values of nIAUGC and K(trans), after a single dose, significantly differed between responders and nonresponders. The radiological response was found to be significantly associated to the clinical outcome. After a single dose, V(tot) was predictive of overall survival (OS), while V(CE-T1) showed a tendency of correlation with OS.
  
  
  CONCLUSIONS
  Tumor subvolumes with increased nIAUGC and K(trans) showed the potential for improving the diagnostic accuracy of DCE. Early assessments of the entire tumor volume, including necrotic areas, may provide complementary information of tumor behavior in response to anti-VEGF therapies and is worth further investigation.
authors.affiliation: Radiology and Diagnostic Imaging Department, Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Piludu
authors.affiliation: Medical Physics Laboratory, Regina Elena National Cancer Institute, Via Elio Chianesi 53, Rome, 00144, Italy. marzi@ifo.it.
authors.forename: Simona
authors.initials: S
authors.lastname: Marzi
authors.affiliation: Neurology Division, Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Pace
authors.affiliation: Neurology Division, Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: Veronica
authors.initials: V
authors.lastname: Villani
authors.affiliation: Oncology Department, Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Fabi
authors.affiliation: Oncologic Surgery Department, Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: Carmine Maria
authors.initials: CM
authors.lastname: Carapella
authors.affiliation: Biostatistics-Scientific Direction, Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: Irene
authors.initials: I
authors.lastname: Terrenato
authors.affiliation: Clinical Pathology, Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Antenucci
authors.affiliation: Radiology and Diagnostic Imaging Department, Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: Antonello
authors.initials: A
authors.lastname: Vidiri
mesh_terms: D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage; D000068258:Bevacizumab / Q000008:administration & dosage*; D015415:Biomarkers; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D003287:Contrast Media; D016903:Drug Monitoring / Q000379:methods; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy* / Q000473:pathology*; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading
chemical_list: D020533:Angiogenesis Inhibitors; D015415:Biomarkers; D003287:Contrast Media; D000068258:Bevacizumab
keywords: Bevacizumab; DCE MRI; High-grade glioma; Perfusion MRI; Quantitative image analysis