title: Assessing vascular effects of adding bevacizumab to neoadjuvant chemotherapy in osteosarcoma using DCE-MRI.
abstract: BACKGROUND
  The purpose of this study was to assess the impact of bevacizumab alone and in combination with cytotoxic therapy on tumour vasculature in osteosarcoma (OS) using DCE-MRI.
  
  
  METHODS
  Six DCE-MRI and three (18)F-FDG PET examinations were scheduled in 42 subjects with newly diagnosed OS to monitor the response to antiangiogenic therapy alone and in combination with cytotoxic therapy before definitive surgery (week 10). Serial DCE-MRI parameters (K(trans), v(p), and v(e)) were examined for correlation with FDG-PET (SUV(max)) and association with drug exposure, and evaluated with clinical outcome.
  
  
  RESULTS
  K(trans) (P=0.041) and v(p) (P=0.001) significantly dropped from baseline at 24 h after the first dose of bevacizumab alone, but returned to baseline by 72 h. Greater exposure to bevacizumab was correlated with larger decreases in v(p) at day 5 (P=0.04) and week 10 (P=0.02). A lower K(trans) at week 10 was associated with greater percent necrosis (P=0.024) and longer event-free survival (P=0.034).
  
  
  CONCLUSIONS
  This is the first study to demonstrate significant changes of the plasma volume fraction and vascular leakage in OS with bevacizumab alone. The combination of demonstrated associations between drug exposure and imaging metrics, and imaging metrics and patient survival during neoadjuvant therapy, provides a compelling rationale for larger studies using DCE-MRI to assess vascular effects of therapy in OS.
authors.affiliation: Department of Diagnostic Imaging, St Jude Children's Research Hospital, 262 Danny Thomas Place, Mail Stop 220, Memphis, TN 38105-3678, USA.
authors.forename: J
authors.initials: J
authors.lastname: Guo
authors.affiliation: Department of Diagnostic Imaging, St Jude Children's Research Hospital, 262 Danny Thomas Place, Mail Stop 220, Memphis, TN 38105-3678, USA.
authors.forename: J O
authors.initials: JO
authors.lastname: Glass
authors.affiliation: Department of Diagnostic Imaging, St Jude Children's Research Hospital, 262 Danny Thomas Place, Mail Stop 220, Memphis, TN 38105-3678, USA.
authors.forename: M B
authors.initials: MB
authors.lastname: McCarville
authors.affiliation: Department of Diagnostic Imaging, St Jude Children's Research Hospital, 262 Danny Thomas Place, Mail Stop 220, Memphis, TN 38105-3678, USA.
authors.forename: B L
authors.initials: BL
authors.lastname: Shulkin
authors.affiliation: Department of Pharmaceutical Sciences, St Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors.forename: V M
authors.initials: VM
authors.lastname: Daryani
authors.affiliation: Department of Pharmaceutical Sciences, St Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors.forename: C F
authors.initials: CF
authors.lastname: Stewart
authors.affiliation: Department of Biostatistics, St Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors.forename: J
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Biostatistics, St Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors.forename: S
authors.initials: S
authors.lastname: Mao
authors.affiliation: Department of Radiology, Rady Children's Hospital, San Diego, CA 92123, USA.
authors.forename: J R
authors.initials: JR
authors.lastname: Dwek
authors.affiliation: The Musculoskeletal Tumor Program, The Johns Hopkins University, Baltimore, MD 21287, USA.
authors.forename: L M
authors.initials: LM
authors.lastname: Fayad
authors.affiliation: Department of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: J E
authors.initials: JE
authors.lastname: Madewell
authors.affiliation: Department of Oncology, St Jude Children's Research Hospital, Memphis, TN 38105, USA.|Department of Pediatrics, College of Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
authors.forename: F
authors.initials: F
authors.lastname: Navid
authors.affiliation: Department of Oncology, St Jude Children's Research Hospital, Memphis, TN 38105, USA.|Division of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: N C
authors.initials: NC
authors.lastname: Daw
authors.affiliation: Department of Diagnostic Imaging, St Jude Children's Research Hospital, 262 Danny Thomas Place, Mail Stop 220, Memphis, TN 38105-3678, USA.
authors.forename: W E
authors.initials: WE
authors.lastname: Reddick
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant / Q000379:methods; D002648:Child; D003287:Contrast Media / Q000008:administration & dosage; D018572:Disease-Free Survival; D005260:Female; D019788:Fluorodeoxyglucose F18; D019786:Gadolinium DTPA; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D020360:Neoadjuvant Therapy / Q000379:methods; D012516:Osteosarcoma / Q000188:drug therapy* / Q000628:therapy*; D049268:Positron-Emission Tomography / Q000379:methods
chemical_list: D020533:Angiogenesis Inhibitors; D003287:Contrast Media; D019788:Fluorodeoxyglucose F18; D000068258:Bevacizumab; D019786:Gadolinium DTPA