title: Early changes in perfusion of glioblastoma during radio- and chemotherapy evaluated by T1-dynamic contrast enhanced magnetic resonance imaging.
abstract: BACKGROUND
  The survival times of patients with glioblastoma differ widely and biomarkers that would enable individualized treatment are needed. The objective of this study was to measure changes in the vascular physiology of tumor using T1-dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) in patients with glioblastoma during early stages of radio- and chemotherapy (Tx) and explore possible correlations with treatment outcomes.
  
  
  METHODS
  An exploratory prospective study was planned. Patients underwent DCE-MRI at baseline, after approximately one and six weeks of Tx and three and six months post-Tx. DCE-MRI at three Tesla generated maps of blood flow (BF), blood volume (BV), permeability (Ki) and volume of distribution (Vd) using a combination of model-free deconvolution and Patlak plots. Regions of interest in contrast enhancing tumor and in normal appearing white matter were contoured. Progression-free survival (PFS) was the primary clinical outcome. Patients with PFS > 6 months were compared with those with PFS < 6 months. Parameters of vascular physiology and changes in these during Tx were compared for these two groups at all time points using non-parametric statistics.
  
  
  RESULTS
  Eleven eligible patients were included and 46 DCE-MRI examinations were carried out. BF in tumor increased for all patients early during Tx (p = 0.005) and then fell to a level below baseline at post-Tx examinations (p = 0.016). A similar but non-significant trend was seen for tumor BV. There was no detectable difference between patients with PFS > 6 months versus PFS < 6 months with regards to baseline values or changes during and after Tx.
  
  
  CONCLUSIONS
  Although no correlations to outcomes were found, the results of this exploratory study may be hypothesis generating and will be examined in a larger patient group.
authors.affiliation: a Department of Oncology , Section for Radiotherapy, Rigshospitalet, University of Copenhagen , Denmark.
authors.forename: Søren
authors.initials: S
authors.lastname: Møller
authors.affiliation: a Department of Oncology , Section for Radiotherapy, Rigshospitalet, University of Copenhagen , Denmark.
authors.forename: Michael
authors.initials: M
authors.lastname: Lundemann
authors.affiliation: b Department of Clinical Physiology , Nuclear Medicine & PET, Rigshospitalet, University of Copenhagen , Denmark.
authors.forename: Ian
authors.initials: I
authors.lastname: Law
authors.affiliation: a Department of Oncology , Section for Radiotherapy, Rigshospitalet, University of Copenhagen , Denmark.|c Department of Radiation Biology , Rigshospitalet, University of Copenhagen , Denmark.
authors.forename: Hans S
authors.initials: HS
authors.lastname: Poulsen
authors.affiliation: b Department of Clinical Physiology , Nuclear Medicine & PET, Rigshospitalet, University of Copenhagen , Denmark.|d Functional Imaging Unit, Department of Clinical Physiology , Nuclear Medicine & PET, Rigshospitalet, University of Copenhagen , Denmark.
authors.forename: Henrik B W
authors.initials: HB
authors.lastname: Larsson
authors.affiliation: a Department of Oncology , Section for Radiotherapy, Rigshospitalet, University of Copenhagen , Denmark.
authors.forename: Svend Aage
authors.initials: SA
authors.lastname: Engelholm
mesh_terms: D001932:Brain Neoplasms / Q000098:blood supply* / Q000473:pathology* / Q000628:therapy; D003287:Contrast Media; D005909:Glioblastoma / Q000098:blood supply* / Q000473:pathology* / Q000628:therapy; D006801:Humans; D021621:Imaging, Three-Dimensional; D008279:Magnetic Resonance Imaging; D008536:Meglumine; D009942:Organometallic Compounds; D011446:Prospective Studies; D050397:Radiotherapy, Intensity-Modulated
chemical_list: D003287:Contrast Media; D009942:Organometallic Compounds; D008536:Meglumine; C072417:gadoterate meglumine