title: Cerebral blood volume, genotype and chemosensitivity in oligodendroglial tumours.
abstract: BACKGROUND
  The biological factors responsible for differential chemoresponsiveness in oligodendroglial tumours with or without the -1p/-19q genotype are unknown, but tumour vascularity may contribute. We aimed to determine whether dynamic susceptibility contrast (DSC) magnetic resonance imaging (MRI) could distinguish molecular subtypes of oligodendroglial tumour, and examined the relationship between relative cerebral blood volume (rCBV) and outcome following procarbazine, lomustine and vincristine (PCV) chemotherapy.
  
  
  METHODS
  Pretherapy rCBV was calculated and inter- and intraobserver variability assessed. Allelic imbalance in 1p36, 19q13, 17p13, 10p12-15, and 10q22-26 and p53 mutation (exons 5-8) were determined. rCBV was compared with genotype and clinicopathological characteristics (n=37) and outcome following PCV chemotherapy (n=33).
  
  
  RESULTS
  1p/19q loss was seen in 6/9 grade II oligodendrogliomas, 6/14 grade II oligoastrocytomas, 4/4 grade III oligodendrogliomas, and 3/10 grade III oligoastrocytomas. rCBV measurements had good inter- and intraobserver variability, but did not distinguish histology subtype or grade. Tumours with 1p/19q loss had higher rCBV values (Student's t-test P=0.001). Receiver operating characteristic analysis revealed a cut-off of 1.59 for identifying genotype (sensitivity 92%, specificity 76%). Tumours with high and low rCBV showed response to chemotherapy. The -1p/-19q genotype, but not rCBV, was strongly associated with response, progression-free and overall survival following PCV chemotherapy. Tumours with high rCBV and intact 1p/19q were associated with shorter progression-free and overall patient survival than those with intact 1p/19q and low rCBV or high rCBV and 1p/19q loss.
  
  
  CONCLUSIONS
  rCBV identifies oligodendroglial tumours with 1p/19q loss, but does not predict chemosensitivity. The prognostic significance of rCBV may differ in oligodendroglial tumours with or without the -1p/-19q genotype.
authors.affiliation: Department of Neurosurgery, The Walton Centre for Neurology and Neurosurgery, Liverpool, UK.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Jenkinson
authors.forename: Trevor S
authors.initials: TS
authors.lastname: Smith
authors.forename: Kathy A
authors.initials: KA
authors.lastname: Joyce
authors.forename: Diane
authors.initials: D
authors.lastname: Fildes
authors.forename: John
authors.initials: J
authors.lastname: Broome
authors.forename: Daniel G
authors.initials: DG
authors.lastname: du Plessis
authors.forename: Brian
authors.initials: B
authors.lastname: Haylock
authors.forename: David J
authors.initials: DJ
authors.lastname: Husband
authors.forename: Peter C
authors.initials: PC
authors.lastname: Warnke
authors.forename: Carol
authors.initials: C
authors.lastname: Walker
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001810:Blood Volume; D001932:Brain Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology*; D005838:Genotype; D006801:Humans; D019656:Loss of Heterozygosity; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008875:Middle Aged; D009837:Oligodendroglioma / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology*; D011237:Predictive Value of Tests; D011446:Prospective Studies; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents