Cerebral blood volume, genotype and chemosensitivity in oligodendroglial tumours.
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.
Jenkinson
Michael D
MD
Department of Neurosurgery, The Walton Centre for Neurology and Neurosurgery, Liverpool, UK.
Smith
Trevor S
TS
Joyce
Kathy A
KA
Fildes
Diane
D
Broome
John
J
du Plessis
Daniel G
DG
Haylock
Brian
B
Husband
David J
DJ
Warnke
Peter C
PC
Walker
Carol
C
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
D000970:Antineoplastic Agents