title: Preoperative biomarkers of tumour vascularity are elevated in patients with glioblastoma multiforme.
abstract: We investigated the correlation between the circulating and imaging biomarkers of tumour vascularity, and examined whether they are prognostic of outcomes in patients with glioblastoma multiforme (GBM). Despite the increasing use of anti-angiogenic agents within neuro-oncology, there are still no validated biomarkers to monitor for a treatment response or relapse. The pre- and postoperative circulating endothelial cell (CEC) and progenitor cell (CEP) levels were assessed. Preoperative perfusion-weighted MRI (PWI) was also performed, and the relative cerebral blood volume (rCBV) histogram statistics of the contrast-enhancing tumour were analysed. A novel PWI parameter (rCBVload) was developed to estimate the total volume of perfused tumour vessels, and it was hypothesised that this parameter would correlate with CEC and CEP concentrations. In total, 24 GBM patients were included. The mean preoperative CEC concentration was significantly higher in GBM patients than the controls (p=0.019), and it then declined significantly postoperatively (p=0.009). The preoperative CEP levels were significantly correlated with the median tumour rCBV (Spearman rank-order coefficient=0.526; p=0.039). Neither CEC nor CEP was correlated with the total tumour vessel volume, as measured by rCBVload. None of the biomarkers that were investigated showed a significant correlation with progression-free or overall survival. We conclude that CEC are potentially useful biomarkers to monitor GBM patients during treatment. We found that CEC are increased in the presence of GBM, and that CEP levels appear to be proportional to tumour vascularity, as measured on PWI. However, in this study, none of the biomarkers of GBM vascularity were highly prognostic of patient outcomes.
authors: Department of Surgery, The University of Melbourne, Grattan Street, Parkville, VIC 3050, Australia.
authors: Iwan E
authors: IE
authors: Bennett
authors: Department of Surgery, The University of Melbourne, Grattan Street, Parkville, VIC 3050, Australia.
authors: Hui
authors: H
authors: Guo
authors: Department of Surgery, The University of Melbourne, Grattan Street, Parkville, VIC 3050, Australia.
authors: Nicole
authors: N
authors: Kountouri
authors: Department of Surgery, The University of Melbourne, Grattan Street, Parkville, VIC 3050, Australia.
authors: Giovanna M
authors: GM
authors: D'abaco
authors: Department of Surgery, The University of Melbourne, Grattan Street, Parkville, VIC 3050, Australia.
authors: Christopher M
authors: CM
authors: Hovens
authors: Department of Radiology, The University of Melbourne, Parkville, VIC, Australia.
authors: Bradford A
authors: BA
authors: Moffat
authors: Department of Radiology, The University of Melbourne, Parkville, VIC, Australia.
authors: Patricia
authors: P
authors: Desmond
authors: Department of Surgery, The University of Melbourne, Grattan Street, Parkville, VIC 3050, Australia; Department of Neurosurgery, The Royal Melbourne Hospital, Parkville, VIC, Australia.
authors: Katharine
authors: K
authors: Drummond
authors: Department of Surgery, The University of Melbourne, Grattan Street, Parkville, VIC 3050, Australia; Department of Neurosurgery, The Royal Melbourne Hospital, Parkville, VIC, Australia.
authors: Andrew H
authors: AH
authors: Kaye
authors: Department of Surgery, The University of Melbourne, Grattan Street, Parkville, VIC 3050, Australia; Department of Neurosurgery, The Royal Melbourne Hospital, Parkville, VIC, Australia. Electronic address: morokoff@unimelb.edu.au.
authors: Andrew P
authors: AP
authors: Morokoff
mesh_terms: D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood*; D001932:Brain Neoplasms / Q000097:blood* / Q000098:blood supply / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000601:surgery; D018450:Disease Progression; D042783:Endothelial Cells / Q000473:pathology; D005260:Female; D005909:Glioblastoma / Q000097:blood* / Q000098:blood supply / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000601:surgery; D006801:Humans; D018810:Magnetic Resonance Angiography; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000097:blood* / Q000098:blood supply / Q000000981:diagnostic imaging / Q000188:drug therapy; D014411:Neoplastic Stem Cells / Q000473:pathology*; D011237:Predictive Value of Tests; D057234:Preoperative Period; D011379:Prognosis; D011859:Radiography
chemical_list: D020533:Angiogenesis Inhibitors; D014408:Biomarkers, Tumor
keywords: Biomarker; Circulating endothelial cells; Glioblastoma multiforme; Perfusion MRI; Relative cerebral blood volume