Preoperative biomarkers of tumour vascularity are elevated in patients with glioblastoma multiforme

• We investigated the utility of cellular (circulating endothelial cell [CEC] and progenitor cell [CEP]) and imaging (perfusion MRI) biomarkers in patients with glioblastoma multiforme (GBM).
• A novel perfusion MRI parameter (rCBVload) was developed to estimate the total volume of perfused tumour vessels.
• CECs were shown to be increased in the presence of GBM.
• CEP levels were found to be proportional to tumour vascularity as measured by perfusion MRI.

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.