UCLA

Purpose

Structural and functional alterations in tumor vasculature are thought to contribute to tumor hypoxia which is a primary driver of malignancy through its negative impact on the efficacy of radiation, immune surveillance, apoptosis, genomic stability, and accelerated angiogenesis. We performed a prospective, multicenter study to test the hypothesis that abnormal tumor vasculature and hypoxia, as measured with MRI and PET, will negatively impact survival in patients with newly diagnosed glioblastoma.

Experimental design

Prior to the start of chemoradiation, patients with glioblastoma underwent MRI scans that included dynamic contrast enhanced and dynamic susceptibility contrast perfusion sequences to quantitate tumor cerebral blood volume/flow (CBV/CBF) and vascular permeability (k^trans) as well as ¹⁸F-Fluoromisonidazole (¹⁸F-FMISO) PET to quantitate tumor hypoxia. ROC analysis and Cox regression models were used to determine the association of imaging variables with progression-free and overall survival.

Results

Fifty patients were enrolled of which 42 had evaluable imaging data. Higher pretreatment ¹⁸F-FMISO SUV_peak (P = 0.048), mean k^trans (P = 0.024), and median k^trans (P = 0.045) were significantly associated with shorter overall survival. Higher pretreatment median k^trans (P = 0.021), normalized RCBV (P = 0.0096), and nCBF (P = 0.038) were significantly associated with shorter progression-free survival. SUV_peak [AUC = 0.75; 95% confidence interval (CI), 0.59-0.91], nRCBV (AUC = 0.72; 95% CI, 0.56-0.89), and nCBF (AUC = 0.72; 95% CI, 0.56-0.89) were predictive of survival at 1 year.

Conclusions

Increased tumor perfusion, vascular volume, vascular permeability, and hypoxia are negative prognostic markers in newly diagnosed patients with gioblastoma, and these important physiologic markers can be measured safely and reliably using MRI and ¹⁸F-FMISO PET. Clin Cancer Res; 22(20); 5079-86. ©2016 AACR.