ACRIN6684: MRI and FMISO PET in newly diagnosed GBM

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 (GBM). Experimental Design: Prior to start of chemoradiation, GBM patients 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 (ktrans) 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 pre-treatment 18F-FMISO SUVpeak (p=0.048), mean ktrans (p=0.024), and median ktrans (p=0.045) were significantly associated with shorter overall survival. Higher pre-treatment median ktrans (p=0.021), normalized RCBV (p=0.0096), and nCBF (p=0.038) were significantly associated with shorter progression free survival. SUVpeak (AUC = 0.75, 95%CI 0.59 to 0.91), nRCBV (AUC=0.72, 95% CI0.56-0.89) and nCBF (AUC = 0.72, 95%CI 0.56 to 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 GBM patients and these important physiological markers can be measured safely and reliably using MRI and 18F-FMISO PET.

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