ACRIN 6684: Assessment of Tumor Hypoxia in Newly Diagnosed Glioblastoma Using 18F-FMISO PET and MRI

Elizabeth R Gerstner, Zheng Zhang, James R Fink, Mark Muzi, Lucy Hanna, Erin Greco, Melissa Prah, Kathleen M Schmainda, Akiva Mintz, Lale Kostakoglu, Edward A Eikman, Benjamin M Ellingson, Eva-Maria Ratai, A Gregory Sorensen, Daniel P Barboriak, David A Mankoff, ACRIN 6684 Trial Group, Elizabeth R Gerstner, Zheng Zhang, James R Fink, Mark Muzi, Lucy Hanna, Erin Greco, Melissa Prah, Kathleen M Schmainda, Akiva Mintz, Lale Kostakoglu, Edward A Eikman, Benjamin M Ellingson, Eva-Maria Ratai, A Gregory Sorensen, Daniel P Barboriak, David A Mankoff, ACRIN 6684 Trial Group

Abstract

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 (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 pretreatment 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 pretreatment 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% 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.

Conflict of interest statement

Dr. Sorensen reports stock ownership and employment with Siemens and patents/royalties/intellectual property with General Electric. Dr Schmainda reports ownership interest in Imaging Biometrics LLC. All other authors report no conflict of interest.

©2016 American Association for Cancer Research.

Figures

Figure 1
Figure 1
Patient Flow Diagram
Figure 2
Figure 2
MRI and PET imaging from a single patient with elevated 18F-FMISO uptake.
Figure 3
Figure 3
MRI and PET imaging from a single patient with low 18F-FMISO uptake.

Source: PubMed

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