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ACRIN 6684: Assessment of Tumor Hypoxia in Newly Diagnosed Glioblastoma Using 18F-FMISO PET and MRI. Clin Cancer Res 2016 Oct 15;22(20):5079-5086 PMID: 27185374 PMCID: PMC5065740

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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) as well as F-Fluoromisonidazole (F-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 F-FMISO SUV (P = 0.048), mean k (P = 0.024), and median k (P = 0.045) were significantly associated with shorter overall survival. Higher pretreatment median k (P = 0.021), normalized RCBV (P = 0.0096), and nCBF (P = 0.038) were significantly associated with shorter progression-free survival. SUV [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 F-FMISO PET. Clin Cancer Res; 22(20); 5079-86. ©2016 AACR.

Author List

Gerstner ER, Zhang Z, Fink JR, Muzi M, Hanna L, Greco E, Prah M, Schmainda KM, Mintz A, Kostakoglu L, Eikman EA, Ellingson BM, Ratai EM, Sorensen AG, Barboriak DP, Mankoff DA, ACRIN 6684 Trial Group


Kathleen M. Schmainda PhD Professor in the Biophysics department at Medical College of Wisconsin


2-s2.0-84991721594   30 Citations

MESH terms used to index this publication - Major topics in bold

Brain Neoplasms
Disease-Free Survival
Magnetic Resonance Imaging
Middle Aged
Neovascularization, Pathologic
Positron-Emission Tomography
Prospective Studies
Tumor Hypoxia
jenkins-FCD Prod-331 a335b1a6d1e9c32173c9534e6f6ff51494143916