Faculty Collaboration Database

Assessment of tumor hypoxia and perfusion in recurrent glioblastoma following bevacizumab failure using MRI and ¹⁸F-FMISO PET. Sci Rep 2021 Apr 07;11(1):7632

Date

04/09/2021

Pubmed ID

33828310

Pubmed Central ID

PMC8027395

DOI

10.1038/s41598-021-84331-5

Scopus ID

2-s2.0-85104042152 (requires institutional sign-in at Scopus site)   15 Citations

Abstract

Tumoral hypoxia correlates with worse outcomes in glioblastoma (GBM). While bevacizumab is routinely used to treat recurrent GBM, it may exacerbate hypoxia. Evofosfamide is a hypoxia-targeting prodrug being tested for recurrent GBM. To characterize resistance to bevacizumab and identify those with recurrent GBM who may benefit from evofosfamide, we ascertained MRI features and hypoxia in patients with GBM progression receiving both agents. Thirty-three patients with recurrent GBM refractory to bevacizumab were enrolled. Patients underwent MR and ¹⁸F-FMISO PET imaging at baseline and 28 days. Tumor volumes were determined, MRI and ¹⁸F-FMISO PET-derived parameters calculated, and Spearman correlations between parameters assessed. Progression-free survival decreased significantly with hypoxic volume [hazard ratio (HR) = 1.67, 95% confidence interval (CI) 1.14 to 2.46, P = 0.009] and increased significantly with time to the maximum value of the residue (Tmax) (HR = 0.54, 95% CI 0.34 to 0.88, P = 0.01). Overall survival decreased significantly with hypoxic volume (HR = 1.71, 95% CI 1.12 to 12.61, p = 0.01), standardized relative cerebral blood volume (srCBV) (HR = 1.61, 95% CI 1.09 to 2.38, p = 0.02), and increased significantly with Tmax (HR = 0.31, 95% CI 0.15 to 0.62, p < 0.001). Decreases in hypoxic volume correlated with longer overall and progression-free survival, and increases correlated with shorter overall and progression-free survival. Hypoxic volume and volume ratio were positively correlated (r_s = 0.77, P < 0.0001), as were hypoxia volume and T1 enhancing tumor volume (r_s = 0.75, P < 0.0001). Hypoxia is a key biomarker in patients with bevacizumab-refractory GBM. Hypoxia and srCBV were inversely correlated with patient outcomes. These radiographic features may be useful in evaluating treatment and guiding treatment considerations.

Author List

Huang S, Michalek JE, Reardon DA, Wen PY, Floyd JR, Fox PT, Clarke GD, Jerabek PA, Schmainda KM, Muzi M, Hyun H, Lee EQ, Brenner AJ

Author

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

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

Adult
Aged
Bevacizumab
Biomarkers, Pharmacological
Brain Neoplasms
Cerebral Blood Volume
Drug Resistance, Neoplasm
Female
Glioblastoma
Humans
Magnetic Resonance Imaging
Male
Middle Aged
Misonidazole
Neoplasm Recurrence, Local
Positron-Emission Tomography
Tumor Hypoxia
Young Adult