Journal
TOMOGRAPHY
Volume 5, Issue 1, Pages 135-144Publisher
GRAPHO PUBLICATIONS
DOI: 10.18383/j.tom.2018.00052
Keywords
glioblastoma; survival; MRI; habitats; cancer evolution
Funding
- National Institutes of Health [U54 CA193489, P30 CA076292, R01 CA116174, R01 NS060752, R01 CA164371, U54 CA210180, U54 CA143970, U01 CA220378]
- James S. McDonnell Foundation [220020400]
- Ivy Foundation
- 2017 Moffitt Team Science Award
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Standard-of-care multiparameter magnetic resonance imaging (MRI) scans of the brain were used to objectively subdivide glioblastoma multiforme (GBM) tumors into regions that correspond to variations in blood flow, interstitial edema, and cellular density. We hypothesized that the distribution of these distinct tumor ecological habitats at the time of presentation will impact the course of the disease. We retrospectively analyzed initial MRI scans in 2 groups of patients diagnosed with GBM, a long-term survival group comprising subjects who survived >36 month postdiagnosis, and a short-term survival group comprising subjects who survived <19 month postdiagnosis. The single-institution discovery cohort contained 22 subjects in each group, while the multi-institution validation cohort contained 15 subjects per group. MRI voxel intensities were calibrated, and tumor voxels clustered on contrast-enhanced T1-weighted and fluid-attenuated inversion-recovery (FLAIR) images into 6 distinct habitats based on low-to medium-to high-contrast enhancement and low-high signal on FLAIR scans. Habitat 6 (high signal on calibrated contrast-enhanced T1-weighted and FLAIR sequences) comprised a significantly higher volume fraction of tumors in the long-term survival group (discovery cohort, 35% +/- 6.5%; validation cohort, 34% +/- 4.8%) compared with tumors in the short-term survival group (discovery cohort, 17% +/- 4.5%, P < .03; validation cohort, 16 +/- 4.0%, P < .007). Of the 6 distinct MRI-defined habitats, the fractional tumor volume of habitat 6 at diagnosis was significantly predictive of long-or short-term survival. We discuss a possible mechanistic basis for this association and implications for habitat-driven adaptive therapy of GBM.
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