Abstract
Hypoxia, a characteristic trait of Glioblastoma (GBM), is known to cause resistance to chemo-radiation treatment and is linked with poor survival. There is hence an urgent need to non-invasively characterize tumor hypoxia to improve GBM management. We hypothesized that (a) radiomic texture descriptors can capture tumor heterogeneity manifested as a result of molecular variations in tumor hypoxia, on routine treatment naïve MRI, and (b) these imaging based texture surrogate markers of hypoxia can discriminate GBM patients as short-Term (STS), mid-Term (MTS), and long-Term survivors (LTS). 115 studies (33 STS, 41 MTS, 41 LTS) with gadolinium-enhanced T1-weighted MRI (Gd-T1w) and T2-weighted (T2w) and FLAIR MRI protocols and the corresponding RNA sequences were obtained. After expert segmentation of necrotic, enhancing, and edematous/nonenhancing tumor regions for every study, 30 radiomic texture descriptors were extracted from every region across every MRI protocol. Using the expression profile of 21 hypoxia-Associated genes, a hypoxia enrichment score (HES) was obtained for the training cohort of 85 cases. Mutual information score was used to identify a subset of radiomic features that were most informative of HES within 3-fold cross-validation to categorize studies as STS, MTS, and LTS. When validated on an additional cohort of 30 studies (11 STS, 9 MTS, 10 LTS), our results revealed that the most discriminative features of HES were also able to distinguish STS from LTS (p = 0.003).
| Original language | English (US) |
|---|---|
| Article number | 7 |
| Journal | Scientific reports |
| Volume | 8 |
| Issue number | 1 |
| DOIs | |
| State | Published - Dec 1 2018 |
Funding
Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under award numbers 1U24CA199374-01, R01CA202752-01A1 R01CA208236-01A1 R21CA179327-01; R21CA195152-01 the National Institute of Diabetes and Digestive and Kidney Diseases under award number R01DK098503-02, National Center for Research Resources under award number 1 C06 RR12463-01 the DOD Prostate Cancer Synergistic Idea Development Award (PC120857); the DOD Lung Cancer Idea Development New Investigator Award (LC130463), the DOD Prostate Cancer Idea Development Award; the DOD Peer Reviewed Cancer Research Program W81XWH-16-1-0329 the Ohio Third Frontier Technology Validation Fund the Wallace H. Coulter Foundation Program in the Department of Biomedical Engineering and the Clinical and Translational Science Award Program (CTSA) at Case Western Reserve University. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The cohort used for retrospective prognostic study using multi-institutional data was obtained from The Cancer Imaging Archive (TCIA). TCIA is an open archive of cancer-specific medical images and associated clinical metadata established by the collaboration between the National Cancer Institute (NCI) and participating institutions in the United States. The HIPPA compliant project in TCGA was conducted in compliance with regulations and policies for the protection of human subjects, and approvals by institutional review boards were appropriately obtained. Competing Interests: Dr. Madabhushi is an equity holder in Elucid Bioimaging and in Inspirata Inc. He is also a scientific advisory consultant for Inspirata Inc and also sits on its scientific advisory board. Additionally his technology has been licensed to Elucid Bioimaging and Inspirata Inc. He is also involved in a NIH U24 grant with PathCore Inc., and an NIH R01 grant with Inspirata Inc. His work is also partially sponsored by Philips Healthcare.
ASJC Scopus subject areas
- General