Nimg-26. Radiomic Features of Glioblastoma on Pre-treatment Gd-t1w Mri Are Predictive of Response to Chemo-radiation Therapy and Associated With Akt and Apoptosis Pathways
Year: 2018
Type: conference-abstract
Abstract: >40% of Glioblastoma patients do not respond to chemo-radiation (Ch-Rx) treatment and recur within 6–8 months, suggesting that they could be better candidates for experimental therapies. We seek to discover radiomic features on pre-treatment MRI that are predictive of response to Ch-Rx. Further, in an attempt to establish biological underpinning of these predictive radiomic features, we then identified radiogenomic correlations between these features with molecular pathways that are known to impact response to Ch-Rx. 49 GBM studies were obtained from publicly available IVYGap (n=29) and TCIA (n=20) databases, with pre-treatment MRI scans (Gd-T1w, T2w, FLAIR) and corresponding RNA-Seq data. Responders were defined as patients with progression-free survival (PFS) of >= 4-months, while non-responders had PFS of <4-months. A total of 1305 3D-radiomic features (Gabor, Haralick, and Laws energy) were extracted from each MRI protocol from expert annotated regions (enhancing, edema/non-enhancing, necrosis) for every study. Top 5 predictive features were obtained from a training set and validated using a support vector machine classifier. 13 signaling pathways that are known to be implicated in Ch-Rx response were curated from the MSigDB HALLMARK cohort. Gene Set Enrichment Analysis (GSEA) scores of these pathways was correlated with the top radiomic features with Bonferroni correction. Laws energy features that characterize appearance of ripples and spots from enhancing region on Gd-T1 MRI were found to best predict Ch-Rx response (sensitivity of 73.3% on validation set). These features were statistically significantly correlated with AKT and apoptosis signaling pathways (p<0.02, FDR = 5%). Activation of AKT pathway facilitates angiogenesis and develops Ch-Rx resistance. Similarly, higher expression of apoptotic proteins in GBM is associated with favorable Ch-Rx response. Our radiogenomic approach may allow for non-invasive CRT response prediction by providing biological understanding of molecular pathways implicated in Ch-Rx response, as manifested on pre-treatment Gd-T1 MRI.
Source: Neuro-Oncology
Institutions: Case Western Reserve University, Cleveland Clinic
Language: English
Subfield: Radiology, Nuclear Medicine and Imaging
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2899965234