Title: NIMG-07. UNIFYING MAGNETIC RESONANCE IMAGING SIGNATURE OF EGFR PATHWAY ACTIVATION IN GLIOBLASTOMA CONSISTENT WITH UNIFORMLY AGGRESSIVELY INFILTRATION
Abstract: Glioblastoma, the most common adult primary malignant brain tumor, has a large degree of inter- and intratumoral radiologic, histologic, and molecular heterogeneity. While various genes are commonly mutated in glioblastoma, the spread of point-mutations within those genes is quite diverse. Epidermal growth factor receptor (EGFR), is found to be mutated or amplified in approximately 60% of glioblastomas, and exhibits a spread of point-mutations accompanying amplification and the EGFR splice variant III (EGFRvIII). EGFRvIII has been shown to increase tumor invasiveness through several downstream pathways, including Akt and Ras/Raf/MAPK. Similar downstream pathway activation has been found in wild-type EGFR amplification in glioblastomas, suggesting a common underlying mechanism for the increased invasion seen in EGFR-activating alterations. This study reports the development of a clinically significant radio-phenotypic signature associated with the activation of the EGFR pathway, irrespective of whether it is through amplification of wild-type EGFR or expression of EGFRvIII or other known activating EGFR point-mutations. This signature is based on a peritumoral heterogeneity index (PHI/φ-index), obtained by comparing the peritumoral perfusion signal in the proximal and distal tissue, relative to the tumor core. A retrospective analysis was conducted on a single-institutional cohort from the University of Pennsylvania with various EGFR alterations and available pre-operative standard and advanced magnetic resonance imaging (MRI). EGFR alterations included tumors with EGFRvIII (n=42), wild-type EGFR amplification (n=6), and the most common EGFR point-mutations (n=25) (i.e. R108K, A289D/T/V, G598V). Lower PHI values, consistent with uniformly aggressively infiltrating tumors throughout the peritumoral edema, was found on tumors with EGFR alterations compared to EGFR non-mutated and non-amplified control cases (n=100). The resulted MRI signature of this study, suggestive of increased tumor invasiveness, matched the anticipated biological impact of the EGFR alterations and represents a marker of EGFR pathway activation in glioblastoma, potentially useful for monitoring targeted treatment-response along this pathway.