Abstract 4217: First pre-clinical validation of radiogenomics in glioblastoma

Abstract

Abstract A plethora of Magnetic Resonance Imaging (MRI) features have been correlated to cancer genomics to date, however, none have established causality. Here, we present an in vivo xenograft RNA interference validated, potentially clinically applicable test method termed “Magnetic Resonance Radiomic Sequencing” (MRRS) for the noninvasive detection of cancer genomics in Glioblastoma. MRRS comprehensively assesses the entire tumor mass using imaging texture-based algorithms that generate thousands of variables (features) inherent to the tumor. Two independent glioblastoma stem cells (GSC1 and GSC3) harboring doxycycline inducible short hairpin RNA against Periostin (POSTN), a gene previously identified in our radiogenomic screen, were implanted at orthotopic location in nude mouse brain. In vivo knockdown of >90% and ∼40% POSTN gene was achieved in GSC3 and GSC1 respectively. The T2 and T1 post MRI texture features, in edema and contrast enhancement phenotype features were compared between doxycycline (POSTN knockdown) and sucrose (control) group of mice using T test statistics. The significant features were included in a Stepwise Forward Logistic Regression analysis to build the final predictive model. The accuracy of the model was tested using ROC cure analysis. Among 3600 features in GSC3 mice cohort, 117 features were significantly (p value<0.05) different between the two groups. The significant features were included in a Stepwise Forward Logistic Regression analysis, 2 textures features (feature 234 of edema T1 and feature 251 of edema T2) were selected to be included in the final predictive model. The AUC of the model with leave one out cross validation method was 100%. The similar analyses were done in the GSC1 mice. The final predictive model in the GSC1 group was statistically insignificant (p value = 0.15) with AUC (95% CI) = 73% (46%-98%), suggesting that MRRS is reflective of underlying gene expression levels. Our results therefore describe the ‘first mouse model derived MRRS signature to describe a causal link of gene alteration to MRRS. This novel test method may open an avenue for human-mouse matched co-clinical trials and noninvasive Radiogenomic diagnostics. Citation Format: Pascal Zinn, Sanjay Singh, Markus M. Luedi, Faramak Zandi, Aikaterini Kotrotsou, Masumeh Hatami, Ginu Thomas, Ahmed Elakkad, Joy Gumin, Erik P. Sulman, Frederick Lang, David Piwnica-Worms, Rivka R. Colen. First pre-clinical validation of radiogenomics in glioblastoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4217.