Magnetic Resonance Imaging (MRI) has been routinely used for the diagnosis and treatment of breast cancer. However, the relationship between the MRI tumor phenotypes and the underlying genetic mechanisms remains under-explored. We integrated multi-omics molecular data from The Cancer Genome Atlas (TCGA) with MRI data from The Cancer Imaging Archive (TCIA) for 91 breast invasive carcinomas. Quantitative MRI phenotypes of tumors (such as tumor size, shape, margin, and blood flow kinetics) were associated with their corresponding molecular profiles (including DNA mutation, miRNA expression, protein expression, pathway gene expression and copy number variation). We found that transcriptional activities of various genetic pathways were positively associated with tumor size, blurred tumor margin, and irregular tumor shape and that miRNA expressions were associated with the tumor size and enhancement texture, but not with other types of radiomic phenotypes. We provide all the association findings as a resource for the research community (available at http://compgenome.org/Radiogenomics/). These findings pave potential paths for the discovery of genetic mechanisms regulating specific tumor phenotypes and for improving MRI techniques as potential non-invasive approaches to probe the cancer molecular status.

Abstract. Genomic and radiomic imaging profiles of invasive breast carcinomas from The Cancer Genome Atlas and The Cancer Imaging Archive were integrated and a comprehensive analysis was conducted to predict clinical outcomes using the radiogenomic features. Variable selection via LASSO and logistic regression were used to select the most-predictive radiogenomic features for the clinical phenotypes, including pathological stage, lymph node metastasis, and status of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). Cross-validation with receiver operating characteristic (ROC) analysis was performed and the area under the ROC curve (AUC) was employed as the prediction metric. Higher AUCs were obtained in the prediction of pathological stage, ER, and PR status than for lymph node metastasis and HER2 status. Overall, the prediction performances by genomics alone, radiomics alone, and combined radiogenomics features showed statistically significant correlations with clinical outcomes; however, improvement on the prediction performance by combining genomics and radiomics data was not found to be statistically significant, most likely due to the small sample size of 91 cancer cases with 38 radiomic features and 144 genomic features. © 2015 Society of Photo-Optical Instrumentation Engineers (SPIE)

There has been an increasing interest in using interval-based Bayesian designs for dose finding, one of which is the modified toxicity probability interval (mTPI) method. We show that the decision rules in mTPI correspond to an optimal rule under a formal Bayesian decision theoretic framework. However, the probability models in mTPI are overly sharpened by the Ockham's razor, which, while in general helps with parsimonious statistical inference, leads to suboptimal decisions in small-sample inference such as dose finding. We propose a new framework that blunts the Ockham's razor, and demonstrate the superior performance of the new method, called mTPI-2. An online web tool is provided for users who can generate the design, conduct clinical trials, and examine operating characteristics of the designs through big data and crowd sourcing.