Predicting the Response of Breast Cancer to Neoadjuvant Therapy Using a Mechanically Coupled Reaction-Diffusion Model

摘要

While there is considerable data on the use of mathematical modeling to describe tumor growth and response to therapy, previous approaches are often not of the form that can be easily applied to clinical data to generate testable predictions in individual patients. Thus, there is a clear need to develop and apply clinically-relevant oncological models that are amenable to available patient data and yet retain the most salient features of response prediction. In this study we show how a biomechanical model of tumor growth can be initialized and constrained by serial patient-specific magnetic resonance imaging data, obtained at two time points early in the course of therapy (before initiation and following one cycle of therapy), to predict the response for individual patients with breast cancer undergoing neoadjuvant therapy. Using our mechanics coupled modeling approach, we are able to predict, after the first cycle of therapy, breast cancer patients that would eventually achieve a complete pathological response and those who would not, with receiver operating characteristic area under the curve (AUC) of 0.87, sensitivity of 92%, and specificity of 84%. Our approach significantly outperformed the AUCs achieved by standard (i.e., not mechanically coupled)reaction-diffusion predictive modeling (0.75), simple analysis of the tumor cellularity estimated from imaging data (0.73), and the Response Evaluation Criteria in Solid Tumors (RECIST; 0.71). Thus, we show the potential for mathematical model prediction for use as a prognostic indicator of response to therapy. The work indicates the considerable promise of image-driven biophysical modeling for predictive frameworks within therapeutic applications.