Dynamic characterization of breast cancer response to neoadjuvant therapy using biophysical metrics of spatial proliferation

Current tools to assess breast cancer response to neoadjuvant chemotherapy cannot reliably predict disease eradication, which if possible, could allow early cessation of therapy. In this work, we assessed the ability of an image data-driven mathematical modeling approach for dynamic characterization of breast cancer response to neoadjuvant therapy. We retrospectively analyzed patients enrolled in the I-SPY 2 TRIAL at the Atrium Health Wake Forest Baptist Comprehensive Cancer Center. Patients enrolled on the study received four MR imaging examinations during neoadjuvant therapy with acquisitions at baseline (T(0)), 3-weeks/early-treatment (T(1)), 12-weeks/mid-treatment (T(2)), and completion of therapy prior to surgery (T(3)). We use a biophysical mathematical model of tumor growth to generate spatial estimates of tumor proliferation to characterize the dynamics of treatment response. Using histogram summary metrics to quantify estimated tumor proliferation maps, we found strong correlation of mathematical model-estimated tumor proliferation with residual cancer burden, with Pearson correlation coefficients ranging from 0.88 and 0.97 between T(0) and T(2), representing a significant improvement from conventional assessment methods of change in mean apparent diffusion coefficient and functional tumor volume. This data shows the significant promise of imaging-based biophysical mathematical modeling methods for dynamic characterization of patient-specific response to neoadjuvant therapy with correlation to residual disease outcomes.