A priori prediction of response in multicentre locally advanced breast cancer (LABC) patients using quantitative ultrasound and derivative texture methods

Purpose: We develop a multi-centric response predictive model using QUS spectral parametric imaging and novel texture-derivate methods for determining tumour responses to neoadjuvant chemotherapy (NAC) prior to therapy initiation. Materials and Methods: QUS Spectroscopy provided parametric images of mid-band-fit (MBF), spectral-slope (SS), spectral-intercept (SI), average-scatterer-diameter (ASD), and average-acoustic-concentration (AAC) in 78 patients with locally advanced breast cancer (LABC) undergoing NAC. Ultrasound radiofrequency data were collected from Sunnybrook Health Sciences Center (SHSC), University of Texas MD Anderson Cancer Center (MD-ACC), and St. Michaels Hospital (SMH) using two different systems. Texture analysis was used to quantify heterogeneities of QUS parametric images. Further, a second-pass texture analysis was applied to obtain texture-derivate features. QUS, texture- and texture-derivate parameters were determined from both tumour core and a 5-mm tumour margin and were used in comparison to histopathological analysis for developing a response predictive model to classify responders versus non-responders. Model performance was assessed using leave-one-out cross-validation. Three standard classification algorithms including a linear discriminant analysis (LDA), k-nearest-neighbors (KNN), and support vector machines-radial basis function (SVM-RBF) were evaluated. Results: A combination of tumour core and margin classification resulted in a peak response prediction performance of 88% sensitivity, 78% specificity, 84% accuracy, 0.86 AUC, 84% PPV, and 83% NPV, achieved using the SVM-RBF classification algorithm. Other parameters and classifiers performed less well running from 66% to 80% accuracy. Conclusions: A QUS-based framework and novel texture-derivative method enabled accurate prediction of responses to NAC. Multi-centric response predictive model provides indications of the robustness of the approach to variations due to different ultrasound systems and acquisition parameters.