Early changes in quantitative ultrasound imaging parameters during neoadjuvant chemotherapy to predict recurrence in patients with locally advanced breast cancer

Background: This study was conducted in order to explore the use of quantitative ultrasound (QUS) based higher-order texture derivatives in predicting recurrence for patients with locally advanced breast cancer (LABC) early during neoadjuvant chemotherapy (NAC). Methods: Eighty-three patients with LABC were scanned with 7 MHz ultrasound before starting NAC (week 0) and during treatment (week 4). Spectral parametric maps were generated corresponding to tumor volume. Twenty-four textural features (QUS-Tex1) were determined from parametric maps acquired using grey-level co-occurrence matrices (GLCM) for each patient, which were further processed to generate 64 texture derivatives (QUS-Tex1-Tex2), leading to a total of 95 features from each time points. Analysis was carried out on week 4 data and compared to baseline (week 0) data. ∆Week 4 data was obtained from the difference in QUS parameters, texture features (QUS-Tex1), and texture derivatives (QUS-Tex1-Tex2) of week 4 data and week 0 data. Patients were divided into two groups based on their clinical status: recurrence and no-recurrence. Machine learning algorithms using k-nearest neighbor (k-NN) and support vector machines (SVM) were used to generate radiomic models. Results: With a median follow up of 69 months (range 7-118 months), 28 patients had disease recurrence. The k-NN classifier was the best performing algorithm at week 4 with sensitivity, specificity, accuracy, and area under curve (AUC) of 87%, 75%, 81%, and 0.83, respectively. The inclusion of texture derivatives (QUS-Tex1-Tex2) in week 4 QUS data analysis led to the improvement of the classifier performances. The AUC increased significantly from 0.70 (without texture derivatives) to 0.83 (with texture derivatives). The most relevant features in separating the two groups were higher-order texture derivatives obtained from scatterer diameter and acoustic concentration-related parametric images. Conclusion: This is the first study highlighting the utility of QUS radiomics in the prediction of recurrence during the treatment of LABC. It reflects that the ongoing treatment-related changes can predict clinical outcomes with higher accuracy as compared to pretreatment features alone. Clinical Trial Registration: ClinicalTrials.gov Identifier: NCT00437879 .Registry name: Clinicaltrials.gov.Date of registration: 20th February 2007URL: https://clinicaltrials.gov/ct2/show/study/NCT00437879