Early Changes in Quantitative Ultrasound Imaging Parameters during Neoadjuvant Chemotherapy to Predict Recurrence in Patients with Locally Advanced Breast Cancer

SIMPLE SUMMARY: Patients diagnosed with breast cancer treated with chemotherapy before surgery were included in this study. The tumor was imaged using ultrasound before the chemotherapy was started and in the middle of chemotherapy treatment (one month after starting). After treatment completion, patients were followed up according to standard clinical practice and categorized into two groups based on disease recurrence until the last follow-up. The ultrasound imaging was analyzed using advanced computational techniques, and artificial intelligence was used to develop models to differentiate between the two outcomes. We demonstrated that using the ultrasound image data, the final outcomes can be predicted as early as within one month of the start of chemotherapy. ABSTRACT: Background: This study was conducted to explore the use of quantitative ultrasound (QUS) 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-Tex(1)) 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-Tex(1)-Tex(2)), leading to a total of 95 features from each time point. 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-Tex(1)), and texture derivatives (QUS-Tex(1)-Tex(2)) of week 4 data and week 0 data. Patients were divided into two groups: recurrence and non-recurrence. Machine learning algorithms using k-nearest neighbor (k-NN) and support vector machines (SVMs) were used to generate radiomic models. Internal validation was undertaken using leave-one patient out cross-validation method. 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-Tex(1)-Tex(2)) in week 4 QUS data analysis led to the improvement of the classifier performances. The AUC increased from 0.70 (0.59 to 0.79, 95% confidence interval) without texture derivatives to 0.83 (0.73 to 0.92) with texture derivatives. The most relevant features separating the two groups were higher-order texture derivatives obtained from scatterer diameter and acoustic concentration-related parametric images. Conclusions: 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.