4D subharmonic aided pressure estimation for monitoring neoadjuvant chemotherapy response of breast cancer

Neoadjuvant chemotherapy is standard of care for localized breast. The patient response to neoadjuvant chemotherapy correlates with survival and early response assessment is therefore beneficial. The purpose of this study was to determine if 4D subharmonic aided pressure estimation (SHAPE) can predict the response of breast cancer to neoadjuvant chemotherapy based on changes in interstitial fluid pressure and breast tumor vascularity. Seventeen patients scheduled for neoadjuvant therapy of a breast cancer underwent 4 ultrasound exams: prior to therapy, at 10%, 60%, and 100% completion of chemotherapy. Ultrasound exams were performed using a modified Logiq 9 scanner with a 4D10L probe (GE Healthcare, Milwaukee, WI, USA). Modified software enabled the collection of radiofrequency data from 4D pulse inversion subharmonic imaging (transmitting at 5.8 MHz and receiving at 2.9 MHz) before and during a continuous infusion of Definity (Lantheus Medical Imaging, N Billerica, MA, USA) at acoustic settings optimized for SHAPE. The ratios of maximum subharmonic magnitude acquired during infusion relative to unenhanced signals were calculated offline in the tumor and surrounding areas for all 4 exams. The difference between ratios in the tumor and the surrounding area were then compared to the final tumor treatment response. Four patients left the study and 2 patients' data were discarded. Patients' clinical outcomes consisted of 6 responders (tumor volume reduction > 90%) and 5 partial/non responders. The results from 10% completion of therapy showed the subharmonic signal increased more in the tumor than in the surrounding area for responders compared to partial/non responders (3.23 ± 1.41 dB vs. −0.88 ± 1.46 dB; p = 0.001). Moreover, 3 patients whose tumor size initially increased during therapy were correctly predicted by SHAPE to be responders. In conclusion, SHAPE has the potential to predict the neoadjuvant chemotherapy response of breast cancer as early as at 10% completion of the therapy; albeit based on a small sample size.