Early differentiating between the chemotherapy responders and nonresponders: Preliminary results with ultrasonic spectrum analysis of the RF time series in preclinical breast cancer models

Abstract

Background: This study was aimed to assess whether ultrasonic spectrum analysis of radiofrequency (RF) time series using a clinical ultrasound system allows for early differentiating between the chemotherapy responders and nonresponders in human breast cancer xenografts that imitate clinical responding and nonresponding tumors. Methods: Clinically responding (n = 20; MCF-7) and nonresponding (n = 20; MBA-MD-231) breast cancer xenografts were established in 40 nude mice. Ten mice from each group received either chemotherapy (adriamycin, 4 mg/kg) or saline as controls. Each tumor was imaged longitudinally with a clinical ultrasound scanner at baseline (day 0) and subsequently on days 2, 4, 6, 8 and 12 following treatment, and the corresponding RF time-series data were collected. Changes in six RF time-series parameters (slope, intercept, S1, S2, S3 and S4) were compared with the measurement of the tumor cell density, and their differential performances of the treatment response were analyzed. Results: Adriamycin significantly inhibited tumor growth and decreased the cancer cell density in responders (P < 0.001) but not in nonresponders (P > 0.05). Fold changes of slope were significantly increased in responders two days after adriamycin treatment (P = 0.002), but not in nonresponders (P > 0.05). Early changes in slope on day 2 could differentiate the treatment response in 100% of both responders (95% CI, 62.9-100.0%) and nonresponders (95% CI, 88.4-100%). Conclusions: Ultrasonic RF time series allowed for the monitoring of the tumor response to chemotherapy and could further serve as biomarkers for early differentiating between the treatment responders and nonresponders.