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

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 0.05). 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.

Keywords

• Ultrasonic RF time series
• Chemotherapy
• Treatment response