Quantitative Ultrasound Evaluation of Tumor Cell Death Response in Locally Advanced Breast Cancer Patients Receiving Chemotherapy

Abstract

Purpose: Quantitative ultrasound techniques have been recently shown to be capable of detecting cell death through studies conducted on in vitro and in vivo models. This study investigates for the first time the potential of early detection of tumor cell death in response to clinical cancer therapy administration in patients using quantitative ultrasound spectroscopic methods.Experimental Design: Patients (n ¼ 24) with locally advanced breast cancer received neoadjuvant chemotherapy treatments. Ultrasound data were collected before treatment onset and at 4 times during treatment (weeks 1, 4, and 8, and preoperatively). Quantitative ultrasound parameters were evaluated for clinically responsive and nonresponding patients.Results: Results indicated that quantitative ultrasound parameters showed significant changes for patients who responded to treatment, and no similar alteration was observed in treatment-refractory patients. Such differences between clinically and pathologically determined responding and nonresponding patients were statistically significant (P < 0.05) after 4 weeks of chemotherapy. Responding patients showed changes in parameters related to cell death with, on average, an increase in mid-band fit and 0-MHz intercept of 9.1 AE 1.2 dBr and 8.9 AE 1.9 dBr , respectively, whereas spectral slope was invariant. Linear discriminant analysis revealed a sensitivity of 100% and a specificity of 83.3% for distinguishing nonresponding patients by the fourth week into a course of chemotherapy lasting several months.Conclusion: This study reports for the first time that quantitative ultrasound spectroscopic methods can be applied clinically to evaluate cancer treatment responses noninvasively. The results form a basis for monitoring chemotherapy effects and facilitating the personalization of cancer treatment.

Multiparametric Monitoring of Chemotherapy Treatment Response in Locally Advanced Breast Cancer Using Quantitative Ultrasound and Diffuse Optical Spectroscopy

“…Earlier reports from our group have indicated that QUS and DOS imaging as independent modalities, may be useful for monitoring treatment response [20,21,36]. A study by Soliman et al studied 10 patients with DOSI, and reported a significant decrease in DOSI parameters such as oxyhemoglobin, deoxy-hemoglobin and scatter power after four weeks of treatment for responders [36].…”

“…Theoretical frameworks in these early QUS studies for cancer imaging have driven efforts to study chemotherapy response in breast cancer in vivo [20,29]. To date, QUS has been demonstrated for functional imaging to monitor treatment response in photodynamic therapy, chemotherapy, and radiation therapy; both in animal and human studies [20,25,[29][30][31][32].…”

“…There is recent evidence to suggest that imaging markers from quantitative ultrasound (QUS) and diffuse optical spectroscopy imaging (DOSI) can reflect early biological response to chemotherapy. Previous studies have monitored treatment using either QUS or DOSI individually, using both laboratory or commercially based imaging devices [20][21][22][23]. Both QUS and DOS imaging modalities have the advantage of being non-invasive, relatively cost effective, quick, and provide functional information about metabolism, physiology, and biological activity.…”

Multidimensional Texture Analysis for Improved Prediction of Ultrasound Liver Tumor Response to Chemotherapy Treatment

“…This heterogeneity in tumor tissue scatterers could span different scatterer densities. Regions within the tumor tissue that respond to treatment exhibit different statistical properties to that of the non-respondent counterpart [2][3][4]6]. Thus it is essential to improve the discriminative abilities of the employed statistical distribution model for better characterization of tumor heterogeneity.…”

“…Others relied on calculating the power spectrum from the Fourier transform of raw RF data, and subsequently deriving the spectral slope, 0-MHz intercept, and mid-band fit quantitative parameters [2]. In another similar work, the maximum mean discrepancy features were extracted on histograms of quantitative ultrasound spectroscopic parametric maps [4].…”