Non-invasive evaluation of breast cancer response to chemotherapy using quantitative ultrasonic backscatter parameters

Tumor response to neoadjuvant chemotherapy in patients (n=30) with locally advanced breast cancer (LABC) was examined using quantitative ultrasound. Three ultrasound backscatter parameters, the integrated backscatter coefficient (IBC), average scatterer diameter (ASD), and average acoustic concentration (AAC), were estimated from tumors prior to treatment and at four times during neoadjuvant chemotherapy treatment (weeks 0, 1, 4, 8, and prior to surgery) and compared to ultimate clinical and pathological tumor responses. Results demonstrated that among all parameters, AAC was the best indicator of tumor response early after starting treatment. The AAC parameter increased substantially in treatment-responding patients as early as one week after treatment initiation, further increased at week 4, and attained a maximum at week 8. In contrast, the backscatter parameters from non-responders did not show any changes after treatment initiation. The two patient populations exhibited a statistically significant difference in changes of AAC (p<0.001) and ASD (p=0.023) over all treatment times examined. The best prediction of treatment response was achieved with the combination of AAC and ASD at week 4 (82% sensitivity, 100% specificity, and 86% accuracy) of 12-18 weeks of treatment. The survival of patients with responsive ultrasound parameters was higher than patients with non-responsive ultrasound parameters (35 ± 11 versus 27 ± 11 months, respectively, p=0.043). This study demonstrates that ultrasound parameters derived from the ultrasound backscattered power spectrum can potentially serve as non-invasive early measures of clinical tumor response to chemotherapy treatments.

[1]  Michael C. Kolios,et al.  Low-frequency quantitative ultrasound imaging of cell death in vivo. , 2013, Medical Physics (Lancaster).

[2]  Gregory J. Czarnota,et al.  Tumor radiation response enhancement by acoustical stimulation of the vasculature , 2012, Proceedings of the National Academy of Sciences.

[3]  Michael C. Kolios,et al.  Quantitative Ultrasound Evaluation of Tumor Cell Death Response in Locally Advanced Breast Cancer Patients Receiving Chemotherapy , 2013, Clinical Cancer Research.

[4]  J. G. Miller,et al.  Interlaboratory comparison of ultrasonic backscatter, attenuation, and speed measurements. , 1999, Journal of ultrasound in medicine : official journal of the American Institute of Ultrasound in Medicine.

[5]  Hany Soliman,et al.  Diffuse optical spectroscopy evaluation of treatment response in women with locally advanced breast cancer receiving neoadjuvant chemotherapy. , 2012, Translational oncology.

[6]  Ronald H. Silverman,et al.  Ultrasonic spectrum analysis for tissue assays and therapy evaluation , 1997, Int. J. Imaging Syst. Technol..

[7]  William D. O'Brien,et al.  Differentiation and characterization of rat mammary fibroadenomas and 4T1 mouse carcinomas using quantitative ultrasound imaging , 2004, IEEE Transactions on Medical Imaging.

[8]  J. Vonesch,et al.  Quantitative ultrasonic tissue characterization as a new tool for continuous monitoring of chronic liver remodelling in mice , 2007 .

[9]  Fiona J Gilbert,et al.  Neoadjuvant chemotherapy in breast cancer: significantly enhanced response with docetaxel. , 2002, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[10]  Jyotsna Sen,et al.  Histopathologic changes following neoadjuvant chemotherapy in various malignancies , 2012, International journal of applied & basic medical research.

[11]  Carlos Caldas,et al.  Analysis of circulating tumor DNA to monitor metastatic breast cancer. , 2013, The New England journal of medicine.

[12]  S M Evans,et al.  Doppler ultrasound imaging detects changes in tumor perfusion during antivascular therapy associated with vascular anatomic alterations. , 2001, Cancer research.

[13]  Michael C. Kolios,et al.  Ultrasonic characterization of whole cells and isolated nuclei. , 2007, Ultrasound in medicine & biology.

[14]  M. Yaffe,et al.  Functional Imaging Using Diffuse Optical Spectroscopy of Neoadjuvant Chemotherapy Response in Women with Locally Advanced Breast Cancer , 2010, Clinical Cancer Research.

[15]  Ali Sadeghi-Naini,et al.  Evaluation of neoadjuvant chemotherapy response in women with locally advanced breast cancer using ultrasound elastography. , 2013, Translational oncology.

[16]  Olsi Rama,et al.  Development of ultrasound tomography for breast imaging: technical assessment. , 2005, Medical physics.

[17]  J W Hunt,et al.  © 1999 Cancer Research Campaign Article no. bjoc.1999.0724 Ultrasound imaging of apoptosis: high-resolution noninvasive , 2022 .

[18]  T. Stein,et al.  Microenvironment of the Involuting Mammary Gland Mediates Mammary Cancer Progression , 2007, Journal of Mammary Gland Biology and Neoplasia.

[19]  Jonathan R Lindner,et al.  Molecular imaging with targeted contrast ultrasound. , 2007, Current opinion in biotechnology.

[20]  Henry M Kuerer,et al.  Locoregional treatment outcomes for inoperable anthracycline-resistant breast cancer. , 2002, International journal of radiation oncology, biology, physics.

[21]  Michael L. Oelze,et al.  Application of Three Scattering Models to Characterization of Solid Tumors in Mice , 2006, Ultrasonic imaging.

[22]  M. Oelze,et al.  Examination of cancer in mouse models using high-frequency quantitative ultrasound. , 2006, Ultrasound in medicine & biology.

[23]  Michael C. Kolios,et al.  Quantitative ultrasound for the monitoring of novel microbubble and ultrasound radiosensitization. , 2012, Ultrasound in medicine & biology.

[24]  F. Foster,et al.  Ultrasonic integrated backscatter coefficient profiling of human coronary arteries in vitro , 2001, IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control.

[25]  M J Yaffe,et al.  Whole‐specimen histopathology: a method to produce whole‐mount breast serial sections for 3‐D digital histopathology imaging , 2007, Histopathology.

[26]  Michael C. Kolios,et al.  Quantitative Ultrasound Characterization of Responses to Radiotherapy in Cancer Mouse Models , 2009, Clinical Cancer Research.

[27]  G. Hortobagyi,et al.  Can early response assessment guide neoadjuvant chemotherapy in early-stage breast cancer? , 2008, Journal of the National Cancer Institute.

[28]  Michael C. Kolios,et al.  Monitoring of cell death in epithelial cells using high frequency ultrasound spectroscopy. , 2009, Ultrasound in medicine & biology.

[29]  E. Feleppa,et al.  Statistics of ultrasonic spectral parameters for prostate and liver examinations , 1997, IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control.

[30]  E J Feleppa,et al.  Diagnostic spectrum analysis in ophthalmology: a physical perspective. , 1986, Ultrasound in medicine & biology.

[31]  L. Esserman,et al.  MRI measurements of breast tumor volume predict response to neoadjuvant chemotherapy and recurrence-free survival. , 2005, AJR. American journal of roentgenology.

[32]  S. Giordano,et al.  Update on locally advanced breast cancer. , 2003, The oncologist.

[33]  E J Feleppa,et al.  Comparison of theoretical scattering results and ultrasonic data from clinical liver examinations. , 1988, Ultrasound in medicine & biology.

[34]  Kevin Brindle,et al.  New approaches for imaging tumour responses to treatment , 2008, Nature Reviews Cancer.

[35]  L. X. Yao,et al.  Backscatter Coefficient Measurements Using a Reference Phantom to Extract Depth-Dependent Instrumentation Factors , 1990, Ultrasonic imaging.

[36]  Mark R Holland,et al.  Characterization of Anisotropic Myocardial Backscatter Using Spectral Slope, Intercept and Midband Fit Parameters , 2007, Ultrasonic imaging.

[37]  William D O'Brien,et al.  Characterization of tissue microstructure using ultrasonic backscatter: theory and technique for optimization using a Gaussian form factor. , 2002, The Journal of the Acoustical Society of America.

[38]  T J Hall,et al.  Parametric Ultrasound Imaging from Backscatter Coefficient Measurements: Image Formation and Interpretation , 1990, Ultrasonic imaging.

[39]  Michael C. Kolios,et al.  Ultrasound imaging of apoptosis in tumor response: novel preclinical monitoring of photodynamic therapy effects. , 2008, Cancer research.

[40]  Ernest J. Feleppa,et al.  Ultrasonic spectral-parameter imaging of the prostate , 1997, Int. J. Imaging Syst. Technol..

[41]  J Perrin,et al.  Global breast attenuation:control group and benign breast diseases. , 1990, Ultrasonic imaging.

[42]  Michael C. Kolios,et al.  Quantitative ultrasound characterization of cancer radiotherapy effects in vitro. , 2008, International journal of radiation oncology, biology, physics.

[43]  S Charrier,et al.  Clinical and pathological response to primary chemotherapy in operable breast cancer. , 1997, European journal of cancer.