Pilot Investigation of Ultrasound Imaging and Spectroscopy and Ultrasound Imaging of Vascular Blood Flow as Early Indicators of Locally-Advanced Breast Cancer Response to Neoadjuvant Treatment
We have previously demonstrated that high-frequency ultrasound and spectroscopy, and
recently conventional-frequency ultrasound and spectroscopy may be used to detect cell death
in vitro, in situ and in vivo. The method can detect different forms of cell death and has
been demonstrated to be sensitive to apoptotic, necrotic and mitotic cell death. The
objectives of this study are to evaluate the use of ultrasound imaging and spectroscopy as a
predictive marker of advanced tumour response to combined chemotherapy and radiotherapy.
Since neoadjuvant treatments may also act on tumour vasculature to "normalize" it we will
also evaluate blood-vessel imaging by standard Doppler-imaging and with standard
higher-resolution imaging using clinically approved microbubble contrast agents.
The main goal, as described above, is to select the best ultrasound spectroscopy parameter
to use as an early predictor of pathological complete response.
Specifically, we will as a primary endpoint correlate changes in ultrasound backscatter
parameters obtained throughout the course of treatment with pathological complete, partial,
or complete and partial response. We ultimately hope to be able to generate a
Receiver-Operator-Curve for each parameter beyond this pilot investigation. The
ultrasound-spectroscopy parameters to be examined include mid-band fit, spectral-slope and
histogram-distribution-fit parameters related to scatterer size and concentration. From
these various receiver-operator curves the best ultrasound parameter for predicting response
will be selected and will aid to define the clinical specificity and sensitivity of the
The secondary endpoint in this study will include examining the change in size of the
tumour, which will also be measured using conventional gold-standard B-scan ultrasound
imaging (length by width by height in addition to volume) and correlating that to the
spectroscopic ultrasound changes determined at different times during patient treatment.
Other secondary endpoints will include measuring changes in blood vessel distribution by
standard Doppler-imaging and standard microbubble contrast agent imaging. As another
secondary endpoint we will also correlate our ultrasound changes with 2 and 5-year long-term
Observational Model: Case-Only, Time Perspective: Prospective
Gregory J. Czarnota, Ph.D. M.D.
Sunnybrook Health Sciences Centre
Canada: Ethics Review Committee