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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

Open (Enrolling)
Locally Advanced Breast Cancer

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Trial Information

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
clinical outcome.

Inclusion Criteria:

The following criteria are necessary for study participation:

1. Histologically or cytologically confirmed locally advanced breast carcinoma which has
not been treated with any first-line therapy and will be treated with neoadjuvant
chemotherapy or neoadjuvant combined chemo-radiotherapy

2. Measurable disease by ultrasound, or MRI performed within 28 days prior to treatment

3. Eastern Co-operative Oncology Group (ECOG) Performance Status of 0 or 1.

4. Life expectancy of at least 6 months

5. Adequate bone marrow, liver and renal function as assessed by the following
laboratory requirements to be conducted within 7 days prior to dosing:

- hemoglobin >90 mg/dL

- leukocytes >3,000/mL

- absolute neutrophil count >1,500/mL

- platelets >100,000/mL

- total bilirubin within normal institutional limits

- AST(SGOT)/ALT(SGPT) <2.5 X institutional upper limit of normal

- creatinine within normal institutional limits or creatinine clearance >60
mL/min/1.73 m2 for patients with creatinine levels above institutional upper
limit of normal

6. Patients should have the ability to understand and the willingness to sign a written
informed consent document. Signed informed consent must be obtained prior to any
study specific procedures

Exclusion Criteria:

The following conditions will exclude women from participation:

1. Chemotherapy, radiotherapy, or major surgery within 4 prior to registering the study
or those who have not recovered from adverse events due to agents administered more
than 4 weeks prior to registration

2. Receiving any other investigational agents

3. Known brain metastases

4. History of allergic reactions attributed to compounds of similar chemical or biologic

5. Contraindications to radiotherapy such as but not limited to:

- previous radiotherapy to an involved area

- active collagen vascular disease

- genetic diseases associated with hyper-radiosensitivity

6. Any clinically serious infections requiring systemic anti-bacterial, antifungal or
antiviral therapy

7. Uncontrolled intercurrent illness including, but not limited to ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, and
cardiac arrhythmia

8. Psychiatric illness/social situations that would limit compliance with study

9. History of active ongoing seizure disorder

10. Substance abuse, medical, psychological or social conditions that may interfere with
the patient's participation in the study or evaluation of the study results

11. Any condition that is unstable or could jeopardize the safety of the patient and
their compliance in the study.

Type of Study:


Study Design:

Observational Model: Case-Only, Time Perspective: Prospective

Principal Investigator

Gregory J. Czarnota, Ph.D. M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

Sunnybrook Health Sciences Centre


Canada: Ethics Review Committee

Study ID:




Start Date:

January 2007

Completion Date:

September 2013

Related Keywords:

  • Locally Advanced Breast Cancer
  • Breast Cancer
  • Ultrasound
  • Breast Neoplasms