Monitoring Neoadjuvant Chemotherapy Response in Breast Cancer Patients Using Diffuse Optical Spectroscopic Imaging

Study Overview
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Brief Summary
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This study seeks to enroll women with breast cancer undergoing neoadjuvant chemotherapy to evaluate the efficacy of an investigational imaging technology known as Diffuse Optical Spectroscopy Imaging (DOSI) in predicting patient response to chemotherapy treatment. DOSI is a noninvasive imaging method that uses harmless near-infrared light using simple wearable probes held against the skin by transparent dressings to predict tumor metabolic activity. It uses nonionizing radiation, requires no external contrast agent and uses low light exposure to human tissue. DOSI scans can be performed frequently at the bedside in settings such as a doctor's office or infusion center.

Detailed Description
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This study seeks to enroll women with breast cancer undergoing neoadjuvant chemotherapy to evaluate the efficacy of an investigational imaging technology known as Diffuse Optical Spectroscopy Imaging (DOSI) in predicting patient response to chemotherapy treatment. DOSI is a noninvasive imaging method that uses harmless near-infrared light using simple wearable probes held against the skin by transparent dressings to predict tumor metabolic activity. It uses nonionizing radiation, requires no external contrast agent and uses low light exposure to human tissue. DOSI scans can be performed frequently at the bedside in settings such as a doctor's office or infusion center. DOSI has already shown promise in monitoring breast cancer patients undergoing preoperative chemotherapy. Several groups have demonstrated optical changes predictive of response in the course of weeks to months of treatment. The investigators group has begun to show that DOSI measurements during drug infusions and at early time-points (first 24 hours) correlate with tumor final pathological response. While this data is provocative, significantly more work is needed to confirm that early time-points are predictive in different treatment groups and tumor molecular subtypes. In this study, breast cancer patients will receive DOSI scans at a subset or all of the following time-points: baseline, during drug infusion, early therapy, mid-therapy and post-therapy. DOSI results will be compared to standard of care pathology results determined after surgery. Additionally, the investigators will correlate DOSI parameters with any additional biopsy specimens taken during treatment (typically for patients on adaptive treatment trials). Each DOSI scan will take about 30-60 minutes/ session, although infusion measurements will take longer. DOSI can potentially help doctors to gain information necessary to make evidence-based changes in treatment strategies of individual patients. The investigators long-term goal is to provide oncologists with a relatively simple, risk-free bedside tool that can help predict response early, thereby maximizing therapeutic response and minimizing unnecessary toxicity. A cohort of 10 additional patients with breast cancer who are not receiving neoadjuvant chemotherapy (NAC) who will only be measured at baseline has been created. Complete characterization of baseline properties in patients is essential for understanding subsequent changes from baseline in response to chemotherapy. Adding an additional 10 patients who are not receiving NAC to be enrolled will allow for better characterization of baseline properties, which in turn will allow for a better understanding of the changes in properties seen in those patients who are undergoing NAC.

Official Title
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Monitoring Neoadjuvant Chemotherapy Response In Breast Cancer Patients Using Diffuse Optical Spectroscopic Imaging (DOSI)

Conditions
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Breast Cancer

Intervention / Treatment
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* Device: Diffuse Optical Spectroscopy Imaging (DOSI) - Neoadjuvant Chemo (NAC) Cohort
* Device: Diffuse Optical Spectroscopy Imaging (DOSI) - Non-NAC Cohort


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria for Neoadjuvant Chemo (NAC) Cohort: Female; Diagnosis of invasive breast cancer by clinical breast examination, by standard of care diagnostic imaging, or by initial tissue biopsy; Planned for primary systemic (neoadjuvant) chemotherapy and surgical resection of residual primary tumor following completion of neoadjuvant chemotherapy; Tumor size ≥ 2cm, measured on imaging or estimated by physical exam; Planned definitive breast surgery (mastectomy or lumpectomy/breast conservation) following completion of neoadjuvant therapy; Age 18 years or older; Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2 (Karnofsky performance status ≥ 60%; Adequate organ and marrow function, as defined at Boston Medical Center (BMC); Postmenopausal for a minimum of one year, OR surgically sterile, OR not pregnant, confirmed by a pregnancy test as per institutional standard of care, and willing to use adequate contraception (hormonal or barrier method of birth control; abstinence) for the duration of study participation; Able to understand and willing to sign a written informed consent document and a Health Insurance Portability and Accountability Act (HIPAA) authorization in accordance with institutional guidelines. Inclusion Criteria for Non-NAC Cohort: Female; Diagnosis of invasive breast cancer by clinical breast examination, by standard of care diagnostic imaging, or by initial tissue biopsy; Tumor size ≥2cm, measured on imaging or estimated by physical exam; Planned definitive breast surgery (mastectomy or lumpectomy/breast conservation) following completion of neoadjuvant therapy; Age 18 years or older; ECOG Performance Status ≤ 2 (Karnofsky performance status ≥ 60%; see Appendix II); Adequate organ and marrow function, as defined at BMC; Postmenopausal for a minimum of one year, OR surgically sterile, OR not pregnant, confirmed by a pregnancy test as per institutional standard of care, and willing to use adequate contraception (hormonal or barrier method of birth control; abstinence) for the duration of study participation; Able to understand and willing to sign a written informed consent document and a HIPAA authorization in accordance with institutional guidelines. Exclusion Criteria for All Cohorts: Previous treatment (chemotherapy, radiation, or surgery) to involved breast; Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements; Medically unstable; Under age 18; Pregnant or nursing; Previous malignancy, other than basal cell or squamous cell carcinoma of the skin or in situ carcinoma of the cervix, from which the patient has been disease free for less than 5 years; No contraindications for primary chemotherapy.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Diffuse Optical Spectroscopy Imaging - Neoadjuvant Chemo (NAC) Cohort<br>Diffuse Optical Spectroscopy Imaging (DOSI) at 6 time points. | Device: Diffuse Optical Spectroscopy Imaging (DOSI) - Neoadjuvant Chemo (NAC) Cohort<br>* Subjects will have up to 9 DOSI scans at 6 different time points during the course of their neoadjuvant chemotherapy. The time course of chemotherapy may vary between 3-9 months depending on the type chemotherapy subjects receive. Depending on chemotherapy schedule, subjects may or may not be asked to participate in all the 6 measurement time points. The number of DOSI scans each subject requires will be decided during consent. Each DOSI scan will take about 30-60 minutes, although scans at infusion time point will take longer in total due to repeated or continuous measurements.<br>|
| Experimental: Diffuse Optical Spectroscopy Imaging - Non-NAC Cohort<br>Diffuse Optical Spectroscopy Imaging (DOSI) at 1 time point. | Device: Diffuse Optical Spectroscopy Imaging (DOSI) - Non-NAC Cohort<br>* Subjects will have 1 DOSI scan at baseline. The DOSI scan will take about 30-60 minutes.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Analysis of differences in longitudinal trends of oxyhemoglobin concentration as related to final pathological response | The longitudinal trends of oxyhemoglobin concentration measured over the early time-points (infusion, first 10 days). Differences in these trends will be analyzed to determine if they are prognostic of the final pathologic response (i.e. pathological complete response or non-complete response) of the primary tumor in patients with locally advanced breast cancer. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Analysis of longitudinal trends of other composite DOSI derived parameters (deoxyhemoglobin, total blood volume, oxygen saturation, water, lips concentrations) | The longitudinal trends of other DOSI derived parameters (deoxyhemoglobin, total blood volume, oxygen saturation, water, lips concentrations) measured over the early time-points (infusion, first 10 days), mid therapy, and end therapy time-points. | 6 months | 
| Analysis of composite DOSI derived parameters (deoxyhemoglobin, total blood volume, oxygen saturation, water, lips concentrations) as related to overall pathologic response and to biopsy results | DOSI derived parameters (deoxyhemoglobin, total blood volume, oxygen saturation, water, lips concentrations) as measured immediately prior to a mid-therapy biopsy. These parameters will be correlated to overall pathologic response and to biopsy results. | up to 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diffuse Optical Spectroscopy Imaging (DOSI)