Monitoring and Predicting Chemotherapy Response Using DOSI

Study Overview
=================
Brief Summary
-----------------
RATIONALE: New imaging procedures, such as diffuse optical spectroscopy imaging, may help measure a patient's response and allow doctors to plan better treatment. PURPOSE: This clinical trial studies diffuse optical spectroscopy imaging in monitoring and predicting response in patients with locally advanced breast cancer undergoing chemotherapy before surgery.

Detailed Description
-----------------
OBJECTIVES: Primary To determine whether the percentage change in the diffuse optical spectroscopy imaging (DOSI) measurement of the tumor/normal (T/N) tissue optical index (TOI) from baseline to mid-therapy is predictive of the final pathologic response of the primary tumor in patients with locally advanced breast cancer treated with neoadjuvant chemotherapy. Secondary To investigate whether change of TOI measurements from baseline to post-therapy are predictive of the final pathologic response in these patients treated with this regimen. To investigate whether baseline TOI measurements are associated with final pathologic response in patients treated with this regimen. To investigate whether TOI measurements at baseline, change from baseline to mid-therapy, and change from baseline to post-therapy correlate with available MRI volumetric imaging measurements. To investigate whether changes on TOI measurements from baseline to mid-therapy, and from baseline to post-therapy, correlate with other standard-of-care imaging and/or any MRI-imaging measurements. To explore whether additional optical endpoints and indices obtained during DOSI measurements can be used to predict final pathologic response in patients treated with this regimen. To determine a cutpoint for the percent change of TOI from baseline to mid-therapy that is predictive of pathological complete response in patients treated with this regimen. OUTLINE: This is a multicenter study. Patients undergo diffuse optical spectroscopy imaging (DOSI) at baseline, 5-10 days after initiation of neoadjuvant chemotherapy, during early- and mid-neoadjuvant therapy, and within 21 days after completion of neoadjuvant therapy. Results are compared to standard-of-care imaging (e.g., MRI, ultrasound, mammography). Patients then undergo surgery.

Official Title
-----------------
Diffuse Optical Spectroscopy Imaging in Monitoring and Predicting Response in Patients With Locally Advanced Breast Cancer Undergoing Chemotherapy Before Surgery

Conditions
-----------------
Breast Cancer

Intervention / Treatment
-----------------
* Procedure: DOSI


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria Pathologically confirmed diagnosis of invasive breast cancer, determined to be a candidate for primary systemic (neoadjuvant) therapy and for surgical resection of residual primary tumor following completion of neoadjuvant therapy; Tumor size >2cm, measured on imaging or estimated by physical exam; No contraindications for primary chemotherapy; Planned definitive breast surgery (mastectomy or lumpectomy/breast conservation) following completion of neoadjuvant therapy; Age 18 years or older; ECOG Performance Status ≤ 2 (Karnofsky ≥ 60%; see Appendix II); Normal organ and marrow function as follows: leukocytes ≥ 3,000/μl; absolute neutrophil count ≥ 1,500/μl; platelets ≥ 100,000/μl; total bilirubin within normal institutional limits; AST(SGOT)/ALT(SGPT) ≤ 2.5 times the institutional upper limit of normal; creatinine within normal institutional limits; OR creatinine clearance ≥ 30 mL/min/1.73 m2 for patients with creatinine levels above institutional normal; If female, postmenopausal for a minimum of one year, OR surgically sterile, OR not pregnant, confirmed by a pregnancy test as per institutional Standard of Care (SOC), 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 Previous treatment (chemotherapy, radiation, or surgery) to involved breast; including hormone therapy; 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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: DOSI Pre-Surgery<br>Participants undergo approximately four assessments of breast health using the DOSI technology during treatment and prior to surgery for breast cancer. | Procedure: DOSI<br>* Bedside DOSI images of the tissue concentrations of deoxy-hemoglobin (ctHHb), oxy-hemoglobin (ctHbO2), water (ctH2O), lipid, tissue oxygen saturation (StO2), and TOI (ctHHb x tH2O/lipid) were acquired on both breasts up to four times during neoadjuvant chemotherapy (NAC) treatment.<br>* Other names: Optical Breast Imaging;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Accuracy of %Change in TOI Between Baseline and Mid-therapy to Predict Pathologic Response (pCR +/-) | This measure will look at the Accuracy of % change in DOSI measured Tumor Optical Index (TOI) from baseline to mid therapy to predict pathologic response (pCR+ v pCR-) Pathologic response (dichotomized into responders (pCR+) and non-responders (pCR-) based pathologic assessment) will be used as the reference standard and Accuracy will be determined using receiver operating characteristic (ROC) analysis to determine the ROC Area Under the Curve (AUC). | From baseline to mid-therapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| %Change in TOI Between Baseline and Mid-therapy to Predict pCR+; Stratified by Progesterone Receptor (PR) Status (Positive, Negative, Unknown ) | Pathologic Complete response vs Non-Complete response, by PR status Progesterone Receptor Status (positive, negative, unknown ) is determined at pathological assessment of the tumor sample. %change in TOI is evaluated from baseline to mid-therapy. | baseline to mid-therapy | 
| Accuracy of %Change in TOI Between Baseline and Mid-therapy to Predict pCR+; Stratified by Oxygen Saturation (St02) | subset analysis, subjects were stratified using the median tumor StO2 %change TOI Between Baseline and Mid-therapy dichotomized at -40% stratified by the set evaluable subjects with baseline tumor StO2 dichotomized at 76.9%. (i.e. population median). Accuracy will be determined using ROC analysis to determine the ROC Area Under the Curve (AUC). | baseline to mid-therapy | 
| Estimate the Optimal Cutpoint for %Change in TOI From Baseline to Mid-therapy to Predict pCR | Determine the optimal cutpoint (aka Youden-index) for %Change in TOI ratio (T/N) to maximize sensitivity and specificity in the predication of pCR | baseline to mid-therapy | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
stage IIIA breast cancer, stage IIIB breast cancer, stage IIIC breast cancer