Monitoring and Predicting Chemotherapy Response Using DOSI

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.

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.