SBIR-STTR Award

In 2005, 72,000 women that underwent breast surgery had to have a second re-excision surgery due to incomplete removal of the cancer during the first surgery. Needing a second surgery means increased cancer recurrence, patient anxiety, complications, and cost. Currently, surgeons have no readily available, cost efficient, intraoperative instruments that ensure that the cancer has been completely excised to prevent re-excision. To improve care, surgeons are seeking real time information on the tumor margins at the site of excision. Prior intraoperative solutions (frozen section and cytology) to prevent re-excision have not been adopted because they required a pathologist in the O.R., take too long during surgery, and only examine less than 1% of the tumor margin. Our long-term objective is to develop a chemically specific and quantitative multi-channel optical assay device for intraoperative assessment of tumor margins in patients undergoing breast conserving surgery (lumpectomy). The optical device will provide non-destructive evaluation of approximately 80% of the tumor margin in the excised specimen (as opposed to 1% provided by touch prep or frozen section); require no specialized personnel or sample processing (cutting and staining); and will require considerably less time than conventional techniques. The goal of the work is to design, fabricate and evaluate a single- channel alpha version of the optical assay device that will provide point measurements, and conduct a pilot clinical study on ex vivo breast tissues to demonstrate the feasibility and effectiveness of our novel technology. The specific aims are to: (1) design and optimize a single-channel optical device using Monte Carlo simulations; (2) build an alpha prototype device based on the simulations, and (3) validate the device's performance against a standard bench- top optical system on synthetic breast tissue phantoms, and determine the sensitivity and specificity on excised human breast tissue specimens in a pilot clinical study. Concurrent with this effort, we are recruiting expertise in management, regulatory and reimbursement strategies so that we will be well positioned to bring this device to market following completion of the R&D program. This device will have significant clinical benefits including: (1) reduced repeat surgeries and hence, reduced local recurrence, (2) reduced tissue removal, which translates to cosmetically-superior lumpectomies at the time of the first surgery, (3) reduced emotional distress, (4) reduced complications due to reduced number of surgeries and shorter recovery times for the patient and (5) reduced cost for the patient and the healthcare system. Successful completion of this project will set the foundation for the development of a fast, multi-pixel optical assay system for intraoperative assessment of tumor margins in patients undergoing breast cancer surgery. The optical assay system will have significant clinical benefits including: (1) reduced re-excision rates, (2) reduced tissue removal, which translates to cosmetically-superior lumpectomies at the time of the first surgery, (3) better margin assessment leading to reduced repeat surgeries and hence, reduced local recurrence, (4) reduced emotional distress, and (5) reduced complications due to reduced number of surgeries and shorter recovery times for the patient.

The American Cancer Society estimates that a total of 240,430 new breast cancers were diagnosed in 2007 (178,400 new cases of invasive breast cancer, and 62,030 new cases of in situ breast cancer). Approximately 180,000 of these patients undergo breast conserving surgery (BCS), also called lumpectomy. Multiple recent studies show that a staggering 20-70% of the 180,000 patients (45% or ~81,000 women on average) have to return for a repeat surgery due to incomplete removal of the cancer at the first BCS. The long-term objective of this research is the market introduction of a clinically useful, intra-operative device for breast tumor margin assessment. The objective of the proposed research is to develop a clinical-trial-ready device and to evaluate its practical utility as a routinely used intra-operative tool. The specific aims of the proposed work are: (1) to design, fabricate and characterize a multi-channel optical spectral imaging system that will provide two- dimensional measurements from a depth of up to 2 mm within breast tissues in order to detect close and positive tumor margins in freshly excised lumpectomy specimens, (2) to perform a verification study of the device design specifications on tissue phantoms and (3) to perform a critical evaluation of the device in a practical clinical setting. The proposed technology will be a multi-channel optical assay device for intraoperative imaging of margins in specimens excised from patients undergoing breast conserving surgery (partial mastectomy). It is theorized that this optical assay system will help guide the surgeon to either complete the surgery, when margins are negative, or re-excise additional tissue, when margins are positive. The proposed clinical study will serve as an important database for future technological developments related to effective intra-operative assessment of tumor margins in patients with breast cancer. Successful completion of the long-term objectives of this research will result in significant benefits to breast cancer patients (preventing tens of thousands of unnecessary surgeries each year) as well as surgeons, hospitals, and health-care providers. The technology proposed in this research could also potentially be utilized in the assessment of tumor margins in patients with other types of cancers, widening the potential health impact of the research.

Public Health Relevance:
The goal of this STTR proposal is to develop a non-invasive multi-channel optical assay device for intra-operative imaging of tumor margins in tissue specimens excised from patients undergoing breast conserving cancer surgery. The proposed research is significantly relevant to public health due to the potential to contribute to the reduction of tens of thousands of unnecessary breast re-excision surgeries each year, and the corresponding lowered risk of local recurrence in patients with invasive and non-invasive breast malignancies who have their cancer fully removed in the first surgery.

Thesaurus Terms:
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