There is considerable interest in developing new quantitative imaging methods to monitor and predict breast cancer response to neoadjuvant chemotherapy, both prior to and as early as possible during the course of treatment. Diffuse optical spectroscopic imaging (DOSI) allows patients to be followed from baseline through treatment and surgery with a cost-effective, bedside, handheld scanning probe. In this work, we propose to significantly advance the development of harmonized DOSI technology platform and evaluate its performance in five clinical sites on up to 90 neoadjuvant chemotherapy patients. In preliminary patient studies, DOSI quantitative functional endpoints have been shown to be effective in predicting tumor response to chemotherapy within the first week of a two - four month treatment regimen. In the proposed work we will optimize and improve DOSI functionality, standardize clinical measurement and analysis procedures, and evaluate whether DOSI can be used with equivalent overall performance by different operators. Our long-term goal is to identify quantitative clinical endpoints that can be used to inform medical decisions on chemotherapy regimen, duration, and timing of surgery. These non-invasive endpoints are obtained rapidly with no risk/discomfort and could be used as surrogate markers of pathologic response, an established indicator of long-term survival. An archived database of breast cancer spectroscopic markers will be made available to the research community in order to further facilitate new technology development and enhance our understanding of breast cancer chemotherapy. Few technologies have bridged the gap between laboratory prototype and clinically disseminated cancer imaging system. We are now poised to make this transition by creating a standardized and validated DOSI platform, necessary next steps in the translational research process. Ultimately this work is expected to lead to a bedside optical imaging technology that can be used to improve patient outcome by maximizing therapeutic response, minimizing unnecessary toxicity, and optimizing clinical decision-making.

Public Health Relevance

We propose to advance the development of a portable, bedside optical imaging technology capable of monitoring and predicting patient response to breast cancer neoadjuvant chemotherapy. The technology, Diffuse Optical Spectroscopic Imaging (DOSI), will be evaluated in a multi-site study designed to validate optical endpoints of clinical response.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA142989-03
Application #
8207928
Study Section
Biomedical Imaging Technology Study Section (BMIT)
Program Officer
Baker, Houston
Project Start
2010-01-01
Project End
2013-12-31
Budget Start
2012-01-01
Budget End
2013-12-31
Support Year
3
Fiscal Year
2012
Total Cost
$576,227
Indirect Cost
$199,608
Name
University of California Irvine
Department
Type
Organized Research Units
DUNS #
046705849
City
Irvine
State
CA
Country
United States
Zip Code
92697
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Cochran, J M; Chung, S H; Leproux, A et al. (2017) Longitudinal optical monitoring of blood flow in breast tumors during neoadjuvant chemotherapy. Phys Med Biol 62:4637-4653
McLaren, Christine E; Chen, Wen-Pin; O'Sullivan, Thomas D et al. (2017) Sample size and power determination when limited preliminary information is available. BMC Med Res Methodol 17:75
Wright, Heather J; Hou, Jue; Xu, Binzhi et al. (2017) CDCP1 drives triple-negative breast cancer metastasis through reduction of lipid-droplet abundance and stimulation of fatty acid oxidation. Proc Natl Acad Sci U S A 114:E6556-E6565
O'Sullivan, Thomas D; No, Keunsik; Matlock, Alex et al. (2017) Vertical-cavity surface-emitting laser sources for gigahertz-bandwidth, multiwavelength frequency-domain photon migration. J Biomed Opt 22:1-8
Hou, Jue; Wright, Heather J; Chan, Nicole et al. (2016) Correlating two-photon excited fluorescence imaging of breast cancer cellular redox state with seahorse flux analysis of normalized cellular oxygen consumption. J Biomed Opt 21:60503
Tromberg, Bruce J; Zhang, Zheng; Leproux, Anaïs et al. (2016) Predicting Responses to Neoadjuvant Chemotherapy in Breast Cancer: ACRIN 6691 Trial of Diffuse Optical Spectroscopic Imaging. Cancer Res 76:5933-5944
Leproux, Anaïs; Kim, You Me; Min, Jun Won et al. (2016) Differential diagnosis of breast masses in South Korean premenopausal women using diffuse optical spectroscopic imaging. J Biomed Opt 21:74001
O'Sullivan, Thomas D; Leproux, Anaïs; Chen, Jeon-Hor et al. (2013) Optical imaging correlates with magnetic resonance imaging breast density and reveals composition changes during neoadjuvant chemotherapy. Breast Cancer Res 15:R14
Roblyer, Darren; O'Sullivan, Thomas D; Warren, Robert V et al. (2013) Feasibility of Direct Digital Sampling for Diffuse Optical Frequency Domain Spectroscopy in Tissue. Meas Sci Technol 24:045501

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