Breast conserving therapy (BCT), lumpectomy and radiation therapy, is a standard of care for early breast cancer. Current practice for assessing surgical margins includes post-operative H&E histology of the surgical specimen as well as intraoperative frozen-section analysis (FSA). However FSA has limitations in sensitivity, destructive effects of freezing on tissue, and increases surgical procedure times. Up to 40% of patients require a second surgery because of positive or close surgical margins. Repeat surgeries can delay adjuvant therapy, increase patient morbidity and increase health care costs. Our hypothesis is that the rate of second surgeries from positive or close margins can be significantly reduced using real-time nonlinear microscopy (multiphoton microscopy) for intraoperative assessment of lumpectomy specimens. We have preliminary data using nonlinear microscopy on freshly excised breast surgical specimens that achieves 95.4% sensitivity and 93.3% specificity for detecting invasive cancer and DCIS versus benign breast tissue, compared with H&E histology in blinded reading by 3 pathologists. This program is a multidisciplinary collaboration between investigators at the Massachusetts Institute of Technology and Departments of Pathology, Radiology and Surgery at Beth Israel Deaconess Medical Center, Harvard Medical School.
Aim 1. This aim will: (1) Develop clinical nonlinear microscopy technology for use in the pathology laboratory. (2) Validate real time nonlinear microscopy margin assessment using simulated lumpectomies from mastectomy specimens. (3) Confirm the exogenous stain used for nonlinear microscopy does not interfere with immunohistochemical assays.
Aim 2. Investigate nonlinear microscopy for intraoperative assessment of surgical specimens and assess impact on the rate of second surgeries. The primary endpoint is the rate of repeat surgeries in a study group with intraoperative margin assessment and standard post- operative histological surgical margin assessment, versus a control group receiving the clinical standard of post-operative histology without intraoperative imaging.
Aim 3. Develop advanced nonlinear microscopy and image processing technology and investigate other cancer pathologies. We will develop advanced methods, such as 3D imaging, multiple contrast channels using selected endogenous or exogenous fluorophores and molecular probes, in addition to image processing and display methods to enhance diagnostic performance or provide quantitative metrics. Pathology imaging will be performed on head and neck, lung and thyroid cancer specimens which may benefit from future intraoperative assessment. If successful, this project could provide an intraoperative pathology imaging technique that could not only significantly reduce the rate of second surgeries in breast cancer lumpectomies, but also have wide spread applications in surgical oncology.

Public Health Relevance

Breast conserving therapy (BCT), lumpectomy and radiation therapy, is a standard of care for early breast cancer, however up to 40% of patients require second surgeries because of cancer on the surgical margin. This program investigates nonlinear microscopy (multiphoton microscopy) as a method for real time imaging of surgical specimens, which could provide intraoperative information and reduce the rate of second surgeries.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
1R01CA178636-01
Application #
8562861
Study Section
Medical Imaging Study Section (MEDI)
Program Officer
Zhang, Yantian
Project Start
2013-09-01
Project End
2018-06-30
Budget Start
2013-09-01
Budget End
2014-06-30
Support Year
1
Fiscal Year
2013
Total Cost
$348,905
Indirect Cost
$95,340
Name
Massachusetts Institute of Technology
Department
None
Type
Organized Research Units
DUNS #
001425594
City
Cambridge
State
MA
Country
United States
Zip Code
02139
Ahsen, Osman O; Lee, Hsiang-Chieh; Giacomelli, Michael G et al. (2014) Correction of rotational distortion for catheter-based en face OCT and OCT angiography. Opt Lett 39:5973-6
Tao, Yuankai K; Shen, Dejun; Sheikine, Yuri et al. (2014) Assessment of breast pathologies using nonlinear microscopy. Proc Natl Acad Sci U S A 111:15304-9