Intraoperative real time breast cancer margin assessment with nonlinear microscop

描述（由申请人提供）：保乳治疗（BCT）、乳房肿瘤切除术和放射治疗是早期乳腺癌的标准治疗。目前用于评估手术切缘的实践包括手术标本的术后H&E组织学以及术中冰冻切片分析（FSA）。然而，FSA在灵敏度、冷冻对组织的破坏性影响以及增加外科手术时间方面具有局限性。高达40%的患者需要第二次手术，因为积极或关闭手术切缘。重复手术会延迟辅助治疗，增加患者发病率并增加医疗保健费用。我们的假设是，使用实时非线性显微镜（多光子显微镜）对乳房肿瘤切除术标本进行术中评估，可以显著降低阳性或接近切缘的二次手术率。我们有初步的数据，使用非线性显微镜对新鲜切除的乳腺手术标本，达到95.4%的敏感性和93.3%的特异性检测浸润性癌和DCIS与良性乳腺组织，相比H&E组织学在盲阅读由3名病理学家。该项目是马萨诸塞州理工学院的研究人员与哈佛医学院贝斯以色列女执事医疗中心的病理学、放射学和外科学部门之间的多学科合作。目标1.这一目标将：（1）发展临床非线性显微镜技术用于病理实验室。(2)使用来自乳房切除术标本的模拟乳房肿块切除术的实时真实的非线性显微镜边缘评估。(3)确认用于非线性显微镜检查的外源性染色剂不会干扰免疫组织化学测定。目标二。研究用于手术标本术中评估的非线性显微镜，并评估对二次手术率的影响。主要终点是研究组（进行术中切缘评估和标准术后组织学手术切缘评估）与对照组（接受临床标准术后组织学检查，未进行术中成像）的重复手术率。目标3。开发先进的非线性显微镜和图像处理技术，并研究其他癌症病理。我们将开发先进的方法，如3D成像，使用选定的内源性或外源性荧光团和分子探针的多个对比通道，以及图像处理和显示方法，以提高诊断性能或提供定量指标。将对头颈部、肺癌和甲状腺癌标本进行病理学成像，这些标本可能受益于未来的术中评估。如果成功，该项目可以提供一种术中病理成像技术，不仅可以显着降低乳腺癌肿块切除术中的二次手术率，而且还可以在外科肿瘤学中广泛应用。

DESCRIPTION (provided by applicant): 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.