Intraoperative real time breast cancer margin assessment with nonlinear microscop

描述(申请人提供)：保乳治疗(BCT)，肿块切除和放射治疗，是早期乳腺癌的标准护理。目前评估手术切缘的方法包括手术标本的术后HE组织学检查以及术中冰冻切片分析(FSA)。然而，FSA在敏感性、冷冻对组织的破坏性影响以及增加手术时间等方面存在局限性。高达40%的患者需要二次手术，因为手术切缘呈阳性或接近。重复手术可能会推迟辅助治疗，增加患者的发病率，并增加医疗成本。我们的假设是，使用实时非线性显微镜(多光子显微镜)对术中肿瘤切除标本进行评估，可以显著减少来自阳性或接近切缘的二次手术的比率。我们在新切除的乳腺手术标本上使用非线性显微镜获得了初步数据，与3位病理学家盲读的H&E组织学相比，该方法在检测浸润性癌和DCIS与良性乳腺组织的敏感度和特异度分别达到95.4%和93.3%。该项目是麻省理工学院的研究人员与哈佛医学院贝丝以色列女执事医学中心的病理学、放射学和外科系之间的多学科合作。目的1.本研究的目标是：(1)发展临床非线性显微技术，应用于病理实验室。(2)使用模拟乳房切除标本验证实时非线性显微边缘评估。(3)确认用于非线性显微镜的外源染色不干扰免疫组织化学分析。目的2.研究用于术中标本评估的非线性显微镜，并评估其对二次手术率的影响。主要终点是接受术中切缘评估和标准术后组织学手术切缘评估的研究组与接受手术后组织学临床标准而不进行术中成像的对照组的重复手术率。目的3.发展先进的非线性显微镜和图像处理技术，研究其他癌症的病理机制。我们将开发先进的方法，如3D成像、使用选定的内源或外源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成像，这些标本可能会在未来的术中评估中受益。如果成功，该项目可以提供一种术中病理成像技术，不仅可以显著降低乳腺癌肿块切除术的二次手术率，而且在外科肿瘤学中有广泛的应用。

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.