Intraoperative real time breast cancer margin assessment with nonlinear microscop

使用非线性显微镜进行术中实时乳腺癌切缘评估

• 批准号: 9513458
• 负责人: James Connolly
• 金额: $ 30.14万
• 依托单位: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-01 至 2020-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9513458
• 关键词: Acridine Orange; Adjuvant Therapy; Benign; Biological Assay; Blinded; Breast; Cellular biology; Clinical; Color; Control Groups; Data; Detection; Diagnostic; Dimensions; Discipline; Fluorescence; Freezing; Frozen Sections; Future; Generations; Head Cancer; Health Care Costs; Histologic; Histology; Image; Image-Guided Surgery; Imaging Techniques; Institutes; Interdisciplinary Study; Israel; Laboratories; Lung; Malignant Neoplasms; Malignant neoplasm of lung; Malignant neoplasm of thyroid; Mammary Gland Parenchyma; Massachusetts; Mastectomy; Measurement; Medical center; Methods; Microscopy; Molecular Probes; Morbidity - disease rate; Neck Cancer; Neurosciences; Noninfiltrating Intraductal Carcinoma; Nuclear; Operative Surgical Procedures; Optics; Pathologist; Pathology; Patients; Performance; Postoperative Period; Radiation therapy; Radiology Specialty; Reading; Repeat Surgery; Research Personnel; Resolution; Sensitivity and Specificity; Specificity; Specimen; Stains; Surface; Surgical Oncology; Surgical margins; Surveys; Technology; Three-Dimensional Imaging; Thyroid Gland; Time; Tissues; breast lumpectomy; cancer invasiveness; diagnostic accuracy; fluorophore; high resolution imaging; image processing; interest; malignant breast neoplasm; medical schools; microscopic imaging; multidisciplinary; novel; pathology imaging; portability; primary endpoint; programs; public health relevance; quantitative imaging; second harmonic; standard of care; two-photon

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.

描述（由申请人提供）：保乳治疗 (BCT)、肿瘤切除术和放射治疗是早期乳腺癌的标准治疗方法。目前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 的灵敏度有限，冷冻对组织有破坏性影响，并且会增加手术时间。高达 40% 的患者由于手术切缘阳性或接近而需要进行第二次手术。重复手术会延迟辅助治疗、增加患者发病率并增加医疗费用。我们的假设是，使用实时非线性显微镜（多光子显微镜）对肿瘤切除标本进行术中评估，可以显着降低阳性或近距离切缘的第二次手术率。我们使用非线性显微镜对新鲜切除的乳腺手术标本进行了初步数据分析，与 3 名病理学家盲读的 H&E 组织学相比，检测浸润性癌症和 DCIS 与良性乳腺组织的灵敏度为 95.4%，特异性为 93.3%。该项目是麻省理工学院和哈佛医学院贝斯以色列女执事医疗中心病理学、放射学和外科部门的研究人员之间的多学科合作。目标 1. 该目标将： (1) 开发用于病理实验室的临床非线性显微镜技术。 (2) 使用乳房切除标本的模拟肿块切除术验证实时非线性显微镜切缘评估。 (3) 确认用于非线性显微镜的外源染色不会干扰免疫组化检测。目标 2. 研究非线性显微镜对手术标本的术中评估，并评估对二次手术率的影响。主要终点是采用术中切缘评估和标准术后组织学手术切缘评估的研究组的重复手术率，与接受术后组织学临床标准但未进行术中影像学检查的对照组的重复手术率。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。除了图像处理和显示方法之外，我们还将开发先进的方法，例如 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，以增强诊断性能或提供定量指标。将对头颈癌、肺癌和甲状腺癌标本进行病理成像，这可能会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的二次手术率，而且可以在外科肿瘤学中广泛应用。