A Fluorescence Histology System for In Vivo Breast Tumor Margin Assessment

用于体内乳腺肿瘤边缘评估的荧光组织学系统

• 批准号: 8096034
• 负责人: JONATHAN QUINCY BROWN
• 金额: $ 19.2万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-03-01 至 2013-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8096034
• 关键词: Adipose tissue; Adoption; Age; Algorithms; Anatomy; Animals; Area; Beds; Body mass index; Breast; Breast-Conserving Surgery; Carcinoma in Situ; Cell Nucleus; Cessation of life; Classification; Clinical; Contrast Media; Detection; Development; Devices; Dyes; Excision; Fiber Optics; Fluorescence; Frozen Sections; Generations; Goals; Gold; Growth; Health Care Costs; Healthcare Systems; Histology; Histopathology; Human; Image; Imaging Device; Industry; Laboratories; Left; Lighting; Malignant - descriptor; Malignant Neoplasms; Mammary Gland Parenchyma; Mammary Neoplasms; Maps; Menopausal Status; Methodology; Metric; Microanatomy; Microscope; Microscopic; Microscopy; Microspheres; Modeling; Mus; Normal tissue morphology; Nuclear; Operating Rooms; Operative Surgical Procedures; Optics; Pathologist; Pathology; Patients; Performance; Phase; Pilot Projects; Postoperative Period; Pre-Clinical Model; Procedures; Process; Protocols documentation; Recurrence; Repeat Surgery; Reporting; Research; Resected; Residual Cancers; Resolution; Rice; Risk; Sampling; Scanning; Source; Specimen; Speed; Staging; Staining method; Stains; Structure; Surgeon; Surgical complication; Surgical margins; Surveys; System; Techniques; Technology; Testing; Time; Tissue Stains; Tissues; Transgenic Organisms; Treatment Cost; Tumor Tissue; Universities; Variant; Woman; Work; breast density; cancer recurrence; cancer surgery; fluorescence imaging; in vivo; malignant breast neoplasm; molecular imaging; mortality; mouse model; neoplastic cell; patient population; pre-clinical; prevent; sarcoma; soft tissue; spectroscopic imaging; tool; tumor

DESCRIPTION (provided by applicant): In 2009, an estimated 197,300 women with early stage invasive breast cancer and/or carcinoma in situ (CIS) received breast conserving surgery (BCS). BCS involves removal of malignant tissue with a surrounding margin of normal breast tissue. Residual cancer found in this margin after surgery is an important predictor of local recurrence of cancer after BCS. Recently, it was found that one death was averted for every four women in which a local recurrence is avoided. Thus, complete tumor excision is essential to reduce the risk of recurrence. As many as 20-70% of BCS patients must undergo re-excision surgery, because their cancer was incompletely removed during the first BCS procedure. This represents an enormous physical burden to the patient (increasing her chances for surgical complications and/or eventual cancer-related mortality) and financial burden to the health care system (effectively doubling the cost of treatment for this group of patients). By 2015, it is expected that the number of patients undergoing BCS will rise from approximately 197,000 to more than 270,000 per year in the U.S., at an annual growth rate of 5.5%. With no industry standard to prevent re-excision, it is expected that there will be a concomitant rise in the number of re-excision surgeries. Thus, there is a significant unmet clinical need for effective intra-operative assessment of breast tumor margins. The long-term research objective of this application is to develop a clinically-viable system for wide-field high-resolution microscopy of the tumor bed in BCS procedures, using a wide-field optically-sectioned scanning imager optimized for in vivo imaging, and non-toxic tissue-enhancing fluorescent contrast agents. This would be combined with automated image classification algorithms, which confer an automatic decision to the surgeon intra-operatively, whether or not additional tissue should be resected from the tumor bed. The objective of this development-phase R21 proposal is to complete a critical technology refinement, and to validate it in a pre-clinical tumor margin model. The specific aims of the current R21 proposal are 1) To develop a practical, non-contact, optically-sectioned wide-field fluorescence imaging system for in vivo tumor bed assessment, and 2) To evaluate the imaging system for in vivo tumor margin assessment in a transgenic murine tumor margin model. Successful completion of the R21 will result in a critical first step towards a clinically-viable system for in vivo fluorescence histology of breast tumor margins. PUBLIC HEALTH RELEVANCE: The successful development of a clinically-viable system and methodology for in vivo microscopic analysis of breast tissue has tremendous implications for the more than 197,000 women who annually undergo breast conserving cancer surgery. There is currently no widely available intra-operative tool to aid surgeons in determining whether surgery has been successful, therefore 20-70% of these women will undergo multiple surgeries to have their cancer fully removed. The development of a system which allows high-resolution microscopic mapping of the tumor bed could allow surgeons to catch bits of tumor left behind in the patient during the first surgery, thereby preventing the need for multiple surgeries, decreasing the patients' chances for surgical complications and tumor recurrence, and drastically reducing the healthcare costs for this growing patient population.

描述（由申请人提供）：2009年，估计有197，300名早期浸润性乳腺癌和/或原位癌（CIS）女性接受了保乳手术（BCS）。BCS涉及切除恶性组织，周围边缘为正常乳腺组织。手术后在该切缘发现的残留癌是BCS后癌症局部复发的重要预测因素。最近发现，每四名避免局部复发的妇女中就有一名避免死亡。因此，完整的肿瘤切除对于降低复发风险至关重要。多达20-70%的BCS患者必须接受再次切除手术，因为他们的癌症在第一次BCS手术中没有完全切除。这给患者带来了巨大的身体负担（增加了手术并发症和/或最终癌症相关死亡率的机会），也给医疗保健系统带来了巨大的经济负担（实际上使这类患者的治疗费用加倍）。到2015年，预计美国接受BCS的患者数量将从每年约197，000人增加到超过270，000人，年增长率为5.5%。由于没有防止再次切除的行业标准，预计再次切除手术的数量将随之增加。因此，对于乳腺肿瘤边缘的有效术中评估存在显著未满足的临床需求。 本申请的长期研究目标是开发一种临床可行的系统，用于BCS手术中肿瘤床的宽视场高分辨率显微镜检查，使用针对体内成像优化的宽视场光学切片扫描成像仪和无毒组织增强荧光造影剂。这将与自动图像分类算法相结合，自动图像分类算法在术中为外科医生提供自动决策，是否应从肿瘤床切除额外的组织。该开发阶段R21提案的目标是完成关键技术改进，并在临床前肿瘤边缘模型中对其进行验证。当前R21提案的具体目标是：1）开发用于体内肿瘤床评估的实用、非接触、光学切片宽视场荧光成像系统，以及2）在转基因小鼠肿瘤边缘模型中评价用于体内肿瘤边缘评估的成像系统。R21的成功完成将为乳腺肿瘤边缘的体内荧光组织学的临床可行系统迈出关键的第一步。 公共卫生关系：成功开发临床可行的系统和方法，用于乳腺组织的体内显微镜分析，对每年接受保乳癌症手术的197，000多名妇女具有巨大的意义。目前还没有广泛使用的术中工具来帮助外科医生确定手术是否成功，因此这些妇女中有20-70%将接受多次手术以完全切除癌症。开发一种允许高分辨率显微镜映射肿瘤床的系统可以使外科医生在第一次手术期间捕获患者留下的肿瘤，从而防止多次手术的需要，减少患者手术并发症和肿瘤复发的机会，并大大降低这一不断增长的患者群体的医疗费用。