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名侵入性乳腺癌和/或原位癌（CIS）的女性接受了乳房保存手术（BCS）。 BCS涉及去除正常乳腺组织边缘的恶性组织。手术后在此边缘发现的残留癌是BCS后癌症局部复发的重要预测指标。最近，发现避免了避免当地复发的每四个妇女，避免了一次死亡。因此，完全肿瘤切除对于降低复发风险至关重要。多达20％至70％的BCS患者必须进行重新筛选手术，因为在第一次BCS手术中，他们的癌症未完全去除。这代表了患者的巨大身体负担（增加了她出于手术并发症和/或最终与癌症相关的死亡率的机会）和对医疗保健系统的经济负担（有效地使这组患者的治疗成本增加了一倍）。到2015年，预计在美国，接受BCS的患者人数将从大约197,000增加到每年270,000多个，年增长率为5.5％。由于没有行业标准可以防止重新拆除，因此可以重新判断手术的数量会增加。因此，对乳腺肿瘤边缘的有效术中评估有很大的临床需求。 该应用的长期研究目标是使用BCS程序中肿瘤床的宽大高分辨率显微镜开发一种可使用的临床可行系统，使用用于体内成像和非毒性组织 - 增强型荧光荧光剂的宽视野光学剖面扫描成像仪。这将与自动图像分类算法结合使用，该算法允许术中外科医生自动决定，是否应从肿瘤床中切除其他组织。该开发相R21提案的目的是完成关键的技术完善，并在临床前肿瘤边缘模型中进行验证。当前R21提案的具体目的是1）开发用于体内肿瘤床评估的实用，非接触，光学剖面的宽视野荧光成像系统，以及2）评估转基因Murine Murine Murine Murine tumor tumor Margin模型中体内肿瘤边缘评估的成像系统。成功完成R21将导致迈向乳腺肿瘤边缘体内荧光组织学的临床可行系统的关键第一步。 公共卫生相关性：成功开发了临床可行的系统和方法论，用于对乳腺组织的体内微观分析，对每年每年进行乳腺保存癌症手术的197,000多名女性具有巨大的影响。目前尚无广泛可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％将接受多次手术以使癌症完全切除。允许对肿瘤床进行高分辨率显微镜图的系统的开发，可以使外科医生在第一次手术期间捕获患者留下的肿瘤，从而阻止了多次手术的需求，从而减少了患者的手术并发症和肿瘤复发的机会，并大大降低了该增长的患者的医疗保健成本。