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: 8225170
• 负责人: JONATHAN QUINCY BROWN
• 金额: $ 13.28万
• 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 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8225170
• 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; public health relevance; 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 名患有早期浸润性乳腺癌和/或原位癌 (CIS) 的女性接受了保乳手术 (BCS)。 BCS 涉及切除恶性组织及其周围正常乳腺组织的边缘。手术后在该边缘发现的残留癌症是 BCS 后癌症局部复发的重要预测因素。最近发现，如果避免了局部复发，每四名女性就可以避免一名死亡。因此，彻底切除肿瘤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 手术中未完全切除。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经济负担（实际上使这组患者的治疗成本加倍）。到2015年，预计美国接受BCS的患者人数将从每年约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会随之增加。因此，对乳腺肿瘤边缘进行有效的术中评估存在着显着的未满足的临床需求。 该应用的长期研究目标是开发一种临床上可行的系统，用于 BCS 程序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，使外科医生在术中自动决定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) 开发一种实用的、非接触式、光学切片的宽视场荧光成像系统，用于体内肿瘤床评估，2) 在转基因小鼠肿瘤边缘模型中评估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体内荧光组织学临床可行的系统迈出关键的第一步。 公共健康相关性：成功开发临床上可行的乳腺组织体内显微分析系统和方法，对每年接受保乳癌症手术的超过 197,000 名女性具有巨大影响。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，因此这些女性中的 20-70% 将接受多次手术以完全切除癌症。开发出一种能够对肿瘤床进行高分辨率显微测绘的系统，可以让外科医生在第一次手术期间捕获患者体内残留的肿瘤碎片，从而避免多次手术的需要，减少患者出现手术并发症和肿瘤复发的机会，并大大降低不断增长的患者群体的医疗费用。