A Fluorescence Histology System for In Vivo Breast Tumor Margin Assessment

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）的女性接受了保乳手术（BCS）。BCS包括切除正常乳腺组织周围边缘的恶性组织。手术后在这一边缘发现的残留肿瘤是BCS术后局部肿瘤复发的重要预测因子。最近发现，每四名避免局部复发的妇女中就有一人免于死亡。因此，完全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的机会），给卫生保健系统带来了经济负担（实际上使这类患者的治疗费用翻了一番）。到2015年，预计美国接受BCS的患者数量将从每年约19.7万增加到27万以上，年增长率为5.5%。由于没有防止再切除的行业标准，预计再切除手术的数量将随之增加。因此，术中对乳腺肿瘤边缘进行有效评估的临床需求尚未得到满足。该应用程序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，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上切除额外的组织。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进行验证。目前R21提案的具体目标是：1)开发一种实用的、非接触的、光学切片的、用于体内肿瘤床评估的宽视场荧光成像系统；2)在转基因小鼠肿瘤边缘模型中对该成像系统进行体内肿瘤边缘评估。R21的成功完成将是迈向临床可行的乳腺肿瘤边缘体内荧光组织学系统的关键的第一步。

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.