Intraoperative Imaging for Lymph Node Metastases

淋巴结转移的术中成像

基本信息

批准号：
10646823
负责人：
Tohru Yamada
金额：
$ 18.69万
依托单位：
UNIVERSITY OF ILLINOIS AT CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-04-01 至 2025-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10646823
关键词：
Animal Cancer Model Animals Area Articular Range of Motion Axilla Axillary Lymph Node Dissection Axillary lymph node group Blinded Breast Cancer Patient Breast Cancer Treatment Breast Cancer cell line Clinical Clinical Research Data Detection Development Diagnosis Diagnostic Procedure Disease Dissection Double-Blind Method Dyes Excision Health Image-Guided Surgery Injections Location Lymph Node Involvement Lymphedema Malignant Neoplasms Mammary Neoplasms Mastectomy Medical Metastatic Neoplasm to Lymph Nodes Metastatic breast cancer Methods Neoplasm Metastasis Operative Surgical Procedures Optical Instrument Outcome Palpable Pathologic Pathological Staging Patients Phase Postoperative Complications Pre-Clinical Model Primary Neoplasm Procedures Process Prognostic Factor Property Protocols documentation Published Comment Radioactive Tracers Reporting Research Sentinel Lymph Node Sentinel Lymph Node Biopsy Seroma Side Staging Stains Surgeon Technetium Testing Time Toxic effect Translating United States National Institutes of Health Unnecessary Surgery Validation Visualization Visualization software afferent nerve arm breast lumpectomy cancer cell cancer surgery collaborative environment cost cost effective flexibility imaging agent imaging approach improved lymph nodes lymphadenopathy malignant breast neoplasm nerve injury operation pre-clinical prevent prognostication real-time images standard of care stem tool tumor

项目摘要

ABSTRACT Breast cancer frequently metastasizes to the axillary lymph nodes (ALN). The cancer spread from the primary breast tumor can occur during the early stages, and ALN metastasis is usually the earliest detectable cancer spread. Sentinel lymph node (SLN) biopsy is the standard approach for axillary staging in breast cancer patients with no palpable axillary adenopathy or when ALN metastasis is not detected during the presurgical diagnosis. Currently, SLN is identified by a peritumoral injection of a radioactive tracer, technetium 99mTc and/or blue dye, followed by a SLN biopsy for pathological examination. Although this peritumoral injection method can identify the location of SLN, it does not intraoperatively distinguish between LN metastases and healthy LN as it stains SLN regardless of the status of LN metastases. Thus, once SLN is identified by 99mTc and/or blue dye, SLN is surgically removed regardless of cancer metastases status in SLN, and sent for pathological assessment. The majority of patients with breast cancer (~70%) who undergo a SLN biopsy are pathologically negative. Although the clinical benefits of a SLN biopsy have been observed, SLN biopsies are often associated with postoperative complications such as lymphedema, seroma formation, sensory nerve injury, and limitation in range of motion. Moreover, after a SLN biopsy, if pathological reports show cancer negative in the SLN, then a complete ALN dissection can be avoided. When SLN is cancer positive, patients need a second operation to complete the ALN dissection. This decision can be made during the primary tumor resection or SLN biopsy if surgeons can detect LN involvement intraoperatively. Therefore, a new intraoperative method for a clinically translated surgical visualization tool that can accurately detect LN involvement is clinically needed to eliminate any delay in treatment and prevent unnecessary surgeries. To overcome previous and current challenges in identifying LN with cancer cells, our approach in this application aims to intraoperatively distinguish LN with cancer cells from normal LN with a real-time visualization tool. Our preliminary results with one breast cancer cell line showed that ICG-p28 preferentially accumulated at the primary breast tumor and LN metastases, but not in healthy LN. Based on our preliminary data, we hypothesize that our real-time imaging approach with ICG-p28 can intraoperatively/accurately distinguish between LN metastases and healthy LN which will substantially improve the health of breast cancer patients. We will test our hypothesis in mimicked intraoperative settings. Each aim/sub-aim will occur in the collaborative and interdisciplinary environment to carry out our proposed research. Our unique imaging approach can potentially provide a significant impact on SLN biopsy procedures. It will potentially provide better treatments for breast cancer patients, which is a major milestone and relevant to the NIH focus area.

抽象的乳腺癌经常转移至腋窝淋巴结（ALN）。癌症从原发性乳腺肿瘤可能发生在早期阶段，ALN 转移通常是最早发现的癌症扩散。前哨淋巴结（SLN）活检是乳腺腋窝分期的标准方法无明显腋窝淋巴结肿大或手术期间未检测到 ALN 转移的癌症患者术前诊断。目前，SLN 通过瘤周注射放射性示踪剂锝来识别 99mTc 和/或蓝色染料，然后进行 SLN 活检进行病理检查。虽然这种瘤周注射法可以识别SLN的位置，术中不能区分LN 无论 LN 转移状态如何，它都会对 SLN 进行染色，从而区分转移灶和健康 LN。因此，一旦 SLN 通过 99mTc 和/或蓝色染料识别，无论 SLN 中的癌症转移状态如何，都会通过手术切除 SLN，并送病理评估。大多数乳腺癌患者 (~70%) 接受 SLN 活检病理结果阴性。尽管已经观察到 SLN 活检的临床益处，但 SLN 活检通常与术后并发症有关，例如淋巴水肿、血清肿形成、感觉神经损伤和运动范围受限。此外，前哨淋巴结活检后，如果病理报告显示 SLN 中的癌症呈阴性，则可以避免完整的 ALN 解剖。当 SLN 是癌症时阳性，患者需要进行第二次手术才能完成 ALN 解剖。该决定可以在如果外科医生可以在术中检测到 LN 受累，则进行原发肿瘤切除或 SLN 活检。所以，一种新的术中方法，用于临床转化的手术可视化工具，可准确检测 LN 临床上需要参与，以消除任何治疗延误并防止不必要的手术。为了克服以前和当前识别淋巴结与癌细胞的挑战，我们的方法应用程序旨在术中实时区分含有癌细胞的 LN 和正常 LN 可视化工具。我们对一种乳腺癌细胞系的初步结果表明，ICG-p28 优先积聚在原发性乳腺肿瘤和淋巴结转移灶中，但不会积聚在健康的淋巴结中。根据我们的初步数据，我们假设我们使用 ICG-p28 的实时成像方法可以在术中/准确地区分淋巴结转移和健康淋巴结，这将大大改善乳房的健康癌症患者。我们将在模拟的术中环境中检验我们的假设。每个目标/子目标都会发生在协作和跨学科环境中开展我们提出的研究。我们独特的成像该方法可能会对 SLN 活检程序产生重大影响。它将有可能提供为乳腺癌患者提供更好的治疗，这是一个重要的里程碑，与 NIH 重点领域相关。