Intraoperative Imaging for Lymph Node Metastases

淋巴结转移的术中成像

• 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
• 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

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.

摘要 乳腺癌经常转移到腋窝淋巴结（ALN）。癌细胞从 原发性乳腺肿瘤可在早期发生，ALN转移通常是最早可检测到的 癌症扩散前哨淋巴结活检是乳腺癌腋窝分期的标准方法 没有可触及的腋窝淋巴结肿大或在检查期间未检测到ALN转移的癌症患者 术前诊断目前，SLN是通过瘤周注射放射性示踪剂锝来识别的 99 mTc和/或蓝色染料，然后SLN活检病理检查。虽然这种肿瘤周围 注射法可确定SLN的位置，术中不能区分LN 转移和健康LN，因为它染色SLN，而不管LN转移的状态。因此，一旦SLN 通过99 mTc和/或蓝色染料鉴定，无论SLN中的癌症转移状态如何， 并送去做病理评估大多数接受SLN的乳腺癌患者（约70%） 活检病理学上是阴性的。尽管已经观察到SLN活检的临床益处， 活组织检查通常与术后并发症有关，例如水肿，血清肿形成， 感觉神经损伤和活动范围受限。此外，在SLN活检后，如果病理报告 如果SLN显示癌阴性，则可以避免完全切除ALN。当SLN是癌症时 阳性，患者需要第二次手术完成ALN剥离。这个决定可以在 如果术中发现淋巴结受累，应行原发肿瘤切除或前哨淋巴结活检。因此，我们认为， 一种新的术中方法，用于临床翻译的手术可视化工具，可以准确检测LN 临床上需要参与，以消除治疗中的任何延误，并防止不必要的手术。 为了克服以前和目前在鉴定LN与癌细胞方面的挑战，我们在本研究中的方法 该应用旨在术中用实时荧光定量分析区分具有癌细胞的LN与正常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 在原发性乳腺肿瘤和淋巴结转移灶中有明显的蓄积，而在健康淋巴结中无蓄积。根据我们初步的 数据，我们假设我们的ICG-p28实时成像方法可以在术中/准确地 区分LN转移和健康LN，这将大大改善乳腺健康 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/子目标将发生 在合作和跨学科的环境中开展我们提出的研究。我们独特的成像 这种方法可能对SLN活检程序产生重大影响。它可能会提供 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的重点领域有关。