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.

抽象的 乳腺癌经常转移到腋窝淋巴结（ALN）。癌症从 原发性乳腺肿瘤可以在早期阶段发生，而ALN转移通常是最早的可检测到的 癌症传播。前哨淋巴结（SLN）活检是乳房中腋窝分期的标准方法 没有明显的腋窝腺病或在未检测到Aln转移的癌症患者 术前诊断。目前，SLN通过腹膜周围注入放射性示踪剂Technetium来识别 99MTC和/或蓝色染料，然后进行SL​​N活检进行病理检查。虽然是周围的 注射方法可以识别SLN的位置，术中没有区分LN 不管LN转移的状态如何，转移和健康的LN染色SLN。因此，一旦SLN为 通过99mtc和/或蓝色染料鉴定，SLN被外科手术去除，而不管SLN中的癌症转移状态如何 并发送进行病理评估。大多数接受SLN的乳腺癌患者（约70％） 活检在病理上是阴性的。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，血清瘤形成， 感觉神经损伤和运动范围的限制。此外，在SLN活检后，如果病理报告 在SLN中显示出癌症阴性，然后可以避免完整的Aln解剖。当SLN为癌症时 阳性，患者需要第二次手术才能完成ALN解剖。可以在 如果外科医生可以在术中检测到LN受累，则原发性肿瘤切除或SLN活检。所以， 一种用于临床翻译的手术可视化工具的新型术中方法，可以准确检测LN 需要临床参与以消除任何治疗延迟并防止不必要的手术。 为了克服以前和当前用癌细胞识别LN的挑战，我们在此方面的方法 应用旨在术中用癌细胞与正常LN区分LN，并实时区分 可视化工具。我们使用一个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LN转移酶中积聚，但不在健康的LN中。基于我们的初步 数据，我们假设使用ICG-P28的实时成像方法可以在术中/准确地进行 区分LN转移和健康LN，这将大大改善乳房的健康 癌症患者。我们将在模仿术中设置中检验我们的假设。每个目标/sub-aim都会发生 在协作和跨学科的环境中，进行我们提出的研究。我们独特的成像 方法可能会对SLN活检程序产生重大影响。它可能会提供 对乳腺癌患者的更好治疗方法，这是一个主要的里程碑，与NIH焦点区域有关。