Contrast Ultrasound Detection of Sentinel Lymph Nodes in Breast Cancer Patients

乳腺癌患者前哨淋巴结的超声造影检测

• 批准号: 9001939
• 负责人: Flemming Forsberg
• 金额: $ 28.55万
• 依托单位: THOMAS JEFFERSON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-02-01 至 2019-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9001939
• 关键词: Anaphylaxis; Anatomy; Animal Model; Animals; Benign; Biopsy; Breast Cancer Patient; Breast Melanoma; Clinical; Clinical Trials; Colloids; Colon; Color; Contrast Media; Deposition; Detection; Diagnosis; Diagnostic; Disease; Dissection; Dose; Drainage procedure; Dyes; Evaluation; Excision; Family suidae; Female; Fluorescein; Funding; Gamma Cameras; Goals; Health; Healthcare; Histopathology; Human; Image; Injection of therapeutic agent; Investigation; Ionizing radiation; Isotopes; Legal patent; Location; Lymphatic; Lymphedema; Malignant - descriptor; Malignant Neoplasms; Maps; Mass in breast; Methods; Methylene blue; Microbubbles; Modeling; Neoplasm Metastasis; Normal Statistical Distribution; Norway; Operative Surgical Procedures; Patients; Physiologic pulse; Radioisotopes; Radiopharmaceuticals; Reference Standards; Reporting; Safety; Schedule; Sentinel Lymph Node; Sentinel Lymph Node Mapping; Side; Staging; Technetium 99m; Technetium Tc 99m Sulfur Colloid; Techniques; Testing; Tissues; Tracer; Translating; Translations; Ultrasonography; United States; United States National Institutes of Health; Woman; base; breast malignancies; contrast enhanced; experience; healthy volunteer; imaging agent; imaging modality; improved; interstitial; lymph nodes; malignant breast neoplasm; melanoma; nanocolloid; subcutaneous; tumor; uptake; volunteer

DESCRIPTION (provided by applicant): Intraoperative lymphatic mapping to localize sentinel lymph nodes (SLNs) and stage breast cancer patients is currently performed after administration of radioisotopes and / or dye. However, each of these methods has potential limitations that can impact the detection of SLNs and the accuracy of disease staging. Furthermore, isotope imaging requires ionizing radiation, blue dye can cause anaphylactic reactions and neither of these techniques provides an accurate noninvasive depiction of lymphatic anatomy. Up to 25% of patients experience complications such as lymphedema. Our group has demonstrated that contrast-enhanced ultrasound imaging (CEUS) after subdermal administration of a tissue-specific ultrasound contrast agent, can be used to noninvasively map lymphatic drainage and localize SLNs (so called "lymphosonography"). Our NIH funded investigations using a swine model with naturally occurring melanomas have confirmed that CEUS is superior to radioisotope imaging detection almost 20 % more SLNs. The fundamental hypothesis of this project is that CEUS can be used to map lymphatic drainage from breast malignancies and localize SLNs in breast cancer patients and that lymphosonography will improve the detection of SLNs compared to isotope mapping leading to improved disease staging. Initially, a dose-finding study will be performed in 12 healthy female volunteers to determine the optimal dose as well as the safety and tolerability of the tissue-specific, contrast agent Sonazoid (GE Healthcare, Oslo, Norway) for human lymphatic applications. Then a clinical trial of lymphosonography will compare SLN identification to that of isotope mapping during surgery of 90 breast cancer patients. A state-of- the-art ultrasound scanner with contrast-specific imaging capabilities will be used to localize lymphatic drainage from breast cancers after subdermal administration of Sonazoid. The number and locations of the SLNs identified by the two imaging modalities (CEUS and isotope mapping) will be compared using McNemar's test for correlated proportions as well as using a one-sided t-test with a Wilcoxon non-parametric adjustment (assuming a normal distribution) with dye-guided surgery as the reference standard for SLN detection. In summary, this study aims to determine the clinical potential of lymphosonography for noninvasive SLN mapping in 90 breast cancer patients and compare the use of CEUS to isotope mapping.

描述(申请人提供)：术中定位前哨淋巴结(SLN)和分期乳腺癌患者的淋巴标测目前是在注射放射性同位素和/或染料后进行的。然而，这些方法中的每一种都有潜在的局限性，可能会影响SLN的检测和疾病分期的准确性。此外，同位素成像需要电离辐射，蓝色染料会引起过敏反应，这两种技术都不能提供准确的非侵入性淋巴解剖描述。多达25%的患者会出现淋巴水肿等并发症。我们小组已经证明，皮下注射组织特异性超声造影剂后的对比增强超声成像(CEUS)可以用于无创地定位淋巴引流和定位SLN(所谓的“淋巴超声造影术”)。美国国立卫生研究院资助的猪自然发生黑色素瘤模型的研究证实，CEUS优于放射性同位素成像检测，几乎多出20%的SLN。该项目的基本假设是，CEUS可以用于绘制乳腺恶性肿瘤淋巴引流的图谱，并定位乳腺癌患者的SLN，与同位素成像相比，淋巴超声检查将改善SLN的检测，从而改善疾病分期。最初，将在12名健康女性志愿者中进行剂量发现研究，以确定人体淋巴应用的组织特异性造影剂Sonazid(GE Healthcare，挪威奥斯陆)的最佳剂量以及安全性和耐受性。然后，一项临床试验将对90名乳腺癌患者在手术中进行淋巴超声检查，并将SLN识别与同位素测绘进行比较。一种具有对比剂特定成像能力的最先进的超声波扫描仪将在皮下给药后用于定位乳腺癌的淋巴引流。两种成像方式(CEU和同位素测绘)确定的SLN的数目和位置将使用McNemar相关比例检验以及使用单侧t检验和Wilcoxon非参数调整(假设为正态分布)进行比较，并将染料引导手术作为SLN检测的参考标准。总之，这项研究旨在确定淋巴超声在90名乳腺癌患者中无创定位SLN的临床潜力，并比较CEUS和同位素定位的使用。