Contrast-Enhanced Ultrasound for Diagnosis and Therapy of Cholangiocarcinoma

超声造影对胆管癌的诊断和治疗

• 批准号: 10356516
• 负责人: Kevin Anton
• 金额: $ 21.88万
• 依托单位: THOMAS JEFFERSON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-12-03 至 2023-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10356516
• 关键词: 3-Dimensional; Ablation; Accounting; Acoustics; Adverse event; Aftercare; Algorithms; Alternative Therapies; Apoptosis; Area Under Curve; Blood Tests; Blood Vessels; Catheters; Chemoembolization; Cholangiocarcinoma; Clinical; Clinical Trials; Computer software; Contrast Media; Curative Surgery; Custom; Data; Disease; Effectiveness; Epithelial; Evaluation; Excision; Frequencies; Funding; Gases; Glass; Hepatic artery; Heterogeneity; Hour; Image; Intercellular Fluid; Intrahepatic Cholangiocarcinoma; Intravenous; Liquid substance; Liver; Liver neoplasms; Magnetic Resonance Imaging; Malignant - descriptor; Malignant neoplasm of liver; Measures; Microbubbles; Microspheres; Monitor; Morbidity - disease rate; Morphology; Neoadjuvant Therapy; Neoplasms in Vascular Tissue; Operative Surgical Procedures; Patient-Focused Outcomes; Patients; Perfusion; Physiologic pulse; Prediction of Response to Therapy; Primary carcinoma of the liver cells; Prognosis; Property; Radiation; Radiation therapy; Radioactive; Radioembolization; Radioisotopes; Radiopharmaceuticals; Residual state; Retreatment; Safety; Schedule; Solid Neoplasm; Standardization; System; Systemic Therapy; Techniques; Therapeutic; Time; Tissues; Ultrasonography; Vascular Endothelial Cell; Vascular blood supply; Visualization; advanced disease; base; biliary tract; cancer imaging; chemotherapy; clinical application; contrast enhanced; cost effective; follow-up; improved; intravenous injection; liver function; nuclear imaging; pancreatic cancer patients; parametric imaging; predicting response; pressure; response; standard of care; treatment response; tumor; ultrasound

Project Summary: Intrahepatic cholangiocarcinoma (ICC) is an aggressive epithelial tumor with poor prognosis and high morbidity arising from the lining of the biliary tract. Management options for ICC are limited and the disease generally carries a poor prognosis. Treatment options for patients not eligible for resection are currently not standardized and include systemic therapies and loco-regional therapies such as ablation, transarterial chemoembolization (TACE), and transarterial radioembolization (TARE). Using TARE, radioactive microspheres are delivered via a catheter placed in the hepatic artery branch supplying the tumor, thereby providing a localized and sustained release of radiation. However, response rates on modified response evaluation criteria in solid tumors (mRECIST) range from 25-60% and median survival remains at approximately 13-15.5 months. Contrast-enhanced ultrasound (CEUS) utilizes the intravenous injection of gas microbubbles. Our group has demonstrated the ability of 2D and 3D dynamic CEUS to predict hepatocellular carcinoma (HCC) response to TACE a priori and also monitor response. We have also shown the ability to use the subharmonic frequency components from these agents to non-invasively measure tumor interstitial fluid pressures (IFP) over the course of chemotherapy. Additionally, a unique property of these ultrasound contrast agents is their ability to generate stable or inertial cavitation using higher intensity ultrasound pulses. Importantly, microbubble cavitation has been shown to sensitize angiogenic vessels to radiotherapy by inducing vascular endothelial-cell apoptosis. The aims of this project are 1) to determine the ability of quantitative volumetric CEUS to predict ICC response to TARE prior to therapy, 2) to characterize the safety and preliminary efficacy of using localized UCA inertial cavitation to improve ICC response to radioembolization, and 3) to determine if CEUS estimated tumor perfusion, IFP, and residual vascularity can predict ICC response to radioembolization 7-14 days post treatment. As part of this clinical trial, patients will undergo 4 volumetric CEUS exams combined with their standard of care radioembolization. Quantitative data from the first exam will be obtained prior to TARE and used to determine if CEUS can predict the likelihood of treatment response (aim 1). CEUS exams 2-4 will be obtained 2 hours to 2 weeks post TARE and will include flash-replenishment sequences to induce inertial microbubble cavitation. Safety and tumor response will then be compared to historical controls to determine the effect of microbubble cavitation on therapy (aim 2). Finally, tumor perfusion and vascularity data obtained during CEUS exams 2-4 will be quantified to determine if these parameters can be used to predict longer term treatment response (aim 3). If successful, the techniques validated in this proposal are expected to improve ICC management by identifying which patients would benefit most from TARE, improving tumoral response to TARE, identifying non-responding disease early and thereby reducing the time to retreatment with alternative therapies.

项目概要： 肝内胆管癌（ICC）是一种侵袭性上皮性肿瘤，预后不良，发病率高 胆道内壁引起的发病。 ICC 的治疗选择有限，并且该疾病 一般预后不良。目前还没有针对不适合切除的患者的治疗选择 标准化，包括全身治疗和局部治疗，例如消融、经动脉治疗 化疗栓塞（TACE）和经动脉放射栓塞（TARE）。使用 TARE，放射性微球 通过放置在供应肿瘤的肝动脉分支中的导管输送，从而提供局部 并持续释放辐射。然而，修改后的固体反应评估标准的反应率 肿瘤 (mRECIST) 范围为 25-60%，中位生存期保持在约 13-15.5 个月。 超声造影 (CEUS) 利用静脉注射微泡。我们组 已证明 2D 和 3D 动态 CEUS 预测肝细胞癌 (HCC) 反应的能力 先验 TACE 并监测反应。我们还展示了使用分谐波频率的能力 这些药物的成分可在整个过程中无创地测量肿瘤间质液压力（IFP） 化疗。此外，这些超声造影剂的一个独特特性是它们能够产生 使用更高强度的超声波脉冲实现稳定或惯性空化。重要的是，微泡空化现象 研究表明，通过诱导血管内皮细胞凋亡，使血管生成血管对放射治疗敏感。 该项目的目标是 1) 确定定量体积 CEUS 预测 ICC 的能力 治疗前对 TARE 的反应，2) 表征使用局部 UCA 的安全性和初步疗效 惯性空化以改善 ICC 对放射栓塞的反应，以及 3) 确定 CEUS 是否估计肿瘤 灌注、IFP 和残余血管分布可以预测 ICC 对治疗后 7-14 天放射栓塞的反应。 作为本临床试验的一部分，患者将接受 4 次体积 CEUS 检查并结合他们的标准 放射栓塞治疗的护理。第一次检查的定量数据将在去皮之前获得并用于 确定 CEUS 是否可以预测治疗反应的可能性（目标 1）。 CEUS考试2-4将获得2 去皮后数小时至 2 周，并将包括快速补充序列以诱导惯性微泡 空化。然后将安全性和肿瘤反应与历史对照进行比较，以确定效果 治疗中的微泡空化（目标 2）。最后，CEUS 期间获得的肿瘤灌注和血管分布数据 检查 2-4 将被量化，以确定这些参数是否可用于预测长期治疗 响应（目标 3）。如果成功，该提案中验证的技术有望改善 ICC 通过确定哪些患者将从 TARE 中受益最大、改善肿瘤对 TARE 的反应来进行管理， 及早发现无反应疾病，从而减少采用替代疗法重新治疗的时间。