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.

项目总结： 摘要肝内胆管细胞癌是一种侵袭性的上皮性肿瘤，预后差，预后高。 胆道衬里引起的发病率。ICC的管理选择有限，而且这种疾病 一般情况下预后很差。不符合切除条件的患者的治疗方案目前不能 标准化，包括全身治疗和局部治疗，如经动脉消融、 化疗栓塞术(TACE)和经动脉放射栓塞术(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，从而提供局部的 以及辐射的持续释放。然而，修改后的响应评估标准的响应率 肿瘤(MRECIST)从25%到60%不等，中位生存期约为13到15.5个月。 超声造影(CEUS)利用静脉注射气体微泡。我们的团队 已证实2D和3D动态CEUS能够预测肝细胞癌(HCC)的反应 先验地进行TACE，并监测反应。我们还展示了使用亚谐频率的能力 这些试剂的成分在整个过程中非侵入性地测量肿瘤间质液体压(IFP) 化疗的结果。此外，这些超声造影剂的一个独特性质是它们能够产生 使用更高强度的超声脉冲进行稳定或惯性空化。重要的是，微泡空化一直是 显示通过诱导血管内皮细胞凋亡而使血管新生血管对放射治疗敏感。 该项目的目的是1)确定定量容量CEU预测ICC的能力 治疗前对Tare的反应，2)表征局部使用UCA的安全性和初步疗效 惯性空化以改善ICC对放射栓塞术的反应，以及3)以确定CEUS是否估计肿瘤 灌注、IFP和残余血管可以预测治疗后7-14天ICC对放射栓塞术的反应。 作为这项临床试验的一部分，患者将接受4次容量CEU检查，并结合他们的标准 接受放射栓塞术治疗。第一次考试的定量数据将在皮重之前获得，并用于 确定CEU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 TARE后数小时至2周，并将包括闪光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 微泡空化治疗(目标2)。最后，在CEUS中获得的肿瘤血流和血管数据 检查2-4将被量化，以确定这些参数是否可以用来预测长期治疗 回应(目标3)。如果成功，本提案中验证的技术有望改善ICC 通过确定哪些患者将从TARE中受益最多，改善肿瘤对TARE的反应， 及早发现无反应的疾病，从而减少采用替代疗法重新治疗的时间。