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: 10532782
• 负责人: Kevin Anton
• 金额: $ 17.87万
• 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 2024-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10532782
• 关键词: 3-Dimensional; Ablation; Accounting; Acoustics; Adjuvant Chemotherapy; 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; Data; Disease; Effectiveness; Epithelium; 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; 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; 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; 3-Dimensional; Ablation; Accounting; Acoustics; Adjuvant Chemotherapy; 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; Data; Disease; Effectiveness; Epithelium; 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; 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; 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.

项目摘要： 肝内胆管癌（ICC）是一种侵略性上皮肿瘤，预后不良且高 胆道的内壁引起的发病率。 ICC的管理选择有限，疾病 通常的预后不良。目前尚未适合不符合切除资格的患者的治疗选择 标准化并包括全身疗法和机车区域疗法，例如消融，跨性别 化学栓塞（TACE）和透射式放射栓塞（TARE）。使用TARE，放射性微球 通过放置在肝动脉分支的导管供应肿瘤，从而提供局部化 并持续释放辐射。但是，对固体的修改响应评估标准的响应率 肿瘤（MRECIST）的范围为25-60％，中位存活率在约13-15.5个月内。 对比增强的超声（CEU）利用静脉注射气体微泡。我们的小组 已经证明了2D和3D动态CEU预测肝细胞癌（HCC）反应的能力 先验并监视响应。我们还显示了使用次谐波频率的能力 从这些药物到非侵入性测量肿瘤间质体压力（IFP）的成分 化学疗法。此外，这些超声对比剂的独特属性是它们产生的能力 使用较高强度超声脉冲的稳定或惯性空化。重要的是，微泡的空化已经 通过诱导血管内皮细胞细胞凋亡，证明可以使血管生成血管对放射疗法敏感。 该项目的目的是1）确定定量体积CEU预测ICC的能力 治疗前对TARE的反应，2）表征使用局部UCA的安全性和初步功效 惯性空化以改善ICC对放射栓塞的反应，3）确定CEUS是否估计肿瘤 治疗后7-14天，灌注，IFP和残留血管可以预测ICC对放射栓塞的反应。 作为这项临床试验的一部分，患者将接受4次体积CEUS考试，并结合其标准 护理放射栓塞。第一次考试的定量数据将在TARE之前获得，并用于 确定CEU是否可以预测治疗反应的可能性（AIM 1）。 CEUS考试2-4将获得2 皮革后的小时至2周，将包括闪存的闪光序列以诱导惯性微气泡 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 疗法的微泡氮（AIM 2）。最后，在CEUS期间获得的肿瘤灌注和血管数据 考试2-4将被量化以确定这些参数是否可以用于预测长期治疗 响应（目标3）。如果成功，则预计在此提案中验证的技术将改善ICC 通过确定哪些患者可以从皮革中受益最大，从而改善对TARE的肿瘤反应， 尽早鉴定出非反应性疾病，从而减少了使用替代疗法撤退的时间。