See, Reach, Treat Tumor-Optimized Transarterial Chemoembolization Drug Delivery

查看、达到、治疗肿瘤优化的经动脉化疗栓塞药物输送

• 批准号: 8699164
• 负责人: JEAN-FRANCOIS H GESCHWIND
• 金额: $ 48.81万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-20 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8699164
• 关键词: Academia; Adverse effects; Animals; Catheters; Chemoembolization; Clinical; Clinical Data; Colorectal Cancer; Comorbidity; Computer Assisted; Computer software; Cone; Data; Decision Making; Decision Modeling; Development; Disease; Dose; Doxorubicin; Drug Delivery Systems; Environment; Excision; Family suidae; Goals; Grant; Hepatic artery; Hospitals; Human; Human Resources; Image; Imagery; Incidence; Industry; Investigation; Liver; Liver neoplasms; Location; Magnetic Resonance Imaging; Malignant Neoplasms; Malignant neoplasm of liver; Measures; Metastatic Neoplasm to the Liver; Methods; Microspheres; Modeling; Modification; Neoplasm Metastasis; Operative Surgical Procedures; Oryctolagus cuniculus; Outcome; Patients; Penetration; Pharmaceutical Preparations; Pilot Projects; Plague; Plasma; Play; Positioning Attribute; Primary carcinoma of the liver cells; Procedures; Process; Prospective Studies; Protocols documentation; Qualifying; Radio; Recording of previous events; Recurrence; Research; Resources; Role; Site; Solutions; Staging; Supportive care; Survival Rate; Symptoms; System; Technology; Testing; Therapeutic Embolization; Time; Tissues; Toxic effect; Translating; Transplantation; X-Ray Computed Tomography; arm; chemotherapeutic agent; chemotherapy; cone-beam computed tomography; experience; improved; killings; oncology; pre-clinical; prospective; response; success; tool; tumor

DESCRIPTION (provided by applicant): Liver cancer is one of the most common cancers worldwide with >500,000 new cases/yr of hepatocellular carcinoma (HCC, primary liver cancer) and >200,000 new cases/yr of liver dominant colorectal cancer metastases (secondary liver cancer). Treatment options are limited and clinical outcomes are generally poor with a median survival rate of less than one year. Given the fact that liver cancer (primary and metastatic) is primarily supplied by the hepatic artery and is generally confined to the liver, drug delivery directly into the hepatic artery has been shown to be effective in the management of these patients. Transcatheter arterial chemoembolization (TACE) is an x-ray imaged guided, interventional oncology procedure in which chemotherapeutic drug is delivered from a catheter in the hepatic artery. Level I evidence has demonstrated that patients have better symptom control and prolonged survival after TACE as compared to those receiving supportive care only (5-year survival rate increases from 3% to 26%); this has resulted in TACE being the mainstay of intermediate stage HCC therapy. Recently, there has been a shift in the chemotherapeutic drug delivery system from the conventional lipiodol-doxorubicin cocktail (c-TACE) to drug-eluting microsphere beads (DEB-TACE). Despite these successes, TACE (with or without using DEBs) relies heavily on clinician experience and subjective decision making during the procedure, which can result in non-target drug delivery and a high recurrence rate (either due to incomplete tumor kill or partial treatment). The goals of this grant are to see, reach, and treat the tumor by 1) removing the subjectivity in catheter placement, 2) optimizing the drug delivery protocol, and 3) quantifying treatment success. The main tool that we will use to realize these goals is the x-ray C-arm cone-beam CT (CBCT). We will greatly expand the limited role CBCT currently plays in the TACE procedure. Specific aims include: (1) Develop new image guidance software to improve tumor imaging and targeting, (2) Optimize the drug delivery protocol and validate it in a clinical pilot study, and (3) Develop quantifiable measures of treatment success and compare these with post-procedure MRI. The academia-industry partnership will help translate results from animal and retrospective human studies into improved commercial products which will then be tested prospectively in humans.

描述（由申请人提供）：肝癌是全球最常见的癌症之一，肝细胞癌（HCC，原发性肝癌）和肝细胞癌的新病例/年肝癌主导型结直肠癌转移（次要肝癌）的肝细胞癌（HCC，原发性肝癌）（二肝癌）。治疗选择有限，临床结果通常很差，中位存活率少于一年。 鉴于肝癌（原发性和转移性）主要由肝动脉提供，并且通常局限于肝脏，因此直接将药物输送到肝动脉中已被证明可以有效地治疗这些患者。经导管动脉化学栓塞（TACE）是X射线成像的介入，介入肿瘤学程序，其中从肝动脉中的导管传递化学治疗药物。 I级证据表明，与仅接受支持护理的患者相比，患者的症状控制更好，而TACE后的生存时间延长（5年生存率从3％增加到26％）；这导致TACE是中级HCC疗法的中流。最近，化学治疗药物递送系统从常规的脂醇 - 二氧化氨酸鸡尾酒（C-TACE）转变为药物洗脱微球珠（DEB-TACE）。 尽管取得了这些成功，但TACE（有或不使用DEB）在过程中很大程度上取决于临床医生的经验和主观决策，这可能导致非目标药物输送和高复发率（由于肿瘤不完全杀死或部分治疗而导致）。 该赠款的目标是通过1）消除导管放置中的主观性，2）优化药物输送方案，以及3）量化治疗成功。我们将用来实现这些目标的主要工具是X射线C臂锥束CT（CBCT）。我们将大大扩展CBCT目前在TACE程序中所扮演的有限角色。 具体目的包括：（1）开发新的图像引导软件以改善肿瘤成像和靶向，（2）在临床初步研究中优化药物输送方案并验证它，以及（3）开发可量化的治疗方法，并将其与后期过程中的MRI进行比较。学术界 - 行业伙伴关系将有助于将动物和回顾性人类研究的结果转化为改进的商业产品，然后将其前瞻性地在人类中进行测试。