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: 8508204
• 负责人: JEAN-FRANCOIS H GESCHWIND
• 金额: $ 49.41万
• 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 2016-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8508204
• 关键词: Academia; Adverse effects; Animals; Catheters; Chemoembolization; Clinical; Clinical Data; Colorectal Cancer; Comorbidity; Computer Assisted; Computer software; 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; Retinal Cone; Role; Site; Solutions; Staging; Supportive care; Survival Rate; Symptoms; System; Technology; Testing; Therapeutic Embolization; Time; Tissues; Toxic effect; Translating; Transplantation; 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(申请人提供)：肝癌是世界上最常见的癌症之一，每年有500,000例肝细胞癌(肝细胞癌，原发性肝癌)和20万例以肝脏为主的结直肠癌转移(继发性肝癌)。治疗选择有限，临床结果普遍较差，中位存活率不到一年。鉴于肝癌(原发癌和转移癌)主要由肝动脉供应，通常局限于肝脏，直接经肝动脉给药已被证明是治疗这些患者的有效方法。经导管肝动脉化疗栓塞术(TACE)是一种在X光图像引导下通过肝动脉导管给药的介入性肿瘤学治疗方法。I级证据表明，与仅接受支持性治疗的患者相比，TACE后患者的症状控制更好，生存时间更长(5年生存率从3%增加到26%)；这使得TACE成为中期肝癌治疗的主要手段。近年来，化疗药物释放系统已经从传统的碘油阿霉素鸡尾酒(c-TACE)转向药物洗脱微球(DEB-TACE)。尽管取得了这些成功，TACE(无论是否使用DEBS)在很大程度上依赖于临床医生的经验和在手术过程中的主观决策，这可能导致非靶向药物输送和高复发率(由于肿瘤杀灭或部分治疗)。这笔赠款的目标是通过1)消除导管放置的主观性，2)优化药物输送方案，3)量化治疗成功，来观察、接触和治疗肿瘤。实现这些目标的主要工具是X-射线C臂锥束CT(CBCT)。我们将大大扩大CBCT目前在TACE程序中发挥的有限作用。具体目标包括：(1)开发新的图像引导软件，以改进肿瘤成像和靶向；(2)优化药物输送方案，并在临床先导研究中进行验证；(3)开发可量化的治疗成功指标，并将其与术后核磁共振进行比较。学术界和产业界的合作将有助于将动物和回溯性人类研究的结果转化为改进的商业产品，然后在人体上进行前瞻性测试。