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，每年新增肝细胞癌（HCC，原发性肝癌）病例超过 500,000 例，每年新增肝显性结直肠癌转移病例（继发性肝癌）超过 200,000 例。治疗选择有限，临床结果通常较差，中位生存率不到一年。 鉴于肝癌（原发性和转移性）主要由肝动脉供血并且通常局限于肝脏，因此将药物直接输送到肝动脉已被证明对这些患者的治疗是有效的。经导管动脉化疗栓塞 (TACE) 是一种 X 射线成像引导的介入肿瘤学手术，其中化疗药物从肝动脉中的导管输送。 I 级证据表明，与仅接受支持治疗的患者相比，TACE 后患者的症状得到更好的控制并延长了生存期（5 年生存率从 3% 增加至 26%）；这使得 TACE 成为中期 HCC 治疗的支柱。最近，化疗药物递送系统从传统的碘油-阿霉素混合物（c-TACE）转变为药物洗脱微球珠（DEB-TACE）。 尽管取得了这些成功，TACE（使用或不使用 DEB）在手术过程中严重依赖临床医生的经验和主观决策，这可能导致非靶向药物输送和高复发率（由于肿瘤杀灭不完全或部分治疗）。 这笔拨款的目标是通过 1) 消除导管放置的主观性，2) 优化药物输送方案，以及 3) 量化治疗成功来观察、触及和治疗肿瘤。我们用于实现这些目标的主要工具是 X 射线 C 形臂锥束 CT (CBCT)。我们将极大地扩展 CBCT 目前在 TACE 手术中发挥的有限作用。 具体目标包括：(1) 开发新的图像引导软件以改善肿瘤成像和靶向，(2) 优化药物输送方案并在临床试点研究中对其进行验证，(3) 开发治疗成功的量化指标，并将其与术后 MRI 进行比较。学术界与工业界的合作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，然后对这些产品进行前瞻性人体测试。