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

简介（申请人提供）：肝癌是世界范围内最常见的癌症之一，每年有50万新发肝细胞癌（HCC，原发性肝癌），每年有20万新发肝显性结直肠癌转移（继发性肝癌）。治疗选择有限，临床结果通常较差，中位生存率不到一年。考虑到肝癌（原发性和转移性）主要由肝动脉供血，通常局限于肝脏，直接给药到肝动脉已被证明是治疗这些患者的有效方法。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导管输送。一级证据表明，与仅接受支持性治疗的患者相比，接受TACE治疗的患者有更好的症状控制和更长的生存期（5年生存率从3%增加到26%）；这导致TACE成为中期HCC治疗的主要方法。最近，化疗药物递送系统从传统的脂醇-阿霉素鸡尾酒（c-TACE）转向药物洗脱微球珠（DEB-TACE）。尽管取得了这些成功，但TACE（使用或不使用DEBs）在很大程度上依赖于临床医生的经验和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（由于肿瘤未完全杀死或部分治疗）。该基金的目标是通过以下方式观察、触及和治疗肿瘤：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。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，以提高肿瘤成像和靶向性；(2)优化给药方案并在临床中试研究中验证；(3)制定治疗成功的量化指标，并将其与术后MRI进行比较。学术界和工业界的伙伴关系将有助于将动物和回顾性人体研究的结果转化为改进的商业产品，然后在人体中进行前瞻性测试。

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.