Randomized trial of doxorubicin beads for arterial embolization of hepatocellular

描述(申请人提供)：肝细胞癌(HCC)是世界上第五大最常见的癌症，随着丙型肝炎发病率的增加而变得更加常见。尽管缺乏证据表明TACE与不化疗的栓塞术相比具有优越性，但TACE已成为无法切除的肝癌患者的标准治疗方法。与化疗的使用相关的财务和毒性问题使得确定最佳的肝细胞癌动脉栓塞术方法变得重要。一种可以装载阿霉素的微珠已经被开发出来，用于肝动脉栓塞术，导致肿瘤内药物的高度延长浓度。为了评估阿霉素在肝动脉肝动脉栓塞术中的作用，我们将进行第一次随机试验，以确定使用普通微珠和填充150毫克阿霉素微珠在治疗反应、进展时间和总存活率方面的差异。在目标1中，我们建议通过增强CT扫描显示存活肿瘤的变化来描述治疗后的放射学反应。AIM 2旨在验证一种评估肿瘤坏死的自动CT体积方法，并将该方法与评估治疗反应的传统方法相关联。目的3将确定药物洗脱微珠的使用是否会增加进展时间或生存时间，以及治疗反应(根据治疗后最初CT扫描中肿瘤坏死的发展情况)是否可以作为结果的替代生物标志物。这项研究很重要，因为它将提供关于阿霉素在肝动脉栓塞术中的作用的客观数据，以及栓塞剂成本增加的理由。我们对毒性的了解可能会改变化疗药物经动脉给药的方式，不仅是对肝癌，而且对任何多血管的肝肿瘤。针对肝肿瘤的靶向化疗有可能对临床结果产生重大影响，并可能改善没有其他公认治疗方法的患者的总体存活率。对于所有癌症患者和癌症研究人员来说，验证一种新的评估治疗反应的成像方法对于所有癌症患者和癌症研究人员都很重要。美国肝细胞癌的发病率正在上升。绝大多数患者在确诊时并不是手术对象，而是接受肝动脉治疗。对于是否需要使用化疗药物进行动脉内治疗存在争议。化疗的使用不仅增加了费用，还增加了潜在的毒性。这项研究旨在确定动脉化疗的增量价值，以及验证评估治疗反应的自动成像方法。

DESCRIPTION (provided by applicant): Hepatocellular cancer (HCC) is the 5th most common cancer in the world, and has become more common with the increased incidence of hepatitis C. Transcatheter chemoembolization (TACE) has become the standard treatment for patients with unresectable HCC, despite the lack of evidence demonstrating the superiority of TACE compared to embolization without chemotherapy. There are financial and toxicity concerns associated with the use of chemotherapy that make it important to define the best method of arterial emboliztion for HCC. A microscopic bead has been developed that can be loaded with doxorubicin and used for hepatic arterial embolization, resulting in high prolonged concentration of drug within the tumor. To assess the role of doxorubicin in hepatic arterial embolization of HCC, we will conduct the first randomized trial to determine the difference in response to treatment, time to progression and overall survival using a plain bead versus the bead loaded with 150 mg of doxorubicin. In Aim 1 we propose to characterize the radiologic response to treatment as manifest by change in viable tumor on contrast enhanced CT scans. Aim 2 is designed to validate an automated CT volumetric method of assessing tumor necrosis, and correlate this method with conventional means of assessing response to treatment. Aim 3 will establish whether use of the drug eluting bead increases the time to progression or survival, and whether response to treatment, as estimated by development of tumor necrosis on the initial post-treatment CT scans, can be used as a surrogate biomarker for outcome. This study is important because it will provide objective data regarding the role of doxorubicin in hepatic arterial embolization, and justification for the increased cost of the embolic agent. What we learn about toxicity will likely change the way that chemotherapeutic agents are administered transarterially, not just for HCC but for any hypervascular liver tumor. Targeting chemotherapy to liver tumors has the potential to have a significant impact on clinical outcome, and may improve the overall survival of patients for whom there is no other recognized treatment. The validation of a new imaging method of assessing response to treatment that might replace current less sensitive methods is important for all cancer patients and cancer investigators The incidence of hepatocellular carcinoma (HCC) in the United States is increasing. The vast majorities of patients are not operative candidates at the time of diagnosis, and are treated with hepatic arterial therapies. Controversy exists regarding the need to use chemotherapeutic agents for intra-arterial treatment. The use of chemotherapy adds not only expense, but potential toxicity. This study is designed to determine the incremental value of arterial chemotherapy, as well as to validate an automated imaging method of assessing response to treatment.