RADIATION DOSE ESCALATION FOR FOCAL LIVER CANCER

局灶性肝癌的辐射剂量增加

• 批准号: 6286908
• 负责人: CORNELIUS J MCGINN
• 金额: $ 31.71万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-01-11 至 2005-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6286908
• 关键词: clinical research; clinical trial phase I; human subject; human therapy evaluation; liver neoplasms; neoplasm /cancer radiation therapy; radiation sensitivity; radiation therapy dosage

It is known that partial volumes of liver can tolerate a tumoricidal dose of therapeutic radiation if sufficient normal liver is spared. However, the exact relationship between dose, volume of normal liver spared, and risk of complication has not been established. The development of 3D radiation treatment planning technology has allowed for a reduction in the volume of normal liver irradiated (more accurate targeting) and provided quantification of the volume of normal liver treated. A mathematical model to predict the normal tissue complication probability (NTCP) for an individual treatment plan has been developed as well. We have utilized 3D technology and an NTCP model to safely escalate the dose of focal hepatic radiation in prior and current phase I clinical trials conducted over the past 10 years. Local control and survival data are encouraging. However, the parameters of the model currently utilized are based on data with substantial uncertainties related to liver motion and patient setup. In specific Aim 1, we plans to complete a phase one study to determine the maximum safe dose of radiation for focal liver malignancies, while accounting for positional uncertainties in the NTCP parameter definitions, allowing delivery of significantly higher doses of radiation than was possible using our earlier approach. Current planning techniques require the inclusion of a margin of normal liver for these uncertainties, to ensure adequate target coverage. In Specific Aim 2, we hypothesize that reduction of liver motion together with investigation of patient setup will allow for treatment of smaller target volumes, which will subsequently permit an increase in the dose delivered without increasing the risk of RILD (radiation induced liver disease). In Specific Aim 3 we will evaluate outcome of patients treated on a phase II trial, to determine if application of improved estimates of parameters for the NTCP model, and reduction in the volume of normal liver irradiated will allow safe delivery of higher radiation doses resulting in improved survival rates in patients with intrahepatic malignancies that warrant further study in a phase III setting.

众所周知，部分肝脏体积可以耐受 如果有足够的正常肝脏存活，则治疗辐射的肿瘤杀伤剂量。 然而，剂量、正常肝脏体积、 并发症的风险尚未确定。3D的发展 放射治疗计划技术允许减少 照射的正常肝脏体积（更准确的靶向），并提供 对所治疗的正常肝脏的体积进行定量。一个数学模型来 预测个体的正常组织并发症概率（NTCP） 治疗方案也已制定。我们利用3D技术， 一个NTCP模型，用于安全地递增既往局灶性肝辐射的剂量 以及过去10年进行的I期临床试验。当地 控制和存活数据令人鼓舞。然而，模型的参数 目前使用的是基于与以下方面有关的大量不确定性的数据， 肝脏运动和患者设置。在具体目标1中，我们计划完成一个阶段， 一项确定局灶性肝脏最大安全辐射剂量的研究 恶性肿瘤，同时考虑NTCP中的位置不确定性 参数定义，允许递送显著更高剂量的 辐射比我们以前的方法更强。当前规划 这些技术需要包括正常肝脏的边缘， 不确定性，以确保充分的目标覆盖面。在Aim Specific 2中，我们 假设肝脏运动减少， 患者设置将允许治疗较小的靶体积，这将 随后允许增加递送的剂量而不增加 放射性肝病（RILD）。在第三阶段，我们将 评估II期试验中接受治疗的患者的结局，以确定 应用改进的NTCP模型参数估计，以及 减少正常肝脏受照射的体积将允许安全输送 更高的辐射剂量导致患者的生存率提高， 肝内恶性肿瘤，值得进一步研究的第三阶段设置。