RADIATION DOSE ESCALATION FOR FOCAL LIVER CANCER

众所周知，部分体积的肝脏可以耐受一种 如果没有足够的正常肝脏，治疗性照射的杀瘤剂量。 然而，剂量、正常肝脏体积、 并发症的风险尚未确定。3D技术的发展 放射治疗计划技术已经允许减少 正常肝脏的照射体积(更精确的定位)并提供 对治疗后的正常肝脏体积进行量化。一种数学模型来 预测个体的正常组织并发症概率(NTCP) 治疗计划也已经制定出来。我们利用了3D技术和 一种安全地增加PERVER肝脏局灶性放射剂量的NTCP模型 以及目前在过去10年中进行的I期临床试验。本地 控制力和存活率数据令人鼓舞。然而，该模型的参数 当前使用的数据基于与以下内容相关的大量不确定性的数据 肝脏运动和病人设置。在具体目标1中，我们计划完成一个阶段 一项确定局灶性肝病最大安全辐射剂量的研究 恶性肿瘤，虽然解释了NTCP中的位置不确定性 参数定义，允许提供显著更高剂量的 比我们早先使用的方法可能产生的辐射更多。当前规划 技术上需要包括正常肝脏的边缘 不确定因素，以确保足够的目标覆盖。在具体目标2中，我们 假设肝脏运动的减少与对 患者设置将允许治疗较小的目标体积，这将 随后允许增加所提供的剂量而不增加 RILD(放射性肝病)的风险。在具体目标3中，我们将 评估患者在II期试验中的治疗结果，以确定 应用改进的NTCP模型参数估计，以及 减少正常肝脏的照射体积将允许安全地输送 较高的辐射剂量可提高癌症患者的存活率 值得在III期环境中进一步研究的肝内恶性肿瘤。

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.