INDIVIDUALIZED DOSE ESCALATION IN VOLUME-EFFECT ORGANS

该提案的长期目标是增加肝内和肺肿瘤剂量， 通过优化肿瘤内的剂量分布和个体化评估正常组织， 组织毒性，通过创新的正常组织成像。这一目标将通过两个具体的 目标。目的1是优化放射治疗在肝内癌治疗中的应用。我们将 逐步增加高剂量非均匀辐射，目的是增加局部控制和可切除性。 治疗期间，我们将使用吲哚菁绿色提取物测量肝功能的总体变化， 动态增强CT扫描局部血流改变评估早期肝损伤。 这些数据将使我们能够开发一种模型，其中肝功能的早期变化可以与 治疗后出现肝毒性。我们还建议使用这个模型来开发一个新的协议，我们重新优化 在治疗过程中进行计划，以尽量减少正常的肝损伤。目标2是优化 放射疗法在治疗III期不可切除肺癌中的应用。我们将评估最佳的 在一项随机的II期试验中，化疗和放疗的时间安排。治疗期间，我们将 测量FDG-PET的变化，以评估早期肿瘤反应，以及全通气-灌注SPECT 扫描和肺功能检查以评估早期肺损伤。这些数据将使我们能够开发一种 FDG-PET成像和肺功能的早期变化与肿瘤反应相关的模型 和肺毒性。我们也建议使用这个模型来开发一个新的协议 我们在治疗过程中重新优化计划，以最大限度地控制肿瘤， 正常组织损伤我们预计这些研究将增加局部控制和切除的， 肝内癌和肺肿瘤的局部控制，同时个体化，从而最大限度地减少风险 正常组织的损伤

The long-term goal of this proposal is to increase intrahepatic and lung tumor dose and intrahepatic tumor resectability by optimizing dose distributions within the tumor and individualizing assessment of normal tissue toxicity though innovative normal tissue imaging. This goal will be carried out through two specific aims. Aim 1 is to optimize the use of radiation therapy in the treatment of intrahepatic cancer. We will escalate high dose non-uniform radiation with the goal of increasing both local control and resectability. During treatment we will measure global changes in hepatic function using indocyanine green extraction, and regional changes in blood flow using dynamic contrast-enhanced CT scanning to assess early liver injury. These data will permit us to develop a model in which early changes in liver function can be correlated with liver toxicity after treatment. We also propose to use this model to develop a new protocol in which we reoptimize planning during the course of treatment to minimize normal liver injury. Aim 2 is to optimize the use of radiation therapy in the treatment of Stage III unresectable lung cancer. We will assess the optimal timing of chemotherapy and escalated radiation in a randomized phase II trial. During treatment we will measure changes in FDG-PET, to assess early tumor response, and full ventilation-perfusion SPECT scanning and pulmonary function tests to assess early lung injury. These data will permit us to develop a model in which early changes in FDG-PET imaging and lung function can be correlated with tumor response and lung toxicity, respectively, after treatment. We also propose to use this model to develop a new protocol in which we re-optimize planning during the course of treatment to maximize tumor control and to minimize normal tissue injury. We anticipate that these studies will increase the local control and resectability of intrahepatic cancers and the local control of lung tumors while individualizing and, thus, minimizing the risk of normal tissue injury.