OPTIMIZATION OF HIGH DOSE CONFORMAL THERAPY

（申请人描述）本项目的总体目标是继续研究和改进癌症的高剂量适形放射治疗方法。之前的项目研究了方案优化、适形给药技术、与患者相关的几何不确定性，并帮助确定了限制正常组织的治疗的剂量/体积耐受边界，同时表明适形治疗可以显著提高肿瘤剂量，而不会增加并发症。目前，越来越复杂的工具（自动优化软件，强度调制放射治疗（IMRT），改进的患者和靶体积定位方法以及开始更全面地表征组织对辐射反应的模型）可用于利用先前资助的进展进一步优化个体患者治疗。因此，该项目将致力于优化整个治疗计划和交付过程。项目1将检查和评估增强的自动化优化能力，该能力开始包括计划/交付过程的所有相关部分。项目2将调查和评估不同优化策略和IMRT输送能力的剂量学影响和局限性。项目3将研究和评估将与患者相关的几何不确定性纳入适形剂量分布的计算、编制和处理的益处。项目4将以前所未有的高剂量水平治疗患者，因为它完成了脑、肝和肺的正常组织耐受剂量递增试验，完成了头颈部和前列腺的正常组织剂量减少研究，并进入II期（肺、肝、脑）和头颈部和前列腺的剂量递增试验。这些项目由核心A（行政和统计支持）、核心B（自动化治疗交付过程）、核心C（优化治疗计划/交付过程的质量保证）和核心D（计算机软件支持）提供支持。研究人员拥有独特的能力组合来成功地完成这项工作，基于超过14年的临床3-D治疗计划，适形治疗，剂量递增和计算机控制治疗递送的经验。

DESCRIPTION (Applicant's Description) The overall objective of this program project is to continue the study and improvement of high dose conformal radiation therapy treatments for cancer. The previous program project studied plan optimization, conformal dose delivery techniques, patient related geometrical uncertainties, and helped define the dose/volume tolerance boundaries of treatment limiting normal tissues while showing that conformal therapy allowed significantly higher tumor doses to be delivered without increasing complications. Currently, increasingly sophisticated tools (automated optimization software, intensity modulated radiation therapy (IMRT), improved methods for patient and target volume localization and models to begin to more fully characterize the response of tissues to irradiation) are available to leverage the progress of the previous grant toward further optimization of individual patient treatments. Thus, this program project will work to optimize the entire treatment planning and delivery process. Project 1 will examine and evaluate enhanced automated optimization capabilities which begin to include all relevant parts of the planning/delivery process. Project 2 will investigate and evaluate the dosimetric impact and limitations of different optimization strategies and IMRT delivery capabilities. Project 3 will research and evaluate the benefits of inclusion of patient-related geometric uncertainties into the calculation, compilation and treatment of conformal dose distributions. Project 4 will treat patients to unprecedented high dose levels as it completes normal tissue tolerance dose escalation trials in the brain, liver, and lung, finishes normal tissue dose reduction studies in the head/neck and prostate, and moves on to Phase II (lung, liver, brain) and head/neck and prostate escalation trials. The projects are supported by Core A (administrative and statistical support), Core B (automated treatment delivery process), Core C (quality assurance for an optimized treatment planning/delivery process), and Core D (computer software support). The investigators possess a unique combination of capabilities to successfully perform this work, based on more than 14 years experience in clinical 3-D treatment planning, conformal therapy, dose escalation, and computer-controlled treatment delivery.