Four-dimensional Adaptive Thoracic Radiotherapy

最近的临床数据显示，常规药物和药物的剂量-肿瘤反应关系明确 分割和低分割非小细胞肺癌放射治疗；几项大型研究证实 肺、食道、心脏和支气管的剂量-毒性关系。然而，肺癌会随着 呼吸，根据骨骼解剖每天改变位置，并普遍减少 放射治疗过程中的体积。这些解剖改变阻碍了准确的成像、计划 以及胸部放射治疗的提供，因此阻碍了我们最大化治疗窗口的能力 在局部控制/存活和治疗引起的并发症之间。 呼吸门控、屏气放射治疗和四维放射治疗的进展 解释了一些呼吸运动问题，然而，这些技术引入了额外的 尚未解决的问题。例如，4D CT采集中的呼吸不规律 过程本身表现为图像伪像，随后表现为整个过程中的系统错误 治疗疗程。解剖运动和呼吸信号之间的时间变化用作 此动议的代理引入了重大错误，因为代理与 解剖运动是依赖于位置的，并且解剖运动和代理运动在不同的周期和 今天是第一天。 该项目的总体目标是系统地量化整个过程中的解剖变异。 对有代表性的患者队列进行放射治疗，制定策略以减轻变异的影响， 因此，在严格考虑残留不确定性的同时，将其临床影响降至最低。至 实现目标的具体目标是： (1)进行临床影像研究，以量化两者间的大小和分布。 分数内的解剖变异，包括肿瘤的时间稳定性与呼吸信号的相关性。 (2)通过(A)推进4D CT数据来改进4D CT图像的采集和重建 收集过程和(B)评估使用不同呼吸输入的4D CT图像重建 除了量化可变形图像配准算法的不确定性外， 4D IGART。 (3)开发和研究基于分数间和分数内概率的4D IGART的有效性 临床应用策略和执行模拟研究以确定剂量学和生物学 从4D IGART系统中获得改进。 该项目的高潮是4D IGART安全性和有效性研究的临床实施。

Recent clinical data demonstrates a clear dose-tumor response relationship for both conventional fractionation and hypofractionated nonsmall-cell lung cancer radiotherapy; several large studies confirm the dose-toxicity relationship for lung, esophagus, heart and bronchus. However, lung tumors move with respiration, change position with respect to skeletal anatomy from day to day, and generally decrease in volume during a course of radiotherapy. These anatomic changes hinder the accurate imaging, planning and delivery of thoracic radiotherapy and, hence, impede our ability to maximize the therapeutic window between local control/survival and treatment-induced complications. Developments in respiratory gating, breath-hold radiotherapy and four-dimensional (4D) radiotherapy account for some of the respiratory motion issues, however, these techniques have introduced additional problems that have yet to be addressed. For example, respiratory irregularities in the 4D CT acquisition process manifest themselves as image artifacts and subsequently as systematic errors throughout the entire treatment course. Temporal variations between anatomy motion and the respiratory signal used as a surrogate for this motion introduce significant errors, since the correlation between the surrogate and anatomy motion is location-dependent, and anatomy and surrogate motions vary from cycle to cycle and day today. The overall goal of the project is to systematically quantify anatomic variations throughout a course of radiotherapy for a representative patient cohort, develop strategies to mitigate the effect of the variations, and, thereby, minimize their clinical impact whilst rigorously accounting for the residual uncertainties. To achieve the goal the specific aimsare: (1) To conduct a clinical imaging study to quantify the magnitude and distribution of inter- and intrafraction anatomic variations, including the temporal stability of the tumor/respiration signal correlation. (2) To improve the acquisition and reconstruction of 4D CT images by (a) advancing the 4D CT data collection process and (b) evaluating 4D CT image reconstruction using different respiratory inputs, in addition to quantifying the uncertainty of deformable image-registration algorithms, a core tool for 4D IGART. (3) To develop and investigate the efficacy of inter- and intrafraction probabilistic-based 4D IGART strategies for clinical application and to perform simulation studies to determine the dosimetric and biological improvement gains from the 4D IGART system. The culmination of the project is the clinical implementation of 4D IGART safety and efficacy studies.