Improving Cancer Outcome--Adaptive Helical Tomotherapy

长期目标是通过使用一种称为螺旋断层疗法的新方法来改善人类癌症的治疗效果。螺旋断层治疗是调强放疗与螺旋ct的结合，具有良好的适形性、连续验证和快速适应能力。它可以验证两个假设：(1)适形剂量递增将改善局部控制，而不会增加epsilon并发症，并且在选定的患者亚群中，可以改善生存。我们建议通过在I期试验中增加每组分的剂量来逐步升级，以便为未来的III期试验确定合适的时间表。(2)适形避开有危险的正常组织，可减少并发症的发生率，提高生活质量。这尤其适用于肿瘤体积不能确定的情况，尽管处于危险中的正常组织可以准确地描绘出来。测试这两种假设的核心是断层治疗提供适应性放射治疗的能力，以适应目标几何形状和治疗递送的持续变化。在研究项目1中，我们将进一步开发优化的断层治疗递送方法，包括实施适应性放疗。这允许一个闭环回路，以纠正以前未检测到的错误在辐射输送持续的基础上。在研究项目2和3中，我们将利用断层治疗的能力通过组分大小递增的共性进行剂量递增。在项目3中，剂量递增将根据前列腺癌的缓慢增殖和减少的照射体积使用分级递增的方法进行。在研究项目4和5中，我们将使用II期临床试验方法测试犬鼻咽癌和人类头颈癌的适形回避策略。这些项目将得到三个核心的支持：行政生物统计学和放射生物学，以及物理学、计算机和剂量学。这个项目代表了一个统一的努力，测试剂量递增和适形避免，使用适应性断层治疗能力，在不同的项目之间有不同程度的协同作用。当这个项目完成后，它将对放射肿瘤学的实践产生巨大的影响，就像20世纪60年代引入线性加速器一样。我们的计划项目将使断层治疗达到科学和技术成熟的水平，在未来，可以通过第三期试验进行技术比较。

The long-range objective is to improve outcome in human cancer by using a new approach called Helical Tomotherapy. Helical Tomotherapy is the integration of intensity modulated radiotherapy with helical computed tomography, and has the ability to provide exquisite conformality, with continuous verification and rapid adaptation. It enables two hypotheses to be tested: (1) Conformal dose escalation will lead to improved local control without increase of epsilon complications and, in selected subsets of patients, to improved survival. We propose to escalate by increasing dose-per-fraction in Phase I trials to identify to appropriate schedules for future for future Phase III testing. (2) Conformal avoidance of normal tissues at risk will reduce the incidence of complications, leading to improved quality of life. This is applicable especially where tumor volumes cannot be determined with certainty although normal tissues at risk can be delineated accurately. Central to the testing of both of these hypotheses is the capability of Tomotherapy to deliver adaptive radiotherapy which accommodates ongoing changes in target geometry and in treatment delivery. In Research Project 1 we shall further develop optimized methods of tomotherapy delivery, including the implementation of adaptive radiotherapy. This allows for a closed circuit loop to correct for previously undetected errors in radiation delivery on an ongoing basis. In Research Projects 2 and 3 we shall perform dose escalation using the capabilities of tomotherapy linked through the commonality of fraction- size escalation. In Project 3 dose escalation will be carried out using fraction-size escalation for prostate cancer based on its slow proliferation as well as on reduced volumes irradiated. In Research Project 4 and 5 we shall test the conformal avoidance strategy in canine nasopharyngeal cancer and human head and neck cancer, using Phase II clinical trial methodology. These projects will be supported by three cores: Administrative Biostatistics and Radiobiology, and Physics, Computers and Dosimetry. This program project represents a unified effort, testing both dose escalation and conformal avoidance, using adaptative tomotherapy capabilities with multiple degrees of synergy between the various projects. When this program project is complete it could have as large an impact on the practice of radiation oncology as the introduction of linear accelerators in the 1960. Our Program Project will allow Tomotherapy to reach a level of scientific and technological maturity where, in the future, technological intercomparisons through Phase III trials may be undertaken.