Improving Cancer Outcome--Adaptive Helical Tomotherapy

长期目标是通过使用一种名为螺旋断层治疗的新方法来改善人类癌症的结果。螺旋断层放射治疗是调强放射治疗和螺旋CT的结合，具有提供精细适形、持续验证和快速适应的能力。它使两个假设得到验证：(1)适形剂量的增加将导致局部控制的改善，而不会增加epsilon并发症，并在选定的患者亚群中，提高存活率。我们建议通过在第一阶段试验中增加每部分的剂量来升级，以确定未来第三阶段测试的适当时间表。(2)适形避开处于危险状态的正常组织将减少并发症的发生率，从而提高生活质量。这是适用的，特别是当肿瘤体积不能确定，虽然正常的危险组织可以准确地描绘。对这两个假说的检验的中心是断层治疗提供适应性放射治疗的能力，该能力适应靶区几何形状和治疗提供的持续变化。在研究项目1中，我们将进一步开发放射治疗的优化方法，包括实施适应性放射治疗。这允许闭合回路在持续的基础上校正辐射传递中先前未检测到的错误。在研究项目2和3中，我们将使用通过分数大小递增的共性链接的断层治疗的能力来执行剂量递增。在项目3中，将根据前列腺癌缓慢的增殖和减少的照射体积，对前列腺癌使用分数尺寸递增进行剂量递增。在研究项目4和5中，我们将使用第二阶段临床试验方法，在犬鼻咽癌和人类头颈癌中测试共形避免策略。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。该计划项目代表了一项统一的努力，使用具有不同项目之间多程度协同的适应性断层治疗能力，测试剂量递增和适形避免。当这一计划项目完成后，它对放射肿瘤学实践的影响可能与1960年代引进的直线加速器一样大。我们的计划项目将使放射治疗达到科学和技术成熟的水平，在未来，可以通过第三阶段试验进行技术相互比较。

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.