Improving Pelvic Cancer Patient Chemoradiotherapy Outcomes with FLT PET Imaging

描述（由申请人提供）：盆腔癌患者的总体生存取决于系统性疾病的控制。如果局部放射治疗使骨髓功能衰竭到必须停止全身治疗的程度，则转移失败的机会显著增加。限制毒性的策略可能使一系列盆腔癌患者受益，包括妇科、肛门、直肠和前列腺癌。化疗和放疗的新组合已经显示出对所有这些疾病部位的改善结果，但它以更高水平的毒性为代价。我们的初步数据显示 的FLT PET，以确定区域的增殖骨髓内的骨盆和监测反应的放化疗治疗的两名宫颈癌患者。该放射物理治疗计划项目建议将FLT PET的这些功能纳入放射治疗计划设计中，以确定保留骨盆骨髓的最佳策略，以减少急性和慢性毒性并改善盆腔癌患者的结局。最初，将在模拟放射治疗计划时拍摄FLT PET图像。该图像将用于在放射治疗计划设计和优化期间识别骨盆中骨髓的活动区域作为避免区域。将通过监测骨髓的剂量反应来评价急性毒性，所述骨髓的剂量反应是使用在一周和两周的放化疗后拍摄的FLT PET图像测量的，与成像时拍摄的全血细胞计数相关。此外，将在放化疗完成后30天和1年进行FLT PET成像和全血细胞计数，以评价骨髓活性的恢复与辐射剂量的关系以及这如何影响慢性毒性。治疗期间对骨髓活性消耗至关重要的剂量阈值和治疗后的恢复可用于改进计划技术和优化治疗设计，以最大限度地减少急性和慢性毒性。这些减少毒性的放射计划策略可能会提高治疗的依从性，从而为盆腔癌患者带来更好的结局。此外，急性和慢性毒性的降低可能为剂量递增提供机会，以便在必要时更好地控制肿瘤或进行挽救治疗。可能的是，最佳的治疗设计，以最大限度地减少毒性和最大限度地提高治疗效果，应考虑患者特异性治疗前骨髓活性空间图之间的相互关系，治疗期间的骨髓反应，治疗后的骨髓恢复。 公共卫生相关性：该项目与公共卫生的相关性非常重要。该项目的目的是通过开发一种非侵入性成像工具来帮助减少对骨髓的辐射剂量，从而最大限度地减少盆腔癌患者放化疗的毒性。这可能通过增加治疗耐受性和完成计划疗程的几率以及通过为患者提供耐受更高剂量的新组合治疗以更好地控制肿瘤的潜力来改善患者结局。

DESCRIPTION (provided by applicant): Overall survival of pelvic cancer patients depends on control of systemic disease. If local radiation therapy depletes bone marrow function to such an extent that systemic therapies must be withheld, the chances of metastatic failure are significantly increased. Strategies to limit toxicities could benefit a range of pelvic cancer patients including gynecologic, anal, rectal, and prostate. New combinations of chemotherapy and radiation therapy have shown improved outcomes for all of these disease sites, but it has come at the cost of higher levels of toxicity. Our preliminary data demonstrates the unique ability of FLT PET to identify regions of proliferating bone marrow within the pelvis and monitor response to chemoradiation therapy for two cervical cancer patients. This radiation physics treatment planning project proposes to incorporate these features of FLT PET into radiation therapy plan design to determine the optimal strategies for sparing bone marrow in the pelvis to reduce acute and chronic toxicities and improve outcomes for pelvic cancer patients. Initially, a FLT PET image will be taken at the time of simulation for radiation therapy planning. This image will be used to identify active regions of bone marrow in the pelvis as avoidance regions during radiation therapy plan design and optimization. Acute toxicity will be evaluated by monitoring the dose response of bone marrow measured with FLT PET images taken after one and two weeks of chemoradiation therapy correlated to complete blood counts taken at the time of imaging. Additionally, FLT PET images and complete blood counts will be taken 30 days and one year after chemoradiation therapy is complete to evaluate the recovery of bone marrow activity as a function of radiation dose and how this affects chronic toxicity. The dose thresholds critical to bone marrow activity depletion during therapy and the recovery after therapy could then be used to refine planning techniques and optimize therapy design to minimize acute and chronic toxicity. These radiation planning strategies for reducing toxicities may improve compliance with therapy which will lead to better outcomes for pelvic cancer patients. In addition, both reduced acute and chronic toxicities may provide the opportunity for dose escalation for better tumor control or salvage therapies if necessary. It may be that the optimal design of therapy to minimize toxicity and maximize therapy outcomes should consider the interrelationships between patient specific pre-therapy bone marrow activity spatial maps, the response of bone marrow during therapy, and the recovery of bone marrow after therapy. PUBLIC HEALTH RELEVANCE: The relevance of this project to public health is significant. The purpose of this project is to minimize the toxicity of chemoradiation therapy for pelvic cancer patients by developing a non-invasive imaging tool to aid in reducing radiation dose to bone marrow. This may improve patient outcomes by increasing tolerance of therapy and the odds of completing the planned course of treatment as well as by providing the potential for patients to tolerate higher doses in new combinations of therapy for better tumor control.