Improving Pelvic Cancer Patient Chemoradiotherapy Outcomes with FLT PET Imaging

描述(申请人提供)：盆腔癌患者的总体生存取决于对全身疾病的控制。如果局部放射治疗耗尽了骨髓功能，以至于必须停止全身治疗，那么转移失败的机会就会显著增加。限制毒性的策略可以使包括妇科、肛门、直肠和前列腺癌在内的一系列盆腔癌患者受益。化疗和放射治疗的新组合显示，所有这些疾病部位的结果都有所改善，但这是以更高水平的毒性为代价的。我们的初步数据证明了这一独特的能力 对两名宫颈癌患者进行Flt PET检查，以确定骨盆内的骨髓增殖区，并监测其对放化疗的反应。这一放射物理治疗计划项目建议将Flt PET的这些功能整合到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预后。最初，在模拟放射治疗计划时将拍摄一张Flt PET图像。这幅图像将用于在放射治疗计划设计和优化期间将骨盆中的骨髓活跃区域识别为回避区域。急性毒性将通过监测在化疗后一周和两周后拍摄的Flt PET图像测量的骨髓剂量反应来评估，该图像与成像时采集的完整血细胞计数相关。此外，在化疗结束30天和一年后，将进行Flt PET成像和完整的血细胞计数，以评估作为辐射剂量函数的骨髓活动的恢复情况，以及这对慢性毒性的影响。治疗过程中对骨髓活性耗竭和治疗后恢复至关重要的剂量阈值可用于改进计划技术和优化治疗设计，以将急性和慢性毒性降至最低。这些减少毒性的放射计划策略可能会改善治疗的依从性，从而为盆腔癌患者带来更好的结果。此外，急性和慢性毒性的降低都可能为剂量的增加提供机会，以便更好地控制肿瘤或在必要时进行抢救治疗。为了最大限度地减少毒性和最大化治疗结果，最优的治疗设计可能应该考虑患者特定的治疗前骨髓活动空间图、治疗期间骨髓反应和治疗后骨髓恢复之间的相互关系。 公共卫生相关性：该项目与公共卫生的相关性很大。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，将骨盆癌患者的化疗放射治疗的毒性降至最低。这可能会通过增加治疗的耐受性和完成计划疗程的几率，以及通过为患者提供在新的治疗组合中耐受更高剂量的潜力，以更好地控制肿瘤，从而改善患者的预后。

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.