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.
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.