FLT PET Quantification of Incomplete Pelvic Bone Marrow Recovery After Chemoradiation

Abstract

To quantify the long-term effects of chemoradiation therapy on pelvic bone marrow with FLT PET imaging. Ten pelvic cancer patients were enrolled and completed an IRB-approved protocol designed to obtain FLT PET/CT images prior to chemoradiation therapy and 30 days and 1 year after chemotherapy was completed. All FLT PET images were registered to the radiation therapy planning CT by first registering the attenuation correction CT using the pelvic bones, and then copying the transformation matrix to the corresponding FLT PET image. Pretherapy images were used as a control for pelvic bone marrow FLT uptake change and to create active bone marrow avoidance regions in IMRT optimization. Radiation therapy plans were created to spare as much active bone marrow identified by the pretherapy FLT PET image as possible without compromising target dose or other normal tissue objectives. In order to analyze bone marrow activity changes as measured by FLT PET images, the dose distributions for each subject were divided into 1 Gy/week dose volume bins within the bony pelvis. The mean FLT PET standardized uptake value (SUV) was then recorded from all images in each dose bin at each time point. Complete blood counts were also collected for each subject at the time of each FLT PET scan. For the ten subjects imaged that completed all five FLT PET images, apparent recovery seen at 30 days was lost at 1 year as measured by FLT uptake in the regions that received radiation doses >25 Gy. On average, bone marrow activity as measured by mean FLT SUV returned to 56.4% ± 17.7% and 54.0% ± 15.5% of its pretherapy level in regions that received 20 – 25 Gy at 30 days and 1 year post therapy, respectively. The percentage of baseline FLT uptake was within 3% or slightly improved at 1 year in bone marrow receiving 25 Gy or less when compared to 30 day images. In regions that received >35 Gy, the percentage of baseline FLT uptake at 30 days was 18.8% ± 1.8% greater than that at 1 year. This pattern of recovery was also seen in CBC metrics. At 30 days, WBCs, platelets, and lymphocytes were statistically significantly lower than baseline values (P < .05, paired t-test). At 1 year; WBCs, platelets, neutrophils, and lymphocytes values were all statistically significantly lower than baseline values (P < .05, paired t-test). FLT PET imaging data measuring the long-term effects of chemoradiation therapy on pelvic bone marrow may indicate that apparent bone marrow recovery 30 days after therapy is not sustained 1 year after therapy in those regions receiving doses more than 25 Gy. Recovery sustained at 1 year is incomplete and inversely proportional to radiation dose.