Using [18F]Fluorothymidine Imaged With Positron Emission Tomography to Quantify and Reduce Hematologic Toxicity Due to Chemoradiation Therapy for Pelvic Cancer Patients

Abstract

The purpose of the present prospective clinical trial was to determine the efficacy of [(18)F]fluorothymidine (FLT)-identified active bone marrow sparing for pelvic cancer patients by correlating the FLT uptake change during and after chemoradiation therapy with hematologic toxicity. Simulation FLT positron emission tomography (PET) images were used to spare pelvic bone marrow using intensity modulated radiation therapy (IMRT BMS) for 32 patients with pelvic cancer. FLT PET scans taken during chemoradiation therapy after 1 and 2weeks and 30days and 1year after completion of chemoradiation therapy were used to evaluate the acute and chronic dose response of pelvic bone marrow. Complete blood counts were recorded at each imaging point to correlate the FLT uptake change with systemic hematologic toxicity. IMRT BMS plans significantly reduced the dose to the pelvic regions identified with FLT uptake compared with control IMRT plans (P<.001, paired t test). Radiation doses of 4Gy caused an ∼50% decrease in FLT uptake in the pelvic bone marrow after either 1 or 2weeks of chemoradiation therapy. Additionally, subjects with more FLT-identified bone marrow exposed to ≥4Gy after 1week developed grade 2 leukopenia sooner than subjects with less marrow exposed to ≥4 Gy (P<.05, Cox regression analysis). Apparent bone marrow recovery at 30days after therapy was not maintained 1year after chemotherapy. The FLT uptake in the pelvic bone marrow regions that received >35Gy was 18.8%±1.8% greater at 30days after therapy than at 1year after therapy. The white blood cell, platelet, lymphocyte, and neutrophil counts at 1year after therapy were all lower than the pretherapy levels (P<.05, paired t test). IMRT BMS plans reduced the dose to FLT-identified pelvic bone marrow for pelvic cancer patients. However, reducing hematologic toxicity is challenging owing to the acute radiation sensitivity (∼4Gy) and chronic suppression of activity in bone marrow receiving radiation doses >35Gy, as measured by the FLT uptake change correlated with the complete blood cell counts.