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

Abstract

Purpose: 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.

Methods and materials: 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 2 weeks and 30 days and 1 year 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.

Results: 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 4 Gy caused an ∼50% decrease in FLT uptake in the pelvic bone marrow after either 1 or 2 weeks of chemoradiation therapy. Additionally, subjects with more FLT-identified bone marrow exposed to ≥4 Gy after 1 week developed grade 2 leukopenia sooner than subjects with less marrow exposed to ≥4 Gy (P<.05, Cox regression analysis). Apparent bone marrow recovery at 30 days after therapy was not maintained 1 year after chemotherapy. The FLT uptake in the pelvic bone marrow regions that received >35 Gy was 18.8% ± 1.8% greater at 30 days after therapy than at 1 year after therapy. The white blood cell, platelet, lymphocyte, and neutrophil counts at 1 year after therapy were all lower than the pretherapy levels (P<.05, paired t test).

Conclusions: 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 (∼4 Gy) and chronic suppression of activity in bone marrow receiving radiation doses >35 Gy, as measured by the FLT uptake change correlated with the complete blood cell counts.

Conflict of interest statement

Conflict of Interest: NIH Grant

Copyright © 2016 Elsevier Inc. All rights reserved.

Figures

Figure 1

1 Gy/week dose bin volumes created within the bony pelvis to analyze FLT uptake changes for one subject.

Figure 2

Tumor and Marrow Volumes-of-Interest (VOIs).

Figure 3

WB FLT PET images acquired for subject FLTPC004 at radiation therapy simulation (Week 0), 1 and 2 weeks after chemoradiation therapy (Week 1 and Week 2), and 30 days and 1-year post chemoradiation therapy (30 Days Post and 1-year).

Figure 4

Mean FLT SUV within the dose bins created for each subject normalized by the week 0 mean FLT SUV measured 1 week and 2 weeks after chemoRT as a function of the maximum radiation dose within a dose bin.

Figure 5

Kaplan-Meier plots of cumulative grade 2 hematologic toxicity probabilities. Subjects were evenly stratified into high and low derived dose categories based on the median value (3.1 G). Follow-up period extends to the time at which all patients experienced a grade 2 event or until the 1 – year follow-up imaging time point.

Figure 6

Mean FLT SUV within the dose bins created for each subject normalized by the week 0 mean FLT SUV measured 30 days and 1-year after chemoradiation therapy was complete as a function of the maximum radiation dose within a dose bin.

Figure 7

Mean WBCs, platelets, lymphocytes, and neutrophils during and after radiation therapy normalized by week 0 (baseline) values taken at the week 0 imaging time point.

Figure 8

Sacral marrow (within RT field) FLT uptake expressed as mean percent of week 0 (baseline) values for subjects with complete data at week 1 and week 2 of therapy and 30 days and 1 year post-therapy by chemotherapy regimen (red = capecitabine, green = IV 5-FU, blue = 5-FU + mitomycin, orange = cisplatin).

Figure 9

Thoracic marrow (outside RT field) FLT uptake expressed as mean percent of week 0 values (baseline) for subjects with complete data at week 1 and week 2 of therapy and 30 days and 1 year post-therapy by chemotherapy regimen (red = capecitabine, green = IV 5-FU, blue = 5-FU + mitomycin, orange = cisplatin).