Purpose18F-Fluorothymidine(FLT)-PET enables sensitive imaging of bone marrow (BM) proliferation. Sequential FLT-PET/CT scans before and during chemoradiation (CRT) for non-small cell lung cancer (NSCLC) were repurposed to investigate dose-response effects of radiation on BM proliferation. Methods and materialsTwenty-six NSCLC patients underwent platinum-based CRT to 60Gy in 30 fractions with FLT-PET/CT scans at baseline, week 2 (20Gy) and week 4 (40Gy). FLT uptake in BM was isolated using Medical Image Merge software. Week 2 and week 4 FLT-PET BM scans were fused with contemporaneous radiation isodose distributions. Relationships between radiation dose and FLT BM uptake (SUVmax and visual parameters) were analyzed using generalized-linear and restricted cubic-spline models. Percentage volumes of total BM without appreciable FLT uptake (“ablated”) on week 2 and week 4 FLT-PET scans were calculated by comparisons with baseline scans. ResultsThoracic FLT uptake was ablated in BM regions exposed to cumulative radiation doses ≥3Gy by week 2. In all cases BM FLT SUVmax declined rapidly as radiation dose increased. BM proliferation significantly decreased by more than 95% after ≥3-4Gy at 2 weeks and ≥4-5Gy at 4 weeks. The ablated BM volume increased from week 2 to week 4 as BM in the penumbra accumulated radiation dose. Median percentage of total BM ablated was 13.1% (range 5.6-20.3) at 2 weeks and 15.7% (range 9.2 - 24.1) at 4 weeks. Mean lymphocyte counts fell from baseline of 2.01×109/L to 0.77 week 2, and 0.60 week 4. Lymphocyte decline strongly correlated with percentage of total BM ablated by week 4 (y=-46 -1.64 x, R2adj = 0.34, p=0.001). ConclusionsBM ablation associated with low dose-radiation exposure during CRT correlated significantly with lower week 4 lymphocyte counts. BM is a potential organ-at-risk and reducing the BM volume exposed to ≥3Gy may help preserve lymphocytes essential for effective adjuvant immunotherapy.
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