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The following is a summary of “Dose-response relationships between radiation exposure, bone marrow function as measured by 18F-FLT PET, and lymphocyte counts during chemoradiation for non-small cell lung cancer,” published in the September 2024 issue of Oncology by MacManus et al.

The use of 18F-Fluorothymidine (FLT)-PET has proven to be a sensitive method for imaging bone marrow (BM) proliferation. This study repurposed sequential FLT-PET/CT scans taken before and during chemoradiation therapy (CRT) for non-small cell lung cancer (NSCLC) to investigate the dose-response effects of radiation on BM proliferation. About 26 patients with NSCLC underwent platinum-based CRT, receiving a total radiation dose of 60 Gy delivered in 30 fractions. FLT-PET/CT scans were performed at baseline and during treatment at week 2 (after 20 Gy) and week 4 (after 40 Gy). BM regions with FLT uptake were isolated using Medical Image Merge software, and the week 2 and week 4 scans were fused with corresponding radiation isodose distributions to assess the relationship between radiation dose and FLT BM uptake, measured through SUVmax and visual parameters. The analysis employed generalized-linear and restricted cubic-spline models to evaluate these relationships. 

Additionally, the percentage volumes of total BM that exhibited no significant FLT uptake (“ablated”) at weeks 2 and 4 were calculated by comparison with baseline scans. The results demonstrated that thoracic BM FLT uptake was effectively ablated in regions exposed to cumulative radiation doses of 3 Gy or more by week 2. Across all patients, a marked decrease in BM FLT SUVmax was observed as the radiation dose increased, with BM proliferation reducing by over 95% after exposure to 3-4 Gy at 2 weeks and 4-5 Gy at 4 weeks. The volume of ablated BM increased from week 2 to week 4, reflecting cumulative radiation exposure in the penumbra. The median percentage of total BM ablated was 13.1% (range 5.6-20.3) at week 2, rising to 15.7% (range 9.2-24.1) by week 4. Correspondingly, mean lymphocyte counts declined significantly from a baseline of 2.01×10⁹/L to 0.77 at week 2 and 0.60 at week 4, with lymphocyte decline strongly correlating with the percentage of total BM ablated by week 4 (y = -46 -1.64x, R²_adj = 0.34, p = 0.001). 

These findings suggest that BM ablation due to low-dose radiation exposure during CRT is significantly associated with reduced lymphocyte counts at week 4. Consequently, BM should be considered a potential organ-at-risk, and minimizing BM exposure to radiation doses of 3 Gy or more could help preserve lymphocytes critical for effective adjuvant immunotherapy.

Source: sciencedirect.com/science/article/abs/pii/S0360301624032905