Purpose/objective; Adjuvant immunotherapy improves survival after chemoradiotherapy (chemoRT) in advanced non-small-cell lung cancer (NSCLC). Immunotherapy requires a functioning immune system. Bone marrow is exquisitely radiosensitive and lymphopenia is common after chemoRT. We used serial 18F-fluorothymidine (FLT)-PET scans to quantify loss of proliferating bone marrow during chemoRT and correlated bone marrow ablation with changes in circulating lymphocyte counts.
Materials/methods; We analysed FLT-PET scans from 28 patients from a prospective observational trial of serial PET imaging in NSCLC patients treated with chemoRT to 60 Gy. FLT-PET scans, performed at baseline and weeks 2 and 4 were available for 28 patients. The bony skeleton was auto-segmented, enabling FLT uptake in bone marrow to be quantified. The percentage of total injected FLT delivered to bone marrow provided a baseline value. Based on quantitative dose response analyses, volumes of bone marrow exposed to >3 Gy at weeks 2 and 4 were considered to have had no FLT-PET-detectable marrow proliferation. The percentage of the total injected dose of FLT missing from the bone marrow in the volume irradiated to >3 Gy was estimated by comparing 3 Gy isodose volumes at weeks 2 and 4 with the baseline scan. Changes in lymphocyte nadir from baseline to week 2 and baseline to week 4 were analysed. Estimated percentage losses of marrow from baseline to weeks 2 and 4 were correlated with percentage loss of lymphocyte counts.
Results; During chemoradiotherapy, proliferation ceased in bone marrow irradiated even to low doses of radiation. A scatter plot of percentage loss of bone marrow vs percentage change in lymphocyte counts at weeks 2 and 4 was produced. The percentage loss of FLT uptake in bone marrow and reductions in lymphocyte counts were positively correlated from baseline to both weeks 2 and 4. The correlation from baseline to week 4 was highly significant (p<0.003).
Conclusion; There was a strong correlation between the estimated percentage of proliferating bone marrow ablated during radiotherapy and reduction in lymphocyte counts from baseline to week 4. Minimising marrow irradiation may preserve lymphocyte counts for effective adjuvant immunotherapy.