Assessment of pulmonary ¹⁸F-FDG-PET uptake and cytokine profiles in non-small cell lung cancer patients treated with radiotherapy and erlotinib

Purpose: To investigate effects of radiotherapy (RT) and erlotinib on pulmonary glucose uptake using 2-deoxy-2-(18F)fluoro-D-glucose (¹⁸F-FDG) positron emission tomography (PET) during and after treatment of non-small cell lung cancer (NSCLC) and to identify associations between serum cytokine levels and lung glucose uptake.

Material and methods: Twenty-seven patients with advanced NSCLC, receiving RT alone or concomitant RT and erlotinib therapy, were examined by ¹⁸F-FDG PET before, during, and after treatment. A total of 57 ¹⁸F-FDG PET scans were analyzed. Pulmonary ¹⁸F-FDG uptake and radiotherapy dose mapping were used to acquire dose-response curves for each patient, where subsequent linear regression gave a glucose uptake level in the un-irradiated parts of the lungs (SUV₀) and a response slope (ΔSUV). Serum cytokine levels at corresponding time points were assessed using a multiplex bioassay. Correlations between the most robust cytokines and lung ¹⁸F-FDG dose response parameters were further investigated.

Results: From the dose response analysis, SUV₀ at post-therapy was significantly higher (P < 0.001) than at mid- and pre-therapy (45% and 58%, respectively) for the group receiving RT + erlotinib. Also, SUV₀ at post-therapy was higher for patients receiving RT + erlotinib compared to RT alone (42%; P < 0.001). No differences in ΔSUV were seen with treatments or time. SUV₀ was positively associated (r = 0.47, P = 0.01) with serum levels of the chemokine C-C motif ligand 21 (CCL21) for patients receiving RT + erlotinib.

Conclusions: Concomitant RT and erlotinib causes an elevation in pulmonary ¹⁸F-FDG uptake post treatment compared to RT alone. Pulmonary glucose uptake is associated with an upregulation of a chemokine (CCL21) involved in inflammatory reactions.