Quantification of CT-assessed radiation-induced lung damage in lung cancer patients treated with or without chemotherapy and cetuximab

Background and Purpose: Prediction models for radiation-induced lung damage (RILD) are still unsatisfactory, with clinical toxicity endpoints that are difficult to quantify objectively. We therefore evaluated RILD more objectively, quantitatively and on a continuous scale measuring the lung tissue density changes per voxel.Material and methods: Patients treated with radiotherapy (RT) alone, sequential and concurrent chemo-RT with and without the addition of cetuximab were studied. Follow-up computed tomography (CT) scans were co-registered using deformable registration to baseline CT scans. CT density changes were correlated to the RT dose delivered in every part of the lungs.Results: One hundred and seventeen lung cancer patients were included. Mean dose to tumor was 60 Gy (range 45-79.2 Gy). Dose response curves showed a linear increase in the dose region between 0 and 65 Gy having a slope (based on coefficients of the multilevel model) expressed as a lung density increase per dose of 0.86 (95% CI 0.73-0.99), 1.31 (95% CI 1.19-1.43), 1.39 (95% CI 1.28-1.50) and 2.07 (95% CI 1.93-2.21) for patients treated only with RT (N=19), sequential chemo-RT (N=30), concurrent chemo-RT (N=49), and concurrent chemo-RT with cetuximab (N=19), respectively.Conclusions: CT density changes allow quantitative assessment of lung damage after fractionated RT, giving complementary information to standard used clinical endpoints. Patients receiving cetuximab showed a significantly larger dose response compared with other treatments.