Incidence and risk factors for pneumonitis among patients with lung cancer who received immune checkpoint inhibitors after palliative thoracic radiotherapy

The aim of this study is to analyze the incidence and risk factors for pneumonitis when immune checkpoint inhibitors (ICIs) are combined with palliative thoracic radiotherapy (RT) for lung cancer. We retrospectively evaluated 29 patients with lung cancer who received ICIs after palliative thoracic RT (30 Gy in 10 fractions). Their ICIs were pembrolizumab (n = 17), nivolumab (n = 8) and atezolizumab (n = 4). Median follow-up period was 10 months. The median interval between starting RT and starting ICI was 25 days. Pneumonitis events were grade 1 (n = 10; 34%), grade 2 (n = 4; 14%) and grade 3 (n = 3; 10%). Obstructive pneumonia was significantly associated with grade ≥ 2 pneumonitis (P = 0.036). Age, sex, ICI agent, interval between RT and ICI and history of ICI before RT were not associated with grade ≥ 2 pneumonitis. Tumor volume; Brinkman index; dosimetric factors, such as lung V5, V10, V20, V30 and mean lung dose (MLD); lactate dehydrogenase; and C-reactive protein did not significantly differ between the grade ≤ 1 and grade ≥ 2 pneumonitis groups. Levels of sialylated carbohydrate antigen KL-6 were evaluated in 27 patients before RT; they significantly differed between patients with grade ≤ 2 pneumonitis (mean: 431 U/ml) and those with grade ≥ 3 pneumonitis (mean: 958 U/ml; P < 0.001). Patients who receive ICI after palliative thoracic RT should be carefully followed-up, especially those who have had obstructive pneumonia or high KL-6 levels.