Pneumonitis after chemoradiotherapy and/or immunotherapy for stage III and IV non-small cell lung cancer is characterized by specific radiologic and quantitative CT features

Background: Patients with unresectable stage III non-small cell lung cancer (NSCLC) receive a combination of chemotherapy (CT), thoracic radiation therapy (RT) and immune checkpoint inhibition (ICI). Stage IV NSCLC with a high PD-L1 tumor proportion score receive first line treatment with ICI. These new therapies and combinations can give rise to pneumonitis due to RT but also due to ICI, both etiologies being notoriously difficult to disentangle. In this work follow-up CT scans with pneumonitis after these treatments were explored in a radiologic pattern and a quantitative CT feature analysis. Materials and methods: This retrospective, single-center study included patients with pneumonitis of any grade who received chemoradiotherapy with or without durvalumab (RT-only group and RT + ICI group) for unresectable stage III NSCLC between 2011 and 2021, as well as patients with pneumonitis who received pembrolizumab as first-line therapy (ICI-only group) for stage IV NSCLC between 2017 and 2021. Clinical data and computed tomography (CT) scans were collected at baseline and follow-up. A radiologist compared CT characteristics among the three groups to identify patterns of radiotherapy-related and ICI-related pneumonitis. Furthermore, quantitative imaging features of lung damage derived from follow-up CT scans were compared between different lung regions within the same patient and across treatment groups. Results: > 0.20). Imaging features from the ICI-only group most closely resembled those from high-dose regions of the RT-only group which may suggest a synergistic effect of radiotherapy and ICI in developing lung injury in the RT + ICI group. Conclusion: A significantly higher incidence of pneumonitis was observed in patients treated with combined RT and ICI. High-grade pneumonitis was more often bilateral, presented with distinct radiologic patterns, developed earlier, and was associated with pre-existing ILD and reduced diffusion capacity. Quantitative CT analysis confirmed that the combination of moderate- to high-dose lung irradiation with ICI therapy leads to greater severity of lung damage.