Combinatie van bestraling en immunotherapie verhoogt pneumonitisrisico bij longkanker, CT-karakteristieken helpen bij differentiatie

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: Seventy-one patients developed pneumonitis: 36/163 in the RT-only group (22.1%), 18/116 in the ICI-only group (15.5%), and 17/36 in the RT + ICI group (47.2%, p < 0.001). The ICI-only group showed involvement of more lobes vs. RT + ICI and RT-only (4.06 vs. 3.41 vs. 3.21 respectively; p = 0.03) and a trend toward more bilateral disease (83%, 65%, and 58%; p = 0.06). RT-only patients exhibited more bronchiectasis vs. RT + ICI and ICI-only (47%, 18%, and 6% respectively; p = 0.003), while consolidations were less frequent in the ICI-only group (50%, 75%, and 75%; p = 0.04). Low-grade pneumonitis (grade < 3) was more often associated with an organizing pneumonia pattern (p = 0.01), whereas higher-grade cases showed other radiologic patterns.Risk factors for high-grade pneumonitis included pre-existing interstitial lung disease (ILD; 14% vs. 2%, p = 0.03) and lower baseline diffusion capacity (52.2 ± 15.3% vs. 71.0 ± 21.4%; p = 0.004). High-grade pneumonitis developed earlier (52.5 ± 49.5 vs. 133.0 ± 101.6 days; p < 0.001) and was more frequently bilateral (100% vs. 59%; p = 0.003).Quantitative CT analysis revealed significant differences between lung regions receiving high (>10 Gy) and low (<10 Gy) radiation doses across all evaluated features. In high-dose regions, the RT + ICI group exhibited more severe lung damage than the RT-only group (e.g., entropy, p = 0.017), whereas no differences were observed in low-dose regions (p > 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.