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In The oncologist

BACKGROUND : Patients with non-small cell lung cancer (NSCLC) may develop pneumonitis after thoracic radiotherapy (RT) and immune-checkpoint inhibitors (ICI). We hypothesize that distinct morphologic features are associated with different pneumonitis etiologies.

MATERIALS AND METHODS : We systematically compared CT features of RT vs. ICI-pneumonitis. Clinical and imaging features were tested for association with pneumonitis severity. Lastly, we constructed an exploratory radiomics-based machine learning (ML) model to discern pneumonitis etiology.

RESULTS : Between 2009 and 2019, 82 patients developed pneumonitis: 29 after thoracic RT, 23 after ICI, and 30 after RT+ICI. Fifty patients had grade 2 pneumonitis, 22 grade 3, and 7 grade 4. ICI-pneumonitis was more likely bilateral (65% vs. 28%, p=0.01), involved more lobes (66% vs. 45% involving ≥3 lobes), and was less likely to have sharp border (17% vs. 59%, p=0.004) compared to RT-pneumonitis. Pneumonitis morphology after RT+ICI was heterogeneous, with 47% bilateral, 37% involving ≥3 lobes and 40% sharp borders. Among all patients, risk factors for severe pneumonitis included poor performance status, smoking history, worse lung function, bilateral and multifocal involvement on CT. A ML model based on seven radiomic features alone could distinguish ICI from RT-pneumonitis with an area under the receiver-operating curve of 0.76, and identified the predominant etiology after RT+ICI concordant with multidisciplinary consensus.

CONCLUSION : RT and ICI-pneumonitis exhibit distinct spatial features on CT. Bilateral and multifocal lung involvement is associated with severe pneumonitis. Integrating these morphologic features in the clinical management of patients who develop pneumonitis after RT and ICI may improve treatment decision making.

IMPLICATIONS FOR PRACTICE : Patients with non-small cell lung cancer often receive thoracic radiation and immune checkpoint inhibitors (ICI), both of which can cause pneumonitis. In this study, we identified similarities and differences in pneumonitis morphology on CT scans among pneumonitis due to RT alone, ICI alone, and the combination of both. Patients who have bilateral CT changes involving ≥3 lobes are more likely to have ICI-pneumonitis, while those with unilateral CT changes with sharp borders are more likely to have radiation pneumonitis. After RT and/or ICI, severe pneumonitis is associated with bilateral and multifocal CT changes. Our results can help guide clinicians in triaging patients who develop pneumonitis after radiation and during ICI treatment.

Chen Xuguang, Sheikh Khadija, Nakajima Erica, Lin Cheng Ting, Lee Junghoon, Hu Chen, Hales Russell K, Forde Patrick M, Naidoo Jarushka, Voong Khinh Ranh


Immune Checkpoint Inhibitor, Immune-Related Adverse Event, Immune-Related Pneumonitis, Non-Small Cell Lung Carcinoma, Radiation Pneumonitis