Khinh Ranh Voong1, Sarah Z Hazell2, Wei Fu3, Chen Hu3, Cheng Ting Lin4, Kai Ding2, Karthik Suresh5, Jonathan Hayman5, Russell K Hales2, Salem Alfaifi2, Kristen A Marrone6, Benjamin Levy7, Christine L Hann7, David S Ettinger7, Josephine L Feliciano7, Valerie Peterson7, Ronan J Kelly7, Julie R Brahmer6, Patrick M Forde6, Jarushka Naidoo6. 1. Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University, Baltimore, MD. Electronic address: Kvoong1@jhmi.edu. 2. Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University, Baltimore, MD. 3. Department of Oncology, Biostatistics, Johns Hopkins University School of Medicine, Baltimore, MD. 4. Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD. 5. Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD. 6. Department of Oncology, Johns Hopkins University, Baltimore, MD; Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University, Baltimore, MD. 7. Department of Oncology, Johns Hopkins University, Baltimore, MD.
Abstract
PURPOSE: To investigate the relationship between radiotherapy (RT), in particular chest RT, and development of immune-related (IR) pneumonitis in non-small-cell lung cancer (NSCLC) patients treated with anti-programmed cell death 1 (PD-1)/programmed death ligand 1 (PD-L1). PATIENTS AND METHODS: Between June 2011 and July 2017, NSCLC patients treated with anti-PD-1/PD-L1 at a tertiary-care academic cancer center were identified. Patient, treatment, prior RT (intent, technique, timing, courses), and IR pneumonitis details were collected. Treating investigators diagnosed IR pneumonitis clinically. Diagnostic IR pneumonitis scans were overlaid with available chest RT plans to describe IR pneumonitis in relation to prior chest RT. We evaluated associations between patient, treatment, RT details, and development of IR pneumonitis by Fisher exact and Wilcoxon rank-sum tests. RESULTS: Of the 188 NSCLC patients we identified, median follow-up was 6.78 (range, 0.30-79.3) months and median age 66 (range, 39-91) years; 54% (n = 102) were male; and 42% (n = 79) had stage I-III NSCLC at initial diagnosis. Patients received anti-PD-1/PD-L1 monotherapy (n = 127, 68%) or PD-1/PD-L1-based combinations (n = 61, 32%). In the entire cohort, 70% (132/188) received any RT, 53% (100/188) chest RT, and 37% (70/188) curative-intent chest RT. Any grade IR pneumonitis occurred in 19% (36/188; 95% confidence interval, 13.8-25.6). Of those who developed IR pneumonitis and received chest RT (n = 19), patients were more likely to have received curative-intent versus palliative-intent chest RT (17/19, 89%, vs. 2/19, 11%; P = .051). Predominant IR pneumonitis appearances were ground-glass opacities outside high-dose chest RT regions. CONCLUSION: No RT parameter was significantly associated with IR pneumonitis. On subset analysis of patients who developed IR pneumonitis and who had received prior chest RT, IR pneumonitis was more common in patients who received curative-intent chest RT. Attention should be paid to NSCLC patients receiving curative-intent RT followed by anti-PD-1/PD-L1 agents.
PURPOSE: To investigate the relationship between radiotherapy (RT), in particular chest RT, and development of immune-related (IR) pneumonitis in non-small-cell lung cancer (NSCLC) patients treated with anti-programmed cell death 1 (PD-1)/programmed death ligand 1 (PD-L1). PATIENTS AND METHODS: Between June 2011 and July 2017, NSCLC patients treated with anti-PD-1/PD-L1 at a tertiary-care academic cancer center were identified. Patient, treatment, prior RT (intent, technique, timing, courses), and IR pneumonitis details were collected. Treating investigators diagnosed IR pneumonitis clinically. Diagnostic IR pneumonitis scans were overlaid with available chest RT plans to describe IR pneumonitis in relation to prior chest RT. We evaluated associations between patient, treatment, RT details, and development of IR pneumonitis by Fisher exact and Wilcoxon rank-sum tests. RESULTS: Of the 188 NSCLC patients we identified, median follow-up was 6.78 (range, 0.30-79.3) months and median age 66 (range, 39-91) years; 54% (n = 102) were male; and 42% (n = 79) had stage I-III NSCLC at initial diagnosis. Patients received anti-PD-1/PD-L1 monotherapy (n = 127, 68%) or PD-1/PD-L1-based combinations (n = 61, 32%). In the entire cohort, 70% (132/188) received any RT, 53% (100/188) chest RT, and 37% (70/188) curative-intent chest RT. Any grade IR pneumonitis occurred in 19% (36/188; 95% confidence interval, 13.8-25.6). Of those who developed IR pneumonitis and received chest RT (n = 19), patients were more likely to have received curative-intent versus palliative-intent chest RT (17/19, 89%, vs. 2/19, 11%; P = .051). Predominant IR pneumonitis appearances were ground-glass opacities outside high-dose chest RT regions. CONCLUSION: No RT parameter was significantly associated with IR pneumonitis. On subset analysis of patients who developed IR pneumonitis and who had received prior chest RT, IR pneumonitis was more common in patients who received curative-intent chest RT. Attention should be paid to NSCLC patients receiving curative-intent RT followed by anti-PD-1/PD-L1 agents.
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