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Pre-existing interstitial lung abnormalities are risk factors for immune checkpoint inhibitor-induced interstitial lung disease in non-small cell lung cancer
Authors:Yu Nakanishi  Takeshi Masuda  Kakuhiro Yamaguchi  Shinjiro Sakamoto  Yasushi Horimasu  Taku Nakashima  Shintaro Miyamoto  Yasuhiro Tsutani  Hiroshi Iwamoto  Kazunori Fujitaka  Yoshihiro Miyata  Hironobu Hamada  Morihito Okada  Noboru Hattori
Affiliation:1. Department of Respiratory Internal Medicine, Hiroshima University Hospital, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan;2. Department of Surgical Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University Hospital, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
Abstract:BackgroundApproximately 5% of non-small cell lung cancer (NSCLC) patients develop immune checkpoint inhibitor (ICI)-induced interstitial lung disease (ICI-ILD), 10% of whom die. However, there are no established risk factors for its occurrence. Interstitial lung abnormalities (ILA) are areas of increased lung density on lung computed tomography (CT) in individuals with no known ILD. This study retrospectively investigated whether any patient characteristics, including ILA, were risk factors for ICI-ILD in patients with NSCLC.MethodsNSCLC patients who received anti-programmed death (PD)-1 antibody treatment at our hospital between September 2015 and December 2017 were enrolled. Information on patient characteristics before anti-PD-1 antibody administration, including chest CT findings and laboratory data, were obtained.ResultsAmong 83 enrolled patients, the incidence of ICI-ILD was 16.9% (14/83). All ICI-ILD cases developed by the third line of treatment. The incidence of ICI-ILD was significantly higher in patients with pre-existing ILA than that in those without (p = 0.007). Furthermore, patients with ground glass attenuation (GGA) in ILA had a higher incidence of ICI-ILD than that in those without (p < 0.001). In univariate logistic analysis, ILA were significant risk factors for ICI-ILD (p = 0.005). Multivariate logistic analysis revealed that only GGA in ILA was a significant risk factor for ICI-ILD (p < 0.001).ConclusionsPre-existing ILA are risk factors for ICI-ILD and GGA in ILA is an independent risk factor for ICI-ILD. Therefore, we should be more aware of the development of ICI-ILD in patients with ILA, especially those with GGA.
Keywords:Corresponding author. Department of Respiratory Internal Medicine, Hiroshima University Hospital, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.  Immune checkpoint inhibitors  Anti-PD-1 antibody  Immune-related adverse events  Interstitial lung abnormalities  Ground glass attenuation  NSCLC  non-small cell lung cancer  ICI-ILD  immune checkpoint inhibitor (ICI)-induced interstitial lung disease  ILA  interstitial lung abnormalities  CT  computed tomography  PD  programmed death  GGA  ground glass attenuation  ir-AEs  immune-related adverse events  HRCT  high-resolution CT  UIP  usual interstitial pneumonia  NSIP  non-specific interstitial pneumonia  OP  organizing pneumonia  OR  odds ratio  CI  confidence interval
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