Association of Preexisting Interstitial Lung Abnormalities With Immune Checkpoint Inhibitor–Induced Interstitial Lung Disease Among Patients With Nonlung Cancers

Shimoji, Kiyofumi; Masuda, Takeshi; Yamaguchi, Kakuhiro; Sakamoto, Shinjiro; Horimasu, Yasushi; Nakashima, Toshikatsu; Miyamoto, Shintaro; Iwamoto, Hiroshi; Fujitaka, Kazunori; Hamada, Hironobu; Takeno, Sachio; Hide, Michihiro; Teishima, Jun; Ohdan, Hideki; Hattori, Noboru

doi:10.1001/jamanetworkopen.2020.22906

Cited by 44 publications

(26 citation statements)

References 27 publications

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“…Conversely, interstitial pneumonia was correlated with symptomatic pneumonitis in this study. Similarly, some studies identified ILD as a risk factor for immune-mediated pneumonitis [ 15 – 18 ]. ILD is also a risk factor in radiation pneumonitis [ 36 , 37 ] and other anticancer drug-related pneumonitis cases [ 38 , 39 ], which should be noted in pneumonitis.…”

Section: Discussionmentioning

confidence: 99%

“…Predictors with p -values < 0.10 in the univariate analysis were included in a multivariate model. ILD is the most common consensus clinical parameter related to the development of pneumonitis [ 15 – 18 ]. We selected ILD from previous studies and also selected the parameters from the results of univariate analysis and performed multivariate analysis.…”

Section: Methodsmentioning

confidence: 99%

“…However, the risk of developing pneumonitis from smoking and lung lesions in patients with other types of cancer, except lung cancer, is unknown. Other than the presence of interstitial lung disease (ILD) [ 15 – 18 ] and differences in carcinoma, the risk factors for pneumonitis are unclear. Therefore, we analyzed risk factors, including smoking and lung metastasis (LM), for pneumonitis in extrapulmonary primary tumors.…”

Section: Introductionmentioning

confidence: 99%

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Risk factors for pneumonitis in advanced extrapulmonary cancer patients treated with immune checkpoint inhibitors

et al. 2022

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Background Immune-mediated pneumonitis has a high mortality rate; however, information regarding the related risk factors remains limited. This study aimed to analyze risk factors for pneumonitis, including smoking and lung metastasis (LM), in patients with extrapulmonary primary tumors. Methods Data of 110 patients treated with immune checkpoint inhibitors (ICIs) (nivolumab/pembrolizumab) for treating extrapulmonary primary tumors at the Shiga University of Medical Science Hospital between January 2015 and December 2019 were retrospectively collected. The association between the onset of pneumonitis and treatment-related factors was analyzed by logistic regression. The severity of pneumonitis was graded according to the Common Terminology Criteria for Adverse Events version 5.0. Risk factors, such as the absence or presence of interstitial lung disease (ILD) and LM, or other clinical factors, including smoking status before ICI administration, were analyzed. Results Multivariate analyses indicated that the amount of smoking was significantly associated with an increase in the development of all-grade pneumonitis types (odds ratio (OR) = 20.33, 95% confidence interval (CI) = 20.03–20.66; p = 0.029). LM and ILD were significantly related to an increase in the development of symptomatic pneumonitis (≥ Grade 2) (OR = 10.08, 95% CI = 1.69–199.81; p = 0.076, and OR = 6.76, 95% CI = 1.13–40.63; p = 0.037, respectively). Conclusions Pre-screening for ILD and LM and recognizing patients’ smoking history is important for determining the risk of ICI-induced pneumonitis and allowing safe ICI administration.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Risk factors for pneumonitis in advanced extrapulmonary cancer patients treated with immune checkpoint inhibitors

et al. 2022

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“…Therefore, the effect of the existing ILD subtypes other than IPF was not investigated. As GGOs were reported to be an independent risk factor for ICI‐ILD in previous reports, 25,26 it is possible that there are populations with high AE risk among the ILDs classified as alternative diagnosis. To clarify the risk of AEs due to ICI in lung cancer complicated by ILDs, a large‐scale study including ILD patients with GGO‐dominant imaging patterns will be necessary.…”

Section: Discussionmentioning

confidence: 92%

Risk factors for acute exacerbation in lung cancer complicated by interstitial lung disease with slight reticular shadows

et al. 2021

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Background The risk of cancer treatment‐related acute exacerbation (AE) in patients with lung cancer and mild interstitial lung disease (ILD) on imaging, classified as indeterminate for usual interstitial pneumonia (UIP), has not previously been clarified. Methods We retrospectively reviewed the clinical records of 27 patients with lung cancer and ILD who were diagnosed and treated from April 2016 to March 2021. Results Among the 27 patients, 21 were classified as indeterminate for UIP and six as UIP/probable UIP; furthermore, 10 (46.6%) and three (50%) patients from each group, respectively, developed treatment‐related AEs. No significant difference was observed regarding the incidence of AEs between the two groups. However, significantly more patients in the AE group received immune checkpoint inhibitors (ICIs) compared to the non‐AE group (p = 0.021). Multivariate analysis revealed that the use of ICIs was a significant independent risk factor for treatment‐related AEs. Conclusions Lung cancer patients with mild ILD suggestive of indeterminate for UIP and UIP patterns are at an increased risk for treatment‐related AEs. Furthermore, ICI use is an independent risk factor for AEs in patients with lung cancer complicated by ILD, and ICIs should be used with great caution.

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“…Thus, the reasons for the association of ILA and lung cancer are not fully clear and future research must clarify whether it is a result of residual confounding or biological mechanisms [ 20 , 65 ]. On that note, ILA have been found to be a risk factor for postoperative complications after lung cancer surgery, such as ARDS, pneumonia and respiratory failure [ 66 ] as well as severe radiation pneumonitis after radiation for small cell lung cancer [ 67 , 68 ] and immune checkpoint inhibitor-induced interstitial lung disease among patients with lung cancer and other malignancies [ 69 , 70 ]. Among other outcomes associated with ILA in lung cancer screening studies are diagnoses of pneumonia, pleural empyema or lung abscesses, and respiratory failure [ 19 ].…”

Section: Clinical Outcomesmentioning

confidence: 99%

Interstitial lung abnormalities – current knowledge and future directions

Axelsson

Guðmundsson

2021

European Clinical Respiratory Journal

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Association of Preexisting Interstitial Lung Abnormalities With Immune Checkpoint Inhibitor–Induced Interstitial Lung Disease Among Patients With Nonlung Cancers

Cited by 44 publications

References 27 publications

Risk factors for pneumonitis in advanced extrapulmonary cancer patients treated with immune checkpoint inhibitors

Risk factors for pneumonitis in advanced extrapulmonary cancer patients treated with immune checkpoint inhibitors

Risk factors for acute exacerbation in lung cancer complicated by interstitial lung disease with slight reticular shadows

Interstitial lung abnormalities – current knowledge and future directions

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