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Multicenter Study
. 2024 Feb 27;19(2):e0298573.
doi: 10.1371/journal.pone.0298573. eCollection 2024.

Impact of combined pulmonary fibrosis and emphysema on lung cancer risk and mortality in rheumatoid arthritis: A multicenter retrospective cohort study

Shunsuke Mori  1 , Yukitaka Ueki  2 , Mizue Hasegawa  3 , Kazuyoshi Nakamura  4 , Kouya Nakashima  5 , Toshihiko Hidaka  6 , Koji Ishii  7 , Hironori Kobayashi  8 , Tomoya Miyamura  9
Affiliations
Multicenter Study

Impact of combined pulmonary fibrosis and emphysema on lung cancer risk and mortality in rheumatoid arthritis: A multicenter retrospective cohort study

Shunsuke Mori et al. PLoS One. .

Abstract

Objective: Combined pulmonary fibrosis and emphysema (CPFE) is a syndrome characterized by the coexistence of emphysema and fibrotic interstitial lung disease (ILD). The aim of this study was to examine the effect of CPFE on lung cancer risk and lung cancer-related mortality in patients with rheumatoid arthritis (RA).

Methods: We conducted a multicenter retrospective cohort study of patients newly diagnosed with lung cancer at five community hospitals between June 2006 and December 2021. Patients were followed until lung cancer-related death, other-cause death, loss to follow-up, or the end of the study. We used the cumulative incidence function with Gray's test and Fine-Gray regression analysis for survival analysis.

Results: A total of 563 patients with biopsy-proven lung cancer were included (82 RA patients and 481 non-RA patients). The prevalence of CPFE was higher in RA patients than in non-RA patients (40.2% vs.10.0%) at lung cancer diagnosis. During follow-up, the crude incidence rate of lung cancer-related death was 0.29 and 0.10 per patient-year (PY) in RA and non-RA patients, and 0.32 and 0.07 per PY in patients with CPFE and patients without ILD or emphysema, respectively. The estimated death probability at 5 years differed between RA and non-RA patients (66% vs. 32%, p<0.001) and between patients with CPFE and patients without ILD or emphysema (71% vs. 24%, p<0.001). In addition to clinical cancer stage and no surgery within 1 month, RA and CPFE were identified as independent predictive factors for increased lung cancer-related mortality (RA: adjusted hazard ratio [HR], 2.49; 95% confidence interval [CI], 1.65-4.76; CPFE: adjusted HR 2.01; 95% CI 1.24-3.23).

Conclusions: RA patients with lung cancer had a higher prevalence of CPFE and increased cancer-related mortality compared with non-RA patients. Close monitoring and optimal treatment strategies tailored to RA patients with CPFE are important to improve the poor prognosis of lung cancer.

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Conflict of interest statement

I have read the journal’s policy and the authors of this manuscript have the following competing interests: S. Mori received honoraria for lectures from AbbVie GK, Eli Lilly Japan K.K., Pfizer Japan Inc., Chugai Pharmaceutical Co. Ltd., Janssen Pharmaceutical K.K., Boehringer Ingelheim Japan, and Taisho Pharma Co., Ltd. and received research funds from AbbVie GK, Asahikasei Pharma Corp, and Chugai Pharmaceutical Co., Ltd. Y. Ueki received honoraria for lectures from AbbVie GK, Eli Lilly Japan K.K., Pfizer Japan Inc., Asahikasei Pharma Corp., Astellas Pharma Inc., Bristol-Myers K.K., Chugai Pharmaceutical Co. Ltd., Janssen Pharmaceutical K.K., Mitsubishi Tanabe Pharma Co., Ono Pharmaceutical Co., and Takeda Pharmaceutical Co., Ltd. T. Hidaka received honoraria for lectures from AbbVie GK, Eli Lilly Japan K.K., Pfizer Japan Inc., Asahi Kasei Pharma Corp., Bristol-Myers K.K., Chugai Pharmaceutical Co., Ltd., and Eisai Co. K. Nakamura received honoraria for lectures from AstraZeneca K.K. The other authors had no financial relationships that could create a potential conflict of interest or the appearance of a conflict of interest with regard to the work. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Figures

Fig 1
Fig 1. Cumulative incidence of lung cancer-related death in RA and non-RA patients.
Using the CIF, the cumulative incidence of lung cancer-related death in patients who were newly given a diagnosis of lung cancer is shown for the RA and non-RA groups. Numbers below these figures represent the number of patients at risk. The cumulative incidence of death over time between both groups was compared using Gray’s test (p < 0.001). RA, rheumatoid arthritis; CIF, cumulative incidence function.
Fig 2
Fig 2. Cumulative incidence of lung cancer-related death in all patients grouped by HRCT-based CPFE diagnosis.
Using the CIF, the cumulative incidence of lung cancer-related death in patients who were newly given a diagnosis of lung cancer is shown in the CPFE group, the ILD or emphysema alone group, and the group without ILD or emphysema. Numbers below these figures represent the number of patients at risk. The cumulative incidence of death over time among groups was compared using Gray’s test with the post hoc Holm’s procedure (p < 0.001 for a comparison among the three groups, CPFE vs. without ILD or emphysema, and ILD or emphysema alone vs. without ILD or emphysema). HRCT, high-resolution computed tomography; CPFE, combined pulmonary fibrosis and emphysema; ILD, interstitial pneumonia; PE, pulmonary emphysema; CIF, cumulative incidence function.
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