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. 2023 Mar;18(3):313-323.
doi: 10.1016/j.jtho.2022.10.020. Epub 2022 Nov 15.

Respiratory and Cardiometabolic Comorbidities and Stages I to III NSCLC Survival: A Pooled Analysis From the International Lung Cancer Consortium

Miguel García-Pardo  1 , Amy Chang  2 , Sabine Schmid  3 , Mei Dong  4 , M Catherine Brown  2 , David Christiani  5 , Hilary Aurora Tindel  6 , Paul Brennan  7 , Chu Chen  8 , Jie Zhang  9 , Brid M Ryan  10 , David Zaridze  11 , Matthew B Schabath  12 , Leticia Ferro Leal  13 , Rui Manuel Reis  14 , Adonina Tardon  15 , Guillermo Fernández-Tardon  15 , Sanjay S Shete  16 , Angeline Andrew  17 , Hermann Brenner  18 , Wei Xu  4 , Rayjean J Hung  19 , Geoffrey Liu  20
Affiliations

Respiratory and Cardiometabolic Comorbidities and Stages I to III NSCLC Survival: A Pooled Analysis From the International Lung Cancer Consortium

Miguel García-Pardo et al. J Thorac Oncol. 2023 Mar.

Abstract

Introduction: We explored the association of respiratory and cardiometabolic comorbidities with NSCLC overall survival (OS) and lung cancer-specific survival (LCSS), by stage, in a large, multicontinent NSCLC pooled data set.

Methods: On the basis of patients pooled from 11 International Lung Cancer Consortium studies with available respiratory and cardiometabolic comorbidity data, adjusted hazard ratios (aHRs) were estimated using Cox models for OS. LCSS was evaluated using competing risk Grey and Fine models and cumulative incidence functions. Logistic regression (adjusted OR [aOR]) was applied to assess factors associated with surgical resection.

Results: OS analyses used patients with NSCLC with respiratory health or cardiometabolic health data (N = 16,354); a subset (n = 11,614) contributed to LCSS analyses. In stages I to IIIA NSCLC, patients with respiratory comorbidities had worse LCCS (stage IA aHR = 1.51, confidence interval [CI]: 1.17-1.95; stages IB-IIIA aHR = 1.20, CI: 1.06-1.036). In contrast, patients with stages I to IIIA NSCLC with cardiometabolic comorbidities had a higher risk of death from competing (non-NSCLC) causes (stage IA aHR = 1.34, CI: 1.12-1.69). The presence of respiratory comorbidities was inversely associated with having surgical resection (stage IA aOR = 0.54, CI: 0.35-0.83; stages IB-IIIA aOR = 0.57, CI: 0.46-0.70).

Conclusions: The presence of either cardiometabolic or respiratory comorbidities is associated with worse OS in stages I to III NSCLC. Patients with respiratory comorbidities were less likely to undergo surgery and had worse LCSS, whereas patients with cardiometabolic comorbidities had a higher risk of death from competing causes. As more treatment options for stages I to III NSCLC are introduced into the practice, accounting for cardiometabolic and respiratory comorbidities becomes essential in trial interpretation and clinical management.

Keywords: COPD; Comorbidity; Early-stage; NSCLC.

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Conflict of interest statement

Disclosure: Ms. Brown is supported by the Alan B. Brown Chair. Dr. Christiani has received funding through grant U01 CA209414. Prof. Reis and Dr. Leal declare funding from the Public Ministry of Labor Campinas (Research, Prevention, and Education of Occupational Cancer, Brazil). Prof. Chen declares funding from the National Cancer Institute, National Institutes of Health through grants U01-CA063673, UM1-CA167462, and U01-CA167462. Dr. Liu was supported by Alan B. Brown Chair and the Lusi Wong Family Fund, Princess Margaret Cancer Foundation. The remaining authors declare no conflict of interest.

Figures

Figure 1.
Figure 1.
Consort diagram describing how the respiratory health and cardiometabolic health data sets were created with the prevalence* of comorbidities that were included in the analyses. *Prevalence of each comorbidity was calculated with the total number of patients reporting with or without the comorbidity, excluding those with missing or unknown comorbidity status. †Other heart diseases include congestive heart failure, arrhythmias, and heart valve disease.
Figure 2.
Figure 2.
Survival curves and adjusted Cox proportional hazard models for comorbidities. (A) Unadjusted Kaplan-Meier OS curves by the presence (blue lines) and absence (red lines) of either cardiometabolic health comorbidity (top row) or respiratory health comorbidity (bottom row). Median OS in years (95% CI, shading) is presented. (B) Adjusted Kaplan-Meier overall survival curves (top graph) and adjusted Cox proportional hazard models of overall survival (bottom table) for the presence (blue line) versus absence (red line) of either cardiometabolic comorbidity or respiratory health comorbidity, separately analyzed. Separate analyses were performed for individual disease stages at the time of diagnosis. Each analysis was adjusted for age, sex, race, education, smoking status, stage (for all stages and stages II and III only), and study sites. CI, confidence interval; OS, overall survival.
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