Risk of Lung Cancer in Lung Transplant Recipients in the United States

Matthew Triplette; Kristina Crothers; Parag Mahale; Elizabeth L. Yanik; Maryam Valapour; Charles F. Lynch; Matthew B. Schabath; David Castenson; Eric A. Engels

Disclosures

American Journal of Transplantation. 2019;19(5):1478-1490. 

In This Article

Abstract and Introduction

Abstract

Lung transplant recipients have an increased risk of lung cancer that is poorly understood. Prior studies are largely descriptive and single-center, and have not examined risk factors or outcomes in this population. This registry-linkage study utilized matched transplant and cancer registry data from 17 US states/regions during 1987–2012. We used standardized incidence ratios (SIRs) to compare incidence with the general population, Poisson models to identify lung cancer risk factors, and Cox models to compare survival after diagnosis. Lung cancer risk was increased among lung recipients (SIR 4.8, 95% confidence interval [CI] 4.1-5.5). Those with single lung transplant had 13-fold (95% CI 11–15) increased risk in the native lung. Native lung cancer risk factors included age, prior smoking, time since transplant, and idiopathic pulmonary fibrosis. Compared with cases in the general population, lung cancers in recipients were more frequently localized stage (P = .02) and treated surgically (P = .05). However, recipients had higher all-cause (adjusted hazard ratio 1.90, 95% CI 1.52-2.37) and cancer-specific mortality (adjusted hazard ratio 1.67, 95% CI 1.28-2.18). In conclusion, lung cancer risk is increased after lung transplant, especially in the native lung of single lung recipients. Traditional risk factors are associated with lung cancer in these patients. Lung cancer survival is worse among lung recipients despite earlier diagnosis.

Introduction

Lung transplant is increasingly utilized for patients with end-stage lung disease, with 13 000 US recipients alive with a functioning transplant in 2016.[1] Lung recipients face many long-term medical issues related to use of immunosuppressive medications, infection, and allograft dysfunction.[2–5] Among these risks, lung recipients have approximately twice the risk of cancer as the general population, and the incidence of lung cancer, specifically, may be even higher.[6–8] Excluding skin cancer, lung cancer represents the most common malignancy to arise after lung transplant.[8]

The increased risk of lung cancer following lung transplant is poorly understood, and may be attributable to immunosuppression, systemic inflammation, or lung infections.[9–11] For the large number of recipients with a single lung transplant (SLT) with a retained native lung, pre-existing pulmonary damage likely plays an important role as well.[12] Case series suggest that most incident lung cancers occur in the native lungs of SLT recipients, among former smokers, and among patients with pre-existing chronic obstructive pulmonary disease (COPD) or idiopathic pulmonary fibrosis (IPF).[13,14] To date, there have been no studies systematically examining specific lung cancer risk factors and outcomes in patients after lung transplant.

To understand the epidemiology of lung cancer following lung transplant, we utilized data from the Transplant Cancer Match (TCM) Study, which links US transplant and cancer registries. Our primary objectives were 3-fold: to evaluate lung cancer risk in lung recipients compared to the general population, distinguishing between cancers in the native and transplanted lungs; to evaluate risk factors for the development of lung cancer; and to compare lung cancer cases between lung recipients and other individuals with respect to histology, stage, treatment, and survival.

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