Abstract

PurposeTo microsimulate the effects of three additional annual CT screening rounds on lung cancer (LC) survival in the National Lung Screening Trial (NLST). MethodsWe used multiple imputation to model the effect of additional screening in the full NLST cohort on the time to LC diagnosis and on LC death in those participants who were diagnosed with LC by the end of NLST. Nodule growth models were derived from a Dutch in-vivo study. Microsimulations were repeated 500 times. The method was validated by simulating three rounds of CT screening in the original chest radiography (CXR) cohort. The times up to which the simulations remained within the 95 % confidence bands of the CT cohort’s original results were used to estimate the validity of the results in the CT cohort with three additional simulated screening rounds. ResultsValidation of the simulation approach on the CXR cohort resulted in a LC mortality reduction which remained well within the 95 % confidence intervals of the original CT cohort up to 6.5 years after the start of simulations. Simulating additional CT screening in the CT cohort led to LCs being diagnosed earlier than originally, resulting in a relative risk reduction in LC mortality of 11 % (95 % confidence bands, 7 %–14 %) at 6.5 years. This is equivalent to preventing 71 % (48 %–94 %) more LC deaths than the original CT cohort achieved in comparison to the original CXR cohort. ConclusionThree additional annual CT screening rounds in the NLST may have led to substantial further LC mortality reduction.

Highlights

  • Lung cancer (LC) is currently the leading cause of cancer-related deaths [1]

  • The National Lung Screening Trial (NLST) was the first randomized controlled trial to find a significant reduction in LC mortality and overall mortality within the annual low-dose computed tomography (CT) screening cohort (n = 26722) compared to chest radiography (CXR) (n = 26730) [2]

  • We summarize the pro­ cedure for each run of the simulation as follows: 1 The first step was to create a copy of the original CXR cohort of participants who were eventually diagnosed with LC and who orig­ inally participated in at least one round of screening

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Summary

Introduction

Lung cancer (LC) is currently the leading cause of cancer-related deaths [1]. One strategy to decrease LC deaths is early detection using low-dose chest computed tomography (CT). The National Lung Screening Trial (NLST) was the first randomized controlled trial to find a significant reduction in LC mortality and overall mortality within the annual low-dose CT screening cohort (n = 26722) compared to chest radiography (CXR) (n = 26730) [2]. A limitation was that participants only underwent three annual screening rounds (T0, T1, and T2), making it difficult to make inferences about the added benefit of screening for extended periods. We hereby aimed to quantify the added benefit to the original NLST findings had screening continued for another three years (T3, T4, and T5) beyond the third screening round (T2). We used retrospective data from NLST participants diagnosed with LC, forced to model new outcomes with three additional CT screening rounds

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