Statistics and Its Interface

Volume 15 (2022)

Number 3

Estimation of preclinical state onset age and sojourn time for heavy smokers in lung cancer

Pages: 349 – 358

DOI: https://dx.doi.org/10.4310/21-SII696

Authors

Dongfeng Wu (Department of Bioinformatics and Biostatistics, University of Louisville, Kentucky, U.S.A.)

Shesh N. Rai (Department of Bioinformatics and Biostatistics, University of Louisville, Kentucky, U.S.A.)

Albert Seow (Department of Radiology, University of Louisville, Kentucky, U.S.A.)

Abstract

Estimation of the three key parameters: onset age of the preclinical state, sojourn time and screening sensitivity is critical in cancer screening, since all other terms are functions of the three. A novel link function to connect sensitivity with time in the preclinical state and the likelihood method were used in this project; since sensitivity depends on how long one has entered the preclinical state relative to the total sojourn time. Simulations using Markov Chain Monte Carlo and maximum likelihood estimate were carried out to estimate the key parameters for male and female heavy smokers separately in the low-dose computed tomography group of the National Lung Screening Trial. Sensitivity for male and female heavy smokers were 0.883 and 0.915 respectively at the onset of the preclinical state, and increased to 0.972 and 0.981 at the end. The mean age to make the transition into the preclinical state was 70.94 or 71.15 for male and female heavy smokers respectively, and 90% of heavy smokers at risk for lung cancer would enter the preclinical state in age interval (55.7, 85.8) for males and (54.2, 87.7) for females, and the transition peaked around age 69 for both genders. The mean sojourn time in the preclinical state was 1.43 and 1.49 years, and the 99% credible intervals for the sojourn time were (0.21, 2.96) and (0.37, 2.69) years for male and female heavy smokers correspondingly. Based on the result, low-dose CT should be started at age 55 and ended before 85 for heavy smokers. This provided important information to policy makers.

Keywords

sensitivity, sojourn time, transition density, low-dose computed tomography, heavy smoker, cancer screening

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This research was partially support by NIH/NCI 1R15CA242482 (Wu). Dr. Rai was supported by the Wendell Cherry Chair in Clinical Trial Research and KY Lung Cancer Program.

Received 4 March 2021

Accepted 10 August 2021

Published 14 February 2022