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Smoking cessation and the manifestation of lung malignancy: A provocative association

Principal Investigator
Name
Mohamed Abazeed
Degrees
MD, PhD
Institution
Cleveland Clinic Foundation
Position Title
Assistant Professor
Email
About this CDAS Project
Study
NLST (Learn more about this study)
Project ID
NLST-85
Initial CDAS Request Approval
Aug 12, 2014
Title
Smoking cessation and the manifestation of lung malignancy: A provocative association
Summary
The etiology of the increased risk of malignancy shortly after tobacco cessation is largely unstudied and results in a substantial number of lung cancers in an era of declining tobacco consumption rates. Tobacco smoke contains more than 7000 chemical and more than 60 known or suspected carcinogens. It has been thoroughly established that tobacco smoke delivers chemicals that mimic the toxicity associated with traditional chemotherapy and radiation (i.e. genotoxic and oxidative stress). We hypothesize that the temporally restricted increased risk of lung cancer after tobacco cessation is a function of the release of tumor-control attributed to inhalation of varied chemicals in tobacco. This time restricted release competes with the more enduring decrease in lung cancer incidence that results from the removal of carcinogenic exposure. The kinetic interplay of these two processes (tobacco smoke-mediated tumor control and tumor-progression by sequential carcinogen-induced genetic alterations) is consistent with the observed incidence curve in the reformed smoker. Herein, we propose to establish clinical and preclinical models for the study of the increased risk of lung cancer after tobacco cessation for the purpose of improved intervention in this putative high-risk group.
Aims

S.A: Evaluate the impact of tobacco cessation on lung cancer incidence in reformed smokers undergoing low dose CT screening.
Hypothesis: There is an increased risk of lung cancer incidence in reformed smokers in the period of up to five years after tobacco cessation compared to current smokers in a modern patient cohort undergoing low dose CT screening.
Rationale: We will expand on the aforementioned epidemiological observations to determine the impact of smoking cessation on patient outcomes in a cohort of patients receiving low dose CT screening using the NLST database. The NLST study is less likely to show reverse causality bias due to the study requirement of exclusion of persons who were symptomatic (hemoptysis, weight loss, et cetera).
Design, Methods, and Expected Outcomes: The NLST database consists of 53,454 current and reformed smokers that were randomly assigned to be screened once a year for 3 years with low-dose CT and chest X-ray (4). 26,722 individuals were screened with low-dose CT; 12,862 were current smokers and 13,860 were reformed smokers. 7,630 of all participants in the low-dose CT arm were reformed smokers who ceased tobacco for 0-5 years prior to or during the period of screening. There were a total of 1060 cancers diagnosed in the low-dose CT group. Taken together, the sample size indicates that this study would have 90% power to detect a 20% increase in incidence in recently (up to five years) reformed smokers compared to current smokers. We will analyze patient outcomes to compare the incidence of lung cancer diagnosis (by histological criteria) and stage of lung cancer in reformed smokers (0-5 years since cessation) and current smokers. Event rates will be defined as the ratio of the number of events to the person-years at risk for the event in each group (current smoker and recently reformed smoker). For the incidence calculations, person-years will be measured from the time of randomization to the date of diagnosis of lung cancer, death, or censoring of data (whichever came first). We will calculate the confidence intervals for incidence ratios assuming a Poisson distribution for the number of events and a normal distribution of the logarithm of the ratio, using asymptotic methods. This analysis will determine the impact of smoking cessation on the incidence of lung cancer and lung cancer progression in a modern patient cohort.

Collaborators

Peter Mazzone, MD
Craig Peacock, PhD
Chandana Reddy, PhD
Tomas Radiyoyevitch, PhD
Rupesh Kotecha, MD