Abstract 2596: Time to first morning cigarette and lung cancer in National Lung Screening Trial
Authors: Gu Fangyi , Katki Hormuzd , Freedman Neal , Marcus Pam , Caporaso Neil 
Published: July 2016

Abstract
In the National Lung Screening Trial (NLST), the effectiveness of lung cancer screening by low-dose computed tomography (CT) depended on individual lung cancer risk. Time to fist cigarette (TTFC) is an easily assessed component of nicotine dependency that may be an independent predictor of lung cancer risk. We validated the independent association of TTFC with lung cancer and assessed whether including TTFC into risk prediction models might improve CT screening effectiveness.
We examined associations between TTFC and lung cancer incidence and mortality in the 18,729 participants of the ACRIN component of the NLST, which included 773 lung cancer diagnoses and 299 lung cancer deaths. Multivariable cox-proportional hazard regression models, adjusted for other metrics of smoking use and lung cancer risk factors, were used. In terms of screening effectiveness, we predicted each participant's 5-year cumulative lung cancer death risk using multivariable models that excluded or included TTFC. We then investigated 3 possible screening strategies based on risk scores from each model (for a total of six strategies): in each model scenario, those with a 5-year risk score above one of three thresholds (0.5%, 0.75%, and 1%) would be screened, whereas others would not. For each risk threshold, we compared screening sensitivities (the percentage who would have been screened among smokers who died of lung cancer) and specificities (the percentages who would not have been screened among smokers without lung cancer) between models without and with TTFC. We also estimated the absolute reduction in lung cancer death risk, due to screening, within each TTFC group (&lt;15, 15-59, ≥60 minutes (min)).
Compared to smokers with TTFC≥60 min, smokers with shorter TTFC had higher lung cancer incidence [hazard ratios (HR) and 95% confidence intervals (CI) for TTFC 30-59 min = 1.69(1.19-2.41), HR15-29min = 1.72(1.22-2.43), HR6-14min = 2.05(1.48-2.84), HR&lt;5min = 2.19(1.59-3.02), p-trend&lt;0.001] and mortality [HR30-59min = 2.10(1.11-3.96), HR15-29min = 1.91(1.02-3.59), HR6-14min = 2.59(1.43-4.69), HR&lt;5min = 2.77(1.54-4.97), p-trend&lt;0.001]. With regards to lung cancer screening, fewer lung cancer deaths would be avoided by screening smokers with TTFC≥60 min compared to screening smokers with TTFC 15-59 min or TTFC&lt;15 min (2.03 vs. 4.99 vs. 7.38 lung cancer deaths avoided per 10000 person-years, respectively). Adding TTFC to the multivariable risk prediction algorithm increased the specificity of screening for all three risk thresholds by 1.6-2% (p&lt;0.01) while maintaining sensitivity.
We confirmed the independent inverse association between TTFC and lung cancer in NLST. Smokers with a TTFC greater than 60 min had less benefit from CT screening than smokers with a shorter TTFC. By increasing specificity and maintaining sensitivity, including TTFC in risk prediction models may more precisely identify those who benefit less from CT lung screening.
Citation Format: Fangyi Gu, Hormuzd Katki, Neal Freedman, Pam Marcus, Neil Caporaso. Time to first morning cigarette and lung cancer in National Lung Screening Trial. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2596.