Personalising lung cancer screening

Randomised clinical trials have shown the efficacy of computed tomography lung cancer screening, initiating discussions on whether and how to implement population-based screening programs. Due to smoking behaviour being the primary risk-factor for lung cancer and part of the criteria for determining screening eligibility, lung cancer screening is inherently risk-based. In fact, the selection of high-risk individuals has been shown to be essential in implementing lung cancer screening in a cost-effective manner. Furthermore, studies have shown that further risk-stratification may improve screening efficiency, allow personalisation of the screening interval and reduce health disparities. However, implementing risk-based lung cancer screening programs also requires overcoming a num

Additional file 1 of Risk prediction models for lung cancer in people who have never smoked: a protocol of a systematic review

Additional file 1: Table S1. PRISMA-P 2015 Checklist. Table S2. Primary literature search. Database: Ovid MEDLINE(R) and Epub Ahead of Print, InProcess, In-Data-Review & Other Non-Indexed Citations, Daily and Versions

Evaluation of the Lung Cancer Risks at Which to Screen Ever- and Never-Smokers: Screening Rules Applied to the PLCO and NLST Cohorts

<div><p>Background</p><p>Lung cancer risks at which individuals should be screened with computed tomography (CT) for lung cancer are undecided. This study's objectives are to identify a risk threshold for selecting individuals for screening, to compare its efficiency with the U.S. Preventive Services Task Force (USPSTF) criteria for identifying screenees, and to determine whether never-smokers should be screened. Lung cancer risks are compared between smokers aged 55–64 and ≥65–80 y.</p><p>Methods and Findings</p><p>Applying the PLCO_m2012 model, a model based on 6-y lung cancer incidence, we identified the risk threshold above which National Lung Screening Trial (NLST, <i>n = </i>53,452) CT arm lung cancer mortality rates were consistently lower than rates in the chest X-ray (CXR) arm. We evaluated the USPSTF and PLCO_m2012 risk criteria in intervention arm (CXR) smokers (<i>n = </i>37,327) of the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO). The numbers of smokers selected for screening, and the sensitivities, specificities, and positive predictive values (PPVs) for identifying lung cancers were assessed. A modified model (PLCO_all2014) evaluated risks in never-smokers. At PLCO_m2012 risk ≥0.0151, the 65th percentile of risk, the NLST CT arm mortality rates are consistently below the CXR arm's rates. The number needed to screen to prevent one lung cancer death in the 65th to 100th percentile risk group is 255 (95% CI 143 to 1,184), and in the 30th to <65th percentile risk group is 963 (95% CI 291 to −754); the number needed to screen could not be estimated in the <30th percentile risk group because of absence of lung cancer deaths. When applied to PLCO intervention arm smokers, compared to the USPSTF criteria, the PLCO_m2012 risk ≥0.0151 threshold selected 8.8% fewer individuals for screening (<i>p<</i>0.001) but identified 12.4% more lung cancers (sensitivity 80.1% [95% CI 76.8%–83.0%] versus 71.2% [95% CI 67.6%–74.6%], <i>p<</i>0.001), had fewer false-positives (specificity 66.2% [95% CI 65.7%–66.7%] versus 62.7% [95% CI 62.2%–63.1%], <i>p<</i>0.001), and had higher PPV (4.2% [95% CI 3.9%–4.6%] versus 3.4% [95% CI 3.1%–3.7%], <i>p<</i>0.001). In total, 26% of individuals selected for screening based on USPSTF criteria had risks below the threshold PLCO_m2012 risk ≥0.0151. Of PLCO former smokers with quit time >15 y, 8.5% had PLCO_m2012 risk ≥0.0151. None of 65,711 PLCO never-smokers had PLCO_m2012 risk ≥0.0151. Risks and lung cancers were significantly greater in PLCO smokers aged ≥65–80 y than in those aged 55–64 y. This study omitted cost-effectiveness analysis.</p><p>Conclusions</p><p>The USPSTF criteria for CT screening include some low-risk individuals and exclude some high-risk individuals. Use of the PLCO_m2012 risk ≥0.0151 criterion can improve screening efficiency. Currently, never-smokers should not be screened. Smokers aged ≥65–80 y are a high-risk group who may benefit from screening.</p><p><i>Please see later in the article for the Editors' Summary</i></p></div

Mortality rates, rate ratios, and rate differences in NLST participants by trial arm and by decile of PLCO_m2012 risk.

<p>PLCO_m2012 model risk decile boundaries were established in PLCO control smokers.</p><p>*Rate difference is incidence rate in CT arm per 10,000 minus incidence rate in CXR arm per 10,000. A negative absolute rate indicates a lower rate of lung cancer death in the CT arm compared to the CXR arm. PLCO_m2012 refers to the lung cancer risk prediction model described in <a href="http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.1001764#pmed.1001764-Tammemgi1" target="_blank">[11]</a>.</p><p>NA, not applicable (because of zero occurring in denominator).</p><p>Mortality rates, rate ratios, and rate differences in NLST participants by trial arm and by decile of PLCO_m2012 risk.</p

Distribution of observations and lung cancer events by USPSTF criteria and PLCO_m2012 risk ≥0.0151 criterion status in PLCO intervention arm smokers.

<p>Bold indicates informative cells in which disagreement exists between the two classification criteria. PLCO_m2012 refers to the lung cancer risk prediction model described in <a href="http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.1001764#pmed.1001764-Tammemgi1" target="_blank">[11]</a>.</p><p>Distribution of observations and lung cancer events by USPSTF criteria and PLCO_m2012 risk ≥0.0151 criterion status in PLCO intervention arm smokers.</p