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• The National Lung Screening Trial only performed 3 annual CT screening rounds. • Effects of 3 additional screening rounds were microsimulated using original data. • Additional screening may have led to substantial further LC mortality reduction. To microsimulate the effects of three additional annual CT screening rounds on lung cancer (LC) survival in the National Lung Screening Trial (NLST). We 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. Validation 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. Three additional annual CT screening rounds in the NLST may have led to substantial further LC mortality reduction. [ABSTRACT FROM AUTHOR]

Objective: To assess the performance of the Brock malignancy risk model for pulmonary nodules detected in routine clinical setting.Methods: In two academic centres in the Netherlands, we established a list of patients aged ≥40 years who received a chest CT scan between 2004 and 2012, resulting in 16 850 and 23 454 eligible subjects. Subsequent diagnosis of lung cancer until the end of 2014 was established through linking with the National Cancer Registry. A nested case-control study was performed (ratio 1:3). Two observers used semiautomated software to annotate the nodules. The Brock model was separately validated on each data set using ROC analysis and compared with a solely size-based model.Results: After the annotation process the final analysis included 177 malignant and 695 benign nodules for centre A, and 264 malignant and 710 benign nodules for centre B. The full Brock model resulted in areas under the curve (AUCs) of 0.90 and 0.91, while the size-only model yielded significantly lower AUCs of 0.88 and 0.87, respectively (p<0.001). At 10% malignancy risk, the threshold suggested by the British Thoracic Society, sensitivity of the full model was 75% and 81%, specificity was 85% and 84%, positive predictive values were 14% and 10% at negative predictive value (NPV) of 99%. The optimal threshold was 6% for centre A and 8% for centre B, with NPVs >99%.Discussion: The Brock model shows high predictive discrimination of potentially malignant and benign nodules when validated in an unselected, heterogeneous clinical population. The high NPV may be used to decrease the number of nodule follow-up examinations. [ABSTRACT FROM AUTHOR]

Objectives: Perifissural nodules (PFNs) are a common finding on chest CT, and are thought to represent non-malignant lesions. However, data outside a lung cancer-screening setting are currently lacking.Methods: In a nested case-control design, out of a total cohort of 16,850 patients ≥ 40 years of age who underwent routine chest CT (2004-2012), 186 eligible subjects with incident lung cancer and 511 controls without were investigated. All non-calcified nodules ≥ 4 mm were semi-automatically annotated. Lung cancer location and subject characteristics were recorded.Results: Cases (56 % male) had a median age of 64 years (IQR 59-70). Controls (60 % male) were slightly younger (p<0.01), median age of 61 years (IQR 51-70). A total of 262/1,278 (21 %) unique non-calcified nodules represented a PFN. None of these were traced to a lung malignancy over a median follow-up of around 4.5 years. PFNs were most often located in the lower lung zones (72 %, p<0.001). Median diameter was 4.6 mm (range: 4.0-8.1), volume 51 mm3 (range: 32-278). Some showed growth rates < 400 days.Conclusions: Our data show that incidental PFNs do not represent lung cancer in a routine care, heterogeneous population. This confirms prior screening-based results.Key Points: • One-fifth of non-calcified nodules represented a perifissural nodule in our non-screening population. • PFNs fairly often show larger size, and can show interval growth. • When morphologically resembling a PFN, nodules are nearly certainly not a malignancy. • The assumed benign aetiology of PFNs seems valid outside the screening setting. [ABSTRACT FROM AUTHOR]