Population trajectories and age-dependent associations of obesity risk factors with body mass index from childhood to adolescence across European regions: A two-cohort study.

OBJECTIVE: To investigate population trajectories of behavioural risk factors of obesity from childhood to adolescence and their associations with body mass index (BMI) in children across European regions. METHODS: Data were harmonised between the European multi-centre IDEFICS/I.Family and the Amsterdam Born Children and their Development Cohort. Participants were aged 2.0-9.9 and 5.0-7.5 years at baseline, respectively, and were followed until age 18 years. Behavioural risk factors of interest included diet, physical activity, media use and sleep. Mixed effects models were used for statistical analyses to account for repeated measurements taken from the same child. RESULTS: The study included a total of 14 328 individuals: 4114, 4582, 3220 and 2412 participants from Northern, Southern, Eastern Europe and Amsterdam, respectively. Risk factor means and prevalences changed with age, but the trajectories were mostly similar across regions. Almost no associations between behavioural factors and BMI were found at the age of 6 years. At 11 years, daily sugar-sweetened foods consumption, use of active transport, sports club membership and longer nocturnal sleep duration were negatively associated with BMI in most regions; positive associations were found with media use. Most associations at 11 years of age persisted to 15 years. CONCLUSIONS: Whilst population trajectories of media use and nocturnal sleep duration are similar across European regions, those of other behavioural risk factors like active transport and daily vegetable consumption differ. Also, associations between behavioural risk factors and BMI become stronger with age and show similar patterns across regions.

Modelling individual infancy growth trajectories to predict excessive gain in BMI z-score: a comparison of growth measures in the ABCD and GECKO Drenthe cohorts.

BACKGROUND: Excessive weight gain during childhood is a strong predictor for adult overweight, but it remains unknown which growth measures in infancy (0-2 years of age), besides predictors known at birth, are the strongest predictors for excessive weight gain between 2 and 5-7 years of age. METHODS: The Amsterdam Born Children and their Development (ABCD) study formed the derivation cohort, and the Groningen Expert Center for Kids with Obesity (GECKO) Drenthe study formed the validation cohort. Change (Δ) in body mass index (BMI) z-score between 2 and 5-7 years was the outcome of interest. The growth measures considered were weight, weight-for-length (WfL), and body mass index (BMI). Formats considered for each growth measure were values at 1, 6, 12, and 24 months, at the BMI peak, the change between aforementioned ages, and prepeak velocity. 10 model structures combining different variable formats and including predictors at birth were derived for each growth measure, resulting in 30 linear regression models. A Parsimonious Model considering all growth measures and a Birth Model considering none were also derived. RESULTS: The derivation cohort consisted of 3139 infants of which 373 (11.9%) had excessive gain in BMI z-score (> 0.67). The validation cohort contained 2201 infants of which 592 (26.9%) had excessive gain. Across the 3 growth measures, 5 model structures which included measures related to the BMI peak and prepeak velocity (derivation cohort area under the curve [AUC] range = 0.765-0.855) achieved more accurate estimates than 3 model structures which included growth measure change over time (0.706-0.795). All model structures which used BMI were superior to those using weight or WfL. The AUC across all models was on average 0.126 lower in the validation cohort. The Parsimonious Model's AUCs in the derivation and validation cohorts were 0.856 and 0.766, respectively, compared to 0.690 and 0.491, respectively, for the Birth Model. The respective false positive rates were 28.2% and 20.1% for the Parsimonious Model and 70.0% and 74.6% for the Birth Model. CONCLUSION: Models' performances varied significantly across model structures and growth measures. Developing the optimal model requires extensive testing of the many possibilities.

Age-Specific Quantification of Overweight/Obesity Risk Factors From Infancy to Adolescence and Differences by Educational Level of Parents.

Objectives: To explore the age-dependent associations between 26 risk factors and BMI in early life, and differences by parental educational level. Methods: Data of 10,310 children (24,155 measurements) aged 2-16 years participating in a multi-centre European cohort from 2007 to 2014 were utilized. Trajectories of overweight/obesity risk factors and their age-specific associations with BMI were estimated using polynomial mixed-effects models. Results: Exposure to most unfavourable factors was higher in the low/medium compared to the high education group, e.g., for PC/TV time (12.6 vs. 10.6 h/week). Trajectories of various risk factors markedly changed at an age of 9-11 years. Having a family history of obesity, maternal BMI, pregnancy weight gain and birth weight were positively associated with BMI trajectories throughout childhood/adolescence in both education groups; associations of behavioural factors with BMI were small. Parental unemployment and migrant background were positively associated with BMI in the low/medium education group. Conclusion: Associations of risk factors with BMI trajectories did not essentially differ by parental education except for social vulnerabilities. The age period of 9-11 years may be a sensitive period for adopting unfavourable behaviours.

Associations of periconceptional oral contraceptive use with pregnancy complications and adverse birth outcomes.

BACKGROUND: Periconceptional use of oral contraceptives (OCs) has been reported to increase risks of pregnancy complications and adverse birth outcomes, but risks are suggested to differ depending on the timing of discontinuation, amount of oestrogen and progestin content. METHODS: Prospective cohort study among 6470 pregnancies included in the PRegnancy and Infant DEvelopment (PRIDE) Study in 2012-19. Exposure was defined as any reported use of OCs within 12 months pre-pregnancy or after conception. Outcomes of interest were gestational diabetes, gestational hypertension, pre-eclampsia, pre-term birth, low birthweight and small for gestational age (SGA). Multivariable Poisson regression using stabilized inverse probability weighting estimated relative risks (RRs) with 95% CIs. RESULTS: Any periconceptional OC use was associated with increased risks of pre-eclampsia (RR 1.38, 95% CI 0.99-1.93), pre-term birth (RR 1.38, 95% CI 1.09-1.75) and low birthweight (RR 1.45, 95% CI 1.10-1.92), but not with gestational hypertension (RR 1.09, 95% CI 0.91-1.31), gestational diabetes (RR 1.02, 95% CI 0.77-1.36) and SGA (RR 0.96, 95% CI 0.75-1.21). Associations with pre-eclampsia were strongest for discontinuation 0-3 months pre-pregnancy, for OCs containing ≥30 µg oestrogen and for first- or second-generation OCs. Pre-term birth and low birthweight were more likely to occur when OCs were discontinued 0-3 months pre-pregnancy, when using OCs containing <30 µg oestrogen and when using third-generation OCs. Associations with SGA were observed for OCs containing <30 µg oestrogen and for third- or fourth-generation OCs. CONCLUSIONS: Periconceptional OC use, particularly those containing oestrogen, was associated with increased risks of pre-eclampsia, pre-term birth, low birthweight and SGA.

Scan-based competing death risk model for re-evaluating lung cancer computed tomography screening eligibility.

BACKGROUND: A baseline computed tomography (CT) scan for lung cancer (LC) screening may reveal information indicating that certain LC screening participants can be screened less, and instead require dedicated early cardiac and respiratory clinical input. We aimed to develop and validate competing death (CD) risk models using CT information to identify participants with a low LC risk and a high CD risk. METHODS: Participant demographics and quantitative CT measures of LC, cardiovascular disease and chronic obstructive pulmonary disease were considered for deriving a logistic regression model for predicting 5-year CD risk using a sample from the National Lung Screening Trial (n=15 000). Multicentric Italian Lung Detection data were used to perform external validation (n=2287). RESULTS: Our final CD model outperformed an external pre-scan model (CD Risk Assessment Tool) in both the derivation (area under the curve (AUC) 0.744 (95% CI 0.727-0.761) and 0.677 (95% CI 0.658-0.695), respectively) and validation cohorts (AUC 0.744 (95% CI 0.652-0.835) and 0.725 (95% CI 0.633-0.816), respectively). By also taking LC incidence risk into consideration, we suggested a risk threshold where a subgroup (6258/23 096 (27%)) was identified with a number needed to screen to detect one LC of 216 (versus 23 in the remainder of the cohort) and ratio of 5.41 CDs per LC case (versus 0.88). The respective values in the validation cohort subgroup (774/2287 (34%)) were 129 (versus 29) and 1.67 (versus 0.43). CONCLUSIONS: Evaluating both LC and CD risks post-scan may improve the efficiency of LC screening and facilitate the initiation of multidisciplinary trajectories among certain participants.

Assisted versus Manual Interpretation of Low-Dose CT Scans for Lung Cancer Screening: Impact on Lung-RADS Agreement.

Purpose To compare the inter- and intraobserver agreement and reading times achieved when assigning Lung Imaging Reporting and Data System (Lung-RADS) categories to baseline and follow-up lung cancer screening studies by using a dedicated CT lung screening viewer with integrated nodule detection and volumetric support with those achieved by using a standard picture archiving and communication system (PACS)-like viewer. Materials and Methods Data were obtained from the National Lung Screening Trial (NLST). By using data recorded by NLST radiologists, scans were assigned to Lung-RADS categories. For each Lung-RADS category (1 or 2, 3, 4A, and 4B), 40 CT scans (20 baseline scans and 20 follow-up scans) were randomly selected for 160 participants (median age, 61 years; interquartile range, 58-66 years; 61 women) in total. Seven blinded observers independently read all CT scans twice in a randomized order with a 2-week washout period: once by using the standard PACS-like viewer and once by using the dedicated viewer. Observers were asked to assign a Lung-RADS category to each scan and indicate the risk-dominant nodule. Inter- and intraobserver agreement was analyzed by using Fleiss κ values and Cohen weighted κ values, respectively. Reading times were compared by using a Wilcoxon signed rank test. Results The interobserver agreement was moderate for the standard viewer and substantial for the dedicated viewer, with Fleiss κ values of 0.58 (95% CI: 0.55, 0.60) and 0.66 (95% CI: 0.64, 0.68), respectively. The intraobserver agreement was substantial, with a mean Cohen weighted κ value of 0.67. The median reading time was significantly reduced from 160 seconds with the standard viewer to 86 seconds with the dedicated viewer (P < .001). Conclusion Lung-RADS interobserver agreement increased from moderate to substantial when using the dedicated CT lung screening viewer. The median reading time was substantially reduced when scans were read by using the dedicated CT lung screening viewer. Keywords: CT, Thorax, Lung, Computer Applications-Detection/Diagnosis, Observer Performance, Technology Assessment Supplemental material is available for this article. © RSNA, 2021.

CT-Detected Subsolid Nodules: A Predictor of Lung Cancer Development at Another Location?

The purpose of this case-cohort study was to investigate whether the frequency and computed tomography (CT) features of pulmonary nodules posed a risk for the future development of lung cancer (LC) at a different location. Patients scanned between 2004 and 2012 at two Dutch academic hospitals were cross-linked with the Dutch Cancer Registry. All patients who were diagnosed with LC by 2014 and a random selection of LC-free patients were considered. LC patients who were determined to be LC-free at the time of the scan and all LC-free patients with an adequate scan were included. The nodule count and types (solid, part-solid, ground-glass, and perifissural) were recorded per scan. Age, sex, and other CT measures were included to control for confounding factors. The cohort included 163 LC patients and 1178 LC-free patients. Cox regression revealed that the number of ground-glass nodules and part-solid nodules present were positively correlated to future LC risk. The area under the receiver operating curve of parsimonious models with and without nodule type information were 0.827 and 0.802, respectively. The presence of subsolid nodules in a clinical setting may be a risk factor for future LC development in another pulmonary location in a dose-dependent manner. Replication of the results in screening cohorts is required for maximum utility of these findings.

Artificial intelligence for detection and characterization of pulmonary nodules in lung cancer CT screening: ready for practice?

Lung cancer computed tomography (CT) screening trials using low-dose CT have repeatedly demonstrated a reduction in the number of lung cancer deaths in the screening group compared to a control group. With various countries currently considering the implementation of lung cancer screening, recurring discussion points are, among others, the potentially high false positive rates, cost-effectiveness, and the availability of radiologists for scan interpretation. Artificial intelligence (AI) has the potential to increase the efficiency of lung cancer screening. We discuss the performance levels of AI algorithms for various tasks related to the interpretation of lung screening CT scans, how they compare to human experts, and how AI and humans may complement each other. We discuss how AI may be used in the lung cancer CT screening workflow according to the current evidence and describe the additional research that will be required before AI can take a more prominent role in the analysis of lung screening CT scans.

Deep Learning for Malignancy Risk Estimation of Pulmonary Nodules Detected at Low-Dose Screening CT.

Background Accurate estimation of the malignancy risk of pulmonary nodules at chest CT is crucial for optimizing management in lung cancer screening. Purpose To develop and validate a deep learning (DL) algorithm for malignancy risk estimation of pulmonary nodules detected at screening CT. Materials and Methods In this retrospective study, the DL algorithm was developed with 16 077 nodules (1249 malignant) collected -between 2002 and 2004 from the National Lung Screening Trial. External validation was performed in the following three -cohorts -collected between 2004 and 2010 from the Danish Lung Cancer Screening Trial: a full cohort containing all 883 nodules (65 -malignant) and two cancer-enriched cohorts with size matching (175 nodules, 59 malignant) and without size matching (177 -nodules, 59 malignant) of benign nodules selected at random. Algorithm performance was measured by using the area under the receiver operating characteristic curve (AUC) and compared with that of the Pan-Canadian Early Detection of Lung Cancer (PanCan) model in the full cohort and a group of 11 clinicians composed of four thoracic radiologists, five radiology residents, and two pulmonologists in the cancer-enriched cohorts. Results The DL algorithm significantly outperformed the PanCan model in the full cohort (AUC, 0.93 [95% CI: 0.89, 0.96] vs 0.90 [95% CI: 0.86, 0.93]; P = .046). The algorithm performed comparably to thoracic radiologists in cancer-enriched cohorts with both random benign nodules (AUC, 0.96 [95% CI: 0.93, 0.99] vs 0.90 [95% CI: 0.81, 0.98]; P = .11) and size-matched benign nodules (AUC, 0.86 [95% CI: 0.80, 0.91] vs 0.82 [95% CI: 0.74, 0.89]; P = .26). Conclusion The deep learning algorithm showed excellent performance, comparable to thoracic radiologists, for malignancy risk estimation of pulmonary nodules detected at screening CT. This algorithm has the potential to provide reliable and reproducible malignancy risk scores for clinicians, which may help optimize management in lung cancer screening. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Tammemägi in this issue.

Microsimulation modeling of extended annual CT screening among lung cancer cases in the National Lung Screening Trial.

PURPOSE: To microsimulate the effects of three additional annual CT screening rounds on lung cancer (LC) survival in the National Lung Screening Trial (NLST). METHODS: 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. RESULTS: 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. CONCLUSION: Three additional annual CT screening rounds in the NLST may have led to substantial further LC mortality reduction.

Combining pulmonary and cardiac computed tomography biomarkers for disease-specific risk modelling in lung cancer screening.

OBJECTIVES: Combined assessment of cardiovascular disease (CVD), COPD and lung cancer may improve the effectiveness of lung cancer screening in smokers. The aims were to derive and assess risk models for predicting lung cancer incidence, CVD mortality and COPD mortality by combining quantitative computed tomography (CT) measures from each disease, and to quantify the added predictive benefit of self-reported patient characteristics given the availability of a CT scan. METHODS: A survey model (patient characteristics only), CT model (CT information only) and final model (all variables) were derived for each outcome using parsimonious Cox regression on a sample from the National Lung Screening Trial (n=15 000). Validation was performed using Multicentric Italian Lung Detection data (n=2287). Time-dependent measures of model discrimination and calibration are reported. RESULTS: Age, mean lung density, emphysema score, bronchial wall thickness and aorta calcium volume are variables that contributed to all final models. Nodule features were crucial for lung cancer incidence predictions but did not contribute to CVD and COPD mortality prediction. In the derivation cohort, the lung cancer incidence CT model had a 5-year area under the receiver operating characteristic curve of 82.5% (95% CI 80.9-84.0%), significantly inferior to that of the final model (84.0%, 82.6-85.5%). However, the addition of patient characteristics did not improve the lung cancer incidence model performance in the validation cohort (CT model 80.1%, 74.2-86.0%; final model 79.9%, 73.9-85.8%). Similarly, the final CVD mortality model outperformed the other two models in the derivation cohort (survey model 74.9%, 72.7-77.1%; CT model 76.3%, 74.1-78.5%; final model 79.1%, 77.0-81.2%), but not the validation cohort (survey model 74.8%, 62.2-87.5%; CT model 72.1%, 61.1-83.2%; final model 72.2%, 60.4-84.0%). Combining patient characteristics and CT measures provided the largest increase in accuracy for the COPD mortality final model (92.3%, 90.1-94.5%) compared to either other model individually (survey model 87.5%, 84.3-90.6%; CT model 87.9%, 84.8-91.0%), but no external validation was performed due to a very low event frequency. CONCLUSIONS: CT measures of CVD and COPD provides small but reproducible improvements to nodule-based lung cancer risk prediction accuracy from 3 years onwards. Self-reported patient characteristics may not be of added predictive value when CT information is available.

Model-based Prediction of Critical Illness in Hospitalized Patients with COVID-19.

Background The prognosis of hospitalized patients with severe coronavirus disease 2019 (COVID-19) is difficult to predict, and the capacity of intensive care units was a limiting factor during the peak of the pandemic and is generally dependent on a country's clinical resources. Purpose To determine the value of chest radiographic findings together with patient history and laboratory markers at admission to predict critical illness in hospitalized patients with COVID-19. Materials and Methods In this retrospective study, which included patients from March 7, 2020, to April 24, 2020, a consecutive cohort of hospitalized patients with real-time reverse transcription polymerase chain reaction-confirmed COVID-19 from two large Dutch community hospitals was identified. After univariable analysis, a risk model to predict critical illness (ie, death and/or intensive care unit admission with invasive ventilation) was developed, using multivariable logistic regression including clinical, chest radiographic, and laboratory findings. Distribution and severity of lung involvement were visually assessed by using an eight-point scale (chest radiography score). Internal validation was performed by using bootstrapping. Performance is presented as an area under the receiver operating characteristic curve. Decision curve analysis was performed, and a risk calculator was derived. Results The cohort included 356 hospitalized patients (mean age, 69 years ± 12 [standard deviation]; 237 men) of whom 168 (47%) developed critical illness. The final risk model's variables included sex, chronic obstructive lung disease, symptom duration, neutrophil count, C-reactive protein level, lactate dehydrogenase level, distribution of lung disease, and chest radiography score at hospital presentation. The area under the receiver operating characteristic curve of the model was 0.77 (95% CI: 0.72, 0.81; P < .001). A risk calculator was derived for individual risk assessment: Dutch COVID-19 risk model. At an example threshold of 0.70, 71 of 356 patients would be predicted to develop critical illness, of which 59 (83%) would be true-positive results. Conclusion A risk model based on chest radiographic and laboratory findings obtained at admission was predictive of critical illness in hospitalized patients with coronavirus disease 2019. This risk calculator might be useful for triage of patients to the limited number of intensive care unit beds or facilities. © RSNA, 2020 Online supplemental material is available for this article.

Association between the number and size of intrapulmonary lymph nodes and chronic obstructive pulmonary disease severity.

PURPOSE: One of the main pathophysiological mechanisms of chronic obstructive pulmonary disease is inflammation, which has been associated with lymphadenopathy. Intrapulmonary lymph nodes can be identified on CT as perifissural nodules (PFN). We investigated the association between the number and size of PFNs and measures of COPD severity. MATERIALS AND METHODS: CT images were obtained from COPDGene. 50 subjects were randomly selected per GOLD stage (0 to 4), GOLD-unclassified, and never-smoker groups and allocated to either "Healthy," "Mild," or "Moderate/severe" groups. 26/350 (7.4%) subjects had missing images and were excluded. Supported by computer-aided detection, a trained researcher prelocated non-calcified opacities larger than 3 mm in diameter. Included lung opacities were classified independently by two radiologists as either "PFN," "not a PFN," "calcified," or "not a nodule"; disagreements were arbitrated by a third radiologist. Ordinal logistic regression was performed as the main statistical test. RESULTS: A total of 592 opacities were included in the observer study. A total of 163/592 classifications (27.5%) required arbitration. A total of 17/592 opacities (2.9%) were excluded from the analysis because they were not considered nodular, were calcified, or all three radiologists disagreed. A total of 366/575 accepted nodules (63.7%) were considered PFNs. A maximum of 10 PFNs were found in one image; 154/324 (47.5%) contained no PFNs. The number of PFNs per subject did not differ between COPD severity groups (p = 0.50). PFN short-axis diameter could significantly distinguish between the Mild and Moderate/severe groups, but not between the Healthy and Mild groups (p = 0.021). CONCLUSIONS: There is no relationship between PFN count and COPD severity. There may be a weak trend of larger intrapulmonary lymph nodes among patients with more advanced stages of COPD.

Typical CT Features of Intrapulmonary Lymph Nodes: A Review.

Several studies investigated the appearance of intrapulmonary lymph nodes (IPLNs) at CT with pathologic correlation. IPLNs are benign lesions and do not require follow-up after initial detection. There are indications that IPLNs represent a considerable portion of incidentally found pulmonary nodules seen at high-resolution CT. The reliable and accurate identification of IPLNs as benign nodules may substantially reduce the number of unnecessary follow-up CT examinations. Typical CT features of IPLNs are a noncalcified solid nodule with sharp margins; a round, oval, or polygonal shape; distanced 15 mm or less from the pleura; and most being located below the level of the carina. The term perifissural nodule (PFN) was coined based on some of these characteristics. Standardization of those CT criteria are a prerequisite for accurate nodule classification. However, four different definitions of PFNs can currently be found in the literature. Furthermore, there is considerable variation in the reported interobserver agreement, malignancy rate, and prevalence of PFNs. The purpose of this review was to provide an overview of what is known about PFNs. In addition, knowledge gaps in defining PFNs will be discussed. A decision tree to guide clinicians in classifying nodules as PFNs is provided. Supplemental material is available for this article. © RSNA, 2020 See also the commentary by White and Rubin in this issue.

Predicting all-cause and lung cancer mortality using emphysema score progression rate between baseline and follow-up chest CT images: A comparison of risk model performances.

PURPOSE: Normalized emphysema score is a protocol-robust CT biomarker of mortality. We aimed to improve mortality prediction by including the emphysema score progression rate-its change over time-into the models. METHOD AND MATERIALS: CT scans from 6000 National Lung Screening Trial CT arm participants were included. Of these, 1810 died (445 lung cancer-specific). The remaining 4190 survivors were sampled with replacement up to 24432 to approximate the full cohort. Three overlapping subcohorts were formed which required participants to have images from specific screening rounds. Emphysema scores were obtained after resampling, normalization, and bullae cluster analysis of the original images. Base models contained solely the latest emphysema score. Progression models included emphysema score progression rate. Models were adjusted by including baseline age, sex, BMI, smoking status, smoking intensity, smoking duration, and previous COPD diagnosis. Cox proportional hazard models predicting all-cause and lung cancer mortality were compared by calculating the area under the curve per year follow-up. RESULTS: In the subcohort of participants with baseline and first annual follow-up scans, the analysis was performed on 4940 participants (23227 after resampling). Area under the curve for all-cause mortality predictions of the base and progression models 6 years after baseline were 0.564 (0.564 to 0.565) and 0.569 (0.568 to 0.569) when unadjusted, and 0.704 (0.703 to 0.704) to 0.705 (0.704 to 0.705) when adjusted. The respective performances predicting lung cancer mortality were 0.638 (0.637 to 0.639) and 0.643 (0.642 to 0.644) when unadjusted, and 0.724 (0.723 to 0.725) and 0.725 (0.725 to 0.726) when adjusted. CONCLUSION: Including emphysema score progression rate into risk models shows no clinically relevant improvement in mortality risk prediction. This is because scan normalization does not adjust for an overall change in lung density. Adjusting for changes in smoking behavior is likely required to make this a clinically useful measure of emphysema progression.

Classification of CT Pulmonary Opacities as Perifissural Nodules: Reader Variability.

Purpose To study interreader variability for classifying pulmonary opacities at CT as perifissural nodules (PFNs) and determine how reliably radiologists differentiate PFNs from malignancies. Materials and Methods CT studies were obtained retrospectively from the National Lung Screening Trial (2002-2009). Nodules were eligible for the study if they were noncalcified, solid, within the size range of 5 to 10 mm, and scanned with a section thickness of 2 mm or less. Six radiologists classified 359 nodules in a cancer-enriched data set as PFN, non-PFN, or not applicable. Nodules classified as not applicable by at least three radiologists were excluded, leaving 316 nodules for post-hoc statistical analysis. Results The study group contained 22.2% cancers (70 of 316). The median proportion of nodules classified as PFNs was 45.6% (144 of 316). All six radiologists uniformly classified 17.7% (56 of 316) of the nodules as PFNs. The Fleiss κ was 0.50. Compared with non-PFNs, nodules classified as PFNs were smaller and more often located in the lower lobes and attached to a fissure (P < .001). Thirteen (18.6%) of 70 cancers were misclassified 21 times as PFNs. Individual readers' misclassification rates ranged from 0% (0 of 125) to 4.9% (eight of 163). Of 13 misclassified malignancies, 11 were in the upper lobes and two were attached to a fissure. Conclusion There was moderate interreader agreement when classifying nodules as perifissural nodules. Less than 2.5% of perifissural nodule classifications were misclassified lung cancers (21 of 865) in this cancer-enriched study. Allowing nodules classified as perifissural nodules to be omitted from additional follow-up in a screening setting could substantially reduce the number of unnecessary scans; excluding perifissural nodules in the upper lobes would greatly decrease the misclassification rate.

Lung cancer risk to personalise annual and biennial follow-up computed tomography screening.

BACKGROUND: All lung cancer CT screening trials used fixed follow-up intervals, which may not be optimal. We developed new lung cancer risk models for personalising screening intervals to 1 year or 2 years, and compared these with existing models. METHODS: We included participants in the CT arm of the National Lung Screening Trial (2002-2010) who underwent a baseline scan and a first annual follow-up scan and were not diagnosed with lung cancer in the first year. True and false positives and the area under the curve of each model were calculated. Internal validation was performed using bootstrapping. RESULTS: Data from 24 542 participants were included in the analysis. The accuracy was 0.785, 0.693, 0.697, 0.666 and 0.727 for the polynomial, patient characteristics, diameter, Patz and PanCan models, respectively. Of the 24 542 participants included, 174 (0.71%) were diagnosed with lung cancer between the first and the second annual follow-ups. Using the polynomial model, 2558 (10.4%, 95% CI 10.0% to 10.8%), 7544 (30.7%, 30.2% to 31.3%), 10 947 (44.6%, 44.0% to 45.2%), 16 710 (68.1%, 67.5% to 68.7%) and 20 023 (81.6%, 81.1% to 92.1%) of the 24 368 participants who did not develop lung cancer in the year following the first follow-up screening round could have safely skipped it, at the expense of delayed diagnosis of 0 (0.0%, 0.0% to 2.7%), 8 (4.6%, 2.2% to 9.2%), 17 (9.8%, 6.0% to 15.4%), 44 (25.3%, 19.2% to 32.5%) and 70 (40.2%, 33.0% to 47.9%) of the 174 lung cancers, respectively. CONCLUSIONS: The polynomial model, using both patient characteristics and baseline scan morphology, was significantly superior in assigning participants to 1-year or 2-year screening intervals. Implementing personalised follow-up intervals would enable hundreds of participants to skip a screening round per lung cancer diagnosis delayed.