Multicentric Italian Lung Detection Research Articles

Fully automated calcium scoring predicts all-cause mortality at 12 years in the MILD lung cancer screening trial.

Coronary artery calcium (CAC) is a known risk factor for cardiovascular (CV) events and mortality but is not yet routinely evaluated in low-dose computed tomography (LDCT)-based lung cancer screening (LCS). The present analysis explored the capacity of a fully automated CAC scoring to predict 12-year mortality in the Multicentric Italian Lung Detection (MILD) LCS trial. The study included 2239 volunteers of the MILD trial who underwent a baseline LDCT from September 2005 to January 2011, with a median follow-up of 190 months. The CAC score was measured by a commercially available fully automated artificial intelligence (AI) software and stratified into five strata: 0, 1-10, 11-100, 101-400, and > 400. Twelve-year all-cause mortality was 8.5% (191/2239) overall, 3.2% with CAC = 0, 4.9% with CAC = 1-10, 8.0% with CAC = 11-100, 11.5% with CAC = 101-400, and 17% with CAC > 400. In Cox proportional hazards regression analysis, CAC > 400 was associated with a higher 12-year all-cause mortality both in a univariate model (hazard ratio, HR, 5.75 [95% confidence interval, CI, 2.08-15.92] compared to CAC = 0) and after adjustment for baseline confounders (HR, 3.80 [95%CI, 1.35-10.74] compared to CAC = 0). All-cause mortality significantly increased with increasing CAC (7% in CAC ≤ 400 vs. 17% in CAC > 400, Log-Rank p-value <0.001). Non-cancer at 12 years mortality was 3% (67/2239) overall, 0.8% with CAC = 0, 1.0% with CAC = 1-10, 2.9% with CAC = 11-100, 3.6% with CAC = 101-400, and 8.2% with CAC > 400 (Grey's test p < 0.001). In Fine and Gray's competing risk model, CAC > 400 predicted 12-year non-cancer mortality in a univariate model (sub-distribution hazard ratio, SHR, 10.62 [95% confidence interval, CI, 1.43-78.98] compared to CAC = 0), but the association was no longer significant after adjustment for baseline confounders. In conclusion, fully automated CAC scoring was effective in predicting all-cause mortality at 12 years in a LCS setting.

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

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. 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). 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). 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.

Managing of screening-detected sub-solid nodules-a European perspective.

Since the National Lung Screening Trial in 2011 showed a 20% reduction in lung cancer mortality using annual low-dose computed tomography (LDCT), several randomised controlled trials and studies have been started in Europe. These include the Italian lung study (ITALUNG), the Dutch-Belgian lung cancer screening trial (NELSON), the UK lung cancer screening trial (UKLS), the Detection and screening of early lung cancer with novel imaging technology (DANTE), the Danish lung cancer screening trial (DLCST), the German lung cancer screening intervention trial (LUSI), the Multicentric Italian lung detection trial (MILD) and the CT screening for lung cancer study (COSMOS). As a result of the increasing number of screening trials and the growing utilization of LDCT, the high detection of subsolid nodules is an increasingly important clinical problem. In the last few years, several guidelines have been published and providing guidance on the optimal management of subsolid nodules, but many controversies still exist. Follow-up imaging plays an important role in clinical assessment and subsequent management of this particular type of lung nodules, since they can be transient inflammatory lesions, and if persistent they can be both benign lesions or lung cancers of variable clinical behaviour. However, the vast majority of subsolid nodules retain an indolent course over many years. The aim of this review is to present a European perspective in management of screening detected subsolid nodules.

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

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. 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. 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. 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.

Lung cancer screening by nodule volume in Lung-RADS v1.1: negative baseline CT yields potential for increased screening interval

ObjectivesThe 2019 Lung CT Screening Reporting & Data System version 1.1 (Lung-RADS v1.1) introduced volumetric categories for nodule management. The aims of this study were to report the distribution of Lung-RADS v1.1 volumetric categories and to analyse lung cancer (LC) outcomes within 3 years for exploring personalized algorithm for lung cancer screening (LCS).MethodsSubjects from the Multicentric Italian Lung Detection (MILD) trial were retrospectively selected by National Lung Screening Trial (NLST) criteria. Baseline characteristics included selected pre-test metrics and nodule characterization according to the volume-based categories of Lung-RADS v1.1. Nodule volume was obtained by segmentation with dedicated semi-automatic software. Primary outcome was diagnosis of LC, tested by univariate and multivariable models. Secondary outcome was stage of LC. Increased interval algorithms were simulated for testing rate of delayed diagnosis (RDD) and reduction of low-dose computed tomography (LDCT) burden.ResultsIn 1248 NLST-eligible subjects, LC frequency was 1.2% at 1 year, 1.8% at 2 years and 2.6% at 3 years. Nodule volume in Lung-RADS v1.1 was a strong predictor of LC: positive LDCT showed an odds ratio (OR) of 75.60 at 1 year (p < 0.0001), and indeterminate LDCT showed an OR of 9.16 at 2 years (p = 0.0068) and an OR of 6.35 at 3 years (p = 0.0042). In the first 2 years after negative LDCT, 100% of resected LC was stage I. The simulations of low-frequency screening showed a RDD of 13.6–21.9% and a potential reduction of LDCT burden of 25.5–41%.ConclusionsNodule volume by semi-automatic software allowed stratification of LC risk across Lung-RADS v1.1 categories. Personalized screening algorithm by increased interval seems feasible in 80% of NLST eligible.Key Points• Using semi-automatic segmentation of nodule volume, Lung-RADS v1.1 selected 10.8% of subjects with positive CT and 96.87 relative risk of lung cancer at 1 year, compared to negative CT.• Negative low-dose CT by Lung-RADS v1.1 was found in 80.6% of NLST eligible and yielded 40 times lower relative risk of lung cancer at 2 years, compared to positive low-dose CT; annual screening could be preference sensitive in this group.• Semi-automatic segmentation of nodule volume and increased screening interval by volumetric Lung-RADS v1.1 could retrospectively suggest a 25.5–41% reduction of LDCT burden, at the cost of 13.6–21.9% rate of delayed diagnosis.

Do we need to see to believe?-radiomics for lung nodule classification and lung cancer risk stratification.

Despite multiple recent advances, the diagnosis and management of lung cancer remain challenging and it continues to be the deadliest malignancy. In 2011, the National Lung Screening Trial (NLST) reported 20% reduction in lung cancer related mortality using annual low dose chest computed tomography (CT). These results led to the approval and nationwide establishment of lung cancer CT-based lung cancer screening programs. These findings have been further validated by the recently published Nederlands-Leuvens Longkanker Screenings Onderzoek (NELSON) and Multicentric Italian Lung Detection (MILD) trials, the latter showing benefit of screening even beyond the 5 years. However, the implementation of lung cancer screening has been impeded by several challenges, including the differentiation between benign and malignant nodules, the large number of false positive studies and the detection of indolent, potentially clinically insignificant lung cancers (overdiagnosis). Hence, the development of non-invasive strategies to accurately classify and risk stratify screen-detected pulmonary nodules in order to individualize clinical management remains a high priority area of research. Radiomics is a recently coined term which refers to the process of imaging feature extraction and quantitative analysis of clinical diagnostic images to characterize the nodule phenotype beyond what is possible with conventional radiologist assessment. Even though it is still in early phase, several studies have already demonstrated that radiomics approaches are potentially useful for lung nodule classification, risk stratification, individualized management and prediction of overall prognosis. The goal of this review is to summarize the current literature regarding the radiomics of screen-detected lung nodules, highlight potential challenges and discuss its clinical application along with future goals and challenges.

Ten-year results of the Multicentric Italian Lung Detection trial demonstrate the safety and efficacy of biennial lung cancer screening

BackgroundThe Multicentric Italian Lung Detection (MILD) trial demonstrated that prolonged low-dose computed tomography (LDCT) screening could achieve a 39% reduction in lung cancer (LC) mortality. We have here evaluated the long-term results of annual vs. biennial LDCT and the impact of screening intensity on overall and LC-specific mortality at 10 years. Patients and methodsBetween 2005 and 2018, the MILD trial prospectively randomised the 2376 screening arm participants to annual (n = 1190) or biennial (n = 1186) LDCT, for a median screening period of 6.2 years and 23,083 person-years of follow-up. The primary outcomes were 10-year overall and LC-specific mortality, and the secondary end-points were the frequency of advanced-stage and interval LCs. ResultsThe biennial LDCT arm showed a similar overall mortality (hazard ratio [HR] 0.80, 95% confidence interval [CI] 0.57–1.12) and LC-specific mortality at 10 years (HR 1.10, 95% CI 0.59–2.05), as compared with the annual LDCT arm. Biennial screening saved 44% of follow-up LDCTs in subjects with negative baseline LDCT, and 38% of LDCTs in all participants, with no increase in the occurrence of stage II-IV or interval LCs. ConclusionsThe MILD trial provides original evidence that prolonged screening beyond five years with biennial LDCT can achieve an LC mortality reduction comparable to annual LDCT, in subjects with a negative baseline examination.

MILD trial, strong confirmation of lung cancer screening efficacy.

In a landmark analysis, investigators of the Multicentric Italian Lung Detection (MILD) trial have confirmed 10-year mortality reductions with lung cancer screening using low-dose helical CT (LDCT). These data complement the reduced lung cancer-specific mortality reported in the National Lung Screening Trial and reinforce the rationale for broad implementation of LDCT screening in high-risk populations.

Benefits and harms in the National Lung Screening Trial: expected outcomes with a modern management protocol

Lung cancer screening is receiving increasing attention worldwide, both in the medical community and the general public. Multiple randomised trials — including the US National Lung Screening Trial (NLST), the Multicentric Italian Lung Detection trial, and preliminary results from the Dutch-Belgian NELSON trial — have provided definitive evidence that low-dose CT screening can reduce lung cancer mortality. However, any screening programme is associated with both benefits and harms, and accurately communicating these to patients and the general public is a complex challenge. Given the complexity of the debate, it is difficult for primary care providers to understand and explain the benefits and harms of screening to their patients. Multiple graphical tools have been developed and published to aid this conversation, each based on the NLST, and other bespoke graphics have been used in pilot studies. However, some of the published graphics can be misleading, and all represent outcomes based on the NLST protocol, which is now nearly 20 years old. We engaged an international group of lung screening experts with the goal of assembling and providing accurate and balanced information on the benefits and harms of NLST-like low-dose CT screening. We compiled these results into an infographic, along with a full-page version with explanatory text. Our new infographic represents a contemporary interpretation of the findings of NLST using a modern protocol.

Prolonged lung cancer screening reduced 10-year mortality in the MILD trial: new confirmation of lung cancer screening efficacy.

BackgroundThe National Lung Screening Trial showed that lung cancer (LC) screening by three annual rounds of low-dose computed tomography (LDCT) reduces LC mortality. We evaluated the benefit of prolonged LDCT screening beyond 5 years, and its impact on overall and LC specific mortality at 10 years.DesignThe Multicentric Italian Lung Detection (MILD) trial prospectively randomized 4099 participants, to a screening arm (n = 2376), with further randomization to annual (n = 1190) or biennial (n = 1186) LDCT for a median period of 6 years, or control arm (n = 1723) without intervention. Between 2005 and 2018, 39 293 person-years of follow-up were accumulated. The primary outcomes were 10-year overall and LC specific mortality. Landmark analysis was used to test the long-term effect of LC screening, beyond 5 years by exclusion of LCs and deaths that occurred in the first 5 years.ResultsThe LDCT arm showed a 39% reduced risk of LC mortality at 10 years [hazard ratio (HR) 0.61; 95% confidence interval (CI) 0.39–0.95], compared with control arm, and a 20% reduction of overall mortality (HR 0.80; 95% CI 0.62–1.03). LDCT benefit improved beyond the 5th year of screening, with a 58% reduced risk of LC mortality (HR 0.42; 95% CI 0.22–0.79), and 32% reduction of overall mortality (HR 0.68; 95% CI 0.49–0.94).ConclusionsThe MILD trial provides additional evidence that prolonged screening beyond 5 years can enhance the benefit of early detection and achieve a greater overall and LC mortality reduction compared with NLST trial.ClinicalTrials.gov identifierNCT02837809.

Are interstitial lung abnormalities associated with COPD? A nested case-control study.

PurposeIn this study, we tested the association between COPD and interstitial lung abnormality (ILA), notably in relation to the presence of computed tomography (CT) signs of lung fibrosis.Patients and methodsCOPD cases were selected from participants undergoing lung cancer screening (Multicentric Italian Lung Detection trial) for airflow obstruction (n=311/2,303, 13.5%) and 146 consecutive patients with clinical COPD. In all, 457 COPD cases were selected and classified according to the stages of Global Initiative for Chronic Obstructive Lung Disease. A nested matching (case:control = 1:2) according to age, sex, and smoking history was operated between each COPD case and two control subjects from Multicentric Italian Lung Detection trial without airflow obstruction. Low-dose CT scans of COPD cases and controls were reviewed for the presence of ILA, which were classified into definite or indeterminate according to the presence of signs of lung fibrosis.ResultsThe frequency of definite ILA was similar between COPD cases and controls (P=0.2), independent of the presence of signs of lung fibrosis (P=0.07). Combined definite and indeterminate ILA was homogeneously distributed across Global Initiative for Chronic Obstructive Lung Disease stages (P=0.6). Definite ILA was directly associated with current smoker status (odds ratio [OR] 4.05, 95% confidence interval [CI]: 2.2–7.4) and increasing pack-years (OR 1.01, 95% CI: 1–1.02). Subjects with any fibrotic ILA were more likely to be older (OR 1.17, 95% CI: 1.10–1.25) and male (OR 8.58, 95% CI: 1.58–68.9).ConclusionThere was no association between COPD and definite ILA. However, low-dose CT signs of lung fibrosis were also observed in COPD, and their clinical relevance is yet to be determined.

A combined smoking cessation intervention within a lung cancer screening trial: a pilot observational study.

The time of lung cancer screening may provide the ideal setting to discuss and initiate a smoking cessation plan that includes pharmacologic aids. No studies to date have fully investigated the potential effectiveness of such combined approach. We prospectively evaluated the biochemically verified 1-year continuous abstinence rate from smoking of 187 persistent smokers enrolled within the Multicentric Italian Lung Detection Trial (MILD), who received a pharmacologic aid to quit smoking with varenicline along with behavioral counseling. The propensity of study subjects to succeed in smoking cessation was also monitored. At 12 months, the continuous abstinence rate from smoking was achieved in 37 out of 187 patients (19.8%), with a propensity to succeed in smoking cessation for the assisted attempt equal to 1.43, as compared to an unassisted MILD patient. At the end of the third month of therapy, 48.7% of subjects showed a continuous abstinence rate, while only 33.7% of patients were abstinent from smoking at 6 months. At baseline, the subgroup of MILD participants who were originally allocated to lung tomography showed higher smoking intensity than those allocated to no screening. A combined smoking cessation intervention can be implemented with satisfactory results within a lung cancer screening program; this preliminary observation needs to be replicated in a prospective investigation. Clinicians should consider that lung cancer screening may be falsely reassuring for persistent smokers; therefore it should always be coupled with a smoking cessation program.

Biomarkers to the Rescue in a Lung Nodule Epidemic

Biomarkers to the Rescue in a Lung Nodule Epidemic

Long-Term Surveillance of Ground-Glass Nodules: Evidence from the MILD Trial

The purpose of this study was to evaluate the natural evolution of ground-glass nodules (GGNs) in the Multicentric Italian Lung Detection (MILD) trial, which adopted a nonsurgical approach to this subset of lesions. From September 2005 to August 2007, 56 consecutive MILD participants with 76 GGNs were identified from 1866 individuals who underwent baseline low-dose computed tomography. The features of GGNs were assessed and compared with the corresponding repeat low-dose computed tomographies after a mean time of 50.26 ± 7.3 months. The GGNs were classified as pure (pGGN) or part-solid (psGGN) GGNs. The average of the maximum and the minimum diameters for both pGGNs and psGGNs and the maximum diameter of the solid portion of psGGNs were manually measured. At follow-up, GGNs were classified as follows: resolved, decreased, stable, or progressed (according to three defined growth patterns). A total of 15 of 48 pGGNs (31.3%) resolved, 4 of 48 (8.3%) decreased in size, 21 of 48 (43.8%) remained stable, and 8 of 48 (16.7%) progressed. Among the psGGNs with a solid component smaller than 5 mm, 3 of 26 (11.5%) resolved, 11 of 26 (42.3%) remained stable, and 12 of 26 (46.2%) progressed. One of the two psGGNs with a solid component larger than 5 mm remained stable, and the other decreased in size. Four lung cancers were detected among the GGN subjects, but only one arose from a psGGN, and was resected in stage Ia. The progression rate of the GGNs toward clinically relevant disease was extremely low in the MILD trial and supports an active surveillance attitude.

Annual or biennial CT screening versus observation in heavy smokers

The efficacy and cost-effectiveness of low-dose spiral computed tomography (LDCT) screening in heavy smokers is currently under evaluation worldwide. Our screening program started with a pilot study on 1035 volunteers in Milan in 2000 and was followed up in 2005 by a randomized trial comparing annual or biennial LDCT with observation, named Multicentric Italian Lung Detection. This included 4099 participants, 1723 randomized to the control group, 1186 to biennial LDCT screening, and 1190 to annual LDCT screening. Follow-up was stopped in November 2011, with 9901 person-years for the pilot study and 17 621 person-years for Multicentric Italian Lung Detection. Forty-nine lung cancers were detected by LDCT (20 in biennial and 29 in the annual arm), of which 17 were identified at baseline examination; 63% were of stage I and 84% were surgically resectable. Stage distribution and resection rates were similar in the two LDCT arms. The cumulative 5-year lung cancer incidence rate was 311/100 000 in the control group, 457 in the biennial, and 620 in the annual LDCT group (P=0.036); lung cancer mortality rates were 109, 109, and 216/100 000 (P=0.21), and total mortality rates were 310, 363, and 558/100 000, respectively (P=0.13). Total mortality in the pilot study was similar to that observed in the annual LDCT arm at 5 years. There was no evidence of a protective effect of annual or biennial LDCT screening. Furthermore, a meta-analysis of the four published randomized trials showed similar overall mortality in the LDCT arms compared with the control arm.

Relationship and Prognostic Value of Modified Coronary Artery Calcium Score, FEV1, and Emphysema in Lung Cancer Screening Population: The MILD Trial

To assess the relationship between a modified coronary artery calcium (mCAC) score and both forced expiratory volume in 1 second (FEV1) and pulmonary emphysema and the associations of such factors with all-cause mortality and cardiovascular events (CVEs) in a lung cancer computed tomographic (CT) screening trial. In this institutional review board-approved study, both clinical and low-dose CT data were evaluated in a cohort of heavy smokers consecutively recruited by the Multicentric Italian Lung Detection, or MILD, trial. Low-dose CT images were analyzed by using software that allowed quantification of mCAC, mean lung attenuation (MLA), and total extent of emphysema. The correlations between mCAC, percentage predicted FEV1, MLA, and emphysema extent were tested by using the Pearson correlation coefficient. Adjusted multiple logistic regression models were applied to assess the relationships between mCAC, FEV1, MLA, and emphysema extent and all-cause mortality and CVEs. The final study cohort consisted of 1159 smokers. There were no significant correlations between mCAC score and FEV1 (r=-0.03, P=.4), MLA (r=-0.01, P=.7), or emphysema extent (r=0.02, P=.6). An mCAC score greater than 400 was the only factor that was independently associated with both all-cause mortality (odds ratio [OR]: 3.73; 95% confidence interval [CI]: 1.05, 13.32; P=.04) and CVEs (OR: 2.87; 95% CI: 1.13, 7.27; P=.03). mCAC is a better predictor of CVE and all-cause mortality than FEV1 and emphysema extent and may contribute to the identification of high-risk individuals in a lung cancer screening setting.

Interstitial lung diseases in a lung cancer screening trial

We assessed the prevalence of interstitial lung disease (ILD) in a cohort of smokers included in a lung cancer screening trial. Two observers independently reviewed, for the presence of findings consistent with ILD, the computed tomography (CT) examinations of 692 heavy smokers recruited by the Multicentric Italian Lung Detection (MILD) trial. Four CT patterns were considered: usual interstitial pneumonia (UIP), other chronic interstitial pneumonia (OCIP), respiratory bronchiolitis (RB) and indeterminate. Subsequently, the evolution of ILD in those subjects who had undergone a repeat CT examination after 3 yrs was assessed. The UIP pattern and the OCIP pattern were identified in two (0.3%) out of 692 and 26 (3.8%) out of 692 patients, respectively; 109 (15.7%) out of 692 patients showed CT abnormalities consistent with RB, while an indeterminate CT pattern was reported in 21 out of 692 (3%) patients. Age, male sex and current smoking status were factors associated with the presence of OCIP and UIP (combined) pattern, although the relationship did not attain statistical significance. A progression of the disease was observed in three (25%) out of 12 subjects with OCIP who underwent repeat CT after 3 yrs. Thin-section CT features of ILD, probably representing smoking-related ILD, are not uncommon in a lung cancer screening population and should not be overlooked.

Pulmonary Nodules: Volume Repeatability at Multidetector CT Lung Cancer Screening

To assess in vivo volumetric repeatability of an automated software algorithm in pulmonary nodules detected during a lung cancer screening trial. This study was approved by an institutional review board. Written informed consent was obtained from all participants. Data were collected from the Multicentric Italian Lung Detection project, a randomized controlled lung cancer screening trial. The first 1236 consecutive baseline computed tomographic (CT) studies performed at the Istituto Nazionale Tumori of Milan were evaluated. Among the enrolled participants, those who underwent repeat low-dose CT after 3 months and had at least one indeterminate nodule with a volume of more than 60 mm(3) (diameter of 4.8 mm or greater) were considered. Nonsolid, part-solid, and pleural-based nodules were excluded from this study. A descriptive analysis was performed by calculating means and standard deviations of nodule volumes at three assessment times (at baseline and 3 and 12 months later). The volume measurement repeatability was determined by using the approach described by Bland and Altman. One hundred one subjects (70 men, 31 women; mean age, 58 years) with 233 eligible nodules (mean volume, 98.3 mm(3); range, 5-869 mm(3)) were identified. The 95% confidence interval for difference in measured volumes was in the range of +/-27%. About 70% of measurements had a relative difference in nodule volume of less than 10%. No malignant lesions were registered during the follow-up of these subjects. Semiautomatic volumetry is sufficiently accurate and repeatable and may be useful in assisting with lung nodule management in a lung cancer screening program.