Integrating Biological and Radiological Data in a Structured Repository: a Data Model Applied to the COSMOS Case Study.

Integrating the information coming from biological samples with digital data, such as medical images, has gained prominence with the advent of precision medicine. Research in this field faces an ever-increasing amount of data to manage and, as a consequence, the need to structure these data in a functional and standardized fashion to promote and facilitate cooperation among institutions. Inspired by the Minimum Information About BIobank data Sharing (MIABIS), we propose an extended data model which aims to standardize data collections where both biological and digital samples are involved. In the proposed model, strong emphasis is given to the cause-effect relationships among factors as these are frequently encountered in clinical workflows. To test the data model in a realistic context, we consider the Continuous Observation of SMOking Subjects (COSMOS) dataset as case study, consisting of 10 consecutive years of lung cancer screening and follow-up on more than 5000 subjects. The structure of the COSMOS database, implemented to facilitate the process of data retrieval, is therefore presented along with a description of data that we hope to share in a public repository for lung cancer screening research.

Inter-observer agreement on the morphology of screening-detected lung cancer: beyond pulmonary nodules and masses.

OBJECTIVES: Pulmonary nodules and masses are the typical presentations of lung cancer. However, a spectrum of focal opacities cannot be defined as either "pulmonary nodule" or "mass," despite representing cancer. We aimed to assess the morphology of screening-detected lung cancers at low-dose computed tomography LDTC and to evaluate inter-observer agreement in their classification. METHODS: Four radiologists with different experiences in thoracic imaging retrospectively reviewed 273 screening-detected lung cancers. Readers were asked to assess if morphology at the time of diagnosis was consistent with the Fleischner Society definition of pulmonary "nodule" or "mass." Cancers not consistent were defined as "non-nodular/non-mass" (NN/NM) and sub-classified as follows: associated with cystic airspaces, stripe-like, scar-like, endobronchial, or not otherwise defined (NOD). Inter-observer agreement was evaluated using Cohen's K statistic among pairs of readers and modified Fleiss' kappa statistic for overall agreement. RESULTS: Two hundred forty-one of the 273 (88%) lesions were defined as pulmonary nodule or mass by complete agreement, while 20/273 (7.3%) were defined as NN/NM. Six (2.2%) of 273 were sub-classified as lesions associated with cystic airspace, six (2.2%) as scar-like, five (1.8%) as endobronchial, and one (0.7%) as NOD by complete agreement. The concordance in defining morphology was excellent (261/273; 96%, 95%CI 92-98%; k 0.85, 95%CI 0.75-0.92) and also in the sub-classification (18/20; 90%, 95%CI 68-99%, k 0.93, 95%CI 0.86-1.00). There was incomplete agreement regarding lesion morphology in 4.4% (12/273) of cases. CONCLUSIONS: A non-negligible percentage of screening-detected lung cancers has a NN/NM appearance at LDCT. The concordance in defining lesion morphology was excellent. The awareness of various presentations can avoid missed or delayed diagnosis. KEY POINTS: • A non-negligible percentage of screening-detected lung cancers have neither nodular nor mass appearance at low-dose CT. • The awareness of various LDCT presentations of lung cancer can avoid missed or delayed diagnosis. • Optimal protocol management in CT screening should take into consideration lung nodules as well as various other focal abnormalities.

E-cigarettes May Support Smokers With High Smoking-Related Risk Awareness to Stop Smoking in the Short Run: Preliminary Results by Randomized Controlled Trial.

Introduction: E-cigarettes may be positively used in tobacco cessation treatments. However, neither the World Health Organization nor the American Food and Drug Administration has recognized them as effective cessation aids. Data about the efficacy and safety of e-cigarettes are still limited and controversial. Methods: This was a double-blind randomized controlled study. The main focus of this article is on a secondary outcome of the study, that is, the assessment of effectiveness and safety of e-cigarettes in achieving smoking cessation in a group of chronic smokers voluntarily involved in long-term lung cancer screening. Participants were randomized into three arms with a 1:1:1 ratio: e-cigarettes (Arm 1), placebo (Arm 2), and control (Arm 3). All subjects also received a low-intensity counseling. Results: Two hundred ten smokers were randomized (70 to nicotine e-cigarettes, 70 nicotine-free placebo e-cigarettes, and 70 to control groups). About 25% of participants who followed a cessation program based on the use of e-cigarettes (Arm 1 and Arm 2) were abstinent after 3 months. Conversely, only about 10% of smokers in Arm 3 stopped. A Kruskal-Wallis test showed significant differences in daily cigarettes smoking across the three arms (K-W = 6.277, p = .043). In particular, participants in Arm 1 reported a higher reduction rate (M = -11.6441, SD = 7.574) than participants in Arm 2 (M = -10.7636, SD = 8.156) and Arm 3 (M = -9.1379, SD = 8.8127). Conclusions: Our findings support the efficacy and safety of e-cigarettes in a short-term period. E-cigarettes use led to a higher cessation rate. Furthermore, although all participants reported a significant reduction of daily cigarette consumption compared to the baseline, the use of e-cigarettes (including those without nicotine) allowed smokers to achieve better results. Implications: E-cigarettes increased the stopping rate as well as the reduction of daily cigarettes in participants who continued smoking. In fact, although all participants reported a significant reduction of tobacco consumption compared to the baseline, the use of e-cigarettes allowed smokers to achieve a better result. It could be worthwhile to associate this device with new ICT-driven models of self-management support in order to enable people to better handle behavioral changes and side effects. This is true for ready-to-quit smokers (such as our participants) but can also be advantageous for less motivated smokers engaged in clinical settings.

Dietary inflammatory index and risk of lung cancer and other respiratory conditions among heavy smokers in the COSMOS screening study.

PURPOSE: To test whether the inflammatory potential of diet, as measured using the dietary inflammatory index (DII), is associated with risk of lung cancer or other respiratory conditions and to compare results obtained with those based on the aMED score, an established dietary index that measures adherence to the traditional Mediterranean diet. METHODS: In 4336 heavy smokers enrolled in a prospective, non-randomized lung cancer screening program, we measured participants' diets at baseline using a self-administered food frequency questionnaire from which dietary scores were calculated. Cox proportional hazards and logistic regression models were used to assess association between the dietary indices and lung cancer diagnosed during annual screening, and other respiratory outcomes that were recorded at baseline, respectively. RESULTS: In multivariable analysis, adjusted for baseline lung cancer risk (estimated from age, sex, smoking history, and asbestos exposure) and total energy, both DII and aMED scores were associated with dyspnoea (p trend = 0.046 and 0.02, respectively) and radiological evidence of emphysema (p trend = 0.0002 and 0.02). After mutual adjustment of the two dietary scores, only the association between DII and radiological evidence of emphysema (Q4 vs. Q1, OR 1.30, 95 % CI 1.01-1.67, p trend = 0.012) remained statistically significant. At univariate analysis, both DII and aMED were associated with lung cancer risk, but in fully adjusted multivariate analysis, only the association with aMED remained statistically significant (p trend = 0.04). CONCLUSIONS: Among heavy smokers, a pro-inflammatory diet, as indicated by increasing DII score, is associated with dyspnoea and radiological evidence of emphysema. A traditional Mediterranean diet, which is associated with a lower DII, may lower lung cancer risk.

Positron emission tomography in the diagnostic work-up of screening-detected lung nodules.

Low-dose computed tomography (CT) screening for lung cancer can reduce lung cancer mortality, but overdiagnosis, false positives and invasive procedures for benign nodules are worrying. We evaluated the utility of positron emission tomography (PET)-CT in characterising indeterminate screening-detected lung nodules. 383 nodules, examined by PET-CT over the first 6 years of the COSMOS (Continuous Observation of Smoking Subjects) study to diagnose primary lung cancer, were reviewed and compared with pathological findings (surgically-treated patients) or follow-up (negative CT for ⩾2 years, considered negative); 196 nodules were malignant. The sensitivity, specificity and accuracy of PET-CT for differentially diagnosing malignant nodules were, respectively, 64%, 89% and 76% overall, and 82%, 92% and 88% for baseline-detected nodules. Performance was lower for nodules found at repeat annual scans, with sensitivity ranging from 22% for nonsolid to 79% for solid nodules (p=0.0001). Sensitivity (87%) and specificity (73%) were high for nodules ⩾15 mm, better (sensitivity 98%) for solid nodules ⩾15 mm. PET-CT was highly sensitive for the differential diagnosis of indeterminate nodules detected at baseline, nodules ⩾15 mm and solid nodules. Sensitivity was low for sub-solid nodules and nodules discovered after baseline for which other methods, e.g. volume doubling time, should be used.

Nutrient intake and nutrient patterns and risk of lung cancer among heavy smokers: results from the COSMOS screening study with annual low-dose CT.

The role of nutrients in lung cancer aetiology remains controversial and has never been evaluated in the context of screening. Our aim was to investigate the role of single nutrients and nutrient patterns in the aetiology of lung cancer in heavy smokers. Asymptomatic heavy smokers (≥20 pack-years) were invited to undergo annual low-dose computed tomography. We assessed diet using a self-administered food frequency questionnaire and collected information on multivitamin supplement use. We performed principal component analysis identifying four nutrient patterns and used Cox proportional Hazards regression to assess the association between nutrients and nutrients patterns and lung cancer risk. During a mean follow-up of 5.7 years, 178 of 4,336 participants were diagnosed with lung cancer by screening. We found a significant risk reduction of lung cancer with increasing vegetable fat consumption (HR for highest vs. lowest quartile = 0.50, 95% CI = 0.31-0.80; P-trend = 0.02). Participants classified in the high "vitamins and fiber" pattern score had a significant risk reduction of lung cancer (HR = 0.57; 95% CI = 0.36-0.90, P-trend = 0.01). Among heavy smokers enrolled in a screening trial, high vegetable fat intake and adherence to the "vitamin and fiber" nutrient pattern were associated with reduced lung cancer incidence.

Estimating overdiagnosis in low-dose computed tomography screening for lung cancer: a cohort study.

BACKGROUND: Lung cancer screening may detect cancer that will never become symptomatic (overdiagnosis), leading to overtreatment. Changes in size on sequential low-dose computed tomography (LDCT) screening, expressed as volume-doubling time (VDT), may help to distinguish aggressive cancer from cases that are unlikely to become symptomatic. OBJECTIVE: To assess VDT for screening-detected lung cancer as an indicator of overdiagnosis. DESIGN: Retrospective estimation of the VDT of cancer detected in a prospective LDCT screening cohort. SETTING: Nonrandomized, single-center screening study involving persons at high risk for lung cancer enrolled between 2004 and 2005 who received LDCT annually for 5 years. PATIENTS: 175 study patients diagnosed with primary lung cancer. MEASUREMENTS: VDT was measured on LDCT and classified as fast-growing (<400 days), slow-growing (between 400 and 599 days), or indolent (≥600 days). RESULTS: Fifty-five cases of cancer were diagnosed at baseline, and 120 were diagnosed subsequently. Of the latter group, 19 cases (15.8%) were new (not visible on previous scans) and fast-growing (median VDT, 52 days); 101 (84.2%) were progressive, including 70 (58.3%) fast-growing and 31 (25.8%) slow-growing (15.0%) or indolent (10.8%) cases. Lung cancer-specific mortality was significantly higher (9.2% per year) in patients with new compared with slow-growing or indolent (0.9% per year) cancer. Sixty percent of fast-growing progressive cancer and 45% of new cancer were stage I, for which survival was good. LIMITATIONS: This is a retrospective study. Volume-doubling time can only indicate overdiagnosis and was estimated for new cancer from 1 measurement (a diameter of 2 mm assumed the previous year). CONCLUSION: Slow-growing or indolent cancer comprised approximately 25% of incident cases, many of which may have been overdiagnosed. To limit overtreatment in these cases, minimally invasive limited resection and nonsurgical treatments should be investigated. PRIMARY FUNDING SOURCE: Italian Association for Cancer Research.

Real-world survival outcomes of wedge resection versus lobectomy for cT1a/b cN0 cM0 non-small cell lung cancer: a single center retrospective analysis.

Background: JCOG0802/WJOG4607L showed benefits in overall survival (OS) of segmentectomy. CALGB 140503 confirmed that sublobar resection was not inferior to lobectomy concerning recurrence-free survival (RFS) but did not provide specific OS and RFS according to the techniques of sublobar resections. Hence, we retrospectively analyze the survival differences between wedge resection and lobectomies for stage IA lung cancer. Methods: We reviewed the clinical records of patients with clinical stage IA NSCLC over 20 years. The inclusion criteria were: preoperative staging with CT scan and whole body CT/PET; tumor size <20 mm; wedge resections or lobectomies with or without lymph node dissection; NSCLC as the only primary tumor during the follow-up period. We excluded: multiple invasive lung cancer; positive resection margin; preoperative evidence of nodal disease; distant metastasis at presentation; follow-up time <5 years. The reverse Kaplan - Meier method estimated the median OS and PFS and compared them by the log-rank test. The stratified backward stepwise Cox regression model was employed for multivariable survival analyses. Results: 539 patients were identified: 476 (88.3%) lobectomies and 63 (11.7%) wedge resections. The median OS time for the whole cohort was 189.7 months (range: 173.7 - 213.9 months). The 5-year wedge resection and lobectomy OS were 82.2% and 87.0%. The 5-year RFS of wedge resection and lobectomy were 17.8% and 28.9%. The log-rank test showed no significant differences (p = 0.39) between wedge resections and lobectomies regarding OS and RFS (p = 0.23). Conclusions: Lobectomy and wedge resection are equivalent oncologic treatments for individuals with cN0/cM0 stage IA NSCLC <20 mm. Validating the current findings requires a prospective, randomized comparison between wedge resection and standard lobectomy to establish the prognostic significance of wedge resection.

Nicotine-Free E-Cigarettes Might Promote Tobacco Smoking Reduction Better Than Nicotine Delivery Devices: Results of a Double-Blind Randomized Controlled Trial at 1 Year.

The purpose of the present study was to determine whether the use of e-cigarettes to aid in quitting contributed to the increase in the pulmonary health of chronic smokers. The efficacy of e-cigarettes to support a successful smoking cessation attempt was also investigated. A total of 210 smokers (78 women) were enrolled in a screening program for the early detection of lung cancer and distributed in three arms: nicotine e-cigarette plus support, nicotine-free e-cigarette plus support, and support. Results showed that participants in the nicotine e-cigarette arm had a significant and fast decrease in daily cigarettes, but that later they resume smoking more than the other two groups. Conversely, participants in the other two arms showed similar daily consumption at the two evaluation points. Among abstinent participants, only 12.5% reported cough, while 48% of current smokers had pulmonary symptoms. Our study suggests that, in the long run, the use of a nicotine-free liquid may favor reducing smoking and could be considered a good option in a clinical setting.

Continuity of Cancer Care: The Surgical Experience of Two Large Cancer Hubs in London and Milan.

The SARS-CoV-2 (COVID-19) pandemic is having a large effect on the management of cancer patients. This study reports on the approach and outcomes of cancer patients receiving radical surgery with curative intent between March and September 2020 (in comparison to 2019) in the European Institute of Oncology, IRCCS (IEO) in Milan and the South East London Cancer Alliance (SELCA). Both institutions implemented a COVID-19 minimal pathway where patients were required to self-isolate prior to admission and were swabbed for COVID-19 within 72 h of surgery. Positive patients had surgery deferred until a negative swab. At IEO, radical surgeries declined by 6% as compared to the same period in 2019 (n = 1477 vs. 1560, respectively). Readmissions were required for 3% (n = 41), and <1% (n = 9) developed COVID-19, of which only one had severe disease and died. At SELCA, radical surgeries declined by 34% (n = 1553 vs. 2336). Readmissions were required for 11% (n = 36), <1% (n = 7) developed COVID-19, and none died from it. Whilst a decline in number of surgeries was observed in both centres, the implemented COVID-19 minimal pathways have shown to be safe for cancer patients requiring radical treatment, with limited complications and almost no COVID-19 infections.

Benefits of e-cigarettes in smoking reduction and in pulmonary health among chronic smokers undergoing a lung cancer screening program at 6 months.

INTRODUCTION: Electronic cigarettes (e-cigarettes) might be a valid and safe device to support smoking cessation. However, the available evidence is divergent. The aim of the present work was to assess the effects of an e-cigarette program on pulmonary health (cough, breath shortness, catarrh) and to evaluate the effectiveness of e-cigarettes in reducing tobacco consumption. METHODS: The study is a double-blind randomized controlled trial. Two hundred and ten smokers were randomized into three groups: nicotine e-cigarette (8 mg/mL nicotine concentration), nicotine-free e-cigarettes (placebo), and control with 1:1:1 ratio. All participants received a 3 months cessation program that included a cognitive-behavioral intervention aimed at supporting people in changing their behavior and improving motivation to quit. RESULTS: Pulmonary health, assessed with self-reported measures, clinical evaluations and the Leicester Cough Questionnaire, improved in participants who stopped smoking compared to their own baseline. No differences in pulmonary health were found between groups. Statistical tests showed a significant effect of Group (F (2, 118) = 4.005, p < .020) on daily cigarette consumption: after 6 months participants in the nicotine e-cigarette group smoked fewer cigarettes than any other group. Moreover, participants in this group showed the lowest level of exhaled carbon monoxide (CO) (M = 12.012, S.D. = 8.130), and the lowest level of dependence (M = 3.12, S.D. = 2.29) compared to the nicotine-free e-cigarette and control conditions. CONCLUSIONS: After 6 months about 20% of the entire sample stopped smoking. Participants who used e-cigarettes with nicotine smoked fewer tobacco cigarettes than any other group after 6 months (p < .020). Our data add to the efficacy and safety of e-cigarettes in helping smokers reducing tobacco consumption and improving pulmonary health status.

Low-dose computed tomography screening for lung cancer in people with workplace exposure to asbestos.

OBJECTIVES: Smoking is the main risk factor for lung cancer, but environmental and occupational exposure to carcinogens also increase lung cancer risk. We assessed whether extending low-dose computed tomography (LDCT) screening to persons with occupational exposure to asbestos may be an effective way reducing lung cancer mortality. MATERIALS AND METHODS: We conducted a nested case-control study within the COSMOS screening program, assessing past asbestos exposure with a questionnaire. LDCT scans of asbestos-exposed participants were reviewed to assess the presence of pulmonary, interstitial and pleural alterations in comparison to matched unexposed controls. We also performed an exhaustive review, with meta-analysis, of the literature on LDCT screening in asbestos-exposed persons. RESULTS: Exposure to asbestos, initially self-reported by 9.8% of COSMOS participants, was confirmed in 216 of 544 assessable cases, corresponding to 2.6% of the screened population. LDCT of asbestos-exposed persons had significantly more pleural plaques, diaphragmatic pleural thickening and pleural calcifications, but similar frequency of parenchymal and interstitial alterations to unexposed persons. From 16 papers, including this study, overall lung cancer detection rates at baseline were 0.81% (95% CI 0.50-1.19) in asbestos-exposed persons, 0.94% (95% CI 0.47-1.53) in asbestos-exposed smokers (12 studies), and 0.11% (95% CI 0.00-0.43) in asbestos-exposed non-smokers (9 studies). CONCLUSION: Persons occupationally exposed to asbestos should be monitored to gather more information about risks. Although LDCT screening is effective in the early detection lung cancer in asbestos-exposed smokers, our data suggest that screening of asbestos-exposed persons with no additional risk factors for cancer does is not viable due to the low detection rate.

Lung cancer screening with low-dose computed tomography: a non-invasive diagnostic protocol for baseline lung nodules.

BACKGROUND: Indeterminate non-calcified lung nodules are frequent when low-dose spiral computed tomography (LD-CT) is used for lung cancer screening. We assessed the diagnostic utility of a non-invasive work-up protocol for nodules detected at baseline in volunteers enrolled in our single-centre screening trial, and followed for at least 1 year. METHODS: 5201 high-risk volunteers, recruited over 1 year from October 2004, underwent baseline LD-CT; 4821 (93%) returned for the first repeat LD-CT. Nodules 8mm received combined CT-positron emission tomography (CT-PET). A subset of nodules >8mm was studied by CT with contrast. Protocol failures were delayed diagnosis with disease progression beyond stage I, and negative surgical biopsy. RESULTS: 2754 (53%) volunteers presented one or more non-calcified nodules. Ninety-two lung cancers were diagnosed: 55 at baseline and 37 at annual screening (66% stage I). Among the 37 incident cancers, 17 had a baseline nodule that remained stage I, 7 had a baseline nodule that progressed beyond stage I, and 13 presented a new malignant nodule. Baseline and annual cancers were 79 (1.5%) and 13 (0.2%), respectively. In 15 of 104 (14%) invasive diagnostic procedures, the lesion was benign. Sensitivity, and specificity were 91 and 99.7%, respectively, for the entire protocol; 88 and 93% for CT-PET; and 100 and 59% for CT with contrast. CONCLUSIONS: The protocol limits invasive diagnostic procedures while few patients have diagnosis delay, supporting the feasibility of lung cancer screening in high-risk subjects by LD-CT. Nevertheless further optimization of the clinical management of screening-detected nodules is necessary.

miR-Test: a blood test for lung cancer early detection.

Lung cancer is the leading cause of cancer death worldwide. Low-dose computed tomography screening (LDCT) was recently shown to anticipate the time of diagnosis, thus reducing lung cancer mortality. However, concerns persist about the feasibility and costs of large-scale LDCT programs. Such concerns may be addressed by clearly defining the target "high-risk" population that needs to be screened by LDCT. We recently identified a serum microRNA signature (the miR-Test) that could identify the optimal target population. Here, we performed a large-scale validation study of the miR-Test in high-risk individuals (n = 1115) enrolled in the Continuous Observation of Smoking Subjects (COSMOS) lung cancer screening program. The overall accuracy, sensitivity, and specificity of the miR-Test are 74.9% (95% confidence interval [CI] = 72.2% to 77.6%), 77.8% (95% CI = 64.2% to 91.4%), and 74.8% (95% CI = 72.1% to 77.5%), respectively; the area under the curve is 0.85 (95% CI = 0.78 to 0.92). These results argue that the miR-Test might represent a useful tool for lung cancer screening in high-risk individuals.

Diagnostic performance of low-dose computed tomography screening for lung cancer over five years.

INTRODUCTION: Low-dose computed tomography (LD-CT) screening can reduce lung cancer mortality; however, it is essential to improve nodule management protocols. We analyze the performance of the diagnostic protocol of the Continuous Observation of SMOking Subjects single-center screening study, after long-term follow-up. METHODS: Between 2004 and 2005, 5203 asymptomatic high-risk individuals (≥20 pack-years, aged 50 years or older) were enrolled to undergo annual LD-CT for 5 years. Nodules 5 mm or smaller underwent repeat LD-CT a year later. Nodules larger than 5.0 mm and 8.0 mm or smaller received LD-CT 3 to 6 months later. Nodules larger than 8.0 mm or growing underwent CT-positron emission tomography. True positives were any stage prevalent lung cancer, progressing nodules diagnosed at stage 1, localized multifocal cancer, or new nodules diagnosed at any stage. False negatives were progressing nodules diagnosed at stage >1. False positives were benign nodules resected surgically. RESULTS: Compliance was 79% over 5 years; 175 primary lung cancers were detected (0.76% per year), 136 (77.7%) were N0M0 and three were interval cancers. Eleven second primary lung cancers were diagnosed. Resectability was 87.4%; postoperative mortality 0.6%. Recall was 6.4% overall, 10.1% at baseline. False negatives were 14 of 175 (8%). Protocol sensitivity was 158 of 175 (90%); specificity 4994 of 5028 (99.4%); positive predictive value was 158 of 187 (84.5%); and negative predictive value was 4994 of 5016 (99.7%). Twenty-nine of 204 (14.2%) benign lesions were diagnosed surgically. Five-year overall and cancer-specific survival were 78% (95% confidence interval, 72-84) and 82% (95% confidence interval, 76%-88%) respectively. CONCLUSIONS: The performance of the CT protocol was satisfactory with an acceptable number of benign lesions biopsied surgically, low recall rate, and good oncological outcomes. However, interval and advanced cancers, and misdiagnoses, need to be reduced, perhaps by risk modeling and use of serum markers.

Screening-detected lung cancers: is systematic nodal dissection always essential?

BACKGROUND: To address whether systematic lymph node dissection is always necessary in early lung cancer, we identified factors predicting nodal involvement in a screening series and applied them to nonscreening-detected cancers. METHODS: In the 97 patients with clinical T1-2N0M0 lung cancer (<3 cm), enrolled in the Continuous Observation of Smoking Subjects computed tomography (CT) screening study, who underwent curative resection with radical mediastinal lymph node dissection, we examined factors associated with hilar extrapulmonary and mediastinal nodal involvement. Nodule size plus positive/negative positron emission tomography (PET)-CT (usually as maximum standard uptake value [maxSUV]) were subsequently evaluated retrospectively for their ability to predict nodal involvement in 193 consecutive patients with nonscreening-detected clinical stage I lung cancer. RESULTS: Among Continuous Observation of Smoking Subjects patients, 91 (94%) were pN0, and six (6.2%) were pN+. All patients with maxSUV <2.0 (p = 0.08) or pathological nodule ≤10 mm (p = 0.027) were pN0 (62 cases). Nodal metastases occurred in 6 cases among the 29 (17%) patients with lung nodule >10 mm and maxSUV ≥2.0 (p = 0.002 versus the other 62 cases). In the nonscreening series, 42 of 43 cases with negative PET-CT (usually maxSUV <2.0) or nodule ≤10 mm were pN0; 33 of 149 (22%) cases with positive PET-CT (usually maxSUV ≥ 2.0) and nodule >10 mm were pN+ (p = 0.001 versus the 43 cases). CONCLUSIONS: This limited experience suggests that in early-stage clinically N0 lung cancers with maxSUV <2.0 or pathological nodule size ≤10 mm, systematic nodal dissection can be avoided as the risk of nodal involvement is very low.

Lung cancer risk prediction to select smokers for screening CT--a model based on the Italian COSMOS trial.

Screening with low-dose helical computed tomography (CT) has been shown to significantly reduce lung cancer mortality but the optimal target population and time interval to subsequent screening are yet to be defined. We developed two models to stratify individual smokers according to risk of developing lung cancer. We first used the number of lung cancers detected at baseline screening CT in the 5,203 asymptomatic participants of the COSMOS trial to recalibrate the Bach model, which we propose using to select smokers for screening. Next, we incorporated lung nodule characteristics and presence of emphysema identified at baseline CT into the Bach model and proposed the resulting multivariable model to predict lung cancer risk in screened smokers after baseline CT. Age and smoking exposure were the main determinants of lung cancer risk. The recalibrated Bach model accurately predicted lung cancers detected during the first year of screening. Presence of nonsolid nodules (RR = 10.1, 95% CI = 5.57-18.5), nodule size more than 8 mm (RR = 9.89, 95% CI = 5.84-16.8), and emphysema (RR = 2.36, 95% CI = 1.59-3.49) at baseline CT were all significant predictors of subsequent lung cancers. Incorporation of these variables into the Bach model increased the predictive value of the multivariable model (c-index = 0.759, internal validation). The recalibrated Bach model seems suitable for selecting the higher risk population for recruitment for large-scale CT screening. The Bach model incorporating CT findings at baseline screening could help defining the time interval to subsequent screening in individual participants. Further studies are necessary to validate these models.