National Lung Screening Trial Criteria Research Articles

Characteristics of Singapore lung cancer patients who miss out on lung cancer screening recommendations.

The National Lung Screening Trial (NLST) identified individuals at high risk for lung cancer and showed that serial low-dose helical computed tomography could identify lung cancer at an earlier stage, leading to mortality reduction. However, there is little evidence regarding the effectiveness of the NLST criteria for the Asian population. We performed a retrospective audit in our hospital from January 2018 to December 2018, with the aim to describe the characteristics of patients diagnosed with lung cancer and to identify patients who would miss out on lung cancer screening when the NLST criteria was applied. We found that only 38.1% of our cohort who were diagnosed with lung cancer met the NLST criteria strictly by age and smoking status. Patients who met the screening criteria would have derived significant benefits from it, as 85.4% of our patients had presented at an advanced stage and 54.6% died within 1 year. When the United States Preventive Services Task Force criteria was applied, it increased the sensitivity of lung cancer diagnosis to 58.7%. Only 15.5% of the female patients with lung cancer met the NLST criteria; their low smoking quantity was a significant contributing factor for exclusion. The majority of Singapore patients diagnosed with lung cancer, especially females, would not have been identified with the NLST criteria. However, those who met the inclusion criteria would have benefited greatly from screening. Extending the screening age upper limit may yield benefits and improved sensitivity in the Singapore context.

Risk-based prediction model for selecting eligible population for lung cancer screening among ever smokers in Korea.

BackgroundThis study developed a new lung cancer risk prediction model for the Korean population and evaluated the performance, compared to the previously reported risk models developed in Western countries.MethodsAmong the 6,811,893 people who received health examinations from the Korean National Health Insurance Service, 969,351 ever-smokers (40–79 years) were included. Performance of Bach, Lung Cancer Risk Models for Screening, PLCOM2012, Pittsburgh, and Liverpool Lung Project models were evaluated. The ever-smokers were divided into the training and validation datasets by random sampling. The lung cancer risk model was developed and validated in the Korean population. The efficiency of model-based selection for lung cancer screening was compared with the eligible criteria of the National Lung Screening Trial (NLST).ResultsThe Korean lung cancer risk model showed the area under the curve and expected/observed (E/O) ratio of 0.816 and 0.983 in the training dataset and 0.816 and 0.988 in the validation dataset. The Korean lung cancer risk model included age-mean of age, square of age-mean of age, sex, square root of pack-years of smoking, years since cessation, physical activity, alcohol consumption, body mass index, and medical history of chronic pulmonary obstructive disease, emphysema, pneumoconiosis, and interstitial pulmonary disease. Compared with the NLST criteria, the Korean lung cancer risk model’s cut-off criteria (>2.1%) had more improved sensitivity (61.4% vs. 44.3%) and positive predictive value (4.1% vs. 2.9%). The Korean lung cancer risk model showed better discrimination and calibration than previously developed models in Western population.ConclusionsThe Korean lung cancer risk model can select eligible population for low-dose computed tomography screening among the Asian population. The efficiency of risk model-based selection for lung cancer screening is superior to that of fixed criteria-based selection.

Association between biomarkers of tobacco consumption and lung cancer risk among daily smokers

ABSTRACT Background Biomarkers of tobacco consumption may play a role in the lung cancer risk assessment. However, the role of salivary biomarkers has not been well studied. The aim of this study is to assess the use of salivary biomarkers of tobacco consumption as lung cancer screening criterion. Research design and methods Data came from the Determinants of cotinine phase 3 project (Barcelona, 2013–2014). We compared the concentrations of TSNAs, including NNAL, NNN and NNK, and cotinine, in saliva samples of 142 daily smokers from the general population according to their risk of lung cancer. High risk of lung cancer was defined as per the inclusion criteria in the US National Lung Screening Trial (NLST) and in the Dutch-Belgian lung cancer screening trial (NELSON). Results Among daily smokers accomplishing the age criterion for lung cancer screening, salivary concentrations of cotinine, NNAL and NNK adjusted for sex were significantly higher (p-value < 0.05) in daily smokers at high risk of lung cancer compared to smokers not at high risk according to both NELSON and NLST criteria. Conclusions Saliva concentrations of cotinine, NNAL and NNK may be used as additional criteria for lung cancer screening. Further research on this topic is guaranteed.

Early detection of lung cancer with an incidental lung nodule program (ILNP).

8553 Background: Lung cancer early detection improves survival, but risk-based low-dose CT screening (LDCT) only identifies a minority of patients. We implemented an ILNP in a community healthcare system, and evaluated its risks and benefits. Methods: Patients with lung lesions on routinely-performed radiologic studies were flagged by radiologists and triaged using evidence-based guidelines. We tracked demographics, clinical characteristics, procedures, complications, and health outcomes. We analyzed ILNP subjects’ eligibility for LDCT by National Lung Screening Trial (NLST), Center for Medicaid Services (CMS), NEderlands Leuvens Screening ONderzoek (NELSON), National Comprehensive Cancer Network (NCCN) Risk Groups 1 and 2 (screening recommended), NCCN Risk Group 3 (screening not currently recommended), and US Preventive Services Task Force (USPSTF) criteria from 2013 and 2020. Statistical analysis used the chi-square test and Kaplan Meier method. Results: From 2015-2020, 13,710 patients were evaluated in the ILNP program: median age, 64 years; 42% male; 65% White, 29% Black; 667 (4.9%) were diagnosed with lung cancer. Lung cancers diagnosed from ILNP were 39% adenocarcinoma / 20% Squamous Cell with clinical stage distribution 49% I, 8% II, 17% III, and 16% IV. 832 (6.1%) had invasive diagnostic testing- CT-guided biopsy (50%), bronchoscopy (30%), and/or EBUS (26%); 11% of the 832 had &gt;1 invasive diagnostic test. The most common complications from invasive testing were pneumothorax and chest tube placement. Only 11%-20% of all ILNP patients would have been eligible for LDCT. In ILNP patients diagnosed with lung cancer, only 33% were eligible for screening by NLST criteria; the proportion increased substantially when USPSTF 2020 or NCCN Group 2 criteria were applied (Table). Compared to NLST, NCCN Group 2 criteria increased screening eligibility among cancer patients by 22% (from 33% to 55%), while only increasing screening eligibility by 6% (from 8% to 14%) in non-cancer patients. Aggregate 1-year and 3-year survival rates for lung cancer patient diagnosed through ILNP were 76% (95% CI: 73, 80) and 64% (95% CI: 59, 69). Conclusions: The ILNP identified early-stage lung cancer more frequently than most LDCT programs, with promising survival rates. The majority of subjects with lung cancer were not eligible for LDCT, we still need to optimize risk-based screening criteria. Even with new, expanded criteria for LDCT, structured ILNP is necessary to expand early detection of lung cancer.[Table: see text]

Analysis of lung cancer risk model (PLCOM2012 and LLPv2) performance in a community-based lung cancer screening programme

IntroductionLow-dose CT (LDCT) screening of high-risk smokers reduces lung cancer (LC) specific mortality. Determining screening eligibility using individualised risk may improve screening effectiveness and reduce harm. Here, we compare the...

Circulating tumour cells as a potential biomarker for lung cancer screening: a prospective cohort study

Lung cancer screening with low-dose chest CT (LDCT) reduces the mortality of eligible individuals. Blood signatures might act as a standalone screening tool, refine the selection of patients at risk, or help to classify undetermined nodules detected on LDCT. We previously showed that circulating tumour cells (CTCs) could be detected, using the isolation by size of epithelial tumour cell technique (ISET), long before the cancer was diagnosed radiologically. We aimed to test whether CTCs could be used as a biomarker for lung cancer screening. We did a prospective, multicentre, cohort study in 21 French university centres. Participants had to be eligible for lung cancer screening as per National Lung Screening Trial criteria and have chronic obstructive pulmonary disease with a fixed airflow limitation defined as post-bronchodilator FEV1/FVC ratio of less than 0·7. Any cancer, other than basocellular skin carcinomas, detected within the previous 5 years was the main exclusion criterion. Participants had three screening rounds at 1-year intervals (T0 [baseline], T1, and T2), which involved LDCT, clinical examination, and a blood test for CTCs detection. Participants and investigators were masked to the results of CTC detection, and cytopathologists were masked to clinical and radiological findings. Our primary objective was to test the diagnostic performance of CTC detection using the ISET technique in lung cancer screening, compared with cancers diagnosed by final pathology, or follow up if pathology was unavailable as the gold standard. This study is registered with ClinicalTrials.gov identifier, number NCT02500693. Between Oct 30, 2015, and Feb 2, 2017, we enrolled 614 participants, predominantly men (437 [71%]), aged 65·1 years (SD 6·5), and heavy smokers (52·7 pack-years [SD 21·5]). 81 (13%) participants dropped out between baseline and T1, and 56 (11%) did between T1 and T2. Nodules were detected on 178 (29%) of 614 baseline LDCTs. 19 participants (3%) were diagnosed with a prevalent lung cancer at T0 and 19 were diagnosed with incident lung cancer (15 (3%) of 533 at T1 and four (1%) of 477 at T2). Extrapulmonary cancers were diagnosed in 27 (4%) of participants. Overall 28 (2%) of 1187 blood samples were not analysable. At baseline, the sensitivity of CTC detection for lung cancer detection was 26·3% (95% CI 11·8-48·8). ISET was unable to predict lung cancer or extrapulmonary cancer development. CTC detection using ISET is not suitable for lung cancer screening. French Government, Conseil Départemental 06, Fondation UNICE, Fondation Aveni, Fondation de France, Ligue Contre le Cancer-Comité des Alpes-Maritimes, ARC (Canc'Air Genexposomics), Claire de Divonne-Pollner, Enca Faidhi, Basil Faidhi, Fabienne Mourou, Michel Mourou, Leonid Fridlyand, cogs4cancer, and the Fondation Masikini.

LDCT lung cancer screening in populations at different risk for lung cancer

IntroductionThe improvement of low-dose CT (LDCT) lung cancer screening selection criteria could help to include more individuals who have lung cancer, or in whom lung cancer will develop, while avoiding...

Adherence to general medical checkup and cancer screening guidelines according to self-reported smoking status: Korea National Health and Nutrition Examination Survey (KNHANES) 2010-2012.

ObjectivesThe National Lung Screening Trial (NLST) revealed that low-dose computed tomography (LDCT) screening could reduce lung cancer mortality in heavy smokers. Lung screening with LDCT was implemented in July 2019 as part of the National Cancer Screening Program in Korea for heavy smokers who meet NLST criteria [smokers aged 55–74 years with 30 pack-years (PY) or more, excluding former smokers with more than 15 years since smoking cessation]. This study evaluated NLST-eligible heavy smokers’ adherence to general medical checkup and cancer screening guidelines.MethodsUsing the Korea National Health and Nutrition Examination Survey (KNHANES) from 2010 to 2012, we compared adherence of Korean adults (55–74 years, n = 5,480) to general medical checkup and cancer (gastric, colorectal, breast, and cervical) screening guidelines according to self-reported smoking status. Smoking and PY data were available, but no data indicating when former smokers ceased smoking were available. Accordingly, smoking status was only classified as NLST (smokers with a history ≥ 30 PY) and non-NLST. Individuals who met NLST criteria were subdivided into current (NLST-current) and former smokers (NLST-former). Multivariable logistic regression was used to evaluate adherence to screening recommendations as a function of the study group (NLST-current, NLST-former, non-NLST) using possible covariates (sociodemographic factors, health-related behaviors, comorbidities, and self-reported health status).ResultsWeighted prevalence of NLST-current was 9.7%, of NLST-former was 9.6%, and of non-NLST was 80.7%. Overall screening rates were 70.7% (medical checkup), 59.1% (stomach cancer), 58.1% (colorectal cancer), 59.1% (breast cancer), and 48.9% (cervical cancer). Adherence to colorectal cancer screening and medical checkup was lower in NLST-current than non-NLST (AOR 0.59; 95% CI 0.44–0.78 for colorectal cancer; AOR 0.70; 95% CI 0.52–0.95 for medical checkup). Screening practices for other cancers were not different.ConclusionsCurrent heavy smokers meeting NLST criteria were less likely to have colorectal cancer screening or general medical checkup. Understanding the screening practices of this target population might enable the development of more effective plans to implement lung screening and improve screening compliance for other cancers.

Estimación del riesgo de cáncer de pulmón en mujeres que participan en un programa de cribado poblacional de cáncer de mama

IntroductionLung cancer mortality is increasing in women. In Spain, estimates suggest that lung cancer mortality may soon surpass breast cancer mortality, the main cause of cancer mortality among women. The aim of this study was to estimate the proportion of women at high risk of developing lung cancer in a group of participants in a population-based breast cancer screening program. MethodsCross-sectional study in a sample of women who participated in a population-based breast cancer screening program in 2016 in Hospitalet de Llobregat (n=1,601). High risk of lung cancer was defined according to the criteria of the National Lung Screening Trial (NLST) and the Dutch-Belgian randomized lung cancer screening trial (NELSON). ResultsAround 20% of smokers according to NLST criteria and 40% of smokers according to NELSON criteria, and around 20% of former smokers according to both criteria, are at high risk of developing lung cancer. A positive and statistically significant trend is observed between the proportion of women at high risk and nicotine dependence measured with the brief Fagerström test. ConclusionsA high proportion of participants in this breast cancer screening program have a high risk of developing lung cancer and would be eligible to participate in a lung cancer screening program. Population-based breast cancer screening programs may be useful to implement lung cancer primary prevention activities.

Quality improvement of lung cancer patient selection using clinic-based spirometry.

282 Background: Coordinating lung cancer screening requires risk assessment for patient selection. Optimal selection can reduce costs and improve efficiency of low dose computed tomography (LDCT) screening of lung cancer. This study evaluated clinic-based spirometry as a tool to improve patient selection for lung cancer screening. Methods: Eligibility criteria for three large LDCT screening studies were retrospectively applied to the highest risk patients enrolled in the Princess Margaret Lung Cancer Screening Program who had received clinic-based research spirometry. The three studies were: Danish Lung Cancer Screening Trial (DLST), National Lung Screening Trial (NLST), and the Ontario Lung Cancer Screening Program (OLCS). Lung cancer incidence was compared between those who would were included by the screening study eligibility criteria (Group I), those who were excluded by the eligibility criteria but demonstrated obstruction on spirometry (defined as a Forced Expiratory Volume in 1 Second % Predicted (FEV1%) &lt; 90%) (Group II), and those who did not meet eligibility criteria and had no obstruction (FEV1% ≥90) (Group III). Results: The 321 highest risk participants of the screening program had a mean age of 65 years and were 39% male. The median number of pack years in this group was 39. After undergoing spirometry, this cohort was screened using LDCT for a median of 3.3 years (range 1–8.1 years). Under DLST criteria, Groups I and II had virtually identical lung cancer incidences detected by screening at 13.1% and 13.6% of the individuals screened, respectively; Group III had a substantially lower incidence at 6.3%. Results were similar by NLST criteria where the incidence of screen-detected lung cancer were 13.7% for Groups I, 11.1% for Group II, and 8.6% for Group III. Under OLCS criteria, these values were 13.4% (Group I), 13.5% (Group II), and 8.2% (Group III). Conclusions: Individuals who were excluded from LDCT screening because they lacked other clinical eligibility criteria, but had a FEV1 &lt; 90%, had similar lung cancer incidence as patients who had met screening study eligibility criteria. Coordinating care for screening of at-risk individuals could be improved by incorporating spirometric tools.

Screening for Lung Cancer Using Low-dose Chest Computed Tomography in Korean Long-term Colorectal Cancer Survivors.

BackgroundThe National Lung Screening Trial (NLST) and NELSON trial showed that low-dose chest computed tomography (LDCT) screening significantly reduced the mortality form lung cancer. Although cancer survivors are known to have high risk for second malignant neoplasm (SMN), the usefulness of LDCT screening for lung cancer in cancer survivors is not clear.MethodsBetween August 2016 and August 2017, 633 long-term colorectal cancer (CRC) survivors visited the survivorship clinic in Cancer Prevention Center, Yonsei Cancer Center, Seoul, Republic of Korea. We surveyed the smoking status and recommended LDCT screening to ever-smoking CRC survivors aged 55–80 years. The participants were classified into three risk groups: risk group 1 (RG1) who met the NLST criteria (Age 55–74 years, ≥ 30 pack-years of smoking, smoking cessation < 15 years); risk group 2 (RG2) who would not meet the NLST criteria but were at increased 6-year risk of lung cancer (PLCOM2012 ≥ 0.0151); risk group 3 (RG3) who did not meet any of the criteria above.ResultsAmong 176 ever-smoking CRC survivors, 173 (98.3%) were male, 32 (18.2%) were current-smoker, and median age was 66 years (range, 55–79 years). We found 38 positive findings (non-calcified nodule ≥ 4 mm), 8 clinically significant findings, 66 minor abnormalities, and 64 negative findings on LDCT. Positive findings were identified in 15 of 79 (19.0%) of RG1, in 9 of 36 (25%) of RG2, and in 14 of 61 (23.0%) of RG3. Second primary lung cancers were found in 2 patients of RG2, and in 1 patient of RG3. SMN was most frequently found in RG2 (11 of 36 patients, 30.6%), compared with RG1 (12.7%) or RG3 (9.8%) (P = 0.016).ConclusionsLDCT screening for lung cancer in Korean CRC survivors is feasible. Well-designed clinical trial for defining high risk patients for lung cancer among CRC survivors is needed.

Smoking pattern and risk of lung cancer among women participating in cancer screening programmes.

The aim of this study was to describe the smoking prevalence, the smoking pattern, and the risk of lung cancer among women who participated in a cancer screening (breast, cervical and colorectal) in Spain. We used data from the Spanish National Health Survey of 2011-12, a cross-sectional study of the adult Spanish population from women in the age of participation in the population cancer screening. We used two definitions of the high risk of lung cancer according to the National Lung Screening Trial (NLST) criteria and the NELSON criteria. Participation in screening was 76.6% in breast cancer, 6.6% in colorectal cancer, and 70.3% in cervical cancer. The percentage of current smokers was 17.1 of women who participated breast cancer, 15.4 of women who participated colorectal cancer, and 26.1 of women who participated cervical cancer. According to NLST criteria, the percentage of current smokers women who had a high risk of lung cancer was 23.1 for breast cancer, 23.5 for colorectal cancer and 4.5 for cervical cancer. These figures were higher with the NELSON criteria. At least 250 000 women in Spain have a high risk of lung cancer and are participating in a cancer screening programme. These programmes might be an opportunity for implementing specific interventions aiming to reduce this risk.

Estimation of the adult population at high risk of developing lung cancer in the European Union

Background Lung cancer mortality accounts for over 266,000 deaths in the European Union (EU) every year, most of them attributed to smoking. The aim of this study was to estimate the prevalence of the adult population at high risk of developing lung cancer in the EU in 2014.Methods This is a cross-sectional study. We used data from the Special Eurobarometer 429 (n = 27,801). The fieldwork was conducted between November-December 2014. High risk of lung cancer was defined using the criteria of the National Lung Screening Trial (NLST) and the Dutch-Belgian Lung Cancer Screening Trial (NELSON).Results One out of ten smokers (11.6% of men and 9.6% of women) according to NLST criteria and one out of four smokers (24.6% of men and 22.4% of women) according to NELSON criteria are currently at high risk of lung cancer in the EU. According to both criteria, the prevalence of former smokers at high risk of lung cancer is under 10%.Conclusion Around 17 million citizens in the EU according to NLST criteria and 34 million according to NELSON criteria (around 4% and 8% of the adult population, respectively) are at high risk of developing lung cancer. Since the implementation of lung cancer screening programs still remains controversial, primary prevention activities should be encouraged.

Identifying high-risk individuals for lung cancer screening: Going beyond NLST criteria.

BackgroundThere are two main types of strategies to identify target population for lung cancer screening: 1) strategies based on age and cumulative smoking criteria, 2) risk prediction models allowing the calculation of an individual risk. The objective of this study was to compare different strategies to identify the proportion of the Spanish population at high risk of developing lung cancer, susceptible to be included in a lung cancer screening programme.MethodsCross-sectional study. We used the data of the Spanish National Interview Health Survey (ENSE) of 2011–2012 (21,006 individuals) to estimate the proportion of participants at high risk of developing lung cancer. This estimation was performed using the U.S. national lung screening trial (NLST) criteria and a 6-year prediction model (PLCOm2012), both independently and in combination.ResultsThe prevalence of individuals at high risk of developing lung cancer according to the NLST criteria was 4.9% (7.9% for men, 2.4% for women). Among the 1,034 subjects who met the NLST criteria, 533 (427 men and 106 women) had a 6-year lung cancer risk ≥2.0%. The combination of these two selection strategies showed that 2.5% of the Spanish population had a high risk of developing lung cancer. However, this selection process did not take into account different groups of subjects <75 years old having an individual risk of lung cancer ≥2%, such as heavy smokers <55 years old who were long-time former smokers, and ever-smokers having smoked <30 pack-years with other risk factors.ConclusionsFurther research is needed to determine which selection strategy achieves a higher benefit/harm ratio and to assess other prevention strategies for individuals with elevated risk for lung cancer but who do not meet the screening eligibility criteria.

Modified Lung-RADS Improves Performance of Screening LDCT in a Population with High Prevalence of Non–smoking-related Lung Cancer

We proposed a modification of the ACR Lung Imaging Reporting and Data System (Lung-RADS) to clarify the characteristics of subsolid nodules with categories 1-11, and to compare the diagnostic accuracy with Lung-RADS and National Lung Screening Trial criteria in an Asian population with high prevalence of adenocarcinoma. We analyzed a retrospective cohort of 1978 consecutive healthy subjects (72.8% nonsmoker) who underwent low-dose computed tomography from August 2013 to October 2014 (1084 men, 894 women). Lung-RADS categories 2 and 3 were modified to include subcategories of 2A/2B/2C and 3A/3B/3C, respectively. Clinical information and nodule characteristics were recorded. Receiver operating characteristic curves were used to compare diagnostic accuracy at different cutoffs. Thirty-two subjects (30 nonsmokers) had pathology-proven adenocarcinoma spectrum lesions in the follow-up period (1.6 ± 0.5 years). Modified Lung-RADS, using modified Lung-RADS category 2C as cutoff, had an area under the curve (AUC) of 0.973 in predicting adenocarcinoma spectrum lesions (sensitivity of 100%, specificity of 89.3%), which was significantly higher than that of Lung-RADS (AUC = 0.815, P < .001) and National Lung Screening Trial (AUC = 0.906, P < .001). Furthermore, modified Lung-RADS showed an AUC of 0.992 in predicting invasive adenocarcinoma (sensitivity of 95%, specificity of 97.8%) when category 3B was used as cutoff. Modified Lung-RADS may substantially improve sensitivity while maintaining specificity for detection of adenocarcinoma spectrum lesions in an Asian population. Compared to Lung-RADS, it has enhanced ability to differentiate invasive from indolent adenocarcinoma by more refined subclassification of subsolid nodules using two cutoff values of category 2C and 3B. The effect of using modified Lung-RADS in clinical practice must be carefully studied in prospective large cohort studies.

MTE 27.01 Who Should be Screened for Lung Cancer?

MTE 27.01 Who Should be Screened for Lung Cancer?

Utility of the National Lung Screening Trial Criteria for Estimation of Lung Cancer in the Korean Population.

PurposeScreening forlung cancerin high-risk patients using the National Lung Screening Trial (NLST) criteria resulted in a decreased lung cancer-related mortality rate. However, whether these criteria are applicable to the Korean has not been investigated thus far. Therefore, we estimated the utility of the NLST criteria as a screening tool for lung cancer in the Korean population.Materials and MethodsThe total number of newly diagnosed lung cancer cases in 2013 was obtained from the Korea National Statistical Office. The proportion of newly diagnosed lung cancer cases that met the NLST criteria was calculated via a retrospective cohort of a tertiary referral hospital. We estimated the nationwide proportion of patients who met the NLST criteria using the 5th Korea National Health and Nutrition Examination Survey conducted during 2010-2012 (KNHANES V).ResultsUsing KNHANES V data, we found that approximately 6.92% of the general population of Korea would meet the NLST criteria. In the tertiary referral hospital, 29.6% of the 2,689 newly diagnosed lung cancer patients met the NLST criteria. In 2013, the total number of newly diagnosed lung cancer cases in Korea was 23,177. The estimated nationwide proportions of lung cancer patients who met and did not meet the NLST criteria were 0.37% and 0.06%, respectively, yielding a ratio of 5.78.ConclusionThe NLST criteria demonstrated sound clinical utility for lung cancer screening of high-risk patients in Korea.

Radiologic Features of Small Pulmonary Nodules and Lung Cancer Risk in the National Lung Screening Trial: A Nested Case-Control Study.

Purpose To extract radiologic features from small pulmonary nodules (SPNs) that did not meet the original criteria for a positive screening test and identify features associated with lung cancer risk by using data and images from the National Lung Screening Trial (NLST). Materials and Methods Radiologic features in SPNs in baseline low-dose computed tomography (CT) screening studies that did not meet NLST criteria to be considered a positive screening examination were extracted. SPNs were identified for 73 incident case patients who were given a diagnosis of lung cancer at either the first or second follow-up screening study and for 157 control subjects who had undergone three consecutive negative screening studies. Multivariable logistic regression was used to assess the association between radiologic features and lung cancer risk. All statistical tests were two sided. Results Nine features were significantly different between case patients and control subjects. Backward elimination followed by bootstrap resampling identified a reduced model of highly informative radiologic features with an area under the receiver operating characteristic curve of 0.932 (95% confidence interval [CI]: 0.88, 0.96), a specificity of 92.38% (95% CI: 52.22%, 84.91%), and a sensitivity of 76.55% (95% CI: 87.50%, 95.35%) that included total emphysema score (odds ratio [OR] = 1.71; 95% CI: 1.39, 2.01), attachment to vessel (OR = 2.41; 95% CI: 0.99, 5.81), nodule location (OR = 3.25; 95% CI: 1.09, 8.55), border definition (OR = 7.56; 95% CI: 1.89, 30.8), and concavity (OR = 2.58; 95% CI: 0.89, 5.64). Conclusion A set of clinically relevant radiologic features were identified that that can be easily scored in the clinical setting and may be of use to determine lung cancer risk among participants with SPNs. © RSNA, 2017 Online supplemental material is available for this article.

Abstract 3261: Gene methylation biomarkers in sputum as a classifier for lung cancer risk

Abstract Lung cancer is the leading cause of cancer death primarily because it is often diagnosed at an advanced stage. Results from the National Lung Screening Trial (NLST) showed that CT screening can reduce lung cancer mortality by 20%, but the high number of false positives and need for additional testing suggest that better risk classification of smokers prior to screening could save more lives with less cost and improved efficiency. Furthermore, eligibility criteria for NLST were restricted to smokers ages of 55-74 with &amp;gt;30 pack-years of smoking and &amp;lt; 15y since smoking cessation, which captures only ~40% of incident lung cancer cases. Molecular biomarkers could augment current risk stratification used to select smokers for screening. We have shown that gene specific promoter hypermethylation detected in sputum provides an assessment of field cancerization within the lungs of smokers that in turn predicts lung cancer. The current study addressed whether our validated 8-gene methylation panel could be extended to improve the existing risk prediction model used to recommend people for a CT screen by evaluating methylation in 487 resected Stage I lung cancer patients from the ECOG-ACRIN5597 trial (field of injury remains), 1378 current and former smokers from the Lovelace Smokers cohort (LSC) and 718 current and former smokers from the PLuSS cohort. Our initial analysis was restricted to individuals from each cohort who met NLST criteria for CT screening (n=371 ECOG-ACRIN, n=466 LSC and n=597 PLuSS). The methylation prevalence of all 8 genes was significantly increased in resected lung cancer patients compared to cancer-free smokers (odds ratios 1.6 to 8.9). The area under the receiver operator characteristic curve (AUC) was used to evaluate classification accuracy of different logistic regression models. Classification accuracy for clinical risk factors alone was 74-76%, methylation alone, 82-86%; and clinical risk factors plus methylation, 87-90% (p&amp;lt;10-9 - 10-16). Setting the sensitivity at 95% improved specificity from 25% to 54% with both methylation and clinical factors in the model. Assessment of the performance of the gene methylation panel in all of the cancer patients and smokers did not reduce classification accuracy or increase specificity. Implementation of gene methylation biomarkers for screening could be a paradigm shift for lung cancer management by providing a much improved risk assessment model that will allow for expanding the number of smokers considered for screening, decreasing by one-third the actual number referred, and reducing mortality through increasing the CT positive predictive value. (Supported largely by R01 CA095568 and in part P30 CA118100) Citation Format: Maria A. Picchi, Shuguang Leng, Guodong Wu, Donna M. Klinge, Cynthia L. Thomas, Elia Casas, Christine A. Stidley, Sandra J. Lee, Seena Aisner, Jill M. Siegfried, Suresh Ramalingam, Fadlo R. Khuri, Daniel D. Karp, Steven A. Belinsky. Gene methylation biomarkers in sputum as a classifier for lung cancer risk [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3261. doi:10.1158/1538-7445.AM2017-3261

Interval lung cancer after a negative CT screening examination: CT findings and outcomes in National Lung Screening Trial participants.

This study retrospectively analyses the screening CT examinations and outcomes of the National Lung Screening Trial (NLST) participants who had interval lung cancer diagnosed within 1year after a negative CT screen and before the next annual screen. The screening CTs of all 44 participants diagnosed with interval lung cancer (cases) were matched with negative CT screens of participants who did not develop lung cancer (controls). A majority consensus process was used to classify each CT screen as positive or negative according to the NLST criteria and to estimate the likelihood that any abnormalities detected retrospectively were due to lung cancer. By retrospective review, 40/44 cases (91%) and 17/44 controls (39%) met the NLST criteria for a positive screen (P < 0.001). Cases had higher estimated likelihood of lung cancer (P < 0.001). Abnormalities included pulmonary nodules ≥4mm (n = 16), mediastinal (n = 8) and hilar (n = 6) masses, and bronchial lesions (n = 6). Cancers were stage III or IV at diagnosis in 32/44 cases (73%); 37/44 patients (84%) died of lung cancer, compared to 225/649 (35%) for all screen-detected cancers (P < 0.0001). Most cases met the NLST criteria for a positive screen. Awareness of missed abnormalities and interpretation errors may aid lung cancer identification in CT screening. • Lung cancer within a year of a negative CT screen was rare. • Abnormalities likely due to lung cancer were identified retrospectively in most patients. • Awareness of error types may help identify lung cancer sooner.