Low-dose Computed Tomography Screening Research Articles

Early Detection of Lung Cancer Using Small RNAs

IntroductionLung cancer remains the deadliest cancer in the world, and lung cancer survival is heavily dependent on tumor stage at the time of detection. Low-dose computed tomography screening can reduce mortality; however, annual screening is limited by low adherence in the United States of America and still not broadly implemented in Europe. As a result, less than 10% of lung cancers are detected through existing programs. Thus, there is a great need for additional screening tests, such as a blood test, that could be deployed in the primary care setting. MethodsWe prospectively recruited 1384 individuals meeting the National Lung Screening Trial demographic eligibility criteria for lung cancer and collected stabilized whole blood to enable the pipetting-free collection of material, thus minimizing preanalytical noise. Ultra-deep small RNA sequencing (20 million reads per sample) was performed with the addition of a method to remove highly abundant erythroid RNAs, and thus open bandwidth for the detection of less abundant species originating from the plasma or the immune cellular compartment. We used 100 random data splits to train and evaluate an ensemble of logistic regression classifiers using small RNA expression of 943 individuals, discovered an 18-small RNA feature consensus signature (miLung), and validated this signature in an independent cohort (441 individuals). Blood cell sorting and tumor tissue sequencing were performed to deconvolve small RNAs into their source of origin. ResultsWe generated diagnostic models and report a median receiver-operating characteristic area under the curve of 0.86 (95% confidence interval [CI]: 0.84–0.86) in the discovery cohort and generalized performance of 0.83 in the validation cohort. Diagnostic performance increased in a stage-dependent manner ranging from 0.73 (95% CI: 0.71–0.76) for stage I to 0.90 (95% CI: 0.89–0.90) for stage IV in the discovery cohort and from 0.76 to 0.86 in the validation cohort. We identified a tumor-shed, plasma-bound ribosomal RNA fragment of the L1 stalk as a dominant predictor of lung cancer. The fragment is decreased after surgery with curative intent. In additional experiments, results of dried blood spot collection and sequencing revealed that small RNA analysis could potentially be conducted through home sampling. ConclusionsThese data suggest the potential of a small RNA-based blood test as a viable alternative to low-dose computed tomography screening for early detection of smoking-associated lung cancer.

Low-Dose Computed Tomography Screening in Relatives With a Family History of Lung Cancer

IntroductionThe role of a family history of lung cancer (LCFH) in screening using low-dose computed tomography (LDCT) has not been prospectively investigated with long-term follow-up. MethodsA multicenter prospective study with up to three rounds of annual LDCT screening was conducted to determine the detection rate of lung cancer (LC) in asymptomatic first- or second-degree relatives of LCFH. ResultsFrom 2007 to 2011, there were 1102 participants enrolled, including 805 and 297 from simplex and multiplex families (MFs), respectively (54.2% women and 70.0% never-smokers). The last follow-up date was May 5, 2021. The overall LC detection rate was 4.5% (50 of 1102). The detection rate in MF was 9.4% (19 of 202) and 4.4% (4 of 91) in never-smokers and in those who smoked, respectively. The corresponding rates for simplex families were 3.7% (21 of 569) and 2.7% (6 of 223), respectively. Of these, 68.0% and 22.0% of cases with stage I and IV diseases, respectively. LC diagnoses within a 3-year interval from the initial screening tend to be younger, have a higher detection rate, and have stage I disease; thereafter, more stage III–IV disease and 66.7% (16 of 24) with negative or semipositive nodules in initial computed tomography scans. Within the 6-year interval, only maternal (modified rate ratio = 4.46, 95% confidence interval: 2.32–8.56) or maternal relative history of LC (modified rate ratio = 5.41, 95% confidence interval: 2.84–10.30) increased the risk of LC. ConclusionsLCFH is a risk factor for LC and is increased with MF history, among never-smokers, younger adults, and those with maternal relatives with LC. Randomized controlled trials are needed to confirm the mortality benefit of LDCT screening in those with LCFH.

Measuring spirometry in a lung cancer screening cohort highlights possible underdiagnosis and misdiagnosis of COPD.

COPD is underdiagnosed, and measurement of spirometry alongside low-dose computed tomography (LDCT) screening for lung cancer is one strategy to increase earlier diagnosis of this disease. Ever-smokers at high risk of lung cancer were invited to the Yorkshire Lung Screening Trial for a lung health check (LHC) comprising LDCT screening, pre-bronchodilator spirometry and a smoking cessation service. In this cross-sectional study we present data on participant demographics, respiratory symptoms, lung function, emphysema on imaging and both self-reported and primary care diagnoses of COPD. Multivariable logistic regression analysis identified factors associated with possible underdiagnosis and misdiagnosis of COPD in this population, with airflow obstruction defined as forced expiratory volume in 1 s/forced vital capacity ratio <0.70. Out of 3920 LHC attendees undergoing spirometry, 17% had undiagnosed airflow obstruction with respiratory symptoms, representing potentially undiagnosed COPD. Compared to those with a primary care COPD code, this population had milder symptoms, better lung function and were more likely to be current smokers (p≤0.001 for all comparisons). Out of 836 attendees with a primary care COPD code who underwent spirometry, 19% did not have airflow obstruction, potentially representing misdiagnosed COPD, although symptom burden was high. Spirometry offered alongside LDCT screening can potentially identify cases of undiagnosed and misdiagnosed COPD. Future research should assess the downstream impact of these findings to determine whether any meaningful changes to treatment and outcomes occur, and to assess the impact on co-delivering spirometry on other parameters of LDCT screening performance such as participation and adherence. Additionally, work is needed to better understand the aetiology of respiratory symptoms in those with misdiagnosed COPD, to ensure that this highly symptomatic group receive evidence-based interventions.

Lung Cancer Screening in Asia: An Expert Consensus Report

IntroductionThe incidence and mortality of lung cancer are highest in Asia compared with Europe and USA, with the incidence and mortality rates being 34.4 and 28.1 per 100,000 respectively in East Asia. Diagnosing lung cancer at early stages makes the disease amenable to curative treatment and reduces mortality. In some areas in Asia, limited availability of robust diagnostic tools and treatment modalities, along with variations in specific health care investment and policies, make it necessary to have a more specific approach for screening, early detection, diagnosis, and treatment of patients with lung cancer in Asia compared with the West. MethodA group of 19 advisors across different specialties from 11 Asian countries, met on a virtual Steering Committee meeting, to discuss and recommend the most affordable and accessible lung cancer screening modalities and their implementation, for the Asian population. ResultsSignificant risk factors identified for lung cancer in smokers in Asia include age 50 to 75 years and smoking history of more than or equal to 20 pack-years. Family history is the most common risk factor for nonsmokers. Low-dose computed tomography screening is recommended once a year for patients with screening-detected abnormality and persistent exposure to risk factors. However, for high-risk heavy smokers and nonsmokers with risk factors, reassessment scans are recommended at an initial interval of 6 to 12 months with subsequent lengthening of reassessment intervals, and it should be stopped in patients more than 80 years of age or are unable or unwilling to undergo curative treatment. ConclusionsAsian countries face several challenges in implementing low-dose computed tomography screening, such as economic limitations, lack of efforts for early detection, and lack of specific government programs. Various strategies are suggested to overcome these challenges in Asia.

Lung Cancer Screening with Low-Dose CT: What We Have Learned in Two Decades of ITALUNG and What Is Yet to Be Addressed.

The ITALUNG trial started in 2004 and compared lung cancer (LC) and other-causes mortality in 55-69 years-aged smokers and ex-smokers who were randomized to four annual chest low-dose CT (LDCT) or usual care. ITALUNG showed a lower LC and cardiovascular mortality in the screened subjects after 13 years of follow-up, especially in women, and produced many ancillary studies. They included recruitment results of a population-based mimicking approach, development of software for computer-aided diagnosis (CAD) and lung nodules volumetry, LDCT assessment of pulmonary emphysema and coronary artery calcifications (CAC) and their relevance to long-term mortality, results of a smoking-cessation intervention, assessment of the radiations dose associated with screening LDCT, and the results of biomarkers assays. Moreover, ITALUNG data indicated that screen-detected LCs are mostly already present at baseline LDCT, can present as lung cancer associated with cystic airspaces, and can be multiple. However, several issues of LC screening are still unaddressed. They include the annual vs. biennial pace of LDCT, choice between opportunistic or population-based recruitment. and between uni or multi-centre screening, implementation of CAD-assisted reading, containment of false positive and negative LDCT results, incorporation of emphysema. and CAC quantification in models of personalized LC and mortality risk, validation of ultra-LDCT acquisitions, optimization of the smoking-cessation intervention. and prospective validation of the biomarkers.

Circulating proteome for pulmonary nodule malignancy.

Although lung cancer screening with low-dose computed tomography is rolling out in many areas of the world, differentiating indeterminate pulmonary nodules remains a major challenge. We conducted one of the first systematic investigations of circulating protein markers to differentiate malignant from benign screen-detected pulmonary nodules. Based on 4 international low-dose computed tomography screening studies, we assayed 1078 protein markers using prediagnostic blood samples from 1253 participants based on a nested case-control design. Protein markers were measured using proximity extension assays, and data were analyzed using multivariable logistic regression, random forest, and penalized regressions. Protein burden scores (PBSs) for overall nodule malignancy and imminent tumors were estimated. We identified 36 potentially informative circulating protein markers differentiating malignant from benign nodules, representing a tightly connected biological network. Ten markers were found to be particularly relevant for imminent lung cancer diagnoses within 1 year. Increases in PBSs for overall nodule malignancy and imminent tumors by 1 standard deviation were associated with odds ratios of 2.29 (95% confidence interval: 1.95 to 2.72) and 2.81 (95% confidence interval: 2.27 to 3.54) for nodule malignancy overall and within 1 year of diagnosis, respectively. Both PBSs for overall nodule malignancy and for imminent tumors were substantially higher for those with malignant nodules than for those with benign nodules, even when limited toLung Computed Tomography Screening Reporting and Data System (LungRADS) category 4 (P < .001). Circulating protein markers can help differentiate malignant from benign pulmonary nodules. Validation with an independent computed tomographic screening study will be required before clinical implementation.

Recurrence After Complete Resection for Non-Small Cell Lung Cancer in the National Lung Screening Trial

BackgroundThe objective of this study was to evaluate patterns, predictors, and long-term outcomes of recurrent disease after complete resection for early-stage non-small cell lung cancer (NSCLC) using the National Lung Screening Trial (NLST). MethodsThe frequency of recurrence in patients with pathologic stage I-II NSCLC who underwent complete resection (lobectomy or bilobectomy) in the NLST was evaluated. Predictors of increased risk of recurrence were assessed by Fine-Gray competing risks regression. ResultsOf the 497 patients meeting study inclusion criteria, 94 experienced a recurrence—a rate of 4.9 (95% CI, 4.0-6.0) per 100 person-years. The 5-year cumulative incidence of recurrence was 20.1% (95% CI, 16.5%-23.9%). Most patients experienced recurrences at distant sites alone (n = 47 [50.0%]) or at both locoregional and distant sites (n = 30 [31.9%]). The median time from resection to recurrence was 18.8 (10.6-30.7) months. The incidence rate of recurrence was significantly lower among patients with lung cancer detected by low-dose computed tomography screening during one of the three screening rounds of the NLST when compared with patients with lung cancer detected by chest radiography screening and patients with lung cancer not detected by any form of screening (ie, those diagnosed after a negative or missed screening exam and those diagnosed during follow-up after the three screening rounds of the NLST were completed) (P < .001). Median survival (from the date of recurrence) of patients with pathologic stage I and stage II disease who had recurrences at locoregional, distant, or both sites was 63.0, 23.1, and 9.8 months and 28.9, 8.7, and 10.2 months, respectively. ConclusionsIn this analysis of NLST participants with completely resected stage I-II NSCLC, the 5-year cumulative incidence of recurrence was 20%. Nearly 82% of recurrences were at distant sites and associated with poor survival.

Rates of colorectal cancer screening versus lung cancer screening: Where does the problem lie?

e22504 Background: In 2021, the U.S. Preventive Services Task Force recommended expanding the population who should undergo routine lung or colorectal cancer screening to include those between 50 and 80, with a 20-pack or more smoking history, and those who are currently smoking or have quit within the last 15 years. According to the Centers for Disease Control, 74.3% of the at-risk population undergo colorectal cancer screening. In contrast, according to the American Lung Association, only 5.8% of the eligible population undergoes lung cancer screening. Methods: This is a retrospective analysis of 158 patients who underwent colorectal cancer screening by colonoscopy between July 2022 and October 2022 at a high-volume hospital in Indiana. Patients were followed up in their primary care office between November 2022 and January 2023 to assess if they had also met the screening criteria for lung cancer with a low dose computed tomography (LDCT) scan. Patients who met the lung screening criteria were interviewed at their subsequent primary care appointment to evaluate their knowledge, attitudes, and compliance with lung cancer screening. Results: Of the 158 participants, 86 (54.4%) met the criteria for lung cancer screening with a LDCT. Only 5 (5.8%) of the eligible subjects underwent LDCT screening. 72 of the 81 patients who were not screened for lung cancer had scheduled follow-ups with their primary care provider during the study time frame. Of these 72 patients, 45 (62.5%) lacked knowledge about LDCT and lung cancer screening, despite meeting the criteria for it. 22 (30.5%) did not think they needed a LDCT, and 5 (6.9%) had no interest in screening despite previous awareness. All 72 patients who had colorectal cancer screening but not lung cancer screening were asked why they underwent the former but not the latter. 68 (94.4%) indicated that colonoscopy was recommended to them and that they knew someone in their families who had it done. Conclusions: Colon cancer screening rates remain high compared to lung cancer screening rates in an at-risk population. A lack of knowledge from patients is the primary reason for not receiving LDCT, despite receiving colon cancer screening.

Presenting symptoms, screening and diagnosis in asian and white patients with stage IV lung cancer.

e18687 Background: Lung cancer (LC) is a leading cancer diagnosis and cause of cancer death in Asian Americans, the fastest growing racial/ethnic group in the US. Some racial/ethnic groups are less likely to be eligible for guideline-recommended LC screening with low-dose computed tomography (LDCT). Data on presenting symptoms (PS) and initial evaluation in Asian patients (AP) with stage IV LC in the US are limited. This retrospective study examines LDCT utilization and patterns of PS for AP and White patients (WP) with stage IV LC at an urban academic medical center serving a large proportion of AP. Methods: Patients newly diagnosed with stage IV LC from 01/01/2014 to 12/31/2019 were identified from Tufts Medical Center cancer registry. Demographics, clinical characteristics, and biomarker data were compared between AP and WP by Mann–Whitney U test and Chi-square/Fisher's exact tests for continuous and categorical variables, respectively. Univariable and multivariable logistic regressions were used to assess associations between PS and race. Results: Of 89 AP and 197 WP, AP had significantly more non-small cell (NSC) histology (85 vs 73%), never-smokers (36 vs 7%) and male representation (72 vs 48%). Similar rates of brain metastasis (35 vs 39%) were observed. Among 219 patients with NSCLC, AP had more driver mutations compared to WP (53 vs 29%), particularly more EGFR alterations (68 vs 15% of observed driver mutations). Similar PD-L1 positivity (34 vs 32%) was noted at diagnosis in AP and WP with stage IV NSCLC. At diagnosis, fewer AP (N = 14) vs WP (N = 47) met USPSTF 2013 eligibility criteria for LDCT screening (16 vs 24%, p = 0.162), however 21% (N = 3) of eligible AP completed LDCT screening compared to 9% (N = 4) of eligible WP (p = 0.336). AP tended to have more primary care (PC) visits prior to diagnosis (51 vs 38%, p = 0.064), but longer median duration of symptoms prior to diagnosis (8 vs 4 weeks, p = 0.003). More AP presented with respiratory symptoms (80 vs 54%, p &lt; 0.001), namely cough (58 vs 33%, p &lt; 0.001), chest pain (20 vs 8%, p = 0.004) and hemoptysis (15 vs 7%, p = 0.050). Fewer AP presented with symptoms due to metastatic disease (34 vs 51%, p = 0.011). Rates of constitutional symptoms (42 vs 35%, p = 0.311) and asymptomatic diagnoses (3.4 vs 3.0%) were similar. Adjusting for age, sub-stage, histology, and smoking status, multivariable logistic regression showed significant association between AP and respiratory symptoms presentation (OR = 3.43, p &lt; 0.001). Conclusions: USPSTF 2013 LC screening criteria did not capture most of the AP and WP diagnosed with stage IV LC in this study and missed racial nuances in LC screening. Although limited in size, this study found that AP, more of whom are nonsmoking, are diagnosed with stage IV LC after longer preceding often respiratory symptoms, despite similar PC utilization and LDCT uptake as compared to WP. Awareness of race and associated PS should inform assessment for LC screening in AP.

The probability of lung cancer in patients with incidentally detected pulmonary nodules detected via low-dose computed tomography screening in China.

10569 Background: Low dose computed tomography (LDCT) screening has been proven to be effective in reducing lung cancer mortality, but the ensuing high false-positive and overdiagnosis rates shackle the effectiveness of lung cancer screening (LCS) in China. Nodule malignancy prediction models may be an applicable solution. Methods: We developed and internally validated the model using data from the ongoing Henan province Cancer Screening Program in Urban China (CanSPUC). From 2013 to 2021, 23031 heavy smokers underwent baseline screening with LDCT; 2553 participants were diagnosed with pulmonary nodules. Detailed questionnaire, physical assessment and follow-up were completed for all participants. We then externally validated the model using the National Lung Screening Trial (NLST) dataset consisting of 10485 lung nodules in 4660 participants. Multivariable Cox proportional risk regression models were used. Data analysis was performed from July 1, 2022, through December 31, 2022. Results: A total of 111 and 1089 lung cancer cases with a median follow-up duration of 3.7 years occurred in the Henan CanSPUC and NLST study, respectively. Age, gender, physical activity, consumption of pickled food, history of silicosis or pneumoconiosis, nodule type, size, calcification, and pleural retraction sign were included into the model. The AUC (95% CI) of the model for 5-year lung cancer risk was 0.857 (0.801, 0.914) and 0.847 (0.829, 0.881) in the training set and validation set, respectively. Compared with Mayo model, VA model, PKU model, and Brock model, the Henan CanSPUC model yield statistically better discriminatory performance (all P values &lt; 0.05). The model calibrated well across the deciles of predicted risk in both the overall population and all subgroups. Conclusions: The model developed and validated in this study may be used to estimate the probability of lung cancer in nodules detected at baseline LDCT, allowing more efficient risk-adapted follow-up in population-based LCS programs.

Real-world program-based lung cancer care.

6581 Background: Low dose CT screening (LDCT) and lung nodule programs (LNP) promote early lung cancer detection, improve survival; Multidisciplinary Care Programs (MDC) promote guideline-concordance. The impact of such program-based care on ‘real-world’ population-level lung cancer survival and mortality is uncertain. We evaluated program-based lung cancer care versus care outside structured programs in a large community healthcare system. Methods: We linked prospective observational databases for LDCT, LNP and MDC with the Tumor Registry of Baptist Cancer Center facilities across Mississippi, Arkansas and Tennessee, categorizing all lung cancer patients between 2011 and 2021, according to program- (LDCT, LNP, MDC) versus non-program-based care. We compared stage distribution, care patterns, survival and mortality by standard statistical methods. Results: Of 12,089 patients, 250 (2%), 1236 (10%), 1045 (7%) and 9558 (79%) were diagnosed through the LDCT, LNP, MDC or no program, respectively; non-program-based care sequentially diminished from 96% in 2011 to 67% in 2021, diagnosis through LDCT increased from 0.3% to 7%, LNP from 0.9% to 21%; and MDC alone decreased from a high of 13% in 2015 to 5% in 2021. Black persons, 28% of the whole cohort, were 13% of LDCT, 25% of LNP, 31% of MDC, and 28% of non-program-based care recipients (p = 0.0005). Median (IQR) tumor size was 20mm (13 – 34), 25mm (17 – 44), 35mm (20 – 55) and 35mm (20 – 55), respectively (p &lt; 0.0001); 40-46% of patients across programs had adenocarcinoma; clinical stage was I or II in 58%, 48%, 38% and 29% and IV in 16%, 27%, 31% and 42% in the respective programs (p &lt; 0.0001). 2609 patients (21.6%) had surgery, including 49.2%, 37.7%, 36.1% and 17.2% in LDCT, LNP, MDC and non-program-based care respectively, among whom aggregate pathologic stage was I in 76%, 71%, 54% and 60% (p = 0.0005). Surgery was the sole treatment modality in 27.6%, 21.5%, 12.9% and 10.6%, respectively (p &lt; 0.0001). Despite higher proportions with more advanced pathologic stage, 30.8% of recipients of non-program-based care received adjuvant therapy, compared to 42% among recipients of program-based care, including 39.0%, 37.1% and 49.3% in LDCT, LNP and MDC, respectively (p &lt; 0.0001); 8.7% of patients in programs received no treatment, compared to 20.1% of non-program-based care. Aggregate 5-year overall survival rates were 60% (95% CI: 52% - 69%), 45% (95% CI: 42% - 49%), 30% (95% CI: 27% - 33%), and 18% (95% CI: 17% - 19%), respectively (p &lt; 0.0001). Adjusting for age, sex, race, patient-level rurality and histology, with non-program-based care as reference, the aHR were 0.3 (95% CI: 0.234 – 0.373), 0.51 (95% CI: 0.464 – 0.556, and 0.66(95% CI: 0.607 – 0.712). Results were consistent even without patients who received no treatment. Conclusions: Program-based care was associated with more favorable lung cancer characteristics, better quality of care and survival. Disseminating program-based care should be explored as a matter of urgent public policy.

Prevalence and clinical characteristics of non-malignant CT detected incidental findings in the SUMMIT lung cancer screening cohort

BackgroundPulmonary and extrapulmonary incidental findings are frequently identified on CT scans performed for lung cancer screening. Uncertainty regarding their clinical significance and how and when such findings should be reported...

CO179 Potential Health and Economic Outcomes of a Blood-Based Genomic Test As a Prescreen for Lung Cancer in the US Medicare Population

Annual screening for lung cancer by low-dose computed tomography (LDCT) reduces mortality. Despite no cost-share for covered individuals, limited availability and frequent ‘false alarm’ findings have impeded widespread adoption, diminishing potential population health gains. We examined a model of the clinical and economic effects of introducing an accessible blood-based genomic test (BGT) used as a pre-screen to support more rapid and refined uptake of LDCT screening within the US Medicare population.

Early detection of lung cancer using small RNAs.

3035 Background: Low-dose computed tomography (LDCT) screening can significantly reduce lung cancer mortality. However, annual screening is limited by low adherence in the USA and still not broadly implemented in Europe. As a result, &lt;10% of lung cancers are detected through existing programs. Thus, there is great need for additional diagnostic modalities, such as a blood test that could be deployed in the primary care setting. Methods: We prospectively recruited 1,189 patients meeting the 2013 USPSTF screening criteria for lung cancer and collected stabilized whole blood. Ultra-deep small RNA sequencing was performed with a method to remove highly abundant erythroid RNAs, opening bandwidth for the detection of less abundant species originating from plasma or the immune cellular compartment. We utilized 100 random data splits to train and evaluate logistic regression classifiers using small RNA expression, discovered an 18-small RNA feature consensus signature (miLung), and validated this in an independent cohort (246 patients). Blood cell sorting and tumor tissue sequencing were performed to deconvolve small RNAs into their source of origin. Results: We generated diagnostic models and report a median ROC AUC of 0.86 (95% CI 0.84-0.86) in the discovery cohort, and generalized performance of 0.84 in the validation cohort. Diagnostic performance increased stage-dependently from 0.73 (95% CI 0.71-0.76) for Stage I to 0.90 (95% CI 0.89-0.90) for Stage IV. We identified a tumor-shed, plasma-bound ribosomal RNA fragment of the L1 stalk as a dominant predictor of lung cancer. The fragment is decreased following surgery with curative intent. In additional experiments, dried blood spot collection and sequencing revealed that small RNA analysis could potentially be conducted via home-sampling. Conclusions: These data suggest the potential of a small RNA-based blood test as a viable alternative to LDCT screening for early detection of smoking-associated lung cancer. Clinical trial information: NCT03452514 . [Table: see text]

Utility of Brock model for risk stratification in patients with high-risk pulmonary nodules: A single center study.

e18824 Background: Owing to the widespread implementation of low-dose CT screening (LDCT), an increasing number of pulmonary nodules are being identified. Per LDCT lung cancer screening protocol, radiologists assign Lung-RADS (LR) scores ranging from 1-4 with L1-2 being at low risk and L3-4 being at intermediate to high risk of malignancy. The Brock model derived from the Pan-Canadian Early Detection of Lung Cancer screening study is a mathematical model that incorporates both clinical (age, sex, family history of lung cancer) and radiological (emphysema, nodule size, location of nodule in the upper lobe, nodule type, nodule count and spiculation) factors to predict the risk of lung cancer, but is not commonly used in the United States. The goal of our study was to estimate whether a higher Brock score can be used to further stratify malignancy potential in patients with LR≥3. Methods: We performed a retrospective analysis at Mercy Catholic Medical Center, where we reviewed LDCT findings of 1090 patients, performed between 1/1/2018 - 6/30/2021 and identified 82 patients with LR≥3. Brock Model was used to calculate the malignancy probability of these pulmonary nodules. All patients were followed until biopsy, resolution of nodule or stability on follow-up imaging. In patients with multiple pulmonary nodules, probability was estimated for the largest nodule. An analysis of area under the receiver operating characteristic curve (AUC) was performed to evaluate efficiency of Brock model in our study population (using GraphPad Prism). We used the British Thoracic Society’s suggested threshold of 10% malignancy risk. Results: 82 patients (43 females and 39 males) were found to have pulmonary nodules with LR≥3. Among these, 10 patients were lost to follow-up and excluded from this study. Out of the 38 patients with LR 4, 16 patients had biopsy-proven lung cancer, 22 patients were found to have benign nodules. Among 34 patients with LR 3, only 3 were found to have lung cancer on follow-up. The mean calculated malignancy risk percentage was 6.69% for benign nodules (n = 51), but 27.14% for malignant nodules (n = 18). The calculated AUC in our study population was 0.85 (95%, CI 0.75-0.95, p &lt; 0.0001). At 10% threshold, sensitivity and specificity were 78.95% and 83.02%, respectively. Conclusions: Based on our data, this model can be used to further assess risk of lung cancer in patients with intermediate to high-risk lung nodules (LR≥3). Similar to the use of Tyrer-Cuzick and Gail models in assessing risk of breast cancer, we may be able to use the Brock Model in predicting malignancy risk of lung nodules. However, a larger study is needed to estimate specific cut-offs. This can potentially lower the need for biopsies in lower risk groups and warrant more aggressive work-up and early diagnosis in higher risk populations.

Enhancing lung cancer screening through ‘Saved by the Scan’: Lessons from a multipronged public service advertising program.

10575 Background: Lung cancer screening rates remain low across the US in populations recommended for screening by low-dose CT (LDCT). Screening rates further declined during the COVID-19 pandemic, particularly in high-risk populations including racial and ethnic minorities. The American Lung Association (ALA) launched a nationwide public service advertising (PSA) program called ‘Saved by the Scan’ to enhance lung cancer screening rates, for which Baptist Health South Florida (BHSF) became the first healthcare system partner. The following work describes this major PSA effort in South Florida to enhance lung cancer screening, and the lessons learned thereof. Methods: A multipronged, institutionally-driven public awareness program, in collaboration with ALA, was initiated in 2021 by BHSF, the largest healthcare organization in the region, and was targeted towards South Florida residents. This innovative multimedia effort used traditional communication modalities, including newspapers, billboards, etc., along with digital modalities, including email and social media, to increase lung cancer screening awareness in both English and Spanish in a locally-adapted manner. Key performance indicators (KPIs), reach, and impact of the program were tracked. The most successful components, as per KPIs, were identified. Deidentified data of screening LDCT done at BHSF was reviewed to determine all individuals screened during 2019-2021 and descriptive statistics were calculated. Results: 4619 individuals from South Florida were screened at BHSF from 2019-2021, 1498 were in 2019, 1193 in 2020, and 1928 in 2021. Screening fell by 20.3% in 2020, likely due to the pandemic, and rose by 61.6% in 2021, helped by the program. Overall, a 21.9% increase from pre-COVID screening rates was seen. In 2022, the total reach of traditional media was estimated to be 4,607,273 individuals. Out of 133,554 emails sent, 36,877 (27.2%) were opened, with a click-through rate of 6.4%. Out of 1,768,438 digital impressions, 16,791 (0.9%) had links clicked. The total number of conversions from digital media was estimated to be 337 individuals with 232 (68.9%) from emails and 105 (31.1%) from social media. Conclusions: Lung cancer screening can be successfully boosted through large organizational efforts, particularly those targeted to needs of the local population. Digital media approaches for improving public health have seemingly low conversion rates but their large outreach provides a high impact. Efforts are warranted to enroll more healthcare systems and scale the program nationwide.

Factors Associated With Nonadherence to Lung Cancer Screening Across Multiple Screening Time Points

Screening with low-dose computed tomography (CT) has been shown to reduce mortality from lung cancer in randomized clinical trials in which the rate of adherence to follow-up recommendations was over 90%; however, adherence to Lung Computed Tomography Screening Reporting & Data System (Lung-RADS) recommendations has been low in practice. Identifying patients who are at risk of being nonadherent to screening recommendations may enable personalized outreach to improve overall screening adherence. To identify factors associated with patient nonadherence to Lung-RADS recommendations across multiple screening time points. This cohort study was conducted at a single US academic medical center across 10 geographically distributed sites where lung cancer screening is offered. The study enrolled individuals who underwent low-dose CT screening for lung cancer between July 31, 2013, and November 30, 2021. Low-dose CT screening for lung cancer. The main outcome was nonadherence to follow-up recommendations for lung cancer screening, defined as failing to complete a recommended or more invasive follow-up examination (ie, diagnostic dose CT, positron emission tomography-CT, or tissue sampling vs low-dose CT) within 15 months (Lung-RADS score, 1 or 2), 9 months (Lung-RADS score, 3), 5 months (Lung-RADS score, 4A), or 3 months (Lung-RADS score, 4B/X). Multivariable logistic regression was used to identify factors associated with patient nonadherence to baseline Lung-RADS recommendations. A generalized estimating equations model was used to assess whether the pattern of longitudinal Lung-RADS scores was associated with patient nonadherence over time. Among 1979 included patients, 1111 (56.1%) were aged 65 years or older at baseline screening (mean [SD] age, 65.3 [6.6] years), and 1176 (59.4%) were male. The odds of being nonadherent were lower among patients with a baseline Lung-RADS score of 1 or 2 vs 3 (adjusted odds ratio [AOR], 0.35; 95% CI, 0.25-0.50), 4A (AOR, 0.21; 95% CI, 0.13-0.33), or 4B/X, (AOR, 0.10; 95% CI, 0.05-0.19); with a postgraduate vs college degree (AOR, 0.70; 95% CI, 0.53-0.92); with a family history of lung cancer vs no family history (AOR, 0.74; 95% CI, 0.59-0.93); with a high age-adjusted Charlson Comorbidity Index score (≥4) vs a low score (0 or 1) (AOR, 0.67; 95% CI, 0.46-0.98); in the high vs low income category (AOR, 0.79; 95% CI, 0.65-0.98); and referred by physicians from pulmonary or thoracic-related departments vs another department (AOR, 0.56; 95% CI, 0.44-0.73). Among 830 eligible patients who had completed at least 2 screening examinations, the adjusted odds of being nonadherent to Lung-RADS recommendations at the following screening were increased in patients with consecutive Lung-RADS scores of 1 to 2 (AOR, 1.38; 95% CI, 1.12-1.69). In this retrospective cohort study, patients with consecutive negative lung cancer screening results were more likely to be nonadherent with follow-up recommendations. These individuals are potential candidates for tailored outreach to improve adherence to recommended annual lung cancer screening.

Initial low-dose computed tomography screening results and summary of participant characteristics: based on the latest Chinese guideline.

Low-dose computed tomography (LDCT) has been promoted as a promising screening strategy for early detection of lung cancer. China released the latest lung cancer screening guideline in 2021. The compliance of the individuals who received LDCT for lung cancer screening with the guideline is unknown yet. It is necessary to summarize the distribution of guideline-defined lung cancer-related risk factors in the Chinese population so as to inform the selection of target population for the future lung cancer screening. A single-center, cross-sectional study design was adopted. All participants were individuals who underwent LDCT at a tertiary teaching hospital in Hunan, China, between 1 January and 31 December 2021. LDCT results were derived along with guideline-based characteristics for descriptive analysis. A total of 5,486 participants were included. Over one-quarter (1,426, 26.0%) of the participants who received screening did not meet the guideline-defined high-risk population, even among non-smokers (36.4%). Most of the participants (4,622, 84.3%) were found to have lung nodules, while no clinical intervention was required basically. The detection rate of positive nodules varied from 46.8% to 71.2% when using different cut-off values for positive nodules. Among non-smoking women, ground glass opacity appeared to be more significantly common compared with non-smoking men (26.7% vs. 21.8%). Over one-quarter of individuals who received LDCT screening did not meet the guideline-defined high-risk populations. Appropriate cut-off values for positive nodules need to be continuously explored. More precise and localized criteria for high-risk individuals are needed, especially for non-smoking women.

A strategy to reduce the false-positive rate after low-dose computed tomography in lung cancer screening: A multicenter prospective cohort study.

The ability of lung cancer screening to manage pulmonary nodules was limited because of the high false-positive rate in the current mainstream screening method, low-dose computed tomography (LDCT). We aimed to reduce overdiagnosis in Chinese population. Lung cancer risk prediction models were constructed using data from a population-based cohort in China. Independent clinical data from two programs performed in Beijing and Shandong, respectively, were used as the external validation set. Multivariable logistic regression models were used to estimate the probability of lung cancer incidence in the whole population and in smokers and nonsmokers. In our cohort, 1,016,740 participants were enrolled between 2013 and 2018. Of 79,581 who received LDCT screening, 5165 participants with suspected pulmonary nodules were allocated into the training set, of which, 149 lung cancer cases were diagnosed. In the validation set, 1815 patients were included, and 800 developed lung cancer. The ages of patients and radiologic factors of nodules (calcification, density, mean diameter, edge, and pleural involvement) were included in our model. The area under the curve (AUC) values of the model were 0.868 (95% CI: 0.839-0.894) in the training set and 0.751 (95% CI: 0.727-0.774) in the validation set. The sensitivity and specificity were 70.5% and 70.9%, respectively, which could reduce the 68.8% false-positive rate in simulated LDCT screening. There was no substantial difference between smokers' and nonsmokers' prediction models. Our models could facilitate the diagnosis of suspected pulmonary nodules, effectively reducing the false-positive rate of LDCT for lung cancer screening.

Metabolic biomarkers in lung cancer screening and early diagnosis (Review).

Late diagnosis is one of the major contributing factors to the high mortality rate of lung cancer, which is now the leading cause of cancer-associated mortality worldwide. At present, low-dose CT (LDCT) screening in the high-risk population, in which lung cancer incidence is higher than that of the low-risk population is the predominant diagnostic strategy. Although this has efficiently reduced lung cancer mortality in large randomized trials, LDCT screening has high false-positive rates, resulting in excessive subsequent follow-up procedures and radiation exposure. Complementation of LDCT examination with biofluid-based biomarkers has been documented to increase efficacy, and this type of preliminary screening can potentially reduce potential radioactive damage to low-risk populations and the burden of hospital resources. Several molecular signatures based on components of the biofluid metabolome that can possibly discriminate patients with lung cancer from healthy individuals have been proposed over the past two decades. In the present review, advancements in currently available technologies in metabolomics were reviewed, with particular focus on their possible application in lung cancer screening and early detection.