Low-dose Computed Tomography Screening Research Articles

Stage Shift Improves Lung Cancer Survival: Real-World Evidence

IntroductionLung cancer is the global leading cause of cancer death. Taiwan initiated several health policies including smoking cessation, precision therapy, and low-dose computed tomography (LDCT) screening in 1997. We aimed to investigate the effect of public policies on lung cancer survival. MethodsWe retrieved the nationwide cancer registry from the Ministry of Health and Welfare to evaluate the smoking prevalence and lung cancer incidence and mortality from 1994 to 2020. We also conducted a retrospective analysis of clinical characteristics and survival on 17,298 patients with lung cancer from 2006 to 2019 using the National Taiwan University Hospital database. ResultsTaiwan initiated an anti-smoking campaign in 1997, reimbursed tyrosine kinase inhibitors since 2004, and conducted an LDCT screening trial in 2015. Lung cancer incidence keeps rising but the annual percent change in mortality rate gradually decreased from 0.41% to −2.41%. The National Taiwan University Hospital data revealed that the 5-year survival substantially improved from 22.1% in 2006 to 2011 to 54.9% in 2015 to 2020. Improvement was observed in all stages, especially late stages (stage III: from 17.2% to 35.2%; stage IV: from 7.9% to 16.5%). Furthermore, a remarkable shift in cancer stage was observed (stage 0, I, and IIincreased from 19.3% to 62.8%, and stage III and IV decreased from 70.9% to 33.8%). The prominent improvement in survival was primarily driven by the stage shift from advanced to localized, potentially curable disease. ConclusionsThis real-world evidence suggested an association between improved survival and LDCT screening and the diagnostic shift from late to early-stage of lung cancer, highlighting the importance of early detection for lung cancer control.

The role of low-dose computed tomography in lung cancer screening

Introduction: Lung cancer is a serious public health problem in Hungary, but currently there is no nationwide screening program for the early detection of the disease. Several technological developments have been carried out recently to improve the effectiveness of lung cancer screening. Low-dose computed tomography (LDCT) is one of these technologies. Objective: The objective of this study is to provide an overview on guidelines and recommendations related to the application of LDCT as a novel lung cancer screening modality and to summarize the scientific literature and screening practices of other countries. Method: We performed a targeted literature review to collect information about LDCT in lung cancer screening. We searched in publicly available databases for guidelines and recommendations as well as scientific publications on screening and early detection of lung cancer. Results: In our literature search, we identified 16 guidelines and recommendations for lung cancer screening and LDCT. Regarding the efficacy of LDCT lung cancer screening, 10 foreign randomized controlled trials and 2 Hungarian trials were reviewed. Information on screening practices of 10 European countries were identified. Discussion: Evidences suggest that LDCT screening improves the detection of lung cancer, especially at early stages, and reduces cancer-specific mortality. Conclusion: In summary, in the high-risk population, LDCT can be considered an effective screening modality for the early-stage detection of lung cancer and for reducing lung cancer mortality. The ongoing Hungarian and foreign pilot programs may provide futher evidence for the implementation of a nationwide LDCT lung cancer screening program.

Stage Migration and Lung Cancer Incidence After Initiation of Low-Dose Computed Tomography Screening

IntroductionDespite evidence from clinical trials of favorable shifts in cancer stage and improvements in lung cancer-specific mortality, the effectiveness of lung cancer screening (LCS) in clinical practice has not been clearly revealed. MethodsWe performed a multicenter cohort study of patients diagnosed with a primary lung cancer between January 1, 2014, and September 30, 2019, at one of four U.S. health care systems. The primary outcome variables were cancer stage distribution and annual age-adjusted lung cancer incidence. The primary exposure variable was receipt of at least one low-dose computed tomography for LCS before cancer diagnosis. ResultsA total of 3678 individuals were diagnosed with an incident lung cancer during the study period; 404 (11%) of these patients were diagnosed after initiation of LCS. As screening volume increased, the proportion of patients diagnosed with lung cancer after LCS initiation also rose from 0% in the first quartile of 2014 to 20% in the third quartile of 2019. LCS did not result in a significant change in the overall incidence of lung cancer (average annual percentage change [AAPC]: −0.8 [95% confidence interval (CI): −4.7 to 3.2]) between 2014 and 2018. Stage-specific incidence rates increased for stage I cancer (AAPC = 8.0 [95% CI: 0.8–15.7]) and declined for stage IV disease (AAPC = −6.0 [95% CI: −11.2 to −0.5]). ConclusionsImplementation of LCS at four diverse health care systems has resulted in a favorable shift to a higher incidence of stage I cancer with an associated decline in stage IV disease. Overall lung cancer incidence did not increase, suggesting a limited impact of overdiagnosis.

The Journey for Lung Cancer Screening where we Stand Today.

Lung cancer remains a leading cause of cancer mortality worldwide with many patients presenting with advanced disease. We reviewed the available literature for lung cancer screening using low dose computed tomography (LDCT). We reviewed the National Lung Screening Trial (NLST), Early Lung Cancer Action Program (ELCAP) and the (Nederlands-Leuvens Longkanker Screenings Onderzoek (NELSON) trials. We also look at different lung cancer risk prediction models that may aid in identifying target populations and also discuss the cost-effectiveness of LDCT screening in different groups of smokers and ex-smokers. Lastly, we discuss recent guideline changes that have occurred in line with new and emerging evidence on lung cancer screening. LDCT has been shown reduce lung cancer mortality in certain groups of current and former smokers and should be considered to help in the early diagnosis of lung cancer.

EP01.06-008 Low Dose CT Screening in Asian Female-Never-Smokers is as Efficacious as in Asian Male-Ever-Smokers. A Systemic Review and Meta-Analysis

Lung cancer in never-smokers is a significant global cancer burden. We performed this systematic review and meta-analysis to compare efficacy of low-dose computed tomography (LDCT) lung cancer screening among never-smokers versus ever-smokers.

EP01.06-007 The Impact of Modified Screening Eligibility Criteria on Race and Sex Disparities in Lung Cancer Screening

Low Dose CT screening (LDCT) redistributes lung cancer to earlier stage at diagnosis and reduces mortality. However, established screening criteria underestimate risk in women and racial minorities, inadvertently exacerbating access disparities. Using a cohort of patients enrolled into an incidental lung nodule program (LNP), we evaluated the impact of criteria modifications on rates of LDCT eligibility and lung cancer detection by race and sex.

OA10.03 A Randomized Trial of Telephone-Based Smoking Cessation Treatment in the Lung Cancer Screening Setting

Lung cancer mortality is reduced via low-dose CT screening and treatment of early-stage disease. Evidence-based smoking cessation treatment delivered in the lung cancer screening setting can further reduce mortality. We report the quit rates, the short-term cost per quit, and long-term cost effectiveness of a trial of telephone counseling and nicotine replacement for individuals who smoke and were undergoing lung screening at 8 US screening facilities.

EP01.05-002 Role of the Lung Cancer Screening MDT in the Manchester Lung Health Check Programme

Low-dose CT (LDCT) screening for lung cancer has been shown to reduce lung cancer mortality and its implementation is currently being examined and considered across multiple countries. In the United Kingdom (UK), the Targeted Lung Health Checks (TLHC) program has initiated small-scale screening programs across several regions of the country. A significant challenge to implementation is the increased demand for quality-assured radiology reporting, as stipulated by the TLHC service protocols, in order to maximize screening efficacy and reduce potential harm to participants from false-positive and false-negative results.

EP01.02-001 Citizens’ Perspective on Combination Screening for Lung Cancer, COPD and CVD

The benefits of screening depend directly on the number of targeted individuals willing to participate. This study aimed to inform policymakers by determining the expected willingness of potential lung cancer screenees to participate in low-dose chest CT (LDCT) screening. Chest LDCT also allows evaluation of early stages of chronic obstructive pulmonary disease (COPD) and cardiovascular disease (CVD). We studied whether screening for combinations of lung cancer with COPD and/or CVD (the Big-3 diseases) would influence willingness to participate.

EP01.05-005 The Accuracy of Baseline Low-dose CT Lung Cancer Screening: A Systematic Review and Meta-analysis

Screening using low-dose computed tomography (LDCT) is a more effective approach and has the potential to detect the lung cancer more accurately. We aimed to conduct a meta-analysis to estimate the accuracy from population-based screening studies primarily assessing baseline LDCT screening for lung cancer.

EP01.01-003 DELFI-L101: Development of a Blood-Based Assay That Evaluates Cell-Free DNA Fragmentation Patterns to Detect Lung Cancer

Uptake of lung cancer screening is low worldwide, including in the US despite established recommendations and national reimbursement for eligible persons. Studies show that screening by low-dose computed tomography (LDCT) can reduce mortality, but the benefits of screening are challenged by barriers that include access to screening, costs, and harms like false-positives and radiation exposure. A tool that can separate the screening-eligible population into groups with higher and lower risk of lung cancer could allow more judicious use of LDCT screening.

EP01.06-006 Impact of Low Dose CT Screening on Cause of Death in Different Socio-Economic Groups

Lower socioeconomic status, as measured by the Index of Multiple Deprivation (IMD), is associated with higher rates of smoking-related disease mortality, and with poor uptake in cancer screening. The UKLS low-dose-CT (LD-CT) screening trial for lung cancer was consistent with a lung cancer mortality benefit for CT screening [Field, et al. (2021) Lung cancer mortality reduction by LDCT screening: UKLS randomised trial results and international meta-analysis. Lancet Regional Health Europe, doi.org/10.1016/j.lanepe.2021.100179].

EP16.02-019 Metabolic Changes in Sputum and Exhaled Breath Condensate of Non-small Cell Lung Cancer Patients after Surgical Resection

Low-dose CT screening of the chest in the high-risk population is the current standard of care for early detection of lung cancer. CT screening is invasive due to radiation exposure and carries the risk of unnecessary biopsies of benign tumors. Here, we demonstrate metabolic changes in sputum and exhaled breath condensate (EBC) obtained from the same early-stage non-small cell lung cancer (NSCLC) patients pre-and post-surgical resection (SR), proposing the individual metabolic signature as a noninvasive diagnostic tool.

Development of a Molecular Blood-Based Immune Signature Classifier as Biomarker for Risks Assessment in Lung Cancer Screening.

Low-dose CT (LDCT) screening trials have shown that lung cancer early detection saves lives. However, a better stratification of the screening population is still needed. In this respect, we generated and prospectively validated a plasma miRNA signature classifier (MSC) able to categorize screening participants according to lung cancer risk. Here, we aimed to deeply characterize the peripheral immune profile and develop a diagnostic immune signature classifier to further implement blood testing in lung cancer screening. Peripheral blood mononuclear cell (PBMC) samples collected from 20 patients with LDCT-detected lung cancer and 20 matched cancer-free screening volunteers were analyzed by flow cytometry using multiplex panels characterizing both lymphoid and myeloid immune subsets. Data were validated in PBMC from 40 patients with lung cancer and 40 matched controls and in a lung cancer specificity set including 27 subjects with suspicious lung nodules. A qPCR-based gene expression signature was generated resembling selected immune subsets. Monocytic myeloid-derived suppressor cell (MDSC), polymorphonuclear MDSC, intermediate monocytes and CD8+PD-1+ T cells distinguished patients with lung cancer from controls with AUCs values of 0.94/0.72/0.88 in the training, validation, and lung cancer specificity set, respectively. AUCs raised up to 1.00/0.84/0.92 in subgroup analysis considering only MSC-negative subjects. A 14-immune genes expression signature distinguished patients from controls with AUC values of 0.76 in the validation set and 0.83 in MSC-negative subjects. An immune-based classifier can enhance the accuracy of blood testing, thus supporting the contribution of systemic immunity to lung carcinogenesis. Implementing LDCT screening trials with minimally invasive blood tests could help reduce unnecessary procedures and optimize cost-effectiveness.

The Introduction of Low-Dose CT Imaging and Lung Cancer Overdiagnosis in Chinese Women

Overdiagnosis of lung cancer by low-dose CT (LDCT) screening has raised concerns globally. LDCT screening has been used widely in employee health examinations in China since2011. Has the increasing use of LDCT in low-risk populations in China led to lung cancer overdiagnosis? A total of 34,152 incident cases of and 27,208 deaths resulting from lung cancer in a population of approximately 3 million were derived from the Cancer Surveillance of Shanghai between 2002 and 2017. Changes in stage-specific and histologic type-specific incidence and mortality and incidence rate ratio (IRR) relative to the base year 2002 or to the period 2002 through 2005 were calculated by sex and were used to evaluate potential overdiagnosisve of lung cancer. In men, both age-adjusted incidence of and mortality as a result of lung cancer decreased significantly up to 2008 and thereafter remained stable; in women, the incidence increased rapidly from 2011 (annual percentage change, 11.98%; 95%CI, 9.57%-14.45%), whereas the mortality declined persistently. The upward trend of incidence mainly was observed in lung adenocarcinoma in both sexes, with a sharper increase from 2012 through 2017. In men, the incidence of early-stage cancer increased 6.9 per 100,000 (95%CI, 5.1-8.7 per 100,000) and was accompanied by 5.5 per 100,000 (95%CI, -9.2 to -1.7 per 100,000) decline in late-stagecancer from 2002 through 2017. In women, early-stage incidence rose 16.1 per 100,000 (95%CI, 14.0-18.3 per 100,000), but no significant decline in late-stage cancer was found (absolute difference, -0.6 per 100,000; 95%CI, -2.8 to 1.7 per 100,000). The IRR was highest in most recent period and increased most in young women, mainly for early-stage cancer or lung adenocarcinoma. The results provide evidence at a population level for lung cancer overdiagnosis in Chinese women resulting from increasing LDCT screening in the low-risk populations. Criteria for LDCT screening and management of screening-detected nodules need to be addressed fully for expanded application of LDCT screening in China.

Impact of low-dose computed tomography (LDCT) screening on lung cancer-related mortality.

Impact of low-dose computed tomography (LDCT) screening on lung cancer-related mortality.

Design and Rationale of the HANSE Study: A Holistic German Lung Cancer Screening Trial Using Low-Dose Computed Tomography

Despite the high prevalence and mortality of lung cancer and proven effectiveness of low-dose computed tomography (LDCT) to reduce mortality, Germany still lacks a national screening program. The German Institute for Quality and Efficiency in Health Care (IQWiG) and the Federal Office for Radiation Protection (BfS) both published positive scientific evaluations recommending a quality-controlled national screening program. IQWiG underlined the importance of a clear risk definition, integrated smoking cessation programs, and quality assurance, highlighting the necessity of procedural optimization.In the HANSE study, former and current smokers aged 55-79 years are assessed for their lung cancer risk by the NELSON and PLCOM2012 risk scores. 5000high-risk participants, defined as PLCOM2012 6-year risk ≥ 1.58 % or fulfilling NELSON risk inclusion criteria, will be screened by LDCT at baseline and after 12 months. Lung nodules are analyzed by a modified Lung-RADS 1.1 score of the HANSE study, and values of emphysema and coronary calcium are determined and randomly reported to the participants. 7100 low-risk participants serve as a control. All patients are followed-up for up to 10 years. The sensitivity and specificity of the two risk assessments and LDCT screening, effects of the randomized LDCT reporting, efficiency of lung nodule management, and several other factors are assessed to analyze the success and quality of the holistic screening program.The HANSE study is designed as a holistic lung cancer screening study in northern Germany to answer pressing questions for a successful implementation of an effective German lung cancer screening program. · HANSE is designed to address pressing questions for the implementation of lung cancer screening in Germany.. · HANSE compares NELSON and PLCOM2012 risk assessments for optimal definition of the high-risk group. . · HANSE integrates cardiac calcium and pulmonary emphysema scoring in a holistic screening approach.. CITATION FORMAT: · Vogel-Claussen J, Lasch F, Bollmann B et al. Design and Rationale of the HANSE Study: A Holistic German Lung Cancer Screening Trial Using Low-Dose Computed Tomography. Fortschr Röntgenstr 2022; 194: 1333 - 1345.

Assessment of Lung Cancer Risk Among Smokers for Whom Annual Screening Is Not Recommended

The US Preventive Services Task Force does not recommend annual lung cancer screening with low-dose computed tomography (LDCT) for adults aged 50 to 80 years who are former smokers with 20 or more pack-years of smoking who quit 15 or more years ago or current smokers with less than 20 pack-years of smoking. To determine the risk of lung cancer in older smokers for whom LDCT screening is not recommended. This cohort study used the Cardiovascular Health Study (CHS) data sets obtained from the National Heart, Lung and Blood Institute, which also sponsored the study. The CHS enrolled 5888 community-dwelling individuals aged 65 years and older in the US from June 1989 to June 1993 and collected extensive baseline data on smoking history. The current analysis was restricted to 4279 individuals free of cancer who had baseline data on pack-year smoking history and duration of smoking cessation. The current analysis was conducted from January 7, 2022, to May 25, 2022. Current and prior tobacco use. Incident lung cancer during a median (IQR) of 13.3 (7.9-18.8) years of follow-up (range, 0 to 22.6) through December 31, 2011. A Fine-Gray subdistribution hazard model was used to estimate incidence of lung cancer in the presence of competing risk of death. Cox cause-specific hazard regression models were used to estimate hazard ratios (HRs) and 95% CIs for incident lung cancer. There were 4279 CHS participants (mean [SD] age, 72.8 [5.6] years; 2450 [57.3%] women; 663 [15.5%] African American, 3585 [83.8%] White, and 31 [0.7%] of other race or ethnicity) included in the current analysis. Among the 861 nonheavy smokers (<20 pack-years), the median (IQR) pack-year smoking history was 7.6 (3.3-13.5) pack-years for the 615 former smokers with 15 or more years of smoking cessation, 10.0 (5.3-14.9) pack-years for the 146 former smokers with less than 15 years of smoking cessation, and 11.4 (7.3-14.4) pack-years for the 100 current smokers. Among the 1445 heavy smokers (20 or more pack-years), the median (IQR) pack-year smoking history was 34.8 (26.3-48.0) pack-years for the 516 former smokers with 15 or more years of smoking cessation, 48.0 (35.0-70.0) pack-years for the 497 former smokers with less than 15 years of smoking cessation, and 48.8 (31.6-57.0) pack-years for the 432 current smokers. Incident lung cancer occurred in 10 of 1973 never smokers (0.5%), 5 of 100 current smokers with less than 20 pack-years of smoking (5.0%), and 26 of 516 former smokers with 20 or more pack-years of smoking with 15 or more years of smoking cessation (5.0%). Compared with never smokers, cause-specific HRs for incident lung cancer in the 2 groups for whom LDCT is not recommended were 10.54 (95% CI, 3.60-30.83) for the current nonheavy smokers and 11.19 (95% CI, 5.40-23.21) for the former smokers with 15 or more years of smoking cessation; age, sex, and race-adjusted HRs were 10.06 (95% CI, 3.41-29.70) for the current nonheavy smokers and 10.22 (4.86-21.50) for the former smokers with 15 or more years of smoking cessation compared with never smokers. The findings of this cohort study suggest that there is a high risk of lung cancer among smokers for whom LDCT screening is not recommended, suggesting that prediction models are needed to identify high-risk subsets of these smokers for screening.

Cytisine Therapy Improved Smoking Cessation in the Randomized Screening and Multiple Intervention on Lung Epidemics Lung Cancer Screening Trial

IntroductionCytisine, a partial agonist-binding nicotine acetylcholine receptor, is a promising cessation intervention. We conducted a single-center, randomized, controlled trial (RCT) in Italy to assess the efficacy and tolerability of cytisine as a smoking cessation therapy among lung cancer screening participants. MethodsFrom July 2019 to March 2020, the Screening and Multiple Intervention on Lung Epidemics RCT enrolled 869 current heavy tobacco users in a low-dose computed tomography screening program, with a randomized comparison of pharmacologic intervention with cytisine plus counseling (N = 470) versus counseling alone (N = 399). The primary outcome was continuous smoking abstinence at 12 months, biochemically verified through carbon monoxide measurement. ResultsAt the 12-month follow-up, the quit rate was 32.1% (151 participants) in the intervention arm and 7.3% (29 participants) in the control arm. The adjusted OR of continuous abstinence was 7.2 (95% confidence interval: 4.6–11.2). Self-reported adverse events occurred more frequently in the intervention arm (399 events among 196 participants) than in the control arm (230 events among 133 participants, p < 0.01). The most common adverse events were gastrointestinal symptoms, comprising abdominal swelling, gastritis, and constipation. ConclusionsThe efficacy and safety observed in the Screening and Multiple Intervention on Lung Epidemics RCT indicate that cytisine, a very low-cost medication, is a useful treatment option for smoking cessation and a feasible strategy to improve low-dose computed tomography screening outcomes with a potential benefit for all-cause mortality.

A Randomized Trial of Telephone-Based Smoking Cessation Treatment in the Lung Cancer Screening Setting.

Lung cancer mortality is reduced via low-dose computed tomography screening and treatment of early-stage disease. Evidence-based smoking cessation treatment in the lung screening setting can further reduce mortality. We report the results of a cessation trial from the National Cancer Institute's Smoking Cessation at Lung Examination collaboration. Eligible patients (n = 818) aged 50-80 years were randomly assigned (May 2017-January 2021) to the intensive vs minimal arms (8 vs 3 phone sessions plus 8 vs 2 weeks of nicotine patches, respectively). Bio-verified (primary) and self-reported 7-day abstinence rates were assessed at 3, 6, and 12 months post random assignment. Logistic regression analyses evaluated the effects of study arm. All statistical tests were 2-sided. Participants reported 48.0 (SD = 17.2) pack-years, and 51.6% were not ready to quit in less than 30 days. Self-reported 3-month quit rates were statistically significantly higher in the intensive vs minimal arm (14.3% vs 7.9%; odds ratio [OR] = 2.00, 95% confidence interval [CI] = 1.26 to 3.18). Bio-verified abstinence was lower but with similar relative differences between arms (9.1% vs 3.9%; OR = 2.70, 95% CI = 1.44 to 5.08). Compared with the minimal arm, the intensive arm was more effective among those with greater nicotine dependence (OR = 3.47, 95% CI = 1.55 to 7.76), normal screening results (OR = 2.58, 95% CI = 1.32 to 5.03), high engagement in counseling (OR = 3.03, 95% CI = 1.50 to 6.14), and patch use (OR = 2.81, 95% CI = 1.39 to 5.68). Abstinence rates did not differ statistically significantly between arms at 6 months (OR = 1.2, 95% CI = 0.68 to 2.11) or 12 months (OR = 1.4, 95% CI = 0.82 to 2.42). Delivering intensive telephone counseling and nicotine replacement with lung screening is an effective strategy to increase short-term smoking cessation. Methods to maintain short-term effects are needed. Even with modest quit rates, integrating cessation treatment into lung screening programs may have a large impact on tobacco-related mortality.