Dataset Information

Estimation of Lead Time via Low-Dose CT in the National Lung Screening Trial.

ABSTRACT: Based on recent reports from the National Lung Screening Trial (NLST), smokers who were screened by low-dose computer tomography (LDCT) had a 20% lower chance of dying from lung cancer than those screened by chest X-rays. However, due to the complexities of lead time bias and over diagnosis, no formal test has been shown to reduce lung cancer mortality. To correctly evaluate survival benefit due to early detection, it is critical to estimate lead time, the length of time that detection of a disease is advanced by screening. We applied a recently developed probability method to estimate lead time, using the LDCT data from NLST, where human lifetime was treated as random and derived from the actuarial life table of the US Social Security Administration. Using Bayesian posterior samples of key parameters extracted from the NLST-LDCT data, simulations on lead time were carried out on 16 hypothetical cohorts with four initial ages (55, 60, 65, and 70) and four future screening intervals (12, 18, 24, and 30 months). For each scenario, the estimated lead time for both screen-detected and interval cases is reported. Results show that the probability of no-early-detection (interval cases) increases monotonically when the screening interval increases for both genders. A male heavy smoker with an initial screening age at 60 has 11.65% (female 6.76%) chance of no-early-detection with annual screenings. This probability increases to 36.35% (female 28.26%) if the screenings were biennial. The mean lead time appears longer for women than for men. The mean lead time decreases when the screening interval increases, but it appears stable across different initial age groups. These results lay a foundation to evaluate survival benefit accurately with LDCT and to schedule future screening exams.

SUBMITTER: Liu R

PROVIDER: S-EPMC8982711 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Estimation of Lead Time via Low-Dose CT in the National Lung Screening Trial.

Liu Ruiqi R Pérez Adriana A Wu Dongfeng D

Journal of healthcare informatics research 20180612 4

Based on recent reports from the National Lung Screening Trial (NLST), smokers who were screened by low-dose computer tomography (LDCT) had a 20% lower chance of dying from lung cancer than those screened by chest X-rays. However, due to the complexities of lead time bias and over diagnosis, no formal test has been shown to reduce lung cancer mortality. To correctly evaluate survival benefit due to early detection, it is critical to estimate lead time, the length of time that detection of a dise ...[more]

PMID: 35415415

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Project description:BackgroundRandomized controlled trials have evaluated the efficacy of low-dose CT (LDCT) lung cancer screening on lung cancer (LC) outcomes.ObjectiveMeta-analyze LDCT lung cancer screening trials.MethodsWe identified studies by searching PubMed, Google Scholar, the Cochrane Registry, ClinicalTrials.gov , and reference lists from retrieved publications. We abstracted data on study design features, stage I LC diagnoses, LC and overall mortality, false positive results, harm from invasive diagnostic procedures, overdiagnosis, and significant incidental findings. We assessed study quality using the Cochrane risk-of-bias tool. We used random-effects models to calculate relative risks and assessed effect modulators with subgroup analyses and meta-regression.ResultsWe identified 9 studies that enrolled 96,559 subjects. The risk of bias across studies was judged to be low. Overall, LDCT screening significantly increased the detection of stage I LC, RR = 2.93 (95% CI, 2.16-3.98), I2 = 19%, and reduced LC mortality, RR = 0.84 (95% CI, 0.75-0.93), I2 = 0%. The number needed to screen to prevent an LC death was 265. Women had a lower risk of LC death (RR = 0.69, 95% CI, 0.40-1.21) than men (RR = 0.86, 95% CI, 0.66-1.13), p value for interaction = 0.11. LDCT screening did not reduce overall mortality, RR = 0.96 (95% CI, 0.91-1.01), I2 = 0%. The pooled false positive rate was 8% (95% CI, 4-18); subjects with false positive results had < 1 in 1000 risk of major complications following invasive diagnostic procedures. The most valid estimates for overdiagnosis and significant incidental findings were 8.9% and 7.5%, respectively.DiscussionLDCT screening significantly reduced LC mortality, though not overall mortality, with women appearing to benefit more than men. The estimated risks for false positive results, screening complications, overdiagnosis, and incidental findings were low. Long-term survival data were available only for North American and European studies limiting generalizability.

Project description:We propose a deep learning-assisted overscan decision algorithm in chest low-dose computed tomography (LDCT) applicable to the lung cancer screening. The algorithm reflects the radiologists' subjective evaluation criteria according to the Korea institute for accreditation of medical imaging (KIAMI) guidelines, where it judges whether a scan range is beyond landmarks' criterion. The algorithm consists of three stages: deep learning-based landmark segmentation, rule-based logical operations, and overscan determination. A total of 210 cases from a single institution (internal data) and 50 cases from 47 institutions (external data) were utilized for performance evaluation. Area under the receiver operating characteristic (AUROC), accuracy, sensitivity, specificity, and Cohen's kappa were used as evaluation metrics. Fisher's exact test was performed to present statistical significance for the overscan detectability, and univariate logistic regression analyses were performed for validation. Furthermore, an excessive effective dose was estimated by employing the amount of overscan and the absorbed dose to effective dose conversion factor. The algorithm presented AUROC values of 0.976 (95% confidence interval [CI]: 0.925-0.987) and 0.997 (95% CI: 0.800-0.999) for internal and external dataset, respectively. All metrics showed average performance scores greater than 90% in each evaluation dataset. The AI-assisted overscan decision and the radiologist's manual evaluation showed a statistically significance showing a p-value less than 0.001 in Fisher's exact test. In the logistic regression analysis, demographics (age and sex), data source, CT vendor, and slice thickness showed no statistical significance on the algorithm (each p-value > 0.05). Furthermore, the estimated excessive effective doses were 0.02 ± 0.01 mSv and 0.03 ± 0.05 mSv for each dataset, not a concern within slight deviations from an acceptable scan range. We hope that our proposed overscan decision algorithm enables the retrospective scan range monitoring in LDCT for lung cancer screening program, and follows an as low as reasonably achievable (ALARA) principle.

Project description:BackgroundAnnual low-dose CT screening for lung cancer has been recommended for high-risk individuals, but the necessity of yearly low-dose CT in all eligible individuals is uncertain. This study examined rates of lung cancer in National Lung Screening Trial (NLST) participants who had a negative prevalence (initial) low-dose CT screen to explore whether less frequent screening could be justified in some lower-risk subpopulations.MethodsWe did a retrospective cohort analysis of data from the NLST, a randomised, multicentre screening trial comparing three annual low-dose CT assessments with three annual chest radiographs for the early detection of lung cancer in high-risk, eligible individuals (aged 55-74 years with at least a 30 pack-year history of cigarette smoking, and, if a former smoker, had quit within the past 15 years), recruited from US medical centres between Aug 5, 2002, and April 26, 2004. Participants were followed up for up to 5 years after their last annual screen. For the purposes of this analysis, our cohort consisted of all NLST participants who had received a low-dose CT prevalence (T0) screen. We determined the frequency, stage, histology, study year of diagnosis, and incidence of lung cancer, as well as overall and lung cancer-specific mortality, and whether lung cancers were detected as a result of screening or within 1 year of a negative screen. We also estimated the effect on mortality if the first annual (T1) screen in participants with a negative T0 screen had not been done. The NLST is registered with ClinicalTrials.gov, number NCT00047385.FindingsOur cohort consisted of 26 231 participants assigned to the low-dose CT screening group who had undergone their T0 screen. The 19 066 participants with a negative T0 screen had a lower incidence of lung cancer than did all 26 231 T0-screened participants (371·88 [95% CI 337·97-408·26] per 100 000 person-years vs 661·23 [622·07-702·21]) and had lower lung cancer-related mortality (185·82 [95% CI 162·17-211·93] per 100 000 person-years vs 277·20 [252·28-303·90]). The yield of lung cancer at the T1 screen among participants with a negative T0 screen was 0·34% (62 screen-detected cancers out of 18 121 screened participants), compared with a yield at the T0 screen among all T0-screened participants of 1·0% (267 of 26 231). We estimated that if the T1 screen had not been done in the T0 negative group, at most, an additional 28 participants in the T0 negative group would have died from lung cancer (a rise in mortality from 185·82 [95% CI 162·17-211·93] per 100 000 person-years to 212·14 [186·80-239·96]) over the course of the trial.InterpretationParticipants with a negative low-dose CT prevalence screen had a lower incidence of lung cancer and lung cancer-specific mortality than did all participants who underwent a prevalence screen. Because overly frequent screening has associated harms, increasing the interval between screens in participants with a negative low-dose CT prevalence screen might be warranted.FundingNone.

Project description:BackgroundIn the National Lung Screening Trial (NLST), screening with low-dose computed tomography (CT) resulted in a 20% reduction in lung-cancer mortality among participants between the ages of 55 and 74 years with a minimum of 30 pack-years of smoking and no more than 15 years since quitting. It is not known whether the benefits and potential harms of such screening vary according to lung-cancer risk.MethodsWe assessed the variation in efficacy, the number of false positive results, and the number of lung-cancer deaths prevented among 26,604 participants in the NLST who underwent low-dose CT screening, as compared with the 26,554 participants who underwent chest radiography, according to the quintile of 5-year risk of lung-cancer death (ranging from 0.15 to 0.55% in the lowest-risk group [quintile 1] to more than 2.00% in the highest-risk group [quintile 5]).ResultsThe number of lung-cancer deaths per 10,000 person-years that were prevented in the CT-screening group, as compared with the radiography group, increased according to risk quintile (0.2 in quintile 1, 3.5 in quintile 2, 5.1 in quintile 3, 11.0 in quintile 4, and 12.0 in quintile 5; P=0.01 for trend). Across risk quintiles, there were significant decreasing trends in the number of participants with false positive results per screening-prevented lung-cancer death (1648 in quintile 1, 181 in quintile 2, 147 in quintile 3, 64 in quintile 4, and 65 in quintile 5). The 60% of participants at highest risk for lung-cancer death (quintiles 3 through 5) accounted for 88% of the screening-prevented lung-cancer deaths and for 64% of participants with false positive results. The 20% of participants at lowest risk (quintile 1) accounted for only 1% of prevented lung-cancer deaths.ConclusionsScreening with low-dose CT prevented the greatest number of deaths from lung cancer among participants who were at highest risk and prevented very few deaths among those at lowest risk. These findings provide empirical support for risk-based targeting of smokers for such screening. (Funded by the National Cancer Institute.).

Project description:ObjectiveTo compare the cost-effectiveness of undertaking low-dose computed tomography (LDCT) screening for early detection of lung cancer (LC) with different frequencies within the healthcare system of China, and estimate the additional national healthcare expenditure and five-year LC mortality associated with different screening frequencies.Material and methodsA Markov model was established using national LC epidemiological data from the Chinese Center for Disease Control and Prevention, demographic data from the Chinese Statistical Yearbook, and cost and effectiveness data mainly from the Cancer Screening Program in China. The model included thirty sex-specific screening strategies, which were classified by initial screening age (30, 35, 40, 45, and 50), and screening intervals (intervals at single time point, 1, 2, 5, 10, and 20 years). The main model outputs were incremental cost-effectiveness ratios (ICERs), additional national healthcare expenditure and five-year LC mortality.ResultsThe ICERs for LDCT screening strategies vs. non-screening strategy ranged from $16,086 per quality-adjusted life-year (QALY) to $3,675,491 per QALY in the male cohort, and from $36,624 per QALY to $5,943,556 per QALY in the female cohort. The annual increment national healthcare expenditures related to LDCT screening were varied from $0.25 to $13.39 billion, with the lower cost in the cohort with older screening ages and lower screening frequencies. More frequent screening with LDCT was associated with a greater reduction in LC death: an annual LDCT screening was linked to an estimated reduction in five-year LC death by 27.27-29.07%, while a one-off screening was linked to a reduction by 5.56-5.83%.ConclusionUnder a willingness-to-pay (WTP) threshold of three times the Chinese gross domestic product (GDP) per capita (US $37,654), annual screening with an initiating age at 50 was most cost-effective in both male and female cohorts. By taking into account both the national healthcare expenditures and the effect of LDCT screening, our study results support undertaking LDCT screening annually from 50 years old in general populations.

Project description:BackgroundLung cancer risk prediction models do not routinely incorporate imaging metrics available on low-dose CT (LDCT) imaging of the chest ordered for lung cancer screening.Research questionWhat is the association between quantitative emphysema measured on LDCT imaging and lung cancer incidence and mortality, all-cause mortality, and airflow obstruction in individuals who currently or formerly smoked and are undergoing lung cancer screening?Study design and methodsIn 7,262 participants in the CT arm of the National Lung Screening Trial, percent low attenuation area (%LAA) was defined as the percentage of lung volume with voxels less than -950 Hounsfield units on the baseline examination. Multivariable Cox proportional hazards models, adjusting for competing risks where appropriate, were built to test for association between %LAA and lung cancer incidence, lung cancer mortality, and all-cause mortality with censoring at 6 years. In addition, multivariable logistic regression models were built to test the cross-sectional association between %LAA and airflow obstruction on spirometry, which was available in 2,700 participants.ResultsThe median %LAA was 0.8% (interquartile range, 0.2%-2.7%). Every 1% increase in %LAA was independently associated with higher hazards of lung cancer incidence (hazard ratio [HR], 1.02; 95% CI, 1.01-1.03; P = .004), lung cancer mortality (HR, 1.02; 95% CI, 1.00-1.05; P = .045), and all-cause mortality (HR, 1.01; 95% CI, 1.00-1.03; P = .042). Among participants with spirometry, 892 had airflow obstruction. The likelihood of airflow obstruction increased with every 1% increase in %LAA (odds ratio, 1.07; 95% CI, 1.06-1.09; P < .001). A %LAA cutoff of 1% had the best discriminative accuracy for airflow obstruction in participants aged > 65 years.InterpretationQuantitative emphysema measured on LDCT imaging of the chest can be leveraged to improve lung cancer risk prediction and help diagnose COPD in individuals who currently or formerly smoked and are undergoing lung cancer screening.

Project description:BackgroundRelatively little is known about various aspects of low-dose CT (LDCT) scan lung cancer screening in US clinical practice, including characteristics of cases diagnosed after screening. We assessed this using the Surveillance, Epidemiology, and End Results (SEER)-Medicare database.Research questionWhat were the characteristics of patients with lung cancer, including stage and survival, whose disease was diagnosed after LDCT scan screenings?Study design and methodsWe created an LDCT scan use cohort consisting of everyone in the 5% SEER-Medicare sample with ≥ 12 months of non-health maintenance organization (HMO) Part A and B coverage while 65 to 77 years of age from 2015 through 2019. LDCT scan use and lung cancer diagnosis rates were assessed in this cohort. Additionally, we created a lung cancer cohort consisting of patients who received a diagnosis between 2015 and 2017 at 65 to 78 years of age with complete (non-HMO Part A and B) coverage the year before diagnosis. The cases cohort comprised those screened or unscreened based on undergoing screening during that period; lung cancer characteristics and survival were compared between these groups.ResultsIn the LDCT scan use cohort (n = 414,358), use rates increased from 0.10 (per 100 person-years) in 2015 to 1.3 in 2019. Among those with first screenings, 39.2% underwent a subsequent screen within 18 months. The 1-year cumulative lung cancer diagnosis rate after initial screenings was 2.4%. Claims for prescreen counseling were infrequent (about 10%). Of 48,891 patients in the lung cancer cohort, 1,150 (2.4%) underwent screening. Among screened patients, 52.3%, 11.0%, 20.7%, and 16.0% received diagnoses of stages I, II, III, and IV disease, respectively. Lung cancer-specific survival through 3 years was significantly greater in screened versus unscreened patients overall and for all stages except stage II; 3-year lung cancer-specific survival was 89.0% in screened patients with stage I disease.InterpretationLDCT scan use was low but increased over time. The lung cancer yield was substantial; cases among those who underwent screening primarily were in the early stage with high survival rates. Although screening rates were unacceptably low, screening outcomes in those Medicare recipients undergoing screening were favorable.

Dataset Information

Estimation of Lead Time via Low-Dose CT in the National Lung Screening Trial.

Publications

Estimation of Lead Time via Low-Dose CT in the National Lung Screening Trial.

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