Combined Biomarker and Computed Tomography Screening Strategies for Lung Cancer: Projections of Health and Economic Tradeoffs in the US Population.
Ontology highlight
ABSTRACT: Background
Lung cancer screening with computed tomography (CT) of individuals who meet certain age and smoking history criteria is the current standard-of-care.Methods
Using a published simulation model, we compared outcomes associated with seven biomarker+CT screening strategies to CT screening alone using CMS eligibility criteria. We assumed that the biomarker: had conditionally independent performance; was used for first-line screening in some, or all, individuals screened; and could be extended to CMS-ineligible smokers. Strategies differed by inclusion criteria (e.g. pack-years) and proportion of individuals for whom CT remained the first-line test. Each model run simulated a combined cohort of one million men and one million women born in 1950. Primary outcomes were cancer-specific mortality reduction and screening costs; biomarker costs were measured relative to CT. Efficiency frontiers identified optimal health and economic trade-offs. Sensitivity analysis evaluated the stability of results.Results
Standard-of-care screening yielded an 8.3% cancer-specific mortality reduction in the simulated U.S. population (screened+unscreened individuals). For a biomarker test with 75% sensitivity and 95% specificity, mortality reductions across biomarker+CT strategies ranged from 7.0% to 23.9%. If the biomarker's cost was >0.86× that of CT, standard-of-care screening remained on the efficiency frontier, indicating that health and economic trade-offs were equally (or more) efficient relative to all biomarker+CT strategies. Biomarker+CT strategy costs were principally driven by biomarker specificity; mortality reduction was driven by sensitivity.Conclusion
Combined biomarker+CT strategies have the potential to improve future lung cancer screening effectiveness in the U.S. and achieve economic efficiency that is greater than the current standard-of-care.
SUBMITTER: Kong CY
PROVIDER: S-EPMC6116540 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:The Lung Computed Tomography Screening Reporting and Data System (Lung-RADS) reduces the false-positive rate of lung cancer screening but introduces prolonged periods of uncertainty for indeterminate findings. We assess the cost-effectiveness of a screening program that assesses indeterminate findings earlier via a hypothetical diagnostic biomarker introduced in place of Lung-RADS 3 and 4A guidelines. We evaluated the performance of the US Preventive Services Task Force (USPSTF) recommendations on lung cancer screening with and without a hypothetical noninvasive diagnostic biomarker using a validated microsimulation model. The diagnostic biomarker assesses the malignancy of indeterminate nodules, replacing Lung-RADS 3 and 4A guidelines, and is characterized by a varying sensitivity profile that depends on nodules' size, specificity, and cost. We tested the robustness of our findings through univariate sensitivity analyses. A lung cancer screening program per the USPSTF guidelines that incorporates a diagnostic biomarker with at least medium sensitivity profile and 90% specificity, that costs $250 or less, is cost-effective with an incremental cost-effectiveness ratio lower than $100 000 per quality-adjusted life year, and improves lung cancer-specific mortality reduction while requiring fewer screening exams than the USPSTF guidelines with Lung-RADS. A screening program with a biomarker costing $750 or more is not cost-effective. The health benefits accrued and costs associated with the screening program are sensitive to the disutility of indeterminate findings and specificity of the biomarker, respectively. Lung cancer screening that incorporates a diagnostic biomarker, in place of Lung-RADS 3 and 4A guidelines, could improve the cost-effectiveness of the screening program and warrants further investigation.
| S-EPMC8564700 | biostudies-literature
Project description:ImportanceChina, which has one-third of the worldwide smoking population, has a substantial cancer burden, with lung cancer being the leading cause of cancer-related death. The effectiveness of lung cancer screening for mortality reduction has been confirmed, but the cost-effectiveness of diverse screening modalities remains unclear.ObjectiveTo compare the cost-effectiveness of low-dose computed tomography (LDCT) with a biomarker (micro-RNA signature classifier [MSC]) with that of LDCT alone by screening interval and cumulative smoking exposure.Design, setting, and participantsIn this economic evaluation, a comparative cost-effectiveness analysis used Markov state transition models that simulated the 1947 to 1971 China birth cohort. Simulated individuals in 8 cohorts of 10 000 entered the study between ages 50 and 74 years and were followed up until death or age 79 years, corresponding to a study period from January 1, 2021, to December 31, 2050. The model was run with a cycle length of 1 year. All the transition probabilities were validated, and health utility values were extracted from published literature. Cost parameters were derived from the databases of local medical insurance bureaus.Main outcomes and measuresPrimary outcomes included life-years, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs) with future costs and outcomes discounted by 5%. Screening strategies with a mean ICER less than Chinese yuan (CNY) 212 676 per QALY gained were deemed to be cost-effective. The cost-effectiveness of 7 alternative screening strategies with a screening starting age of 50 years, minimum cumulative smoking exposure of 20 vs 30 pack-years, and screening interval of annual vs 1 time was estimated, including the 2021 China guideline-recommended strategy (LDCT, annual, 30 pack-years) and the 2018 China guideline-recommended strategy (LDCT, annual, 20 pack-years).ResultsIn a simulated population of 80 000 individuals, the conjunctive LDCT and MSC screening strategy was estimated to obtain an ICER of CNY -793 995.17 to 254 417.46 (minimum cumulative smoking exposure, 20-30 pack-years) per QALY gained compared with LDCT screening alone. China's 2021 guideline-recommended strategy was not cost-effective compared with the 2018 guideline-recommended strategy, with higher costs and fewer QALYs gained; the QALY loss ranged from 0.02 to 0.15 per person and the increase in cost ranged from CNY 945.89 to CNY 5131.29 per person. LDCT and MSC screening beginning at age 70 to 74 years in individuals with a 20 pack-year smoking history was the most cost-effective strategy, with an ICER of CNY -793 995.17 per QALY gained. Lowering the minimum cumulative smoking exposure for screening from 30 to 20 pack-years and maintaining annual screening were associated with greater cost savings regardless of the screening tool.Conclusions and relevanceThis economic evaluation found that China's 2018 recommendation for lung cancer screening was more cost-effective than the 2021 recommendation. Moreover, the cost-effectiveness of lung cancer screening was improved when MSC was included with LDCT. These findings may be useful for the modification of guidelines for lung cancer screening.
| S-EPMC9131747 | biostudies-literature
Project description:Screening for lung cancer has the potential to reduce mortality, but in addition to detecting aggressive tumors, screening will also detect indolent tumors that otherwise may not cause clinical symptoms. These overdiagnosis cases represent an important potential harm of screening because they incur additional cost, anxiety, and morbidity associated with cancer treatment.To estimate overdiagnosis in the National Lung Screening Trial (NLST).We used data from the NLST, a randomized trial comparing screening using low-dose computed tomography (LDCT) vs chest radiography (CXR) among 53?452 persons at high risk for lung cancer observed for 6.4 years, to estimate the excess number of lung cancers in the LDCT arm of the NLST compared with the CXR arm.We calculated 2 measures of overdiagnosis: the probability that a lung cancer detected by screening with LDCT is an overdiagnosis (PS), defined as the excess lung cancers detected by LDCT divided by all lung cancers detected by screening in the LDCT arm; and the number of cases that were considered overdiagnosis relative to the number of persons needed to screen to prevent 1 death from lung cancer.During follow-up, 1089 lung cancers were reported in the LDCT arm and 969 in the CXR arm of the NLST. The probability is 18.5% (95% CI, 5.4%-30.6%) that any lung cancer detected by screening with LDCT was an overdiagnosis, 22.5% (95% CI, 9.7%-34.3%) that a non-small cell lung cancer detected by LDCT was an overdiagnosis, and 78.9% (95% CI, 62.2%-93.5%) that a bronchioalveolar lung cancer detected by LDCT was an overdiagnosis. The number of cases of overdiagnosis found among the 320 participants who would need to be screened in the NLST to prevent 1 death from lung cancer was 1.38.More than 18% of all lung cancers detected by LDCT in the NLST seem to be indolent, and overdiagnosis should be considered when describing the risks of LDCT screening for lung cancer.
| S-EPMC4040004 | biostudies-literature
Project description:The National Lung Screening Trial (NLST) demonstrated that screening with low-dose CT versus chest radiography reduced lung cancer mortality by 16% to 20%. More recently, a cost-effectiveness analysis (CEA) of CT screening for lung cancer versus no screening in the NLST was performed. The CEA conformed to the reference-case recommendations of the US Panel on Cost-Effectiveness in Health and Medicine, including the use of the societal perspective and an annual discount rate of 3%. The CEA was based on several important assumptions. In this paper, I review the methods and assumptions used to obtain the base case estimate of $81,000 per quality-adjusted life-year gained. In addition, I show how this estimate varied widely among different subsets and when some of the base case assumptions were changed and speculate on the cost-effectiveness of CT screening for lung cancer outside the NLST.
| S-EPMC4890607 | biostudies-literature
Project description:The National Lung Screening Trial (NLST) has provided compelling evidence of the efficacy of lung cancer screening using low-dose helical computed tomography (LDCT) to reduce lung cancer mortality. The NLST randomized 53,454 older current or former heavy smokers to receive LDCT or chest radiography (CXR) for three annual screens. Participants were observed for a median of 6.5 years for outcomes. Vital status was available in more than 95% of participants. LDCT was positive in 24.2% of screens, compared with 6.9% of CXRs; more than 95% of all positive LDCT screens were not associated with lung cancer. LDCT detected more than twice the number of early-stage lung cancers and resulted in a stage shift from advanced to early-stage disease. Complications of LDCT screening were minimal. Lung cancer-specific mortality was reduced by 20% relative to CXR; all-cause mortality was reduced by 6.7%. The major harms of LDCT are radiation exposure, high false-positive rates, and the potential for overdiagnosis. This review discusses the risks and benefits of LDCT screening as well as an approach to LDCT implementation that incorporates systematic screening practice with smoking cessation programs and offers opportunities for better determination of appropriate risk cohorts for screening and for better diagnostic prediction of lung cancer in the setting of screen-detected nodules. The challenges of implementation are considered for screening programs, for primary care clinicians, and across socioeconomic strata. Considerations for future research to complement imaging-based screening to reduce the burden of lung cancer are discussed.
| S-EPMC3589698 | biostudies-literature
Project description:ImportanceThe American College of Radiology (ACR) has recognized the importance of minimizing radiation doses used for lung cancer screening (LCS) computed tomography (CT). However, without standard protocols, doses could still be unnecessarily high, reducing screening margin of benefit.ObjectiveTo characterize LCS CT radiation doses and identify factors explaining variation.Design, setting, and participantsWe prospectively collected LCS examination dose metrics, from 2016 to 2017, at US institutions in the University of California, San Francisco International Dose Registry. Institution-level factors were collected through baseline survey. Mixed-effects linear and logistic regression models were estimated using forward variable selection. Results are presented as percentage excess dose and odds ratios (ORs) with 95% confidence intervals (CIs). The analysis was conducted between 2018 and 2019.Main outcomes and measuresLog-transformed measures of (1) mean volume CT dose index (CTDIvol, mGy), reflecting the average radiation dose per slice; (2) mean effective dose (ED, mSv), reflecting the total dose received and estimated future cancer risk; (3) proportion of CT scans using radiation doses above ACR benchmarks (CTDIvol >3 mGy, ED >1 mSv); and (4) proportion of CT scans using radiation doses above 75th percentile of registry doses (CTDIvol >2.7 mGy, ED >1.4 mSv).ResultsData were collected for 12 529 patients undergoing LCS CT scans performed at 72 institutions. Overall, 7232 participants (58%) were men, and the median age was 65 years (interquartile range [IQR], 60-70). Of 72 institutions, 15 (21%) had median CTDIvol and 47 (65%) had median ED above ACR guidelines. Institutions allowing any radiologists to establish protocols had 44% higher mean CTDIvol (mean dose difference [MDD], 44%; 95% CI, 19%-69%) and 27% higher mean ED (MDD, 27%; 95% CI, 5%-50%) vs those limiting who established protocols. Institutions allowing any radiologist to establish protocols had higher odds of examinations exceeding ACR CTDIvol guidelines (OR, 12.0; 95% CI, 2.0-71.4), and 75th percentile of registry CTDIvol (OR, 19.0; 95% CI, 1.9-186.7) or ED (OR, 8.5; 95% CI, 1.7-42.9). Having lead radiologists establish protocols resulted in lower odds of doses exceeding ACR ED guidelines (OR, 0.01; 95% CI, 0.001-0.1). Employing external vs internal medical physicists was associated with increased odds of exceeding ACR CTDIvol guidelines (OR, 6.1; 95% CI, 1.8-20.8). Having medical physicists establish protocols was associated with decreased odds of exceeding 75th percentile of registry CTDIvol (OR, 0.09; 95% CI, 0.01-0.59). Institutions reporting protocol updates as needed had 27% higher mean CTDIvol (MDD, 27%; 95% CI, 8%-45%).Conclusions and relevanceFacilities varied in LCS CT radiation dose distributions. Institutions limiting protocol creation to lead radiologists and having internal medical physicists had lower doses.
| S-EPMC6764003 | biostudies-literature
Project description:BackgroundThe optimum screening policy for lung cancer is unknown.ObjectiveTo identify efficient computed tomography (CT) screening scenarios in which relatively more lung cancer deaths are averted for fewer CT screening examinations.DesignComparative modeling study using 5 independent models.Data sourcesThe National Lung Screening Trial; the Prostate, Lung, Colorectal, and Ovarian Cancer Screening trial; the Surveillance, Epidemiology, and End Results program; and the U.S. Smoking History Generator.Target populationU.S. cohort born in 1950.Time horizonCohort followed from ages 45 to 90 years.PerspectiveSocietal.Intervention576 scenarios with varying eligibility criteria (age, pack-years of smoking, years since quitting) and screening intervals.Outcome measuresBenefits included lung cancer deaths averted or life-years gained. Harms included CT examinations, false-positive results (including those obtained from biopsy/surgery), overdiagnosed cases, and radiation-related deaths.Results of best-case scenarioThe most advantageous strategy was annual screening from ages 55 through 80 years for ever-smokers with a smoking history of at least 30 pack-years and ex-smokers with less than 15 years since quitting. It would lead to 50% (model ranges, 45% to 54%) of cases of cancer being detected at an early stage (stage I/II), 575 screening examinations per lung cancer death averted, a 14% (range, 8.2% to 23.5%) reduction in lung cancer mortality, 497 lung cancer deaths averted, and 5250 life-years gained per the 100,000-member cohort. Harms would include 67,550 false-positive test results, 910 biopsies or surgeries for benign lesions, and 190 overdiagnosed cases of cancer (3.7% of all cases of lung cancer [model ranges, 1.4% to 8.3%]).Results of sensitivity analysisThe number of cancer deaths averted for the scenario varied across models between 177 and 862; the number of overdiagnosed cases of cancer varied between 72 and 426.LimitationsScenarios assumed 100% screening adherence. Data derived from trials with short duration were extrapolated to lifetime follow-up.ConclusionAnnual CT screening for lung cancer has a favorable benefit-harm ratio for individuals aged 55 through 80 years with 30 or more pack-years' exposure to smoking.Primary funding sourceNational Cancer Institute.
| S-EPMC4116741 | biostudies-literature
Project description:This supplementary data is supportive to the research article entitled 'Cost-effectiveness of lung cancer screening with low-dose computed tomography (LDCT) in heavy smokers: A micro-simulation modelling study' (Yihui Du et al. 2020). This supplementary contains a description of the model input and the related model output data that were not included in the research article. The input data used for the tumour growth model and the self-detected tumour size model are provided. The output data of this article include the data used for cost-effectiveness analysis of lung cancer LDCT screening with the Dutch and international discount rates, the data of the sensitivity analysis, and the data of the model validation.
| S-EPMC7352064 | biostudies-literature
Project description:A randomized trial has demonstrated that lung cancer screening reduces mortality. Identifying participant and program characteristics that influence the cost-effectiveness of screening will help translate trial results into benefits at the population level.Six U.S. cohorts (men and women aged 50, 60, or 70 years) were simulated in an existing patient-level lung cancer model. Smoking histories reflected observed U.S. patterns. We simulated lifetime histories of 500,000 identical individuals per cohort in each scenario. Costs per quality-adjusted life-year gained ($/QALY) were estimated for each program: computed tomography screening; stand-alone smoking cessation therapies (4-30% 1-year abstinence); and combined programs.Annual screening of current and former smokers aged 50 to 74 years costs between $126,000 and $169,000/QALY (minimum 20 pack-years of smoking) or $110,000 and $166,000/QALY (40 pack-year minimum), when compared with no screening and assuming background quit rates. Screening was beneficial but had a higher cost per QALY when the model included radiation-induced lung cancers. If screen participation doubled background quit rates, the cost of annual screening (at age 50 years, 20 pack-year minimum) was below $75,000/QALY. If screen participation halved background quit rates, benefits from screening were nearly erased. If screening had no effect on quit rates, annual screening costs more but provided fewer QALYs than annual cessation therapies. Annual combined screening/cessation therapy programs at age 50 years costs $130,500 to $159,700/QALY, when compared with annual stand-alone cessation.The cost-effectiveness of computed tomography screening will likely be strongly linked to achievable smoking cessation rates. Trials and further modeling should explore the consequences of relationships between smoking behaviors and screen participation.
| S-EPMC3202298 | biostudies-literature
Project description:BackgroundAlthough screening programmes of smokers have detected resectable early lung cancers more frequently than expected, their efficacy in reducing mortality remains debatable. To elucidate the biological features of computed tomography (CT) screening detected lung cancer, we examined the mRNA signatures on tumours according to the year of detection, stage and survival.MethodsGene expression profiles were analysed on 28 patients (INT-IEO training cohort) and 24 patients of Multicentre Italian Lung Detection (MILD validation cohort). The gene signatures generated from the training set were validated on the MILD set and a public deposited DNA microarray data set (GSE11969). Expression of selected genes and proteins was validated by real-time RT-PCR and immunohistochemistry. Enriched core pathway and pathway networks were explored by GeneSpring GX10.FindingsA 239-gene signature was identified according to the year of tumour detection in the training INT-IEO set and correlated with the patients' outcomes. These signatures divided the MILD patients into two distinct survival groups independently of tumour stage, size, histopathological type and screening year. The signatures can also predict survival in the clinically detected cancers (GSE11969). Pathway analyses revealed tumours detected in later years enrichment of the PI3K/PTEN/AKT pathway, with up-regulation of PDPK1, ITGB1 and down-regulation of FOXO1A. Analysis of normal lung tissue from INT-IEO cohort produced signatures distinguishing patients with early from late detected tumours.InterpretationThe distinct pattern of "indolent" and "aggressive" tumour exists in CT-screening detected lung cancer according to the gene expression profiles. The early development of an aggressive phenotype may account for the lack of mortality reduction by screening observed in some cohorts.
| S-EPMC4563137 | biostudies-literature