Lung Cancer Screening: Optimization through risk stratification

Lung cancer is the leading cause of cancer related mortality worldwide. However, results from randomized controlled trials indicate that lung cancer mortality can be reduced by early detection through computed tomography screening. This thesis describes the development of a microsimulation model for the evaluation of lung cancer screening programs, based on individual-level data from two large randomized controlled trials. It then evaluates the long-term benefits and harms of implementing lung cancer screening programs. Finally, it investigates how risk stratification may be used to optimize lung cancer screening programs

Green Function Monte Carlo with Stochastic Reconfiguration

A new method for the stabilization of the sign problem in the Green Function Monte Carlo technique is proposed. The method is devised for real lattice Hamiltonians and is based on an iterative ''stochastic reconfiguration'' scheme which introduces some bias but allows a stable simulation with constant sign. The systematic reduction of this bias is in principle possible. The method is applied to the frustrated J1-J2 Heisenberg model, and tested against exact diagonalization data. Evidence of a finite spin gap for J2/J1 >~ 0.4 is found in the thermodynamic limit.Comment: 13 pages, RevTeX + 3 encapsulated postscript figure

Uptake of minimally invasive surgery and stereotactic body radiation therapy for early stage non-small cell lung cancer in the USA

BACKGROUND: We aimed to assess the uptake of minimally invasive surgery (MIS) and stereotactic body radiation therapy (SBRT) among early stage (stage IA-IIB) non-small cell lung cancer (NSCLC) cases in the USA, and the rate of conversions from MIS to open surgery. MATERIALS AND METHODS: Data were obtained from the US National Cancer Database, a nationwide facility-based cancer registry capturing up to 70% of incident cancer cases in the USA. We included cases diagnosed with early stage (clinical stages IA-IIB) NSCLC between 2010 and 2014. In an ecological analysis, we assessed changes in treatment by year of diagnosis. Among surgically treated cases, we assessed the uptake of MIS and whether conversion to open surgery took place. For cases that received thoracic radiotherapy, we assessed the uptake of SBRT. RESULTS: Among 117 370 selected cases, radiotherapy use increased 3.4 percentage points between 2010 and 2014 (p<0.0001). Surgical treatments decreased 3.5 percentage points (p<0.0001). Rates of non-treatment remained stable (range: 10.0%-10.6% (p=0.4066)). Among surgically treated stage IA cases, uptake of MIS increased from 28.7% (95% CI 27.8% to 29.7%) in 2010 to 48.6% (95% CI 47.6% to 49

Assessing the impact of increasing lung screening eligibility by relaxing the maximum years-since-quit threshold. A simulation modeling study

BackgroundIn 2021, the US Preventive Services Task Force expanded its lung screening recommendation to include persons aged 50–80 years who had ever smoked and had at least 20 pack-years of exposure and less than 15 years since quitting (YSQ). However, studies have suggested that screening persons who formerly smoked with longer YSQ could be beneficial.MethodsThe authors used two validated lung cancer models to assess the benefits and harms of screening using various YSQ thresholds (10, 15, 20, 25, 30, and no YSQ) and the age at which screening was stopped. The impact of enforcing the YSQ criterion only at entry, but not at exit, also was evaluated. Outcomes included the number of screens, the percentage ever screened, screening benefits (lung cancer deaths averted, life-years gained), and harms (false-positive tests, overdiagnosed cases, radiation-induced lung cancer deaths). Sensitivity analyses were conducted to evaluate the effect of restricting screening to those who had at least 5 years of life expectancy.ResultsAs the YSQ criterion was relaxed, the number of screens and the benefits and harms of screening increased. Raising the age at which to stop screening age resulted in additional benefits but with more overdiagnosis, as expected, because screening among those older than 80 years increased. Limiting screening to those who had at least 5 years of life expectancy would maintain most of the benefits while considerably reducing the harms.ConclusionsExpanding screening to persons who formerly smoked and have greater than 15 YSQ would result in considerable increases in deaths averted and life-years gained. Although additional harms would occur, these could be moderated by ensuring that screening is restricted to only those with reasonable life expectancy

Extrapolation of pre-screening trends: Impact of assumptions on overdiagnosis estimates by mammographic screening

Background: Overdiagnosis by mammographic screening is defined as the excess in breast cancer incidence in the presence of screening compared to the incidence in the absence of screening. The latter is often estimated by extrapolating the pre-screening incidence trend. The aim of this theoretical study is to investigate the impact of assumptions in extrapolating the pre-screening incidence trend of invasive breast cancer on the estimated percentage of overdiagnosis. Methods: We extracted data on invasive breast cancer incidence and person-years by calendar year (1975-2009) and 5-year age groups (0-85 years) from Dutch databases. Different combinations of assumptions for extrapolating the pre-screening period were investigated, such as variations in the type of regre

Trends in lung cancer risk and screening eligibility affect overdiagnosis estimates

Objectives: The degree of overdiagnosis due to lung cancer screening in the general US population remains unknown. Estimates may be influenced by the method used and by decreasing smoking trends, which reduce lung cancer risk and screening eligibility over time. Therefore, we aimed to estimate the degree of overdiagnosis due to lung cancer screening in the general US population, using three distinct methods. Material and methods: The MISCAN-Lung model was used to project lung cancer incidence and overdiagnosis in the general US population between 2018–2040, assuming perfect adherence to the United States Preventive Task Force recommendations. MISCAN-Lung was calibrated to the NLST and PLCO trials and incorporates birth-cohort-specific smoking trends and life expectancies. We estimated overdiagnosis using the cumulative excess-incidence approach, the annual excess-incidence approach, and the microsimulation approach. Results: Using the cumulative excess-incidence approach, 10.5 % of screen-detected cases were overdiagnosed in the 1950 birth-cohort compared to 5.9 % in the 1990 birth-cohort. Incidence peaks and drops due to screening were larger for older birth-cohorts than younger birth-cohorts. In the general US population, these differing incidence peaks and drops across birth-cohorts overlap. Therefore, annual excess-incidence would be absent between 2029–2040, suggesting no overdiagnosis occurs. Using the microsimulation approach, overdiagnosis among screen-detected cases increased from 7.1 % to 9.5 % between 2018–2040, while overdiagnosis among all lung cancer cases decreased from 3.7 % to 1.4 %. Conclusion: Overdiagnosis studies should use appropriate methods to account for trends in background risk and screening eligibility in the general population. Estimates from randomized trials, based on the cumulative excess-incidence app

Umsetzung von Lungenkrebs-Screening

Two large-scale and sufficiently powered randomized-controlled trials and several smaller European trials have provided evidence on the effectiveness and feasibility of screening for lung cancer by means of low-dose computed tomography (LDCT) for a high-risk population. These findings support the implementation and upscaling of lung cancer screening to nationwide programs in Germany and the rest of Europe. At the same time, lung cancer screening efficiency can still be improved by further personalization and risk stratification, to maintain or improve the benefits while substantially reducing harms and costs (such as CT examinations needed, false-positive results and subsequent follow-up procedures). This review discusses the most pressing issues, such as the further development of adequate recruitment methods, risk-based eligibility and screening intervals, improved nodule detection and management, integrated smoking cessation programs, and a unified approach of the early detection of smoking-related diseases. The 4-IN-THE-LUNG-RUN (acronym for: Towards INdividually tailored INvitations, screening INtervals and INtegrated co-morbidity reducing strategies in lung cancer screening) is the first European multi-centred implementation trial on volume CT lung cancer screening amongst 24,000 high-risk subjects, across five countries. Germany is one of the participating countries, represented by the Deutsche Krebsforschungszentrum and the Universitätsklinikum (Ruhrlandklinik) Essen. The trial is expected to provide answers to the remaining issues, so that a high-quality screening program can be made accessible to those who might benefit most from lung cancer screening while keeping individual and societal harms at a minimum.</p

Umsetzung von Lungenkrebs-Screening

Two large-scale and sufficiently powered randomized-controlled trials and several smaller European trials have provided evidence on the effectiveness and feasibility of screening for lung cancer by means of low-dose computed tomography (LDCT) for a high-risk population. These findings support the implementation and upscaling of lung cancer screening to nationwide programs in Germany and the rest of Europe. At the same time, lung cancer screening efficiency can still be improved by further personalization and risk stratification, to maintain or improve the benefits while substantially reducing harms and costs (such as CT examinations needed, false-positive results and subsequent follow-up procedures). This review discusses the most pressing issues, such as the further development of adequate recruitment methods, risk-based eligibility and screening intervals, improved nodule detection and management, integrated smoking cessation programs, and a unified approach of the early detection of smoking-related diseases. The 4-IN-THE-LUNG-RUN (acronym for: Towards INdividually tailored INvitations, screening INtervals and INtegrated co-morbidity reducing strategies in lung cancer screening) is the first European multi-centred implementation trial on volume CT lung cancer screening amongst 24,000 high-risk subjects, across five countries. Germany is one of the participating countries, represented by the Deutsche Krebsforschungszentrum and the Universitätsklinikum (Ruhrlandklinik) Essen. The trial is expected to provide answers to the remaining issues, so that a high-quality screening program can be made accessible to those who might benefit most from lung cancer screening while keeping individual and societal harms at a minimum.</p

Treatment capacity required for full-scale implementation of lung cancer screening in the United States

BACKGROUND: Full-scale implementation of lung cancer screening in the United States will increase detection of early stages. This study was aimed at assessing the capacity required for treating those cancers. METHODS: A well-established microsimulation model was extended with treatment data from the National Cancer Database. We assessed how treatment demand would change when implementing lung cancer screening in 2018. Three policies were assessed: 1) annual screening of current smokers and former smokers who quit fewer than 15 years ago, aged 55 to 80 years, with a smoking history of at least 30 pack-years (US Preventive Services Task Force [USPSTF] recommendations); 2) annual screening of current smokers and former smokers who quit fewer than 15 years ago, aged 55 to 77 years, with a smoking history of at least 30 pack-years (Centers for Medicare and Medicaid Services [CMS] recommendations); and 3) annual screening of current smokers and former smokers who quit fewer than 10 years ago, aged 55 to 75 years, with a smoking history of at least 40 pack-years (the most cost-effective policy in Ontario [Ontario]). The base-case screening adherence was a constant 50%. Sensitivity analyses assessed other adherence levels, including a linear buildup to 50% between 2018 and 2027. RESULTS: The USPSTF policy would require 37.0% more lung cancer surgeries in 2015-2040 than no screening, 2.2% less radiotherapy, and 5.4% less chemotherapy; 5.7% more patients would require any therapy. The increase in surgical demand would be 96.1% in 2018, 46.0% in 2023, 38.3% in 2028, and 24.9% in 2040. Adherence strongly influenced results. By 2018, surgical demand would range from 52,619 (20% adherence) to 96,121 (80%). With a gradual buildup of adherence, the increase in surgical demand would be 9.6% in 2018, 38.3% in 2023, 42.0% in 2028, and 24.4% in 2040. Results for the CMS and Ontario policies were similar, although the changes in comparison with no screening were smaller. CONCLUSIONS: Full-scale implementation of lung cancer screening causes a major increase in surgical demand, with a peak within the first 5 years. A gradual buildup of adherence can spread this peak over time. Careful surgical capacity planning is essential for successfully implementing screening. Cancer 2019;125:2039-2048. © 2019 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made