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      Lung cancer mortality reduction by LDCT screening: UKLS randomised trial results and international meta-analysis

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          Abstract

          Background

          The NLST reported a significant 20% reduction in lung cancer mortality with three annual low-dose CT (LDCT) screens and the Dutch-Belgian NELSON trial indicates a similar reduction. We present the results of the UKLS trial.

          Methods

          From October 2011 to February 2013, we randomly allocated 4 055 participants to either a single invitation to screening with LDCT or to no screening (usual care). Eligible participants (aged 50–75) had a risk score (LLPv2) ≥ 4.5% of developing lung cancer over five years. Data were collected on lung cancer cases to 31 December 2019 and deaths to 29 February 2020 through linkage to national registries. The primary outcome was mortality due to lung cancer. We included our results in a random-effects meta-analysis to provide a synthesis of the latest randomised trial evidence.

          Findings

          1 987 participants in the intervention and 1 981 in the usual care arms were followed for a median of 7.3 years (IQR 7.1–7.6), 86 cancers were diagnosed in the LDCT arm and 75 in the control arm. 30 lung cancer deaths were reported in the screening arm, 46 in the control arm, (relative rate 0.65 [95% CI 0.41–1.02]; p=0.062). The meta-analysis indicated a significant reduction in lung cancer mortality with a pooled overall relative rate of 0.84 (95% CI 0.76–0.92) from nine eligible trials.

          Interpretation

          The UKLS trial of single LDCT indicates a reduction of lung cancer death of similar magnitude to the NELSON and NLST trials and was included in a meta-analysis of nine randomised trials which provides unequivocal support for lung cancer screening in identified risk groups.

          Funding

          NIHR Health Technology Assessment programme; NIHR Policy Research programme; Roy Castle Lung Cancer Foundation.

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          Most cited references44

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          Reduced lung-cancer mortality with low-dose computed tomographic screening.

          (2011)
          The aggressive and heterogeneous nature of lung cancer has thwarted efforts to reduce mortality from this cancer through the use of screening. The advent of low-dose helical computed tomography (CT) altered the landscape of lung-cancer screening, with studies indicating that low-dose CT detects many tumors at early stages. The National Lung Screening Trial (NLST) was conducted to determine whether screening with low-dose CT could reduce mortality from lung cancer. From August 2002 through April 2004, we enrolled 53,454 persons at high risk for lung cancer at 33 U.S. medical centers. Participants were randomly assigned to undergo three annual screenings with either low-dose CT (26,722 participants) or single-view posteroanterior chest radiography (26,732). Data were collected on cases of lung cancer and deaths from lung cancer that occurred through December 31, 2009. The rate of adherence to screening was more than 90%. The rate of positive screening tests was 24.2% with low-dose CT and 6.9% with radiography over all three rounds. A total of 96.4% of the positive screening results in the low-dose CT group and 94.5% in the radiography group were false positive results. The incidence of lung cancer was 645 cases per 100,000 person-years (1060 cancers) in the low-dose CT group, as compared with 572 cases per 100,000 person-years (941 cancers) in the radiography group (rate ratio, 1.13; 95% confidence interval [CI], 1.03 to 1.23). There were 247 deaths from lung cancer per 100,000 person-years in the low-dose CT group and 309 deaths per 100,000 person-years in the radiography group, representing a relative reduction in mortality from lung cancer with low-dose CT screening of 20.0% (95% CI, 6.8 to 26.7; P=0.004). The rate of death from any cause was reduced in the low-dose CT group, as compared with the radiography group, by 6.7% (95% CI, 1.2 to 13.6; P=0.02). Screening with the use of low-dose CT reduces mortality from lung cancer. (Funded by the National Cancer Institute; National Lung Screening Trial ClinicalTrials.gov number, NCT00047385.).
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            Reduced Lung-Cancer Mortality with Volume CT Screening in a Randomized Trial

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              Twenty five year follow-up for breast cancer incidence and mortality of the Canadian National Breast Screening Study: randomised screening trial

              Objective To compare breast cancer incidence and mortality up to 25 years in women aged 40-59 who did or did not undergo mammography screening. Design Follow-up of randomised screening trial by centre coordinators, the study’s central office, and linkage to cancer registries and vital statistics databases. Setting 15 screening centres in six Canadian provinces,1980-85 (Nova Scotia, Quebec, Ontario, Manitoba, Alberta, and British Columbia). Participants 89 835 women, aged 40-59, randomly assigned to mammography (five annual mammography screens) or control (no mammography). Interventions Women aged 40-49 in the mammography arm and all women aged 50-59 in both arms received annual physical breast examinations. Women aged 40-49 in the control arm received a single examination followed by usual care in the community. Main outcome measure Deaths from breast cancer. Results During the five year screening period, 666 invasive breast cancers were diagnosed in the mammography arm (n=44 925 participants) and 524 in the controls (n=44 910), and of these, 180 women in the mammography arm and 171 women in the control arm died of breast cancer during the 25 year follow-up period. The overall hazard ratio for death from breast cancer diagnosed during the screening period associated with mammography was 1.05 (95% confidence interval 0.85 to 1.30). The findings for women aged 40-49 and 50-59 were almost identical. During the entire study period, 3250 women in the mammography arm and 3133 in the control arm had a diagnosis of breast cancer, and 500 and 505, respectively, died of breast cancer. Thus the cumulative mortality from breast cancer was similar between women in the mammography arm and in the control arm (hazard ratio 0.99, 95% confidence interval 0.88 to 1.12). After 15 years of follow-up a residual excess of 106 cancers was observed in the mammography arm, attributable to over-diagnosis. Conclusion Annual mammography in women aged 40-59 does not reduce mortality from breast cancer beyond that of physical examination or usual care when adjuvant therapy for breast cancer is freely available. Overall, 22% (106/484) of screen detected invasive breast cancers were over-diagnosed, representing one over-diagnosed breast cancer for every 424 women who received mammography screening in the trial.
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                Author and article information

                Contributors
                Journal
                Lancet Reg Health Eur
                Lancet Reg Health Eur
                The Lancet Regional Health - Europe
                Elsevier
                2666-7762
                11 September 2021
                November 2021
                11 September 2021
                : 10
                : 100179
                Affiliations
                [a ]Department of Molecular and Clinical Cancer Medicine, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, 6 West Derby Street, Liverpool L7 8TX, UK
                [b ]Centre for Prevention, Detection and Diagnosis, Wolfson Institute of Population Health, Queen Mary University of London, London, UK
                [c ]Respiratory Medicine Unit, David Evans Research Centre, Department of Respiratory Medicine, Nottingham University Hospitals, Nottingham, UK
                [d ]Division of Population Medicine, College of Biomedical and Life Sciences, Cardiff University, Cardiff, UK
                [e ]Department of Radiology, Royal Brompton Hospital, London, and National Heart and Lung Institute, Imperial College, London, UK
                [f ]Department of Oncology, University of Cambridge, Cambridge, UK
                [g ]Department of Pathology, Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK
                [h ]Department of Radiology, Liverpool Heart and Chest Hospital, Liverpool, UK
                [i ]Lung Cancer Patient Advocate, Liverpool, UK
                [j ]Department of Pathology, Aberdeen Royal Infirmary, Aberdeen, UK
                [k ]Department of Respiratory Medicine, Liverpool Heart and Chest Hospital, Liverpool, UK
                [l ]Division of Population Medicine, College of Biomedical and Life Sciences, Cardiff University, Cardiff, UK
                [m ]Department of Radiology, University College, London Hospital, London, UK
                [n ]Department of Thoracic Surgery, Liverpool Heart and Chest Hospital, Liverpool, UK
                [o ]MRC Clinical Trials Unit, University College London, London, UK
                [p ]Department of Pathology, Papworth Hospital NHS Foundation Trust, Cambridge, UK
                [q ]Department of Thoracic Oncology, Royal Papworth Hospital NHS Foundation Trust, Cambridge, UK
                [r ]School of Clinical Sciences and Community Health, University of Edinburgh, Edinburgh, UK
                [s ]School of Economics, University of Nottingham, Nottingham, UK
                [t ]Department of Biostatistics, University of Liverpool, Liverpool, UK
                [u ]Faculty of Population Health Sciences, University College London, London, UK.
                [v ]Center for Evaluation and Methods, Wolfson Institute of Population Health. Queen Mary University of London, London, UK
                Author notes
                [* ]Corresponding author. J.K.Field@ 123456liverpool.ac.uk
                Article
                S2666-7762(21)00156-3 100179
                10.1016/j.lanepe.2021.100179
                8589726
                34806061
                10a38f63-13d8-4104-a70a-b0a2f63d3d1e
                © 2021 The Authors

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                Categories
                Research Paper

                lung cancer,ct screening,lung cancer mortality,meta-analysis

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