Protocol and Rationale for the International Lung Screening Trial

Rationale: The NLST (National Lung Screening Trial) reported a 20% reduction in lung cancer mortality with low-dose computed tomography screening; however, important questions on how to optimize screening remain, including which selection criteria are most accurate at detecting lung cancers and what nodule management protocol is most efficient. The PLCOm2012 (Prostate, Lung, Colorectal and Ovarian) Cancer Screening Trial 6-year and PanCan (Pan-Canadian Early Detection of Lung Cancer) nodule malignancy risk models are two of the better validated risk prediction models for screenee selection and nodule management, respectively. Combined use of these models for participant selection and nodule management could significantly improve screening efficiency. Objectives: The ILST (International Lung Screening Trial) is a prospective cohort study with two primary aims: 1) Compare the accuracy of the PLCOm2012 model against U.S. Preventive Services Task Force (USPSTF) criteria for detecting lung cancers and 2) evaluate nodule management efficiency using the PanCan nodule probability calculator-based protocol versus Lung-RADS. Methods: ILST will recruit 4,500 participants who meet USPSTF and/or PLCOm2012 risk ≥1.51%/6-year selection criteria. Participants will undergo baseline and 2-year low-dose computed tomography screening. Baseline nodules are managed according to PanCan probability score. Participants will be followed up for a minimum of 5 years. Primary outcomes for aim 1 are the proportion of individuals selected for screening, proportion of lung cancers detected, and positive predictive values of either selection criteria, and outcomes for aim 2 include comparing distributions of individuals and the proportion of lung cancers in each of three management groups: next surveillance scan, early recall scan, or diagnostic evaluation recommended. Statistical powers to detect differences in the four components of primary study aims were ≥82%. Conclusions: ILST will prospectively evaluate the comparative accuracy and effectiveness of two promising multivariable risk models for screenee selection and nodule management in lung cancer screening. Clinical trial registered with www.clinicaltrials.gov (NCT02871856).

[1]  A. Jemal,et al.  Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries , 2018, CA: a cancer journal for clinicians.

[2]  S. Lam,et al.  Participant selection for lung cancer screening by risk modelling (the Pan-Canadian Early Detection of Lung Cancer [PanCan] study): a single-arm, prospective study. , 2017, The Lancet. Oncology.

[3]  M. Oudkerk,et al.  Small pulmonary nodules in baseline and incidence screening rounds of low-dose CT lung cancer screening. , 2017, Translational lung cancer research.

[4]  D. Manners,et al.  Identifying high risk individuals for targeted lung cancer screening: Independent validation of the PLCOm2012 risk prediction tool , 2017, International journal of cancer.

[5]  K. Fong,et al.  The effect of different radiological models on diagnostic accuracy and lung cancer screening performance , 2017, Thorax.

[6]  Bram van Ginneken,et al.  Malignancy risk estimation of screen-detected nodules at baseline CT: comparison of the PanCan model, Lung-RADS and NCCN guidelines , 2017, European Radiology.

[7]  M. Jantz,et al.  The American College of Radiology Lung Imaging Reporting and Data System: Potential Drawbacks and Need for Revision , 2017, Chest.

[8]  A. Bankier,et al.  Guidelines for Management of Incidental Pulmonary Nodules Detected on CT Images: From the Fleischner Society 2017. , 2017, Radiology.

[9]  M. Tonelli,et al.  Recommendations on screening for lung cancer , 2016, Canadian Medical Association Journal.

[10]  A. McWilliams,et al.  Lung cancer screening in Australia: progress or procrastination? , 2016, The Medical journal of Australia.

[11]  N J Wald,et al.  UK Lung Cancer RCT Pilot Screening Trial: baseline findings from the screening arm provide evidence for the potential implementation of lung cancer screening , 2015, Thorax.

[12]  A. Scarsbrook,et al.  Risk of malignancy in pulmonary nodules: A validation study of four prediction models. , 2015, Lung cancer.

[13]  M. Callister,et al.  British Thoracic Society guidelines for the investigation and management of pulmonary nodules. , 2015 .

[14]  M. Prokop,et al.  British Thoracic Society guidelines for the investigation and management of pulmonary nodules: accredited by NICE , 2015, Thorax.

[15]  E. Kazerooni,et al.  Performance of Lung-RADS in the National Lung Screening Trial , 2015, Annals of Internal Medicine.

[16]  Colin Jacobs,et al.  Predictive Accuracy of the PanCan Lung Cancer Risk Prediction Model -External Validation based on CT from the Danish Lung Cancer Screening Trial , 2015, European Radiology.

[17]  Brady J. McKee,et al.  Performance of ACR Lung-RADS in a clinical CT lung screening program. , 2015, Journal of the American College of Radiology : JACR.

[18]  Timothy R. Church,et al.  Evaluation of the Lung Cancer Risks at Which to Screen Ever- and Never-Smokers: Screening Rules Applied to the PLCO and NLST Cohorts , 2014, PLoS medicine.

[19]  Arash Naeim,et al.  Cost-effectiveness of CT screening in the National Lung Screening Trial. , 2014, The New England journal of medicine.

[20]  Heidi Roberts,et al.  Resource Utilization and Costs during the Initial Years of Lung Cancer Screening with Computed Tomography in Canada , 2014, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer.

[21]  Jihyoun Jeon,et al.  Comparative analysis of 5 lung cancer natural history and screening models that reproduce outcomes of the NLST and PLCO trials , 2014, Cancer.

[22]  Stephen Lam,et al.  Screening for lung cancer using low dose computed tomography , 2014, BMJ : British Medical Journal.

[23]  J. Peto,et al.  The clinical effectiveness and cost-effectiveness of primary human papillomavirus cervical screening in England: extended follow-up of the ARTISTIC randomised trial cohort through three screening rounds. , 2014, Health technology assessment.

[24]  V. Moyer Screening for Lung Cancer: U.S. Preventive Services Task Force Recommendation Statement , 2014, Annals of Internal Medicine.

[25]  William Hazelton,et al.  Benefits and Harms of Computed Tomography Lung Cancer Screening Strategies: A Comparative Modeling Study for the U.S. Preventive Services Task Force , 2014, Annals of Internal Medicine.

[26]  Rongwei Fu,et al.  Screening for Lung Cancer With Low-Dose Computed Tomography: A Systematic Review to Update the U.S. Preventive Services Task Force Recommendation , 2013, Annals of Internal Medicine.

[27]  J. Rathmell,et al.  Results of the two incidence screenings in the National Lung Screening Trial. , 2013, The New England journal of medicine.

[28]  S. Lam,et al.  Probability of cancer in pulmonary nodules detected on first screening CT. , 2013, The New England journal of medicine.

[29]  C. Berg,et al.  Targeting of low-dose CT screening according to the risk of lung-cancer death. , 2013, The New England journal of medicine.

[30]  Michael J Abramson,et al.  Screening for lung cancer. , 2013, The Cochrane database of systematic reviews.

[31]  H. D. de Koning,et al.  Characteristics of lung cancers detected by computer tomography screening in the randomized NELSON trial. , 2013, American journal of respiratory and critical care medicine.

[32]  Timothy R Church,et al.  Selection criteria for lung-cancer screening. , 2013, The New England journal of medicine.

[33]  Jihyoun Jeon,et al.  Chapter 5: Actual and Counterfactual Smoking Prevalence Rates in the U.S. Population via Microsimulation , 2012, Risk analysis : an official publication of the Society for Risk Analysis.

[34]  C. Gatsonis,et al.  Reduced Lung-Cancer Mortality with Low-Dose Computed Tomographic Screening , 2012 .

[35]  P. Prorok,et al.  Lung cancer risk prediction: Prostate, Lung, Colorectal And Ovarian Cancer Screening Trial models and validation. , 2011, Journal of the National Cancer Institute.

[36]  Harry J de Koning,et al.  Management of lung nodules detected by volume CT scanning. , 2009, The New England journal of medicine.

[37]  A. Dirksen,et al.  The Danish Randomized Lung Cancer CT Screening Trial—Overall Design and Results of the Prevalence Round , 2009, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer.

[38]  V. Beral,et al.  Cohort Profile: The 45 and Up Study , 2007, International journal of epidemiology.

[39]  E. Elkin,et al.  Decision Curve Analysis: A Novel Method for Evaluating Prediction Models , 2006, Medical decision making : an international journal of the Society for Medical Decision Making.

[40]  Patrick Royston,et al.  Multiple Imputation of Missing Values: Update of Ice , 2005 .

[41]  J. Austin,et al.  Guidelines for management of small pulmonary nodules detected on CT scans: a statement from the Fleischner Society. , 2005, Radiology.

[42]  L. Brown,et al.  Interval Estimation for a Binomial Proportion , 2001 .

[43]  D B Rubin,et al.  Multiple imputation in health-care databases: an overview and some applications. , 1991, Statistics in medicine.

[44]  E. McFadden,et al.  Toxicity and response criteria of the Eastern Cooperative Oncology Group , 1982, American journal of clinical oncology.

[45]  M. Callister,et al.  How should pulmonary nodules be optimally investigated and managed? , 2016, Lung cancer.

[46]  Ella A Kazerooni,et al.  ACR CT accreditation program and the lung cancer screening program designation. , 2015, Journal of the American College of Radiology : JACR.

[47]  W. Kinnear,et al.  British Thoracic Society Standards of Care Committee , 2014 .

[48]  Matthijs Oudkerk,et al.  International Association for the Study of Lung Cancer Computed Tomography Screening Workshop 2011 report. , 2012, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer.

[49]  Martin Fortin,et al.  Canadian Task Force on Preventive Health Care , 2012 .

[50]  M. L. R. D. Christenson,et al.  Guidelines for Management of Small Pulmonary Nodules Detected on CT Scans: A Statement From the Fleischner Society , 2006 .