National Lung Screening Trial (NLST) Screening

NCT ID: NCT00047385

Last Updated: 2014-05-20

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

53454 participants

Study Classification

INTERVENTIONAL

Study Start Date

2002-08-31

Study Completion Date

2010-10-31

Brief Summary

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RATIONALE: Effective screening tests should help doctors detect lung cancer early and plan curative treatment. It is not yet known whether low-dose helical computed tomography (LDCT) screening is more effective than chest radiography (CXR) screening in reducing death from lung cancer.

PURPOSE: Randomized clinical trial to compare the effectiveness of LDCT scan with that of CXR in screening individuals who are at high risk for developing lung cancer.

Detailed Description

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OBJECTIVES:

* Compare whether screening with low-dose helical CT scan vs chest x-ray reduces lung cancer-specific mortality in participants who are at high risk for developing lung cancer.

OUTLINE:

NLST participants were randomized to either low-dose helical CT or chest x-ray in equal proportions. A total of 53,454 participants were enrolled (26,722 in low-dose CT and 26,732 in chest radiography) at 33 screening centers across the United States. Screening was offered three times (at baseline and two annual follow-up examinations). The primary endpoint of the study was lung cancer mortality. The study arms were compared with regard to overall mortality, lung cancer incidence, and screening-related complications.

All low-dose scanners and chest x-ray machines were certified for use and met NLST protocol requirements and American College of Radiology guidelines. Low-dose CT acquisitions and chest radiographs were interpreted by trained radiologists. Participants and their health care provider were informed of study examination results. Participants with abnormalities suspicious for lung cancer were contacted for information regarding diagnostic evaluation. Medical records were collected on diagnostic evaluation, medical complications, and initial treatment.

Participants were then contacted at least annually by mail or telephone.

The National Lung Screening Trial (NLST) represents the union of two NCI-sponsored efforts, the NCI Lung Screening Study and the American College of Radiology Imaging Network (ACRIN).

Conditions

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Lung Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

SCREENING

Blinding Strategy

NONE

Study Groups

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Low-Dose CT

Group Type EXPERIMENTAL

low-dose helical computed tomography

Intervention Type DEVICE

A LDCT is a computerized tomography image with low-dose technique without contrast. The scan is done from the neck to the diaphragm in one breath-hold.

Chest X-ray

Group Type EXPERIMENTAL

chest radiography

Intervention Type DEVICE

The chest x-ray in this study was a single posterior-anterior film done with the participant upright.

Interventions

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low-dose helical computed tomography

A LDCT is a computerized tomography image with low-dose technique without contrast. The scan is done from the neck to the diaphragm in one breath-hold.

Intervention Type DEVICE

chest radiography

The chest x-ray in this study was a single posterior-anterior film done with the participant upright.

Intervention Type DEVICE

Other Intervention Names

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LDCT CXR

Eligibility Criteria

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Inclusion Criteria

* Age 55-74 years (pack-years = packs per day \* years smoked)
* 30 or more pack-years of cigarette smoking history
* Former smokers: quit smoking within the previous 15 years
* Ability to lie on the back with arms raised over the head
* Signed informed consent form

Exclusion Criteria

* Metallic implants or devices in the chest or back, such as pacemakers or Harrington fixation rods
* Treatment for, or evidence of, any cancer other than nonmelanoma skin cancer or carcinoma in situ (with the exception of transitional cell carcinoma in situ or bladder carcinoma in situ) in the 5 years prior to eligibility assessment
* History of lung cancer
* History of removal of any portion of the lung, excluding needle biopsy
* Requirement for home oxygen supplementation
* Participation in another cancer screening trial
* Participation in a cancer prevention study, other than a smoking cessation study
* Unexplained weight loss of more than 15 pounds in the 12 months prior to eligibility assessment
* Recent hemoptysis
* Pneumonia or acute respiratory infection treated with antibiotics in the 12 weeks prior to eligibility assessment
* Chest CT examination in the 18 months prior to eligibility assessment
Minimum Eligible Age

55 Years

Maximum Eligible Age

74 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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American College of Radiology Imaging Network

NETWORK

Sponsor Role collaborator

National Cancer Institute (NCI)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Christine D. Berg, MD

Role: STUDY_DIRECTOR

NCI - Early Detection Research Group

Denise R. Aberle, MD

Role: PRINCIPAL_INVESTIGATOR

Jonsson Comprehensive Cancer Center

Locations

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University of Alabama at Birmingham

Birmingham, Alabama, United States

Site Status

Univeristy of California, San Diego

La Jolla, California, United States

Site Status

Jonsson Comprehensive Cancer Center, UCLA

Los Angeles, California, United States

Site Status

University of Colorado Denver

Denver, Colorado, United States

Site Status

Georgetown University Medical Center

Washington D.C., District of Columbia, United States

Site Status

Mayo Clinic

Jacksonville, Florida, United States

Site Status

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, United States

Site Status

Emory University School of Medicine

Atlanta, Georgia, United States

Site Status

Pacific Health Research & Education Institute

Honolulu, Hawaii, United States

Site Status

Northwestern University

Chicago, Illinois, United States

Site Status

University of Iowa

Iowa City, Iowa, United States

Site Status

Jewish Hopsital Heart and Lung Institute

Louisville, Kentucky, United States

Site Status

Ochsner Medical Foundation Hospital

New Orleans, Louisiana, United States

Site Status

Johns Hopkins University

Baltimore, Maryland, United States

Site Status

Brigham and Women's Hospital

Boston, Massachusetts, United States

Site Status

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Site Status

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, United States

Site Status

Henry Ford Health System

Detroit, Michigan, United States

Site Status

University of Minnesota School of Public Health

Minneapolis, Minnesota, United States

Site Status

Mayo Clinic Cancer Center

Rochester, Minnesota, United States

Site Status

Washington University School of Medicine

St Louis, Missouri, United States

Site Status

Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, United States

Site Status

Cancer Institute of New Jersey at Hamilton

Hamilton, New Jersey, United States

Site Status

Wake Forest University

Winston-Salem, North Carolina, United States

Site Status

St Elizabeth Health Center

Youngstown, Ohio, United States

Site Status

University of Pennsylvania Medical Center

Philadelphia, Pennsylvania, United States

Site Status

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States

Site Status

Brown University, Rhode Island Hospital

Providence, Rhode Island, United States

Site Status

Medical University of South Carolina

Charleston, South Carolina, United States

Site Status

Vanderbilt University

Nashville, Tennessee, United States

Site Status

University of Texas - MD Anderson Cancer Center

Houston, Texas, United States

Site Status

University of Utah Health Sciences Center

Salt Lake City, Utah, United States

Site Status

Marshfield Clinic Research Foundation

Marshfield, Wisconsin, United States

Site Status

Countries

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United States

References

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National Lung Screening Trial Research Team; Aberle DR, Berg CD, Black WC, Church TR, Fagerstrom RM, Galen B, Gareen IF, Gatsonis C, Goldin J, Gohagan JK, Hillman B, Jaffe C, Kramer BS, Lynch D, Marcus PM, Schnall M, Sullivan DC, Sullivan D, Zylak CJ. The National Lung Screening Trial: overview and study design. Radiology. 2011 Jan;258(1):243-53. doi: 10.1148/radiol.10091808. Epub 2010 Nov 2.

Reference Type BACKGROUND
PMID: 21045183 (View on PubMed)

Cody DD, Kim HJ, Cagnon CH, Larke FJ, McNitt-Gray MM, Kruger RL, Flynn MJ, Seibert JA, Judy PF, Wu X. Normalized CT dose index of the CT scanners used in the National Lung Screening Trial. AJR Am J Roentgenol. 2010 Jun;194(6):1539-46. doi: 10.2214/AJR.09.3268.

Reference Type BACKGROUND
PMID: 20489094 (View on PubMed)

Clark KW, Gierada DS, Marquez G, Moore SM, Maffitt DR, Moulton JD, Wolfsberger MA, Koppel P, Phillips SR, Prior FW. Collecting 48,000 CT exams for the lung screening study of the National Lung Screening Trial. J Digit Imaging. 2009 Dec;22(6):667-80. doi: 10.1007/s10278-008-9145-9. Epub 2008 Sep 6.

Reference Type BACKGROUND
PMID: 18777192 (View on PubMed)

Gierada DS, Garg K, Nath H, Strollo DC, Fagerstrom RM, Ford MB. CT quality assurance in the lung screening study component of the National Lung Screening Trial: implications for multicenter imaging trials. AJR Am J Roentgenol. 2009 Aug;193(2):419-24. doi: 10.2214/AJR.08.1995.

Reference Type BACKGROUND
PMID: 19620438 (View on PubMed)

National Lung Screening Trial Research Team; Aberle DR, Adams AM, Berg CD, Black WC, Clapp JD, Fagerstrom RM, Gareen IF, Gatsonis C, Marcus PM, Sicks JD. Reduced lung-cancer mortality with low-dose computed tomographic screening. N Engl J Med. 2011 Aug 4;365(5):395-409. doi: 10.1056/NEJMoa1102873. Epub 2011 Jun 29.

Reference Type RESULT
PMID: 21714641 (View on PubMed)

Singh S, Pinsky P, Fineberg NS, Gierada DS, Garg K, Sun Y, Nath PH. Evaluation of reader variability in the interpretation of follow-up CT scans at lung cancer screening. Radiology. 2011 Apr;259(1):263-70. doi: 10.1148/radiol.10101254. Epub 2011 Jan 19.

Reference Type RESULT
PMID: 21248232 (View on PubMed)

National Lung Screening Trial Research Team; Aberle DR, Adams AM, Berg CD, Clapp JD, Clingan KL, Gareen IF, Lynch DA, Marcus PM, Pinsky PF. Baseline characteristics of participants in the randomized national lung screening trial. J Natl Cancer Inst. 2010 Dec 1;102(23):1771-9. doi: 10.1093/jnci/djq434. Epub 2010 Nov 22.

Reference Type RESULT
PMID: 21119104 (View on PubMed)

Park ER, Ostroff JS, Rakowski W, Gareen IF, Diefenbach MA, Feibelmann S, Rigotti NA. Risk perceptions among participants undergoing lung cancer screening: baseline results from the National Lung Screening Trial. Ann Behav Med. 2009 Jun;37(3):268-79. doi: 10.1007/s12160-009-9112-9. Epub 2009 Aug 27.

Reference Type RESULT
PMID: 19711141 (View on PubMed)

Gierada DS, Pilgram TK, Ford M, Fagerstrom RM, Church TR, Nath H, Garg K, Strollo DC. Lung cancer: interobserver agreement on interpretation of pulmonary findings at low-dose CT screening. Radiology. 2008 Jan;246(1):265-72. doi: 10.1148/radiol.2461062097. Epub 2007 Nov 16.

Reference Type RESULT
PMID: 18024436 (View on PubMed)

Marcinkiewicz AM, Buchwald M, Shanbhag A, Bednarski BP, Killekar A, Miller RJH, Builoff V, Lemley M, Berman DS, Dey D, Slomka PJ. AI for Multistructure Incidental Findings and Mortality Prediction at Chest CT in Lung Cancer Screening. Radiology. 2024 Sep;312(3):e240541. doi: 10.1148/radiol.240541.

Reference Type DERIVED
PMID: 39287522 (View on PubMed)

Venkadesh KV, Aleef TA, Scholten ET, Saghir Z, Silva M, Sverzellati N, Pastorino U, van Ginneken B, Prokop M, Jacobs C. Prior CT Improves Deep Learning for Malignancy Risk Estimation of Screening-detected Pulmonary Nodules. Radiology. 2023 Aug;308(2):e223308. doi: 10.1148/radiol.223308.

Reference Type DERIVED
PMID: 37526548 (View on PubMed)

Xu K, Khan MS, Li TZ, Gao R, Terry JG, Huo Y, Lasko TA, Carr JJ, Maldonado F, Landman BA, Sandler KL. AI Body Composition in Lung Cancer Screening: Added Value Beyond Lung Cancer Detection. Radiology. 2023 Jul;308(1):e222937. doi: 10.1148/radiol.222937.

Reference Type DERIVED
PMID: 37489991 (View on PubMed)

Kinsey CM, Billatos E, Mori V, Tonelli B, Cole BF, Duan F, Marques H, de la Bruere I, Onieva J, San Jose Estepar R, Cleveland A, Idelkope D, Stevenson C, Bates JHT, Aberle D, Spira A, Washko G, San Jose Estepar R. A simple assessment of lung nodule location for reduction in unnecessary invasive procedures. J Thorac Dis. 2021 Jul;13(7):4207-4216. doi: 10.21037/jtd-20-3093.

Reference Type DERIVED
PMID: 34422349 (View on PubMed)

Tammemagi MC, Ten Haaf K, Toumazis I, Kong CY, Han SS, Jeon J, Commins J, Riley T, Meza R. Development and Validation of a Multivariable Lung Cancer Risk Prediction Model That Includes Low-Dose Computed Tomography Screening Results: A Secondary Analysis of Data From the National Lung Screening Trial. JAMA Netw Open. 2019 Mar 1;2(3):e190204. doi: 10.1001/jamanetworkopen.2019.0204.

Reference Type DERIVED
PMID: 30821827 (View on PubMed)

Wong JYY, Bassig BA, Seow WJ, Hu W, Ji BT, Blair A, Silverman DT, Lan Q. Lung cancer risk in welders and foundry workers with a history of heavy smoking in the USA: The National Lung Screening Trial. Occup Environ Med. 2017 Jun;74(6):440-448. doi: 10.1136/oemed-2016-104168. Epub 2017 Jan 9.

Reference Type DERIVED
PMID: 28069970 (View on PubMed)

Patz EF Jr, Greco E, Gatsonis C, Pinsky P, Kramer BS, Aberle DR. Lung cancer incidence and mortality in National Lung Screening Trial participants who underwent low-dose CT prevalence screening: a retrospective cohort analysis of a randomised, multicentre, diagnostic screening trial. Lancet Oncol. 2016 May;17(5):590-9. doi: 10.1016/S1470-2045(15)00621-X. Epub 2016 Mar 18.

Reference Type DERIVED
PMID: 27009070 (View on PubMed)

Marcus PM, Doria-Rose VP, Gareen IF, Brewer B, Clingan K, Keating K, Rosenbaum J, Rozjabek HM, Rathmell J, Sicks J, Miller AB. Did death certificates and a death review process agree on lung cancer cause of death in the National Lung Screening Trial? Clin Trials. 2016 Aug;13(4):434-8. doi: 10.1177/1740774516638345. Epub 2016 Mar 22.

Reference Type DERIVED
PMID: 27006427 (View on PubMed)

Tanner NT, Gebregziabher M, Hughes Halbert C, Payne E, Egede LE, Silvestri GA. Racial Differences in Outcomes within the National Lung Screening Trial. Implications for Widespread Implementation. Am J Respir Crit Care Med. 2015 Jul 15;192(2):200-8. doi: 10.1164/rccm.201502-0259OC.

Reference Type DERIVED
PMID: 25928649 (View on PubMed)

Clark MA, Gorelick JJ, Sicks JD, Park ER, Graham AL, Abrams DB, Gareen IF. The Relations Between False Positive and Negative Screens and Smoking Cessation and Relapse in the National Lung Screening Trial: Implications for Public Health. Nicotine Tob Res. 2016 Jan;18(1):17-24. doi: 10.1093/ntr/ntv037. Epub 2015 Mar 6.

Reference Type DERIVED
PMID: 25746779 (View on PubMed)

Black WC. Computed tomography screening for lung cancer in the National Lung Screening Trial: a cost-effectiveness analysis. J Thorac Imaging. 2015 Mar;30(2):79-87. doi: 10.1097/RTI.0000000000000136.

Reference Type DERIVED
PMID: 25635704 (View on PubMed)

Black WC, Gareen IF, Soneji SS, Sicks JD, Keeler EB, Aberle DR, Naeim A, Church TR, Silvestri GA, Gorelick J, Gatsonis C; National Lung Screening Trial Research Team. Cost-effectiveness of CT screening in the National Lung Screening Trial. N Engl J Med. 2014 Nov 6;371(19):1793-802. doi: 10.1056/NEJMoa1312547.

Reference Type DERIVED
PMID: 25372087 (View on PubMed)

Osinusi A, Kohli A, Marti MM, Nelson A, Zhang X, Meissner EG, Silk R, Townsend K, Pang PS, Subramanian GM, McHutchison JG, Fauci AS, Masur H, Kottilil S. Re-treatment of chronic hepatitis C virus genotype 1 infection after relapse: an open-label pilot study. Ann Intern Med. 2014 Nov 4;161(9):634-8. doi: 10.7326/M14-1211.

Reference Type DERIVED
PMID: 25364884 (View on PubMed)

Pinsky PF, Gierada DS, Hocking W, Patz EF Jr, Kramer BS. National Lung Screening Trial findings by age: Medicare-eligible versus under-65 population. Ann Intern Med. 2014 Nov 4;161(9):627-33. doi: 10.7326/M14-1484.

Reference Type DERIVED
PMID: 25199624 (View on PubMed)

Aberle DR, DeMello S, Berg CD, Black WC, Brewer B, Church TR, Clingan KL, Duan F, Fagerstrom RM, Gareen IF, Gatsonis CA, Gierada DS, Jain A, Jones GC, Mahon I, Marcus PM, Rathmell JM, Sicks J; National Lung Screening Trial Research Team. Results of the two incidence screenings in the National Lung Screening Trial. N Engl J Med. 2013 Sep 5;369(10):920-31. doi: 10.1056/NEJMoa1208962.

Reference Type DERIVED
PMID: 24004119 (View on PubMed)

National Lung Screening Trial Research Team; Church TR, Black WC, Aberle DR, Berg CD, Clingan KL, Duan F, Fagerstrom RM, Gareen IF, Gierada DS, Jones GC, Mahon I, Marcus PM, Sicks JD, Jain A, Baum S. Results of initial low-dose computed tomographic screening for lung cancer. N Engl J Med. 2013 May 23;368(21):1980-91. doi: 10.1056/NEJMoa1209120.

Reference Type DERIVED
PMID: 23697514 (View on PubMed)

Singh SP, Gierada DS, Pinsky P, Sanders C, Fineberg N, Sun Y, Lynch D, Nath H. Reader variability in identifying pulmonary nodules on chest radiographs from the national lung screening trial. J Thorac Imaging. 2012 Jul;27(4):249-54. doi: 10.1097/RTI.0b013e318256951e.

Reference Type DERIVED
PMID: 22627615 (View on PubMed)

Matsuoka S, Washko GR, Dransfield MT, Yamashiro T, San Jose Estepar R, Diaz A, Silverman EK, Patz S, Hatabu H. Quantitative CT measurement of cross-sectional area of small pulmonary vessel in COPD: correlations with emphysema and airflow limitation. Acad Radiol. 2010 Jan;17(1):93-9. doi: 10.1016/j.acra.2009.07.022. Epub 2009 Sep 30.

Reference Type DERIVED
PMID: 19796970 (View on PubMed)

Dransfield MT, Washko GR, Foreman MG, Estepar RS, Reilly J, Bailey WC. Gender differences in the severity of CT emphysema in COPD. Chest. 2007 Aug;132(2):464-70. doi: 10.1378/chest.07-0863. Epub 2007 Jun 15.

Reference Type DERIVED
PMID: 17573503 (View on PubMed)

Related Links

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http://www.cancer.gov/nlst

Web site for additional information

Other Identifiers

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U01CA079778

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U01CA080098

Identifier Type: NIH

Identifier Source: secondary_id

View Link

N1CN25476A-85-0-1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NIH/NCI

Identifier Type: OTHER

Identifier Source: secondary_id

CDR0000257938

Identifier Type: REGISTRY

Identifier Source: secondary_id

NCI-2012-02002

Identifier Type: -

Identifier Source: org_study_id

NCT00028808

Identifier Type: -

Identifier Source: nct_alias

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