National Lung Screening Trial (NLST) Screening

This study has been completed.
Sponsor:
Collaborator:
American College of Radiology Imaging Network
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00047385
First received: October 3, 2002
Last updated: May 2, 2014
Last verified: October 2012
Results First Received: May 30, 2012  
Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Screening
Condition: Lung Cancer
Interventions: Device: low-dose helical computed tomography
Device: chest radiography

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Recruitment was from August 2002 through April 2004 at 33 NLST sites.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Participants signed a study informed consent prior to being randomized to a study arm.

Reporting Groups
  Description
Low-Dose CT Participants undergo low-dose helical CT examination.
Chest X-ray Participants undergo chest x-ray examination.

Participant Flow:   Overall Study
    Low-Dose CT     Chest X-ray  
STARTED     26722     26732  
COMPLETED     26455 [1]   26232  
NOT COMPLETED     267     500  
Death before any screening                 2                 5  
Lung Cancer diagnosed before screening                 5                 3  
Eligible for screening but had no screen                 260                 492  
[1] Had at least one screening exam.



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Low-Dose CT Participants undergo low-dose helical CT examination.
Chest X-ray Participants undergo chest x-ray examination.
Total Total of all reporting groups

Baseline Measures
    Low-Dose CT     Chest X-ray     Total  
Number of Participants  
[units: participants]
  26722     26732     53454  
Age  
[units: participants]
     
<=18 years     0     0     0  
Between 18 and 65 years     19612     19622     39234  
>=65 years     7110     7110     14220  
Age  
[units: years]
Mean ± Standard Deviation
  61.4  ± 5.0     61.4  ± 5.0     61.4  ± 5.0  
Gender  
[units: participants]
     
Female     10952     10970     21922  
Male     15770     15762     31532  
Region of Enrollment  
[units: participants]
     
United States     26,722     26,732     53454  



  Outcome Measures
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1.  Primary:   Lung Cancer Deaths   [ Time Frame: All events through December 31, 2009; median follow-up 6.5 years. ]

Measure Type Primary
Measure Title Lung Cancer Deaths
Measure Description Lung cancer deaths confirmed in participants by Endpoint Verification if available, otherwise by death certificate.
Time Frame All events through December 31, 2009; median follow-up 6.5 years.  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All participants randomized were analyzed. An intention-to-treat analysis was performed.

Reporting Groups
  Description
LDCT Screening Participants randomized to receive three annual low-dose helical CT exams of the chest.
CXR Screening Participants randomized to receive three annual chest radiographs.

Measured Values
    LDCT Screening     CXR Screening  
Number of Participants Analyzed  
[units: participants]
  26722     26732  
Lung Cancer Deaths  
[units: Participants]
  356     443  


Statistical Analysis 1 for Lung Cancer Deaths
Groups [1] All groups
Method [2] Weighted log-rank (details below)
P Value [3] 0.004
Hazard Ratio (HR) [4] 0.800
95% Confidence Interval ( 0.733 to 0.932 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
 

Alternative hypothesis: LDCT screening reduces lung cancer mortality relative to chest x-ray.

Power: 90% for a 20% reduction in lung cancer mortality.

[2] Other relevant method information, such as adjustments or degrees of freedom:
  Weights in weighted log-rank statistic increased linearly from zero at randomization to full weight at 4 years and thereafter.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  P-value is adjusted for multiple comparisons.
[4] Other relevant estimation information:
  No text entered.



2.  Secondary:   Deaths From All Causes in All Randomized Participants.   [ Time Frame: All events through December 31, 2009; median follow-up 6.5 years. ]

Measure Type Secondary
Measure Title Deaths From All Causes in All Randomized Participants.
Measure Description Deaths from all causes were compared between the low-dose CT group and the chest radiography group among all randomized participants.
Time Frame All events through December 31, 2009; median follow-up 6.5 years.  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All participants randomized were analyzed. An intention-to-treat analysis was performed.

Reporting Groups
  Description
LDCT Screening Participants randomized to receive three annual low-dose helical CT exams of the chest.
CXR Screening Participants randomized to receive three annual chest radiographs.

Measured Values
    LDCT Screening     CXR Screening  
Number of Participants Analyzed  
[units: participants]
  26722     26732  
Deaths From All Causes in All Randomized Participants.  
[units: Participants]
  1877     2000  


Statistical Analysis 1 for Deaths From All Causes in All Randomized Participants.
Groups [1] All groups
Method [2] Weighted log-rank (details below)
P Value [3] 0.02
Hazard Ratio (HR) [4] 0.933
95% Confidence Interval ( 0.864 to 0.988 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Alternative hypothesis: LDCT screening reduced all-cause mortality relative to chest x-ray.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  Weights in weighted log-rank statistic increased linearly from zero at randomization to full weight at 4 years and thereafter.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No adjustment for multiple comparisons. Only one analysis performed.
[4] Other relevant estimation information:
  No text entered.



3.  Secondary:   Lung Cancer Diagnoses   [ Time Frame: All events through December 31, 2009; median follow-up 6.5 years ]

Measure Type Secondary
Measure Title Lung Cancer Diagnoses
Measure Description Lung cancer diagnoses confirmed by medical record abstraction.
Time Frame All events through December 31, 2009; median follow-up 6.5 years  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All participants randomized were analyzed. An intention-to-treat analysis was performed.

Reporting Groups
  Description
LDCT Screening Participants randomized to receive three annual low-dose helical CT exams of the chest.
CXR Screening Participants randomized to receive three annual chest radiographs.

Measured Values
    LDCT Screening     CXR Screening  
Number of Participants Analyzed  
[units: participants]
  26722     26732  
Lung Cancer Diagnoses  
[units: Participants]
  1060     941  


Statistical Analysis 1 for Lung Cancer Diagnoses
Groups [1] All groups
Hazard Ratio (HR) [2] 1.13
95% Confidence Interval ( 1.03 to 1.23 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant estimation information:
  Denominator: LDCT Group Numerator: CXR Group



4.  Secondary:   Complications of Diagnostic Evaluation Following a Positive Screening Test.   [ Time Frame: One year from screening examination ]

Measure Type Secondary
Measure Title Complications of Diagnostic Evaluation Following a Positive Screening Test.
Measure Description Number of participants who experienced complications during diagnostic work-up of a screening CT or CXR that was suspicious for lung cancer.
Time Frame One year from screening examination  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The units analyzed were positive screening exams with documented diagnostic follow-up. If participant received 3 positive screens with documented follow-up after each one, he/she would be counted 3 times in the number of units analyzed.

Reporting Groups
  Description
LDCT Screening Participants randomized to receive three annual low-dose helical CT exams of the chest.
CXR Screening Participants randomized to receive three annual chest radiographs.

Measured Values
    LDCT Screening     CXR Screening  
Number of Participants Analyzed  
[units: participants]
  26722     26732  
Number of Positive Screens with Follow-up Analyzed  
[units: Positive Screens with Follow-up]
  17702     4953  
Complications of Diagnostic Evaluation Following a Positive Screening Test.  
[units: Pos. screens w/ complications]
  245     81  

No statistical analysis provided for Complications of Diagnostic Evaluation Following a Positive Screening Test.



5.  Secondary:   T0 (Baseline) Screening Results   [ Time Frame: T0 (at study entry) ]

Measure Type Secondary
Measure Title T0 (Baseline) Screening Results
Measure Description Results of radiologist's interpretation of images from LDCT or CXR screening exam at T0.
Time Frame T0 (at study entry)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All participants randomized were analyzed.

Reporting Groups
  Description
LDCT Screening Participants randomized to receive three annual low-dose helical CT exams of the chest.
CXR Screening Participants randomized to receive three annual chest radiographs.

Measured Values
    LDCT Screening     CXR Screening  
Number of Participants Analyzed  
[units: participants]
  26722     26732  
T0 (Baseline) Screening Results  
[units: Participants]
   
Positive     7191     2387  
Significant abnor. not suspicious for lung cancer     2695     785  
No, or minor abnormality     16423     22863  
Eligible but not screened     406     689  
Not eligible for screen     7     8  

No statistical analysis provided for T0 (Baseline) Screening Results



6.  Secondary:   T1 Screening Results   [ Time Frame: T1 (one year after entry) ]

Measure Type Secondary
Measure Title T1 Screening Results
Measure Description Results of radiologist's interpretation of images from LDCT or CXR screening exam at T1. Includes a comparison with images from T0 screen.
Time Frame T1 (one year after entry)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All participants randomized were analyzed

Reporting Groups
  Description
LDCT Screening Participants randomized to receive three annual low-dose helical CT exams of the chest.
CXR Screening Participants randomized to receive three annual chest radiographs.

Measured Values
    LDCT Screening     CXR Screening  
Number of Participants Analyzed  
[units: participants]
  26722     26732  
T1 Screening Results  
[units: Participants]
   
Positive     6901     1482  
Significant abnor. not suspicious for lung cancer     1519     429  
No, or minor abnormality     16295     22178  
Eligible but not screened     1570     2321  
Not eligible for screen     437     322  

No statistical analysis provided for T1 Screening Results



7.  Secondary:   T2 Screening Results   [ Time Frame: T2 (two years after entry) ]

Measure Type Secondary
Measure Title T2 Screening Results
Measure Description Results of radiologist's interpretation of images from LDCT or CXR screening exam at T2. Includes a comparison with images from T0 and T1 screens.
Time Frame T2 (two years after entry)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All participants randomized were analyzed

Reporting Groups
  Description
LDCT Screening Participants randomized to receive three annual low-dose helical CT exams of the chest.
CXR Screening Participants randomized to receive three annual chest radiographs.

Measured Values
    LDCT Screening     CXR Screening  
Number of Participants Analyzed  
[units: participants]
  26722     26732  
T2 Screening Results  
[units: Participants]
   
Positive     4054     1174  
Significant abnor. not suspicious for lung cancer     1408     361  
No, or minor abnormality     18640     21811  
Eligible but not screened     1840     2764  
Not eligible for screen     780     622  

No statistical analysis provided for T2 Screening Results




  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
NLST utilized institutions with special expertise. The "healthy volunteer" effect may apply. Scanners are now more technologically advanced. Ongoing LDCT screening may reduce the rate of lung cancer deaths more than three rounds done in NLST.


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