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Programs & Resources

Early Detection Research Group (EDRG)

Key Programs

Lung Screening Feasibility Study (LSS)
LSS Presentation at May 2001 ARRS Meeting
Presentation at the American Roentgen Ray Society Meeting

May 2001 presentation at the annual meeting of the American Roentgen Ray Society: The Lung Screening Study: A Randomized Study of Spiral CT

Richard Fagerstrom, PhD
Division of Cancer Prevention
National Cancer Institute

Motivation for LSS

  • Uncertainty about efficacy of spiral CT in reducing lung cancer mortality
  • Concern about potential for substantial overdiagnosis
  • Questions regarding feasibility
    • Background use of spiral CT
    • Receptiveness to randomization
  • Development of a small-scale RCT as a special study of the PLCO Trial to determine feasibility (Phase I of LSS)

PLCO Cancer Screening Trial

  • On-going RCT screening for Prostate, Lung, Colorectal and Ovarian cancers
  • For L, annual CXR vs. usual care
  • 153,000 participants (men and women)
  • Sized to detect a 20% reduction in lung cancer mortality at 13 years of follow-up

Critical Information from Phase I of LSS

  • Whether eligible participants can be enrolled at a suitable rate
  • Medical burden of diagnostic work-up following a positive spiral CT screen
  • Estimate of compliance of participants

For further information, consult LSS Manual of Operations and Procedures.

Eligibility Criteria

  • Age 55 - 74 at enrollment
  • Current smoker or former smoker who quit within 10 years of enrollment
  • Cigarette smoking history of at least 30 pack-years

Exclusion Criteria

  • Spiral CT of lungs or chest in past 2 yrs
  • Personal history of lung cancer
  • Current treatment for cancer other than non-melanoma skin cancer
  • Previous removal of any portion of lungs
  • Participation in cancer screening trial (including PLCO) or cancer primary prevention trial

Phase I LSS Screening Centers

  • Georgetown University Medical Center
  • Henry Ford Health System
  • University of Minnesota School of Public Health
  • Washington University School of Medicine
  • Marshfield Medical Research and Education Foundation
  • University of Alabama at Birmingham

Other Key Players

  • NCI - responsible for design, analysis, and oversight of all aspects of study
  • Westat - coordinating center

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Steps to Enrollment

  • Potential participants receive recruitment materials from mass mailings
    • Introductory letter
    • Information on eligibility
    • FAQ sheet
    • Reply card to indicate interest
  • Screening center contacts interested potential participant and administers Eligibility Screener
    • Informed consent is obtained in one of two ways
    • Consent form mailed and returned
    • Consent form signed by participant in orientation session at screening center
  • Eligible individuals are randomized to either spiral CT arm or chest x-ray arm

Recruitment Statistics
Pieces mailed653,417 
Responses12,2701.9%
Eligibles4,8280.7%
Ineligibles due to previous CT148< 2.0%
Randomized3,4140.5 %

Randomization

  • 3414 participants randomized
    • 1707 chest x-ray
    • 1707 spiral CT
  • Began on Sept. 5, 2000 and concluded on Nov. 15, 2000
  • Occurred via Internet access to secure Web site at coordinating center
  • Stratified by gender and age group within each center

Screening

  • Participants randomized to spiral CT arm received 1 CT scan
  • Participants randomized to CXR arm received 1 PA x-ray
  • Board-certified radiologists reviewed images
  • Results recorded on forms developed for LSS
  • Results sent by mail to participants and primary care physicians within 3 weeks of exam
  • Concluded on Jan. 31, 2001

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Equipment Specifications - CT

  • 120 - 140 kVp
  • 60 mA
  • 1 sec scan time
  • 5 mm collimation
  • Pitch of 2 or equivalent
  • Lung windows (std width 1500, std level -650)
  • Mediastinal windows (std width 400 - 500, std level 10 - 30)

Equipment Specifications - CXR

  • 110 - 150 kVp
  • Tube-to-receiver distance 6 - 10 ft
  • Wide latitude film
  • 12 to 1 standard grid or higher
  • Thoravision, CR systems, and conventional systems allowed

Compliance with Screening
Total screened321095.4%
Screened by CT162496.4%
Screened by CXR158694.3%

Positive Screens

  • Non-calcified nodules / masses > 3 mm
  • Spiculated non-calcified nodules / masses < 4 mm
  • Focal parenchymal opacification (consolidation or ground-glass attenuation)
  • Endobronchial lesions
  • Other (e.g., large hilar masses, large mediastinal masses, bony or pleural masses)

Quality Control of Exam Interpretations

  • At each center, random sample of 20 SCTs reinterpreted by second (QA) radiologist
  • At each center, random sample of 20 CXRs reinterpreted by second (QA) radiologist
  • QA radiologists blinded to results of initial interpretation
  • "Worst case" result reported to participant

Follow-up to Positive Screens

  • Participants notified by phone or, if unreachable by phone, certified mail
  • Physicians received results by phone, fax, or certified mail
  • Letters to participants and physicians strongly urge diagnostic follow-up
  • Participant contacted within 4 weeks of positive screen to determine whether follow-up with physician has been scheduled
  • No formal recommendations for diagnostic follow-up

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Diagnostic Evaluation Procedures

  • ~ 4 wks after follow-up appointment confirmed, request for medical records made
  • At each screening center, Certified Medical Record Abstractors review medical records and abstract diagnostic information onto Diagnostic Evaluation Forms
  • Random sample of 10% of participants with collected medical records have records re-abstracted at coordinating center

Assessment of Post-randomization Contamination

  • Refers to assessment of extent to which participants receive screening exams outside of study
  • Measured by Health Assessment Questionnaire (HAQ)
  • Each center administers HAQ to 40 participants having negative CXR with no abnormalities
  • Each center administers HAQ to 20 participants having negative SCT with no abnormalities

Accomplishments of LSS Phase I

  • Phase I of LSS has shown:
    • Spiral CT use is not pervasive
    • Receptiveness to randomization
    • High compliance to screening exams
  • Rapid development of:
    • Protocol
    • Manual of Operations and Procedures

Future of LSS

Upcoming LSS Activities
May 2001Complete receipt of diagnostic evaluation forms
Begin assessment of post-randomization contamination
June 2001Complete assessment of post-randomization contamination
Begin data analysis
August 2001Complete data analysis
Prepare study report

Considerations for Phase II of LSS

  • Expansion to over 15,000 participants
  • Addition of 2 annual screens for total of 3 screens
  • Lung cancer mortality endpoint
  • Collaboration with ACRIN trial

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