Welcome to the National Lung Screening Trial at the University of Colorado Denver, Anschutz Medical Campus
NLST Protocol Summary
To download this document, click here.
- Background
- Purpose
- Methods
- Who Can Participate?
- Number and Distribution of Subjects
- Estimated Duration of the Study
Background:
Lung cancer is the leading cause of cancer-related death in the United States. It is estimated that there were 157,000 deaths due to lung cancer in 2000. Although the most straightforward way to reduce lung cancer risk is to stop smoking, smoking cessation programs have had limited success. Furthermore, an elevation in lung cancer risk is believed to remain, at least in the short-term, for persons who are recent quitters. Because symptoms of lung cancer often do not appear before the disease is advanced, secondary prevention is an appealing option.
Attempts to evaluate lung cancer screening modalities began over 50 years ago, with the majority of studies observing no significant impact of screening. Since then, other possible lung cancer screening modalities have been suggested. The most promising modality is a modified version of helical computed tomography. Helical computed tomography, commonly referred to as "spiral CT," is an established lung cancer diagnostic tool that can generate, with excellent resolution, three-dimensional images of lung cancer lesions, including very small lesions.
The most extensive results regarding the usefulness of low-radiation-dose spiral CT as a lung cancer screening modality come from the Early Lung Cancer Action Project (ELCAP). The findings of ELCAP are noteworthy, but limitations of the study, including the lack of a randomized comparison group and the resulting inability to examine a possible reduction in lung cancer mortality, leave important questions regarding the usefulness of low-dose spiral CT unanswered. Most importantly, it is unknown if all lesions detected by spiral CT in the ELCAP population had any clinical relevance; that is, it is uncertain whether every lesion would have been diagnosed in the absence of screening. Also, the identification of more lesions on spiral CT as compared with chest x-ray in ELCAP does not guarantee that screening spiral CT saves lives.
The NCI's Division of Cancer Prevention (DCP) recognized the need for further study of screening spiral CT prior to establishment of mass screening programs. A feasibility was conducted which was highly successful and has assuaged concerns regarding the feasibility of a larger trial.
Purpose:
To assess the usefulness of annual lung cancer screening with spiral CT, the National Cancer Institute (NCI) in collaboration with the American College of Radiology Imaging Network (ACRIN) is conducting the National Lung Screening Trial (NLST), a randomized controlled trial (RCT). The primary objective of the NLST is to determine whether screening with spiral CT, as compared with chest x-ray, reduces lung cancer mortality among high-risk individuals.
All participants will receive three annual screens as well as follow-up from date of enrollment. Diagnostic evaluation information will be obtained for participants with positive screening examination results and/or reported cancers. Treatment information will be obtained for participants with a reported lung cancer diagnosis. In addition, tumor tissue slides will be collected from participants diagnosed with lung cancer.
Methods:
Recruitment:
NLST Screening Centers (SCs) will primarily use mass mailings in an attempt to enroll participants. Recruitment will be initiated at all SC's with a press release from the NCI announcing the trial. Local coverage of the press release will serve as the first line of recruitment, with mass mailings targeting smokers and then to the general population serving as the main source of recruitment. Other potential recruitment methods include posters in medical facilities, recommendations from clinical practitioners, and advertisements in newspapers or magazines. The information package to be either mass-mailed or supplied to interested persons will contain a cover letter, a fact sheet, a toll-free phone number to call if the potential participant has questions, and a reply card for the participant to return if he or she is interested in participating.
Consent Procedure:
Eligibility will be determined over the phone. Eligible participants will be invited to attend a recruitment seminar where the study will be presented by an NLST staff member. The consent form will be reviewed and participants will be given an opportunity to ask questions about the study. Eligible participants who are unwilling or unable to attend a recruitment seminar will have the option to receive the consent form via mail.
Randomization:
Randomization will be stratified by gender and age group within each Screening Center. Randomization procedures will result in roughly equal numbers of participants in the study arms (spiral CT and chest x-ray).
Intervention:
Participants randomized to the spiral CT arm receive three spiral CT scans spaced 1 year apart; participants randomized to the chest x-ray arm receive three PA chest x-rays according to the same schedule. The initial screening tests are to occur within 1 month of randomization. Board certified radiologists review the chest x-rays and the CT scans; findings are noted on standardized chest x-ray and spiral CT forms.
A medical history questionnaire will be administered to all study participants. Test results are sent by mail to participants and their health care providers within 3 weeks of exams. If a screening test is suspicious for lung cancer (positive), the SC staff also notifies the participant by telephone. If the participant is unavailable by telephone, results are sent via certified mail. Positive screening results are transmitted to health care providers either via telephone, fax, or certified mail. The letters to the participant and his/her health care provider accompanying the screening results report encourage appropriate diagnostic work-up. If the participant does not have a health care provider, s/he is offered a list from which to choose a referral health care provider.
Background information regarding appropriate work-up options for the spiral CT screen that are consistent with evolving opinion among experts is provided by the SCs to health care providers who request such information, but specific recommendations on work-up are not made. When it has been determined that diagnostic work-up has been declined by a participant, this fact shall be recorded and dated, and any supporting information should be included in the participant's file.
Who Can Participate?
Eligibility Criteria:
- Ages 55-74 on date of randomization
- Current smoker or former smoker who has quit within 15 years of randomization; and
- A history of long-time and/or heavy cigarette smoking.
Exclusion Criteria:
- Spiral CT exam of the lungs or chest in the 18 months prior to randomization;
- Prior diagnosis of lung cancer;
- Currently undergoing treatment for any cancer other than non-melanoma skin cancer;
- Previous history of surgical removal of any portion of the lung, excluding biopsy;
- Unwilling or unable to sign informed consent;
- Participation in another cancer screening trial, including PLCO;
- Participation in a primary cancer prevention trial, other than smoking cessation;
- Inability to lie flat on the back with arms raised over the head for up to thirty minutes;
- Metallic implant or metallic device in the chest or back (pacemakers or Harringtron fixation rods, etc.)
- Requirement for home oxygen supplementation;
- Present symptoms suggestive of current lung cancer, including unexplained weight loss or over 15 pounds within the past 12 months, and/or hemoptysis, and
- Individuals within 12 weeks of a pneumonia or acute respiratory infection treated with antibiotics by a physician.
- Morbid Obesity.
Number and Distribution of Subjects:
4500 eligible men and women will be enrolled at the UCHSC site over 2 years. Nationwide 50,000 participants will be enrolled in the trial. Participants will be randomized to the spiral CT or Chest X-ray arms in equal numbers and will be stratified by age and gender.
Estimated Duration of the Study:
July 1, 2002-June 30, 2009