CT Scans in Screening for Lung Cancer in Current and Former Smokers
Condition: Lung Cancer
MeSH terms: Lung Neoplasms
Study type: Observational

Summary: 
      RATIONALE: Screening tests, such as CT scanning, may help doctors find cancer cells early and
      plan better treatment for lung cancer.

      PURPOSE: This clinical trial is studying how well a lung cancer screening program using CT
      scanning works in current and former smokers.
    

Detailed description: 
      OBJECTIVES:

        -  To assess the feasibility of establishing a lung cancer screening program at the
           University of Nebraska Medical Center using CT scanning in normal study participants
           with at least a 30 pack-year history of cigarette smoking.

        -  To determine if it is possible to screen 100 high-risk individuals with high-resolution
           CT scanning for the presence of suspicious pulmonary nodules.

        -  To compare an effective and definitive work-up on all study participants with abnormal
           results within a defined time period from initial screening.

      OUTLINE: Study participants complete a detailed questionnaire (paper or electronic version)
      at baseline to provide personal and family information for inclusion in the registry
      database. Registry data includes information on participants' medical history, diet,
      lifestyle habits, and any past or current environmental exposures, as well as family history
      of cancer within each participant's extended family tree. An instruction manual on completing
      the questionnaires is provided to all study participants. The System Coordinator of the
      registry may provide additional information or clarification of the information provided in
      the questionnaires via a structured telephone interview. Data on study participants and their
      families is entered into the registry database either manually via the paper-based
      questionnaires or electronically via interactive Web-based questionnaires completed by
      participants through the registry website.

      Study participants also undergo a low-dose spiral CT scan at baseline. The resulting images
      are stored electronically and linked to the web-based participant registry. A radiologist
      then reviews the images, reports on any abnormalities, and renders an interpretation of the
      scan as being positive or negative for lung nodules. The radiologist's findings are then
      conveyed to the study participant's primary care physician and the following determinations
      are made: participants with negative findings (i.e., non-calcified solid nodules < 5 mm or
      non-solid nodules < 8 mm) are returned home and scheduled for a repeat CT scan in 1 year;
      participants with abnormalities not related to lung cancer are referred to their primary care
      physician for further action; and participants with positive findings undergo additional
      diagnostic work-up and treatment* as described below.

        -  Non-calcified solid nodules ≥ 5 and ≤ 15 mm: Study participants undergo a course of
           antibiotics followed by a high-resolution CT scan at 3 months. If the CT findings are
           stable, then participants return for a repeat CT scan in 1 year. If the nodules are
           growing, participants undergo additional diagnostic work-up, which may include biopsy of
           the positive nodule by their treating clinician.

        -  Non-solid nodule ≥ 8 mm: Study participants undergo treatment with an antibiotic, CT
           follow-up, and additional diagnostic work-up, if appropriate, as described previously.

        -  Non-calcified solid nodules > 15 mm: Study participants undergo work-up for a positive
           nodule, as above.

      NOTE: *Study participants who demonstrate radiographic abnormalities that are suspected to be
      of an inflammatory nature are given a 10-day course of a broad spectrum respiratory
      antibiotic, preferably a fluoroquinolone, by the participating physician who enrolled that
      participant into the study.

      Study participants with negative CT findings undergo CT screening once yearly for up to five
      years, in the absence of a diagnosed malignancy. Diagnostic work-up for repeat CT scans is as
      follows:

        -  Any new lesion: Study participants undergo a work-up as previously described for
           non-calcified solid or non-solid nodules.

        -  Any non-calcified nodule that was present earlier and grew in size:

             -  Growth < 3 mm: Study participants undergo a repeat CT scan in 6 months. If there is
                further growth, participants are worked-up for a positive nodule, or, if the scan
                is stable, participants undergo a repeat scan 1 year after the most recent scan.

             -  Growth between 3 mm and 5 mm: Study participants undergo a high-resolution CT scan
                in 3 months and further diagnostic work-up for a positive nodule, as described
                previously, if there is growth. If there is complete resolution of the nodule,
                participants undergo repeat screening CT scan in 1 year after the most recent scan.
                If there is partial resolution of the nodule, another high-resolution CT scan is
                performed 3 months later. Participants with a stable nodule undergo repeat
                screening CT scan 1 year after the most recent scan.

             -  Growth ≥ 5 mm: Study participants receive a course of an antibiotic and undergo
                high-resolution CT scanning after 1 month. The following assessments are also
                performed: work-up for a positive nodule, if there is further growth; repeat
                screening CT scan in 1 year after the most recent scan, if there is complete
                resolution of the nodule; high-resolution CT scan in 3 months, if there is partial
                resolution of the nodule; and repeat screening CT scan 1 year after the most recent
                scan, if the nodule is stable.

      All study participants undergo blood sample collection at baseline for use in future studies.
      Additional blood samples are obtained from study participants with positive CT scans for
      future research on smoking-related diseases. Tissue samples obtained from diagnostic biopsy
      or surgical specimens are also stored for future research.

      Once a malignancy is diagnosed and a definitive intervention is performed, study participants
      are followed periodically thereafter.
    

Intervention name(s): questionnaire administration; computed tomography; evaluation of cancer risk factors; study of high risk factors
Intervention type(s): Other; Procedure; Procedure; Procedure
Intervention description(s): Subjects will be asked to complete an additional detailed questionnaire regarding personal information about themselves, their medical history, their diet and lifestyle habits, any past or current environmental exposures and to re-create their family tree for any cancers that have occurred in any of their family members.; The baseline and repeat screening CT scans will be performed with a multi-slice helical CT scanner (8 or more rows), at a low-dose setting (120kVp, 40-80mA, slice thickness of 1.25 mm or less). In a single breath-hold, contiguous slices from the thoracic inlet to the adrenal glands will be obtained. Contrast material will not be used. Multi-slice scanners will be used because they provide higher-resolution images. Diagnostic studies, including HRCT will be performed with a multi-slice helical CT at diagnostic settings (120kVp, 140-300mA, slice thickness of 1.25 or less) with the nodule retrospectively reconstructed at a 15cm field of view.; When the CT scan at baseline does not lead to the diagnosis of malignancy, repeat screening will be scheduled 12 months later. If the initial scan led to further evaluation, the repeat scan will be performed 12 months after the most recent scan. The subjects will be allowed to add relevant health information to their record in the web-based database as it develops. Similarly, when in the first repeat screening malignancy is not diagnosed; the second repeat screening will be scheduled 12 months later for a total period of 5 years.; When the CT scan at baseline does not lead to the diagnosis of malignancy, repeat screening will be scheduled 12 months later. If the initial scan led to further evaluation, the repeat scan will be performed 12 months after the most recent scan. The subjects will be allowed to add relevant health information to their record in the web-based database as it develops. Similarly, when in the first repeat screening malignancy is not diagnosed; the second repeat screening will be scheduled 12 months later for a total period of 5 years.
Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Normal subjects with at least a 30 pack-year history of cigarette smoking.
      
Biospecimen description: 
      Collection of blood sample: At the time of the initial CT scan, every subject will be asked
      to donate a small blood sample, approximately 10 ml in a yellow EDTA tube (less than 1
      tablespoon) from their arm by standard blood drawing techniques, for storage for use in
      future studies. The blood sample will be number coded, and serum from the blood sample will
      be stored frozen and held at UNMC for future studies. All studies will be proposed in future
      IRB submissions.
    
Keywords: lung cancer