Nashville Early Diagnosis Lung Cancer Project

• To identify and validate new biomarkers that are associated with lung cancer risk factors and premalignant lesions. [ Time Frame: at baseline and yearly to year 5 ] [ Designated as safety issue: No ]
  Blood, sputum, urine, nasal washings, buccal epithelium, endobronchial tissue, and bronchioalveolar washings are examined for presently unknown biomarkers that occur in patients with lung cancer and in patients who do not have lung cancer but who may be at further increased risk of lung cancer.
• To assess changes in prevalence and grade of pre-invasive lesions in this cohort. [ Time Frame: baseline, at years 2 and 5 (abnormal tissue will re-examined every 6 months) ] [ Designated as safety issue: No ]
  Endobronchial tissue will be examined under a microscope for presence of changes in the cells that are abnormal but which are not invasive cancer.
• To describe patients eligible for future chemoprevention clinical trials. [ Time Frame: at year 5 ] [ Designated as safety issue: No ]
  Inclusion criteria for those patients who, based on their biomarker profile, are at increased risk of invasive lung cancer and who may benefit from clinical trials that will study chemoprevention strategies for lung cancer.

• To identify and validate new biomarkers that are associated with lung cancer risk factors and premalignant lesions. [ Time Frame: at year 5 ] [ Designated as safety issue: No ]
• To assess changes in prevalence and grade of preinvasive lesions in this cohort. [ Time Frame: at year 5 ] [ Designated as safety issue: No ]
• To describe this high-risk cohort and to identify the patients eligible for future clinical trials. [ Time Frame: at year 5 ] [ Designated as safety issue: No ]

This screening study will address the lack of molecular strategies for the early detection of lung cancer and integrate those with epidemiological and imaging strategies.

The hypothesis is that the repeated measure of biomarkers of risk obtained from the molecular analysis of biological specimens including those from bronchoscopy (bronchial brushings and biopsies) may contribute to the refinement of high-risk populations and allow an earlier clinical diagnosis.

The goal of the investigators study is to provide screening for lung cancer in a high-risk population. In this prospective cohort it will be tested whether repeated measure of biomarkers of risk allows early detection of lung cancer.

It is proposed to test the hypotheses in a screening study of high risk individuals (characterized by an established prediction rule). The expected prevalence of lung cancer in this high risk group is estimated to be 2% per year. All individuals benefit from clinic visit, low-dose Chest CT, spirometry and auto-fluorescence bronchoscopy at baseline, Chest CT, follow-up doctor visit, and auto-fluorescence bronchoscopy at least at year 2 and 5.

By physician referral, medical professional referral or self-referral

• Procedure: Sputum sample
  This is a collection of sputum (mucous) you cough up. Three morning samples will be collected at one time. Sputum will be collected at baseline, year 1, year 2 and year 5.
• Procedure: Pulmonary function tests
  A series of different breathing tests designed to measure lung function and to determine the presence or absence of chronic obstructive pulmonary disease will be performed at baseline.
• Radiation: Computerized tomography (CT) scan of the chest
  A CT scan uses x-rays to take detailed pictures of the chest. Performed at baseline, year 2 and year 5. If nodules are present, CT scans will be performed every 3 months for the first year of the study.
• Other: Buccal epithelium collection
  Collect cells from the inside of the cheek. Samples will be collected at baseline and yearly to year 5.
• Procedure: Nasal brushings
  A cytobrush is used to remove cells on the surface of the inside of the nose. Samples will be collected at baseline and yearly to year 5.
• Procedure: Bronchoscopy
  A flexible tube with a light and a camera will be inserted through the nose or mouth, and into the lungs to look at the airway. Bronchial tissue will be obtained.
• Procedure: Bronchoalveolar lavage
  During a bronchoscopy, a flexible tube with a light and a camera is passed through the mouth or nose into the lungs and fluid is squirted into a small part of the lung and collected for examination. Bronchoscopies will be performed at baseline and at year 5.
• Procedure: Blood sample collection
  A venous blood sample will be collected for testing of biomarkers and other relevant tests. Blood will be taken at baseline and yearly to year 5.
• Procedure: Urine sample
  Urine will be collected for routine urine tests at baseline and yearly to year 5.
• Procedure: Questionnaire-data collection
  A questionnaire about the patient's health, medical, and smoking history. Administered at baseline and yearly to year 5. Data will be taken from patient interviews and from the medical record.

Inclusion Criteria:

• 10 year Bach risk model >2.5%, (55 - 74 years of age, Current smoker with at least 25 years of smoking, at least 10 cigarettes/day, or Former smoker at least 20 pack-per-year (PPK) history of cigarette smoking total, who quit 20 years ago or less)
• Plus one of the following:
• Forced expiratory volume in 1 second (FEV1) <70% predicted
• Or at least one first-degree relative with a diagnosis of lung cancer
• Or emphysema , moderate or severe
• Or history of resected lung cancer with no evidence of disease at 2 year follow up.
• Or history of treated head/neck and/or esophageal cancer with no evidence of disease at 1 year post intervention.

Exclusion Criteria:

• History of diagnosis/treatment of lung cancer in the past 2 years or of head/neck or esophageal cancer in the last 1 year.
• Inability to provide informed consent
• Chest CT within the last 12 months