Meeting Abstracts
» Lung Cancer Screening Trials and Early Detection / Diagnosis

James R. Jett, M.D., Mayo Clinic, Rochester, MN

The Mayo Clinic Spiral CT Screening Trial for lung cancer has been in existence since 1999. As part of the yearly spiral CT examination, we also collected a blood sample for normal DNA and serum that had been stored for future genetic and proteomics research. Additionally, participants were asked to provide a yearly-induced sputum sample and three-day pooled sputum sample that was mailed in. These sputum samples from patients with a subsequent diagnosis of lung cancer (screen detected) and match controls are being shared with the University of Colorado and Lovelace Research Institute researchers to test for methylation of specific genes such as p16, MGMT, RASSFIA, and H-cadherin. A preliminary report suggests that the presence of any methylation marker increases the odds ratio of developing lung cancer by four-fold. Additionally, the presence of severe atypia markedly increases the risk of subsequent lung cancer. Further studies are in progress to try and determine early markers of lung cancer in the sputum of high-risk subjects.

In 2003, we will obtain sputum samples on approximately 800 subjects in the spiral CT screening trial. These sputum samples will be graded for the degree of atypia according to the WHO grading scale and will be judged as being normal or mild, moderate or severe atypia or carcinoma in situ. Patients judged as having moderate or severe atypia or CIS will be offered bronchoscopy. Auto-fluorescence bronchoscopy will also be performed simultaneously and abnormal areas biopsied. These patients will be offered the opportunity to participate in a lung cancer chemoprevention trial.

Many participants in the spiral CT scan screening trial at Mayo have been found to have small non-calcified nodules (NCN). In the first year, 51% of our 1520 participants had NCN. We have now followed up those nodules for at least two years and have good data available on the rate of malignancy based on size. This data will be reviewed. To date, 8 participants have undergone thoracotomy for benign disease. Accordingly, we are now including a PET scan evaluation, just before proceeding to thoracotomy. A negative PET scan will result in the patient being followed longer. Further growth of the nodule will result in biopsy or an operation. Participants with a positive PET scan proceed to thoracotomy. The data on the sensitivity and specificity of PET in this situation will be presented.

Additionally, we are conducting a study on use of FISH (fluorescence in situ hybridization) analysis of cytologic specimens from patients undergoing bronchoscopy for a chest x-ray abnormality that might be lung cancer. We are comparing FISH versus conventional cytology for diagnosing lung cancer. Sensitivity and specificity data will be presented. It appears that FISH is significantly more sensitive at diagnosing lung cancer than standard cytology from bronchial brushings.

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