SURVEILLANCE AND CHEMOPREVENTION FOR SECOND LUNG CANCERS

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One of the major obstacles in treating lung cancer is its late presentation, when the options for treatment are primarily palliative. The lack of effective therapy underscores the urgency to reevaluate current management strategies. With recent advances in diagnostic technology and understanding of tumor biology, it is time to revisit the potential impact of early lung cancer detection and to explore new frontiers of treatment such as chemoprevention. Previous studies have shown that patients who have had curative surgical treatment for their lung cancer have a high risk of developing second primary lung cancer (SPLC). Yet, there are no specific guidelines for monitoring or intervention. Therefore, the objectives of this pilot proposal are to 1) evaluate the feasibility and impact of combined sputum analysis (cytology and immunostaining), fluorescence (LIFE) bronchoscopy and spiral CT as surveillance strategies for SPLC and/or recurrence after curative surgical treatment, 2) to evaluate the efficacy and feasibility of cyclooxygenase-2 (Cox-2) inhibition for chemoprevention of second primary tumors or recurrent neoplastic lesions, and 3) to evaluate the pattern of Cox-2 expression in this patient cohort to provide biologic insight into the role of cox-2 inhibitors. To achieve these objectives, 120 individuals with a history of stage I non-small cell lung cancer (NSCLC), who have had curative resection, will be recruited. All subjects will be followed with serial tests including sputum analysis, LIFE bronchoscopy and spiral CT according to a pre-determined algorithm. Subjects will also be randomized in a double blind fashion, to receive either placebo or a Cox-2 inhibitor-oral celecoxib as a chemopreventive agent. Because lung cancer-specific mortality and survival statistics may not be meaningful over the proposed five year project, additional surrogate end-points will be assessed: development of SPLC and/or cancer recurrence, TMN stage and resectability, and progression of pre- or early malignant lesions. Moreover, serial tissues and serum specimen, respiratory and health questionnaires will be archived for further analysis. The finding from this pilot project will provide important insight into surveillance strategies for detection of subsequent lung cancer, the management of pre- or early malignant lesions in the airway, and to the design and conduct of future chemopreventive trials.