? Approximately 45,000 new patients are diagnosed with locally advanced non-small cell lung cancer (stage III NSCLC) each year in the United States. Such disease extent precludes a primary resection for most and at the present time, the best survival rates are achieved by administering concurrent chemotherapy and radiotherapy followed by surgical resection for some or by additional chemotherapy for others. However, definite criteria to select patients for either therapeutic approach are not established. Furthermore, the optimal therapy for stage III NSCLC is not yet known and the search for it remains empirical. These limitations result in part from an inability to assess the response of these tumors to chemoradiotherapy with standard anatomically based imaging as Computed Tomography (CT) often overestimates or underestimates residual tumor after therapy. These difficulties are compounded by the lack of tumor markers able to predict or track tumor response. The proposed study plans to develop a novel and more accurate measure of tumor response by evaluating stage III NSCLC patients with FDG PET and FLT (3'-deoxy-3'-[F-18]fluorothymidine) PET prior to and at the conclusion of chemoradiotherapy. PET imaging findings will be compared to clinical and pathological tumor response and to patient outcome. Although FDG PET has demonstrated its usefulness and accuracy as a staging tool in untreated patients, its efficacy in the evaluation of the primary tumor and lymph node response is limited. However, FDG PET will provide valuable information regarding the development of distant metastatic disease outside of radiotherapy ports, an important aspect of the overall response assessment. The new tracer FLT has shown its potential as a tracer of cellular proliferation in lung cancer making it ideally suited to evaluating NSCLC response to chemoradiotherapy. We also propose to make comparisons of these dual tracer studies with tumor specimen-derived markers of proliferation and tumor resistance to validate the significance of FLT uptake in tumor response. Finally, we propose to develop a model to predict the outcome of stage III NSCLC patients treated with chemoradiotherapy by using PET-derived measures of response and specimen-derived measures of resistance. This study will constitute the initial validation of FLT as a PET imaging agent to assess tumor response to therapy. At the conclusion of this study, the insight gained in the response of stage III NSCLCs will allow clinicians to plan the best therapy for these patients. ? ?
