Squamous cell cancer of the head and neck affects over 40,000 Americans each year. Treatment options for these cancers currently include surgery, radiation and chemotherapy either alone or in combination. These cancers and their treatment can have a profound impact on the ability to eat, speak, breathe and other important functions. Current treatment approaches are not uniformly successful, but all treatments produce significant morbidity. One key challenge to improving care for patients with this type of cancer is to use a treatment most likely to produce cure and least likely to produce toxicity for any individual patient. No test is available to determine which treatment approach is likely to help an individual patient. Treatment efficacy is currently determined months after completion of therapy. Preclinical and clinical data suggest changes in cell cycle kinetics following a brief exposure to radiotherapy, either alone or with chemotherapy, can be used to determine ultimate treatment efficacy in terms of locoregional control, disease free survival and overall survival. Determining changes in cell cycle kinetics involves infusion of potentially toxic analogs of DNA precursors and multiple biopsies, precluding routine assessment. Preclinical data also suggests that cell cycle kinetics can be inferred from the degree of avidity or uptake of radiolabeled DNA precursors. Work with one such precursor, 3'-deoxy, 3'[18F]Fluorolabeled Thymidine (FLT), suggests that rapidly dividing tissues have a higher avidity for FLT. The 18F label allows this agent to be imaged using Positron Emission Tomography (PET). The hypothesis of this proposal is that FLT uptake by the tumor before treatment, and changes in tumor uptake of FLT following a brief course of chemoradiotherapy will serve as predictors of ultimate response. This hypothesis will be examined in a clinical trial by specific aims designed to rigorously develop FLT PET imaging and optimize how imaging data is collected and analyzed. Dynamic FLT PET imaging will be obtained concurrently with serial venous and arterial blood sampling to ensure accurate FLT kinetic data. The optimal timing, correlations between blood analyses and image intensity and which imaging characteristics, such as mean or maximum intensity are most useful, will be determined. Using optimized FLT PET conditions, pretreatment and early mid treatment FLT studies will be obtained in subjects undergoing chemoradiation treatment for their head and neck cancer. Baseline FLT uptake values and the degree of change in FLT uptake will be tested for predictive value for overall survival and locoregional control in these subjects. The overall goal of this project is to develop a non-invasive, image-based tool to better individualize cancer therapy. FLT imaging may provide a means to individualize cancer treatment for patients with head and neck cancer allowing for more effective and less toxic therapy for patients with this disease. The relevance of this project to public health is significant. The purpose of this project is to develop a means of determining if cancer therapy is effective during the early stages of treatment, when alternative approaches can still be tried. The studies proposed here will refine and characterize a non-invasive imaging test that may allow treatment responses to be determined shortly after treatment has begun. ? ? ?
