The overall goal of this pilot clincal imaging project is to determine the efficacy of 3'-deoxy-3'-18F- fluorothymidine (18F-FLT) PET to accurately predict pathological complete response (pathCR) early during treatment in patients with esophageal carcinoma undergoing preoperative chemoradiation. Approximately 600,000 new cases of esophageal cancer are diagnosed each year in the world, including approximately 13,900 new cases in the United States. Despite significant improvements in surgical management, long-term survival rates in patients with esophageal cancer have not changed dramatically. Achievement of pathCR after pre-operative chemoradiotherapy (CRT) is associated with improved patient outcomes; however, there is no effective method to predict pathological response before surgery. Thus, a patient with pathCR, for whom esophagectomy may be unnecessary, still undergoes surgery and faces the prohibitive side effects of this drastic surgical procedure. Additionally, CRT is associated with considerable morbidities and tools to predict and avoid ineffective therapy are lacking. Because deregulated proliferation is one of the hallmarks of cancer and its proliferation rate is associated with aggressive biologic behavior and response to therapy, imaging the proliferative state of cancer cells by non-invasive functional imaging is of great interest. Recently, 18F-FLT has been reported as a promising PET radiopharmaceutical for imaging cancer proliferation and has been validated in several in vitro and in vivo models. However, only a limited number of studies addressed its role in depicting changes in cancer proliferation and assessing response to CRT, and none of these studies have focused on esophageal cancer. We propose to conduct a clinical study to determine the optimal FLT PET imaging timepoint during the early course of CRT that has the highest predictive value for pathCR in patients with esophageal cancer. Esophgeal cancer was chosen for the reason that early prediction of pathCR could significantly impact clinical management decision, and, most importantly, it allows easy access for repeated biopsies to address the correlation between FLT PET signal and pathological changes in tumor proliferation. ? ? ?
