Molecular imaging for guiding oncologic prognosis and therapy in esophageal adenocarcinoma

In the past 30 years, the incidence of esophageal adenocarcinoma (ACA) has increased significantly. Sadly, advances in treatment have not followed the same trend, and the prognosis for patients with esophageal ACA remains poor, with a 5-year survival rate of only 15%. Like most cancers, early detection is the key to improving prognosis, but this outcome has proven difficult in the esophagus for several reasons: 1) patients present with advanced disease because "alarm symptoms," such as dysphagia, occur at a late stage, and 2) high-grade dysplasia (HGD) and early ACA are not visible on routine surveillance endoscopy. Currently, the recommended surveillance strategy involves collection of random biopsies, an imperfect technique that is limited by sampling error and is infrequently used because of the considerable time and cost it requires. Even in patients with biopsy-proven dysplasia, adequate guidance for clinical management decisions is still lacking. Dysplasia alone is not an entirely reliable biomarker for the risk of progression to ACA because the natural history of this condition is extremely variable. Clearly, there is a need for additional biomarkers that can better characterize this disease and thus improve our ability to treat patients on an individual basis. As we better understand the molecular changes that lead to the development of this cancer, new molecular biomarkers are needed to allow for more personalized diagnoses, surveillance, and treatment. Targeted agents against epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), and vascular endothelial growth factor (VEGF) are currently being evaluated for their role in combination chemotherapy for metastatic esophageal ACA. As these studies progress, a reliable approach for determining receptor status in individual patients is essential. Molecular imaging uses fluorescent probes that target specific cell-surface receptors, and has the potential to evaluate an individual patient's gene expression profile. By topically applying fluorescent probes to dysplastic epithelium during endoscopy, a variety of receptors can be visualized, and the response to treatment can be monitored in real time. This technique can mitigate the limitations of current surveillance protocols, allow for improved cancer detection, and be used for personalized treatment in the future.