Rectal cancer affects 40,000 individuals in the US every year. The primary treatment is surgical resection when possible but a growing number of patients receive pre-operative chemo-radiation therapy before surgery to improve outcomes. In up to 30% of these patients, the tissue removed from the rectum after chemo-radiation is found to have no evidence of the original tumor. However, at present, the only accurate way to find out if the tumor responded completely to pre-operative chemo-radiation is to go through with surgery. There are no established biomarkers that can identify patients with complete response before surgery so that they may be potentially saved from a morbid operation. In previous work, we have shown that cancer mutations can be detected in blood plasma from advanced cancer patients. We have also shown that changes in the circulating levels of these mutations correlate with tumor burden. In this project, we are evaluating detection of cancer mutations in plasma from patients with rectal cancer as a potential biomarker. Our goal is to identify patients with rectal cancer whose tumors have completely receded after completing chemo-radiation before they under go surgery. These results will set the stage for prospective follow-up studies to enable biomarker-guided non-operative management of localized rectal cancers.