RT Journal Article SR Electronic T1 Circulating tumor DNA analysis detects minimal residual disease and predicts recurrence in patients with stage II colon cancer JF Science Translational Medicine FD American Association for the Advancement of Science SP 346ra92 OP 346ra92 DO 10.1126/scitranslmed.aaf6219 VO 8 IS 346 A1 Tie, Jeanne A1 Wang, Yuxuan A1 Tomasetti, Cristian A1 Li, Lu A1 Springer, Simeon A1 Kinde, Isaac A1 Silliman, Natalie A1 Tacey, Mark A1 Wong, Hui-Li A1 Christie, Michael A1 Kosmider, Suzanne A1 Skinner, Iain A1 Wong, Rachel A1 Steel, Malcolm A1 Tran, Ben A1 Desai, Jayesh A1 Jones, Ian A1 Haydon, Andrew A1 Hayes, Theresa A1 Price, Tim J. A1 Strausberg, Robert L. A1 Diaz, Luis A. A1 Papadopoulos, Nickolas A1 Kinzler, Kenneth W. A1 Vogelstein, Bert A1 Gibbs, Peter YR 2016 UL http://stm.sciencemag.org/content/8/346/346ra92.abstract AB Stage II colon cancer, which has spread through the wall of the colon but has not metastasized to the lymph nodes, can present a therapeutic dilemma. On one hand, these tumors can usually be completely removed by surgery, and the majority does not recur even without chemotherapy. On the other hand, it is difficult to determine which of these tumors will recur and to identify patients who would benefit from adjuvant chemotherapy after surgery. Tie et al. show that the presence of circulating tumor DNA in a patient’s blood after surgery is a sign of persistent tumor and a greatly increased risk of relapse, suggesting that this group of patients may require chemotherapy to prevent recurrence.Detection of circulating tumor DNA (ctDNA) after resection of stage II colon cancer may identify patients at the highest risk of recurrence and help inform adjuvant treatment decisions. We used massively parallel sequencing–based assays to evaluate the ability of ctDNA to detect minimal residual disease in 1046 plasma samples from a prospective cohort of 230 patients with resected stage II colon cancer. In patients not treated with adjuvant chemotherapy, ctDNA was detected postoperatively in 14 of 178 (7.9%) patients, 11 (79%) of whom had recurred at a median follow-up of 27 months; recurrence occurred in only 16 (9.8 %) of 164 patients with negative ctDNA [hazard ratio (HR), 18; 95% confidence interval (CI), 7.9 to 40; P < 0.001]. In patients treated with chemotherapy, the presence of ctDNA after completion of chemotherapy was also associated with an inferior recurrence-free survival (HR, 11; 95% CI, 1.8 to 68; P = 0.001). ctDNA detection after stage II colon cancer resection provides direct evidence of residual disease and identifies patients at very high risk of recurrence.