Circulating tumor DNA analysis detects minimal residual disease and predicts recurrence in patients with stage II colon cancer
Jeanne Tie, Yuxuan Wang, Cristian Tomasetti, Lu Li, Simeon Springer, Isaac Kinde, Natalie Silliman, Mark Tacey, Hui-Li Wong, Michael Christie, Suzanne Kosmider, Iain Skinner, Rachel Wong, Malcolm Steel, Ben Tran, Jayesh Desai, Ian Jones, Andrew Haydon, Theresa Hayes, Tim J Price, Robert L Strausberg, Luis A Diaz Jr, Nickolas Papadopoulos, Kenneth W Kinzler, Bert Vogelstein, Peter Gibbs, Jeanne Tie, Yuxuan Wang, Cristian Tomasetti, Lu Li, Simeon Springer, Isaac Kinde, Natalie Silliman, Mark Tacey, Hui-Li Wong, Michael Christie, Suzanne Kosmider, Iain Skinner, Rachel Wong, Malcolm Steel, Ben Tran, Jayesh Desai, Ian Jones, Andrew Haydon, Theresa Hayes, Tim J Price, Robert L Strausberg, Luis A Diaz Jr, Nickolas Papadopoulos, Kenneth W Kinzler, Bert Vogelstein, Peter Gibbs
Abstract
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.
Conflict of interest statement
Competing interests: K.W.K., N.P, L.A.D., and B.V. are founders of PapGene and Personal Genome Diagnostics and members of the Scientific Advisory Boards of Morphotek and Sysmex-Inostics. I.K. is an employee of PapGene. These companies and others have licensed patent applications on genetic technologies from Johns Hopkins, some of which result in royalty payments to K.W.K., N.P., L.A.D., B.V., and I.K. The terms of these arrangements are being managed by Johns Hopkins University in accordance with its conflict of interest policies.
Copyright © 2016, American Association for the Advancement of Science.
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Source: PubMed