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 & 6 others Robert L. Strausberg, Luis A. Diaz, Nickolas Papadopoulos, Kenneth W. Kinzler, Bert Vogelstein, Peter Gibbs

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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.

Original languageEnglish
Article number346ra92
Pages (from-to)1-10
Number of pages10
JournalScience Translational Medicine
Volume8
Issue number346
DOIs
Publication statusPublished - 6 Jul 2016

Cite this

Tie, Jeanne ; Wang, Yuxuan ; Tomasetti, Cristian ; Li, Lu ; Springer, Simeon ; Kinde, Isaac ; Silliman, Natalie ; Tacey, Mark ; Wong, Hui-Li ; Christie, Michael ; Kosmider, Suzanne ; Skinner, Iain ; Wong, Rachel ; Steel, Malcolm ; Tran, Ben ; Desai, Jayesh ; Jones, Ian ; Haydon, Andrew ; Hayes, Theresa ; Price, Tim J. ; Strausberg, Robert L. ; Diaz, Luis A. ; Papadopoulos, Nickolas ; Kinzler, Kenneth W. ; Vogelstein, Bert ; Gibbs, Peter. / Circulating tumor DNA analysis detects minimal residual disease and predicts recurrence in patients with stage II colon cancer. In: Science Translational Medicine. 2016 ; Vol. 8, No. 346. pp. 1-10.
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title = "Circulating tumor DNA analysis detects minimal residual disease and predicts recurrence in patients with stage II colon cancer",
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.",
author = "Jeanne Tie and Yuxuan Wang and Cristian Tomasetti and Lu Li and Simeon Springer and Isaac Kinde and Natalie Silliman and Mark Tacey and Hui-Li Wong and Michael Christie and Suzanne Kosmider and Iain Skinner and Rachel Wong and Malcolm Steel and Ben Tran and Jayesh Desai and Ian Jones and Andrew Haydon and Theresa Hayes and Price, {Tim J.} and Strausberg, {Robert L.} and Diaz, {Luis A.} and Nickolas Papadopoulos and Kinzler, {Kenneth W.} and Bert Vogelstein and Peter Gibbs",
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Tie, J, Wang, Y, Tomasetti, C, Li, L, Springer, S, Kinde, I, Silliman, N, Tacey, M, Wong, H-L, Christie, M, Kosmider, S, Skinner, I, Wong, R, Steel, M, Tran, B, Desai, J, Jones, I, Haydon, A, Hayes, T, Price, TJ, Strausberg, RL, Diaz, LA, Papadopoulos, N, Kinzler, KW, Vogelstein, B & Gibbs, P 2016, 'Circulating tumor DNA analysis detects minimal residual disease and predicts recurrence in patients with stage II colon cancer', Science Translational Medicine, vol. 8, no. 346, 346ra92, pp. 1-10. https://doi.org/10.1126/scitranslmed.aaf6219

Circulating tumor DNA analysis detects minimal residual disease and predicts recurrence in patients with stage II colon cancer. / Tie, Jeanne; Wang, Yuxuan; Tomasetti, Cristian; Li, Lu; Springer, Simeon; Kinde, Isaac; Silliman, Natalie; Tacey, Mark; Wong, Hui-Li; Christie, Michael; Kosmider, Suzanne; Skinner, Iain; Wong, Rachel; Steel, Malcolm; Tran, Ben; Desai, Jayesh; Jones, Ian; Haydon, Andrew; Hayes, Theresa; Price, Tim J.; Strausberg, Robert L.; Diaz, Luis A.; Papadopoulos, Nickolas; Kinzler, Kenneth W.; Vogelstein, Bert; Gibbs, Peter.

In: Science Translational Medicine, Vol. 8, No. 346, 346ra92, 06.07.2016, p. 1-10.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Tie, Jeanne

AU - Wang, Yuxuan

AU - Tomasetti, Cristian

AU - Li, Lu

AU - Springer, Simeon

AU - Kinde, Isaac

AU - Silliman, Natalie

AU - Tacey, Mark

AU - Wong, Hui-Li

AU - Christie, Michael

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AU - Skinner, Iain

AU - Wong, Rachel

AU - Steel, Malcolm

AU - Tran, Ben

AU - Desai, Jayesh

AU - Jones, Ian

AU - Haydon, Andrew

AU - Hayes, Theresa

AU - Price, Tim J.

AU - Strausberg, Robert L.

AU - Diaz, Luis A.

AU - Papadopoulos, Nickolas

AU - Kinzler, Kenneth W.

AU - Vogelstein, Bert

AU - Gibbs, Peter

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N2 - 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.

AB - 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.

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