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; Nickolas Papadopoulos; Kenneth W. Kinzler; Bert Vogelstein; Peter Gibbs

doi:10.1126/scitranslmed.aaf6219

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. PriceRobert 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 language	English (US)
Article number	346ra92
Journal	Science translational medicine
Volume	8
Issue number	346
DOIs	https://doi.org/10.1126/scitranslmed.aaf6219
State	Published - Jul 6 2016

ASJC Scopus subject areas

General Medicine

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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., ... Gibbs, P. (2016). Circulating tumor DNA analysis detects minimal residual disease and predicts recurrence in patients with stage II colon cancer. Science translational medicine, 8(346), Article 346ra92. https://doi.org/10.1126/scitranslmed.aaf6219

Tie, J, Wang, Y, Tomasetti, C, Li, L, Springer, S, Kinde, I, Silliman, N, Tacey, M, Wong, HL, 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. https://doi.org/10.1126/scitranslmed.aaf6219

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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 Wong, {Hui Li} 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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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

AU - Kosmider, Suzanne

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

PY - 2016/7/6

Y1 - 2016/7/6

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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Circulating tumor DNA analysis detects minimal residual disease and predicts recurrence in patients with stage II colon cancer

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