TY - JOUR
T1 - Circulating tumor DNA analysis detects minimal residual disease and predicts recurrence in patients with stage II colon cancer
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
N1 - Funding Information:
We thank all participating hospitals (Western Health, Royal Melbourne Hospital, Eastern Health, Alfred Hospital, Austin Health, Cabrini Health, Border Medical Oncology, Canberra Hospital, South West Oncology, Queen Elizabeth Hospital, Flinders Centre for Innovation in Cancer, Barwon Health, and Royal Women's and Brisbane Hospital) for patient enrollment and sample collection; J. Ptak, J. Schaeffer, L. Dobbyn, and C. Blair for expert technical assistance; N. Turner, P. Robertson, M. Chapman, A. Woolley, and S. Carroll for administrative assistance; and Victorian Cancer Biobank for sample processing. This study is supported by the Virginia and D.K. Ludwig Fund for Cancer Research, the Conrad N. Hilton Foundation, the Sol Goldman Sequencing Facility at Johns Hopkins, NIH grants (CA57345, R37-CA43460, U01-CA152753, and P30-CA006973), Victorian Cancer Agency Translational Research Grant, and Victorian Cancer Agency Clinical Research Fellowship (to J.T.). 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.
Publisher Copyright:
© 2016, American Association for the Advancement of Science. All rights reserved.
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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U2 - 10.1126/scitranslmed.aaf6219
DO - 10.1126/scitranslmed.aaf6219
M3 - Article
C2 - 27384348
AN - SCOPUS:84978062740
SN - 1946-6234
VL - 8
JO - Science Translational Medicine
JF - Science Translational Medicine
IS - 346
M1 - 346ra92
ER -