Clinical implications of monitoring circulating tumor DNA in patients with colorectal cancer

Lone V Schøler; Thomas Reinert; Mai-Britt W Ørntoft; Christine Gaasdal Kassentoft; Sigrid S Árnadóttir; Søren Vang; Iver Nordentoft; Michael Knudsen; Philippe Lamy; Ditte Andreasen; Frank V Mortensen; Anders Riegels Knudsen; Katrine Stribolt; Kim Sivesgaard; Peter Mouritzen; Hans Jørgen Nielsen; Søren Laurberg; Torben F Ørntoft; Claus L Andersen

doi:10.1158/1078-0432.CCR-17-0510

Clinical implications of monitoring circulating tumor DNA in patients with colorectal cancer

Lone V Schøler, Thomas Reinert, Mai-Britt W Ørntoft, Christine Gaasdal Kassentoft, Sigrid S Árnadóttir, Søren Vang, Iver Nordentoft, Michael Knudsen, Philippe Lamy, Ditte Andreasen, Frank V Mortensen, Anders Riegels Knudsen, Katrine Stribolt, Kim Sivesgaard, Peter Mouritzen, Hans Jørgen Nielsen, Søren Laurberg, Torben F Ørntoft, Claus L Andersen

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

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Abstract

Purpose: We investigated whether detection of ctDNA after resection of colorectal cancer identifies the patients with the highest risk of relapse and, furthermore, whether longitudinal ctDNA analysis allows early detection of relapse and informs about response to intervention. Experimental Design: In this longitudinal cohort study, we used massively parallel sequencing to identify somatic mutations and used these as ctDNA markers to detect minimal residual disease and to monitor changes in tumor burden during a 3-year follow-up period. Results: A total of 45 patients and 371 plasma samples were included. Longitudinal samples from 27 patients revealed ctDNA postoperatively in all relapsing patients (n = 14), but not in any of the nonrelapsing patients. ctDNA detected relapse with an average lead time of 9.4 months compared with CT imaging. Of 21 patients treated for localized disease, six had ctDNA detected within 3 months after surgery. All six later relapsed compared with four of the remaining patients [HR, 37.7; 95% confidence interval (CI), 4.2–335.5; P < 0.001]. The ability of a 3-month ctDNA analysis to predict relapse was confirmed in 23 liver metastasis patients (HR 4.9; 95% CI, 1.5–15.7; P = 0.007). Changes in ctDNA levels induced by relapse intervention (n = 19) showed good agreement with changes in tumor volume (k = 0.41; Spearman r = 0.4). Conclusions: Postoperative ctDNA detection provides evidence of residual disease and identifies patients at very high risk of relapse. Longitudinal surveillance enables early detection of relapse and informs about response to intervention. These observations have implications for the postoperative management of colorectal cancer patients.

Original language	English
Journal	Clinical Cancer Research
Volume	23
Issue	18
Pages (from-to)	5437-5445
Number of pages	9
ISSN	1078-0432
DOIs	https://doi.org/10.1158/1078-0432.CCR-17-0510
Publication status	Published - 15 Sept 2017

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Journal Article

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10.1158/1078-0432.CCR-17-0510

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Schøler, L. V., Reinert, T., Ørntoft, M.-B. W., Kassentoft, C. G., Árnadóttir, S. S., Vang, S., Nordentoft, I., Knudsen, M., Lamy, P., Andreasen, D., Mortensen, F. V., Knudsen, A. R., Stribolt, K., Sivesgaard, K., Mouritzen, P., Nielsen, H. J., Laurberg, S., Ørntoft, T. F., & Andersen, C. L. (2017). Clinical implications of monitoring circulating tumor DNA in patients with colorectal cancer. Clinical Cancer Research, 23(18), 5437-5445. https://doi.org/10.1158/1078-0432.CCR-17-0510

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title = "Clinical implications of monitoring circulating tumor DNA in patients with colorectal cancer",

abstract = "Purpose: We investigated whether detection of ctDNA after resection of colorectal cancer identifies the patients with the highest risk of relapse and, furthermore, whether longitudinal ctDNA analysis allows early detection of relapse and informs about response to intervention. Experimental Design: In this longitudinal cohort study, we used massively parallel sequencing to identify somatic mutations and used these as ctDNA markers to detect minimal residual disease and to monitor changes in tumor burden during a 3-year follow-up period. Results: A total of 45 patients and 371 plasma samples were included. Longitudinal samples from 27 patients revealed ctDNA postoperatively in all relapsing patients (n = 14), but not in any of the nonrelapsing patients. ctDNA detected relapse with an average lead time of 9.4 months compared with CT imaging. Of 21 patients treated for localized disease, six had ctDNA detected within 3 months after surgery. All six later relapsed compared with four of the remaining patients [HR, 37.7; 95% confidence interval (CI), 4.2–335.5; P < 0.001]. The ability of a 3-month ctDNA analysis to predict relapse was confirmed in 23 liver metastasis patients (HR 4.9; 95% CI, 1.5–15.7; P = 0.007). Changes in ctDNA levels induced by relapse intervention (n = 19) showed good agreement with changes in tumor volume (k = 0.41; Spearman r = 0.4). Conclusions: Postoperative ctDNA detection provides evidence of residual disease and identifies patients at very high risk of relapse. Longitudinal surveillance enables early detection of relapse and informs about response to intervention. These observations have implications for the postoperative management of colorectal cancer patients.",

keywords = "Journal Article",

author = "Sch{\o}ler, {Lone V} and Thomas Reinert and {\O}rntoft, {Mai-Britt W} and Kassentoft, {Christine Gaasdal} and {\'A}rnad{\'o}ttir, {Sigrid S} and S{\o}ren Vang and Iver Nordentoft and Michael Knudsen and Philippe Lamy and Ditte Andreasen and Mortensen, {Frank V} and Knudsen, {Anders Riegels} and Katrine Stribolt and Kim Sivesgaard and Peter Mouritzen and Nielsen, {Hans J{\o}rgen} and S{\o}ren Laurberg and {\O}rntoft, {Torben F} and Andersen, {Claus L}",

note = "Copyright {\textcopyright}2017, American Association for Cancer Research.",

year = "2017",

month = sep,

day = "15",

doi = "10.1158/1078-0432.CCR-17-0510",

language = "English",

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Schøler, LV, Reinert, T , Ørntoft, M-BW , Kassentoft, CG, Árnadóttir, SS, Vang, S , Nordentoft, I , Knudsen, M , Lamy, P, Andreasen, D, Mortensen, FV , Knudsen, AR, Stribolt, K, Sivesgaard, K, Mouritzen, P, Nielsen, HJ, Laurberg, S , Ørntoft, TF & Andersen, CL 2017, 'Clinical implications of monitoring circulating tumor DNA in patients with colorectal cancer', Clinical Cancer Research, vol. 23, no. 18, pp. 5437-5445. https://doi.org/10.1158/1078-0432.CCR-17-0510

Clinical implications of monitoring circulating tumor DNA in patients with colorectal cancer. / Schøler, Lone V; Reinert, Thomas ; Ørntoft, Mai-Britt W et al.
In: Clinical Cancer Research, Vol. 23, No. 18, 15.09.2017, p. 5437-5445.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

TY - JOUR

T1 - Clinical implications of monitoring circulating tumor DNA in patients with colorectal cancer

AU - Schøler, Lone V

AU - Reinert, Thomas

AU - Ørntoft, Mai-Britt W

AU - Kassentoft, Christine Gaasdal

AU - Árnadóttir, Sigrid S

AU - Vang, Søren

AU - Nordentoft, Iver

AU - Knudsen, Michael

AU - Lamy, Philippe

AU - Andreasen, Ditte

AU - Mortensen, Frank V

AU - Knudsen, Anders Riegels

AU - Stribolt, Katrine

AU - Sivesgaard, Kim

AU - Mouritzen, Peter

AU - Nielsen, Hans Jørgen

AU - Laurberg, Søren

AU - Ørntoft, Torben F

AU - Andersen, Claus L

PY - 2017/9/15

Y1 - 2017/9/15

N2 - Purpose: We investigated whether detection of ctDNA after resection of colorectal cancer identifies the patients with the highest risk of relapse and, furthermore, whether longitudinal ctDNA analysis allows early detection of relapse and informs about response to intervention. Experimental Design: In this longitudinal cohort study, we used massively parallel sequencing to identify somatic mutations and used these as ctDNA markers to detect minimal residual disease and to monitor changes in tumor burden during a 3-year follow-up period. Results: A total of 45 patients and 371 plasma samples were included. Longitudinal samples from 27 patients revealed ctDNA postoperatively in all relapsing patients (n = 14), but not in any of the nonrelapsing patients. ctDNA detected relapse with an average lead time of 9.4 months compared with CT imaging. Of 21 patients treated for localized disease, six had ctDNA detected within 3 months after surgery. All six later relapsed compared with four of the remaining patients [HR, 37.7; 95% confidence interval (CI), 4.2–335.5; P < 0.001]. The ability of a 3-month ctDNA analysis to predict relapse was confirmed in 23 liver metastasis patients (HR 4.9; 95% CI, 1.5–15.7; P = 0.007). Changes in ctDNA levels induced by relapse intervention (n = 19) showed good agreement with changes in tumor volume (k = 0.41; Spearman r = 0.4). Conclusions: Postoperative ctDNA detection provides evidence of residual disease and identifies patients at very high risk of relapse. Longitudinal surveillance enables early detection of relapse and informs about response to intervention. These observations have implications for the postoperative management of colorectal cancer patients.

AB - Purpose: We investigated whether detection of ctDNA after resection of colorectal cancer identifies the patients with the highest risk of relapse and, furthermore, whether longitudinal ctDNA analysis allows early detection of relapse and informs about response to intervention. Experimental Design: In this longitudinal cohort study, we used massively parallel sequencing to identify somatic mutations and used these as ctDNA markers to detect minimal residual disease and to monitor changes in tumor burden during a 3-year follow-up period. Results: A total of 45 patients and 371 plasma samples were included. Longitudinal samples from 27 patients revealed ctDNA postoperatively in all relapsing patients (n = 14), but not in any of the nonrelapsing patients. ctDNA detected relapse with an average lead time of 9.4 months compared with CT imaging. Of 21 patients treated for localized disease, six had ctDNA detected within 3 months after surgery. All six later relapsed compared with four of the remaining patients [HR, 37.7; 95% confidence interval (CI), 4.2–335.5; P < 0.001]. The ability of a 3-month ctDNA analysis to predict relapse was confirmed in 23 liver metastasis patients (HR 4.9; 95% CI, 1.5–15.7; P = 0.007). Changes in ctDNA levels induced by relapse intervention (n = 19) showed good agreement with changes in tumor volume (k = 0.41; Spearman r = 0.4). Conclusions: Postoperative ctDNA detection provides evidence of residual disease and identifies patients at very high risk of relapse. Longitudinal surveillance enables early detection of relapse and informs about response to intervention. These observations have implications for the postoperative management of colorectal cancer patients.

KW - Journal Article

UR - http://www.scopus.com/inward/record.url?scp=85029517104&partnerID=8YFLogxK

U2 - 10.1158/1078-0432.CCR-17-0510

DO - 10.1158/1078-0432.CCR-17-0510

M3 - Journal article

C2 - 28600478

SN - 1078-0432

VL - 23

SP - 5437

EP - 5445

JO - Clinical Cancer Research

JF - Clinical Cancer Research

IS - 18

ER -

Clinical implications of monitoring circulating tumor DNA in patients with colorectal cancer

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