Circulating tumour DNA and risk of recurrence in patients with asymptomatic versus symptomatic colorectal cancer

Nadia Øgaard; Sarah Østrup Jensen; Mai-Britt Worm Ørntoft; Christina Demuth; Mads Heilskov Rasmussen; Tenna Vesterman Henriksen; Jesper Nors; Amanda Frydendahl; Iben Lyskjær; Marijana Nesic; Christina Therkildsen; Jakob Kleif; Mikail Gögenur; Lars Nannestad Jørgensen; Jesper Vilandt; Jakob Benedict Seidelin; Kåre Anderson Gotschalck; Claudia Jaensch; Berit Andersen; Uffe Schou Løve; Ole Thorlacius-Ussing; Per Vadgaard Andersen; Thomas Kolbro; Alessio Monti; Jeppe Kildsig; Peter Bondeven; Nis Hallundbæk Schlesinger; Lene Hjerrild Iversen; Morten Rasmussen; Ismail Gögenur; Jesper Bertram Bramsen; Claus Lindbjerg Andersen

doi:10.1038/s41416-024-02867-5

Circulating tumour DNA and risk of recurrence in patients with asymptomatic versus symptomatic colorectal cancer

Nadia Øgaard
, Sarah Østrup Jensen
, Mai-Britt Worm Ørntoft
, Christina Demuth
, Mads Heilskov Rasmussen
, Tenna Vesterman Henriksen
, Jesper Nors
, Amanda Frydendahl
, Iben Lyskjær
, Marijana Nesic
, Christina Therkildsen
, Jakob Kleif
, Mikail Gögenur
, Lars Nannestad Jørgensen
, Jesper Vilandt
, Jakob Benedict Seidelin
, Kåre Anderson Gotschalck
, Claudia Jaensch
, Berit Andersen
, Uffe Schou Løve

Ole Thorlacius-Ussing, Per Vadgaard Andersen, Thomas Kolbro, Alessio Monti, Jeppe Kildsig, Peter Bondeven, Nis Hallundbæk Schlesinger, Lene Hjerrild Iversen, Morten Rasmussen, Ismail Gögenur, Jesper Bertram Bramsen, Claus Lindbjerg Andersen^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Research › peer-review

Abstract

BACKGROUND: Multiple initiatives aim to develop circulating tumour DNA (ctDNA) tests for early cancer detection in asymptomatic individuals. The few studies describing ctDNA-testing in both asymptomatic and symptomatic patients report lower ctDNA detection in the asymptomatic patients. Here, we explore if asymptomatic patients differ from symptomatic patients e.g. by including a 'low-ctDNA-shedding' and 'less-aggressive' subgroup.

METHODS: ctDNA assessment was performed in two independent cohorts of consecutively recruited patients with asymptomatic colorectal cancer (CRC) (Cohort#1: n = 215, Cohort#2: n = 368) and symptomatic CRC (Cohort#1: n = 117, Cohort#2: n = 722).

RESULTS: After adjusting for tumour stage and size, the odds of ctDNA detection was significantly lower in asymptomatic patients compared to symptomatic patients (Cohort#1: OR: 0.4, 95%CI: 0.2-0.8, Cohort#2: OR: 0.7, 95%CI: 0.5-0.9). Further, the recurrence risk was lower in asymptomatic patients (Cohort#1: sHR: 0.6, 95%CI: 0.3-1.2, Cohort#2: sHR: 0.6, 95%CI: 0.4-1.0). Notably, ctDNA-negative asymptomatic patients had the lowest recurrence risk compared to the symptomatic patients (Cohort#1: sHR: 0.2, 95%CI: 0.1-0.6, Cohort#2: sHR: 0.3, 95%CI: 0.2-0.6).

CONCLUSIONS: Our study suggests that asymptomatic patients are enriched for a 'low-ctDNA-shedding-low-recurrence-risk' subgroup. Such insights are needed to guide ctDNA-based early-detection initiatives and should prompt discussions about de-escalation of therapy and follow-up for ctDNA-negative asymptomatic CRC patients.

Original language	English
Pages (from-to)	1707-1715
Number of pages	9
Journal	British Journal of Cancer
Volume	131
Issue number	10
Early online date	10 Oct 2024
DOIs	https://doi.org/10.1038/s41416-024-02867-5
Publication status	Published - Nov 2024

Keywords

Aged
Asymptomatic Diseases
Biomarkers, Tumor/blood
Circulating Tumor DNA/blood
Cohort Studies
Colorectal Neoplasms/genetics
Early Detection of Cancer/methods
Female
Humans
Male
Middle Aged
Neoplasm Recurrence, Local/genetics
Prognostic-significance
Validation

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10.1038/s41416-024-02867-5

Cite this

Øgaard, N., Jensen, S. Ø., Ørntoft, M.-B. W., Demuth, C., Rasmussen, M. H., Henriksen, T. V., Nors, J., Frydendahl, A., Lyskjær, I., Nesic, M., Therkildsen, C., Kleif, J., Gögenur, M., Jørgensen, L. N., Vilandt, J., Seidelin, J. B., Gotschalck, K. A., Jaensch, C., Andersen, B., ... Andersen, C. L. (2024). Circulating tumour DNA and risk of recurrence in patients with asymptomatic versus symptomatic colorectal cancer. British Journal of Cancer, 131(10), 1707-1715. https://doi.org/10.1038/s41416-024-02867-5

@article{b570ccc075ba47d6851ca19e03acff69,

title = "Circulating tumour DNA and risk of recurrence in patients with asymptomatic versus symptomatic colorectal cancer",

abstract = "BACKGROUND: Multiple initiatives aim to develop circulating tumour DNA (ctDNA) tests for early cancer detection in asymptomatic individuals. The few studies describing ctDNA-testing in both asymptomatic and symptomatic patients report lower ctDNA detection in the asymptomatic patients. Here, we explore if asymptomatic patients differ from symptomatic patients e.g. by including a 'low-ctDNA-shedding' and 'less-aggressive' subgroup.METHODS: ctDNA assessment was performed in two independent cohorts of consecutively recruited patients with asymptomatic colorectal cancer (CRC) (Cohort\#1: n = 215, Cohort\#2: n = 368) and symptomatic CRC (Cohort\#1: n = 117, Cohort\#2: n = 722).RESULTS: After adjusting for tumour stage and size, the odds of ctDNA detection was significantly lower in asymptomatic patients compared to symptomatic patients (Cohort\#1: OR: 0.4, 95\%CI: 0.2-0.8, Cohort\#2: OR: 0.7, 95\%CI: 0.5-0.9). Further, the recurrence risk was lower in asymptomatic patients (Cohort\#1: sHR: 0.6, 95\%CI: 0.3-1.2, Cohort\#2: sHR: 0.6, 95\%CI: 0.4-1.0). Notably, ctDNA-negative asymptomatic patients had the lowest recurrence risk compared to the symptomatic patients (Cohort\#1: sHR: 0.2, 95\%CI: 0.1-0.6, Cohort\#2: sHR: 0.3, 95\%CI: 0.2-0.6).CONCLUSIONS: Our study suggests that asymptomatic patients are enriched for a 'low-ctDNA-shedding-low-recurrence-risk' subgroup. Such insights are needed to guide ctDNA-based early-detection initiatives and should prompt discussions about de-escalation of therapy and follow-up for ctDNA-negative asymptomatic CRC patients.",

keywords = "Aged, Asymptomatic Diseases, Biomarkers, Tumor/blood, Circulating Tumor DNA/blood, Cohort Studies, Colorectal Neoplasms/genetics, Early Detection of Cancer/methods, Female, Humans, Male, Middle Aged, Neoplasm Recurrence, Local/genetics, Prognostic-significance, Validation",

author = "Nadia {\O}gaard and Jensen, \{Sarah {\O}strup\} and {\O}rntoft, \{Mai-Britt Worm\} and Christina Demuth and Rasmussen, \{Mads Heilskov\} and Henriksen, \{Tenna Vesterman\} and Jesper Nors and Amanda Frydendahl and Iben Lyskj{\ae}r and Marijana Nesic and Christina Therkildsen and Jakob Kleif and Mikail G{\"o}genur and J{\o}rgensen, \{Lars Nannestad\} and Jesper Vilandt and Seidelin, \{Jakob Benedict\} and Gotschalck, \{K{\aa}re Anderson\} and Claudia Jaensch and Berit Andersen and L{\o}ve, \{Uffe Schou\} and Ole Thorlacius-Ussing and Andersen, \{Per Vadgaard\} and Thomas Kolbro and Alessio Monti and Jeppe Kildsig and Peter Bondeven and Schlesinger, \{Nis Hallundb{\ae}k\} and Iversen, \{Lene Hjerrild\} and Morten Rasmussen and Ismail G{\"o}genur and Bramsen, \{Jesper Bertram\} and Andersen, \{Claus Lindbjerg\}",

note = "{\textcopyright} 2024. The Author(s).",

year = "2024",

month = nov,

doi = "10.1038/s41416-024-02867-5",

language = "English",

volume = "131",

pages = "1707--1715",

journal = "British Journal of Cancer",

issn = "0007-0920",

publisher = "Springer Nature",

number = "10",

}

Øgaard, N, Jensen, SØ, Ørntoft, M-BW, Demuth, C, Rasmussen, MH, Henriksen, TV, Nors, J, Frydendahl, A, Lyskjær, I, Nesic, M, Therkildsen, C, Kleif, J, Gögenur, M, Jørgensen, LN, Vilandt, J, Seidelin, JB, Gotschalck, KA, Jaensch, C, Andersen, B, Løve, US, Thorlacius-Ussing, O, Andersen, PV, Kolbro, T, Monti, A, Kildsig, J, Bondeven, P, Schlesinger, NH, Iversen, LH, Rasmussen, M, Gögenur, I, Bramsen, JB & Andersen, CL 2024, 'Circulating tumour DNA and risk of recurrence in patients with asymptomatic versus symptomatic colorectal cancer', British Journal of Cancer, vol. 131, no. 10, pp. 1707-1715. https://doi.org/10.1038/s41416-024-02867-5

TY - JOUR

T1 - Circulating tumour DNA and risk of recurrence in patients with asymptomatic versus symptomatic colorectal cancer

AU - Øgaard, Nadia

AU - Jensen, Sarah Østrup

AU - Ørntoft, Mai-Britt Worm

AU - Demuth, Christina

AU - Rasmussen, Mads Heilskov

AU - Henriksen, Tenna Vesterman

AU - Nors, Jesper

AU - Frydendahl, Amanda

AU - Lyskjær, Iben

AU - Nesic, Marijana

AU - Therkildsen, Christina

AU - Kleif, Jakob

AU - Gögenur, Mikail

AU - Jørgensen, Lars Nannestad

AU - Vilandt, Jesper

AU - Seidelin, Jakob Benedict

AU - Gotschalck, Kåre Anderson

AU - Jaensch, Claudia

AU - Andersen, Berit

AU - Løve, Uffe Schou

AU - Thorlacius-Ussing, Ole

AU - Andersen, Per Vadgaard

AU - Kolbro, Thomas

AU - Monti, Alessio

AU - Kildsig, Jeppe

AU - Bondeven, Peter

AU - Schlesinger, Nis Hallundbæk

AU - Iversen, Lene Hjerrild

AU - Rasmussen, Morten

AU - Gögenur, Ismail

AU - Bramsen, Jesper Bertram

AU - Andersen, Claus Lindbjerg

PY - 2024/11

Y1 - 2024/11

N2 - BACKGROUND: Multiple initiatives aim to develop circulating tumour DNA (ctDNA) tests for early cancer detection in asymptomatic individuals. The few studies describing ctDNA-testing in both asymptomatic and symptomatic patients report lower ctDNA detection in the asymptomatic patients. Here, we explore if asymptomatic patients differ from symptomatic patients e.g. by including a 'low-ctDNA-shedding' and 'less-aggressive' subgroup.METHODS: ctDNA assessment was performed in two independent cohorts of consecutively recruited patients with asymptomatic colorectal cancer (CRC) (Cohort#1: n = 215, Cohort#2: n = 368) and symptomatic CRC (Cohort#1: n = 117, Cohort#2: n = 722).RESULTS: After adjusting for tumour stage and size, the odds of ctDNA detection was significantly lower in asymptomatic patients compared to symptomatic patients (Cohort#1: OR: 0.4, 95%CI: 0.2-0.8, Cohort#2: OR: 0.7, 95%CI: 0.5-0.9). Further, the recurrence risk was lower in asymptomatic patients (Cohort#1: sHR: 0.6, 95%CI: 0.3-1.2, Cohort#2: sHR: 0.6, 95%CI: 0.4-1.0). Notably, ctDNA-negative asymptomatic patients had the lowest recurrence risk compared to the symptomatic patients (Cohort#1: sHR: 0.2, 95%CI: 0.1-0.6, Cohort#2: sHR: 0.3, 95%CI: 0.2-0.6).CONCLUSIONS: Our study suggests that asymptomatic patients are enriched for a 'low-ctDNA-shedding-low-recurrence-risk' subgroup. Such insights are needed to guide ctDNA-based early-detection initiatives and should prompt discussions about de-escalation of therapy and follow-up for ctDNA-negative asymptomatic CRC patients.

AB - BACKGROUND: Multiple initiatives aim to develop circulating tumour DNA (ctDNA) tests for early cancer detection in asymptomatic individuals. The few studies describing ctDNA-testing in both asymptomatic and symptomatic patients report lower ctDNA detection in the asymptomatic patients. Here, we explore if asymptomatic patients differ from symptomatic patients e.g. by including a 'low-ctDNA-shedding' and 'less-aggressive' subgroup.METHODS: ctDNA assessment was performed in two independent cohorts of consecutively recruited patients with asymptomatic colorectal cancer (CRC) (Cohort#1: n = 215, Cohort#2: n = 368) and symptomatic CRC (Cohort#1: n = 117, Cohort#2: n = 722).RESULTS: After adjusting for tumour stage and size, the odds of ctDNA detection was significantly lower in asymptomatic patients compared to symptomatic patients (Cohort#1: OR: 0.4, 95%CI: 0.2-0.8, Cohort#2: OR: 0.7, 95%CI: 0.5-0.9). Further, the recurrence risk was lower in asymptomatic patients (Cohort#1: sHR: 0.6, 95%CI: 0.3-1.2, Cohort#2: sHR: 0.6, 95%CI: 0.4-1.0). Notably, ctDNA-negative asymptomatic patients had the lowest recurrence risk compared to the symptomatic patients (Cohort#1: sHR: 0.2, 95%CI: 0.1-0.6, Cohort#2: sHR: 0.3, 95%CI: 0.2-0.6).CONCLUSIONS: Our study suggests that asymptomatic patients are enriched for a 'low-ctDNA-shedding-low-recurrence-risk' subgroup. Such insights are needed to guide ctDNA-based early-detection initiatives and should prompt discussions about de-escalation of therapy and follow-up for ctDNA-negative asymptomatic CRC patients.

KW - Aged

KW - Asymptomatic Diseases

KW - Biomarkers, Tumor/blood

KW - Circulating Tumor DNA/blood

KW - Cohort Studies

KW - Colorectal Neoplasms/genetics

KW - Early Detection of Cancer/methods

KW - Female

KW - Humans

KW - Male

KW - Middle Aged

KW - Neoplasm Recurrence, Local/genetics

KW - Prognostic-significance

KW - Validation

U2 - 10.1038/s41416-024-02867-5

DO - 10.1038/s41416-024-02867-5

M3 - Article

C2 - 39390251

SN - 0007-0920

VL - 131

SP - 1707

EP - 1715

JO - British Journal of Cancer

JF - British Journal of Cancer

IS - 10

ER -

Circulating tumour DNA and risk of recurrence in patients with asymptomatic versus symptomatic colorectal cancer

Abstract

Keywords

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