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 LøveOle 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

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
Journal	British Journal of Cancer
Volume	131
Pages (from-to)	1707-1715
Number of pages	9
ISSN	0007-0920
DOIs	https://doi.org/10.1038/s41416-024-02867-5
Publication status	E-pub ahead of print - 10 Oct 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

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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, 1707-1715. Advance online publication. https://doi.org/10.1038/s41416-024-02867-5

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, pp. 1707-1715. https://doi.org/10.1038/s41416-024-02867-5

@article{9639d2f52c1c451f8e6d4b17d67dac9b,

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",

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 = oct,

day = "10",

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

language = "English",

volume = "131",

pages = "1707--1715",

journal = "British Journal of Cancer",

issn = "0007-0920",

publisher = "Nature Publishing Group",

}

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 - 2024/10/10

Y1 - 2024/10/10

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

UR - http://www.scopus.com/inward/record.url?scp=85206372236&partnerID=8YFLogxK

U2 - 10.1038/s41416-024-02867-5

DO - 10.1038/s41416-024-02867-5

M3 - Journal article

C2 - 39390251

SN - 0007-0920

VL - 131

SP - 1707

EP - 1715

JO - British Journal of Cancer

JF - British Journal of Cancer

ER -

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

Abstract

Keywords

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