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

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Title: Circulating tumour DNA and risk of recurrence in patients with asymptomatic versus symptomatic colorectal cancer
Authors: 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
Source: Br J Cancer
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, Løve, U S, Thorlacius-Ussing, O, Andersen, P V, Kolbro, T, Monti, A, Kildsig, J, Bondeven, P, Schlesinger, N H, Iversen, L H, Rasmussen, M, Gögenur, I, Bramsen, J B & Andersen, C L 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
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, Løve, U S, Thorlacius-Ussing, O, Andersen, P V, Kolbro, T, Monti, A, Kildsig, J, Bondeven, P, Schlesinger, N H, Iversen, L H, Rasmussen, M, Gögenur, I, Bramsen, J B & Andersen, C L 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
Publisher Information: Springer Science and Business Media LLC, 2024.
Publication Year: 2024
Subject Terms: Male, Middle Aged, Colorectal Neoplasms/genetics, Local/genetics, Article, Circulating Tumor DNA, Cohort Studies, Circulating Tumor DNA/blood, Neoplasm Recurrence, Asymptomatic Diseases, Biomarkers, Tumor, Tumor/blood, Humans, Female, Early Detection of Cancer/methods, Neoplasm Recurrence, Local, Colorectal Neoplasms, Biomarkers, Early Detection of Cancer, Aged
Description: 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.
Document Type: Article
Other literature type
File Description: application/pdf
Language: English
ISSN: 1532-1827
0007-0920
DOI: 10.1038/s41416-024-02867-5
Access URL: https://pubmed.ncbi.nlm.nih.gov/39390251
https://pure.au.dk/portal/en/publications/d6196e55-bbaa-4d78-9fc3-a5d171b9619c
https://curis.ku.dk/ws/files/413568345/s41416_024_02867_5.pdf
https://pure.au.dk/portal/en/publications/d6196e55-bbaa-4d78-9fc3-a5d171b9619c
https://doi.org/10.1038/s41416-024-02867-5
https://pure.au.dk/ws/files/433369374/Circulating_tumour_DNA_and_risk_of_recurrence_in_patients_with_asymptomatic_versus_symptomatic_colorectal_cance.pdf
http://www.scopus.com/inward/record.url?scp=85206372236&partnerID=8YFLogxK
Rights: CC BY
Accession Number: edsair.doi.dedup.....4673e28babcfb42d42f670deb46128a5
Database: OpenAIRE
Description
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.
ISSN:15321827
00070920
DOI:10.1038/s41416-024-02867-5