Circulating tumour DNA as a biomarker in resectable and irresectable stage IV colorectal cancer; a systematic review and meta-analysis
Circulating tumour DNA as a biomarker in resectable and irresectable stage IV colorectal cancer; a systematic review and meta-analysis
Background: For patients with metastatic colorectal cancer, stratification for treatment (surgery or chemotherapy) is often based on crude clinicopathological characteristics like tumour size and number of lesions. Circulating tumour DNA (ctDNA) acts as a potential biomarker of disease trajectory and biology, allowing better stratification. This study aims to systematically review ctDNA in stage IV colorectal cancer to assess its potential role as a prospective biomarker to guide management decisions. Methods: A literature search was performed to identify studies where the measurement of ctDNA in stage IV colorectal cancer was correlated with a clinical outcome (radiological response, secondary resection rate, PFS, DFS or OS). Results: Twenty-eight studies were included, reporting on 2823 patients. Circulating tumour DNA was detectable in between 80% and 90% of patients prior to treatment. Meta-analysis identified a strong correlation between detectable ctDNA after treatment (surgery or chemotherapy) and overall survival (HR 2.2, 95% CI 1.79–2.69, p < 0.00001), as well as progression-free survival (HR 3.15, 95% CI 2.10–4.73, p < 0.00001). ctDNA consistently offered an early marker of long-term prognosis in irresectable disease, with changes after one cycle of systemic therapy demonstrating prognostic value. In resectable disease treated with curative intent, detection of ctDNA offered a lead time over radiological recurrence of 10 months. Conclusion: Circulating tumour DNA is detectable in the majority of resectable and irresectable patients. The presence of ctDNA is clearly associated with shorter overall survival, with changes in ctDNA an early biomarker of adverse disease behaviour. Prospective trials are essential to test its clinical efficacy.
Biomarker, Cancer, Colorectal, ctDNA
368-381
Jones, Robert P
8432125b-39cb-4463-90ba-b47709ae985f
Pugh, Siân A
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Graham, Janet
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Primrose, John N
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Barriuso, Jorge
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February 2021
Jones, Robert P
8432125b-39cb-4463-90ba-b47709ae985f
Pugh, Siân A
e0d0bdb3-f772-48b2-84bd-fb25045bef94
Graham, Janet
0e9daa54-2f69-40a0-9cca-5ac75fb25d97
Primrose, John N
d85f3b28-24c6-475f-955b-ec457a3f9185
Barriuso, Jorge
41a3fa7f-8120-4ea3-a159-e83cb3f96da0
Jones, Robert P, Pugh, Siân A, Graham, Janet, Primrose, John N and Barriuso, Jorge
(2021)
Circulating tumour DNA as a biomarker in resectable and irresectable stage IV colorectal cancer; a systematic review and meta-analysis.
European Journal of Cancer, 144, .
(doi:10.1016/j.ejca.2020.11.025).
Abstract
Background: For patients with metastatic colorectal cancer, stratification for treatment (surgery or chemotherapy) is often based on crude clinicopathological characteristics like tumour size and number of lesions. Circulating tumour DNA (ctDNA) acts as a potential biomarker of disease trajectory and biology, allowing better stratification. This study aims to systematically review ctDNA in stage IV colorectal cancer to assess its potential role as a prospective biomarker to guide management decisions. Methods: A literature search was performed to identify studies where the measurement of ctDNA in stage IV colorectal cancer was correlated with a clinical outcome (radiological response, secondary resection rate, PFS, DFS or OS). Results: Twenty-eight studies were included, reporting on 2823 patients. Circulating tumour DNA was detectable in between 80% and 90% of patients prior to treatment. Meta-analysis identified a strong correlation between detectable ctDNA after treatment (surgery or chemotherapy) and overall survival (HR 2.2, 95% CI 1.79–2.69, p < 0.00001), as well as progression-free survival (HR 3.15, 95% CI 2.10–4.73, p < 0.00001). ctDNA consistently offered an early marker of long-term prognosis in irresectable disease, with changes after one cycle of systemic therapy demonstrating prognostic value. In resectable disease treated with curative intent, detection of ctDNA offered a lead time over radiological recurrence of 10 months. Conclusion: Circulating tumour DNA is detectable in the majority of resectable and irresectable patients. The presence of ctDNA is clearly associated with shorter overall survival, with changes in ctDNA an early biomarker of adverse disease behaviour. Prospective trials are essential to test its clinical efficacy.
Text
Revised ctDNA systematic review 260620 RJ JP JG JB
- Accepted Manuscript
More information
Accepted/In Press date: 15 November 2020
e-pub ahead of print date: 7 January 2021
Published date: February 2021
Additional Information:
Funding Information:
RPJ was supported by the Association of Upper GI Surgery of United Kingdom and Ireland (AUGIS)/Bowel Cancer UK Specialty Study Lead Initiative.
Publisher Copyright:
© 2020 Elsevier Ltd
Keywords:
Biomarker, Cancer, Colorectal, ctDNA
Identifiers
Local EPrints ID: 446557
URI: http://eprints.soton.ac.uk/id/eprint/446557
ISSN: 0959-8049
PURE UUID: 1246d999-8b1b-40fb-b3ae-0a7a8902d84a
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Date deposited: 15 Feb 2021 17:30
Last modified: 17 Mar 2024 06:15
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Contributors
Author:
Robert P Jones
Author:
Siân A Pugh
Author:
Janet Graham
Author:
Jorge Barriuso
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