TY - JOUR
T1 - Circulating tumour DNA as a biomarker in resectable and irresectable stage IV colorectal cancer; a systematic review and meta-analysis
AU - Jones, Robert P.
AU - Pugh, Sian
AU - Graham, Janet
AU - Primrose, John N.
AU - Barriuso, Jorge
PY - 2020/11/30
Y1 - 2020/11/30
N2 - 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) offers a potential biomarker of disease trajectory and biology, allowing better stratification. This study aimed 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 80-90% 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.
AB - 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) offers a potential biomarker of disease trajectory and biology, allowing better stratification. This study aimed 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 80-90% 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.
M3 - Article
SN - 0959-8049
JO - European Journal of Cancer
JF - European Journal of Cancer
ER -