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Cancer Epidemiol Biomarkers Prev. 2016 Feb;25(2):399-406. doi: 10.1158/1055-9965.EPI-15-0893. Epub 2015 Nov 24.

Circulating DNA and Survival in Solid Tumors.

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Translational Oncology Unit, Albacete University Hospital, Albacete, Spain.
Translational Oncology Unit, Albacete University Hospital, Albacete, Spain.
Department of Medical Oncology and Hematology, Kantonsspital St. Gallen, St. Gallen, Switzerland.
Divisions of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Department of Medicine, University of Toronto, Toronto, Canada.
Department of Medical Oncology, Institute of Oncology Ljubljana, Ljubljana, Slovenia.
IBMCC-CSIC, Universidad de Salamanca, Salamanca, Spain.



The ability to undertake molecular analysis to inform on prognosis and predictors of response to therapy is limited by accessibility of tissue. Measurement of total circulating free DNA (cfDNA) or circulating tumor DNA (ctDNA) in peripheral blood may allow easier access to tumor material and help to predict clinical outcomes.


A systematic review of electronic databases identified publications exploring the association between cfDNA or ctDNA and overall survival (OS) in solid tumors. HRs for OS were extracted from multivariable analyses and included in a meta-analysis. Pooled HRs were computed and weighted using generic inverse variance and random-effect modeling. For studies not reporting multivariable analyses, univariable ORs were estimated from Kaplan-Meier curves for OS at 1 and 3 years.


Thirty-nine studies comprising 4,052 patients were included in the analysis. Detection of ctDNA was associated with a significantly worse OS in multivariable analyses [HR, 2.70; 95% confidence interval (CI), 2.02-3.61; P < 0.001). Similar results were observed in the univariable analyses at 3 and 1 year (OR, 4.83; 95% CI, 3.20-7.28; P < 0.001).There was also a statistically significant association between high total cfDNA and worse OS for studies reporting multivariable and univariate data at 3 years (HR, 1.91; 95% CI, 1.59-2.29; P < 0.001 and OR, 2.82; 95% CI, 1.93-4.13; P < 0.001, respectively).


High levels of total cfDNA and presence of ctDNA are associated with worse survival in solid tumors.


Circulating DNA is associated with worse outcome in solid tumors.

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