INTRODUCTION: Tumour burden is a prognostic biomarker in metastatic melanoma. 
However, tumour burden is difficult to measure and there are currently no 
reliable surrogate biomarkers to easily and reliably determine it. The aim of 
this study was to assess the potential of plasma total cell free DNA as 
biomarker of tumour burden and prognosis in metastatic melanoma patients.
MATERIALS AND METHODS: A prospective biomarker cohort study for total plasma 
circulating cell-free DNA (cfDNA) concentration was performed in 43 metastatic 
melanoma patients. For 38 patients, paired blood collections and scan 
assessments were available before treatment and at first response evaluation. 
Tumour burden was calculated as the sum of volumes from three-dimensional 
radiological measurements of all metastatic lesions in individual patients.
RESULTS: Baseline cfDNA concentration correlated with pre-treatment tumour 
burden (ρ = 0.52, P < 0.001). Baseline cfDNA levels correlated significantly 
with hazard of death and overall survival, and a cut off value of 89 pg/μl 
identified two distinct prognostic groups (HR = 2.22 for high cfDNA, P = 0.004). 
Patients with cfDNA ≥89 pg/μl had shorter OS (10.0 versus 22.7 months, 
P = 0.009; HR = 2.22 for high cfDNA, P = 0.004) and the significance was 
maintained when compared with lactic dehydrogenase (LDH) in a multivariate 
analysis. We also found a correlation between the changes of cfDNA and 
treatment-related changes in tumour burden (ρ = 0.49, P = 0.002). In addition, 
the ratio between baseline cfDNA and tumour burden was prognostic (HR = 2.7 for 
cfDNA/tumour volume ≥8 pg/(μl*cm3), P = 0.024).
CONCLUSIONS: We have demonstrated that cfDNA is a surrogate marker of tumour 
burden in metastatic melanoma patients, and that it is prognostic for overall 
survival.