Fragment size and level of cell-free DNA provide prognostic information in patients with advanced pancreatic cancer

BackgroundIt was recently demonstrated that the size of cell-free DNA (cfDNA) fragments that originates from tumor cells are shorter than cfDNA fragments that originates from non-malignant cells. We investigated whether cfDNA fragment size and cfDNA levels might have prognostic value in patients with advanced pancreatic cancer.MethodsBlood samples were obtained from patients with advanced pancreatic cancer, before (n=61) initiation of chemotherapy and after the first cycle of chemotherapy (n=39). Samples were separated with density centrifugation and plasma DNA was isolated. Mode cfDNA fragment size and cfDNA levels were then determined using a 2100 Bioanalyzer. A cohort of partially age-matched healthy volunteers (n=28) constituted the control group.ResultsBoth a pre-treatment cfDNA fragment size of167bp (mode) and high pre-treatment cfDNA levels were associated with shorter progression-free survival (PFS) (p=0.002 and p<0.001, respectively) and overall survival (OS) (p=0.001 and p=0.001, respectively). Furthermore, multivariable Cox regression analyses demonstrated that pre-treatment cfDNA levels could independently predict prognosis for both PFS (HR=3.049, p=0.005) and OS (HR=2.236, p=0.028).ConclusionThis study demonstrates that cfDNA fragment size and cfDNA levels can be used to predict disease outcome in patients with advanced pancreatic cancer. The described approach, using a rapid, economic and simple test to reveal prognostic information, has potential for future treatment stratification and monitoring.