Circulating nucleic acids are associated with outcomes of patients with pancreatic cancer

Liquid biopsies from 194 patients treated for localised or metastatic pancreatic adenocarcinoma (425 samples before and during therapy) and 37 disease controls were analysed by droplet digital PCR for KRAS mutant allele fraction in circulating tumour DNA and exosome DNA, with 123 serial samples from 34 patients. In 34 patients with potentially resectable tumours, a rise in exosome DNA after neoadjuvant therapy was associated with disease progression (P = .003), while ctDNA was not. Concordance of KRAS mutations between resected tissue and liquid biopsy exceeded 95%. In metastatic disease, detectable baseline ctDNA gave a progression-free survival hazard ratio of 1.8 and overall survival hazard ratio of 2.8; exosome DNA allele fraction of 5% or more predicted progression-free (2.28) and overall survival (3.46), and detecting both at 5% or more gave an overall survival hazard ratio of 7.73.