Detection of circulating tumor DNA in early- and late-stage human malignancies

Digital PCR-based methods were used to look for circulating tumour DNA in 640 patients with a range of cancers. It was detectable in more than 75 per cent of patients with advanced pancreatic, ovarian, colorectal, bladder, gastro-oesophageal, breast, melanoma, hepatocellular and head and neck cancers, but in less than 50 per cent with primary brain, renal, prostate or thyroid cancers. In localised disease it was detected in 73, 57, 48 and 50 per cent of patients with colorectal, gastro-oesophageal, pancreatic and breast cancer respectively. It was often present without detectable circulating tumour cells.

In 206 patients with metastatic colorectal cancer, plasma detected clinically relevant KRAS mutations with 87.2 per cent sensitivity and 99.2 per cent specificity. In 24 patients who responded to EGFR blockade and then relapsed, 23 (96 per cent) developed one or more mutations in MAPK pathway genes.