Tumor fraction in circulating free DNA as a biomarker of disease dynamics in metastatic prostate cancer.

195Background: Quantification of circulating free DNA (cfDNA) has been proposed both as a prognostic biomarker and as a biomarker of response and resistance to therapy. However, dynamics of cfDNA derived from both tumor and non-cancerous tissues through dense longitudinal monitoring over the course of treatment with multiple therapeutic modalities have not been well described. Methods: CfDNA isolated from banked and prospectively collected plasma samples from pts with metastatic castration-resistant prostate cancer (mCRPC) was subject to ultra-low pass (~0.1x coverage) whole genome sequencing (ULP-WGS). The fraction of cfDNA derived from tumor rather than non-cancerous tissues (i.e. the tumor fraction, or TFx) in each sample was estimated using a novel computational tool called ichorCNA, and was correlated with clinical features and response to therapy. Results: 663 plasma samples from 140 pts were included (median 3 samples/pt; range 1-20). TFx was correlated with the number of bone metastases (median TF...