Serial ctDNA monitoring to predict response to systemic therapy in metastatic gastrointestinal cancers

Introduction: ctDNA offers a promising, non-invasive approach to monitor therapeutic efficacy in real-time. We explored whether the quantitative percent change in ctDNA early after therapy initiation can predict treatment response and PFS in metastatic GI cancer patients. Methods: 138 patients with metastatic GI cancers and tumor profiling by NGS had serial blood draws pre-treatment and at scheduled intervals during therapy. ctDNA was assessed using individualized droplet digital PCR measuring the mutant allele fraction in plasma of mutations identified in tumor biopsies. ctDNA changes were correlated with tumor makers and radiographic response. Results: 138 patients enrolled. 101 were evaluable for ctDNA and 68 for tumor markersat four weeks. Percent change of ctDNA by four weeks predicted partial response (PR, p 30% for all PR patients. ctDNA change at eight-weeks, but not two-weeks, also predicted CB (p