Utility of Circulating Tumor DNA for Detection and Monitoring of Endometrial Cancer Recurrence and Progression

Esther L Moss 1 2, Diviya N Gorsia 1, Anna Collins 1, Pavandeep Sandhu 1, Nalini Foreman 1, Anupama Gore 2, Joey Wood 2, Christopher Kent 2, Lee Silcock 3, David S Guttery 1

Affiliations

PMID: 32785174
DOI: 10.3390/cancers12082231

Abstract

Despite the increasing incidence of endometrial cancer (EC) worldwide and the poor overall survival of patients who recur, no reliable biomarker exists for detecting and monitoring EC recurrence and progression during routine follow-up. Circulating tumor DNA (ctDNA) is a sensitive method for monitoring cancer activity and stratifying patients that are likely to respond to therapy. As a pilot study, we investigated the utility of ctDNA for detecting and monitoring EC recurrence and progression in 13 patients, using targeted next-generation sequencing (tNGS) and personalized ctDNA assays. Using tNGS, at least one somatic mutation at a variant allele frequency (VAF) > 20% was detected in 69% (9/13) of patient tumors. The four patients with no detectable tumor mutations at >20% VAF were whole exome sequenced, with all four harboring mutations in genes not analyzed by tNGS. Analysis of matched and longitudinal plasma DNA revealed earlier detection of EC recurrence and progression and dynamic kinetics of ctDNA levels reflecting treatment response. We also detected acquired high microsatellite instability (MSI-H) in ctDNA from one patient whose primary tumor was MSI stable. Our study suggests that ctDNA analysis could become a useful biomarker for early detection and monitoring of EC recurrence. However, further research is needed to confirm these findings and to explore their potential implications for patient management.

Keywords: circulating tumor DNA; digital droplet PCR; endometrial cancer; ion torrent; whole exome sequencing.