DNA-junction-based personalized liquid biopsy assays could inform management of aggressive endometrial cancer

Objective: We investigated the clinical validity and feasibility of a DNA junction-based quantitative polymerase chain reaction assay to detect and quantitate circulating tumor DNA (ctDNA) in the blood of high-risk patients with endometrial cancer. Methods: Whole genome sequencing tumor data was analyzed from 36 patients to select prominent somatic tumor-specific DNA junctions. Personalized quantitative polymerase chain reaction assays were developed for each junction and applied to available blood specimens to measure levels of ctDNA. Results: Pre-surgical blood ctDNA was detected in 71% of the cases tested (56% early-stage vs 88% advanced-stage). In patients with available pre-amplified pre-surgical ctDNA (n = 15), pre-surgical ctDNA levels were elevated in patients with vital status or “alive with disease” or “died of disease” compared to patients with “no evidence of disease” (p < .005). Among 17 patients followed serially, ctDNA detection preceded clinical detection of recurrence in 5 of 8 cases and was concurrent in 1, with the caveat that imaging was rarely concurrent with blood draw timing. Conclusions: Personalized junction-based measurement of ctDNA demonstrated promising clinical validity in pre-surgical prognosis and relapse prediction.