Dynamic changes in mutated circulating tumor DNA predicts outcome of patients with high-grade ovarian carcinomas.

There is a lack of biomarkers to predict outcome following initial treatment in patients with high-grade ovarian cancer. We hypothesized that monitoring mutation () in circulating tumor DNA (ctDNA) could be a tumor-specific biomarker. Patients enrolled in a prospective study (NCT03010124) consented to analysis of biological samples through the disease course. ctDNA was extracted and analyzed to detect the presence of Next-generation sequencing was performed on tumor tissue to detect and on whole blood to detect clonal hematopoiesis of indeterminate potential (CHIP).A total of 102 samples were sequentially collected from 26 patients. ctDNA was detected in all patients at diagnosis. The same was found in ctDNA and tumor tissue in 77% of patients. in ctDNA was not CHIP related. During neoadjuvant chemotherapy, increasing ctDNA was associated with failure to achieve complete interval cytoreductive surgery in 60% of patients. Rising ctDNA or de novo seemed to be associated with a trend for worst survival compared with decrease or complete clearance: progression-free survival 10 versus 26.5 months, HR 3.2. Despite macroscopically complete surgery, 30% of patients had detectable ctDNA post-operatively and had worse survival than those with undetectable ctDNA. Monitoring TP53m in ctDNA during chemotherapy or after surgery could help guide the best adjuvant therapy.