Prospective study of the efficacy and utility of TP53 mutations in circulating tumor DNA as a non-invasive biomarker of treatment response monitoring in patients with high-grade serous ovarian carcinoma

摘要

Objective Somatic TP53 mutation ( TP53supmut/sup ) is a characteristic finding in high-grade serous ovarian cancer (HGSOC). The aim of this study was to assess the clinical efficacy and utility of TP53supmut/sup circulating tumor DNA (ctDNA) monitoring as a biomarker for managing HGSOC. Methods TP53supmuts/sup were evaluated in patients who received primary treatment for suspected ovarian cancer at Asan Medical Center. In patients diagnosed with HGSOC and with TP53supmut/sup , ctDNA, cancer antigen 125 (CA 125), and computed tomography were followed up according to the treatment course. Results Direct sequencing analysis of 103 tumor tissues from 61 HGSOC patients confirmed TP53supmuts/sup in 41 patients (67.2%). All these patient-specific somatic mutations were detected in plasma cell-free DNA. The mean value of preoperative TP53 mutant allele count (TP53MAC) in stage III patients was 12.2 copies/μL and in stage IV patients was 45.3 copies/μL. TP53MAC was significantly reduced by treatment and there was no significant difference in the rate of decrease compared to CA 125 by the generalized linear mixed model. When patients were divided into a low TP53MAC group (0.2 copies/μL) and a high TP53MAC group (≥0.2 copies/μL) based on the TP53MAC value at 3 months after the end of chemotherapy, there was a significant difference in time to progression between the two groups (p=0.038). Conclusion TP53supmut/sup ctDNA shows potential as a tumor-specific biomarker for treatment response monitoring in HGSOC. TP53supmut/sup ctDNA levels at 3 months post treatment has a significant prognostic utility than that of CA 125.