Circulating tumor DNA-based molecular residual disease detection for the monitoring of high-grade serous ovarian cancer.

Abstract

e17600 Background: The current standard treatment of epithelial ovarian cancer includes surgery and platinum-based chemotherapy. Most of the patients are sensitive, but still over 70% of patients have recurrence or disease progression. Post-operative circulating tumor DNA (ctDNA)-based minimal residual disease (MRD) test can be a potential biomarker for monitoring the disease. Methods: Stage II-IV high-grade serous ovarian cancer (HGSOC) patients were recruited in this study. Tumor tissues were collected for whole exome sequencing (WES; 300x). Germline mutations were excluded by paired white blood cell test. Proprietary algorithm was used to select 30-40 single nucleotide variants (SNV) for each patient. Blood samples were collected at diagnosis, after surgery, after chemotherapy, and during adjuvant treatment, and MRD was detected by multiplex polymerase chain reaction (PCR)-based sequencing (100,000x) using the customized panel. Results: At the time of analysis, WES was performed in 20 patients, of which 11 of them harbored HRR pathway-related mutations, including 5 BRCA1, 4 BRCA2, 1 ATM, and 1 FANCL. 7 patients had completed MRD monitoring for 3 times (pre-surgery, post-surgery, and post-chemotherapy). 71.4% (5/7) of patients were positive for MRD at baseline, with a median variant allelic frequency (VAF) of 2.79%. The VAF at baseline was positively associated with CA125 level at baseline (Pearson R = 0.937，p = 0.002). 2 patients were positive for MRD after surgery (VAF = 0.09% and 0.04%). One of them presented with multiple diverse lesions and the CA125 level returned normal after surgery and 8 cycles of chemotherapy. Another patient had an abnormal CA125 level of 1597 U/ml after surgery. All the 7 patients were negative for MRD after completion of chemotherapy. Follow-up is ongoing. Conclusions: We preliminary proved the feasibility of dynamic monitoring with MRD in epithelial ovarian cancer patients. Over 70% of HGSOC patients were MRD-positive at baseline. The MRD status was generally consistent with the clinical status of the patients. The performance of MRD in predicting recurrence of HGSOC is still under investigation. Clinical trial information: NCT05027828 .