Circulating tumor DNA monitoring for early recurrence detection in epithelial ovarian cancer. Gynecologic oncology Hou, J. Y., Chapman, J. S., Kalashnikova, E., Pierson, W., Smith-McCune, K., Pineda, G., Vattakalam, R. M., Ross, A., Mills, M., Suarez, C. J., Davis, T., Edwards, R., Boisen, M., Sawyer, S., Wu, H., Dashner, S., Aushev, V. N., George, G. V., Malhotra, M., Zimmermann, B., Sethi, H., ElNaggar, A. C., Aleshin, A., Ford, J. M. 2022


OBJECTIVE: Epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy. We examined the utility of circulating tumor DNA (ctDNA) as a prognostic biomarker for EOC by assessing its relationship with patient outcome and CA-125, pre-surgically and during post-treatment surveillance.METHODS: Plasma samples were collected from patients with stage I-IV EOC. Cohort A included patients with pre-surgical samples (N = 44, median follow-up: 2.7 years), cohort B and C included: patients with serially collected post-surgically (N = 12) and, during surveillance (N = 13), respectively (median follow-up: 2 years). Plasma samples were analyzed using a tumor-informed, personalized multiplex-PCR NGS assay; ctDNA status and CA-125 levels were correlated with clinical features and outcomes.RESULTS: Genomic profiling was performed on the entire cohort and was consistent with that seen in TCGA. In cohort A, ctDNA-positivity was observed in 73% (32/44) of presurgical samples and was higher in high nuclear grade disease. In cohort B and C, ctDNA was only detected in patients who relapsed (100% sensitivity and specificity) and preceded radiological findings by an average of 10 months. The presence of ctDNA at a single timepoint after completion of surgery +/- adjuvant chemotherapy and serially during surveillance was a strong predictor of relapse (HR:17.6, p = 0.001 and p < 0.0001, respectively), while CA-125 positivity was not (p = 0.113 and p = 0.056).CONCLUSIONS: The presence of ctDNA post-surgically is highly prognostic of reduced recurrence-free survival. CtDNA outperformed CA-125 in identifying patients at highest risk of recurrence. These results suggest that monitoring ctDNA could be beneficial in clinical decision-making for EOC patients.

View details for DOI 10.1016/j.ygyno.2022.09.004

View details for PubMedID 36117009