Evaluation of Circulating Cell-Free DNA Levels in Predicting Operability During Interval Cytoreduction for Advanced Epithelial Ovarian Cancers

Background This study aims to evaluate the role of circulating cell-free DNA (cfDNA) levels in predicting optimal cytoreduction (OCR) during interval cytoreduction for advanced epithelial ovarian cancers. Methods This prospective study included 24 patients of stage IIIC high-grade serous ovarian cancer treated with neoadjuvant chemotherapy (NACT) followed by interval cytoreduction. Quantitative analysis of cfDNA was done at diagnosis and after 3 cycles of NACT. The surgical outcome was correlated with the cfDNA levels. This was compared with the traditional methods used for assessment post-NACT, CA-125 and imaging using contrast-enhanced computerized tomography (CECT). The association between two categorical variables was done using Chi-square or Fisher’s exact test. The cutoff values were obtained using receiver operator characteristic (ROC) curve. Results Twenty-four patients were included in the study. Post-neo-adjuvant chemotherapy cfDNA value less than 6.6 significantly predicted OCR ( p = 0.02), while post-chemo CA-125 (cutoff-35) did not predict OCR ( p = 0.67). Patients with post-chemo cfDNA level < 6.6 and a partial/complete response on CECT had better OCR rates (sensitivity—100%, specificity—90%, NPV—100%) compared to patients with complete/partial response who had CA-125 levels normalized to < 35 post-chemotherapy (sensitivity—81.2%,specificity—75%, NPV—66%). Pre-chemo CA-125 and cfDNA value did not correlate with optimal cytoreduction. Conclusions Post-NACT cfDNA level < 6.6 may be considered as a cutoff in predicting patients more likely to achieve OCR, indicating the potential for use of cfDNA levels as a predictor for OCR and thereby survival of the patient. Key Messages Post-NACT cfDNA level < 6.6 may be considered as a cutoff for predicting optimal cytoreduction. A combination of post-chemo cfDNA and CT response may be used to assess response after NACT, rather than CA-125 and CT response which are routinely used. Graphical Abstract