Abstract

Background: In recent years there has been increasing interest in the study of circulating tumor cells (CTC) and plama cell-free circulating DNA (cfDNA) as a new biomarker in neoplastic diseases. Our work aims to clarify its clinical role in ovarian epithelial carcinoma (OEC). Methods: A prospective, multicenter, observational study has been conducted for 3 years in patients with advanced or responsive OEC. The predictive value and prognosis of CTC and cfDNA have been determined for both progression-free survival (PFS) and overall survival (OS). Their values have been compared with a control group. CTC were analysed by the CellSearch method and cfDNA by ALU-sequences-based quantitative PCR using two primers (ALU115 and ALU247); cfDNA integrity was calculated by ALU247/ALU115 ratio. This study was approved by the Central Research Ethics Committee. Updated data are presented. Results: This study was conducted from November 2013 until December 2016. We recruited 88 patients, 15 benign tumors and 16 healthy subjects. Clinical characteristics were similar to other series, with a mean age of 57 years, 68.2% serous high grade subtype and 55.7% with stage IIIC. CTC were positive in 23.8% of patients (>1CTC/7,5mL). Levels of cfDNA were significantly elevated in patients than in the group of benign tumors and healthy control. CTC proved to be a negative prognostic factor of OS, with an average of 19.8 months versus 30.4 months (log-rank 4,649, p < 0.031). A high cfDNA value was also a negative prognostic factor for OS, with 22.5 months versus 28.7 months (log-rank 7.308, p < 0.007). The reduction in the integrity of cfDNA greater than 50% after chemotherapy was an early marker of resistance, with PFS of 6.4 months versus 16.0 months (HR 0.027, p < 0.02). The baseline value of cfDNA was also a negative prognostic factor for SLP, with 10 months versus 18 months (log-rank 7.233, p < 0.007). The baseline level of cfDNA and its integrity presented a predictive value of response to chemotherapy and the outcome of surgery, respectively. Conclusions: In summary, CTC and cfDNA in advanced ovarian epithelial carcinoma have been prognostic factors for survival. In addition, cfDNA has a predictive value of response. These two biomarkers may be useful in clinical practice. Legal entity responsible for the study: University Clinical Hospital Virgen Arrixaca - Murcia/ES Funding: None Disclosure: All authors have declared no conflicts of interest.

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