Baseline value and longitudinal kinetics of circulating nucleosomes during neo-adjuvant chemotherapy in newly diagnosed ovarian cancer: Results from a GINECO/GINEGEPS study of the randomized phase II CHIVA trial

Purpose Circulating nucleosomes (DNA wound around histone proteins) are emerging cancer biomarkers. We investigated their association with clinical outcomes in advanced ovarian cancer. Patients and methods Circulating levels and longitudinal kinetics of two nucleosomes (H3K27Me3 and H3K36Me3, log-scale) were assessed at baseline, during neoadjuvant chemotherapy after interval cytoreductive surgery, and at progression in patients with advanced ovarian cancer patients from the randomized phase II CHIVA trial. Nucleosomes were measured with Nu.Q® immunoassays,compared to those from 201 healthy subjects, and analyzed in relation to surgical outcomes, progression-free survival, with respect to the modeled CA–25 ELIMination rate constant K (KELIM) along with established clinical covariates. Results H3K27Me3 and H3K36me3 nucleosome concentrations were available for 148/188 patients. Both nucleosomes were significantly higher in ovarian cancer patients compared with healthy controls and showed correlated baseline levels. Lower baseline H3K36Me3 was independently associated with complete interval cytoreduction surgery and progression-free survival, complementary to CA–25 KELIM. Longitudinal changes in nucleosome levels showed a decrease during neoadjuvant chemotherapy, but were not associated with radiological response, completeness of interval cytoreductive surgery or progression-free survival. Conclusion Baseline H3K36Me3 and H3K27Me3 levels may represent non-invasive biomarkers in advanced ovarian cancer and warrant further evaluation for their potential clinical utility.