Liquid Biopsies for Improving the Pre-operative Diagnosis of Ovarian Cancer

An accurate preoperative diagnosis of an ovarian tumor is important for the patients' surgical work-up, proper referral to oncological centers and for the patients' mental wellbeing since uncertainty about the nature (benign vs malignant) of an ovarian tumor may cause anxiety. Currently, the Risk of Malignancy Index (RMI), with a cut-off value of 200, is often used in the Netherlands to select patients with an increased risk of ovarian cancer that should be referred to an oncologic center. However sensitivity and specificity of the RMI-score are far from optimal. Around 40% of the referred patients have benign disease in final pathological examination. Therefore, other models have been developed, such as the IOTA (International Ovarian Tumor Analysis) consortium algorithms, but these models require training, expertise and are subjective. To determine the nature of an ovarian tumor, histological examination is the golden standard. However, a pre-operative biopsy of an ovarian tumor is undesirable because of the risk of spill of tumor cells in the abdominal cavity. Therefore, there is an urgent need for non-invasive diagnostic tools to determine the nature of an ovarian tumor pre-operatively. Liquid biopsies could be such a non-invasive tool. Currently, circulating tumor DNA (ctDNA) circulating tumor cells (CTC), microRNA (miRNA) and tumor-educated platelets (TEPs) are available and can function as a potential blood-based biosource for (early) cancer diagnostics. Previous studies show promising results of liquid biopsies are used in (early) detection of cancer, also for ovarian cancer. Therefore, a diagnostic algorithm will be developed using ct-DNA and TEPs as liquid biomarkers in combination with the existing ultrasound models (RMI and IOTA-models) and tumor markers (CA125 and HE4) to differentiate between early ovarian cancer and benign ovarian tumors pre-operatively. Nature and extent of the burden and risks associated with participation, benefit and group relat