PO-483 Improved sensitivity for non-invasive diagnosis of high-grade serous ovarian cancer

Introduction Large screening studies in ovarian cancer (OC) using CA125 and transvaginal ultrasound have not shown a significant improvement in mortality. There is a need for new diagnostic biomarkers in OC. High-grade serous ovarian cancer (HGSOC) is characterised by ubiquitous TP53 mutations and extreme genomic rearrangement. Circulating tumour DNA (ctDNA) can be detected in plasma in >80% of women with relapsed HGSOC. However, detection of ctDNA in untreated, early stage patients is more challenging due to small disease volume and low levels of ctDNA. We aim to assess the proportion of women with newly diagnosed HGSOC with detectable ctDNA using a combination of sequencing assays including a new, sensitive, whole genome sequencing analysis method. Material and methods Targeted sequencing for TP53 and shallow whole genome sequencing (sWGS) were performed on 148 plasma samples collected from women with newly diagnosed, untreated HGSOC. Results and discussions Using targeted sequencing for TP53 ctDNA can be detected in 50% of newly diagnosed HGSOC. The addition of a genome wide measure of copy number aberration (t-MAD) and in-silico size selection of DNA fragments between 90–150 bp increases rates of ctDNA detection. Using the size selected t-MAD score we see a sensitivity of 80% for a specificity of 95% to discriminate HGSOC cases from healthy controls. Conclusion Plasma ctDNA can be detected in women with newly diagnosed HGSOC using targeted sequencing for TP53 and sWGS. By combining these low cost, high throughput sequencing assays we show that ctDNA has the potential be used in a diagnostic setting in HGSOC.