792 Circulating tumour DNA as prognostic factor in endometrial cancer – final results from an international multicenter study

Introduction/Background Analysis of circulating tumour DNA (ctDNA) is a promising non-invasive technique that may serve as a diagnostic, prognostic, and disease-monitoring marker. Aim of this study is to investigate the association of ctDNA with clinicopathological characteristics and oncological outcome in endometrial cancer patients. Methodology Blood plasma samples were collected pre-operatively from 83 patients diagnosed with endometrial cancer and treated at the Bern University Hospital, Switzerland (n= 36), Oslo University Hospital (n= 34) and Haukeland University Hospital (n= 13), Norway. cfDNA was isolated and selected mutations were detected using the Oncomine™ Pan-Cancer cell free assay. Comparative analysis of whole exome sequencing data from tumour tissue was performed. Results Baseline clinicopathological data and their association with ctDNA status are provided in table 1. Mean concentration of cfDNA was 11.4 ng/ml. 16 (19.3%) patients were considered ctDNA positive with at least one mutation found in plasma. Mutations in ctDNA were found for the following genes: TP53, ESR1, CTNNB1, PIK3CA, KRAS, NRAS, GNAS, and CCND3. Most mutations were concordant between the solid and liquid biopsies. Interestingly, although 52% of patients presented mutations in PTEN in their primary tumour, the same alteration was not found in the ctDNA. Mean follow-up was 45.7 months. Patients with positive ctDNA presented with a significantly shorter recurrence-free (P= .048) and disease-specific (P= .014) survival compared to ctDNA negative patients. In multivariable Cox regression analysis including stage, histological subtype, grading, and lymphovascular space invasion, ctDNA positivity remained an independent predictor of recurrence (HR 6.0, 95% CI 1.7 – 21.4, p= .009) and disease-specific death (HR 19.4, 95% CI 2.7 – 139.7, p= .004). Conclusion This study shows the feasibility of using a gene panel to identify ctDNA positive patients which will facilitate its use on a larger scale. ctDNA positivity was significantly associated with worse oncological outcome. Disclosures No conflicts of interests related to this work. This study was supported by grants from Swiss National Science Foundation, Foundation for clinical-experimental cancer research, SAKK/ Dr. Paul Jannsen Fellowship, Rakel og Otto Kristian Bruun's Legat.