Introduction/Background Knowledge regarding homologous recombination deficiency (HRD) status at diagnosis is essential to manage patients with advanced epithelial ovarian cancer (EOC). These genomic tests are performed on tumor samples and unfortunately the analysis of tumor DNA are missing 15–19% of cases.
Methodology We collected ascites or peritoneal washings (20ml) from 53 patients undergoing primary or secondary laparoscopy for suspicion of EOC, or therapeutic paracentesis. A Cancer Gene Panel (CGP) was analyzed by Next generation sequencing (NGS) for TP53 genes and HR genes and shallow Whole Genome Sequencing (sWGS) was used to measure genomic instability on cftDNA from peritoneal fluid
Results A total of 53 patients were included. Cell-free DNA (cfDNA) was detectable in 49/53 patients (92,5%) even when there was little peritoneal fluid (<100cc) at laparoscopy (n=7). Median cfDNA extracted from 20ml peritoneal fluid or washings was high at 3700 ng/ml (range 109 – 65 000 ng/ml) and median turn-around testing time was 21 days. 42 patients (86%) had a TP53 pathogenic variant, all cases were HGSOC. Seven (14%) and 5 (10%) had a BRCA1 or BRCA2 pathogenic variant, respectively. The sensitivity, specificity and concordance of acfDNA compared with tumor testing for TP53 pathogenic variant detection were 97% (95% IC : 86%-100%), 83% (95% IC : 43%-100%) and 95% (K = 0,81: P <0,001) respectively. NGS CGP on cftDNA was contributive in 5 patients with failed NGS CGP on tumor DNA from tissue, including one patient with a BRCA2 pathogenic variant identified in cftDNA. Genomic instability was assessed by sWGS on cftDNA and provided a contributive result for all samples tested, including 7 for which matching tissue-based GIS testing failed.
Conclusion Genomic profiling on cftDNA from peritoneal fluid is feasible and yields high quantity of tumor DNA.HRD testing on cfDNA from peritoneal fluid should be proposed to every patient undergoing primary laparoscopy.
Disclosures Work supported by donations from patients and families through the ‘Parrainage Cancers Gynécologiques’ program
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