1223P - Homologous recombination deficiency (HRD) testing on ovarian cancer ascites: A feasibility study

Background

BRCA1/2 and HRD tumor testing should be performed at diagnosis for patients with high-grade epithelial ovarian cancers (EOC). Peritoneal fluids drainage is carried out for those patients during and/or before surgery for staging and palliative intents. We previously demonstrated the feasibility of BRCA testing on malignant ascites. We sought to investigate the feasibility of HRD testing on the cytology specimens from EOC ascites.

Methods

At least 200 ml of ascitic fluid were prospectively collected during primary surgery from patients with EOC. The fluids were overturned, poured into four 50 ml tubes and centrifuged at 1700 rpm for 10 minutes at room temperature. Pellets were included in agarose gel and formalin-fixed paraffin-embedded (FFPE) cell blocks were obtained. DNA extracted from tumor-positive cell blocks was subjected to the SOPHiA DDM™ Dx HRD Solution. Concordances of BRCA1/2 and HRD status, TP53 mutation and CCNE1 copy number gain (CNG) between ascites and matched tissue tumor samples were assessed.

Results

Data were available for 8 ascites specimens with a median tumor cell content of 65% (range: 20-80%). BRCA1/2 status was evaluable for all samples with 100% concordance between cytology and tissue samples, including 6 BRCA1/2 wild-type cases and 2 cases harboring variants of unknown significance. HRD status was determined in 7/8 ascites specimens. HRD status was undetermined in 1 tissue sample with informative HRD testing on matched ascites. HRD status concordance among 6 evaluable paired cytology-tissue samples was 83%, including 5 HRD-negative and one HRD-positive case. Discordant and undetermined results were seen from ascites specimens with low tumor cell content. TP53 mutations and CCNE1 CNG were detected in 4 and 1 cytology samples, respectively, with 88% of concordance with matched tissue analysis.

Conclusions

This exploratory study showed that HRD testing on cytological specimens from EOC ascites is feasible but standardized pre-analytical procedures are required to ensure adequate samples for the analysis. Ascites might represent a valid alternative for early BRCA1/2 and HRD status evaluation in women with EOC when tissue samples are inadequate/insufficient.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Massimo Barberis.

Funding

Has not received any funding.

Disclosure

E. Guerini Rocco: Financial Interests, Personal and Institutional, Advisory Board, Invited Speaker, Funding: AstraZeneca, GSK; Financial Interests, Personal, Advisory Board, Invited Speaker: Novartis; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal and Institutional, Funding, Invited Speaker: ThermoFisher Scientific. N. Colombo: Financial Interests, Personal, Advisory Board, Various: Roche, PharmaMar, AstraZeneca, MSD/Merck, Clovis Oncology, GSK, Pfizer, Immunogen, Mersana; Financial Interests, Personal, Invited Speaker, Congress, Symposia, Lectures: AstraZeneca; Financial Interests, Personal, Invited Speaker, Lectures: Novartis; Financial Interests, Personal, Advisory Board, Lectures: Eisai; Financial Interests, Personal, Advisory Board, Advisory role: Nuvation Bio, Pieris; Financial Interests, Personal, Advisory Board, Advisory Role: Onxerna; Financial Interests, Institutional, Research Grant: AstraZeneca, PharmaMar, Roche; Non-Financial Interests, Other, Steering committee member Clinical Guidelines: ESMO; Non-Financial Interests, Leadership Role, Chair, Scientific Committee: ACTO( Alleanza Contro il Tumore Ovarico). N. Fusco: Financial Interests, Personal, Invited Speaker: Merck Sharp & Dohme (MSD), Boehringer Ingelheim, AstraZeneca, Daiichi Sankyo, GSK, Gilead; Financial Interests, Personal and Institutional, Research Grant: Novartis. All other authors have declared no conflicts of interest.