Pilot experience using tumor-based next generation sequencing increases compliance and reduces barriers for ovarian cancer genetic testing

Objectives: Although hereditary risk assessment is advised for all ovarian/tubal/peritoneal (OTP) cancer patients, a variety of barriers limit universal compliance. A workflow using tumor-based next generation sequencing (NGS) germline testing implemented by the pathologist at the time of primary or interval debulking surgery. The objective of this study is to report compliance and turnaround time of a pilot workflow of germline testing via tumor-based NGS in OTP cancer. may reduce some of these barriers. Methods: We identified all patients with a new diagnosis of epithelial OTP carcinoma who underwent primary or interval debulking surgery from January to August 2020. All patients were recommended to undergo tumor and germline sequencing, either through our institutional NGS platform or through commercial sequencing. We compared time to results as well as influence of results on maintenance/second-line therapy. Results: We identified 35 patients with a median age of 61 (range 29-78) and a median follow-up time of 5 months (range 0-13). Our stage breakdown included 8 Stage I, 4 Stage II, 20 Stage III, and 3 Stage IV patients. A total of 24 patients had high grade serous carcinoma, with 5 endometrioid, 3 clear cell, 2 mucinous, and one high grade NOS tumor. A total of 11 patients underwent interval debulking surgery after neoadjuvant chemotherapy. All but 2 (94.2%) of patients received a genetic counseling referral. A total of 2 patients did not have sequencing performed, while 1 patient did not have enough tumor for sequencing at the time of interval debulking surgery. A total of 10 patients had both tumor and germline sequencing performed at the time of tumor testing, while 20 others had tumor only sequencing. For those patients who did not have a known hereditary germline mutation prior to surgery, the mean turnaround time for germline genetic testing results was 26.5 days (range 19-51) in the NGS + germline group whereas the median turnaround time after commercial testing was 75 days (regardless of primary or interval debulking, range 19-202), p=0.006. A total of 5 patients were identified as germline carriers of the BRCA1 or BRCA2 mutation, with 1 addition germline finding of a pathogenic variant in ATM. An additional 5 patients had somatic pathogenic mutations in homologous recombination repair pathway genes, all of whom are receiving or being considered for PARP inhibitor maintenance after primary treatment. Conclusions: Combining somatic and germline tumor testing at the time of staging/debulking surgery requires upfront coordination with pathology and patient consent, but streamlines the genetic testing process to improve testing rates allow timely results for treatment planning. This approach may also identify additional patients with homologous recombination deficient tumors through simultaneous somatic mutation assessment.