Abstract 756P
Background
Early detection of ovarian cancer progression is crucial in improving prognosis. However, existing tests based on biomarker and radiological imaging are insufficient for the early detection of recurrent ovarian cancer. This study aimed to assess the feasibility of using circulating tumor DNA (ctDNA) as a biomarker for post-operative cancer progression in ovarian cancer patients.
Methods
For ctDNA analysis, 10 mL of blood samples were collected from patients (pts) diagnosed with epithelial ovarian tumors. Samples were collected at baseline right before surgery and every three months after that, alongside the usual surveillance by CA-125, HE4, MRI, and PET-CT. We used custom NGS target gene panel including ARID1A, BRCA1, BRCA2, CCNE1, KRAS, MYC, PIK3CA, PTEN, and TP53. Variants are classified into four tier system established by the Association for Molecular Pathology.
Results
We analyzed 233 blood samples from 143 pts, including 90 pts with carcinoma (high or low-grade serous, mucinous, clear cell, or endometrioid) and 53 pts with benign/borderline tumors. 70.0% (63/90) carcinoma pts were identified with tier I/II(pathogenic) somatic mutations from samples at baseline. No pathogenic mutations were identified in benign/borderline tumor pts (0/53). For the genes covered by ctDNA and tissue-NGS assays, a total number of 76 tier I/II somatic mutations were detected in 42 pts’ tissue samples, of which 90.8% (69/76) were also detected temporally matched blood samples. Of the 42 tissue samples with mutations, 92.9% (39/42) had at least one concordant genomic mutation in ctDNA analysis. Among ten pts with cancer progression, 80.0% (8/10) pts were identified with the same list of mutations as the baseline. In these eight pts, ctDNA enabled early detection of future progression by an average of 41 days (maximum of 143 days) than the conventional methods.
Conclusions
Our preliminary analysis suggests that ctDNA-based surveillance may serve an important role in the early detection of disease progression in ovarian cancer, and further applicability of ctDNA in clinical decision making may be explored. Samples are currently under consecutive collection, and newly added examples will allow more comprehensive analysis to evaluate the role of ctDNA.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Dxome Co., Ltd.
Disclosure
S.T. Lee, J.R. Choi: Financial Interests, Personal and Institutional, Stocks/Shares: Dxome Co., Ltd. All other authors have declared no conflicts of interest.