Efficacy, prognostic value of circulating tumor DNA (ctDNA) in ovarian cancer patients (122)

Abstract

<b>Objectives:</b> Detection of ovarian cancer progression is crucial in improving patient prognosis. However, existing tests based on biomarker and radiological imaging are insufficient for the early detection of recurrent ovarian cancer. Blood sample-based ctDNA samples are easily obtained and can be used for disease monitoring in ovarian cancer patients undergoing primary surgery. <b>Methods:</b> Patients diagnosed with epithelial ovarian carcinoma and control patients undergoing surgery for benign ovarian mass with CA-125 above 35 were enrolled. For ctDNA analysis, 10 mL of Whole blood samples were collected before surgery and 3, 6, 9, 12 months after surgery. Library preparation and target capture were done using a commercial kit and custom target gene panel targeting nine genes (<i>ARID1A, BRCA1, BRCA2, CCNE1, KRAS, MYC, PIK3CA, PTEN,</i> and <i>TP53</i>). Next-generation sequencing (NGS) was done with the NextSeq 550Dx System (Illumina, USA). Data analysis was performed using the custom analysis pipeline (Dxome, Korea). Variants are classified into four tiers based on their clinical significance in cancer diagnosis, prognosis, and therapeutics following the standards and guidelines established by the Association for Molecular Pathology, American Society of Clinical Oncology, and College of American Pathologists. We curated only tier I/II variants as a meaningful variation. <b>Results:</b> We analyzed 352 whole blood samples from 172 patients, including 93 patients with carcinoma (high or low-grade serous, mucinous, clear cell, or endometrioid) and 79 patients with the benign or borderline ovarian disease. Among 93 patients with carcinoma, 69.9% (65/93) were identified with tier I/II (pathogenic) somatic mutations (<i>TP53, BRCA1, BRCA2, ARID1A, MYC, PIK3CA, PTEN, KRAS</i>) from preoperatively collected samples at baseline. No pathogenic mutations were identified in benign/borderline tumor patients (0/79). For the genes covered by ctDNA and tissue-NGS assays, a total number of 76 tier I/II somatic mutations were detected in 42 patients' tissue samples, of which 90.8% (69/76) were also detected temporally matched whole 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 patients with cancer progression, 80.0% (8/10) patients were identified with the same list of mutations as the baseline. In these eight patients, ctDNA enabled early detection of future progression by an average of 41 days (maximum of 143 days) than the conventional methods. Based on three months of follow-up ctDNA, persistently elevated group patients had a worse prognosis than other groups (zero conversion, non-detectable) (figure 1).Fig. 1 <b>Conclusions:</b> Our preliminary analysis suggests that ctDNA-based surveillance may serve an important role in detecting disease progression in ovarian cancer, providing genetic characteristics of cancer. Further applicability of ctDNA in clinical decision-making should be explored.