Abstract 588P
Background
Effective detection of ovarian cancer progression and recurrence is crucial in improving patient prognosis. Existing tests based on biomarker (CA-125) 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 disease progression in ovarian cancer patients undergoing debulking surgery followed by adjuvant therapy.
Methods
10 mL of blood samples were collected from patient with ovarian carcinoma at Severance Hospital, Seoul, Korea (Oct 2019–Feb 2022). Samples were collected at baseline just prior to surgery and every three months thereafter. Conventional post operative monitoring was performed using CA125, HE4, MRI, and PET-CT. Custom target gene panel targeting nine genes (TP53, BRCA1, BRCA2, ARID1A, CCNE1, KRAS, MYC, PIK3CA and PTEN). Next-generation sequencing was done with the NextSeq System (Illumina, USA). Data analysis was performed using the custom pipeline (Dxome, Korea). Retrospective chart review was done to obtain relevant clinical information.
Results
We analyzed a total of 703 whole blood samples from 243 patients, including 170 patients with carcinoma (high or low-grade serous, mucinous, clear cell, or endometrioid) and 73 patients with benign/borderline ovarian disease. 71.2% (121/170) carcinoma patients were identified with tier I/II (pathogenic) somatic mutations from preoperative samples at baseline. No pathogenic mutations were identified in benign/borderline tumor patients (0/73). Of the 38 progressive patients with baseline ctDNA mutation, 92.1% (35/38) patients were identified with the same list of mutations at the baseline. In these 35 patients, ctDNA enabled early detection of future progression by an average of 50.9 days (maximum of 267 days) than the conventional diagnostic methods. Based on 6 months follow up ctDNA analysis, persistent elevated group showed a shorter median survival compared with zero conversion group (7.9 vs 31.2 months; P < 0.001).
Conclusions
Our analysis suggests that ctDNA-based surveillance may serve an important role in the early detection of disease progression in ovarian cancer, allowing prognostic stratification and prompt clinical decision making with progression.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
DXOME CO., LTD.
Disclosure
S. Lee: Financial Interests, Personal and Institutional, Member of the Board of Directors: DXOME CO., LTD. J.R. Choi: Financial Interests, Personal and Institutional, Member of the Board of Directors: DXOME CO., LTD. All other authors have declared no conflicts of interest.