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Serial Circulating Tumor DNA Analysis with a Tumor-Naïve Next-Generation Sequencing Panel Detects Minimal Residual Disease and Predicts Outcome in Ovarian Cancer

 Jinho Heo  ;  Yoo-Na Kim  ;  Saeam Shin  ;  Kyunglim Lee  ;  Ji-Hyun Lee  ;  Yong Jae Lee  ;  Zisun Choi  ;  Jihyang Park  ;  Seungki Min  ;  Sang Wun Kim  ;  Jong Rak Choi  ;  Sunghoon Kim  ;  Seung-Tae Lee  ;  Jung-Yun Lee 
 CANCER RESEARCH, Vol.84(3) : 468-478, 2024-02 
Journal Title
Issue Date
Biomarkers, Tumor / genetics ; Circulating Tumor DNA* / genetics ; Female ; High-Throughput Nucleotide Sequencing ; Humans ; Mutation ; Neoplasm Recurrence, Local / genetics ; Neoplasm Recurrence, Local / pathology ; Neoplasm, Residual / diagnosis ; Neoplasm, Residual / genetics ; Ovarian Neoplasms* / genetics
Circulating tumor DNA (ctDNA) may aid in personalizing ovarian cancer therapeutic options. Here, we aimed to assess the clinical utility of serial ctDNA testing using tumor-naïve, small-sized next-generation sequencing (NGS) panels. A total of 296 patients, including 201 with ovarian cancer and 95 with benign or borderline disease, were enrolled. Samples were collected at baseline (initial diagnosis or surgery) and every 3 months after that, resulting in a total of 811 blood samples. Patients received adjuvant therapy based on the current standard of care. Cell-free DNA was extracted and sequenced using an NGS panel of 9 genes: TP53, BRCA1, BRCA2, ARID1A, CCNE1, KRAS, MYC, PIK3CA, and PTEN. Pathogenic somatic mutations were identified in 69.2% (139/201) of patients with ovarian cancer at baseline but not in those with benign or borderline disease. Detection of ctDNA at baseline and/or at 6 months follow-up was predictive of progression-free survival (PFS). PFS was significantly poorer in patients with detectable pathogenic mutations at baseline that persisted at follow-up than in patients that converted from having detectable ctDNA at baseline to being undetectable at follow-up; survival did not differ between patients without pathogenic ctDNA mutations in baseline or follow-up samples and those that converted from ctDNA positive to negative. Disease recurrence was also detected earlier with ctDNA than with conventional radiologic assessment or CA125 monitoring. These findings demonstrate that serial ctDNA testing could effectively monitor patients and detect minimal residual disease, facilitating early detection of disease progression and tailoring of adjuvant therapies for ovarian cancer treatment.
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1. College of Medicine (의과대학) > Dept. of Laboratory Medicine (진단검사의학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Obstetrics and Gynecology (산부인과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Sang Wun(김상운) ORCID logo https://orcid.org/0000-0002-8342-8701
Kim, Sung Hoon(김성훈) ORCID logo https://orcid.org/0000-0002-1645-7473
Kim, Yoo‐Na(김유나)
Shin, Saeam(신새암) ORCID logo https://orcid.org/0000-0003-1501-3923
Lee, Kyunglim(이경림)
Lee, Seung-Tae(이승태) ORCID logo https://orcid.org/0000-0003-1047-1415
Lee, Yong Jae(이용재) ORCID logo https://orcid.org/0000-0003-0297-3116
Lee, Jung-Yun(이정윤) ORCID logo https://orcid.org/0000-0001-7948-1350
Lee, Ji Hyun(이지현)
Choi, Jong Rak(최종락) ORCID logo https://orcid.org/0000-0002-0608-2989
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