Mutations in circulating tumor DNA detected in the postoperative period predict poor survival in patients with ovarian cancer

Angel Chao, Shu Jen Chen, Hua Chien Chen, Kien Thiam Tan, Wen Hsiao, Shih Ming Jung, Lan Yan Yang, Kuan Gen Huang, Hung Hsueh Chou, Huei Jean Huang, Ting Chang Chang, An Shine Chao, Yun Hsien Lee, Ren Chin Wu*, Chyong Huey Lai*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

5 Scopus citations

Abstract

Background: We investigated whether mutations in plasma circulating tumor DNA (ctDNA) can provide prognostic insight in patients with different histological types of ovarian carcinoma. We also examined the concordance of mutations detected in ctDNA samples with those identified in the corresponding formalin-fixed paraffin-embedded (FFPE) tumor specimens. Methods: Between July 2016 and December 2017, 29 patients with ovarian carcinoma were prospectively enrolled. FFPE tumor specimens were obtained from all participants. A total of 187 blood samples for ctDNA analysis were collected before surgery (C0), immediate after surgery before adjuvant chemotherapy (C1), and at six-month intervals. Progression-free survival (PFS) and overall survival (OS) served as the main outcome measures. Results: The study cohort consisted of 13 (44.8%) patients with high-grade serous carcinomas (HGSC), 9 (31.0%) with clear cell carcinoma, 2 (6.9%) with mucinous carcinomas, 4 (13.8%) with low-grade serous carcinomas, and 1 (3.4%) with endometrioid carcinoma. Twenty-four (82.8%) patients had at least one detectable ctDNA variant. The concordance rate between mutations identified in pretreatment ctDNA and corresponding FFPE tumor specimens was 92.3% for patients with HGSC and 58.6% for the entire cohort. The median follow-up time was 33.15 months (range: 0.79–46.13 months). Patients with an advanced stage disease more likely had detectable ctDNA mutations before surgery (C0) and after surgery at C1, while those with HGSC more likely had ctDNA mutations detected before surgery. The presence of ctDNA mutations at C1 was an independent predictor of worse OS with a hazard ratio of 6.56 (95% confidence interval, (1.07–40.17) for detectable versus undetectable C1 ctDNA variants, p = 0.042). Conclusions: ctDNA mutations are common in patients with ovarian carcinoma. The presence of ctDNA mutations after surgery was an independent predictor of less favorable PFS and OS.

Original languageEnglish
Article number100563
Pages (from-to)100563
JournalBiomedical Journal
Volume46
Issue number5
DOIs
StatePublished - 10 2023

Bibliographical note

Copyright © 2022 Chang Gung University. Published by Elsevier B.V. All rights reserved.

Keywords

  • Circulating tumor DNA
  • Clear cell carcinoma
  • High-grade serous carcinoma
  • Ovarian cancer
  • Prognosis
  • Carcinoma
  • Circulating Tumor DNA/genetics
  • Mutation/genetics
  • Humans
  • Postoperative Period
  • Ovarian Neoplasms/genetics
  • Biomarkers, Tumor/analysis
  • Female

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