ArticleTherapeutic advances in medical oncology2025
Pretreatment circulating tumor DNA and tissue genomic profiling concordance in ovarian cancer: a prospective observational study of influencing factors and clinical implications.
Article in Therapeutic advances in medical oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Next-generation sequencing (NGS) of plasma circulating tumor DNA (ctDNA) shows promise as a minimally invasive alternative to tissue sequencing. However, concordance between genomic alterations in tumor tissue and plasma ctDNA remains incompletely characterized in ovarian cancer, particularly in the pretreatment setting. Objectives: To identify factors influencing concordance between tissue and ctDNA genomic profiling and explore the potential clinical implications (including treatment and survival outcomes) of this concordance. Design: A prospective, single-center, observational study. Methods: A total of 40 matched pretreatment tumor specimens and blood samples were prospectively collected from patients with ovarian cancer and subsequently sequenced using a customized gene panel. Overall and individual concordance rates were calculated as the ratio of total concordant mutations to total tissue mutations, with patients stratified into highly concordant (⩾50%) and poorly concordant (<50%) groups. Results: The overall tissue-plasma concordance rate was 40.8%, with shared variants exhibiting identical abundance patterns across sample types and capturing the majority of functionally relevant mutations. Single-nucleotide variants in tissue showed a higher detection rate in plasma than structural variants. Individual concordance rates displayed significant inter-patient variability. Higher tissue tumor mutation burden (odds ratio (OR) 2.165, 95% confidence interval (CI) 1.183-3.965) and plasma ctDNA fraction (OR 1.433, 95% CI 1.063-1.933) were independently associated with high concordance rates. In advanced-stage patients, the poorly concordant group showed lower CA125 elimination rate constant K (KELIM) scores (median 0.7 vs 1.3; 15.0% vs 68.8% patients with score ⩾1), indicating reduced chemosensitivity. The poorly concordant group demonstrated a higher disease recurrence rate (40.0% vs 6.2%) and elevated early recurrence risk (12-month progression-free survival rate 82.0% vs 100.0%) compared with the highly concordant group. Conclusion: In the field of ovarian cancer, NGS of ctDNA showed moderate concordance with tissue-based sequencing in the pretreatment setting, influenced by both technical and biological factors. The tissue-plasma concordance may serve as a chemosensitivity and prognostic indicator.
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