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Original research
Circulating tumor DNA as a biomarker for predicting progression-free survival and overall survival in patients with epithelial ovarian cancer: a systematic review and meta-analysis
  1. Cristina Taliento1,2,
  2. Giampaolo Morciano3,
  3. Camilla Nero4,5,
  4. Wouter Froyman2,6,
  5. Giuseppe Vizzielli7,
  6. Matteo Pavone4,8,
  7. Stefano Salvioli9,
  8. Mara Tormen1,
  9. Francesco Fiorica10,
  10. Gennaro Scutiero1,
  11. Giovanni Scambia4,
  12. Carlotta Giorgi3,
  13. Pantaleo Greco1 and
  14. Paolo Pinton3
    1. 1Department of Medical Sciences, Obstetrics and Gynecology Unit, "S. Anna" University Hospital, University of Ferrara, Ferrara, Italy
    2. 2Department of Development and Regeneration, KU Leuven, Leuven, Belgium
    3. 3Department of Medical Sciences, Section of Experimental Medicine and Laboratory for Technologies of Advanced Therapies (LTTA), University of Ferrara, Ferrara, Italy
    4. 4Department of Women and Child Health, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
    5. 5Università Cattolica del Sacro Cuore Dipartimento Scienze della Vita e Sanità Pubblica, Rome, Italy
    6. 6Department of Obstetrics and Gynecology, University Hospitals KU Leuven, Leuven, Belgium
    7. 7Department of Obstetrics and Gynecology, University of Udine Medical Area Department, Udine, Italy
    8. 8IHU Strasbourg, Institute of Image Guided Surgery, Strasbourg, France
    9. 9Department of Neuroscience and Rehabilitation, University of Ferrara, Ferrara, Italy
    10. 10Azienda ULSS 9 Scaligera, Verona, Veneto, Italy
    1. Correspondence to Professor Paolo Pinton, Section of Experimental Medicine and Laboratory for Technologies of Advanced Therapies (LTTA), University of Ferrara Department of Medical Sciences, Ferrara 44121, Italy; paolo.pinton{at}unife.it

    Abstract

    Objectives Circulating tumor DNA (ctDNA) is emerging as a potential prognostic biomarker in multiple tumor types. However, despite the many studies available on small series of patients with ovarian cancer, a recent systematic review and meta-analysis is lacking. The objective of this study was to determine the association of ctDNA with progression-free-survival and overall survival in patients with epithelial ovarian cancer.

    Methods An electronic search was conducted using PubMed (MEDLINE), Embase, CENTRAL (Cochrane Library), and CINAHL-Complete from January 2000 to September 15, 2023. To be included in the analysis the studies had to meet the following pre-specified inclusion criteria: (1) evaluable ctDNA; (2) progression-free-survival and overall survival reported as hazard ratio (HR); and (3) the patient population had epithelial ovarian cancer at the time of ctDNA detection. We evaluated the association of ctDNA with progression-free survival and overall survival. Secondary outcomes focused on sub-group analysis of genomic alterations and international Federation of Gynecology and Obstetrics (FIGO) stage.

    Results A total of 26 studies reporting on 1696 patients with epithelial ovarian cancer were included. The overall concordance rate between plasma-based and tissue-based analyses was approximately 62%. We found that a high level of ctDNA in epithelial ovarian cancer was associated with worse progression-free survival (HR 5.31, 95% CI 2.14 to 13.17, p<0.001) and overall survival (HR 2.98, 95% CI 1.86 to 4.76, p<0.0001). The sub-group analysis showed a greater than threefold increase in the risk of relapse in patients with positive HOXA9 meth-ctDNA (HR 3.84, 95% CI 1.57 to 9.41, p=0.003).

    Conclusions ctDNA was significantly associated with worse progression-free survival and overall survival in patients with epithelial ovarian cancer. Further prospective studies are needed.

    PROSPERO registration number CRD42023469390.

    • Carcinoma, Ovarian Epithelial
    • Gynecologic Surgical Procedures
    • Gynecology
    • Neoplasm Recurrence, Local
    • Ovarian Neoplasms

    Data availability statement

    Data are available upon reasonable request. All data relevant to the study are included in the article or uploaded as supplementary information.

    https://doi.org/10.1136/ijgc-2024-005313

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      Data availability statement

      Data are available upon reasonable request. All data relevant to the study are included in the article or uploaded as supplementary information.

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      Footnotes

      • X @giusvizzielli

      • Contributors Concept and design: CT, GM, PP, CG, PG. Acquisition, analysis, or interpretation of data: CT, SS, MT, MP. Drafting of the manuscript: CT, GM, CN, WF. Critical revision of the manuscript for important intellectual content: GV, PP, PG, CG, MP, FF, WF. Statistical analysis: CT, SS. Administrative, technical, or material support: GM, PP. Supervision: GM, PP, WF, PG, GScu, GSca, GV. Guarantors: CT, PP.

      • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

      • Competing interests CN: travel support from AZ, Illumina. Sponsored talks from Veeva, Illumina, MDS, AZ.

      • Provenance and peer review Not commissioned; externally peer reviewed.

      • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.