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

Cristina Taliento; Giampaolo Morciano; Camilla Nero; Wouter Froyman; Giuseppe Vizzielli; Matteo Pavone; Stefano Salvioli; Mara Tormen; Francesco Fiorica; Gennaro Scutiero; Giovanni Scambia; Carlotta Giorgi; Pantaleo Greco; Paolo Pinton

doi:10.1136/ijgc-2024-005313

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

Int J Gynecol Cancer. 2024 Apr 23:ijgc-2024-005313. doi: 10.1136/ijgc-2024-005313. Online ahead of print.

Authors

Cristina Taliento^{1

2}, Giampaolo Morciano³, Camilla Nero^{4

5}, Wouter Froyman^{2

6}, Giuseppe Vizzielli⁷, Matteo Pavone^{4

8}, Stefano Salvioli⁹, Mara Tormen¹, Francesco Fiorica¹⁰, Gennaro Scutiero¹, Giovanni Scambia⁴, Carlotta Giorgi³, Pantaleo Greco¹, Paolo Pinton¹¹

Affiliations

¹ Department of Medical Sciences, Obstetrics and Gynecology Unit, "S. Anna" University Hospital, University of Ferrara, Ferrara, Italy.
² Department of Development and Regeneration, KU Leuven, Leuven, Belgium.
³ Department of Medical Sciences, Section of Experimental Medicine and Laboratory for Technologies of Advanced Therapies (LTTA), University of Ferrara, Ferrara, Italy.
⁴ Department of Women and Child Health, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy.
⁵ Università Cattolica del Sacro Cuore Dipartimento Scienze della Vita e Sanità Pubblica, Rome, Italy.
⁶ Department of Obstetrics and Gynecology, University Hospitals KU Leuven, Leuven, Belgium.
⁷ Department of Obstetrics and Gynecology, University of Udine Medical Area Department, Udine, Italy.
⁸ IHU Strasbourg, Institute of Image Guided Surgery, Strasbourg, France.
⁹ Department of Neuroscience and Rehabilitation, University of Ferrara, Ferrara, Italy.
¹⁰ Azienda ULSS 9 Scaligera, Verona, Veneto, Italy.
¹¹ Department of Medical Sciences, Section of Experimental Medicine and Laboratory for Technologies of Advanced Therapies (LTTA), University of Ferrara, Ferrara, Italy paolo.pinton@unife.it.

PMID: 38658022
DOI: 10.1136/ijgc-2024-005313

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.

Keywords: Carcinoma, Ovarian Epithelial; Gynecologic Surgical Procedures; Gynecology; Neoplasm Recurrence, Local; Ovarian Neoplasms.