Cell-free DNA dynamics and progression-free survival in metastatic gastroesophageal adenocarcinoma: insights from the REGIRI-PRODIGE 58 ancillary study

Cell-free DNA (cfDNA) analysis is an emerging tool for diagnosis, prognosis, and monitoring in cancer. This ancillary study of the REGIRI-PRODIGE 58 trial (NCT03722108) evaluated cfDNA dynamics in patients with metastatic gastroesophageal adenocarcinoma (mGA) treated with regorafenib plus irinotecan. Plasma samples from 34 patients in the experimental arm were analyzed (239 samples at baseline, post-treatment initiation [days 2, 8, 15 of Cycle 1; days 1, 8, 15 of Cycle 2]). cfDNA was extracted, quantified by fluorimetry, and characterized by fragment analysis. Baseline concentrations were dichotomized into "low" and "high" subgroups using a 2.07 ng/µL threshold. Changes from baseline to the final timepoint defined four dynamic subgroups (low-low, low-high, high-low, high-high). At baseline, 27 patients (79.4%) had low cfDNA concentrations and 7 (20.5%) high ctDNA. Progression-free survival (PFS) was longer in the low group (median 4.51 months) versus the high group (median 1.60 months; p = 0.0084). Longitudinally, the low-low subgroup had longer PFS than the high-high subgroup (3.61 vs 1.45 months; p = 0.0004). Baseline and dynamic cfDNA concentrations were significantly associated with PFS in patients with mGA treated with regorafenib plus irinotecan, supporting cfDNA as a potential prognostic biomarker for validation in larger cohorts.

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Journal
npj Precision Oncology
Published
2026-06-26
DOI
https://doi.org/10.1038/s41698-026-01564-1
Primary Topic
Cancer Genomics and Diagnostics
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article
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article

Cell-free DNA dynamics and progression-free survival in metastatic gastroesophageal adenocarcinoma: insights from the REGIRI-PRODIGE 58 ancillary study

Alexandre Harlé, Méher Ben Abdelghani, Damien Botsen, Emmanuelle Samalin et al.
npj Precision Oncology
Cancer Genomics and Diagnostics
article

Cell-free DNA dynamics and progression-free survival in metastatic gastroesophageal adenocarcinoma: insights from the REGIRI-PRODIGE 58 ancillary study

Alexandre Harlé, Méher Ben Abdelghani, Damien Botsen, Emmanuelle Samalin, Faïza Khemissa, Ludovic Evesque, Hélène Senellart, Slimane Dermeche, Audrey Hennequin, Nicolas De Sousa Carvalho, Emmanuel Guardiola, David Tougeron, Christelle De La Fouchardière, Anthony Turpin, Olivier Bouché, Anthony Lopez, Aziz Zaanan, Valérie Ly Le Brun, Olivier Dubreuil, Alix Mérigout
article en

Abstract

Cell-free DNA (cfDNA) analysis is an emerging tool for diagnosis, prognosis, and monitoring in cancer. This ancillary study of the REGIRI-PRODIGE 58 trial (NCT03722108) evaluated cfDNA dynamics in patients with metastatic gastroesophageal adenocarcinoma (mGA) treated with regorafenib plus irinotecan. Plasma samples from 34 patients in the experimental arm were analyzed (239 samples at baseline, post-treatment initiation [days 2, 8, 15 of Cycle 1; days 1, 8, 15 of Cycle 2]). cfDNA was extracted, quantified by fluorimetry, and characterized by fragment analysis. Baseline concentrations were dichotomized into "low" and "high" subgroups using a 2.07 ng/µL threshold. Changes from baseline to the final timepoint defined four dynamic subgroups (low-low, low-high, high-low, high-high). At baseline, 27 patients (79.4%) had low cfDNA concentrations and 7 (20.5%) high ctDNA. Progression-free survival (PFS) was longer in the low group (median 4.51 months) versus the high group (median 1.60 months; p = 0.0084). Longitudinally, the low-low subgroup had longer PFS than the high-high subgroup (3.61 vs 1.45 months; p = 0.0004). Baseline and dynamic cfDNA concentrations were significantly associated with PFS in patients with mGA treated with regorafenib plus irinotecan, supporting cfDNA as a potential prognostic biomarker for validation in larger cohorts.

npj Precision Oncology
Centre National de la Recherche Scientifique (FR), Inserm (FR), Université Paris Cité (FR), Université de Lille (FR), Centre Hospitalier Universitaire de Lille (FR), Centre Hospitalier de Perpignan (FR), Lille’s Cardiology Hospital (FR), Centre Georges François Leclerc (FR), Assistance Publique – Hôpitaux de Paris (FR), Institut de Cancérologie de Lorraine (FR), Hôpital Européen Georges-Pompidou (FR), Centre Léon Bérard (FR), Centre Hospitalier Universitaire de Reims (FR), Hôpital Européen (FR), Centre Hospitalier Universitaire de Poitiers (FR), Groupe Hospitalier Diaconesses Croix Saint-Simon (FR), Institut Génétique Nantes Atlantique (FR), Institut de Recherche en Cancérologie de Montpellier (FR), UniCancer Group (FR), Hôpital Universitaire Dupuytren (FR), Institut Paoli-Calmettes (FR), Centre Antoine Lacassagne (FR), Institut Jean Godinot (FR), Université de Lorraine (FR), Université de Reims Champagne-Ardenne (FR)
Good health and well-being
Openalex Percentile: Top 8%
Cancer Genomics and Diagnostics
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