<p>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; <i>p</i> = 0.0084). Longitudinally, the low-low subgroup had longer PFS than the high–high subgroup (3.61 vs 1.45 months; <i>p</i> = 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.</p>

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

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

摘要

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.