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Publications

Journal Article Ahead of print

PubMed: 42385345 DOI: 10.1016/j.tranon.2026.102896

Baseline value and longitudinal kinetics of circulating nucleosomes during neo-adjuvant chemotherapy in newly diagnosed ovarian cancer: Results from a GINECO/GINEGEPS study of the randomized phase II CHIVA trial.

Transl Oncol 71:102896

Authors: Pauline Corbaux, Olivier Colomban, Gaelle Lescuyer, Isabelle Ray-Coquard, Gaëtan De Rauglaudre, Florence Joly, Cyril Abdeddaim, Pierre Combe, Cyriac Blonz, Guillaume Bataillon, Jérôme Meunier, Jérôme Alexandre, Dominique Berton, Marie-Christine Kaminsky, Diana Bello Roufai, Alexandra Leary, Laurence Venat, Nadine Dohollou, Christophe Louvet, Coriolan Lebreton, Sophie Abadie-Lacourtoisie, Jean-Pierre Lotz, Laure Favier, Michel Fabbro, Nathalie Bonichon-Lamichhane, Jean-Emmanuel Kurtz, Philippe Follana, Eric Pujade-Lauraine, Lea Payen, Benoit You

Affiliations

  • Center for Innovation in Cancerology of Lyon (CICLY) EA 3738, Hospices Civils of Lyon, Faculty of Medicine and Maieutic Lyon Sud, Claude Bernard University Lyon I, 69921, Oullins, France; Medical Oncology, Institut de Cancérologie et d'Hématologie Universitaire de Saint-Étienne (ICHUSE), Centre Hospitalier Universitaire de Saint-Etienne, France; GINECO (Groupe d'Investigateurs Nationaux pour l'Etude des Cancers de l'Ovaire), France.
  • Center for Innovation in Cancerology of Lyon (CICLY) EA 3738, Hospices Civils of Lyon, Faculty of Medicine and Maieutic Lyon Sud, Claude Bernard University Lyon I, 69921, Oullins, France.
  • Center for Innovation in Cancerology of Lyon (CICLY) EA 3738, Hospices Civils of Lyon, Faculty of Medicine and Maieutic Lyon Sud, Claude Bernard University Lyon I, 69921, Oullins, France; Department of Biochemistry and Molecular Biology, Lyon-Sud Hospital, Hospices Civils de Lyon, Pierre-Bénite, France.
  • GINECO (Groupe d'Investigateurs Nationaux pour l'Etude des Cancers de l'Ovaire), France; Centre Léon Bérard, Lyon, France.
  • Institut Sainte-Catherine, Avignon, France.
  • GINECO (Groupe d'Investigateurs Nationaux pour l'Etude des Cancers de l'Ovaire), France; Centre François Baclesse, Caen, France.
  • Centre Oscar Lambret, Lille, France.
  • GINECO (Groupe d'Investigateurs Nationaux pour l'Etude des Cancers de l'Ovaire), France; Hôpital Européen Georges Pompidou, Paris, France.
  • GINECO (Groupe d'Investigateurs Nationaux pour l'Etude des Cancers de l'Ovaire), France; Hôpital Privé du Confluent, Nantes, France.
  • GINECO (Groupe d'Investigateurs Nationaux pour l'Etude des Cancers de l'Ovaire), France; Department of Pathology, Institut Universitaire du Cancer de Toulouse-Oncopole, Toulouse, France.
  • Centre Hospitalier Régional d'Orléans, Orléans, France.
  • GINECO (Groupe d'Investigateurs Nationaux pour l'Etude des Cancers de l'Ovaire), France; Université Paris Centre, AP-HP, Hôpital Cochin, Paris, France.
  • GINECO (Groupe d'Investigateurs Nationaux pour l'Etude des Cancers de l'Ovaire), France; Institut de Cancérologie de l'Ouest - ICO, site René Gauducheau, Saint-Herblain, France.
  • ICL Institut de Cancérologie de Lorraine, Vandoeuvre-Les-Nancy, France.
  • GINECO (Groupe d'Investigateurs Nationaux pour l'Etude des Cancers de l'Ovaire), France; Institut Curie - Hôpital René Huguenin, Saint-Cloud, France.
  • GINECO (Groupe d'Investigateurs Nationaux pour l'Etude des Cancers de l'Ovaire), France; Institut Gustave Roussy, Villejuif, France; INSERM 0981, Université Paris-Saclay, France.
  • Centre Hospitalier Universitaire Dupuytren, Limoges, France.
  • Polyclinique Bordeaux Nord, Bordeaux, France.
  • Institut Mutualiste Montsouris, Paris, France.
  • GINECO (Groupe d'Investigateurs Nationaux pour l'Etude des Cancers de l'Ovaire), France; Institut Bergonié, Bordeaux, France; GINEGEPS (GINEco Group on Early Phase Studies), France.
  • ICO - Institut de Cancérologie de l'Ouest, site Paul Papin, Angers, France.
  • Hôpital Tenon, Paris, France.
  • Centre Georges François Leclerc, Dijon, France.
  • GINECO (Groupe d'Investigateurs Nationaux pour l'Etude des Cancers de l'Ovaire), France; Institut du Cancer de Montpellier - ICM Val d'Aurelle, Montpellier, France.
  • Clinique Tivoli, Bordeaux, France.
  • GINECO (Groupe d'Investigateurs Nationaux pour l'Etude des Cancers de l'Ovaire), France; ICANS - Institut de cancérologie Strasbourg Europe, Strasbourg, France.
  • GINECO (Groupe d'Investigateurs Nationaux pour l'Etude des Cancers de l'Ovaire), France; Centre Antoine Lacassagne, Nice, France.
  • ARCAGY-GINECO, Paris, France.
  • Center for Innovation in Cancerology of Lyon (CICLY) EA 3738, Hospices Civils of Lyon, Faculty of Medicine and Maieutic Lyon Sud, Claude Bernard University Lyon I, 69921, Oullins, France; GINECO (Groupe d'Investigateurs Nationaux pour l'Etude des Cancers de l'Ovaire), France; GINEGEPS (GINEco Group on Early Phase Studies), France; Hospices Civils de Lyon, Lyon, France.

Abstract

PURPOSE

Circulating nucleosomes (DNA wound around histone proteins) are emerging cancer biomarkers. We investigated their association with clinical outcomes in advanced ovarian cancer.

PATIENTS AND METHODS

Circulating levels and longitudinal kinetics of two nucleosomes (H3K27Me3 and H3K36Me3, log-scale) were assessed at baseline, during neoadjuvant chemotherapy after interval cytoreductive surgery, and at progression in patients with advanced ovarian cancer patients from the randomized phase II CHIVA trial. Nucleosomes were measured with Nu.Q® immunoassays,compared to those from 201 healthy subjects, and analyzed in relation to surgical outcomes, progression-free survival, with respect to the modeled CA-25 ELIMination rate constant K (KELIM) along with established clinical covariates.

RESULTS

H3K27Me3 and H3K36me3 nucleosome concentrations were available for 148/188 patients. Both nucleosomes were significantly higher in ovarian cancer patients compared with healthy controls and showed correlated baseline levels. Lower baseline H3K36Me3 was independently associated with complete interval cytoreduction surgery and progression-free survival, complementary to CA-25 KELIM. Longitudinal changes in nucleosome levels showed a decrease during neoadjuvant chemotherapy, but were not associated with radiological response, completeness of interval cytoreductive surgery or progression-free survival.

CONCLUSION

Baseline H3K36Me3 and H3K27Me3 levels may represent non-invasive biomarkers in advanced ovarian cancer and warrant further evaluation for their potential clinical utility.

MeSH

Cytoreduction Surgical Procedures, Progression-Free Survival, Ovary, Neoplasms, Nucleosomes, Drug Therapy, Biomarkers, Chemotherapy, Adjuvant, Ovarian Neoplasms, Chemotherapy