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Journal Article Ppublish 4 citations

PubMed: 39481880 DOI: 10.1136/ijgc-2024-005815

Tumor-intrinsic chemosensitivity assessed by KELIM and prognosis by BRCA status in patients with advanced ovarian carcinomas.

Int J Gynecol Cancer 35(5):101866

Authors: Ondine Becker, Alice Durand, Marion Chevrier, Laetitia Collet, Laurence Gladieff, Florence Joly, Baptiste Sauterey, Christophe Pomel, Hélène Costaz, Patricia Pautier, Cécile Guillemet, Thibault de la Motte Rouge, Renaud Sabatier, Jean-Marc Classe, Thierry Petit, Eric Leblanc, Frédéric Marchal, Pierre-Emmanuel Colombo, Emmanuel Barranger, Aude-Marie Savoye, Lise Bosquet, Isabelle Ray-Coquard, Matthieu Carton, Oliver Colomban, Benoit You, Manuel Rodrigues

Affiliations

  • Medical Oncology, Institut Curie, Paris, France.
  • Medical Oncology, Hospices Civils de Lyon, Lyon, France.
  • Biostatistical Unit, Institut Curie, Paris, France.
  • Medical Oncology, Centre Leon Berard, Lyon, France; Breast Cancer Translational Research Laboratory (BCTL), Institut Jules Bordet, Brussels, Belgium.
  • Medical Oncology, Institut Claudius Regaud, Toulouse, France.
  • Medical Oncology, Centre François Baclesse Centre de Lutte Contre le Cancer, Caen, France.
  • Medical Oncology, ICO Site Paul Papin, Angers, France.
  • Surgical Oncology, Jean Perrin Centre, Clermont-Ferrand, France.
  • Surgical Oncology, Centre Georges-François Leclerc, Dijon, France. Electronic address: https://twitter.com/HCostaz.
  • Medical Oncology, Gustave Roussy, Villejuif, France.
  • Medical Oncology, Henri Becquerel Cancer Institute, Rouen, France.
  • Medical Oncology, Centre Eugène Marquis, Rennes, France.
  • Medical Oncology, Paoli-Calmettes Institute, Marseille, France; SESSTIM (Economic and Social Sciences of Health & Medical Information Processing), Marseille, France.
  • Surgical Oncology, Institut de Cancérologie de l'Ouest, Saint Herblain, France.
  • Medical Oncology Department, Paul Strauss Cancer Centre, Strasbourg, France.
  • Surgical Oncology, Oscar Lambret Cancer Centre, Lille, France.
  • Surgical Oncology, Institut de Cancérologie de Lorraine, Vandoeuvre-les-Nancy, France.
  • Surgical Oncology, Institut Régional du Cancer de Montpellier, Montpellier, France.
  • Surgical Oncology, Centre Antoine-Lacassagne, Nice, France.
  • Medical Oncology, Godinot Institute, Reims, France.
  • UNICANCER (Network of French Comprehensive Cancer Centres), Paris, France.
  • Medical Oncology, Centre Leon Berard, Lyon, France; Laboratoire HESPER, Université Claude Bernard Lyon 1, Villeurbanne, France.
  • Université Claude Bernard Lyon 1, Lyon, France.
  • Medical Oncology, Hospices Civils de Lyon, Lyon, France; Université Claude Bernard Lyon 1, Lyon, France.
  • Medical Oncology, Institut Curie, Paris, France; INSERM U1339/UMR 3666, DNA Repair and Uveal Melanoma (D.R.U.M.), PSL Research University, Paris, France.

Abstract

OBJECTIVE

Treatment of high-grade serous ovarian carcinomas relies on surgery and chemotherapy, potentially followed by bevacizumab and/or poly (ADP-ribose) polymerase inhibitors (PARPi). The modeled CA-125 ELIMination rate constant K (KELIM) is a pragmatic indicator of tumor primary chemosensitivity. Although it is well established that BRCA mutations are associated with platinum sensitivity, the relationship between BRCA status and KELIM score has yet to be elucidated. This study aimed to evaluate the interactions between BRCA and KELIM, and their respective prognostic values.

METHODS

We retrospectively collected data from 743 patients with high-grade serous ovarian carcinomas included in a French nationwide registry (NCT03275298) treated with neoadjuvant platinum-based chemotherapy followed by surgery. We analyzed the interactions between BRCA and KELIM, and their impacts on progression-free survival and overall survival.

RESULTS

BRCA-mutated (BRCAm) patients had higher standardized KELIM than BRCA-wild type (BRCAwt) tumors (median 1.16 vs 1.06, respectively; p=0.001). The prognostic value of the KELIM score was independent of BRCA in multivariate analyses. KELIM score and BRCA could be combined to define three prognostic groups: (1) an unfavorable prognostic group with both BRCAwt and unfavorable KELIM (median progression-free survival 12.0months); (2) an intermediate prognostic group with either BRCAm and unfavorable KELIM, or BRCAwt and favorable KELIM (median progression-free survival of 16.0 and 18.8months, respectively; HR 0.64 compared with the unfavorable group, p<0.001); and (3) a favorable prognostic group with both BRCAm and favorable KELIM (median progression-free survival 28.8 months; HR 0.37 compared with the unfavorable group, p<0.001).

CONCLUSIONS

The KELIM score provides complementary prognostic information with respect to BRCA, and discriminates different prognoses within BRCAm or BRCAwt patients. Patients with both BRCAwt/unfavorable KELIM have a poor prognosis, underscoring the urgent need for novel therapeutic strategies.

MeSH

Poly(Adp-Ribose) Polymerases, Progression-Free Survival, Ovary, Genital Neoplasms, Female, Neoplasms, Poly Adenosine Diphosphate Ribose, Drug Therapy, Respect, Ovarian Neoplasms, Therapeutics, Prognosis, Chemotherapy