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2022-RA-1088-ESGO Chitinase response after 3 cycles of chemotherapy as a promising marker of chemosensitivity an ancillary analysis of the GINECO-ENGOT EWOC-1 trial
  1. Karim Chikh1,2,3,
  2. Charlotte Cuerq4,5,
  3. Marie Valero6,
  4. Olivier Colomban7,
  5. Aude-Marie Savoye8,
  6. Dominique Berton9,
  7. Laëtitia Stefani10,
  8. Michel Fabbro11,
  9. Cyriac Blonz12,
  10. Olivier Tredan13,
  11. Margot Noblecourt14,
  12. Oana Cojocarasu15,
  13. Delphine Mollon-Grange16,
  14. Fabrice Barlesi17,
  15. Eric Pujade-Lauraine18,
  16. Gilles Freyer19,
  17. Benoit You20,
  18. Hubert Vidal21 and
  19. Claire Falandry22
  1. 1Laboratoire de Biochimie et Biologie Moléculaire – Centre Hospitalier Lyon Sud, Lyon, France
  2. 2ISPB, Faculté de Pharmacie de Lyon- UCBL1, Lyon, France
  3. 3Laboratoire CARMEN INSERM U1060, INRA U1397, Université Lyon 1, INSA Lyon, Oullins, France
  4. 4Biochemistry Department, Hospices Civils de Lyon, Pierre-Benite, France
  5. 5INSERM U1060, INRA UMR 1397, INSA-Lyon, CarMeN Laboratory, Université Lyon 1, Pierre-Benite, France
  6. 6Hôpital Lyon-Sud -Hospices Civils de Lyon, Lyon, France
  7. 7Université Lyon, Université Claude Bernard Lyon 1, Faculté de Médecine Lyon-Sud, EA UCBL/HCL 3738 CICLY, Lyon, France
  8. 8Institut Jean Godinot, Reims, France
  9. 9Institut de Cancérologie de l’Ouest (ICO), Saint-Herblain, France
  10. 10GINECO and Centre Hospitalier Annecy Genevois, Pringy, France
  11. 11GINECO and Institut du Cancer de Montpellier, Montpellier, France
  12. 12Hôpital Privé du Confluent S.A.S., Nantes, France
  13. 13GINECO and Centre Léon Bérard, Lyon, France
  14. 14GINECO and Centre Hospitalier de Cholet, Cholet, France
  15. 15Centre Hospitalier du Mans, Le Mans, France
  16. 16CH CORNOUAILLE, Quimper, France
  17. 17Gustave ROUSSY, Villejuif, France
  18. 18ARCAGY-GINECO, Paris, France
  19. 19GINECO and Centre Hospitalier Lyon-Sud, Lyon, France
  20. 20Medical Oncology, Institut de Cancérologie des Hospices Civils de Lyon (IC-HCL), CITOHL, Université Lyon, CICLY and GINECO, Lyon, France
  21. 21’Laboratoire CarMeN INSERM U.1060/Université Lyon1/INRAE U. 1397/Hospices Civils Lyon Bâtiment CENS-ELI 2D Hôpital Lyon Sud Secteur 2, Pierre-Benite, France
  22. 22Geriatrics, Hospices Civils de Lyon – Centre Hospitalier Lyon Sud, Saint-Genis-Laval, France


Introduction/Background Older patients with ovarian cancer have poor outcomes; the geriatric vulnerability score (GVS) was validated as a prognostic factor for survival. During aging the circulating Chitinase 3-like-1 (CHI3L1), and its related chitinase enzymatic activity increase, leading to propose them as ‘aging biomarkers’. However, recent data supported the implication of chitinase-like proteins in the proliferation of several cancers. The EWOC-1 trial (NCT02001272) showed a lower efficacy of the carboplatin monotherapy (Cmono) arm compared to carboplatin-paclitaxel (CP) in vulnerable patients; a serum sampling was provided on inclusion, after 3 and 6 courses of chemotherapy for the measurement of chitinase activity in each arm (A: standard CP; B: Cmono; C: 3weeks/4 CP), to identify whether its association with patients’ outcomes and inversely, the differential impact of the distinct treatment regimens on it.

Methodology Chitinase activity was assessed as previously published. Were analyzed both its absolute value on inclusion (‘chitinase baseline’) and its kinetics after 3 chemotherapy courses (‘chitinase response’).

Results Serum samples could be retrieved for 46/120 patients on inclusion and 33 after 3 chemotherapy courses. Chitinase baseline median activity (in U/L, IQR) was 1727.9 (1459.3; 1878.3) at inclusion, similar in the 3 arms; no association was shown with any of the geriatric vulnerability parameters, nor the GVS, nor overall survival. Chitinase response was significantly different in the 3 arms, with a median (in U/L, IQR) of -160 (-297; 35.2) in the total cohort, -272 (-376; -122) in arm A, 105 (-109; 221) in arm B and -160 (-663; -109) in arm C, p=0.008. High chitinase response was associated with high CA-125 ELIMination rate constant K (KELIM), a marker of chemosensitivity (Fisher exact test, p=0.042).

Conclusion Chitinase activity should not be considered, in the context of ovarian cancer as an aging biomarker, but chitinase response appears as a promising marker of chemosensitivity.

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