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PR068/#811  Genomic alterations predictive of outcome in early staged cervical cancer: a translational investigation from the Senticol III trial
  1. Maryame El Gani1,
  2. Sabrina Ibadioune2,
  3. Zakhia El Beaino3,
  4. Abderraouf Hamza2,
  5. Sophie Vacher2,
  6. Emmanuelle Jeannot4,
  7. Julien Masliah-Planchon2,
  8. Anne Salomon5,
  9. Alexandre Degnieau6,
  10. Amelie Charveriat7,
  11. Sandrine Martin-Françoise8,
  12. Helene Costaz9,
  13. Sophie Richard10,
  14. Sofiane Bendifallah11,
  15. Serge Douvier12,
  16. Marie Plante13,
  17. Patrice Mathevet14,
  18. Maud Kamal15,
  19. Fabrice Lecuru16 and
  20. Ivan Bieche2
  1. 1Hotel Dieu Quebec, Division of Gynecologic Oncology, Québec City, Canada
  2. 2Institut Curie, Department of Genetics, Paris, France
  3. 3Hopital Foch, Department of Pathology, Suresnes, France
  4. 4Institut Curie, Department of Genetics and Department of Pathology, Paris, France
  5. 5Institut Curie, Department of Pathology, Paris, France
  6. 6Institut Curie, Biological Resources Center, Paris, France
  7. 7CHU de Poitiers, Service De Gynécologie-obstétrique Et Médecine De La Reproduction, Poitiers, France
  8. 8Centre François Baclesse, Chirurgie Gynécologique, Caen, France
  9. 9Centre Georges François Leclerc, Chirurgie Gynécologique, Dijon, France
  10. 10Clinique Tivoli, Chirurgie Gynécologique, Bordeaux, France
  11. 11Hopital Tenon, Service De Gynécologie-obstétrique Et Médecine De La Reproduction, Paris, France
  12. 12CHRU de Dijon, Division of Obstetrics and Gynecology, Dijon, France
  13. 13Hotel Dieu Quebec, Gynecologic Oncology, Québec City, Canada
  14. 14CHUV, Gynecologic Oncology, Lausanne, Switzerland
  15. 15Institut Curie, Drug Development and Innovation Department, Paris, France
  16. 16Institut Curie, Department of Gyneacological Oncology and Breast Surgery, Paris, France

Abstract

Introduction Our translational study aims to identify prognostic and actionable biomarkers in early-staged cervical cancer from Senticol III cohort.

Methods Tumoral slides of the first 150 randomized patients were analyzed based on SEDLIS criteria, TIL’s infiltration, PD-L1 expression and HPV status. Sequencing of tumor DNA was carried out using an in-house targeted next-generation sequencing panel of 571 genes. Relapse-free survival (RFS) was defined as the time between randomization and relapse of any type. We performed univariate and multivariate analysis to compare distributions of categorical variables.

Results The sequencing quality control criteria were met for 135 samples. PIK3CA was the most commonly altered gene (17%). Loss-of-function variants in KMT2-family genes were found in 16% of samples, and in 6% for ARID1A. There were 6 relapses, of which 4 were considered as low-risk based on SEDLIS criteria. KMT2C (p=0,018) and ARID1A (p < 0,001) pathogen variants were significantly associated with RFS. On multivariate analysis, alteration of ARID1A was independently associated with relapse. We found 32% of genomic alterations actionable for a target therapy.

Conclusion/Implications Genes involved in chromatin remodeling (ARID1A and KMT2C) are prognostic biomarkers of clinical interest in ESCC. On multivariate analysis, only alteration of ARID1A remains an independent biomarker predictive of relapse. Actionable molecular alterations were identified in 32% of the patients, highlighting the relevance of personalized therapeutic approaches including epidrugs in ESCC.

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