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EV195/#922  Long survival in patients with adnexal high-grade serous carcinoma who underwent suboptimal cytoreductive surgery: a whole-genome analysis
  1. Mackenzie Sullivan1,
  2. David Brown2,
  3. Arnaud Da Cruz Paula2,
  4. Thomas Boerner1,
  5. Roisin O’cearbhaill3,
  6. William Tew3,
  7. Rachel Grisham3,
  8. Yukio Sonoda1,
  9. Mario Leitao1,
  10. Vance Broach1,
  11. Ginger Gardner1,
  12. M Herman Chui2,
  13. Dennis Chi1,
  14. Britta Weigelt2 and
  15. Kara Long Roche1
  1. 1Memorial Sloan Kettering Cancer Center, Surgery, New York, USA
  2. 2Memorial Sloan Kettering Cancer Center, Pathology and Laboratory Medicine, New York, USA
  3. 3Memorial Sloan Kettering Cancer Center, Medicine, New York, USA

Abstract

Introduction We explored the genomic profiles of advanced high-grade serous carcinoma (HGSC) in patients who underwent suboptimal cytoreduction and had long survival outcomes.

Methods Patients with advanced HGSC who underwent suboptimal primary cytoreduction and had OS >10 years were retrospectively identified. OS was defined from the date of initial surgery to date of death or last follow-up. Whole-genome sequencing was performed. Bioinformatic analyses included the assessment of somatic mutations, copy number alterations, rearrangements, mutational signatures, and homologous recombination deficiency (HRD).

Results Six patients were included, with a median age of 68 years (range, 56-73). Five patients had stage IIIC disease and 1 had stage IV disease. All patients were treated with platinum-taxane doublet chemotherapy. Median time to recurrence (n=5) was 33.3 months (range, 14.5-60.8). Three patients died of their disease (OS range, 128.4-141.4 months). Surviving patients have OS ranging from 133.3 to 141.2 months. Three patients had a TP53 biallelic somatic mutation. All patients but one had high levels of genomic instability, with a median fraction of genome altered of 66% (range, 54%-80%). All tumors but one displayed genomic features of HRD. In addition to 1 germline BRCA2 mutation, homozygous deletions affecting the HR-related genes BRCC3 (n=2) and ATM (n=1) were found. All patients but one displayed mutational signatures 3 and/or 8, which are characteristic of HRD.

Conclusion/Implications Genomic features of HRD, which are generally found in approximately one-half of all HGSCs, were present in all tumors but one from patients with suboptimal cytoreduction who were studied, coupled with loss-of-function alterations in HRD-related genes.

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