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<p>High-grade serous ovarian cancer (HGSOC) remains a leading cause of gynecological cancer mortality, with only &lt;15% of patients achieving long-term, relapse-free survival. Using data from the VIVROVAIRE (NCT03418844) and CHIVA (NCT03418844) clinical trials, this study investigated the molecular and immunophenotypic characteristics of long-term recurrence-free survivors (LTS) compared with short-term survivors (STS). Tumor samples from 37 LTS (recurrence-free ≥3 years) and 105 STS were analyzed using next-generation sequencing, <i>BRCA1/RAD51C</i> promoter methylation assays, shallow whole genome and multiplex immunofluorescence. Homologous recombination deficiency (HRD) was defined by <i>BRCA1/2</i> or <i>RAD51C/D</i> alterations, and genomic instability scores (GIS). Immune profiling included quantification of CD4<sup>+</sup>, CD8<sup>+</sup>, CD20<sup>+</sup>, and FOXP3<sup>+</sup> cells. LTS were younger and had a lower prevalence of FIGO stage IV disease. Molecularly, LTS showed fewer <i>TP53</i> mutations, enrichment of <i>BRCA2</i> mutations and <i>BRCA1</i> and <i>RAD51C</i> promoter methylation, and a strong association between <i>RB1</i> loss co-occurring with a <i>BRCA</i> alteration. Conversely, <i>CCNE1</i> amplification was underrepresented in LTS. Immune profiling demonstrated increased stromal and intraepithelial CD8<sup>+</sup> T-cell infiltration and reduced FOXP3<sup>+</sup> regulatory T cells in LTS. Overall, exceptional survival in HGSOC is associated with younger age, enrichment of <i>BRCA2</i> mutations and <i>BRCA1/RAD51C</i> methylation, reduced <i>CCNE1</i> amplification, and a competent antitumor immune response. These findings highlight potential biomarkers for refining risk stratification and guiding personalized therapeutic strategies in ovarian cancer management.</p>

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Immuno-molecular features associated with exceptional recurrence–free survivorship from Ovarian Cancer in the pre-PARP era

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年4月23日

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  • Félix Blanc–Durand,
  • Elisa Yaniz Galende,
  • Gwénaël Ferron,
  • Marie-Christine Kaminsky,
  • Elsa Kalbacher,
  • Sophie Abadie-Lacourtoisie,
  • Florence Joly,
  • Jerome Meunier,
  • Olivier Tredan,
  • Coriolan Lebreton,
  • Jerome Alexandre,
  • Alain Zannetti,
  • Christophe Louvet,
  • Cyriak Blonz,
  • Nadine Dohollou,
  • Dominique Berton,
  • Christophe Desauw,
  • Elisabeth Carola,
  • Michel Fabbro,
  • Philippe Follana,
  • Eric Pujade-Lauraine,
  • Louis Mourani,
  • Audrey Le Formal,
  • Hortense Gaultier De Saint Basile,
  • Catherine Genestie,
  • Etienne Rouleau,
  • Alexandra Leary

摘要

High-grade serous ovarian cancer (HGSOC) remains a leading cause of gynecological cancer mortality, with only <15% of patients achieving long-term, relapse-free survival. Using data from the VIVROVAIRE (NCT03418844) and CHIVA (NCT03418844) clinical trials, this study investigated the molecular and immunophenotypic characteristics of long-term recurrence-free survivors (LTS) compared with short-term survivors (STS). Tumor samples from 37 LTS (recurrence-free ≥3 years) and 105 STS were analyzed using next-generation sequencing, BRCA1/RAD51C promoter methylation assays, shallow whole genome and multiplex immunofluorescence. Homologous recombination deficiency (HRD) was defined by BRCA1/2 or RAD51C/D alterations, and genomic instability scores (GIS). Immune profiling included quantification of CD4+, CD8+, CD20+, and FOXP3+ cells. LTS were younger and had a lower prevalence of FIGO stage IV disease. Molecularly, LTS showed fewer TP53 mutations, enrichment of BRCA2 mutations and BRCA1 and RAD51C promoter methylation, and a strong association between RB1 loss co-occurring with a BRCA alteration. Conversely, CCNE1 amplification was underrepresented in LTS. Immune profiling demonstrated increased stromal and intraepithelial CD8+ T-cell infiltration and reduced FOXP3+ regulatory T cells in LTS. Overall, exceptional survival in HGSOC is associated with younger age, enrichment of BRCA2 mutations and BRCA1/RAD51C methylation, reduced CCNE1 amplification, and a competent antitumor immune response. These findings highlight potential biomarkers for refining risk stratification and guiding personalized therapeutic strategies in ovarian cancer management.