Graves Stephen, Sullivan Mackenzie W, Adkoli Anusha, Zhou Qin, Iasonos Alexia, Selenica Pier, Aghajanian Carol, Liu Ying L, Tew William, Sonoda Yukio, Ellenson Lora H, Chi Dennis, O'Cearbhaill Roisin E, Weigelt Britta, Grisham Rachel N
Gynecology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Department of Obstetrics and Gynecology, Robert Wood Johnson University Hospital, New Brunswick, NJ, USA.
Gynecol Oncol. 2025 Jan;192:120-127. doi: 10.1016/j.ygyno.2024.11.011. Epub 2024 Dec 7.
We sought to describe the association between genomic instability score (GIS) and progression-free survival (PFS) and overall survival (OS) in patients with newly diagnosed, non-BRCA1/2 ovarian cancer.
Homologous recombinant deficiency (HRD) status was based on a cutoff of ≥42 GIS; patients <42 were categorized with homologous recombination proficiency (HRP). We collected type and duration of maintenance therapy, among other variables, and built a multivariate model with landmark analysis at 6 months from baseline and applied it for time-dependent variables.
Increasing GIS as a continuous variable was associated with improved PFS and OS in our cohort. Overall, median PFS was significantly longer in patients with HRD ovarian cancer (35.4 months, 25.4-NE) than in those with HRP disease (14.9 months, 13.1-16.2; p < 0.001). Median OS was 36.2 months (32.4-NE) for HRP and not reached for HRD (p = 0.002). Notably, in patients with HRP ovarian cancer, we observed a shorter median PFS in those who received a poly (adenosine diphosphate-ribose) polymerase inhibitor (PARPi) than in those who did not (12.7 months for HRP with PARPi vs 15.2 months for HRP without PARPi).
Our results demonstrate that in newly diagnosed advanced non-BRCA1/2 ovarian cancer, GIS as a continuous variable is associated with longer PFS and OS. In patients with HRP ovarian cancer, PARPi treatment may be associated with shorter PFS, which warrants further evaluation.
我们试图描述新诊断的非BRCA1/2卵巢癌患者的基因组不稳定评分（GIS）与无进展生存期（PFS）和总生存期（OS）之间的关联。
同源重组缺陷（HRD）状态基于GIS≥42的临界值；GIS<42的患者被归类为同源重组 proficient（HRP）。我们收集了维持治疗的类型和持续时间等变量，并建立了一个多变量模型，在基线后6个月进行标志性分析，并将其应用于时间依赖性变量。
在我们的队列中，GIS作为连续变量增加与PFS和OS改善相关。总体而言，HRD卵巢癌患者的中位PFS（35.4个月，25.4 - 未达到）显著长于HRP疾病患者（14.9个月，13.1 - 16.2；p < 0.001）。HRP的中位OS为36.2个月（32.4 - 未达到），HRD未达到（p = 0.002）。值得注意的是，在HRP卵巢癌患者中，我们观察到接受聚（二磷酸腺苷 - 核糖）聚合酶抑制剂（PARPi）的患者中位PFS比未接受的患者短（接受PARPi的HRP患者为12.7个月，未接受PARPi的HRP患者为15.2个月）。
我们的结果表明，在新诊断的晚期非BRCA1/2卵巢癌中，GIS作为连续变量与更长的PFS和OS相关。在HRP卵巢癌患者中，PARPi治疗可能与较短的PFS相关，这值得进一步评估。
