文章：

根据腹膜扩散类型将同源重组缺陷阴性高级别卵巢癌分层为两组具有不同生存结局

Stratification of Homologous Recombination Deficiency-Negative High-Grade Ovarian Cancer by the Type of Peritoneal Spread into Two Groups with Distinct Survival Outcomes

原文发布日期：3 June 2024

DOI: 10.3390/cancers16112129

类型: Article

开放获取: 是

英文摘要：

Background: Homologous recombination deficiency (HRD) has evolved into a major diagnostic marker in high-grade ovarian cancer (HGOC), predicting the response to poly (adenosine diphosphate-ribose) polymerase inhibitors (PARPi) and also platinum-based therapy. In addition to HRD, the type of peritoneal tumor spread influences the treatment response and patient survival; miliary type tumor spread has a poorer predicted outcome than non-miliary type tumor spread. Methods: Known methods for HRD assessment were adapted for our technical requirements and the predictive-value integrated genomic instability score (PIGIS) for HRD assessment evolved as an outcome. PIGIS was validated in HGOC samples from 122 patients. We used PIGIS to analyze whether the type of tumor spread correlated with HRD status and whether this had an impact on survival. Results: We demonstrated that PIGIS can discriminate HRD-positive from HRD-negative samples. Tumors with a miliary tumor spread are HRD-negative and have a very bad prognosis with a progression-free survival (PFS) of 15.6 months and an overall survival (OS) of 3.9 years. However, HRD-negative non-miliary spreading tumors in our cohort had a much better prognosis (PFS 35.4 months, OS 8.9 years); similar to HRD-positive tumors (PFS 34.7 months, OS 8.9 years). Conclusions: Our results indicate that in a predominantly PARPi naïve cohort, the type of tumor spread and concomitant cytoreduction efficiency is a better predictor of survival than HRD and that HRD may be an accidental surrogate marker for tumor spread and concomitant cytoreduction efficiency. It remains to be determined whether this also applies for sensitivity to PARPi.

摘要翻译： 

背景：同源重组缺陷（HRD）已发展成为高级别卵巢癌（HGOC）的重要诊断标志物，可预测聚腺苷二磷酸核糖聚合酶抑制剂（PARPi）及铂类药物的治疗反应。除HRD外，腹膜肿瘤播散类型亦影响治疗反应和患者生存；粟粒型播散较非粟粒型播散预后更差。方法：本研究根据技术需求调整现有HRD评估方法，开发出预测值整合基因组不稳定性评分（PIGIS）作为HRD评估工具。通过对122例HGOC患者样本验证PIGIS效能，并利用该指标分析肿瘤播散类型与HRD状态的相关性及其对生存期的影响。结果：PIGIS可有效区分HRD阳性与阴性样本。粟粒型播散肿瘤均为HRD阴性，预后极差，其中位无进展生存期（PFS）为15.6个月，总生存期（OS）为3.9年。而本队列中HRD阴性的非粟粒型播散肿瘤预后显著改善（PFS 35.4个月，OS 8.9年），与HRD阳性肿瘤预后相近（PFS 34.7个月，OS 8.9年）。结论：在未接受PARPi治疗的队列中，肿瘤播散类型及伴随的肿瘤细胞减灭术效果比HRD状态更能预测生存结局，HRD可能仅是肿瘤播散类型与减灭术效果的间接替代标志物。该结论是否适用于PARPi敏感性预测尚待进一步验证。

原文链接：

Stratification of Homologous Recombination Deficiency-Negative High-Grade Ovarian Cancer by the Type of Peritoneal Spread into Two Groups with Distinct Survival Outcomes