Rădoi Viorica-Elena, Țurcan Mihaela, Maioru Ovidiu Virgil, Dan Andra, Bohîlțea Laurentiu Camil, Dumitrescu Elena Adriana, Gheorghe Adelina Silvana, Stănculeanu Dana Lucia, Thodi Georgia, Loukas Yannis L, Săbău Ileana-Delia
Department of Medical Genetics, "Carol Davila" University of Medicine and Pharmacy, 020021 Bucharest, Romania.
"Alessandrescu-Rusescu" National Institute for Maternal and Child Health, 20382 Bucharest, Romania.
Diagnostics (Basel). 2023 May 29;13(11):1896. doi: 10.3390/diagnostics13111896.
The Homologous Recombination Deficiency (HRD) Score, determined by evaluating genomic instability through the assessment of loss of heterozygosity (LOH), telomeric allelic imbalance (TAI), and large-scale state transitions (LST), serves as a crucial biomarker for identifying patients who might benefit from targeted therapies, such as PARP inhibitors (PARPi). This study aimed to investigate the efficacy of HRD testing in high-grade serous ovarian carcinoma, tubal, and peritoneal cancer patients who are negative for somatic BRCA1 and BRCA2 mutations and to evaluate the impact of HRD status on Bevacizumab and PARPi therapy response. A cohort of 100 Romanian female patients, aged 42-77, was initially selected. Among them, 30 patients had unsuitable samples for HRD testing due to insufficient tumor content or DNA integrity. Using the OncoScan C.N.V. platform, HRD testing was successfully performed on the remaining 70 patients, with 20 testing negative and 50 testing positive for HRD. Among the HRD-positive patients, 35 were eligible for and benefited from PARPi maintenance therapy, resulting in a median progression-free survival (PFS) increase from 4 months to 8.2 months. Our findings support the importance of HRD testing in ovarian cancer patients, demonstrating the potential therapeutic advantage of PARPi therapy in HRD-positive patients without somatic BRCA1/2 mutations.
同源重组缺陷（HRD）评分通过评估杂合性缺失（LOH）、端粒等位基因失衡（TAI）和大规模状态转换（LST）来确定基因组不稳定性，是识别可能从靶向治疗中获益的患者的关键生物标志物，如聚（ADP-核糖）聚合酶抑制剂（PARPi）。本研究旨在调查HRD检测在体细胞BRCA1和BRCA2突变阴性的高级别浆液性卵巢癌、输卵管癌和腹膜癌患者中的疗效，并评估HRD状态对贝伐单抗和PARPi治疗反应的影响。最初选择了一组100名年龄在42至77岁之间的罗马尼亚女性患者。其中，30名患者因肿瘤含量不足或DNA完整性问题而没有适合进行HRD检测的样本。使用OncoScan C.N.V.平台，成功对其余70名患者进行了HRD检测，其中20名检测为HRD阴性，50名检测为HRD阳性。在HRD阳性患者中，35名符合PARPi维持治疗条件并从中获益，无进展生存期（PFS）中位数从4个月增加到8.2个月。我们的研究结果支持HRD检测在卵巢癌患者中的重要性，证明了PARPi治疗在无体细胞BRCA1/2突变的HRD阳性患者中的潜在治疗优势。
