How Jeffrey A, Jazaeri Amir A, Fellman Bryan, Daniels Molly S, Penn Suzanna, Solimeno Cara, Yuan Ying, Schmeler Kathleen, Lanchbury Jerry S, Timms Kirsten, Lu Karen H, Yates Melinda S
Department of Gynecologic Oncology and Reproductive Medicine, the University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Department of Biostatistics, the University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Cancers (Basel). 2021 Feb 24;13(5):946. doi: 10.3390/cancers13050946.
New therapies, such as poly-ADP ribose polymerase inhibitors (PARPi), and immunotherapy treatments have generated great interest in enhancing individualized molecular profiling of epithelial ovarian cancer (EOC) to improve management of the disease. In EOC patients, putative biomarkers for homologous recombination deficiency (HRD), microsatellite instability (MSI), and tumor mutational burden (TMB) were characterized and correlated with survival outcomes. A series of 300 consecutive EOC patients were enrolled. Patients underwent neoadjuvant chemotherapy ( = 172) or primary cytoreductive surgery ( = 128). Molecular profiling and survival analyses were restricted to the primary cytoreductive surgery cohort due to tissue availability. All patients underwent germline testing for HRD- and MSI-related gene mutations. When sufficient tissue was available, screening for somatic BRCA1/2 mutations, BRCA1 promoter methylation, HRD score (a measure of genomic instability), MSI, and TMB testing were performed. HRD score ≥33 was associated with improved overall survival on multivariable analysis. In the era of biomarker-driven clinical care, HRD score ≥33 may be a useful adjunctive prognostic tool and should be evaluated in future studies to predict PARPi benefits.
新的治疗方法,如聚-ADP核糖聚合酶抑制剂(PARPi)和免疫治疗,已引发了人们对加强上皮性卵巢癌(EOC)个体化分子谱分析以改善疾病管理的极大兴趣。在EOC患者中,对同源重组缺陷(HRD)、微卫星不稳定性(MSI)和肿瘤突变负荷(TMB)的假定生物标志物进行了表征,并与生存结果相关联。连续纳入了300例EOC患者。患者接受了新辅助化疗(n = 172)或初次肿瘤细胞减灭术(n = 128)。由于组织可用性,分子谱分析和生存分析仅限于初次肿瘤细胞减灭术队列。所有患者均接受了HRD和MSI相关基因突变的种系检测。当有足够的组织时,进行体细胞BRCA1/2突变、BRCA1启动子甲基化、HRD评分(基因组不稳定性的一种衡量指标)、MSI和TMB检测。多变量分析显示,HRD评分≥33与总生存期改善相关。在生物标志物驱动的临床治疗时代,HRD评分≥33可能是一种有用的辅助预后工具,应在未来研究中进行评估以预测PARPi的疗效。