Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana.
Center for Health Services Research, Regenstrief Institute, Indianapolis, Indiana.
Clin Cancer Res. 2018 Dec 15;24(24):6204-6211. doi: 10.1158/1078-0432.CCR-18-1472. Epub 2018 Aug 21.
Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer with lack of predictive biomarkers. We conducted a study to assess DNA damage repair (DDR) gene mutations as a predictive biomarker in PDAC patients treated with FOLFIRINOX.
Indiana University Simon Cancer Center pancreatic cancer database was used to identify patients with metastatic PDAC, treated with FOLFIRINOX and had tissue available for DNA sequencing. Baseline demographic, clinical, and pathologic information was gathered. DNA isolation and targeted sequencing was performed using the Ion AmpliSeq protocol. Overall survival (OS) analysis was conducted using Kaplan-Meier, logistic regression and Cox proportional hazard methods. Multivariate models were adjusted for age, gender, margin status, CA 19-9, adjuvant chemotherapy, tumor and nodal stage.
Overall, 36 patients were sequenced. DDR gene mutations were found in 12 patients. Mutations were seen in BRCA1 ( = 7), BRCA2 ( = 5), PALB2 ( = 3), MSH2 ( = 1), and FANCF ( = 1) of all the DDR genes sequenced. Median age was 65.5 years, 58% were male, 97.2% were Caucasian and 51.4% had any family history of cancer. The median OS was near significantly superior in those with DDR gene mutations present vs. absent [14 vs. 5 months; HR, 0.58; 95% confidence interval (CI), 0.29-1.14; log-rank = 0.08]. Multivariate logistic (OR, 1.47; 95% CI, 1.04-2.06; = 0.04) and Cox regression (HR, 0.37; 95% CI, 0.15-0.94; = 0.04) showed presence of DDR gene mutations was associated with improved OS.
In a single institution, retrospective study, we found that the presence of DDR gene mutations are associated with improved OS in PDAC patients treated with FOLFIRINOX.
胰腺导管腺癌（PDAC）是一种致命的癌症，缺乏预测性生物标志物。我们进行了一项研究，以评估 DNA 损伤修复（DDR）基因突变作为接受 FOLFIRINOX 治疗的 PDAC 患者的预测性生物标志物。
印第安纳大学西蒙癌症中心的胰腺癌数据库被用于鉴定接受 FOLFIRINOX 治疗且有组织可供 DNA 测序的转移性 PDAC 患者。收集了基线人口统计学、临床和病理信息。使用 Ion AmpliSeq 方案进行 DNA 分离和靶向测序。使用 Kaplan-Meier、逻辑回归和 Cox 比例风险方法进行总生存期（OS）分析。多变量模型根据年龄、性别、切缘状态、CA19-9、辅助化疗、肿瘤和淋巴结分期进行调整。
总共对 36 名患者进行了测序。在 12 名患者中发现了 DDR 基因突变。在所有测序的 DDR 基因中，BRCA1（7 例）、BRCA2（5 例）、PALB2（3 例）、MSH2（1 例）和 FANCF（1 例）均发现突变。中位年龄为 65.5 岁，58%为男性，97.2%为白种人，51.4%有任何家族癌症史。与 DDR 基因突变缺失相比，存在 DDR 基因突变的患者中位 OS 明显更长[14 个月 vs. 5 个月；HR，0.58；95%CI，0.29-1.14；log-rank = 0.08]。多变量逻辑（OR，1.47；95%CI，1.04-2.06； = 0.04）和 Cox 回归（HR，0.37；95%CI，0.15-0.94； = 0.04）显示，DDR 基因突变的存在与 OS 的改善相关。
在一项单机构、回顾性研究中，我们发现 DDR 基因突变的存在与接受 FOLFIRINOX 治疗的 PDAC 患者的 OS 改善相关。
