Yu Shun, Agarwal Parul, Mamtani Ronac, Symecko Heather, Spielman Kelsey, O'Hara Mark, O'Dwyer Peter J, Schneider Charles, Teitelbaum Ursina, Nathanson Katherine L, Domchek Susan M, Reiss Kim A
University of Pennsylvania, Philadelphia, PA.
Abramson Cancer Center, University of Pennsylvania, West Chester, PA.
JCO Precis Oncol. 2019 Dec;3:1-11. doi: 10.1200/PO.18.00271.
Germline mutations in the homologous recombination genes , , and confer an increased risk for pancreatic ductal adenocarcinoma (PDAC). Tumors associated with mutations in homologous recombination genes are sensitive to DNA-damaging agents. We retrospectively studied patients with resected PDAC and a pathogenic germline mutation in one of these three genes. The planned analyses included overall survival (OS) and changes therein when platinum chemotherapy was used in the perioperative setting.
Thirty-two individuals with pathogenic germline mutations in , , or and resected PDAC (mutation positive) were matched in a 1:2 fashion to patients who were noncarriers or untested (mutation negative) by age, year of diagnosis, stage, and sex. Patients were identified via one of two available databases at University of Pennsylvania: the Basser Center for BRCA Registry or the electronic medical record. The primary outcome was OS.
Patients in the mutation-positive group had a median OS (mOS) of 46.6 months; those in the mutation-negative group had an mOS of 23.2 months (hazard ratio [HR], 0.49; 95% CI, 0.27 to 0.88). With platinum exposure in the perioperative setting, mOS in the mutation-positive group had not yet been met versus a mOS of 23.1 months in the mutation-negative group (HR, 0.12; 95% CI, 0.01 to 1.00). When neither group was treated with platinum, there was no significant OS difference between groups (HR, 0.52; 95% CI 0.12 to 2.24). Patients in the mutation-positive group who received perioperative treatment with platinum had a trend toward improved mOS compared with those who did not (HR, 0.15; 95% CI, 0.02 to 1.23; = .07).
Platinum-based chemotherapy may confer a survival benefit in patients with resected PDAC and a pathogenic germline , , or mutation. Knowledge of a germline mutation may be important to determine best choice of perioperative chemotherapy.
同源重组基因、和中的胚系突变会增加胰腺导管腺癌（PDAC）的发病风险。与同源重组基因突变相关的肿瘤对DNA损伤剂敏感。我们对接受手术切除的PDAC且这三个基因之一存在致病胚系突变的患者进行了回顾性研究。计划分析包括总生存期（OS）以及围手术期使用铂类化疗时OS的变化情况。
32例在、或基因存在致病胚系突变且接受手术切除的PDAC患者（突变阳性），按照年龄、诊断年份、分期和性别以1:2的比例与非携带者或未检测者（突变阴性）进行匹配。患者通过宾夕法尼亚大学的两个可用数据库之一进行识别：巴塞尔BRCA登记中心或电子病历。主要结局指标为OS。
突变阳性组患者的中位总生存期（mOS）为46.6个月；突变阴性组患者的mOS为23.2个月（风险比[HR]，0.49；95%置信区间，0.27至0.88）。在围手术期接受铂类治疗的情况下，突变阳性组的mOS尚未达到，而突变阴性组的mOS为23.1个月（HR，0.12；95%置信区间，0.01至1.00）。当两组均未接受铂类治疗时，两组之间的总生存期无显著差异（HR，0.52；95%置信区间0.12至2.24）。与未接受围手术期铂类治疗的突变阳性组患者相比，接受围手术期铂类治疗的患者mOS有改善趋势（HR，0.15；95%置信区间，0.02至1.23；P = 0.07）。
基于铂类的化疗可能会使接受手术切除的PDAC且存在致病胚系、或突变的患者获得生存获益。了解胚系突变对于确定围手术期化疗的最佳选择可能很重要。
