Windon Annika L, Loaiza-Bonilla Arturo, Jensen Christopher E, Randall Michael, Morrissette Jennifer J D, Shroff Stuti G
Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA, USA.
Medical Oncology, Cancer Treatment Centers of America, Philadelphia, PA, USA.
J Gastrointest Oncol. 2018 Feb;9(1):1-10. doi: 10.21037/jgo.2017.10.14.
The oncogene is a driver mutation and is present in greater than 90% of pancreatic ductal adenocarcinomas (PDAC). A subset of these tumors, however, do not harbor mutations in (wild type ). Studies have shown that patients with mutated have a poorer survival on first-line gemcitabine-based chemotherapy compared to wild type . In this study, we examined a cohort of patients with PDAC at our institution who were either wild type or mutant for the gene and assessed for differences in survival and response to different chemotherapeutic regimens.
We examined clinical records of patients treated at the Abramson Cancer Center of the University of Pennsylvania from 2013 to 2017. Patients with a pancreatic mass and a histologic diagnosis of pancreatic or pancreaticobiliary adenocarcinoma were identified. Thirty-nine patients with PDAC who underwent tumor sequencing at Penn Medicine's Center for Personalized Diagnostics (CPD) were selected for further study. Twelve patients were identified whose tumors were wild type. Twenty-seven patients with PDAC whose tumors harbored mutations were selected as controls ( mutant).
We noted a longer overall survival (OS) among wild type patients compared to mutant patients (P=0.026). This was independent of the age at diagnosis, patient gender, stage of diagnosis, tumor morphology, mismatch repair (MMR) status, and chemotherapeutic regimen.
Similar to previously reported studies, PDAC with a wild type mutational profile has a better prognosis with a longer OS. This improved prognosis is independent of the protocol utilized in therapy for these patients. Our findings suggest that future clinical trials in pancreatic cancer should take into consideration the presence of mutations in their pre-planned analysis when assessing the efficacy of a novel therapeutic approach. This may be a crucial factor in trial concepts and outcomes.
癌基因是一种驱动突变，存在于超过90%的胰腺导管腺癌（PDAC）中。然而，这些肿瘤中的一部分（野生型）并不携带该基因突变。研究表明，与野生型患者相比，携带该基因突变的患者在一线吉西他滨化疗中的生存期更短。在本研究中，我们对本机构中一组PDAC患者进行了研究，这些患者的该基因要么是野生型，要么是突变型，并评估了生存期差异以及对不同化疗方案的反应。
我们查阅了2013年至2017年在宾夕法尼亚大学阿布拉姆森癌症中心接受治疗的患者的临床记录。确定了患有胰腺肿物且组织学诊断为胰腺或胰胆管腺癌的患者。选择了39例在宾夕法尼亚大学医学个性化诊断中心（CPD）进行肿瘤测序的PDAC患者进行进一步研究。确定了12例肿瘤为该基因野生型的患者。选择27例肿瘤携带该基因突变的PDAC患者作为对照（突变型）。
我们注意到该基因野生型患者的总生存期（OS）比突变型患者更长（P = 0.026）。这与诊断时的年龄、患者性别、诊断阶段、肿瘤形态、错配修复（MMR）状态和化疗方案无关。
与先前报道的研究相似，具有该基因野生型突变特征的PDAC预后较好，总生存期更长。这种改善的预后与用于这些患者治疗的方案无关。我们的研究结果表明，未来胰腺癌的临床试验在评估新治疗方法的疗效时，应在预先计划的分析中考虑该基因突变的存在。这可能是试验概念和结果的关键因素。
