背景:胰腺导管腺癌(PDAC)是一种具有挑战性的疾病,手术是唯一可能的治疗方法.然而,尽管做了手术,大多数患者经历复发。最近的证据表明,围手术期KRAS突变的循环肿瘤DNA(ctDNA)可能具有预后价值。因此,我们进行了系统评价和荟萃分析,以探讨术前和术后KRAS突变ctDNA检测在切除的PDAC中的预后意义.
方法:我们搜索了PubMed/MEDLINE,Embase,和Cochrane中央对照试验注册数据库,用于报道术前和术后KRAS突变的ctDNA对切除的PDAC的总生存期(OS)和/或无复发生存期(RFS)的影响。我们使用随机效应模型来确定合并的OS和RFS风险比(HR)及其相应的95%置信区间(CI)。
结果:我们确定了15项符合分析条件的研究(868例患者)。在术前设置,在8项研究中,ctDNA阳性与较差的RFS相关(HR,2.067;95%CI,1.346-3.174,P<0.001),10项研究中OS较差(HR,2.170;95%CI,1.451-3.245,P<0.001)与阴性ctDNA相比。在术后设置中,在9项研究中,阳性ctDNA与较差的RFS相关(HR,3.32;95%CI,2.19-5.03,P<0.001),6项研究中OS较差(HR,6.62;95%CI,2.18-20.16,P<0.001)与阴性ctDNA相比。
结论:我们的荟萃分析支持术前和术后KRAS突变的ctDNA检测作为切除的PDAC的预后指标。需要进一步的对照研究来证实这些结果并研究阳性KRAS突变的ctDNA的潜在治疗意义。
BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a challenging disease, with surgery being the only possible cure. However, despite surgery, the majority of patients experience recurrence. Recent evidence suggests that perioperative KRAS-mutated circulating tumor DNA (ctDNA) may have prognostic value. Therefore, we conducted a systematic
review and meta-analysis to explore the prognostic significance of preoperative and postoperative KRAS-mutated ctDNA testing in resected PDAC.
METHODS: We searched PubMed/MEDLINE, Embase, and Cochrane Central Register of Controlled Trials databases for studies that reported the effect of preoperative and postoperative KRAS-mutated ctDNA on overall survival (OS) and/or relapse-free survival (RFS) in resected PDAC. We used a random-effects model to determine the pooled OS and RFS hazard ratios (HR) and their corresponding 95 % confidence intervals (CI).
RESULTS: We identified 15 studies (868 patients) eligible for analysis. In the preoperative setting, positive ctDNA correlated with worse RFS in 8 studies (HR, 2.067; 95 % CI, 1.346-3.174, P < 0.001) and worse OS in 10 studies (HR, 2.170; 95 % CI, 1.451-3.245, P < 0.001) compared to negative ctDNA. In the postoperative setting, positive ctDNA correlated with worse RFS across 9 studies (HR, 3.32; 95 % CI, 2.19-5.03, P < 0.001) and worse OS in 6 studies (HR, 6.62; 95 % CI, 2.18-20.16, P < 0.001) compared to negative ctDNA.
CONCLUSIONS: Our meta-analysis supports the utility of preoperative and postoperative KRAS-mutated ctDNA testing as a prognostic marker for resected PDAC. Further controlled studies are warranted to confirm these results and to investigate the potential therapeutic implications of positive KRAS-mutated ctDNA.