Alqahtani Ali, Alloghbi Abdurahman, Coffin Philip, Yin Chao, Mukherji Reetu, Weinberg Benjamin A
The Ruesch Center for the Cure of Gastrointestinal Cancers, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC, 20057, USA; Medical Oncology Department, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
Cancer Research Unit and Department of Oncology, King Khalid University, Abha, Saudi Arabia.
Surg Oncol. 2023 Dec;51:102007. doi: 10.1016/j.suronc.2023.102007. Epub 2023 Oct 10.
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.
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).
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.
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.
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愈方法。然而，尽管进行了手术，大多数患者仍会复发。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，我们进行了一项系统评价和荟萃分析，以探讨术前和术后KRAS突变的ctDNA检测在切除的PDAC中的预后意义。
我们在PubMed/MEDLINE、Embase和Cochrane对照试验中央注册库数据库中搜索了报告术前和术后KRAS突变的ctDNA对切除的PDAC总生存期（OS）和/或无复发生存期（RFS）影响的研究。我们使用随机效应模型来确定汇总的OS和RFS风险比（HR）及其相应的95%置信区间（CI）。
我们确定了15项符合分析条件的研究（868例患者）。在术前情况下，与ctDNA阴性相比，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项研究中与较差的OS相关（HR，2.170；95%CI，1.451 - 3.245，P < 0.001）。在术后情况下，与ctDNA阴性相比，9项研究中ctDNA阳性与较差的RFS相关（HR，3.32；95%CI，2.19 - 5.03，P < 0.001），6项研究中与较差的OS相关（HR，6.62；95%CI，2.18 - 20.16，P < 0.001）。
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预后标志物的实用性。需要进一步的对照研究来证实这些结果，并研究KRAS突变的ctDNA阳性的潜在治疗意义。
