Pan Yundi, Ran Taojing, Zhang Xianda, Qin Xianzheng, Zhang Yao, Zhou Chunhua, Zou Duowu
Department of Gastroenterology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, China.
Endosc Ultrasound. 2024 Nov-Dec;13(6):366-375. doi: 10.1097/eus.0000000000000097. Epub 2024 Dec 30.
A majority of pancreatic malignancies are unresectable at the time of presentation and require EUS-guided fine-needle aspiration or fine-needle biopsy (EUS-FNA/FNB) for diagnosis. With the advent of precision therapy, there is an increasing need to use EUS-FNA/FNB sample for genetic analysis. Next-generation sequencing (NGS) is a preferred technology to detect genetic mutations with high sensitivity in small specimens. We performed a meta-analysis to evaluate the adequacy of EUS-FNA/FNB for NGS in pancreatic malignancies.
PubMed, Embase, Cochrane Library, and Web of Science were searched from database inception to November 11, 2023. The primary outcome was the proportion of sufficient sample acquired by EUS-FNA/FNB in pancreatic malignancies for NGS. Secondary outcomes were the proportion of sufficient sample for NGS in pancreatic ductal adenocarcinoma (PDAC) and the detection rates of mutations in KRAS, TP53, CDKN2A, and SMAD4 and actionable mutations in PDAC. The pooled proportions were calculated using a random-effects model. Potential sources of heterogeneity were investigated with subgroup analyses and meta-regression.
Twenty studies with 881 samples were included. The pooled adequacy of EUS-FNA/FNB sample for NGS was 89.9% (95% CI, 80.8%-96.7%) in pancreatic malignancies and 92.0% (95% CI, 81.3%-98.8%) in PDAC. Screening sample suitability before NGS testing was associated with lower adequacy in subgroup analysis (79.7% 98.4%, = 0.001). The pooled prevalences of mutations in KRAS, TP53, CDKN2A, and SMAD4 in PDAC were 87.4% (95% CI, 83.2%-91.2%), 62.6% (95% CI, 53.2%-71.7%), 20.6% (95% CI, 11.9%-30.8%), and 19.4% (95% CI, 11.2%-29.1%), respectively. The pooled prevalence of potentially actionable mutations in PDAC was 14.5% (95% CI, 8.2%-22.0%).
In the majority of cases, EUS-FNA/FNB can acquire adequate sample for NGS and identify tumor-specific mutations in patients with pancreatic malignancies. Strict pre-analysis screening criteria may negatively impact the sample adequacy and the success rate for NGS.
大多数胰腺恶性肿瘤在初诊时无法切除，需要通过超声内镜引导下细针穿刺抽吸或细针活检（EUS-FNA/FNB）进行诊断。随着精准治疗的出现，越来越需要使用EUS-FNA/FNB样本进行基因分析。二代测序（NGS）是在小样本中高灵敏度检测基因突变的首选技术。我们进行了一项荟萃分析，以评估EUS-FNA/FNB在胰腺恶性肿瘤中用于NGS的样本充足性。
检索了从数据库建立到2023年11月11日的PubMed、Embase、Cochrane图书馆和Web of Science。主要结局是EUS-FNA/FNB在胰腺恶性肿瘤中获取的用于NGS的充足样本比例。次要结局是胰腺导管腺癌（PDAC）中用于NGS的充足样本比例，以及KRAS、TP53、CDKN2A和SMAD4的突变检测率和PDAC中可操作突变的检测率。使用随机效应模型计算合并比例。通过亚组分析和meta回归研究潜在的异质性来源。
纳入了20项研究，共881个样本。在胰腺恶性肿瘤中，EUS-FNA/FNB样本用于NGS的合并充足率为89.9%（95%CI，80.8%-96.7%），在PDAC中为92.0%（95%CI，81.3%-98.8%）。在亚组分析中，NGS检测前筛查样本适用性与较低的充足率相关（79.7%对98.4%，P=0.001）。PDAC中KRAS、TP53、CDKN2A和SMAD4突变的合并患病率分别为87.4%（95%CI，83.2%-91.2%）、62.6%（95%CI，53.2%-71.7%）、20.6%（95%CI，11.9%-30.8%）和19.4%（95%CI，11.2%-29.1%）。PDAC中潜在可操作突变的合并患病率为14.5%（95%CI，8.2%-22.0%）。
在大多数情况下，EUS-FNA/FNB可以获取用于NGS的充足样本，并识别胰腺恶性肿瘤患者的肿瘤特异性突变。严格的分析前筛查标准可能会对样本充足性和NGS成功率产生负面影响。
