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手术切除后循环肿瘤 DNA 作为分子微小残留病灶标志物对胰腺癌患者的预后影响。

Prognostic impact of postoperative circulating tumor DNA as a molecular minimal residual disease marker in patients with pancreatic cancer undergoing surgical resection.

机构信息

Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, Japan.

Department of Surgery I, Yamagata University Graduate School of Medical Science, Yamagata, Japan.

出版信息

J Hepatobiliary Pancreat Sci. 2023 Jun;30(6):815-824. doi: 10.1002/jhbp.1282. Epub 2022 Dec 1.

Abstract

PURPOSE

We aimed to clarify the prognostic impact of postoperative circulating tumor DNA (ctDNA) shortly after pancreatectomy in patients with pancreatic ductal adenocarcinoma (PDAC).

METHODS

Preoperative and paired postoperative blood samples were obtained from 66 patients in patients with PDAC. Cell-free DNA was extracted from the plasma, and KRAS mutations, as a benchmark of ctDNA, were examined using droplet digital PCR. Disease-free survival (DFS) and overall survival (OS) were compared between patients with presence and absence of ctDNA.

RESULTS

In univariate analysis, patients with detectable postoperative ctDNA showed worse survival than those with undetectable in both DFS (P = .034) and OS (P = .022). Multivariate analysis also revealed that the presence of postoperative ctDNA was an independent risk factor for recurrence (hazard ratio: 2.677, P = .011). In contrast, preoperative ctDNA detection did not affect long-term outcomes. These trends persisted in 34 patients with resectable PDAC who underwent resection after neoadjuvant chemotherapy. Patients with detectable postoperative ctDNA were more prone to developing hepatic recurrence than those with undetectable postoperative ctDNA (P = .039).

CONCLUSION

Postoperative ctDNA, as a minimal residual marker, can be useful for predicting the risk of recurrence in patients with PDAC even after curative resection.

摘要

目的

我们旨在阐明胰腺导管腺癌(PDAC)患者胰腺切除术后短时间内循环肿瘤 DNA(ctDNA)的预后影响。

方法

从 66 例 PDAC 患者中采集术前和术后配对的血液样本。从血浆中提取无细胞 DNA,并使用液滴数字 PCR 检测 KRAS 突变作为 ctDNA 的基准。比较有和无 ctDNA 的患者的无病生存(DFS)和总生存(OS)。

结果

在单因素分析中,与无法检测到术后 ctDNA 的患者相比,检测到术后 ctDNA 的患者在 DFS(P =.034)和 OS(P =.022)方面的生存情况更差。多因素分析还表明,术后 ctDNA 的存在是复发的独立危险因素(危险比:2.677,P =.011)。相比之下,术前 ctDNA 的检测并不影响长期结果。这些趋势在 34 例接受新辅助化疗后行切除术的可切除 PDAC 患者中仍然存在。与无法检测到术后 ctDNA 的患者相比,检测到术后 ctDNA 的患者更倾向于发生肝转移(P =.039)。

结论

术后 ctDNA 作为最小残留标志物,即使在根治性切除术后,也可用于预测 PDAC 患者的复发风险。

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