OBJECTIVE The primary objective was to determine the prognostic significance of circulating tumor DNA (ctDNA) in patients receiving neoadjuvant chemotherapy (NAC) for localized pancreatic ductal adenocarcinoma (PDAC) using digital droplet polymerase chain reaction (ddPCR). SUMMARY AND BACKGROUND DATA Increasingly, ctDNA is being used for clinical decision-making in a variety of solid malignancies. However, the detection and prognostic value of KRAS ctDNA as assessed by ddPCR during NAC has yet to be characterized. METHODS Patients with localized PDAC eligible to receive NAC were prospectively enrolled. Peripheral blood samples were obtained at diagnosis, after NAC, and after resection and analyzed for ctDNA using ddPCR. Log-rank tests and Cox proportional hazards model were used to assess for association with OS. RESULTS 84 patients were included in the analysis. Mutant KRAS ctDNA was detected in 49.3% of patients at diagnosis, 69.6% of patients after NAC, and 69.7% of patients after resection, respectively. There were 15 (17.9%) patients that cleared mutational ctDNA over the course of treatment. Clearance of ctDNA during NAC was associated with improved overall survival (OS) (18.4 mo. vs NR, P<0.05). Detection of mutant KRAS G12V after NAC and resection was associated with shorter OS (18.0 versus NR months, P<0.031). Detection of the KRAS G12V mutation after resection was associated with reduced OS (aHR 36.75, 95% CI 2.93-461.38). CONCLUSIONS Throughout treatment, KRAS ctDNA is detectable by ddPCR in patients with localized PDAC treated with NAC. Detection of mutant KRAS G12V after resection was associated with reduced OS.

中文翻译：

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循环肿瘤 DNA 中的突变 KRAS 作为新辅助化疗患者局限性胰腺癌的生物标志物。


目的 主要目的是使用数字液滴聚合酶链反应 （ddPCR） 确定接受新辅助化疗 （NAC） 治疗局限性胰腺导管腺癌 （PDAC） 的患者循环肿瘤 DNA （ctDNA） 的预后意义。摘要和背景数据 ctDNA 越来越多地用于各种实体恶性肿瘤的临床决策。然而，在 NAC 期间通过 ddPCR 评估的 KRAS ctDNA 的检测和预后价值尚未确定。方法 前瞻性纳入符合接受 NAC 条件的局部 PDAC 患者。在诊断时、NAC 后和切除后获取外周血样本，并使用 ddPCR 分析 ctDNA。采用对数秩检验和 Cox 比例风险模型评估与 OS 的相关性。结果 84 例患者被纳入分析。诊断时 49.3% 的患者、NAC 后 69.6% 的患者和切除后 69.7% 的患者分别检测到突变的 KRAS ctDNA。有 15 例 （17.9%） 患者在治疗过程中清除了突变的 ctDNA。NAC 期间 ctDNA 的清除与总生存期 （OS） 的改善相关 （（18.4 mo. vs NR， P<0.05）。NAC 和切除术后检测到突变的 KRAS G12V 与较短的 OS 相关 （18.0 个月 vs NR 月，P<0.031）。切除后检测到 KRAS G12V 突变与 OS 降低相关 （aHR 36.75,95% CI 2.93-461.38）。结论 在整个治疗过程中，在 NAC 治疗的局部 PDAC 患者中，通过 ddPCR 可检测到 KRAS ctDNA。切除后检测到突变的 KRAS G12V 与 OS 降低相关。