胰腺导管腺癌是全球预后最差的实体瘤之一，辅助或新辅助治疗后复发率很高。循环肿瘤 DNA 分析被认为是一种有前景的非侵入性工具，可用于表征肿瘤基因组学和评估治疗反应。在这项研究中，通过下一代测序对手术肿瘤组织和连续血液样本进行了分析，并将其与临床和病理特征相关联。纳瓦拉大学医院治疗的 30 名可切除/交界性胰腺导管腺癌患者被纳入其中。循环肿瘤 DNA 测序鉴定出 KRAS 和 TP53 以及其他癌症相关基因的致病变异。在预后较差的患者中检测到诊断时的致病变异，并且与交界性胰腺导管腺癌患者对新辅助治疗的反应相关。诊断时较高的变异等位基因频率与较差的预后相关，并且进展时样本中变异等位基因频率的总和更大。我们的结果建立在循环肿瘤 DNA 对非转移性胰腺导管腺癌患者的潜在价值之上，通过补充组织遗传信息并作为治疗决策的非侵入性工具。需要验证性研究来证实这些发现。© 2024。作者。

Pancreatic ductal adenocarcinoma represents one of the solid tumors showing the worst prognosis worldwide, with a high recurrence rate after adjuvant or neoadjuvant therapy. Circulating tumor DNA analysis raised as a promising non-invasive tool to characterize tumor genomics and to assess treatment response. In this study, surgical tumor tissue and sequential blood samples were analyzed by next-generation sequencing and were correlated with clinical and pathological characteristics. Thirty resectable/borderline pancreatic ductal adenocarcinoma patients treated at the Hospital Universitario de Navarra were included. Circulating tumoral DNA sequencing identified pathogenic variants in KRAS and TP53, and in other cancer-associated genes. Pathogenic variants at diagnosis were detected in patients with a poorer outcome, and were correlated with response to neoadjuvant therapy in borderline pancreatic ductal adneocarcinoma patients. Higher variant allele frequency at diagnosis was associated with worse prognosis, and thesum of variant allele frequency was greater in samples at progression. Our results build on the potential value of circulating tumor DNA for non-metastatic pancreatic ductal adenocarcinoma patients, by complementing tissue genetic information and as a non-invasive tool for treatment decision. Confirmatory studies are needed to corroborate these findings.© 2024. The Author(s).