PDF(Pubmed)
Abstract：
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.
摘要：
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高。循环肿瘤DNA分析是表征肿瘤基因组学和评估治疗反应的一种有前途的非侵入性工具。在这项研究中,手术肿瘤组织和序贯血液样本通过下一代测序进行分析,并与临床和病理特征相关.包括在纳瓦拉大学医院接受治疗的30名可切除/交界性胰腺导管腺癌患者。循环肿瘤DNA测序鉴定了KRAS和TP53以及其他癌症相关基因的致病变异。诊断时在预后较差的患者中检测到致病性变异，并且与临界胰腺导管型肾上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，在进展时，样本中变异等位基因频率的总和更大。我们的结果建立在非转移性胰腺导管腺癌患者循环肿瘤DNA的潜在价值，通过补充组织遗传信息，并作为治疗决策的非侵入性工具。需要进行验证性研究来证实这些发现。
