Building on the clinical applicability of ctDNA analysis in non-metastatic pancreatic ductal adenocarcinoma

Abstract Background. Pancreatic ductal adenocarcinoma (PDAC) represents one of the worst prognostic cancers worldwide, with a high recurrence rate after adjuvant or neoadjuvant therapy (NAT). Circulating tumor DNA (ctDNA) analysis raised as a promising non-invasive tool to characterize tumor genomics and to assess treatment response.Methods. 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 PDAC patients treated at the Hospital Universitario de Navarra (HUN) were included.Results. ctDNA 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 NAT in borderline PDAC patients. Higher variant allele frequency (VAF) at diagnosis was associated with worse prognosis, and VAF sum was greater in samples at progression.Conclusion. Our results build on the potential value of ctDNA for non-metastatic PDAC patients, by complementing tissue genetic information and as a non-invasive tool for treatment decision. Confirmatory studies are needed to corroborate these findings.