Dynamics of Circulating Tumor DNA (ctDNA) Predict Treatment Efficacy and Prognosis in Patients With Advanced Pancreatic Cancer: A Prospective Large-Cohort Study

Abstract

Current methods for assessing treatment response and prognosis in pancreatic ductal adenocarcinoma (PDAC) have intrinsic limitations, necessitating novel biomarkers. This prospective cohort study evaluated whether early dynamic changes in ctDNA predict treatment efficacy and outcomes in advanced PDAC. We enrolled 127 patients receiving first-line therapy, with peripheral blood collected at baseline (B1), first response assessment (B2), and subsequent timepoints for high-depth next-generation sequencing. The ctDNA detection rates significantly decreased from 78.7% at B1 to 55.7% at B2. Elevated CA19-9 levels, ctDNA, and maximum somatic allele frequency (MSAF) were associated with disease progression. Higher B1 ctDNA and MSAF correlated with shorter progression-free survival (PFS) and overall survival (OS), consistent with an external validation cohort. The Cox regression confirmed that MSAF and CA19-9 were significant prognostic factors. In CA19-9-negative PDAC patients, increased ctDNA levels were associated with shorter PFS. This study demonstrated that high ctDNA levels and MSAF values are indicators of poor prognosis. Conversely, a decrease or clearance of ctDNA and MSAF suggests better disease control. In addition, in CA19-9-negative patients, dynamic ctDNA monitoring was able to indicate disease control and predict patient prognosis.

Keywords

advanced pancreatic cancer / ctDNA dynamics / treatment efficacy

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