Background: Pancreatic ductal adenocarcinoma (PDAC) carries a poor prognosis and is frequently unresectable at presentation, underscoring the need for minimally invasive biomarkers to guide care. Circulating tumour DNA (ctDNA can be repeatedly sampled to provide near real-time molecular readouts. Compared with CA19-9 and cross-sectional imaging, ctDNA may better capture spatial tumour heterogeneity, emerging resistance, and early treatment effects. Although detectability (“shedding”) and mutant allele fraction often reflect tumour burden, the prognostic value of a single pre-treatment ctDNA measurement remains uncertain, and dynamic on-treatment kinetics may ultimately yield more informative predictors of outcome.
Methods: The OSCILLATE (An Observational Study following Circulating tumour DNA during multi-Agent Therapy in PDAC) study is a multi-centre, prospective cohort study that aimed to investigate the predictive value of mutant KRAS ctDNA level throughout the course of multi-agent therapy in the unresectable PDAC patients. This preliminary analysis used only baseline (pre-chemotherapy) measurements. Patients were classified as ctDNA “shedders” or “non-shedders.”
Results: 35 patients were enrolled. Of 19 cases analysed so far, 6 (31.6%) subjects were non-shedders. Kaplan–Meier analysis indicated that baseline shedding status was not associated with OS (log-rank P= 0.655). Among shedders, the correlation between baseline mutant KRAS ctDNA level and OS was negative but not significant (Spearman’s ρ= -0.099, P= 0.748). The correlation between baseline ctDNA and CA19-9 was positive but not significant (ρ= 0.105, P= 0.746). In univariate Cox analysis, baseline ctDNA level was not a significant predictor of OS (hazard ratio: 1.002; 95% CI, 1.000-1.005; P= 0.071).
Conclusions: Baseline mutant KRAS ctDNA (considered either as shedding status or as a continuous level) did not significantly associate with OS and was not an independent predictor at treatment start. Ongoing longitudinal analyses within OSCILLATE will evaluate on-treatment ctDNA kinetics and their potential to improve risk stratification and therapeutic monitoring.
Keywords: Pancreatic ductal adenocarcinoma; Circulating tumour DNA; KRAS mutation; Chemotherapy; Prognosis