Detecting circulating tumor DNA (ctDNA) mutations in localized pancreatic cancer patients undergoing neoadjuvant chemotherapy can guide surgical decisions and predict outcomes.

• 49.3% of patients had mutant KRAS ctDNA at diagnosis; this rose to 69.6% after chemotherapy.
• Patients who cleared ctDNA during treatment had improved overall survival (18.4 months vs. not reached, p < 0.05).

Identifying mutant KRAS G12V after surgery indicated worse survival (18 months vs. not reached, p < 0.031).

• Detection of G12V post-resection linked to significantly reduced overall survival (HR 36.75, 95% CI: 2.93-461.38).