Clinical significance of monitoring KRAS in the blood of pancreatic cancer patients.

Abstract

e23042 Background: KRAS monitoring provides valuable information for early diagnosis and prediction of treatment outcome in colorectal cancer. KRAS mutation is observed in only half of colon cancer patients, whereas it is detected in 90% of pancreatic cancer patients. Therefore, investigating tumor DNA in blood by KRAS monitoring may be even more valuable in pancreatic cancer patients. In this study, we elucidated the clinical significance of KRAS monitoring in pancreatic cancer patients during treatment. Methods: KRAS in tumor tissues was analyzed for mutations by Scorpion ARMS or RASKET in 38 patients with pancreatic tumors. KRAS in blood was analyzed for mutations (G12D, G12V, G12C, G12A, G12S, G12R, G13D, Q61L, and Q61H) using droplet digital polymerase chain reaction in 23 patients who underwent chemotherapy and who had KRAS mutation in their tissues. Results: KRAS mutation in tumor tissues was detected in 27 of 38 patients (71.1%). These 27 patients showed significantly poorer prognosis (24.4 months median overall survival time [MST]) than the six patients without mutation (p = 0.04), who were all alive. Patients with mutation of 12D in tumor tissues showed better prognosis than patients with other types of mutation; thus, mutation of 12D may have a different biological effect to other mutations. Monitoring of KRAS in blood revealed KRAS mutation in 14 of 23 patients (60.9%). These 14 patients exhibited significantly poorer treatment outcomes than patients without mutation. The MST of patients with KRAS mutation in their blood was significantly shorter than that of patients without KRAS mutation (17.7 months vs. 44.3 months, p = 0.03). Conclusions: KRAS mutation in blood could be a valuable predictive and prognostic biomarker in pancreatic cancer patients who undergo chemotherapy. Additionally, assessment of KRAS in tumor tissues may provide information about individual tumor biology.