Mutant KRAS Circulating Tumor DNA Is an Accurate Tool for Pancreatic Cancer Monitoring

Abstract

Avoiding futile chemotherapy in metastatic pancreatic ductal adenocarcinoma (PDAC) patients by monitoring response to treatment is of utmost importance. A novel biomarker for monitoring treatment response in PDAC, using mutant circulating tumor DNA (ctDNA), is proposed. Results, although limited by small sample numbers, suggest that ctDNA can be an effective marker for disease monitoring and that ctDNA level over time is a better predictor of survival than the dynamics of the commonly used biomarker CA19-9. Therefore, ctDNA analysis can be a useful tool for monitoring PDAC treatment response. These results should be further validated in larger sample numbers.

Circulating tumor DNA quantity is related to tumor volume and both predict survival in metastatic pancreatic ductal adenocarcinoma

“…At baseline, there was no statistically significant relationship between CA19.9 and ctDNA ( n = 47; p = 0.170). Other studies have shown a correlation between CA19.9 and ctDNA, although the cohorts were of limited size . Surprisingly, we did not find ECOG status to be a significant prognosticator in the regression analysis.…”

“…The prognostic value of ctDNA for OS ( p = 0.005) is in line with the results of a recent meta‐analysis of ctDNA in PDAC . In our study, ctDNA was an predictor of OS after adjustment for CA19.9 and treatment regimen, while CA19.9 was not an independent predictor after adjustment for ctDNA, an observation also reported by others . At baseline, there was no statistically significant relationship between CA19.9 and ctDNA ( n = 47; p = 0.170).…”

“…This provides a good representation of the patient population but might have resulted in lower detection rates. In most other studies with mPDAC patients, patient flow and selection methods were unclear, hampering comparisons . Our finding that higher ctDNA detection rates occurred in patients with liver metastases of PDAC has also been reported for colorectal cancer .…”

“…The ctDNA detection rate of 46% in the total cohort and 75% in patients with high tumor volume and liver metastases are within the ranges reported in literature. Studies reporting exclusively on mPDAC showed detection rates of 29.3–33% . When various tumor stages were studied, a sensitivity between 38.8% and 86.1% was determined for those patients with metastatic disease .…”

Liquid biopsy in pancreatic ductal adenocarcinoma: current status of circulating tumor cells and circulating tumor DNA

“…In metastatic PDAC, undetectable KRAS mutant ctDNA was significantly associated with survival benefit (8 months vs . 37.5 months, P < 0.004) (Perets et al ., ). For patients with resectable disease, MST of patients in whom ctDNA was detected were significantly shorter than those of patients in whom ctDNA was not detected (3.9 months vs .…”