Comparative Circulating Tumor DNA Levels for KRAS Mutations in Non-Resectable Pancreatic Cancer Patients
Patients with non-resectable advanced/metastatic pancreatic cancer have a wide range of median time for overall survival (OS). Currently, there is a lack of diagnostic tools to predict the patient outcome at diagnosis. KRAS mutations are present in the vast majority of pancreatic tumors. The study objective was to determine if quantitative baseline and longitudinal monitoring of KRAS mutations from plasma circulating tumor DNA (ctDNA) could be used to stratify patients for predicting the outcome.
Clinical Study Design
- Archived plasma samples (up to 6 years) were prospectively collected from 182 patients with locally advanced or metastatic pancreatic cancer in the Danish BIOPAC study.
- Cohort consisted of non-resectable patients undergoing palliative treatment with gemcitabine or FOLFIRINOX.
- 640 longitudinal plasma samples were analyzed for KRAS mutational burden in circulating tumor (ctDNA) using the Trovagene quantitative KRAS ctDNA assay.
- Potential clinical utility of ctDNA KRAS burden to predict patient survival was investigated.
- Timepoints assayed: baseline, before cycle 2 of chemotherapy, and subsequent samples collected approximately every 2-3 months.
Highlighted Tables and Graphs
Association between Baseline ctDNA KRAS Counts and Overall Survival
Monitoring KRAS ctDNA Burden Over Time
- We developed a quantitative PCR-NGS mutation enrichment assay for the detection of KRAS codon 12/13 mutations in highly fragmented plasma ctDNA. KRAS ctDNA assay has a single copy sensitivity and the ability to detect 0.0055% mutant DNA in a background of WT DNA.
- In a prospective-retrospective study of 182 patients with metastatic pancreatic cancer, a statistically significant negative association was found between baseline ctDNA KRAS counts and OS (p < 0.0001), indicating that patients with lower KRAS burden in ctDNA survive longer.
- Ability to monitor KRAS ctDNA burden over time is demonstrated.
- Longitudinal monitoring of KRAS ctDNA burden over time indicated that patients with the longest survival were usually associated with a continued low copy number of ctDNA KRAS mutations over time.
- Stratification at baseline of non-resectable pancreatic cancer patients by ctDNA KRAS mutation copy number may be clinically useful for prognosis.