CLINICAL EVIDENCE

Circulating Tumor DNA Assay Performance for Detection and Monitoring of KRAS Mutations in Urine from Patients with Advanced Cancers

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Introduction

  • Noninvasive urinary ctDNA-based liquid biopsy approach can be used to detect and track cancer driver mutations for rapid diagnosis and disease monitoring.
  • Using a highly sensitive ctDNA mutation detection platform, we examined detection of KRAS G12/13 mutations in urine obtained from patients with advanced cancers assessed urine sample requirements and compared the results with matched tumor tissue.

Study Design

  • Urine and plasma samples collected from 41 patients with advanced or metastatic cancers positive for KRAS G12/13 mutations in tissue (colorectal, n=26; lung, n=6; pancreatic, n=4; ovarian, n=2; melanoma, n=1; breast, n=1; other, n=1).

Highlighted Tables and Graphs

Clinical Sensitivity of KRAS G12/13 ctDNA Assay

Longitudinal Monitoring by ctDNA KRAS G12/13

Conclusions

  • Mutation enrichment NGS assay for KRAS G12/13 mutation detection in ctDNA has a single copy analytical sensitivity (0.002%-0.006%).
  • In a blinded study of 41 patients with advanced or metastatic cancers, including colorectal, pancreatic, ovarian, lung, melanoma, and breast cancers, KRAS G12/13 mutation concordant with tissue was detected in 80% of urine samples with recommended volume of at least 90 mL and 83% of plasma samples with volumes 1-4 mL. In a colorectal cancer cohort, KRAS G12/13 mutation detection sensitivity was 100% for both urine and plasma.
  • Kinetics of KRAS G12/13 mutation signal in urine ctDNA corresponds to treatment outcomes.
  • Analysis of urine and plasma may be a viable approach for diagnostic detection of KRAS mutations and therapeutic monitoring of patients with advanced cancers.