KRAS ctDNA Detection in Patients With Resectable Lung Adenocarcinoma
Meghan L De Meo1, Joseph Seitlinger2, Roni F Rayes3
1Cancer Research Program, Research Institute of the McGill University Health Centre, Montreal, Canada; Department of Experimental Surgery, McGill University, Montreal, Canada; Department of Surgery, Division of Thoracic Surgery, McGill University, Montreal, Canada.
Clinical Lung Cancer
|July 9, 2025
Summary
Liquid biopsy detecting KRAS ctDNA can identify patients with lung adenocarcinoma for KRAS inhibitor trials. This accessible method aids in selecting patients for neoadjuvant therapy, improving treatment efficacy.
Area of Science:
- Oncology
- Molecular Diagnostics
- Genetics
Background:
- Clinical trials are evaluating KRAS G12C inhibitors for neoadjuvant treatment in lung adenocarcinoma (LUAD).
- Accurate patient selection is crucial for the efficacy of these targeted therapies.
- Investigating the utility of circulating tumor DNA (ctDNA) for identifying suitable LUAD patients is essential.
Purpose of the Study:
- To assess the clinical utility of ctDNA for identifying resectable LUAD patients with KRAS-driven disease.
- To determine if ctDNA detection can aid in patient selection for neoadjuvant KRAS inhibitor trials.
Main Methods:
- Retrospective analysis of 47 treatment-naïve, resectable LUAD patients with KRAS mutations.
- Isolation of cell-free DNA (cfDNA) from plasma and preamplification.
- Tumor-informed digital droplet PCR (ddPCR) to detect KRAS G12C, KRAS G12V, and wild-type KRAS ctDNA.
Main Results:
- KRAS G12C ctDNA was detected in 14% of clinical stage II and 36% of pathological stage III LUAD patients.
- KRAS G12V ctDNA was detected in various stages, including 100% of clinical stage III patients.
- KRAS ctDNA positivity correlated with shorter overall survival and advanced pathological stage, including nodal involvement.
Conclusions:
- ctDNA detection via liquid biopsy is a cost-effective and accessible method for patient triage.
- This approach can facilitate patient selection for clinical trials involving neoadjuvant KRAS inhibitors in LUAD.
- ctDNA analysis offers a valuable tool for optimizing targeted therapy in lung cancer.
