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KRAS ctDNA Detection in Patients With Resectable Lung Adenocarcinoma.

Meghan De Meo,J. Seitlinger,R. Rayes,Lyndon C. Walsh,M. H. Shahzad,Thupten Tsering,R. Saleh,Nicole Ezer,Benjamin Shieh,Annick Wong,S. Owen,Logan Walsh,P. Fiset,J. Burnier,Jonathan D. Spicer

Published 2025 in Clinical Lung Cancer

ABSTRACT

INTRODUCTION/BACKGROUND Clinical trials are assessing the suitability of KRASG12C inhibitors in the neoadjuvant setting. Appropriate patient selection is paramount to ensure therapeutic efficacy. Here we sought to investigate the clinical utility of ctDNA to identify resectable lung adenocarcinoma (LUAD) patients with KRAS-driven disease. MATERIALS & PATIENTS From our institution's clinical database and biobank, we identified 47 patients based on our inclusion criteria: research-consented, treatment-naïve, NGS-confirmed KRAS-mutated resectable stage IA-IIIB LUAD with available pre-operative blood. cfDNA was isolated from 700-2000µL plasma and was preamplified. In a tumour-informed approach, digital droplet polymerase chain reaction (ddPCR) was performed to identify hotspot KRASG12C & KRASG12V ctDNA and wild-type KRAS cfDNA in the same reaction based on prior tumor tissue profiling. RESULTS In overall clinical staging, KRASG12C ctDNA was detected in liquid biopsies of stage II (1/7, 14%) and III (2/5, 40%) patients. In overall pathological staging, KRASG12C ctDNA was detected exclusively in liquid biopsies of stage III patients (4/11, 36%). KRASG12V ctDNA was detected in liquid biopsies of overall clinical stage I (1/3, 33%) and III (1/1, 100%) patients and in pathological stage II (1/3, 33%) and III (1/2, 50%) patients. KRAS ctDNA positivity was associated with shorter overall survival (median OS 21 months vs. 41 months, P < .05). KRASG12C ctDNA positivity was associated with larger tumour size, presence of nodal involvement, and higher overall pathological stage. CONCLUSION ctDNA positivity from liquid biopsy is a low-cost and accessible method for triaging patients with LUAD towards trials evaluating KRAS inhibitors in the neoadjuvant setting.

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