Pretreatment KRAS-Mutant Circulating Tumor DNA Predicts Incidence and Patterns of Recurrence in Patients Undergoing
Ke Lin1, Cailun Wang1, Bin Qiao1
1Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
Purpose:
This prospective study aimed to evaluate the prognostic significance of pretreatment KRAS-mutant circulating tumor DNA (ctDNA) in predicting recurrence incidence and patterns in patients with colorectal liver metastasis (CRLM) undergoing radiofrequency ablation (RFA).
Methods:
Seventy-eight patients with CRLM treated with curative-intent RFA were enrolled. Pretreatment plasma ctDNA was analyzed using droplet digital polymerase chain reaction for KRAS mutations. Clinicopathologic data, recurrence patterns, and progression-free survival (PFS) were correlated with ctDNA and KRAS status. Transcriptomic profiling of tumor tissues was performed to explore biological mechanisms.
Results:
Pretreatment ctDNA was detected positive in 26.9% (21/78) of patients. Patients who harbored KRAS-mutant ctDNA exhibited significantly higher recurrence rates (71.4% v 31.6%, P = .004) and shorter median PFS (352 days v not reached, P < .001). Multivariate Cox analysis confirmed that >3 hepatic lesions (adjusted hazard ratio [HR], 7.66 [95% CI, 2.70 to 21.8], P < .001) and positive ctDNA status (adjusted HR, 3.20 [95% CI, 1.60 to 6.42], P = .001) were independent predictors of recurrence. Moreover, ctDNA-positive patients predominantly developed lung metastases (60%), while ctDNA-negative patients showed liver-dominant recurrence (61.1%). Transcriptomic analysis linked ctDNA positivity to epithelial-mesenchymal transition and DNA repair pathways, with elevated nicotinamide N-methyltransferase expression correlating with aggressive phenotypes.
Conclusion:
Pretreatment KRAS-mutant ctDNA predicts higher recurrence risk and shows an association with lung-predominant metastasis in patients with CRLM after RFA. Integrating ctDNA and KRAS profiling enhances risk stratification and supports personalized surveillance strategies.
