Combined RAS and SMAD4 Mutations and Microsatellite Instability Predict Outcomes in Colorectal Lung Metastases...

Area of Science:

• Oncology
• Molecular Biology
• Interventional Radiology

Background:

• Image-guided thermal ablation (IGTA) offers a minimally invasive treatment for colorectal cancer lung metastases (CRLM).
• Predictive biomarkers for IGTA outcomes in CRLM are debated.
• This study investigates the combined prognostic value of RAS/SMAD4 mutational status and microsatellite instability (MSI).

Purpose of the Study:

• To evaluate if combined RAS/SMAD4 mutational status and MSI predict outcomes after IGTA in CRLM patients.
• To address the controversy surrounding prognostic biomarkers in CRLM treatment.

Main Methods:

• A multicenter retrospective study of 412 CRLM patients undergoing CT-guided IGTA.
• Patients stratified by microsatellite status (MSS vs. MSI) and RAS/SMAD4 genotype.
• Primary endpoints: local tumor progression (LTP), progression-free survival (PFS), and overall survival (OS).

Main Results:

• Poorer OS independently predicted by lesion size ≥20 mm, ≥3 lesions, synchronous metastases, MSI, and RAS mutation.
• Shorter PFS predicted by RAS and SMAD4 mutations.
• In MSI tumors, concurrent RAS/SMAD4 mutations worsened OS/PFS (p < 0.05). In MSS tumors, single RAS/SMAD4 mutations also reduced survival.
• MSI status independently associated with higher mortality risk (HR 1.67, p = 0.005).

Conclusions:

• Concurrent RAS/SMAD4 alterations and MSI status identify high-risk CRLM patients post-IGTA.
• Integrating these molecular markers can enhance risk stratification.
• Personalized treatment strategies can be guided by these biomarkers.