Combating colorectal lung metastases via systemic therapy and thermal ablation: RAS mutation impact.

Area of Science:

• Oncology
• Interventional Radiology
• Molecular Diagnostics

Background:

• Colorectal lung metastases (CRLM) present a significant clinical challenge.
• Image-guided thermal ablation (IGTA) is a treatment option for CRLM.
• The prognostic role of RAS mutations in CRLM treated with IGTA requires further investigation.

Purpose of the Study:

• To determine the prognostic value of RAS mutation status and subtypes in CRLM patients undergoing IGTA.
• To evaluate survival outcomes based on different systemic therapy regimens in this patient cohort.

Main Methods:

• A multicenter retrospective-prospective cohort study included 387 CRLM patients treated with IGTA.
• Patients were stratified by RAS genotype (KRAS/NRAS wild-type vs. mutant).
• Survival outcomes (LTPFS, PFS, OS) were analyzed using Cox regression, with subgroup analyses for systemic therapies.

Main Results:

• KRAS mutations were associated with a higher 3-year local tumor progression (LTP) rate (25.0% vs. 15.0%) and predicted inferior progression-free survival (PFS).
• Median overall survival (OS) was significantly reduced in both KRAS (17.9 months) and NRAS-mutant patients (22.1 months) compared to wild-type.
• In KRAS-mutant patients, FOLFOX plus bevacizumab showed improved OS over cetuximab.

Conclusions:

• RAS mutations are independent predictors of poor local control and survival following IGTA for CRLM.
• Further research should explore interactions between RAS genotype and targeted agents in the peri-ablative setting.
• These findings support genotype-guided ablation planning and peri-ablative systemic therapy strategies for CRLM.