The Predictive Value Of KRAS Gene For Local Tumor Progression And Local Tumor Progression Free Survival Of Colorectal Liver Metastases After Radiofrequency Ablation

Background:Radiofrequency ablation(RFA)is a common local technique for the treatment of colorectal liver metastases(CLMs).The colorectal cancer with mutant KRAS has aggressive and metastatic oncology behavior and poor therapeutic effect of chemotherapy.Objective:The purpose of this study is to evaluate the relationship between KRAS gene and local tumor progression(LTP),local tumor progression free survival(LTPFS)and to assess BRAF gene,NRAS gene and other variables affecting local tumor progression,local tumor progression free survival in patients with CLMs treated by RFA.Methods:The clinical and imaging data from 120 patients(212 lesions)with CLMs who underwent RFA in our Hospital from January 2017 to December 2019 were analyzed.LTP was defined as the appearance of tumor foci within 1 cm of the edge of the ablation zone on contrast-enhanced CT or magnetic resonance images after at least one contrast-enhanced post-ablation follow-up study had documented adequate ablation and an absence of viable tissue in the target tumor and surrounding ablation margin.LTPFS was measured in months from the date of first ablation session to the date when local tumor progression was detected on cross-sectional imaging or last follow-up.Results:The study included 120 patients who underwent ablation of 212 CLMs.Forty-nine patients(40.8%)had mutant KRAS.Rates of local tumor progression were 18.3%(13/71)for patients with wild-type KRAS and 30.6%(15/49)for patients with mutant KRAS.Actuarial local tumor progression-free survival after RFA were worse in patients with mutant KRAS than wild-type KRAS(1-year local tumor progression free survival rate: 51.0% vs 76.1%,p=0.004).There was no significant difference between the follow-up time of wild-type KRAS patients and that of mutant KRAS patients(16.20±5.03 vs 15.89±3.96 months,p>0.05).The mean LTPFS of 120 patients were 12.89 months.In multivariable analysis,positive predictors of local tumor progression were wild-type KRAS(hazard ratio [HR] 0.239,95% confidence interval [CI] 0.081–0.706;p=0.010),wild-type NRAS(HR 0.190,95% CI 0.043–0.840;p=0.028)and maximum diameter of the ablated CLMs <30mm(HR 0.31,95% CI 0.097–0.992;p=0.048);a positive predictor of local tumor progression of wild-type RAS was maximum diameter of the ablated CLMs <30mm(HR 0.052,95% CI 0.008–0.357;p=0.003);negative predictors of local tumor progression free survival were mutant KRAS(HR 3.97,95% CI 1.65–9.55;p=0.002)and mutant BRAF(HR 4.35,95% CI 1.47–12.86;p=0.008);a positive predictor of local tumor progression free survival of wild-type RAS was maximum diameter of the ablated CLMs <30mm(HR 0.118,95% CI 0.029–0.479;p=0.003).Conclusion:KRAS gene status of liver metastatic lesions was associated with LTP and LTPFS after RFA of CLMs.Maximum diameter of the ablated CLMs≥30mm was associated with a higher rate of local tumor progression in patients undergoing ablation of CLMs.