The Association of KRAS Mutation and Primary Tumor Location with Recurrence in Colorectal Liver Metastases Undergoing Radiofrequency Ablation

Abstract Purpose KRAS mutation and Primary tumor location are important factors affecting the prognosis of patients with colorectal liver metastases (CLM). However, some studies showed there may be an interaction between the two. We sought to investigate the association of KRAS mutations with recurrence in patients with CLM undergoing radiofrequency ablation (RFA) according to the primary tumor location. Methods CLM patients with a known KRAS gene status who underwent RFA were enrolled from January 1, 2012 to December 31, 2018. Clinicopathological data, recurrence, and survival dates were evaluated retrospectively. Results 164 patients (mean age: 58.0 ± 9.8 years, range: 34–83) who underwent percutaneous RFA of 325 CLM (mean sizes: 2.2 ± 1.0 cm, range: 0.7–5.0) were included in the study; 89 (54.3%) cases were KRAS wild-type and 75 (45.7%) cases had KRAS mutation. Of the patients, 22.0% (36 of 164) had local tumor progression (LTP), and 23 of 75 patients (30.7%) in the KRAS mutation group had LTP, which was significantly higher than in patients with KRAS wild-type (13 of 89 patients (14.6%)) ( p = 0.013). Of the 126 (76.8%) patients with recurrence after RFA, 101 (61.6%) had intrahepatic recurrence, while 88 (53.7%) had extrahepatic recurrence. Among patients with left-sided colorectal cancer (CRC), intrahepatic recurrence rates were higher among patients with KRAS mutation than among patients with the wild type KRAS (77.2% vs 52.5%, p = 0.003); the median intrahepatic recurrence-free survival (RFS) was worse in KRAS mutation patients (25 vs 15 months, P = 0.007). In patients with right-sided CRC, there was no significant difference in intrahepatic recurrence between the KRAS wild-type and KRAS mutation groups (P＞0.05). Further, KRAS gene had no impact on extrahepatic recurrence irrespective of the primary tumor site. In the multivariable analysis, KRAS mutation and positive lymph nodes remained independently associated with a worse RFS among patients (HR: 1.526, 95% confidence interval [CI]: 1.056–2.207, P = 0.025; HR: 1.602, 95% CI: 1.008–2.545, P = 0.046). Conclusions KRAS status is associated with recurrence of CLM after RFA depending on primary tumor location.