149P - Rare RAS mutations are associated with recurrence patterns and recurrence-free survival in colon cancer: First results from Morocco

Background

RAS mutations have been reported to be associated with the worst overall survival in colon cancer. However, the effect of RAS mutation on recurrence-free survival and recurrence patterns remains unclear. This exploratory study aimed to evaluate the impact of RAS mutations, especially the rare mutations type in recurrence patterns in patients with stage I-IV CRC, and to identify the risk factors predicting recurrence-free survival in colon cancer.

Methods

Full RAS mutations were analyzed using Sanger and pyrosequencing for 270 patients. The MSI status was determined using immunohistochemical analysis. The correlation between Molecular alterations and recurrence patterns and recurrence-free survival was investigated. Statistical analysis was performed using the Kaplan–Meier method and the log-rank test.

Results

The mean patient's age was 55,4±14.7 with a moderate dominance of the male sex (n=146; 54.1%). The rate of recurrence after the first-line therapy was 31.5% (n=85). 13 (15,3%) patients had local recurrence, and 72 (84,7%) had distal recurrence. The most common distal recurrence site was the liver (n=34 ; 40,0%), followed by the lung (n=19 ; 22,4%). Of the 270 patients, 85 (31,5%) experienced recurrence, among whom 52,9% had mutant full RAS status, and 48,2% had KRAS mutations. Outside KRAS exon 2 mutations or rare mutations, were identified in 22 (8.1%) patients. The p.Q61L (Nras exon 3) mutation had the highest frequency in the rare mutation group (n=5 ; 22,7%), followed by the p.A146T (Kras exon 4) variant (n=4 ; 18,2%). RAS mutation status, KRAS mutations, and rare mutations were more common in patients with lung recurrence. Rare mutation status was correlated with worse recurrence-free survival (p=0,001). Multivariate logistic regression analysis revealed that differentiation, perineural invasion, full RAS mutant status, and KRAS codon 12 mutations were independent factors for recurrence-free survival in colon cancer.

Conclusions

In this cohort, recurrence patterns seemed to be associated with rare RAS mutations. KRAS codon 12 mutations were the worst predictor of recurrence-free survival at all stages in our population.

Editorial acknowledgement

Clinical trial identification

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.