Prognostic value of KRAS and BRAF mutations in curatively resected colorectal cancer

AIM: To investigate the prognostic role of KRAS and BRAF mutations after adjustment for microsatellite instability(MSI) status in Japanese colorectal cancer(CRC) population.METHODS: We assessed KRAS and BRAF mutations and MSI status in 813 Japanese patients with curatively resected, stage Ⅰ-Ⅲ CRC and examined associations of these mutations with disease-free survival(DFS) and overall survival(OS) using uni- and multivariate Cox proportional hazards models.RESULTS: KRAS and BRAF mutations were detected in 312(38%) of 812 and 40(5%) of 811 tumors, respectively. KRAS mutations occurred more frequently in females than in males(P = 0.02), while the presence of BRAF mutations was significantly associated with the female gender(P = 0.006), proximal tumor location(P < 0.001), mucinous or poorly differentiated histology(P < 0.001), and MSI-high tumors(P < 0.001). After adjusting for relevant variables, including MSI status, KRAS mutations were associated with poorer DFS(HR = 1.35; 95%CI: 1.03-1.75) and OS(HR = 1.46; 95%CI: 1.09-1.97). BRAF mutations were poor prognostic factors for DFS(HR = 2.20; 95%CI: 1.19-4.06) and OS(HR = 2.30; 95%CI: 1.15-4.71). Neither the BRAF by MSI interaction test nor the KRAS by MSI interaction test yielded statistically significant results for DFS and OS.CONCLUSION: KRAS and BRAF mutations are associated with inferior survival, independent of MSI status, inJapanese patients with curatively resected CRC.

Serum squamous cell carcinoma antigen is a predictive factor of outcomes in patients with locally advanced unresectable esophageal squamous cell carcinoma treated by definitive chemoradiotherapy

Aim:Definitive chemoradiotherapy(dCRT)is the standard treatment for locally advanced unresectable esophageal squamous cell carcinoma(LU-ESCC).This study aimed to describe the results of dCRT for T4 ESCC and evaluate the pretherapeutic predictive factors of the outcomes.Methods:A total of 133 patients with T4 ESCC who received dCRT were grouped into those who achieved a complete response(CR)or those who had residual disease(RD).The clinicopathologic variables were compared between the groups and the overall survival(OS)was evaluated.The predictive factor of RD was assessed and the prognostic factor for OS was identified.Results:Among the 133 patients,31(23%)achieved CR.The CR group had a significantly better OS than the RD group(89.9 months vs.10.7 months;hazard ratio=0.096;95%confidence interval:0.05-0.19;P<0.001).Multivariate analysis showed that a supracarinal tumor(OR=3.21;P=0.016),higher pretherapeutic serum SCC-Ag level(>1.6 ng/mL)(OR=2.86;P=0.018),and metastatic node invasion(OR=3.19;P=0.048)were independent predictors of RD.The increased level of pretherapeutic serum squamous cell carcinoma antigen(>1.6 ng/mL)(OR=1.61;P=0.022)was an independent predictor of poor survival.Conclusions:Among the patients who underwent dCRT for LU-ESCC,23%achieved CR,and the long-term outcome of these patients was favorable.Increased levels of pretherapeutic serum squamous cell carcinoma antigen were also found to be predictive of treatment failure.