Impact of BRAF mutations on clinical outcomes following liver surgery for colorectal liver metastases: An updated meta-analysis.

BACKGROUND: Data regarding clinical outcomes of patients undergoing hepatic resection for BRAF-mutated colorectal liver metastases (CRLM) are scarce. Most of the studies report an impaired median overall survival (OS) in BRAF-mutated patients, but controversial Results regarding both recurrence-free survival (RFS) and recurrence patterns. The purpose of this updated meta-analysis was to better precise the impact of BRAF mutations on clinical outcomes following liver surgery for CRLM study, especially on recurrence. METHODS: A systematic literature review was performed to identify articles reporting clinical outcomes including both OS and RFS, recurrence patterns, and clinicopathological details of patients who underwent complete liver resection for CRLM, stratified according to BRAF mutational status. RESULTS: Thirteen retrospective studies, including 5192 patients, met the inclusion criteria. The analysis revealed that both OS (OR = 1.981; 95% CI = [1.613-2.432]) and RFS (OR = 1.49; 95% CI [1.01-2.21]) were impaired following liver surgery for CRLM in BRAF-mutated patients. Risks of both hepatic (OR = 0.42; 95% CI [0.18-0.98]) and extrahepatic recurrences (OR = 0.53; 95% CI [0.33-0.83] were significantly higher in BRAF-mutated patients. These patients tended to have higher rates of right-sided colon primary tumors, primary positive lymph nodes, and multiple CRLM. CONCLUSIONS: This meta-analysis confirms that BRAF mutations impair both OS and RFS following liver surgery. Therefore, BRAF mutational status should probably be included in further prognostic scores for the assessment of the expected clinical outcomes following surgery for CRLM.

Performance of two prognostic scores that incorporate genetic information to predict long-term outcomes following resection of colorectal cancer liver metastases: An external validation of the MD Anderson and JHH-MSK scores.

INTRODUCTION: Two novel clinical risk scores (CRS) that incorporate KRAS mutation status were developed: modified CRS (mCRS) and GAME score. However, they have not been tested in large national and international cohorts. The aim of this study was to validate the prognostic discrimination utility and determine the clinical usefulness of the two novel CRS. METHODS: Patients undergoing hepatectomy for CRLM (2000-2018) in 10 centers were included. The discriminatory abilities of mCRS, GAME, and Fong CRS were evaluated using Harrell's C-index and Akaike's Information Criterion. RESULTS: In the entire cohort, the C-index of the GAME score (0.61) was significantly higher than those of Fong score (0.57) and mCRS (0.54), while the C-Index of mCRS was significantly lower than that of Fong score. When we compared the models in the various geographical regions, the C-index of GAME score was significantly higher than that of mCRS in North America, Europe, and South America. The AIC of Fong score, mCRS, and GAME score were 14 405, 14 447, and 14 319, respectively. CONCLUSION: In conclusion, using the largest and most heterogenous population of CRLM patients with known KRAS status, this independent, external validation demonstrated that the GAME score outperforms both the traditional Fong score and mCRS.