Federica Tosi1, Elena Magni1, Alessio Amatu1, Gianluca Mauri1, Katia Bencardino1, Mauro Truini1, Silvio Veronese1, Luciano De Carlis2, Giovanni Ferrari1, Michele Nichelatti1, Andrea Sartore-Bianchi3, Salvatore Siena4. 1. Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milano, Italy. 2. Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milano, Italy; Dipartimento di Medicina e Chirurgia, Università degli Studi di Milano-Bicocca, Milano, Italy. 3. Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milano, Italy. Electronic address: andrea.sartorebianchi@ospedaleniguarda.it. 4. Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milano, Italy; Dipartimento di Oncologia e Emato-Oncologia, Università degli Studi di Milano, Milano, Italy.
Abstract
BACKGROUND: The purpose of the study was to evaluate whether the mutational status of Kirsten rat sarcoma viral oncogene homolog (KRAS) or b-viral oncogene homolog B1 (BRAF) could be an independent prognostic factor in the subset of patients with colorectal cancer liver metastases (CRLM) who undergo complete liver resection. MATERIALS AND METHODS: A systematic literature review was performed to identify articles reporting relapse-free survival (RFS) and/or overall survival (OS) of patients who underwent complete liver resection for CRLM, stratified according to KRAS and BRAF mutational status. Hazard ratios (HRs) from multivariate analyses were pooled in the meta-analysis. RESULTS: Eleven studies, including 1833 patients, were eligible for the meta-analysis. Nine of them reported OS stratified according to KRAS mutation. The pooled analysis revealed that KRAS mutation was negatively associated with OS (HR, 1.674; 95% confidence interval [CI], 1.341-2.089; P < .001). Nine among 11 studies reported RFS stratified according to KRAS mutation and HRs in multivariate analysis were available in 7. In a pooled analysis, KRAS mutation was negatively associated with RFS (HR, 1.529; 95% CI, 1.287-1.817; P < .001). In 3 studies HRs of the multivariate analysis regarding the OS according to BRAF mutational status were also available, showing a negative association with OS (HR, 3.055; 95% CI, 1.794-5.204; P < .001). CONCLUSION: KRAS mutations are negatively associated with OS and RFS in patients who undergo complete liver resection for CRLM. A similar negative effect on OS was observed also for BRAF mutation, although fewer studies were included. These data support integration of KRAS and BRAF mutational status into a combined predictive score for prospective assessment of outcome after resection of CRLM in clinical studies.
BACKGROUND: The purpose of the study was to evaluate whether the mutational status of Kirsten ratsarcoma viral oncogene homolog (KRAS) or b-viral oncogene homolog B1 (BRAF) could be an independent prognostic factor in the subset of patients with colorectal cancer liver metastases (CRLM) who undergo complete liver resection. MATERIALS AND METHODS: A systematic literature review was performed to identify articles reporting relapse-free survival (RFS) and/or overall survival (OS) of patients who underwent complete liver resection for CRLM, stratified according to KRAS and BRAF mutational status. Hazard ratios (HRs) from multivariate analyses were pooled in the meta-analysis. RESULTS: Eleven studies, including 1833 patients, were eligible for the meta-analysis. Nine of them reported OS stratified according to KRAS mutation. The pooled analysis revealed that KRAS mutation was negatively associated with OS (HR, 1.674; 95% confidence interval [CI], 1.341-2.089; P < .001). Nine among 11 studies reported RFS stratified according to KRAS mutation and HRs in multivariate analysis were available in 7. In a pooled analysis, KRAS mutation was negatively associated with RFS (HR, 1.529; 95% CI, 1.287-1.817; P < .001). In 3 studies HRs of the multivariate analysis regarding the OS according to BRAF mutational status were also available, showing a negative association with OS (HR, 3.055; 95% CI, 1.794-5.204; P < .001). CONCLUSION:KRAS mutations are negatively associated with OS and RFS in patients who undergo complete liver resection for CRLM. A similar negative effect on OS was observed also for BRAF mutation, although fewer studies were included. These data support integration of KRAS and BRAF mutational status into a combined predictive score for prospective assessment of outcome after resection of CRLM in clinical studies.
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