Can KRAS and BRAF mutations limit the benefit of liver resection in metastatic colorectal cancer patients? A systematic review and meta-analysis

Passiglia, Francesco; Bronte, Giuseppe; Bazan, Viviana; Galvano, Antonio; Vincenzi, Bruno

doi:10.1016/j.critrevonc.2015.12.015

Cited by 87 publications

(80 citation statements)

References 55 publications

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“…In all previous studies, BRAF mutation was associated with a higher rate of recurrence after surgery and earlier recurrence, within the first year after surgery. In these studies, patients with mutated BRAF were extracted from databases of patients who had surgery for CRLMs, and patients who had BRAF mutations were not comparable with those who had wild‐type BRAF .…”

Section: Discussionmentioning

confidence: 99%

BRAF mutation is not associated with an increased risk of recurrence in patients undergoing resection of colorectal liver metastases

Bachet

Moreno-Lopez

Viganò

et al. 2019

British Journal of Surgery

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Background BRAF mutation is associated with a poor prognosis in patients with metastatic colorectal cancer. For patients with resectable colorectal liver metastases (CRLMs), the prognostic impact of BRAF mutation is unknown and the benefit of surgery debated. This nationwide intergroup (ACHBT, FRENCH, AGEO) study aimed to evaluate the oncological outcome of patients undergoing liver resection for BRAF‐mutated CRLMs. Methods The study included patients who underwent resection for BRAF‐mutated CRLMs in 24 centres between 2012 and 2016. A case‐matched comparison was made with 183 patients who underwent resection of CRLMs with wild‐type BRAF during the same interval. Results Sixty‐six patients who underwent resection for BRAF‐mutated CRLMs in 24 centres were compared with 183 patients with wild‐type BRAF. The 1‐ and 3‐year disease‐free survival (DFS) rates were 46 and 19 per cent for the BRAF‐mutated group, and 55·4 and 27·8 per cent for the group with wild‐type BRAF (P = 0·430). In multivariable analysis, BRAF mutation was not associated with worse DFS (hazard ratio 1·16, 95 per cent c.i. 0·72 to 1·85; P = 0·547). The 1‐ and 3‐year overall survival rates after surgery were 94 and 54 per cent respectively among patients with BRAF mutation, and 95·8 and 82·9 per cent in those with wild‐type BRAF (P = 0·004). Median survival after disease progression was 23·0 (95 per cent c.i. 11·0 to 35·0) months among patients with mutated BRAF and 44·3 (35·9 to 52·6) months in those with wild‐type BRAF (P = 0·050). Multisite disease progression was more common in the BRAF‐mutated group (48 versus 29·8 per cent; P = 0·034). Conclusion These results support surgical treatment for resectable BRAF‐mutated CRLM, as BRAF mutation by itself does not increase the risk of relapse after resection. BRAF mutation is associated with worse survival in patients whose disease relapses after resection of CRLM, as for non‐metastatic colorectal cancer.

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Section: Discussionmentioning

confidence: 99%

BRAF mutation is not associated with an increased risk of recurrence in patients undergoing resection of colorectal liver metastases

Bachet

Moreno-Lopez

Viganò

et al. 2019

British Journal of Surgery

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“…Moreover, KRAS mutations in CRC patients were significantly associated with the number of pulmonary metastasis and with the lung as first site of recurrence after pulmonary metastasectomy13. Besides, KRAS mutation has been reported to be a potential negative prognostic factor in patients with liver metastatic colorectal cancer in various treatment modalities141516.…”

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confidence: 99%

KRAS-mutation incidence and prognostic value are metastatic site-specific in lung adenocarcinoma: poor prognosis in patients with KRAS mutation and bone metastasis

Lohinai

Klikovits

Moldvay

et al. 2017

Sci Rep

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Current guidelines lack comprehensive information on the metastatic site-specific role of KRAS mutation in lung adenocarcinoma (LADC). We investigated the effect of KRAS mutation on overall survival (OS) in this setting. In our retrospective study, 500 consecutive Caucasian metastatic LADC patients with known KRAS mutational status were analyzed after excluding 32 patients with EGFR mutations. KRAS mutation incidence was 28.6%. The most frequent metastatic sites were lung (45.6%), bone (26.2%), adrenal gland (17.4%), brain (16.8%), pleura (15.6%) and liver (11%). Patients with intrapulmonary metastasis had significantly increased KRAS mutation frequency compared to those with extrapulmonary metastases (35% vs 26.5%, p = 0.0125). In contrast, pleural dissemination and liver involvement were associated with significantly decreased KRAS mutation incidence (vs all other metastatic sites; 17% (p < 0.001) and 16% (p = 0.02) vs 33%, respectively). Strikingly, we found a significant prognostic effect of KRAS status only in the bone metastatic subcohort (KRAS-wild-type vs KRAS-mutant; median OS 9.7 v 3.7 months; HR, 0.49; 95% CI, 0.31 to 0.79; p = 0.003). Our study suggests that KRAS mutation frequency in LADC patients shows a metastatic site dependent variation and, moreover, that the presence of KRAS mutation is associated with significantly worse outcome in bone metastatic cases.

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“…This may explain why the incidence of BRAF mutations is much lower in surgical than medical cohorts. According to a recent meta‐analysis, the incidence of BRAF mutants in surgical cohorts was 50% lower compared with medically treated cohorts (2%‐4% vs 5%‐10%, respectively) …”

Section: Resultsmentioning

confidence: 99%

Mutation status and surgical selection

Margonis

Kreis

Wolfgang

et al. 2019

Journal of Surgical Oncology

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Current evidence cannot support denying metastasectomy in otherwise resectable patients solely based on their overall KRAS or BRAF mutational status. The combination of KRAS or BRAF mutational status with certain clinicopathologic characteristics has defined groups of patients who may not derive benefit from metastasectomy, but external validation is needed. The effect of certain KRAS or BRAF variants on survival may be more pronounced and therefore future studies should consider them for surgical selection.

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Can KRAS and BRAF mutations limit the benefit of liver resection in metastatic colorectal cancer patients? A systematic review and meta-analysis

Cited by 87 publications

References 55 publications

BRAF mutation is not associated with an increased risk of recurrence in patients undergoing resection of colorectal liver metastases

BRAF mutation is not associated with an increased risk of recurrence in patients undergoing resection of colorectal liver metastases

KRAS-mutation incidence and prognostic value are metastatic site-specific in lung adenocarcinoma: poor prognosis in patients with KRAS mutation and bone metastasis

Mutation status and surgical selection

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