Association of <i>BRAF</i> Mutations With Survival and Recurrence in Surgically Treated Patients With Metastatic Colorectal Liver Cancer

Margonis, Georgios Antonios; Buettner, Stefan; Andreatos, Nikolaos; Kim, Yuhree; Wagner, Doris; Sasaki, Kazunari; Beer, Andrea; Schwarz, Christoph; Løes, Inger Marie; Smolle, Maria Anna; Kamphues, Carsten; He, Jin; Pawlik, Timothy M.; Kaczirek, Klaus; Poultsides, George A.; Lønning, Per Eystein; Cameron, John L.; Burkhart, Richard A.; Gerger, Armin; Aucejo, Federico; Kreis, Martin E.; Wolfgang, Christopher L.; Weiss, Matthew J.

doi:10.1001/jamasurg.2018.0996

Cited by 173 publications

(175 citation statements)

References 49 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%

“…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 . Patients with BRAF mutations were older and more frequently had locally advanced primary tumours (stage T4 or N+), synchronous and multiple CRLMs, and extrahepatic disease. These factors all have a negative impact on long‐term DFS and the differences between the groups based on these criteria could have biased the analysis of the impact of BRAF mutation on DFS after surgery.…”

Section: Discussionmentioning

confidence: 99%

“…reported that better outcomes among patients with mutated BRAF were associated with node‐negative primary tumours, a CEA level no higher than 200 μg/l and less than four CRLMs. In addition, Margonis and colleagues reported that V600E, but not non‐V600E, mutation was associated with worse OS and DFS. However, definitive conclusions concerning the selection of appropriate candidates for surgery cannot be reached easily from either study, because of the small numbers in the statistical analysis of the BRAF ‐mutated subgroup.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, Margonis and colleagues reported that V600E, but not non‐V600E, mutation was associated with worse OS and DFS. However, definitive conclusions concerning the selection of appropriate candidates for surgery cannot be reached easily from either study, because of the small numbers in the statistical analysis of the BRAF ‐mutated subgroup. Another limitation of these studies was the lack of data on the mismatch repair system.…”

Section: Discussionmentioning

confidence: 99%

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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%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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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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“…Margonis et al from JHH reported on 43 patients with BRAF‐mutated CRLM (six patients had concurrent extrahepatic disease). The median RFS was 9.9 months and the OS for patients with BRAF‐mutated tumors and wild‐type tumors were 26 and 60 months, respectively ( P < 0.05).…”

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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Optimizing Outcomes in Minimally Invasive Resections of Colorectal Liver Metastases

Mavani,

Shah

2024

JAMA Netw Open

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Association of BRAF Mutations With Survival and Recurrence in Surgically Treated Patients With Metastatic Colorectal Liver Cancer

Abstract: The presence of the V600E BRAF mutation was associated with worse prognosis and increased risk of recurrence. The V600E mutation was not only a stronger prognostic factor than KRAS but also was the strongest prognostic determinant in the overall cohort.

Cited by 173 publications

References 49 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

Mutation status and surgical selection

Optimizing Outcomes in Minimally Invasive Resections of Colorectal Liver Metastases

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