Effect of KRAS and BRAF Mutations on Survival of Metastatic Colorectal Cancer After Liver Resection: A Systematic Review and Meta-Analysis

Tosi, Federica; Magni, Elena; Amatu, Alessio; Mauri, Gianluca; Bencardino, Katia; Truini, Mauro; Veronese, Silvio; Carlis, Luciano De; Ferrari, C; Nichelatti, Michele; Sartore-Bianchi, Andrea; Siena, Salvatore

doi:10.1016/j.clcc.2017.01.004

Cited by 117 publications

(93 citation statements)

References 72 publications

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“…42 However, recurrent disease occurs in the majority of patients, and even with contemporary multimodal treatment only one in five patients is cured. 44,45 The current study population displayed distributions of age, sex and tumour sidedness and mutational status in agreement with other reports on isolated CLM. 44,45 The current study population displayed distributions of age, sex and tumour sidedness and mutational status in agreement with other reports on isolated CLM.…”

Section: Discussionsupporting

confidence: 92%

Antitumour immunity invoked by hepatic arterial infusion of first‐line oxaliplatin predicts durable colorectal cancer control after liver metastasis ablation: 8–12 years of follow‐up

Abrahamsson

Jensen

Berven

et al. 2020

Intl Journal of Cancer

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In colorectal cancer (CRC), hepatic arterial infusion (HAI) chemotherapy may convert primarily unresectable CRC liver metastases (CLM) into resectability, although the risk of metastatic recurrence remains high after CLM ablation. We investigated the role of antitumour immunity invoked by first-line oxaliplatin-HAI for long-term CLM outcome. In a prospective study cohort of primarily unresectable CLM, we assessed patients' fms-related tyrosine kinase 3 ligand (FLT3LG) in serum, reflecting opportune intratumoural immune activity, at baseline and following 1-3 sequences of oxaliplatin-HAI. The end points were CLM resectability and overall survival. Patients who presented an immediate twofold increment of circulating FLT3LG during the treatment and at its completion were scored as CLM resectable (16.4% with both features), were alive at final follow-up 8-12 years later. All patients experienced FLT3LG increase during the treatment course, but those who remained unresectable or had the disease converted but presented a slow and gradual FLT3LG accretion, later died of the metastatic disease. These data provide further support to our previous findings that tumour-directed immunity invoked by oxaliplatin-containing therapy predicts excellent outcome of early advanced CRC if macroscopic tumour ablation is rendered possible by the 'classic' tumour response to the cytotoxic treatment.Additional Supporting Information may be found in the online version of this article.

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Section: Discussionsupporting

confidence: 92%

Antitumour immunity invoked by hepatic arterial infusion of first‐line oxaliplatin predicts durable colorectal cancer control after liver metastasis ablation: 8–12 years of follow‐up

Abrahamsson

Jensen

Berven

et al. 2020

Intl Journal of Cancer

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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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“…On the other hand, if KRAS is found mutant in more advanced stages of rectal cancer, this may be a consequence (22) and concluded that, KRAS mutant status is negatively associated with overall survival (OS) and relapse-free survival (RFS) in patient who underwent liver resection for metastatic CRC. Brudvik et al (23), reported similar findings in their meta-analysis of 1809 cases, published in 2015.…”

Section: Discussionmentioning

confidence: 99%

KRAS Mutant Status May Be Associated with Distant Recurrence in Early-stage Rectal Cancer

Sideris

Moorhead

Díaz‐Cano

et al. 2017

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Effect of KRAS and BRAF Mutations on Survival of Metastatic Colorectal Cancer After Liver Resection: A Systematic Review and Meta-Analysis

Cited by 117 publications

References 72 publications

Antitumour immunity invoked by hepatic arterial infusion of first‐line oxaliplatin predicts durable colorectal cancer control after liver metastasis ablation: 8–12 years of follow‐up

Antitumour immunity invoked by hepatic arterial infusion of first‐line oxaliplatin predicts durable colorectal cancer control after liver metastasis ablation: 8–12 years of follow‐up

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

KRAS Mutant Status May Be Associated with Distant Recurrence in Early-stage Rectal Cancer

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