medwireNews: The presence of the BRAF V600E mutation in colorectal liver metastases (CRLM) is associated with a worse prognosis and increased risk for recurrence, according to findings from an international retrospective cohort study.
Overall, 44.2% of 849 patients who underwent CRLM resection with curative intent died over the median follow-up of 28.3 months, while 55.7% patients experienced recurrence or metastasis during the study.
Those whose disease carried the BRAF V600E mutation were more than twice as likely to die or experience recurrence as those with wild-type (wt)BRAF, with significant hazard ratios of 2.76 for overall survival and 2.04 for disease-free survival on multivariable analysis. Non-V600E BRAF mutations, however, were not associated with a worse prognosis.
The BRAF V600E mutation had the greatest prognostic influence of all the factors investigated for both overall and disease-free survival, and more than three times greater prognostic influence than a KRAS mutation for both outcomes.
This suggests, say Matthew Weiss (Johns Hopkins University, Baltimore, Maryland, USA) and colleagues in JAMA Surgery, “that BRAF and KRAS mutations should not be used interchangeably as markers of aggressive tumor biology,” and that the BRAF V600E mutation “may serve as a more useful tool for preoperative patient selection than KRAS mutation status.”
They believe that their study involved the largest cohort of surgically treated patients with CRLM and BRAF mutations reported in the literature to date. Among 849 patients, 43 (5.1%) had mutant (mt)BRAF/wtKRAS disease, 480 (56.5%) had wtBRAF/wtKRAS disease, and 326 (38.4%) had a wtBRAF/mtKRAS genotype.
Compared with patients with wtBRAF/wtKRAS disease, those whose cancer was mtBRAF/wtKRAS were significantly more likely to be 65 years or older and female, and the primary tumor was significantly more likely to be on the right versus the left side and to be of a more advanced T stage. These individuals were also more likely to present with metachronous liver metastases.
The researchers describe the finding that the V600E mutation alone, rather than V600E and non-V600E mutations together, confers a distinct clinical phenotype that drives the poor prognosis associated with BRAF mutations as “novel.”
But they warn that this should be interpreted with caution as only six patients had a non-V600E mutation and four had a nonspecified BRAF mutation.
“Although the number of patients with non-V600E BRAF mutations can be considered to be too small to draw definitive conclusions, our results indicate that different BRAF mutations may have a distinct association with survival,” the team concludes.
By Catherine Booth
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