BRAF mutations tied to post-surgery prognosis in colorectal liver cancer

Last Updated: 2018-05-24

By David Douglas

NEW YORK (Reuters Health) - The V600E BRAF mutation is associated with poorer prognosis and increased risk of recurrence in patients who have undergone resection of colorectal liver metastases (CRLM), according to a large cohort study.

There is evidence that both KRAS and BRAF mutations are of prognostic value in resectable CRLM, write Dr. Georgios Antonios Margonis of Johns Hopkins University, in Baltimore, Maryland, and colleagues in JAMA Surgery, online May 16. However, the influence of BRAF mutations has not been well studied in such patients because of its low incidence compared with KRAS mutations.

"Our study aimed to answer what is the prognostic impact of BRAF mutant genotype on survival and recurrence among patients with colorectal liver metastases and how it compares with other important prognostic determinants or surrogates of tumor biology, such as KRAS mutation," Dr. Margonis explained in an email to Reuters Health.

The researchers retrospectively examined multinational data and analyzed outcome in 849 patients who met inclusion criteria.

Forty-three (5.1%) had a mutated (mut) BRAF/wild-type (wt) KRAS (V600E and non-V600E) genotype, 480 (56.5%) had a wtBRAF/wtKRAS genotype and 326 (38.4%), a wtBRAF/mutKRAS genotype.

On multivariable analysis, the researchers found, V600E but not non-V600E BRAF mutation was tied to significantly worse overall survival (hazard ratio, 2.76) and disease-free survival (HR, 2.04).

"V600E BRAF had an at least three fold stronger impact on overall and disease-free survival compared to KRAS mutation and was the most powerful prognostic determinant in this multi-institutional cohort," said Dr. Margonis.

Nevertheless, he and his colleagues stress that further studies are needed.

"No recommendations can be made regarding the selection of surgical or medical treatment for patients with BRAF-mutated CRLM based on our findings," they caution.

Dr. Frank A. Sincrope, who is co-leader of the GI Cancer Program at the Mayo Clinic, in Rochester, Minnesota, said the findings "provide further evidence for the association of BRAF V600E mutations with poor outcome. In this study, BRAF V600E mutations were a stronger prognostic factor than were KRAS mutations and these results are consistent with published data showing a stronger association of BRAF V600E mutations with poor prognosis in CRC patients with tumor recurrence versus non recurrence."

However, Dr. Sincrope told Reuters Health by email, an important limitation of the study "is the lack of data on DNA mismatch repair status since tumors with defective MMR are enriched with BRAF V600E mutations and results for BRAF are ideally interpreted in the context of MMR status which is also known to influence patient prognosis."

SOURCE: https://bit.ly/2J9nLEi

JAMA Surg 2018.