Real‐world treatment and outcomes of patients with metastatic BRAF mutant colorectal cancer

Abstract

Background BRAF mutation occurs in 5%–10% of metastatic colorectal cancers (mCRCs). Patients with BRAF mutant mCRC exhibit a specific metastatic pattern and poor prognosis. Survival outcomes are heterogeneous in cases of mCRC with a BRAF mutation. The optimal first‐line therapy is still controversial. Methods We retrospectively reviewed the medical records of patients with mCRC between June 2010 and December 2021. Clinicopathologic characteristics, treatment and BRAF mutation testing results were collected. Patients with a BRAF mutation were included. Kaplan–Meier methods and log‐rank tests were used to analyze and compare survival. Cox proportional hazards regression was used to establish the predictive nomogram model. Results Of the 4475 mCRC, 261 have a BRAF mutation, including 240 V600E and 21 non‐V600E mutants. The median overall survival (OS) was 18.2 months in the BRAF V600E mutant group versus 38.0 months in the non‐V600E mutant group (p = 0.022). ECOG score, tumor differentiation, liver metastasis, bone metastasis and primary tumor resection were independent prognostic factors for the OS of BRAF V600E mutant mCRC. A nomogram model was established using these factors. The median OS was 39.3 m, 18.2 m and 10.7 m for the low‐risk, intermediate‐risk and high‐risk groups defined by this model, respectively (p < 0.0001). Patients who received first‐line triplet chemotherapy ± bevacizumab had comparable progression free survival (PFS) and OS compared with those treated with doublets ± bevacizumab. Conclusion BRAF V600E mutant mCRCs exhibit unfavorable and heterogeneous prognosis. The first‐line intensive chemotherapy did not confer a marked impact on the PFS and OS.

Nomogram for predicting occurrence and prognosis of liver metastasis in elderly colorectal cancer patients: a population-based study

“…Accompanying a greater awareness of the genetic drivers of tumor biology, there is speculation regarding the potential correlation between certain molecular cancer biomarkers, such as ras and braf, and the incidence and prognostic implications of CRLM ( 40 ). The occurrence of KRAS mutations among CRC exceeds 50%, whereas the occurrence of HRAS and NRAS mutations is rather infrequent ( 41 ).…”

“…Research conducted in China has revealed contrasting clinical characteristics between Chinese and Western patients with BRAF mutations in metastatic CRC. These disparities mostly emerge as an earlier beginning age and a reduced occurrence of microsatellite instability among Chinese patients ( 40 ). In a multicenter retrospective study conducted in China, it was observed that BRAF V600E, the most common kind of BRAF mutation, is the key factor impacting OS in patients with CRLM ( 44 ).…”

High-Fidelity Identification of Single Nucleotide Polymorphism by Type V CRISPR Systems

“…This specific SNP mutation is tumorigenic to human cells by disrupting the normal growth cycle and interfering with extracellular signaling pathways. Therefore, the BRAF V600E mutation is often regarded as a biomarker of aggressive tumor growth in different cancers, such as metastatic melanoma, papillary thyroid cancer, and colorectal cancer. , …”

“…Therefore, the BRAF V600E mutation is often regarded as a biomarker of aggressive tumor growth in different cancers, such as metastatic melanoma, papillary thyroid cancer, and colorectal cancer. 3,4 Due to its exceptional programmability and high sensitivity, the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) system has attracted much attention in recent years. 5 The type V CRISPR system (including Cas12a, Cas12b, Cas12f, etc.…”

“…Colorectal cancer is the third most common cancer and the leading cause of cancer-related deaths worldwide. BRAF mutation occurs in around 10% of colorectal cancers. , Various concentrations of the BRAF WT gene were mixed with the BRAF V600E gene to obtain the variant allele frequency ranging from 0.01% to 10%. The mixtures were amplified using BDA to increase the fraction of BRAF V600E in the amplicons.…”