Metastatic pattern is a prognostic factor in BRAFV600E mutant colorectal cancer

Jingran Ji; Jaideep Sandhu; Chongkai Wang; Marwan Fakih

doi:10.1016/j.ctarc.2023.100714

Metastatic pattern is a prognostic factor in BRAF^V600E mutant colorectal cancer

Cancer Treat Res Commun. 2023:35:100714. doi: 10.1016/j.ctarc.2023.100714. Epub 2023 Apr 28.

Authors

Jingran Ji¹, Jaideep Sandhu¹, Chongkai Wang¹, Marwan Fakih²

Affiliations

¹ Department of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center, Duarte, California, USA.
² Department of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center, Duarte, California, USA. Electronic address: mfakih@coh.org.

PMID: 37126990
DOI: 10.1016/j.ctarc.2023.100714

Abstract

Background: Despite recent advancements in the treatment of metastatic BRAF^V600E colorectal cancer (CRC), prognosis remains poor. However, a some patients with BRAF^V600E disease have superior outcomes compared to the overall cohort and the prognostic factors associated with this improved survival are not well understood.

Methods: We conducted a single center retrospective review of patients with metastatic CRC and available next generation sequencing data. Patients with confirmed BRAF^V600E disease were selected for the final analysis. We collected baseline demographic characteristics, concurrent mutations, and metastatic pattern. The primary endpoint was overall survival (OS). Univariate and multivariable logistic regression was used to examine the association between baseline concurrent somatic mutations and sites of metastatic disease with survival.

Results: Of 466 patients with metastatic CRC, 50 harbored BRAF^V600E disease and 42 were included in the final analysis. The median OS in this cohort was 18.7 months (95% CI: 5.55-31.8). There was no association between baseline concurrent somatic mutations and OS. On univariate analysis, patients with lymph node only disease at the time of metastatic disease were more likely to have longer OS (hazard ratio [HR] = 0.30, 95% CI: 0.09-0.98, p = 0.047) and patients with peritoneal disease were more likely to have shorter OS (HR = 2.78, 95% CI: 1.12-6.88, p = 0.03). However, these associations did not retain statistical significance on multivariable analysis.

Conclusions: The pattern of metastatic disease in BRAF^V600E CRC may be a prognostic factor and future studies are needed to better understand the underlying mechanisms and potentially change clinical practice for a select patient population.

Microabstract: Select patients with metastatic BRAF^V600E colorectal cancer may have better than expected survival but are not well characterized. We conducted a retrospective review of 42 patients with metastatic BRAF^V600E colorectal cancer and showed that lymph node only disease at the time of metastatic disease was associated with superior survival.

Keywords: BRAF(V600E); Colorectal cancer; Metastatic pattern; Prognostic marker.

MeSH terms

Colorectal Neoplasms* / drug therapy
Colorectal Neoplasms* / genetics
Colorectal Neoplasms* / pathology
Humans
Mutation
Neoplasm Metastasis*
Prognosis
Proportional Hazards Models
Proto-Oncogene Proteins B-raf* / genetics

Substances

BRAF protein, human
Proto-Oncogene Proteins B-raf