The Investigation of Clinical Profile and Outcomes of Metastatic Colorectal Cancer Patients with RAS or BRAF Mutations in Iran

Abstract

Background: Patients with RAS/BRAF mutations in metastatic colorectal cancer (mCRC) exhibit distinct clinical characteristics, yet precise data on their features and prognosis — particularly among Asian populations, including Iranians — remain limited. This retrospective study aimed at evaluating the clinical characteristics and outcomes of mCRC patients harboring specific RAS/BRAF mutations in Iran. Objectives: This retrospective study aimed at assessing the clinical characteristics and prognostic outcomes — including tumor location, differentiation, metastasis patterns, and overall survival (OS)/progression-free survival (PFS) — in Iranian patients with mCRC based on RAS/BRAF mutation status (KRAS, NRAS, BRAF, and wild-type). Methods: This retrospective study was conducted on patients whose RAS/BRAF tissue testing was performed between 2021 and 2023. The study included 74 patients with mCRC. RAS/BRAF mutation status was evaluated using tumor samples collected from either primary or metastatic sites. Statistical analyses included Kaplan-Meier survival estimation and log-rank tests to compare OS and PFS across subgroups. Hazard ratios (HRs) were calculated using Cox proportional hazards models where applicable. Results: The findings of this study indicated that tumor locations in the rectum, sigmoid colon, and ascending colon were the most common, with no significant variation among mutated subgroups (P = 0.412). Tumor differentiation was predominantly moderate or excellent, with a minority showing poor differentiation (P = 0.284). Hepatic metastasis was more common among patients with one metastasis. Patients were divided into 4 groups in terms of gene mutation: NRAS mutant, KRAS mutant, BRAF mutant, and the wild type group (group without mutation). The median OS was 18 months, the KRAS subgroup had an OS at 20 months, and the wild-type subgroup at 13 months. There was no significant difference in OS between wild type and KRAS subgroups. In terms of PFS, the median PFS was 9 months, with the KRAS subgroup exhibiting the highest PFS rate (12 months), followed by wild-type (8 months). Conclusions: This analysis explores tumor characteristics and survival in RAS/BRAF subgroups of Iranian mCRC patients. The preliminary findings require validation through larger, multicenter studies to elucidate mechanisms driving subgroup outcome differences and guide personalized therapy.