Clinical and survival characteristics of patients with BRAF-mutated metastatic colorectal cancer (mCRC) who receive metastases surgery in a Spanish cohort.
Authors: Soto Javier , Bringas Marianela , Gutiérrez Alonso Natalia , Muñoz Martín Andrés J. , Calvo Ferrándiz Aitana , Torres Pérez-Solero Gabriela , Ortega Laura , Martín Lozano Rocío , Jiménez Rodríguez Roberto , Gonzalez Caraballo Irene , López Jiménez Carlos , Gutierrez Ortiz de la Tabla Ana , Juliao Caamaño David Salomon , Muñoz Marc Ariant Cañete , de Lucas Mónica Benavente , Gómez María Palma , Alva Bianchi Manuel , Martínez Delfrade Íñigo , Martin Miguel , Garcia-Alfonso Pilar 
Published: January 2023

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Background: Patients with mCRC harboring BRAF mutation have worse prognosis and poor outcomes. However, those who have resectable metastatic disease and undergo surgery may have better outcomes compared to those who do not. Differences in clinical characteristics are not well known and may be critical to identify patients with better prognosis. Methods: We performed a retrospective analysis of 299 patients with mCRC in a tumor registry from 2015 to 2021. We compared the clinical characteristics and survival trends of both cohorts (BRAF mutated and BRAF wild type). Furthermore, we analyzed clinical and survival features of 23 patients with BRAF mutated mCRC who received metastases resection. Results: We identified 34 patients with BRAF mutation (11.37%). Several characteristics were significantly more frequent in this group: age <65 years (n = 24, OR 1.38, p = 0.03), female sex (n = 24, OR 1.74, p = 0.008), primary tumor in the right colon (n = 15, OR 1.93, p = 0.003), peritoneal carcinomatosis (n = 18, OR 2.29, p = 0.007) and increased CA19.9 levels at diagnosis (n = 18, OR 1.79, p = 0.003). They received more peritoneal surgery (n = 12, OR 4.27, p = 0.000) and less liver metastases resection (n = 7, OR 0.51, p = 0.011). Median PFS in the first line of treatment was shorter in patients with BRAF mutation (9.5 vs 12.6 months; HR 1.69; IC 95%: 1.16 – 2.45; p = 0.006); however, we did not found differences in OS. Within the 23 patients with BRAF mutated mCRC who underwent surgery (67,64%), we found significant differences compared with those without metastases surgery: primary tumor resection (n = 21, OR 2.51, p = 0.0017) and having a single metastatic location (n = 18, OR 2.04, p = 0.01). Other features were more frequent in patients who underwent surgery but did not reach statistical significance: right colon location (63.6% vs 37.5%), metachronic disease (47.8% vs 18.2%), normal CEA (50% vs 25%) and CA19.9 (45% vs 12%) at diagnosis, and receiving 3 or more lines of systemic treatment (57% vs 22%). Median PFS after metastasectomy was 14.9 months, but we found no differences between both groups. Conclusions: In our cohort, BRAF mutated mCRC patients were more frequently younger, women, had right-sided primary tumors, higher rates of peritoneal metastases and abnormal CA19.9 levels at diagnosis, including worse outcomes in terms of PFS. On the other hand, resection of the primary tumor and single metastatic location were associated with higher probability of having metastases surgery, although in this study no subsequent survival benefit was found, probably due to the small number of BRAF mutated patients analyzed.