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Characteristics of BRAF V600E Mutant, Deficient Mismatch Repair/Proficient Mismatch Repair, Metastatic Colorectal Cancer: A Multicenter Series of 287 Patients

机译:BRAF V600E突变特性,缺陷不匹配/熟练不匹配修复,转移性结直肠癌:多中心系列287名患者

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Background BRAF V600E mutations occurring in about 10% of metastatic colorectal cancers (mCRCs) are usually associated with a poor outcome. However, their prognostic factors are unknown. Materials and Methods We built a multicenter clinico-biological database gathering data from patients with BRAF V600E -mutant mCRC treated in one of the 16 French centers from 2006 to 2017. The primary endpoint was to identify prognostic factors using a Cox model. Results We included 287 patients (median age, 67 years [28–95]; female, 57%). Their median overall survival was 20.8 months (95% confidence interval [CI], 17.97–27.04), and median progression-free survival in the first-line setting was 4.34 months (95% CI, 3.81–5.03). Chemotherapy regimen and biological agents (antiangiogenic or anti-epidermal growth factor receptor) were not associated with overall and progression-free survival. Stage IV disease (synchronous metastases) and absence of curative-intent surgery were statistically associated with poor overall survival. Among the 194 patients with mismatch repair (MMR) status available, overall survival was significantly longer in patients with deficient MMR tumors compared with those with proficient MMR tumors (adjusted hazard ratio = 0.56; p = .009). Conclusion Despite that BRAF V600E -mutant mCRCs are associated with poor overall and progression-free-survival, patients with deficient MMR tumors and/or resectable disease experienced a longer survival. These results highlight the importance of MMR testing and resectability discussion in patients with BRAF V600E mCRC in day-to-day practice. Implications for Practice Mismatch repair (MMR) testing and resectability discussion in patients with BRAF V600E metastatic colorectal cancer (mCRC) should be performed in day-to-day practice to steer treatment decision making in patients with BRAF V600E -mutant mCRC.
机译:背景技术在大约10%的转移性结肠直肠癌(MCRC)中发生的BRAF V600E突变通常与差的结果相关。然而,他们的预后因素是未知的。材料和方法我们建造了来自2006年至2017年16名法国中心之一的BRAF V600E -MUTANT MCRC患者的多中心临床生物数据库收集数据。主要终点是使用COX模型鉴定预后因素。结果我们包括287名患者(中位年龄,67岁[28-95];女性,57%)。它们的中位数生存率为20.8个月(95%的置信区间[CI],17.97-27.04)和一线设置中的中位进展生存率为4.34个月(95%CI,3.81-5.03)。化疗方案和生物药物(抗血管生成或抗表皮生长因子受体)与总体和无进展的存活无关。阶段静脉疾病(同步转移)和没有治愈性手术的疾病与整体存活差异有统计学相关。在194名不匹配的维修患者中(MMR)现状中,与具有熟练MMR肿瘤的患者(调整后危险比= 0.56)相比,缺乏MMR肿瘤的患者的整体存活率明显更长。结论尽管BRAF v600E - 富矿MCRCs与差的整体和渐进生存有关,但缺乏MMR肿瘤和/或可重症疾病的患者的存活率较长。这些结果突出了在日常练习中BRAF V600E MCRC患者MMR测试和重新入心讨论的重要性。对于BRAF V600E转移性结肠直肠癌(MCRC)患者的实践不匹配修复(MMR)测试和重新入心讨论的影响应在日常做法中进行,以引导患有BRAF V600E - 级别MCRC患者的治疗决策。

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