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真实世界中转移性 BRAF 突变型结直肠癌患者的治疗及结局。

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

机构信息

Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing, China.

出版信息

Cancer Med. 2023 May;12(9):10473-10484. doi: 10.1002/cam4.5783. Epub 2023 Mar 13.

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.

摘要

背景

BRAF 突变发生在 5%-10%的转移性结直肠癌(mCRC)患者中。BRAF 突变的 mCRC 患者具有特定的转移模式和不良预后。mCRC 伴 BRAF 突变患者的生存结果存在异质性。最佳一线治疗仍存在争议。

方法

我们回顾性分析了 2010 年 6 月至 2021 年 12 月期间 mCRC 患者的病历。收集了临床病理特征、治疗和 BRAF 突变检测结果。纳入 BRAF 突变患者。采用 Kaplan-Meier 方法和对数秩检验进行生存分析和比较。采用 Cox 比例风险回归建立预测列线图模型。

结果

在 4475 例 mCRC 中,有 261 例存在 BRAF 突变,其中 240 例为 V600E 突变,21 例为非 V600E 突变。BRAF V600E 突变组的中位总生存期(OS)为 18.2 个月,而非 V600E 突变组为 38.0 个月(p=0.022)。ECOG 评分、肿瘤分化程度、肝转移、骨转移和原发灶切除是 BRAF V600E 突变 mCRC OS 的独立预后因素。使用这些因素建立了一个列线图模型。该模型定义的低危、中危和高危组的中位 OS 分别为 39.3、18.2 和 10.7 个月(p<0.0001)。接受一线三联化疗±贝伐珠单抗治疗的患者与接受二联化疗±贝伐珠单抗治疗的患者相比,无进展生存期(PFS)和 OS 相当。

结论

BRAF V600E 突变 mCRC 预后不良且具有异质性。一线强化化疗对 PFS 和 OS 没有显著影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/788e/10225206/7c4f3377df4d/CAM4-12-10473-g002.jpg

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