Is Hepatectomy Justified for BRAF Mutant Colorectal Liver Metastases? A Multi-institutional Analysis of 1497 Patients
Is Hepatectomy Justified for BRAF Mutant Colorectal Liver Metastases? A Multi-institutional Analysis of 1497 Patients
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DOI：
10.1097/sla.0000000000002968
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发表时间：
2020-01-01
影响因子：
9
通讯作者：
D'Angelica, Michael, I
中科院分区：
文献类型：
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作者：
Gagniere, Johan;Dupre, Aurelien;D'Angelica, Michael, I
目的：分析因BRAF突变（BRAF-mut）结直肠肝转移（CRLM）而接受肝切除术的患者的临床结局和预后变量。背景：BRAF-mut CRLM肝切除术后的结局尚未得到充分研究。研究方法：分析了2001年至2016年期间在3个高容量中心接受CRLM肝切除术的所有患者，这些患者完全切除且已知BRAF状态。结果：在4124例因CRLM接受肝切除术的患者中，1497例完全切除并已知BRAF状态。35例（2%）患者为BRAF-mut，其中71%为V600 E突变。与BRAF野生型（BRAF-wt）相比，BRAF-mut患者年龄更大，更常见的阿萨评分更高，同时，多个和更小的CRLM，经历了更多的主要肝切除术，但肝外疾病较少。BRAF-wt患者的中位总生存期（OS）为81个月，BRAF-mut患者的中位总生存期（OS）为40个月（P < 0.001）。BRAF-wt和BRAF-mut患者的中位无复发生存期（RFS）分别为22个月和10个月（P < 0.001）。对于BRAF-mut，与较差OS相关的因素是淋巴结阳性原发肿瘤、癌胚抗原（CEA）>200 μ g/L和临床风险评分（CRS）>= 4。与RFS恶化相关的因素是原发肿瘤淋巴结阳性、CRLM>= 4和肝切缘阳性。V600 E突变与OS或RFS恶化无关。预后临床病理因素的病例对照匹配分析证实BRAF-mut组的OS和RFS较短（P < 0.001）。结论：可切除的BRAF-mut CRLM患者在选择手术的患者中很少见，更常见的是多发性同步肿瘤。BRAF突变与较差的预后相关;然而，长期生存是可能的，并且与淋巴结阴性的原发性肿瘤CEA相关。
Objective: To analyze clinical outcomes and prognostic variables of patients undergoing hepatic resection for BRAF mutant (BRAF-mut) colorectal liver metastases (CRLM). Background: Outcomes following hepatectomy for BRAF-mut CRLM have not been well studied. Methods: All patients who underwent hepatectomy for CRLM with complete resection and known BRAF status during 2001 to 2016 at 3 high-volume centers were analyzed. Results: Of 4124 patients who underwent hepatectomy for CRLM, 1497 had complete resection and known BRAF status. Thirty-five (2%) patients were BRAF-mut, with 71% of V600E mutation. Compared with BRAF wild-type (BRAF-wt), BRAF-mut patients were older, more commonly presented with higher ASA scores, synchronous, multiple and smaller CRLM, underwent more major hepatectomies, but had less extrahepatic disease. Median overall survival (OS) was 81 months for BRAF-wt and 40 months for BRAF-mut patients (P < 0.001). Median recurrence-free survival (RFS) was 22 and 10 months for BRAF-wt and BRAF-mut patients (P < 0.001). For BRAF-mut, factors associated with worse OS were node-positive primary tumor, carcinoembryonic antigen (CEA) >200 mu g/L, and clinical risk score (CRS) >= 4. Factors associated with worse RFS were node-positive primary tumor, >= 4 CRLM, and positive hepatic margin. V600E mutations were not associated with worse OS or RFS. A case-control matching analysis on prognostic clinicopathologic factors confirmed shorter OS (P < 0.001) and RFS (P < 0.001) in BRAF-mut. Conclusions: Patients with resectable BRAF-mut CRLM are rare among patients selected for surgery and more commonly present with multiple synchronous tumors. BRAF mutation is associated with worse prognosis; however, long-term survival is possible and associated with node-negative primary tumors, CEA