BRAF and RAS mutations as prognostic factors in metastatic colorectal cancer patients undergoing liver resection.
BRAF and RAS mutations as prognostic factors in metastatic colorectal cancer patients undergoing liver resection.
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DOI：
10.1038/bjc.2015.142
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发表时间：
2015-06-09
影响因子：
8.8
通讯作者：
Falcone A
中科院分区：
文献类型：
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作者：
Schirripa M;Bergamo F;Cremolini C;Casagrande M;Lonardi S;Aprile G;Yang D;Marmorino F;Pasquini G;Sensi E;Lupi C;De Maglio G;Borrelli N;Pizzolitto S;Fasola G;Bertorelle R;Rugge M;Fontanini G;Zagonel V;Loupakis F;Falcone A
尽管转移性结直肠癌(MCRC)的治疗取得了重大进展，但复发率仍然很高，需要可靠的预后标记物。为了评估BRAF和RAS突变对大范围肝切除患者预后的影响，我们回顾了3024例mCRC患者的病历。选择符合条件的接受潜在根治性肝切除的病例。采用焦磷酸测序和质谱仪基因分型方法检测原发灶和(或)转移灶的BRAF和RAS突变状态。主要终点为无复发生存期(RFS)。在最终研究人群(N=309)中，BRAF突变、RAS突变和所有野生型(Wt)患者分别为12例(4%)、160例(52%)和137例(44%)。中位RFS分别为5.7月、11.0和14.4月，差异有统计学意义(LOG-RANK，P=0.043)。在多因素分析中，BRAF突变的复发风险高于所有wt(多变量危险比(HR)=2.31；95%CI1.09~4.87；P=0.029)和RAS突变(多变量HR=2.06；95%CI1.02~4.14；P=0.044)。在总体存活率方面也得到了类似的结果。与所有wt患者相比，RAS突变患者的死亡风险更高(HR=1.47；95%CI，1.05~2.07；P=0.025)，但这种作用在多因素分析中被忽略。BRAF突变与肝切除后中位RFS极差以及复发和死亡的可能性较高有关。了解BRAF突变状态可能会优化mCRC患者的临床决策，这些患者有可能接受肝脏手术。在这种情况下，RAS状态作为有用的标记可能需要进一步研究。
Despite major advances in the management of metastatic colorectal cancer (mCRC) with liver-only involvement, relapse rates are high and reliable prognostic markers are needed. To assess the prognostic impact of BRAF and RAS mutations in a large series of liver-resected patients, medical records of 3024 mCRC patients were reviewed. Eligible cases undergoing potentially curative liver resection were selected. BRAF and RAS mutational status was tested on primary and/or metastases by means of pyrosequencing and mass spectrometry genotyping assay. Primary endpoint was relapse-free survival (RFS). In the final study population (N=309) BRAF mutant, RAS mutant and all wild-type (wt) patients were 12(4%), 160(52%) and 137(44%), respectively. Median RFS was 5.7, 11.0 and 14.4 months respectively and differed significantly (Log-rank, P=0.043). At multivariate analyses, BRAF mutant had a higher risk of relapse in comparison to all wt (multivariate hazard ratio (HR)=2.31; 95% CI, 1.09–4.87; P=0.029) and to RAS mutant (multivariate HR=2.06; 95% CI, 1.02–4.14; P=0.044). Similar results were obtained in terms of overall survival. Compared with all wt patients, RAS mutant showed a higher risk of death (HR=1.47; 95% CI, 1.05–2.07; P=0.025), but such effect was lost at multivariate analyses. BRAF mutation is associated with an extremely poor median RFS after liver resection and with higher probability of relapse and death. Knowledge of BRAF mutational status may optimise clinical decision making in mCRC patients potentially candidate to hepatic surgery. RAS status as useful marker in this setting might require further studies.