KRAS突变与接受辅助性FOLFOX治疗的III期或高危II期结肠癌患者的预后较差有关。
KRAS mutation is associated with worse prognosis in stage III or high-risk stage II colon cancer patients treated with adjuvant FOLFOX.
作者信息
Lee Dae-Won, Kim Kyung Ju, Han Sae-Won, Lee Hyun Jung, Rhee Ye Young, Bae Jeong Mo, Cho Nam-Yun, Lee Kyung-Hun, Kim Tae-Yong, Oh Do-Youn, Im Seock-Ah, Bang Yung-Jue, Jeong Seung-Yong, Park Kyu Joo, Park Jae-Gahb, Kang Gyeong Hoon, Kim Tae-You
机构信息
Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.
出版信息
Ann Surg Oncol. 2015 Jan;22(1):187-94. doi: 10.1245/s10434-014-3826-z. Epub 2014 Jun 3.
BACKGROUND
Although KRAS mutation has a predictive role in stage IV colorectal cancer (CRC) patients treated with anti-EGFR therapy, there have been controversies in the prognostic impact of KRAS mutation in stage II or III disease. The purpose of this study was to assess the prognostic impact of KRAS and BRAF mutation in patients treated with adjuvant 5-fluorouracil/leucovorin/oxaliplatin (FOLFOX).
METHODS
KRAS exon 2 and BRAF codon 600 were analyzed in patients with stage II and III CRC who underwent curative resection followed by adjuvant FOLFOX. Clinicopathologic features and disease-free survival (DFS) were compared.
RESULTS
Among a total of 437 patients, mutational data of KRAS and BRAF were available in 388 and 433 patients, respectively. KRAS mutation (codon 12 and 13) and BRAF V600E mutation was found in 26.5 and 3.7 % of patients. DFS was significantly worse in the KRAS mutant patients compared to KRAS wild type patients (3-year DFS 79 and 92 %, p = 0.006). Multivariate analysis revealed KRAS mutation as an independent negative prognostic factor for DFS (adjusted hazard ratio 2.30, 95 % confidence interval 1.23-4.32). Among the various subtypes of KRAS mutation, G13D (3-year DFS 76 %, p = 0.008) was significantly associated with poor DFS, while G12D was not associated with prognosis (3-year DFS 86 %, p = 0.61). There was no association between BRAF mutation and DFS.
CONCLUSIONS
KRAS mutation has an adverse prognostic impact on stage II or III CRC treated with adjuvant FOLFOX.
背景
尽管KRAS突变在接受抗表皮生长因子受体（EGFR）治疗的IV期结直肠癌（CRC）患者中具有预测作用，但KRAS突变对II期或III期疾病的预后影响一直存在争议。本研究的目的是评估KRAS和BRAF突变对接受辅助性5-氟尿嘧啶/亚叶酸钙/奥沙利铂（FOLFOX）治疗患者的预后影响。
方法
对接受根治性切除并随后接受辅助性FOLFOX治疗的II期和III期CRC患者的KRAS第2外显子和BRAF第600密码子进行分析。比较临床病理特征和无病生存期（DFS）。
结果
在总共437例患者中，分别有388例和433例患者获得了KRAS和BRAF的突变数据。KRAS突变（第12和13密码子）和BRAF V600E突变分别在26.5%和3.7%的患者中发现。与KRAS野生型患者相比，KRAS突变患者的DFS明显更差（3年DFS分别为79%和92%，p = 0.006）。多变量分析显示KRAS突变是DFS的独立负面预后因素（校正风险比2.30，95%置信区间1.23 - 4.32）。在KRAS突变的各种亚型中，G13D（3年DFS 76%，p = 0.008）与较差的DFS显著相关，而G12D与预后无关（3年DFS 86%，p = 0.61）。BRAF突变与DFS之间无关联。
结论
KRAS突变对接受辅助性FOLFOX治疗的II期或III期CRC具有不良预后影响。
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