KRAS mutation influences recurrence patterns in patients undergoing hepatic resection of colorectal metastases.
KRAS mutation influences recurrence patterns in patients undergoing hepatic resection of colorectal metastases.
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DOI：
10.1002/cncr.28954
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发表时间：
2014-12-15
期刊：
影响因子：
6.2
通讯作者：
D'Angelica MI
中科院分区：
文献类型：
--
作者：
Kemeny NE;Chou JF;Capanu M;Gewirtz AN;Cercek A;Kingham TP;Jarnagin WR;Fong YC;DeMatteo RP;Allen PJ;Shia J;Ang C;Vakiani E;D'Angelica MI
KRAS突变作为无复发生存期(RFS)或总生存期(OS)的预测指标的有效性尚不清楚。这项研究调查了KRAS基因突变是否降低了接受肝切除的结直肠癌患者的RFS或OS。对有KRAS资料的切除结直肠癌肝转移患者进行评估，这些患者接受了辅助肝动脉灌注(HAI)加全身治疗。采用Fisher‘s精确检验评价KRAS与临床因素的相关性。使用Kaplan-Meier方法估计总体RFS和OS的中位数。169例患者包括118例KRAS野生型(WT)和51例突变(MUT)。KRAS WT组3年RFS为46%[95%CI：35-56%]，MUT患者为30%[95%CI：16-44%](p=0.005)。KRAS WT和MUT患者的3年OS分别为95%[87%~98%]和81%[62%~95%](p=0.07)。经多因素分析，KRAS仍是RFS的显著预测因子(HR：1.9)。3年累积复发率：骨转移分别为2%和13.4%(p=0.01)，脑分别为2%和14.5%(p=0.05)，肺分别为33.2%和58%(p=0.01)，肝脏分别为30%和47%(p=0.10)。在接受HAI辅助治疗和系统治疗的切除结直肠癌肝转移患者中，KRAS突变患者的3年生存率分别为46%和30%(P=0.005)。KRAS MUT患者的骨、脑和肺转移的累积发生率显著高于WT患者。
The validity of KRAS mutation as a predictor of recurrence free survival (RFS) or overall survival (OS) is unclear. This study investigated whether KRAS mutation decreases RFS or OS in patients with colorectal cancer who underwent liver resection. Patients with resected colorectal liver metastases who were treated with adjuvant hepatic arterial infusion (HAI) plus systemic therapy and in whom KRAS data was available were evaluated. Correlation between KRAS and clinical factors was evaluated using Fisher's exact test. Kaplan-Meier methods were used to estimate median overall RFS and OS. 169 patients were evaluated: 118 KRAS wild type (WT) and 51 mutated (MUT). Three year RFS was 46% for KRAS WT [95%CI: 35-56%], and 30% [95%CI: 16-44%] for MUT patients (p=0.005). Three year OS was 95% [87%-98%] and 81% [62%-95%] for KRAS WT and MUT patients, respectively (p=0.07). By multivariate analysis, KRAS remained a significant predictor of RFS (HR: 1.9). Cumulative recurrence by 3 years in sites showed: 2% versus 13.4% for bone metastases (p=<0.01), 2% versus 14.5% for brain (p=0.05), 33.2% versus 58% for lung (p=<0.01), and 30 versus 47% for liver (p=0.10) in KRAS WT versus MUT patients, respectively. In patients with resected colorectal liver metastases treated with adjuvant HAI plus systemic therapy, patients with KRAS mutation had a significantly worse 3 year RFS of 46% versus 30% (p=0.005) for KRAS WT vs MUT, respectively. Cumulative incidence of bone, brain, and lung metastases was significantly higher for KRAS MUT patients as compared to WT patients.