Liang Li, Tian Jiawen, Yu Yiyi, Wang Zhiming, Peng Ke, Liu Ruiqi, Wang Yan, Xu Xiaojing, Li Hong, Zhuang Rongyuan, Cui Yuehong, Zhu Chouwen, Liu Tianshu
Department of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai, China.
Department of Internal Medicine, Huadong Hospital, Fudan University, Shanghai, China.
Cell Physiol Biochem. 2018;50(2):768-782. doi: 10.1159/000494242. Epub 2018 Oct 11.
BACKGROUND/AIMS: Non-radical primary tumour resection (PTR) of asymptomatic metastatic colorectal cancer (mCRC) can prolong survival time of some patients. Patients with mutated RAS gene have worse survival outcome. This study aimed to investigate the impact of RAS gene mutations on the prognosis of asymptomatic unresectable mCRC patients who underwent PTR.
A retrospective observational cohort study was deduced among mCRC patients who experienced PTR or had intact primary tumour (IPT). All of them had the primary tumour tissue genotyping tested for RAS (KRAS and NRAS) gene mutations. The tumour-related overall survival (OS) time and progression-free survival (PFS) time was estimated. From January 2011 to June 2014, 421 mCRC patients with asymptomatic, unresectable, metastatic disease were enrolled in this study. Among them, 282 patients underwent PTR and 139 patients had IPT.
The mutation rate of RAS was 53.8% (221/411). With a median followed-up time of 46.5 months, the overall survival time of mCRC patients harboring wtRAS or mtRAS was 28.0 versus 22.0 months (p = 0.043) in PTR group and was 21.6 versus 17.8 months (p=0.071) in IPT groups. A Multivariate regression analysis suggested that RAS gene (p=0.039, HR=1.288,95%CI [1.072∼2.911]), metastatic organ number (p=0.033, HR=3.091,95%CI [1.090∼5.755]) and systemic therapy response (p=0.019, HR=0.622,95%CI [0.525∼0.811]) were independent prognostic factors in PTR population.
We found that wild-type RAS gene was a favorable factor for the asymptomatic unresectable mCRC patients experiencing PTR.
背景/目的：无症状转移性结直肠癌（mCRC）的非根治性原发性肿瘤切除术（PTR）可延长部分患者的生存时间。RAS基因突变的患者生存结局较差。本研究旨在探讨RAS基因突变对接受PTR的无症状不可切除mCRC患者预后的影响。
对接受PTR或原发性肿瘤完整（IPT）的mCRC患者进行一项回顾性观察队列研究。所有患者均对原发性肿瘤组织进行RAS（KRAS和NRAS）基因突变的基因分型检测。评估肿瘤相关的总生存（OS）时间和无进展生存（PFS）时间。2011年1月至2014年6月，421例无症状、不可切除、转移性疾病的mCRC患者纳入本研究。其中，282例患者接受了PTR，139例患者有IPT。
RAS基因突变率为53.8%（221/411）。中位随访时间为46.5个月，PTR组中携带野生型RAS（wtRAS）或突变型RAS（mtRAS）的mCRC患者的总生存时间分别为28.0个月和22.0个月（p = 0.043），IPT组分别为21.6个月和17.8个月（p = 0.071）。多因素回归分析表明，RAS基因（p = 0.039，HR = 1.288，95%CI [1.072∼2.911]）、转移器官数量（p = 0.033，HR = 3.091，95%CI [1.090∼5.755]）和全身治疗反应（p = 0.019，HR = 0.622，95%CI [0.525∼0.811]）是PTR人群的独立预后因素。
我们发现野生型RAS基因是接受PTR的无症状不可切除mCRC患者的有利因素。
