a Department of Medical Oncology , The Canberra Hospital , Garran , Canberra , Australia.
b Department of Medical Oncology , Flinders Medical Centre , Bedford Park , Australia.
Acta Oncol. 2018 Nov;57(11):1438-1444. doi: 10.1080/0284186X.2018.1487581. Epub 2018 Jul 23.
Pattern of spread in patients with metastatic colorectal cancer (mCRC) is variable and may reflect different biology in subsets of patients. This is a retrospective study to explore the outcome of patients with mCRC based on their site of metastasis at diagnosis and to explore the association between tumor characteristics [KRAS/RAS, BRAF, mismatch repair (MMR) status, site of primary] and the site of metastasis.
Patients from two Australian databases were divided into six groups based on site of metastasis at time of diagnosis of metastatic disease; lung-only, liver-only, lymph node-only or any patients with brain, bone or peritoneal metastases. Primary endpoint was overall survival (OS) of each cohort compared with the rest of the population. A Mantel-Haenszel chi-squared test used to explore the association between site of metastasis and selected tumor characteristics.
Five thousand nine hundred and sixty-seven patients were included. In a univariate analysis, median OS was significantly higher when metastases were limited to lung or liver and shorter for those with brain, bone or peritoneal metastases (p < .001) in both datasets. BRAF mutation was strongly associated with peritoneal metastases (relative risk = 1.8, p < .001) with lower incidence of lung (RR = 0.3, p = .004) and liver (RR = 0.7, p = .005) limited metastases. Lung-only metastases were more frequent with KRAS/RAS mutation (RR = 1.4, p = .007). Left colon tumors were associated with bone (RR = 1.6, p < .001) and lung-only metastases (RR = 2.3, p = .001) while peritoneal spread was less frequent compared with right colon tumors (RR = 0.6, p < .001). Rectal cancer was associated with brain, bone and lung metastases (RR = 1.7; p = .002, 1.7; p < .001, 2.0; p < .001). Liver-only metastases were less frequent in deficient MMR tumors (RR = 0.7, p = .01).
Survival duration with mCRC is related to the site of metastases with lung limited disease showing a more favorable survival outcome compared to other single metastatic site disease. The BRAF mutation and primary rectal cancer were associated with poor prognostic metastatic sites.
转移性结直肠癌（mCRC）患者的转移模式各不相同，可能反映了患者亚群的不同生物学特性。本研究为回顾性研究，旨在探讨 mCRC 患者基于初诊时转移部位的生存结局，并探讨肿瘤特征（KRAS/RAS、BRAF、错配修复（MMR）状态、原发部位）与转移部位之间的关系。
根据 mCRC 患者初诊时转移部位，将来自澳大利亚两个数据库的患者分为六组：肺转移组、肝转移组、淋巴结转移组或脑转移、骨转移或腹膜转移患者。主要终点为每个队列与其余人群的总生存（OS）比较。采用 Mantel-Haenszel χ²检验探讨转移部位与选定肿瘤特征之间的关系。
共纳入 5967 例患者。在单因素分析中，两组数据中，当转移局限于肺或肝时，中位 OS 显著较高，而脑、骨或腹膜转移时，中位 OS 显著较短（均 P<0.001）。BRAF 突变与腹膜转移密切相关（相对风险=1.8，P<0.001），肺转移（相对风险=0.3，P=0.004）和肝转移（相对风险=0.7，P=0.005）的发生率较低。肺转移组中 KRAS/RAS 突变更为常见（相对风险=1.4，P=0.007）。左半结肠癌与骨转移（相对风险=1.6，P<0.001）和肺转移（相对风险=2.3，P=0.001）相关，而与右半结肠癌相比，腹膜转移较少（相对风险=0.6，P<0.001）。直肠肿瘤与脑转移、骨转移和肺转移相关（相对风险=1.7；P=0.002，1.7；P<0.001，2.0；P<0.001）。错配修复缺陷型肿瘤中肝转移较少（相对风险=0.7，P=0.01）。
mCRC 患者的生存时间与转移部位有关，与其他单一转移部位疾病相比，肺局限性疾病的生存结局更为有利。BRAF 突变和原发直肠肿瘤与预后不良的转移性部位相关。
