Association between oncogenic status and risk of venous thromboembolism in patients with non-small cell lung cancer.

Preclinical data suggest that oncogene (EGFR and KRAS) events regulate tumor procoagulant activity. However, few studies have prospectively investigated the clinical relevance between the presence of EGFR or KRAS mutations and occurrence of venous thromboembolism(VTE) in patients with non-small cell lung cancer (NSCLC). A total of 605 Chinese patients with newly diagnosed NSCLC were included and were followed for a maximum period of 4.5 years. EGFR and KRAS mutations were determined by amplification refractory mutation system polymerase chain reaction method at inclusion. The main outcome was objectively confirmed VTE. Of the 605 patients, 40.3% (244) had EGFR mutations and 10.2% (62) of patients had KRAS mutations. In multivariable analysis including age, sex, tumor histology, tumor stage, performance status, EGFR and KRAS status, EGFR wild-type (sub-distribution hazard ratio 1.81, 95% confidence interval 1.07–3.07) were associated with the increased risk of VTE. In competing risk analysis, the probability of developing VTE was 8.3% in those with and 13.2% in those without EGFR mutations after 1 year; after 2 years, the corresponding risks were 9.7 and 15.5% (Gray test P = 0.047). EGFR mutations have a negative association with the risk of VTE in Chinese patients with NSCLC.

临床前数据表明，癌基因（表皮生长因子受体和KRAS）事件可调节肿瘤促凝活性。然而，很少有研究前瞻性地探讨非小细胞肺癌（NSCLC）患者中表皮生长因子受体或KRAS突变的存在与静脉血栓栓塞（VTE）发生之间的临床相关性。 共纳入605例新诊断的中国NSCLC患者，最长随访4.5年。在纳入时通过扩增阻滞突变系统聚合酶链反应法确定表皮生长因子受体和KRAS突变。主要结局是经客观确认的VTE。 在605例患者中，40.3%（244例）存在表皮生长因子受体突变，10.2%（62例）的患者存在KRAS突变。在包括年龄、性别、肿瘤组织学、肿瘤分期、体能状态、表皮生长因子受体和KRAS状态的多变量分析中，表皮生长因子受体野生型（亚分布风险比1.81，95%置信区间1.07 - 3.07）与VTE风险增加相关。在竞争风险分析中，1年后有表皮生长因子受体突变者发生VTE的概率为8.3%，无突变者为13.2%；2年后，相应风险分别为9.7%和15.5%（Gray检验P = 0.047）。 在中国NSCLC患者中，表皮生长因子受体突变与VTE风险呈负相关。