Association of ALK rearrangement and risk of venous thromboembolism in patients with non-small cell lung cancer: A prospective cohort study

Background: Isolated reports are inconsistent regarding the risk of venous thromboembolism (VTE) in patients with anaplastic lymphoma kinase (ALK) rearranged non-small cell lung cancer (NSCLC). This study examined whether ALK rearrangement could have an influence on VTE in a prospective cohort.Methods: In a cohort of 836 consecutive patients with NSCLC, patients with epidermal growth factor receptor (EGFR) or kitten rat sarcoma (KRAS) mutations were ruled out for VTE interference. Finally, 341 qualified patients were observed. The median follow up period is 7.5 months (3.1-15.4m). ALK rearrangement was detected by fluorescence in situ hybridization at baseline.Results: Overall VTE events occurred in 37 (10.9%) of 341 patients. In multivariable analysis including age, sex, tumor histology, tumor stage, performance status, and ALK status, ALK rearrangement (sub-distribution hazard radio 2.47, 95% confidence interval 1.04-5.90) was associated with the increased risk of VTE. The cumulative incidence of VTE was 26.9% and 9.2% in the patients with and without ALK rearrangement after 6 months. After 1 year the corresponding cumulative incidence was 26.9% and 9.7% respectively (Gray test P = .005).Conclusions: The presence of ALK rearrangement is associated with increased risk of VTE in patients with NSCLC.

背景：关于间变性淋巴瘤激酶（ALK）重排的非小细胞肺癌（NSCLC）患者静脉血栓栓塞（VTE）的风险，孤立的报告并不一致。本研究在前瞻性队列中检验了ALK重排是否会对VTE产生影响。 方法：在836例连续的NSCLC患者队列中，排除了表皮生长因子受体（EGFR）或 Kirsten大鼠肉瘤（KRAS）突变的患者以避免对VTE的干扰。最终观察了341例符合条件的患者。中位随访时间为7.5个月（3.1 - 15.4个月）。在基线时通过荧光原位杂交检测ALK重排。 结果：341例患者中有37例（10.9%）发生了总体VTE事件。在包括年龄、性别、肿瘤组织学、肿瘤分期、体能状态和ALK状态的多变量分析中，ALK重排（亚分布风险比2.47，95%置信区间1.04 - 5.90）与VTE风险增加相关。6个月后，有ALK重排和无ALK重排的患者VTE累积发生率分别为26.9%和9.2%。1年后相应的累积发生率分别为26.9%和9.7%（Gray检验P = 0.005）。 结论：ALK重排与NSCLC患者VTE风险增加相关。