Liu Yiwei, Wang Wanying, Wu Fengying, Gao Guanghui, Xu Jian, Li Xuefei, Zhao Chao, Yang Shuo, Mao Shiqi, Pan Yingying, Jia Keyi, Shao Chuchu, Chen Bin, Ren Shengxiang, Zhou Caicun
Department of Medical Oncology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China.
Department of Lung Cancer and Immunology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China.
Transl Lung Cancer Res. 2021 Mar;10(3):1512-1524. doi: 10.21037/tlcr-20-1290.
Acute complications, such as venous thromboembolism (VTE), are common in patients with advanced severe lung cancers. However, current VTE risk scores cannot adequately identify high-risk patients with non-small cell lung cancer (NSCLC). The study proposed to elucidated the incidence of thromboembolism (TE) in patients with different oncogenic aberrations and the impact of these aberrations on the efficacy of targeted therapy in patients with NSCLC.
A systemic review was conducted in Web of Science, PubMed, Embase and the Cochrane Library to evaluate the incidence of TE in different molecular subtypes of NSCLC. Data from patients diagnosed of advanced NSCLC who harboring anaplastic lymphoma kinase (ALK) or ROS proto-oncogene 1 receptor tyrosine kinase (ROS1) rearrangements since 2016 to 2019 were also retrospectively collected. A meta-analysis with random-effects model, sensitivity analysis and publication bias were performed. The principal summary measure was incidence of thrombotic events in NSCLC patients. And the efficacy of tyrosine kinase inhibitor (TKI) therapy was compared between the two subgroups.
A total of 5,767 cases from 20 studies were included in the analysis of the incidence of thrombosis in patients with different oncogenic alterations. The pooled analysis showed a higher risk of thrombosis in ROS1-fusion types (41%, 95% CI: 35-47%) and ALK-fusion types (30%, 95% CI: 24-37%) than in EGFR-mutation (12%, 95% CI: 8-17%), KRAS-mutation (25%, 95% CI: 13-50%), and wild-type (14%, 95% CI: 10-20%) cases. A high prevalence of thrombosis (ALK: 24.4%; ROS1: 32.6%) was observed in the Shanghai Pulmonary Hospital (SPH) cohort of 224 patients with ALK or ROS1 fusion. Furthermore, patients with embolism had significantly shorter progression-free survival (PFS) after TKI therapy than those without embolism, both in the ALK+ cohort (5.6 12.9 months, P<0.0001) and in the ROS1+ cohort (9.6 17.6 months, P=0.0481).
NSCLC patients with ALK/ROS1 rearrangements are more likely to develop thrombosis than patients with other oncogenic alterations. Thrombosis may also be associated with an inferior response and PFS after TKI therapy.
急性并发症，如静脉血栓栓塞症（VTE），在晚期重症肺癌患者中很常见。然而，目前的VTE风险评分不能充分识别非小细胞肺癌（NSCLC）的高危患者。该研究旨在阐明不同致癌畸变患者的血栓栓塞（TE）发生率以及这些畸变对NSCLC患者靶向治疗疗效的影响。
在Web of Science、PubMed、Embase和Cochrane图书馆进行了一项系统评价，以评估NSCLC不同分子亚型中TE的发生率。还回顾性收集了2016年至2019年诊断为晚期NSCLC且携带间变性淋巴瘤激酶（ALK）或ROS原癌基因1受体酪氨酸激酶（ROS1）重排的患者的数据。进行了随机效应模型的荟萃分析、敏感性分析和发表偏倚分析。主要汇总指标是NSCLC患者血栓形成事件的发生率。并比较了两个亚组酪氨酸激酶抑制剂（TKI）治疗的疗效。
共有来自20项研究的5767例病例纳入了不同致癌改变患者血栓形成发生率的分析。汇总分析显示，ROS1融合型（41%，95%CI：35 - 47%）和ALK融合型（30%，95%CI：24 - 37%）患者发生血栓的风险高于表皮生长因子受体（EGFR）突变型（12%，95%CI：8 - 17%）、KRAS突变型（25%，95%CI：13 - 50%）和野生型（14%，95%CI：10 - 20%）病例。在上海肺科医院（SPH）的224例ALK或ROS1融合患者队列中观察到血栓形成的高发生率（ALK：24.4%；ROS1：32.6%）。此外，无论是在ALK阳性队列（5.6对比12.9个月，P<0.0001）还是ROS1阳性队列（9.6对比17.6个月，P = 0.0481）中，发生栓塞的患者在TKI治疗后的无进展生存期（PFS）均显著短于未发生栓塞的患者。
与其他致癌改变的患者相比，ALK/ROS1重排的NSCLC患者更易发生血栓形成。血栓形成也可能与TKI治疗后的反应较差和PFS相关。
