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ROS1 基因重排与诊断前血栓栓塞事件风险升高相关。

ROS1 Gene Rearrangements Are Associated With an Elevated Risk of Peridiagnosis Thromboembolic Events.

机构信息

Division of Medical Oncology, University of Colorado, Aurora, Colorado.

Department of Pediatrics, Cancer Center Biostatistics Core, University of Colorado and Children's Hospital Colorado, Aurora, Colorado.

出版信息

J Thorac Oncol. 2019 Apr;14(4):596-605. doi: 10.1016/j.jtho.2018.12.001. Epub 2018 Dec 10.


DOI:10.1016/j.jtho.2018.12.001
PMID:30543838
Abstract

INTRODUCTION: This study aims to determine whether advanced ROS1 gene-rearranged NSCLC (ROS1+ NSCLC) has a higher than expected thromboembolic event (TEE) rate. METHODS: Venous and arterial TEEs within ±365 days of diagnosis of ROS1+, ALK+, EGFR+, or KRAS+ advanced NSCLC at five academic centers in the United States and China were captured (October 2002-April 2018). The primary endpoint was incidence of TEE in ROS1+ compared to anaplastic lymphoma kinase (ALK)+, EGFR+, and KRAS+ NSCLC within ±90 days of diagnosis. Logistic regression was used to assess if the odds of TEE differed among oncogene drivers. RESULTS: Eligible data from 95 ROS1+, 193 ALK+, 300 EGFR+, and 152 KRAS+ NSCLC patients were analyzed. The incidence rate of TEE was 34.7% (n = 33), 22.3% (n = 43), 13.7% (n = 41), and 18.4% (n = 28), respectively. In univariate analysis, the odds of a TEE in ROS1+ NSCLC were higher than ALK+, EGFR+, and KRAS+ cohorts. In multivariable analysis, the odds of a TEE were significantly higher for ROS1+ compared to EGFR+ and KRAS+ cohorts, the odds ratio (OR) was 2.44, with a 95% confidence interval of 1.31-4.57 (p = 0.005), and OR: 2.62, with a 95% confidence interval of 1.26-5.46 (p = 0.01), respectively. Although numerically superior, the odds for a TEE with ROS1+ compared to ALK+ was not statistically significant (OR: 1.45, p = 0.229). Overall survival was not significantly different in patients with or without TEE within ±90 days of diagnosis in the overall study cohort or within each molecular group. CONCLUSIONS: The risk of peridiagnostic TEEs is significantly elevated in patients with advanced ROS+ NSCLC compared to EGFR+ and KRAS+ cases. TEE risk may be similarly elevated in ALK+ NSCLC.

摘要

简介:本研究旨在确定 ROS1 基因重排的晚期非小细胞肺癌(ROS1+ NSCLC)的血栓栓塞事件(TEE)发生率是否高于预期。

方法:在美国和中国的五家学术中心,在诊断为 ROS1+、ALK+、EGFR+或 KRAS+晚期 NSCLC 后±365 天内,捕获静脉和动脉 TEE(2002 年 10 月至 2018 年 4 月)。主要终点是在诊断后±90 天内,ROS1+与间变性淋巴瘤激酶(ALK+)、表皮生长因子受体(EGFR+)和 KRAS+ NSCLC 相比,TEE 的发生率。采用 logistic 回归评估肿瘤基因驱动因素之间 TEE 发生的几率是否不同。

结果:对 95 例 ROS1+、193 例 ALK+、300 例 EGFR+和 152 例 KRAS+ NSCLC 患者的合格数据进行了分析。TEE 的发生率分别为 34.7%(n=33)、22.3%(n=43)、13.7%(n=41)和 18.4%(n=28)。单因素分析显示,ROS1+ NSCLC 发生 TEE 的几率高于 ALK+、EGFR+和 KRAS+队列。多变量分析显示,与 EGFR+和 KRAS+队列相比,ROS1+发生 TEE 的几率显著更高,比值比(OR)为 2.44,95%置信区间为 1.31-4.57(p=0.005),OR:2.62,95%置信区间为 1.26-5.46(p=0.01)。虽然数值上更高,但与 ALK+相比,ROS1+发生 TEE 的几率无统计学意义(OR:1.45,p=0.229)。在整个研究队列或在每个分子组中,诊断后±90 天内有或没有 TEE 的患者的总生存没有显著差异。

结论:与 EGFR+和 KRAS+病例相比,ROS+晚期 NSCLC 患者发生围诊断性 TEE 的风险显著升高。ALK+ NSCLC 中 TEE 风险可能同样升高。

相似文献

[1]
ROS1 Gene Rearrangements Are Associated With an Elevated Risk of Peridiagnosis Thromboembolic Events.

J Thorac Oncol. 2018-12-10

[2]
Risk of thromboembolism in non-small-cell lung cancers patients with different oncogenic drivers, including ROS1, ALK, and EGFR mutations.

ESMO Open. 2022-12

[3]
ROS1 Fusions Rarely Overlap with Other Oncogenic Drivers in Non-Small Cell Lung Cancer.

J Thorac Oncol. 2017-5

[4]
Clinical features and therapeutic options in non-small cell lung cancer patients with concomitant mutations of EGFR, ALK, ROS1, KRAS or BRAF.

Cancer Med. 2019-4-24

[5]
Patients with ROS1 rearrangement-positive non-small-cell lung cancer benefit from pemetrexed-based chemotherapy.

Cancer Med. 2016-10

[6]
Epidermal Growth Factor Receptor (EGFR) Mutations and Anaplastic Lymphoma Kinase/Oncogene or C-Ros Oncogene 1 (ALK/ROS1) Fusions Inflict Non-Small Cell Lung Cancer (NSCLC) Female Patients Older Than 60 Years of Age.

Med Sci Monit. 2018-12-23

[7]
The frequency and impact of ROS1 rearrangement on clinical outcomes in never smokers with lung adenocarcinoma.

Ann Oncol. 2013-6-19

[8]
Concurrent classic driver oncogenes mutation with ROS1 rearrangement predicts superior clinical outcome in NSCLC patients.

Genes Genomics. 2023-1

[9]
Computed Tomography Imaging Features and Distribution of Metastases in ROS1-rearranged Non-Small-cell Lung Cancer.

Clin Lung Cancer. 2020-3

[10]
Actionable Mutation Profiles of Non-Small Cell Lung Cancer patients from Vietnamese population.

Sci Rep. 2020-2-17

引用本文的文献

[1]
The Association Between Thromboembolic Events and ALK, ROS1, RET Rearrangements or EGFR Mutations in Patients With Advanced Lung Adenocarcinoma: A Retrospective Cohort Study.

Thorac Cancer. 2025-8

[2]
Efficacy and Clinical Outcomes of Crizotinib in Patients with ROS1-Rearranged NSCLC: A Multicenter Study.

Medicina (Kaunas). 2025-3-12

[3]
Genetic Background in Patients with Cancer Therapy-Induced Cardiomyopathy.

J Clin Med. 2025-2-15

[4]
Prevention and Treatment of Venous Thromboembolism Associated with Amivantamab-Based Therapies in Patients with Lung Cancer-Provisional Clinical Opinion Based on Existing Clinical Practice Guidelines.

Cancers (Basel). 2025-1-14

[5]
Targeted anti-cancer agents and risk of venous thromboembolism.

Haematologica. 2024-12-1

[6]
Non-bacterial thrombotic endocarditis in -rearranged lung cancer: a report of two cases.

Transl Lung Cancer Res. 2024-1-31

[7]
Oncogenic alterations in advanced NSCLC: a molecular super-highway.

Biomark Res. 2024-2-12

[8]
Phloretin targets SIRT1 to alleviate oxidative stress, apoptosis, and inflammation in deep venous thrombosis.

Toxicol Res. 2023-8-30

[9]
From Development to Place in Therapy of Lorlatinib for the Treatment of ALK and ROS1 Rearranged Non-Small Cell Lung Cancer (NSCLC).

Diagnostics (Basel). 2023-12-25

[10]
Oncogenes and cancer associated thrombosis: what can we learn from single cell genomics about risks and mechanisms?

Front Med (Lausanne). 2023-12-20

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