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

Terry L. Ng, Derek E. Smith, Rao Mushtaq, Tejas Patil, Anastasios Dimou, Shuo Yang, Qian Liu, Xuefei Li, Caicun Zhou, Robert T. Jones, Megan M. Tu, Flora Yan, I. Alex Bowman, Stephen V. Liu, Siera Newkirk, Joshua Bauml, Robert C. Doebele, Dara L. Aisner, Dexiang Gao, Shengxiang RenD. Ross Camidge

Research output: Contribution to journalArticlepeer-review

13 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)596-605
Number of pages10
JournalJournal of Thoracic Oncology
Issue number4
StatePublished - Apr 2019


  • ALK
  • Lung cancer
  • Oncogene driver
  • ROS1
  • Thrombosis

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine

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