Tumor Genomic Profile Is Associated With Arterial Thromboembolism Risk in Patients With Solid Cancer

Stephanie Feldman, Dipti Gupta, Babak B. Navi, Ka Wai Grace Ho, Peter Willeit, Sean Devlin, Kelly L. Bolton, Maria E. Arcila, Simon Mantha

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


Background: Patients with cancer have an increased risk for arterial thromboembolism (ATE). Scant data exist about the impact of cancer-specific genomic alterations on the risk for ATE. Objectives: The aim of this study was to determine whether individual solid tumor somatic genomic alterations influence the incidence of ATE. Methods: A retrospective cohort study was conducted using tumor genetic alteration data from adults with solid cancers who underwent Memorial Sloan Kettering–Integrated Mutation Profiling of Actionable Cancer Targets testing between 2014 and 2016. The primary outcome, ATE, was defined as myocardial infarction, coronary revascularization, ischemic stroke, peripheral arterial occlusion, or limb revascularization and identified through systematic electronic medical record assessments. Patients were followed from date of tissue-matched blood control accession to first ATE event or death, for up to 1 year. Cause-specific Cox proportional hazards regression was used to determine HRs of ATE for individual genes adjusted for pertinent clinical covariates. Results: Among 11,871 eligible patients, 74% had metastatic disease, and there were 160 ATE events. A significantly increased risk for ATE independent of tumor type was noted for the KRAS oncogene (HR: 1.98; 95% CI: 1.34-2.94; multiplicity-adjusted P = 0.015) and the STK11 tumor suppressor gene (HR: 2.51; 95% CI: 1.44-4.38; multiplicity-adjusted P = 0.015). Conclusions: In a large genomic tumor-profiling registry of patients with solid cancers, alterations in KRAS and STK11 were associated with an increased risk for ATE independent of cancer type. Further investigation is needed to elucidate the mechanism by which these mutations contribute to ATE in this high-risk population.

Original languageEnglish
Pages (from-to)246-255
Number of pages10
JournalJACC: CardioOncology
Issue number2
StatePublished - Apr 2023


  • arterial thromboembolism
  • cancer
  • ischemic stroke
  • myocardial infarction
  • tumor genomic alteration


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