Incidence of venous thromboembolism in patients with colorectal cancer according to oncogenic status

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RESEARCH ARTICLE

Incidence of venous thromboembolism in patients with colorectal cancer according to oncogenic status L. Ortega Morán1,2   · P. García Alfonso1 · I. Aguilar Caballero1 · B. Morón García1 · V. Tirado Anula1 · M. de Toro Carmena1 · J. Soto Alsar1 · N. Gutiérrez Alonso1 · M. Bringas Beranek1 · M. Martín Jiménez1 · A. J. Muñoz Martín1,2  Received: 6 March 2020 / Accepted: 16 March 2020 © Federación de Sociedades Españolas de Oncología (FESEO) 2020

Abstract Background  There are conflicting data regarding the role of KRAS mutation on the risk of venous thromboembolism (VTE) in colorectal cancer (CRC) patients. Moreover, the role of other biomarkers such as NRAS or BRAF has not been studied. Purpose  To analyze the incidence of VTE in a cohort of patients with CRC based on KRAS, NRAS, and BRAF status. Methods  We performed a retrospective review of patients with unresectable locally advanced and metastatic CRC (mCRC) and known KRAS/NRAS/BRAF status, attended in the Medical Oncology Department of the Hospital General Universitario Gregorio Marañón (Madrid, Spain). The primary outcome was VTE defined as any venous thromboembolic event that occurred either 6 months before or at any time after the diagnosis of CRC. The biomarker status (KRAS, NRAS, and BRAF) and other predictors of thrombosis were collected. Results  One hundred and ninety-four patients were identified and included in the analysis. Forty-one patients (21.1%) experienced VTE. The incidence was 19.1% in RAS-mutated patients, 28.6% in BRAF-mutated patients and 21% in triple wild-type patients (p = NS). In multivariate analysis, ECOG ≥ 2 was the only independent predictor of VTE (OR 8.73; CI 95% 1.32–57.82; p = 0.025). Conclusions  In our study, biomarkers have not been associated with an increased risk of VTE in CRC patients. A high incidence of VTE in BRAF-mutated patients has been observed and should be explored in further studies. Keywords  Cancer-associated thrombosis · Venous thromboembolism · Colorectal cancer · Biomarkers

Introduction Venous thromboembolism (VTE) is a frequent complication in cancer patients. Moreover, it has been associated with a negative impact on survival [1]. Current guidelines do not recommend routine thromboprophylaxis in ambulatory cancer patients, but it should be considered in high-risk patients L. O. Morán and P. G. Alfonso contributed equally to this work. * A. J. Muñoz Martín [email protected] 1



Medical Oncology Department, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón, Universidad Complutense, Madrid, España



Cancer and Thrombosis Section, Spanish Society of Medical Oncology (SEOM), Madrid, Spain

2

[2–6]. Several tools have been developed to identify patients at high risk in the outpatient setting [7–14]. In addition, various molecular markers have been identified as risk factors of thrombosis in cancer patients [15, 16]. The association between oncogenic status and thrombosis is based on preclinical studies. Thus, the activation of