Ahmed Sadek, MD
Ahmed A. Sadek MD*, Harvey Roweth PhD, Jonathan Ayash BS, William G. Richards PhD, Elisabeth M. Battinelli MD, PhD, Raphael Bueno MD
Raphael Bueno MD
Background: Malignancy is an established risk factor for the development of venous thromboembolism (VTE) with reported absolute risk between 0.5-20% depending on cancer type. Pleural Mesothelioma (PM) incurs a particularly high risk of VTE with observed rates of 32%. Activation of platelets within the tumor microenvironment is a proposed mechanism for development of a prothrombotic state in malignancy. However, tumor genetic and transcriptomic factors that may promote VTE in PM are unknown. This study aims to characterize patient, tumor, and clinical factors associated with VTE among patients with PM.
Methods: With IRB approval, clinical and pathological data were retrospectively reviewed from PM patients who underwent surgical resection between 2006-2015, including preoperative labs, surgery type, lower extremity noninvasive ultrasound results, VTE diagnosis, tumor histological subtype, and tumor volume.
Results: Charts were reviewed for 395 PM patients. VTE was documented in 33.7% (n=133) of patients. Patients with thrombocytosis (defined as platelet count >450 K/ul) were more likely to develop VTE than patients with normal platelet counts (45% vs 31%, p=0.019). Male patients were more likely to develop VTE than female patients (37% vs 19%, p=0.004). Patients with thrombocytosis had larger tumor volumes (Median 704 cm^3, IQR 274.5-1158) than patients with normal platelet counts (Median 232.5 cm^3, IQR 58.2-494.2); p< 0.001. There was no significant difference between tumor histological subtypes in the development of VTE (x^2= 2.637 p= 0.267).
Conclusions: Thrombocytosis is significantly associated with larger tumor volumes as well as the development of VTE in PM patients. This suggests a role for platelets in the development of a prothrombotic state of PM, possibly affecting either platelet production or clearance. We will use bulk tumor RNA sequencing to evaluate expression of platelet activation factors within the tumor microenvironment, and to develop unique transcriptional signatures that could predict the development of VTE.
Malignancy is a known risk factor for the development of venous thromboembolic disease (VTE). Rates of VTE in pleural mesothelioma (PM) are particularly high, even when compared to other cancer types. With such high rates of VTE seen in PM, our group routinely screens all surgical PM patients with lower extremity non-invasive ultrasounds. Through this clinical cohort, PM can serve as a unique model to answer the questions of how and why malignancy predisposes patients to VTEs. To answer these questions, we have performed bulk tumor RNA sequencing to identify the transcriptomic signatures associated with VTE. We aim to determine the tumor genetic and transcriptional factors (i.e. platelet activation signatures) that may play a role in the pathogenesis of VTE and its relationship to tumor growth with the ultimate goal of developing clinically relevant screening, prevention, and treatment strategies for VTE in PM.