PET/CT Imaging of Venous Thromboembolism in Pediatric, Adolescent, and Young Adult Oncology

PROJECT SUMMARY The long-term goal of this work is to develop a non-invasive imaging strategy for quantifying chemotherapy- induced vascular toxicity to better understand the potential role of image-derived measures of venous inflammation for predicting risk for venous thromboembolism (VTE) in pediatric, adolescent, and young adult (AYA) patients undergoing cancer treatment. Chemotherapy is known to have off-target vascular effects that increase the risk for VTE. In spite of this recognized risk, risk models are not regularly used to guide preventative anticoagulation in young cancer patients and preventative thromboprophylaxis is traditionally avoided due to a high risk of bleeding associated with cancer and concurrent chemotherapy. Therefore, there is a need for biomarkers that can assess chemotherapy-induced toxicity, identify patients at highest risk for VTE, and detect the potential anti-inflammatory vascular effects of thromboprophylaxis. In this proposal, we will validate and test a molecular imaging approach for characterizing chemotherapy-induced venous toxicity from PET/CT images acquired as part of routine care in pediatric and AYA patients undergoing treatment for lymphoma. To accomplish this overarching goal, we will first pre-clinically validate 18F-FDG PET/CT imaging as a non-invasive biomarker of chemotherapy-induced venous toxicity. We will then clinically evaluate the prognostic value of our imaging approach for predicting risk for VTE by collecting whole-body PET/CT images from a large multi-site cohort of pediatric and AYA patients with lymphoma and prospectively monitoring occurrence of VTE events. Following pre-clinical validation and clinical testing of our approach, we will assess the utility of 18F-FDG PET/CT imaging for detecting the anti-inflammatory actions of standard thromboprophylaxis methods. Validation of PET/CT imaging for detecting venous toxicity, risk for VTE, and responses to thromboprophylaxis could provide a non-invasive approach for enabling real-time monitoring of adverse vascular effects associated with cancer treatment in pediatric and AYA patients and identifying those at high risk for VTE.