Validation of a Risk Score for Cancer-Associated Thrombosis Using Nationwide EHR Data

Venous thromboembolism (VTE) is associated with increased mortality and morbidity in patients with cancer. Existing risk prediction models are typically validated within individual sites, a fragmented approach that limits clinical adoption.

To validate the electronic health record cancer-associated thrombosis (EHR-CAT) score compared with the benchmark Khorana score in a contemporary cohort of patients with cancer across the nation, before and after treatment, excluding those at high risk of bleeding.

This prognostic study included patients in a nationwide longitudinal EHR database from January 2018 to December 2023 with follow-up continuing to April 2025. Patients with newly diagnosed, invasive, solid, or hematologic malignant neoplasms (defined using validated International Statistical Classification of Diseases, Tenth Revision, Clinical Modification [ICD-10-CM] algorithms) receiving systemic therapy (defined using the first antineoplastic medication) were included. Those with recent history of acute VTE diagnosis or anticoagulant prescription were excluded.

Demographics, risk model variables, and common anticoagulant trial exclusion criteria (as a proxy for identifying people at high risk of bleeding) were extracted on or before index therapy initiation date.

Incident VTE and bleeding outcomes at 6 months were defined using validated ICD-10-CM algorithms.

A total of 732 594 patients (median [IQR] age, 65.0 [56.9-73.0] years; 425 124 female [58.0%]; 25 634 Asian [3.5%], 94 269 Black [12.9%], 48 266 Hispanic [6.6%], 583 047 White [76.9%]) with active cancer receiving systemic therapy between 2018 and 2023 from 184 health systems were identified. With a median (IQR) follow-up of 676 (340-1151) days, the incidence of 6-month VTE, bleeding, and mortality was 4.7% (34 499 patients), 3.7% (26 993 patients), and 8.4% (60 239 patients), respectively. Bleeding risk was higher in the 26.0% of patients (190 413) meeting anticoagulant trial exclusion criteria (7.2% vs 2.4%; hazard ratio, 2.5 [95% CI, 2.5-2.5]). The EHR-CAT score stratified patients into discriminative risk groups (C statistic, 0.70-0.71) both before and after exclusion for bleeding risk. When compared with the benchmark Khorana score (C statistic, 0.63), EHR-CAT reclassified 20% of patients into revised categories with improved prediction accuracy. Furthermore, EHR-CAT had consistent calibration in subgroups by age, sex, race, ethnicity, and individual health system sites.

This prognostic study of the EHR-CAT risk score demonstrated the external validity and feasibility of using readily available structured EHR data to estimate VTE risk in patients with cancer.