Venous Thromboembolism Risk Model Predicts Early Progression and Overall Mortality in Cancer Patients Receiving Chemotherapy
Authors: Kuderer Nicole M. , Khorana Alok A. , Francis Charles W. , Culakova Eva , Ortel Thomas L. , Falanga Anna , Lyman Gary H. 
Published: April 2020

Abstract
Background: Venous Thromboembolism (VTE) is a common complication of cancer and is strongly associated with early all-cause mortality during the course of cancer chemotherapy (Kuderer et al. ASCO 2008). A clinical model for predicting the risk of VTE in cancer patients initiating chemotherapy has been recently developed and validated (Khorana et al. Blood 2008). Risk of VTE in low (group I), intermediate (group II) and high risk patients (group III) was 0.8%, 1.8% and 7.1%, respectively. The aim of current study is to evaluate the ability of the VTE risk model to predict disease progression and early all-cause mortality.
Methods: A prospective study of 4,458 adult cancer patients with solid tumors or malignant lymphoma initiating a new chemotherapy regimen was conducted between 2002 and 2006 at 115 randomly selected practice sites throughout the USA. Demographic, clinical and treatment-related information was captured prospectively at baseline and during the first four cycles of chemotherapy, including rates of documented VTE, disease recurrence and deaths from all causes. Progression-free survival (PFS) and overall survival (OS) within 4 months of starting chemotherapy were estimated by the method of Kaplan-Meier and adjusted hazard ratios (HR ± 95% CI) were estimated by a Cox regression model, incorporating VTE as a time-dependent covariate.
Results: Patient age ranged from 18–97 with a mean of 60 years. VTE occurred in 3% of patients by 4 months with a median of 38 days following initiation of chemotherapy. The HR for VTE occurrence among risk score groups II and III, compared to group I, were 3.07 [1.39–6.77] and 11.73 [5.22–16.37], (P&lt;0.0001) respectively. Within 4 months, disease progression occurred in 298 patients and 137 patients died. Death or disease progression was reported in 7%, 18% and 28% of risk score groups I, II and III, respectively. HR for reduced PFS among risk groups II and III compared to group I were 2.77 [1.97–3.87] and 4.27 [2.90–6.27], respectively (P&lt;0.0001). Death from all causes within 4 months of treatment initiation was reported in 1.2%, 5.9% and 12.7% patients for risk groups I, II and III. HR estimates for mortality among groups II and III were 3.56 [1.91–6.66] and 6.89 [3.50–13.57], respectively (P&lt;0.0001). In multivariate analysis, the risk score and VTE occurrence were both significant independent predictors for early mortality and reduced PFS after adjusting for major prognostic factors including: age, stage, cancer type, ECOG performance status, Charlson comorbidity index, body mass index, relative dose intensity, and year of enrollment.
Conclusions: VTE is strongly associated with increased early all-cause mortality during the course of cancer chemotherapy. A recently validated risk score is not only predictive of VTE occurrence, but also of progression-free and overall survival demonstrating a strong association with prognostic factors for disease progression and mortality.