Development and Validation of a Clinical Score for Cardiovascular Risk Stratification of Long-Term Childhood Cancer Survivors

Abstract

Abstract Background Long-term childhood cancer survivors (CCS) are at increased risk of adverse cardiovascular events; however, there is a paucity of risk-stratification tools to identify those at higher-than-normal risk. Subjects, Materials, and Methods This was a population-based study using data from the Surveillance, Epidemiology, and End Results Program (1973–2013). Long-term CCS (age at diagnosis ≤19 years, survival ≥5 years) were followed up over a median time period of 12.3 (5–40.9) years. Independent predictors of cardiovascular mortality (CVM) were combined into a risk score, which was developed in a derivation set (n = 22,374), and validated in separate patient registries (n = 6,437). Results In the derivation registries, older age at diagnosis (≥10 years vs. reference group of 1–5 years), male sex, non-white race, a history of lymphoma, and a history of radiation were independently associated with an increased risk of CVM among long-term CCS (p < .05). A risk score derived from this model (Childhood and Adolescence Cancer Survivor CardioVascular score [CHACS-CV], range: 0–8) showed good discrimination for CVM (Harrell's C-index [95% confidence interval (CI)]: 0.73 [0.68–0.78], p < .001) and identified a high-risk group (CHACS-CV ≥6), with cumulative CVM incidence over 30 years of 6.0% (95% CI: 4.3%–8.1%) versus 2.6% (95% CI: 1.8%–3.7%), and 0.7% (95% CI: 0.5%–1.0%) in the mid- (CHACS-CV = 4–5) and low-risk groups (CHACS-CV ≤3), respectively (plog-rank < .001). In the validation set, the respective cumulative incidence rates were 4.7%, 3.1%, and 0.8% (plog-rank < .001). Conclusion We propose a simple risk score that can be applied in everyday clinical practice to identify long-term CCS at increased cardiovascular risk, who may benefit from early cardiovascular screening, and risk-reduction strategies. Implications for Practice Childhood cancer survivors (CCS) are known to be at increased cardiovascular risk. Currently available prognostic tools focus on treatment-related adverse events and late development of congestive heart failure, but there is no prognostic model to date to estimate the risk of cardiovascular mortality among long-term CCS. A simple clinical tool is proposed for cardiovascular risk stratification of long-term CCS based on easily obtainable information from their medical history. This scoring system may be used as a first-line screening tool to assist health care providers in identifying those who may benefit from closer follow-up and enable timely deployment of preventive strategies.