Development of a multivariable clinical prediction model for liposomal doxorubicin-induced cardiotoxicity in adult breast cancer patients: a retrospective multicenter study

Abstract

BackgroundThe clinical use of anthracyclines is limited by the risk of cardiotoxicity. So, we aim to develop a clinical prediction model for liposomal doxorubicin-induced cardiotoxicity in adult breast cancer patients.MethodsWe designed a multicenter retrospective cohort study. A total of 257 hospitalized breast cancer patients treated with doxorubicin liposomes were finally enrolled in the study, including 58 patients from Beijing Friendship Hospital and 199 from Beijing Cancer Hospital. In all, 32 cases developed cardiotoxicity, including 4 at the Beijing Friendship Hospital and 28 at the Beijing Cancer Hospital. The study involved breast cancer patients with no pre-existing heart disease, whose clinical data were collected from their medical records. All patients underwent electrocardiogram (ECG) and/or left ventricular ejection fraction (LVEF) measurements prior to treatment with doxorubicin liposomes. Patients were clinically assessed after each cycle of treatment, and ECG and/or LVEF measurements were performed at least once after treatment. Liposomal doxorubicin-induced cardiotoxicity was defined when one of the following three conditions was met: (I) a reduction in LVEF of at least 5% from the baseline and the absolute value was less than 55%, accompanied by congestive heart failure (CHF) symptoms or signs; (II) a reduction in LVEF of at least 10% to an absolute value of less than 55%, without CHF symptoms or signs; (III) the definite diagnosis of CHF. Variables associated with cardiotoxicity were identified by univariate and multivariate logistic regression, and the consistency and differentiation of the final model were evaluated.ResultsIn our final model, age [odds ratio (OR): 5.626, 95% confidence interval (CI): 2.321 to 13.639], cancer metastasis (OR: 3.873, 95% CI: 1.220 to 12.299), paclitaxel (OR: 3.601, 95% CI: 1.010 to 12.843), and hypertension (OR: 2.435, 95% CI: 1.046 to 5.671) were significantly associated with cardiotoxicity. The final model was tested for Hosmer-Lemeshow goodness-of-fit, the χ2 was 2.696 and the P value was 0.747, and the resultant predictive model had an area under the receiver operating characteristic (ROC; AUC) curve of 0.781.ConclusionsThis study established a risk prediction model for liposomal doxorubicin-induced cardiotoxicity in breast cancer patients and performed a stratified risk scores