Risk prediction models for antineoplastic-associated cardiotoxicity in treatment of breast cancer: A systematic review

Abstract

Purpose: The objective of this systematic review is to assess methodology of published models to predict the risk of antineoplastic-associated cardiotoxicity in patients with breast cancer.

Methods: We searched PubMed and Embase for studies that developed or validated a multivariable risk prediction model. Data extraction and quality assessments were performed according to the Prediction Model Risk of Bias Assessment Tool (PROBAST).

Results: We identified 2,816 unique publications and included 8 eligible studies (7 new risk models and 1 validation of a risk stratification tool) that modeled risk with trastuzumab (n = 5), anthracyclines (n = 2), and anthracyclines with or without trastuzumab (n = 1). The most common final predictors were previous or concomitant chemotherapy (n = 5) and age (n = 4). Three studies incorporated measures of myocardial mechanics that may not be frequently available. Model discrimination was reported in 7 studies (range of area under the receiver operating characteristic curve, 0.56-0.88), while calibration was reported in 1 study. Internal and external validation were performed in 4 studies and 1 study, respectively. Using the PROBAST methodology, we rated the overall risk of bias as high for 7 of 8 studies and unclear for 1 study. Concerns for applicability were low for all studies.

Conclusion: Among 8 models to predict the risk of cardiotoxicity of antineoplastic agents for breast cancer, 7 were rated as having a high risk of bias and all had low concerns for clinical applicability. Most evaluated studies reported positive measures of model performance but did not perform external validation. Efforts to improve development and reporting of these models to facilitate their use in practice are warranted.

Keywords: anthracycline; breast cancer; cardiotoxicity; risk prediction; systematic review; trastuzumab.