Cardiac biomarkers for the detection of cardiotoxicity in childhood cancer—a meta‐analysis

Abstract

Aims Childhood cancer therapy is associated with a significant risk of therapy-related cardiotoxicity. This meta-analysis aims to evaluate cardiac biomarkers for the detection of cancer therapy-related left ventricular (LV) dysfunction in childhood cancer patients. Methods and results PubMed, Cochrane Library, Wiley Library, and Web of Science were screened for studies investigating brain natriuretic peptide (BNP)/N-terminal proBNP (NT-proBNP) or cardiac troponin in childhood cancer patients. The odds ratios (OR) for elevation of cardiac biomarkers and association with LV dysfunction were calculated using a random-effects model. Data from 27 studies with 1651 subjects were included. BNP/NT-proBNP levels were higher post-treatment compared with controls or pre-treatment values [standardized mean difference = 1.0; 95% confidence interval (CI) = 0.6-1.4; n = 320; P < 0.001]. LV dysfunction was present in 11.76% of included patients, and risk for LV dysfunction was increased in patients with elevated BNP/NT-proBNP (OR = 7.1; 95% CI = 2.0-25.5; n = 350; P = 0.003). The sensitivity of BNP/NT-proBNP for the detection of LV dysfunction was 33.3%, and the specificity was 91.5%. Sensitivity increased when selecting for studies that assessed patients < 5 years after anthracycline exposure and for studies including high cumulative anthracycline doses. Anthracycline chemotherapy was associated with an increased frequency of elevated troponin (OR = 3.7; 95% CI = 2.1-6.5; n = 348; P < 0.001). The available evidence on the association between elevated troponin and LV dysfunction was insufficient for an adequate analysis. In five included studies, the frequency of LV dysfunction was not increased in patients with elevated troponin (OR = 2.5; 95% CI = 0.5-13.2; n = 179; P = 0.53). Conclusions BNP/NT-proBNP is associated with cardiotoxicity in paediatric cancer patients receiving anthracycline therapy, but owing to low sensitivity, BNP/NT-proBNP has to be evaluated in the context of further parameters including clinical assessment and echocardiography. Future studies are needed to determine whether troponin serves as a marker for cardiotoxicity in children. Standardized recommendations for the application of cardiac biomarkers in children undergoing cardiotoxic cancer therapy may benefit management and clinical outcome.

Role of Cardiac Biomarkers in Cancer Patients

“…Adult patients who were treated with beta-blockers and angiotensin converting enzyme inhibitors during chemotherapy had a significantly lower mean serum troponin peak than untreated patients (OR 4.1). Moreover, in the adult population, patients with positive troponin assays were more at risk of developing left ventricular dysfunction and troponin was shown to have a high negative predictive value (93%) for a future EF decrease; on the contrary this evidence was not strong enough for pediatric patients [39,40].…”

Diagnosis, Prevention, Treatment and Surveillance of Anthracycline-Induced Cardiovascular Toxicity in Pediatric Cancer Survivors

“…Before, during, and after treatment, children with ALL had increased levels of NT-proBNP, suggesting its role as a biomarker to detect cardiac stress [61]. Similar to its early elevation in cardiac troponin levels, elevated NT-proBNP levels during the first 90 days of anthracycline chemotherapy in pediatric patients with ALL was predictive of an abnormal LV thickness to dimension ratio by echocardiography 4 years later [61], with a sensitivity of~33% or 92% predicting subsequent acute or subacute cardiac dysfunction, respectively [70]. Abnormal NT-proBNP levels have been detected in 20-30% of asymptomatic survivors [69,71].…”

Genetic Therapy and Molecular Targeted Therapy in Oncology: Safety, Pharmacovigilance, and Perspectives for Research and Clinical Practice

“…Patients with pre-existing risk factors to CAR-T treatment need to be appropriately monitored [ 45 ]. Biomarkers (i.e., troponins, natriuretic peptides, nitric oxid metabolites, and microRNAs) also appear to be important for the detetection of patients at increased risk of CAR-T cardiotoxicity, both in adult and pediatric patients [ 46 , 47 ].…”