Biomarkers for detection of anthracycline-induced cardiomyopathy in childhood cancer survivors: a case-control study in the Dutch LATER cohort study

Abstract

Abstract Introduction Plasma biomarkers may aid in the surveillance for anthracycline-induced cardiomyopathy (ACM) in long-term childhood cancer survivors and provide insight into the pathophysiological mechanisms involved. In this pilot study, we aimed to identify new plasma markers associated with ACM. Methods A case-control study within the Dutch Late Effects After Childhood Cancer Cohort study (Dutch LATER) was conducted. We compared 184 plasma markers (Olink) between ACM cases (LVEF<45%) and anthracycline treated controls (LVEF≥53%), matched on sex, time since cancer diagnosis and anthracycline dose. Associations of plasma markers with ACM were assessed with conditional logistic regression. Pathway analysis was performed with STRING (string-db.org). Significant markers were evaluated in multivariable models next to anthracyclines dose, sex and time after cancer. Results In total, 28 ACM cases (median anthracycline dose 351 mg/m2; median age at study 38 years, 29% chest radiotherapy) and 29 controls (median anthracycline dose 300 mg/m2; median age at study 44 years, 7% chest radiotherapy) were included. Eight markers were significantly associated with ACM (Table 1) and were implicated in ventricular wall stress, apoptosis, inflammation and endothelial dysfunction (Figure 1). The AUC of the model including only the clinical variables was 0.73 (95% confidence interval (CI) 0.60–0.86), and improved to 0.82 (95% CI 0.71–0.94) with the addition of NT-proBNP and further to 0.86 (95% CI 0.76–0.97) with the addition of all 8 markers. Conclusion In this biomarker discovery study, 8 markers related to ventricular wall stress, apoptosis, inflammation and endothelial dysfunction were associated with ACM. We intend to validate these markers quantitatively in the Dutch LATER cohort study. Figure 1. Pathway analysis of significant markers Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Dutch Heart Foundation Grant; Amsterdam University Funding