A Biomarker-Based Diagnostic Model for Cardiac Dysfunction in Childhood Cancer Survivors

Jan M. Leerink*, Elizabeth A.M. Feijen, Esmee C. de Baat, Remy Merkx, Helena J.H. van der Pal, Wim J.E. Tissing, Marloes Louwerens, Marry M. van den Heuvel-Eibrink, A. Birgitta Versluys, Elvira C. van Dalen, Margriet van der Heiden-van der Loo, Dorine Bresters, Cécile M. Ronckers, Andrica C.H. de Vries, Sebastian Neggers, Livia Kapusta, Jacqueline Loonen, Yigal M. Pinto, Leontien C.M. Kremer, Annelies M.C. Mavinkurve-GroothuisWouter E.M. Kok

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


Background: Childhood cancer survivors at risk for heart failure undergo lifelong echocardiographic surveillance. Previous studies reported the limited diagnostic accuracy of N-terminal pro–B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT) in detecting left ventricular (LV) dysfunction. However, potential enhanced diagnostic accuracy through the combination of biomarkers and clinical characteristics has been suggested. Objectives: The aim of this study was to develop and internally validate a diagnostic model that combines cardiac biomarkers with clinical characteristics for effectively ruling in or ruling out LV dysfunction in childhood cancer survivors. Methods: A multicenter cross-sectional study included 1,334 survivors (median age 34.2 years) and 278 siblings (median age 36.8 years). Logistic regression models were developed and validated through bootstrapping, combining biomarkers with clinical characteristics. Results: Abnormal NT-proBNP levels were observed in 22.1% of survivors compared with 5.4% of siblings, whereas hs-cTnT levels exceeding 10 ng/L were uncommon in both survivors (5.9%) and siblings (5.0%). The diagnostic models demonstrated improvement upon the addition of NT-proBNP and hs-cTnT to clinical characteristics, resulting in an increased C statistic from 0.69 to 0.73 for LV ejection fraction (LVEF) <50% and a more accurate prediction of more severe LV dysfunction, with the C statistic increasing from 0.80 to 0.86 for LVEF <45%. For LVEF <50% (prevalence 10.9%), 16.9% of survivors could be effectively ruled out with high sensitivity (95.4%; 95% CI: 90.4%-99.3%) and negative predictive value (97.5%; 95% CI: 94.6%-99.7%). Similarly, for LVEF <45% (prevalence 3.4%), 53.0% of survivors could be ruled out with moderate to high sensitivity (91.1%; 95% CI: 79.2%-100%) and high negative predictive value (99.4%; 95% CI: 98.7%-100%). Conclusions: The biomarker-based diagnostic model proves effective in ruling out LV dysfunction, offering the potential to minimize unnecessary surveillance echocardiography in childhood cancer survivors. External validation is essential to confirm these findings. (Early Detection of Cardiac Dysfunction in Childhood Cancer Survivors; A DCOG LATER Study; https://onderzoekmetmensen.nl/nl/trial/23641)

Original languageEnglish
Pages (from-to)236-247
Number of pages12
JournalJACC: CardioOncology
Issue number2
StatePublished - Apr 2024


FundersFunder number
Martha Grootenhuis, Flora van Leeuwen, Lideke van der Steeg
Geert Janssens, Hanneke van Santen


    • biomarkers
    • cardio-oncology
    • childhood cancer survivors
    • diagnostic accuracy


    Dive into the research topics of 'A Biomarker-Based Diagnostic Model for Cardiac Dysfunction in Childhood Cancer Survivors'. Together they form a unique fingerprint.

    Cite this