Late-onset Cardiotoxicity in Childhood Cancer Survivors; Exploring Different Screening Methods

GENERAL INTRODUCTION AND OUTLINE OF THE THESIS

Survival of children with cancer has significantly improved over the last decades. It is estimated that in 2020 half a million EU citizens are alive and cured from childhood cancer.1 Cure-rates are currently up to 80% in children and adolescents with cancer and are still improving. Anthracyclines exert their anti-tumor effect through different mechanisms which have been summarized by Minotti et al.2 Recent advances also show more insight into other possible mechanisms.3 A major limitation in the use of anthracyclines is its cardiotoxic effect, presenting as acute, early- or late-onset cardiotoxicity. Late effects may persist following an acute episode, may develop within the first 5 years after treatment, or can even develop decades later. Late effects can present in many organ systems (cardiorespiratory, neurological, gastro-intestinal and endocrine systems), making targeted investigation during follow-up vital for early detection.4 Cardiotoxicity in childhood cancer survivors (CCS) can lead to a six-fold higher risk of cardiomyopathy or heart failure specific mortality compared to the general population.5 The estimated risk of symptomatic cardiac failure varies between 5-20%, 30 to 40 years after treatment with cardiotoxic chemotherapy.6,7 Mediastinal radiotherapy increases this risk from 10.6% to 27.8%.6