Determinants and early detection of late cardiotoxic effects of anthracyclines in childhood cancer survivors Public
Ryerson, Aliza Blythe (2013)
Abstract
Anthracyclines are used extensively in cancer treatment protocols and more than half of all childhood cancer survivors in the U.S. have been exposed. An important adverse effect of anthracyclines is cardiotoxicity, which requires continued monitoring of cardiac function to avoid further injury and ensure timely treatment. Childhood cancer survivors may also be at increased risk for cardiovascular disease because of their propensity for sedentary lifestyles. This dissertation explores the use of different screening techniques to assess cardiac and morbidity-related late effects of anthracyclines in childhood cancer survivors, and estimates the proportion of cardiac events preventable through exercise intervention.
We conducted resting and exercise echocardiography on 80 asymptomatic childhood cancer survivors at least 5 years post-treatment and asked participants to completed a Pediatric Quality of Life Inventory (PedsQL). We also analyzed data from the Childhood Cancer Survivor Study (CCSS) to assess the late effects following treatment. Using CCSS data and a new methodology we decomposed the influence anthracyclines have on cardiac outcomes into direct (treatment-related) and indirect (through physical inactivity) effects.
We found no clinical benefit of adding exercise echocardiography to screen for anthracycline cardiotoxicity. However, the results confirmed that cancer survivors at highest risk for cardiotoxicity had some evidence of diastolic filling abnormalities at rest despite normal systolic function, and addition of Tissue Doppler Imaging to resting echocardiography may be useful. With exercise, participants augmented their systolic and diastolic function to achieve relatively normal maximal aerobic capacity despite impaired stroke volume. In the PedsQL study, we observed a dose-response effect of exposure to anthracyclines on overall and physical health-related quality of life underscoring the importance of ongoing psychosocial assessments during survivorship. In the decomposition analysis we found very little, if any, evidence that cardiac outcomes among anthracycline-treated long-term childhood cancer survivors can be attributed to physical inactivity.
This dissertation research extends the literature on our understanding of the effects of anthracycline exposure in childhood cancer survivors. Continued research on the late effects and ways to detect them early is needed to support consensus-based clinical recommendations.
Table of Contents
Chapter 1: Introduction.........................................................................................................................................................................1
Chapter 2: Literature review...................................................................................................................................................................4
Chapter 3: Dissertation goals and data sources.........................................................................................................................................22
Chapter 4: Assessing cardiac function in anthracycline-treated childhood cancer survivors utilizing advanced exercise echocardiography ..................33
Chapter 5: Pediatric quality of life in long-term survivors of childhood cancer treated with anthracyclines............................................................51
Chapter 6: The effect exercise has on preventing late cardiac outcomes among childhood cancer survivors treated with anthracyclines....................65
Chapter 7: Conclusions and future directions............................................................................................................................................97
References.......................................................................................................................................................................................103
Appendices.......................................................................................................................................................................................133
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