Physical functioning and cardiovascular disease among survivors of childhood cancer.

Sláma, Tomáš (2024). Physical functioning and cardiovascular disease among survivors of childhood cancer. (Unpublished). (Dissertation, University of Bern, Faculty of Medicine, the Faculty of Science and the Vetsuisse Faculty)

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Introduction:
Childhood cancer survivors (CCS) are at risk of developing a number of chronic health conditions (CHC) as a result of their cancer treatment. The most common cause of non-cancer-related morbidity and mortality in adult CCS is cardiovascular disease (CVD). CVD among CCS is caused by cardiotoxic treatment—i.e. anthracyclines and heart-relevant radiotherapy (RT)—and modifiable risk factors—such as metabolic syndrome—that may contribute to disease severity.
In addition, CHC can also lead to a decline in physical functioning—the ability to perform activities of daily living—among CCS. Cancer-related fatigue (CRF)—another adverse effect of cancer and its treatment—negatively affects physical functioning of
CCS. While some aspects of this research area have been described abroad, there is a lack of literature on physical functioning and CVD among Swiss CCS.

Objectives:
The overall aim of this thesis was to improve our understanding of the physical functioning of Swiss CCS and the development of cardiovascular disease in this population. More specifically, I aimed 1) to compare one aspect of physical functioning—lower body muscular strength and endurance—of Swiss CCS to the general population, investigate risk factors for a reduced physical functioning, and study the longitudinal course of physical functioning among CCS; 2) to describe the prevalence of CRF and its risk factors among CCS; 3) to describe the prevalence of right ventricular (RV) dysfunction and its risk factors among CCS; and 4) to investigate whether cardiovascular disease is also prevalent among survivors of a rare childhood neoplasia—Langerhans cell histiocytosis (LCH).

Results:
The results of this thesis consist of 4 articles. The main results are summarised below:
Publication I: Lower body muscular strength and endurance of CCS was half a standard deviation lower compared to the general population. Obesity, cumulative cisplatin dose, and cumulative cranial RT dose were risk factors for a reduced lower body muscular strength and endurance. There was no change in this parameter over follow-up time of 2–5 years.

Publication II: Approximately one fifth of CCS reported increased CRF, but none reported a severe CRF. Female sex, CNS tumours, sleep disturbance, and endocrine disorders were associated with increased CRF. Lower CRF levels were observed among CCS aged 30–39 years compared to younger CCS.

Publication III: The prevalence of RV dysfunction in our cohort was 4%. Risk factors for reduced RV function were cumulative heart-relevant RT dose, hematopoietic stem cell transplantation, relapse, cisplatin, diabetes mellitus, and abdominal obesity.
Publication IV: Cardiovascular chronic health conditions were more frequent among
LCH survivors compared to siblings. Multifocal bone LCH, mercaptopurine, and overweight or obesity were associated with cardiovascular CHC. The most common cardiovascular CHC among LCH survivors were hypertension and arrhythmia.

Conclusion:
In conclusion, my thesis showed that the physical functioning of Swiss CCS is impaired compared to the general population, that CRF is prevalent among CCS, and that CCS suffer from a number of CVD. Long-term follow-up of CCS is necessary to improve their physical functioning, help mitigate modifiable risk factors, and to perform regular cardiac surveillance of those exposed to cardiotoxic treatment.

Item Type:	Thesis (Dissertation)
Division/Institute:	04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Social and Preventive Medicine (ISPM)
Graduate School:	Graduate School for Cellular and Biomedical Sciences (GCB)
UniBE Contributor:	Sláma, Tomáš, Kühni, Claudia
Subjects:	600 Technology > 610 Medicine & health 300 Social sciences, sociology & anthropology > 360 Social problems & social services
Language:	English
Submitter:	Beatrice Minder Wyssmann
Date Deposited:	01 Jul 2024 14:32
Last Modified:	11 Jul 2024 14:56
Additional Information:	Doctor of Medicine and Philosophy (MD,PhD)
URI:	https://boris.unibe.ch/id/eprint/198340