Defense Date


Document Type


Degree Name

Doctor of Philosophy


Rehabilitation and Movement Science

First Advisor

Antonio Abbate, MD, PhD

Second Advisor

Ronald Evans, PhD

Third Advisor

Ryan Garten, PhD

Fourth Advisor

Benjamin Van Tassell, PharmD

Fifth Advisor

Elisabeth Weiss, MD


Cancer (CA) is the second leading cause of death in the United States preceded only by cardiovascular disease (CVD). Over the past 30 years, the 5-year survival rate for all cancers combined has increased by more than 20%. This improved survival rate is due to early diagnosis and advances in treatment involving a multimodality treatment approach that includes radiotherapy [RT] with about half of all CA patients receiving some type of RT sometime during the course of their treatment. Cardiotoxicity is one of the most important adverse reactions of RT and leads to a meaningful risk of CVD-related morbidity and mortality. Radiotherapy-related cardiotoxicity is a heterogeneous clinical syndrome characterized by symptoms related to impaired cardiac function due to radiation-injury to one or more cardiac structures. Furthermore, the relative risk of CVD increases with increasing incidental radiation dose to the heart.

There is not a unified consensus on the definition of CA-related cardiotoxicity although most trials have focused on changes in resting systolic function, and/or development of cardiac symptoms.Commonly used tools to assess cardiac function are insensitive to minor injury hence subtle changes may go unnoticed for many years. Cardiotoxicity definitions should include a dynamic functional assessment of the CV system. This may allow detection of latent CV abnormalities before the precipitous decline of resting myocardial function or the development of CV symptomology that may impact quality of life.

Cardiopulmonary exercise testing (CPET) including measurement of peak oxygen consumption (VO2) is the gold standard for the assessment of cardiorespiratory fitness (CRF). Cardiorespiratory fitness is a strong, independent predictor of mortality, CVD-related mortality, HF-related morbidity and mortality, CA-related mortality and may be involved in the pathophysiologic link between anti-CA related treatments and the increased risk of late CVD events. Emerging evidence indicates CRF may be reduced in CA survivors and have utility to detect subclinical cardiotoxicity, but this has not been evaluated in CA survivors treated with RT with significant heart involvement. This dissertation consists of one literature review and one comprehensive paper that will examine the ability of CPET to detect subclinical cardiotoxicity.


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