Survivors of childhood cancer treated with thoracic radiation therapy (TRT) are at risk for cardiovascular and pulmonary morbidity. In the general population, adults with cardiovascular or pulmonary disease demonstrate brain white matter abnormalities and/or stroke on brain magnetic resonance imaging (MRI), and neurocognitive problems. Many cancer survivors also report poor sleep quality and excessive fatigue, though limited data is available on specific sleep disorders. We recently collected polysomnography on 30 randomly selected adult survivors of childhood cancer treated with TRT (median age 35 years, range 20-53); 14 (47%) met clinical criteria for obstructive sleep apnea (OSA). This frequency is substantially higher than reported for similar aged community adults. In a larger cohort of 163 participants, we identified OSA symptoms twice as often in 72 survivors treated with TRT compared to the 91 community controls. In both preliminary studies, OSA [symptoms] in survivors were not associated with body mass index or neck girth, common predictors of OSA in the general population and in our controls. This suggests a different pathology for OSA in the survivors, possibly reduced muscle tone in the neck or diaphragm related to the TRT. In our preliminary studies, cardiac morbidity and cognitive impairment were associated with the presence of OSA [symptoms] in survivors, but not controls. This novel pilot data leads us to propose a more comprehensive follow-up with a larger sample to examine the pathophysiology of OSA in survivors. Specifically, we propose: 1) to compare the frequency of OSA in adult survivors of childhood cancer treated with thoracic radiation compared to age, gender and race matched community controls; 2) to identify specific therapeutic factors associated with OSA in adult survivors of childhood cancer treated with thoracic radiation; 3) to identify biomarkers of OSA in adult survivors of childhood cancer treated with thoracic radiation; and 4) to examine associations between OSA and cardiac morbidity and brain integrity in the adult survivors. These survivors are already at risk for cardiac and pulmonary morbidity due to cancer therapy. Undiagnosed sleep apnea could significantly exacerbate this risk, potentially leading to catastrophic cardiovascular events. Results of this study have the potential to significantly impact current standard of care; cancer survivors who were treated with thoracic radiation are not routinely screened for sleep apnea symptoms. Findings will be used to develop specific pilot interventions aimed at treating sleep apnea and reducing risk for resultant cardiac and cerebrovascular injury.
Statement This proposal will identify prevalence and predictors of obstructive sleep apnea in a large cohort of Hodgkin lymphoma survivors at risk for cardiac and pulmonary morbidity. We will also examine potential cardiac, cognitive and brain integrity outcomes based on sleep apnea risk. Results will inform new long-term follow-up guidelines and development of interventions and risk-based prevention trials.