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.
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