Abstract
BACKGROUND: Afferent baroreflex failure (ABF) is an underrecognized but debilitating complication among head and neck cancer survivors, especially in oropharyngeal cancer (OPC), a malignancy with excellent prognosis. ABF is mainly caused by radiation therapy (RT), with neck surgery and some chemotherapies also contributing. It manifests as blood pressure lability, including severe hypertension or hypotension, syncope, and arrhythmias. OBJECTIVES: To determine the prevalence and predictors of ABF-associated manifestations among OPC survivors treated with modern RT. METHODS: We retrospectively studied OPC patients treated with RT at a tertiary cancer center between 2016-2019. Clinical data were collected from RT initiation to last follow-up or death. ABF-associated manifestations included new or worsening hypertension, hypotension requiring intervention, arrhythmias, and syncope. Secondary endpoints included new or worsened carotid artery atherosclerosis, stenosis, transient ischemic attack (TIA), stroke, and all-cause mortality. RESULTS: Among 393 patients (88% men, 91% White, mean age 61±10 years), 9.4% developed hypertension, 5.3% hypotension, 3.8% syncope, and 3.3% arrhythmias over median 6.3-year follow-up. Overall, 19.1% developed at least one ABF-associated manifestations. New or worsened carotid atherosclerosis occurred in 38.9%, with 7.1% developing >50% stenosis and 2.3% experiencing TIA or stroke. Mortality was 21.4%. On cause-specific multivariable Cox analysis, older age (adjusted hazard ratio [aHR] 1.03; 95% confidence interval [CI] 1.01-1.06), valvular disease (aHR 2.85; CI 1.03-7.92), T4 cancer (aHR 1.90; CI 1.10-3.27), and platinum-taxane chemotherapy (aHR 1.86; CI 1.13-3.05) independently increased risk of ABF-associated manifestations. CONCLUSIONS: Nearly 1 in 5 OPC survivors treated with RT develop ABF-associated manifestations, highlighting the need for early recognition and surveillance.