Autonomic dysfunction in patients with advanced cancer; prevalence, clinical correlates and challenges in assessment

BACKGROUND: The results of a small number of studies of autonomic function in patients with advanced cancer suggest that autonomic dysfunction (AD) is common. In other disease-specific groups this is associated with decreased survival, falls and symptoms such as postural hypotension, nausea, early satiety and fatigue. The contribution of AD to symptoms in advanced cancer is unknown. METHODS: We conducted a prospective cohort study designed to identify the risk factors for falls in patients with advanced cancer. Ambulant adult patients admitted consecutively to palliative care services were invited to participate. Participants underwent an assessment at baseline which included standard clinical tests of autonomic function, assessment of symptom severity, muscle strength, anthropometric measurements, walking speed, medication use, comorbidities and demographics. Information regarding survival was recorded ten months following cessation of recruitment. The clinical correlates of AD, defined as definite or severe dysfunction using Ewing's classification, were examined by univariate and multivariate logistic regression analysis. Survival analysis was conducted using Kaplan-Meier plots and the log rank test. RESULTS: Of 185 patients recruited, 45% were unable to complete all of the clinical tests of autonomic function. Non-completion was associated with scoring high on clinical indicators of frailty. It was possible to accurately classify 138/185 (74.6%) of participants as having either definite or severe versus normal, early or atypical AD: 110 (80%) had definite/severe AD. In logistic regression analysis, age (OR = 1.07 [95% CI; 1.03-1.1] P = 0.001) and increased severity of fatigue (OR = 1.26 [95% CI; 1.05-1.5] p = 0.016) were associated with having definite/severe AD. In analysis adjusted for age, median survival of participants with definite/severe AD was shorter than in those with normal/early/atypical classification (χ(2 )= 4.3, p = 0.038). CONCLUSIONS: Autonomic dysfunction is highly prevalent in patients with advanced cancer and is associated with increased severity of fatigue and reduced survival. Due to frailty, up to 45% of participants were unable to complete standard clinical tests of autonomic function. In order to further investigate the impact of AD and the therapeutic potential of treatment of AD in patients with advanced cancer, the validity of alternative novel methods of assessing autonomic function must be appraised.