The Association Between Autonomic Dysfunction and Survival in Male Patients with Advanced Cancer: A Preliminary Report

Context: Autonomic nervous system dysfunction (AD) is a common syndrome in patients with advanced cancer. It is associated with decreased survival in several patient populations, including diabetes mellitus, heart failure, and neurological diseases. Based on this evidence, we hypothesized that autonomic dysfunction is associated with decreased survival in patients with advanced cancer. Objectives: The objective of this preliminary study was to test the association between AD, as measured by the standardized Ewing test and heart rate variability (HRV) measures, and survival in this patient population. Methods: We examined the relationship between survival and parameters of AD in subjects who participated in a prospective study of autonomic dysfunction and hypogonadism in male patients with advanced cancer. Eligibility criteria were defined based on the prospective study protocol. We collected demographic information, date of death (obtained from the online Social Security Death Index database), date of study entry, and Ewing and HRV scores. We defined survival as the interval between study entry and date of death. A survival analysis was used to test the association between survival (in days) and Ewing test (0-5) and measures of HRV, including time domain (standard deviation of normal to normal beat interval [SDNN]) and frequency domain (ultra low, very low, low, and high). Four patients were still alive at the time of this study and included in the survival analysis as being censored. Results: Forty-seven male patients were included in this study. Median age was 59 years (range: 20-79), and 30 out of 47 (63%) were Caucasians. AD, defined as Ewing score greater than 2, was present in 38 out of 47 (80%) of the patients. Median Ewing score was 3 (1-5), indicating moderate to severe AD. Spearman correlation for Ewing score and SDNN was 0.44 (P = 0.002). There was a significant association between abnormal Ewing score and survival (P < 0.0001) and abnormal SDNN HRV and survival (P = 0.056). Conclusion: AD is associated with shorter survival in male patients with advanced cancer. Further longitudinal research in a large cohort is justified based on.