title: Vagal nerve activity predicts overall survival in metastatic pancreatic cancer, mediated by inflammation.
abstract: Recent research findings suggest neuro-modulation of tumors. Finding new modifiable prognostic factors paves the way for additional treatments, which is crucial in advanced cancer, particularly pancreatic cancer. This study examined the relationship between vagal nerve activity, indexed by heart rate variability (HRV), and overall survival (OS) in patients (N=272) with advanced pancreatic cancer. A "historical prospective" design was employed, where vagal activity and other confounders were retroactively obtained from medical charts at diagnosis, and subsequent OS was examined. HRV was obtained from 10 sec ECGs near diagnosis. Levels of C-reactive protein (CRP) were measured as an inflammatory marker. OS and survival date were obtained from medical charts and the Belgian national registry. Patients with high HRV (>20 msec) survived on average more than double the days (133.5) than those with low HRV (64.0). In a multivariate cox regression, higher initial HRV was significantly correlated with lower risk of death, independent of confounders including age and cancer treatments. This relationship was statistically mediated (accounted for) by CRP levels. Importantly, in patients who lived up to one month from diagnosis only, HRV was unrelated to CRP, while in patients surviving longer, HRV was significantly inversely related to CRP (r=-0.20, p<0.05). These results are in line with possible vagal nerve protection in a fatal cancer, and propose that the mechanism may involve neuroimmuno-modulation. Future studies must test whether vagal nerve activation may help patients with advanced cancers.
authors.affiliation: Mental Health and Wellbeing Research Group, Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel (VUB), 103 Laarbeeklaan, 1090 Brussels, Belgium. Electronic address: marijke.de.couck@vub.ac.be.
authors.forename: Marijke
authors.initials: M
authors.lastname: De Couck
authors.affiliation: Department of Gastroenterology, GI Cancer Unit Erasme Universitary Hospital Université Libre de Bruxelles, 808, route de Lennik, 1070 Brussels, Belgium.
authors.forename: Raphaël
authors.initials: R
authors.lastname: Maréchal
authors.affiliation: Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel (VUB), 103 Laarbeeklaan, 1090 Brussels, Belgium.
authors.forename: Sofie
authors.initials: S
authors.lastname: Moorthamers
authors.affiliation: Department of Gastroenterology, GI Cancer Unit Erasme Universitary Hospital Université Libre de Bruxelles, 808, route de Lennik, 1070 Brussels, Belgium.
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Van Laethem
authors.affiliation: Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel (VUB), 103 Laarbeeklaan, 1090 Brussels, Belgium.
authors.forename: Yori
authors.initials: Y
authors.lastname: Gidron
mesh_terms: D000328:Adult; D000369:Aged, 80 and over; D005260:Female; D006339:Heart Rate / Q000502:physiology*; D006801:Humans; D007249:Inflammation / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D015213:Neuroimmunomodulation / Q000502:physiology*; D010190:Pancreatic Neoplasms / Q000401:mortality* / Q000473:pathology / Q000503:physiopathology*; D011446:Prospective Studies; D014630:Vagus Nerve / Q000502:physiology*
keywords: Autonomic nervous system; Inflammation; Neuroimmuno-modulation; Pancreatic cancer; Vagus nerve