Abstract
BACKGROUND: Less than 5% of patients with glioblastoma will survive five years after the diagnosis. Currently, the extent of tumor resection is the only modifiable prognostic variable associated with overall survival. Over the past two decades, the role of vagal nerve activity has been correlated with survival in various types of malignancies. The rationale for examining the prognostic role of vagal nerve activity in cancer is due to its inhibition of inflammation and sympathetic activity, both which otherwise promote tumors. The aim of this study was to examine the prognostic value of vagal nerve activity in patients with newly diagnosed glioblastoma. METHODS: 89 patients with newly diagnosed glioblastoma who underwent biopsy or tumor resection in the neurosurgery department at Rambam medical center were included in this cohort. The predictor was vagal nerve activity indexed by heart rate variability (HRV) and obtained retroactively from 10 s ECGs. The main endpoint was overall survival (OS). RESULTS: The mean (SD) age was 60.1 (11.2) years. Age and KPS were significantly correlated with OS. HRV significantly predicted OS independently of confounders such as age, performance status, or extent of tumor resection (EOR), only among younger patients (<65 years old). Patients with low and high HRV had OS of 13.2 and 20.2 months respectively (p<0.05). We found evidence for a moderating effect of HRV in relation to other prognostic factors. Specifically, EOR predicted death only in patients with low HRV but not with high HRV. CONCLUSIONS: In this study, we have shown for the first time the clinical and prognostic value of vagal nerve activity indexed by measurement of HRV in patients with newly diagnosed glioblastoma. If replicated in prospective studies, vagal nerve activity may have the potential to be a new therapeutic target in newly diagnosed glioblastoma.