# The prognostic and protective roles of heart-rate variability in glioblastoma: making GBM less vague

## TL;DR

This study shows that heart-rate variability, a measure of vagal nerve activity, can predict survival in younger glioblastoma patients and may offer new therapeutic potential.

## Contribution

This is the first study to demonstrate the prognostic and potential therapeutic role of vagal nerve activity in newly diagnosed glioblastoma patients.

## Key findings

- HRV significantly predicted overall survival in younger glioblastoma patients, independent of age and tumor resection extent.
- The effect of tumor resection and performance status on survival was observed only in patients with low HRV.
- Higher HRV was associated with longer survival (20.2 months) compared to lower HRV (13.2 months).

## Abstract

Recent data has shown the role of vagal nerve activity in cancer prognosis. This study examined the prognostic value of vagal nerve activity in patients with newly diagnosed glioblastoma.

Eighty-eight patients underwent a surgical resection or biopsy of glioblastoma in a single institution between 2003 and 2023. Inclusion criteria were: (1) age over 18; (2) diagnosed with newly diagnosed glioblastoma; (3) having an ECG prior to surgery. 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).

HRV significantly predicted OS independent of confounders such as age, performance status, or extent of tumor resection (EOR), but 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. Similarly, KPS tended to predict death only in patients with low, but not high HRV.

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.