The promising prognostic value of vagal nerve activity at the initial management of ovarian cancer

François Cherifi; Sophie Lefevre Arbogast; Jonaz Font; Cyril Abdeddaim; Stephanie Becourt; Nicolas Penel; Elodie Coquan; Justine Lequesne; Yori Gidron; Florence Joly

doi:10.3389/fonc.2022.1049970

The promising prognostic value of vagal nerve activity at the initial management of ovarian cancer

Front Oncol. 2022 Nov 29:12:1049970. doi: 10.3389/fonc.2022.1049970. eCollection 2022.

Authors

François Cherifi^{1

2}, Sophie Lefevre Arbogast^{2

3}, Jonaz Font⁴, Cyril Abdeddaim⁵, Stephanie Becourt⁵, Nicolas Penel⁵, Elodie Coquan^{1

2}, Justine Lequesne², Yori Gidron⁶, Florence Joly^{1

3}

Affiliations

¹ Department of Medical Oncology, Centre François Baclesse, Caen, France.
² Department of Clinical Research, Centre Francois Baclesse, Caen, France.
³ Normandie Université, UNICAEN, Institut National de la Santé et de la Recherche Médicale (Inserm) U1086, ANTICIPE, Caen, France.
⁴ Department of Cardiology, Centre Hospitalier Universitaire de Caen, Caen, France.
⁵ Department of Medical Oncology, Centre Oscar Lambret, Lille, France.
⁶ Department of Nursing, Faculty of Health Sciences, Haifa University, Haifa, Israel.

Abstract

Objective: Identifying new modifiable prognostic markers is important for ovarian cancer (OC). Low parasympathic activity is associated with inflammation, oxidative stress and sympathetic nervous system activation. Previous studies reported that low vagal nerve activity, measured by low heart rate variability (HRV), may predict poor cancer prognosis. We aimed to examine the prognostic value of HRV in OC.

Methods: This bicentric retrospective study included patients diagnosed with serous OC FIGO stage ≥IIB, between January 2015 and August 2019, with electrocardiograms (ECG) available around diagnosis. HRV was measured from ECG using the time domain parameter of standard deviation of all normal-to-normal heartbeat intervals (SDNN). Optimal SDNN cut-off was determined using the Youden index criteria of time-dependent ROC curves. We used multivariate cox proportional hazard models to investigate the association between HRV and overall survival (OS), while adjusting for well-known OC prognostic factors.

Results: The 202 patients included were 65.7 years-old on average, 93% had stage FIGO IIIC/IV, 56% had complete surgical resection. Median OS was 38.6 months [95%CI:34.4-47.4]. The median SDNN was 11.1ms, with an optimal cut-off of 10ms to predict OS. OS was shorter for patients with low HRV compared to high HRV (26.4 vs 45.1 months; p<0.001). In multivariate analysis, HRV remained an independent prognostic factor with a two-fold higher risk of death among patients with low SDNN compared to those with high SDNN (HR=2.03, 95%CI=1.35-3.06, p<0.001).

Conclusion: Low HRV, was associated with worse OS in OC patients, supporting previous studies on the prognostic role of HRV in cancer. If replicated in prospective studies, vagal nerve activity may be a new therapeutic target in OC.

Keywords: autonomic nervous system; heart rate variability (HRV); ovarian cancer; parasympathetic activity; prognostic factor and survival; vagus nerve.