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

Abstract

ObjectiveIdentifying 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.MethodsThis 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.ResultsThe 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).ConclusionLow 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.

The relationship between heart rate variability and TNM stage, co-morbidity, systemic inflammation and survival in patients with primary operable colorectal cancer

“…Given the association of reduced HRV and advanced disease stage 13 , 29 , tumour stage may be a major confounding factor to the relationship between HRV and survival 9 . Indeed, the median SDNN (24.0 ms) and RMSSD (29.8 ms) reported in the present study were higher than those reported by Cherifi and co-workers (Median SDNN 11.1 ms and median RMSSD 11.5 ms 26 . Therefore, further study across a range of disease stages is required to delineate the potential prognostic value of HRV to survival outcomes in patients with cancer.…”

“…A recent study of 272 patients with advanced pancreatic cancer by De Couck and co-workers reported that in patients with longer survival, HRV was inversely associated with a systemic inflammation (CRP) 12 . However, Cherifi and co-workers, in a study of 202 patients with mainly locally advanced or metastatic ovarian cancer, reported that a low HRV was independently associated with survival when adjusted for inflammatory response (Neutrophil: lymphocyte ratio) 26 . Furthermore, to date, the majority of studies that reported a significant association between HRV and survival outcomes in cancer have been of patients with locally advanced or metastatic disease 12 , 26 – 28 .…”

“…However, Cherifi and co-workers, in a study of 202 patients with mainly locally advanced or metastatic ovarian cancer, reported that a low HRV was independently associated with survival when adjusted for inflammatory response (Neutrophil: lymphocyte ratio) 26 . Furthermore, to date, the majority of studies that reported a significant association between HRV and survival outcomes in cancer have been of patients with locally advanced or metastatic disease 12 , 26 – 28 . Given the association of reduced HRV and advanced disease stage 13 , 29 , tumour stage may be a major confounding factor to the relationship between HRV and survival 9 .…”