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Abstract
Introduction/Background Finding new modifiable prognostic markers is important in ovarian cancer (OC). The autonomic nervous system plays an important role in cancer initiation and progression. Low parasympathetic nervous system activity is associated with inflammation, oxidative stress and sympathetic activation. Low vagal nerve activity, measured by low heart rate variability (HRV) predicts poor cancer prognosis. Our study examined the prognostic value of HRV in OC.
Methodology We conducted a bicentric retrospective study. We analyzed patients diagnosed with serous OC stage FIGO≥IIB, between January 2015 to August 2019, with an electrocardiogram (ECG) available around diagnosis. We used the time domain HRV parameter of the standard deviation of all normal-to-normal beat interval (SDNN) in 10 seconds ECG. Optimal SDNN cut-off was found using the Youden index criteria of time-dependent ROC curve. We carried out multivariable analysis including HRV and well-known OC prognostic factors.
Results We included 202 patients with a median age of 65 years, 93% had stage FIGO IIIC/IV, 56% had complete surgical resection. Median overall survival (OS) was 38.6 months [95%CI:34.4–47.4]. The median SDNN was 11.1 ms (min=1.93; max=74.5), with an optimal cut off of 10 ms to predict OS. Median OS was significantly shorter for patients with low HRV compared to high HRV (26.4 vs 45.1 months; p<0.001). In a multivariable analysis, HRV remained a strong independent prognostic factor with a two-fold higher risk of death among patients with low SDNN compared to those with high SDNN (HR=2.09 [1.40–3.124],p<0.001); other associated factors with higher risk of death were ECOG>0, high CA125 level and incomplete resection.
Overall survival (A) and progression-free survival (B) according to heart rate variability activity (low versus high)
Conclusion High vagal nerve activity, indexed by HRV, is significantly and independently associated with better OS. These results support previous studies on the prognostic role of HRV in cancer and if confirmed in longitudinal studies, call for testing effects of vagal nerve activation among OC patients.