Cardiac autonomic dysfunction in patients with cancer: exploring the role of physical exercise.

Introduction

Advances in early detection and therapeutic strategies have significantly increased five-year survival among patients with cancer (Allemani et al. 2018 ), leading to a high number of survivors (WHO 2021 ). Despite enhancements in the oncological outcomes, patients and survivors have a high risk of morbidity and mortality from non-cancer causes, including cardiovascular disease (CVD) (Aleman et al. 2014 ). In this sense, a population-based study found that 11.3% of patients with cancer died from CVD, and among these, 76.3% of deaths were from heart disease (Sturgeon et al. 2019 ). Patients with cancer are likely at elevated risk of developing CVD, mainly due to age-related diseases, unhealthy lifestyle behaviors, as well as the direct effects of anticancer treatment (e.g., chemotherapy), also known as cardiovascular toxicity (Gilchrist, Barac et al. 2019 ). Cardiac autonomic dysfunction, i.e., impairment of autonomic control of the cardiovascular system, is considered an early marker for CVD (Kirkham et al. 2019 ), and it is highly prevalent in patients with cancer, affecting up to 80% of individuals (Coumbe and Groarke 2018 ). Among the possible strategies, physical exercise has been suggested as a potential intervention to prevent and ameliorate autonomic dysfunction due to improvement in autonomic function. Whereas the importance of cardiac autonomic modulation and the effect of exercise on it is widely studied and recognized, particularly in healthy subjects or populations affected by CVD, less is known within the oncological context. With these premises, the aim of the current review is to provide an overview of the assessment methods and clinical implications of autonomic dysfunction in patients with cancer. Moreover, we examine the factors influencing autonomic function in cancer patients, as well as the potential benefits of physical exercise to prevent and/or mitigate its dysregulation.

Cardiac autonomic control and methods of assessment

The autonomic nervous system modulates heart activity, contributing to its function by regulating heart rate, cardiac output, and the contraction force of the heart. The cardiac plexus comprises sympathetic and parasympathetic fibers with afferent and efferent nerves (Drew and Sinoway 2012 ). The sympathetic part derives from the lower cervical and upper thoracic ganglia, and its axons reach the heart, innervating the sinoatrial node, the heart’s conduction system, and the coronary vessels, and are distributed throughout the atrial and ventricular musculature (Drew and Sinoway 2012 ). The sympathetic branch is responsible for increasing heart rate, increasing the force of contraction of the myocardium, and coronary vasoconstriction (Drew and Sinoway 2012 ). The parasympathetic fibers directed to the heart originate in the dorsal motor nucleus of the vagus nerve and the nucleus ambiguous (Drew and Sinoway 2012 ). Their axons, as part of the vagus nerve, reach the postganglionic neurons located in the cardiac plexus, walls of the atria and end in the sinoatrial and atrioventricular nodes, as well as atrial musculature (Drew and Sinoway 2012 ). The parasympathetic branch is responsible for reducing heart rate, blood pressure, and the heart contraction force and counterbalancing the sympathoexcitation (Drew and Sinoway 2012 ). The balance between sympathetic and parasympathetic systems determines the autonomic control of the heart, which is considered a marker of the body’s homeostasis (see Fig. 1 .). Dysregulation of the normal autonomic regulation (i.e., autonomic dysfunction) usually refers to an increase in sympathetic activity and a reduction in the parasympathetic pathways and is associated with several adverse effects, such as promotion of carcinogenesis, CVDs, oxidative stress and chronic inflammation (Goldberger et al. 2019 ).

Cardiac autonomic function can be assessed through a variety of techniques (Goldberger et al. 2019 ). Among the heart-based tests, resting heart rate, recovery heart rate, or QT-RR slope are simple and frequently used methods to quantify autonomic dysfunction (Goldberger et al. 2019 ); nevertheless, heart rate variability (HRV), i.e. the quantification of fluctuations in R-wave to R-wave intervals, is considered a more robust measure for evaluating cardiac parasympathetic modulation (Goldberger et al. 2019 ). An adaptive response of the autonomic nervous system and sinoatrial node to environmental fluctuations leads to heightened HRV, typically suggestive of a robust and healthy heart (Martinez et al. 2024 ). Conversely, a decrease in HRV usually signals a diminished capacity or dampening in the responsiveness of the autonomic nervous system or sinoatrial node to changes (Martinez et al. 2024 ). Assessments of HRV can be categorized into time-domain (the quantification of the variability of interbeat interval), frequency-domain (the determination of the power distribution), and non-linear (the quantification of the unpredictability of a time series) analysis (Goldberger et al. 2019 ). More than 70 variables may be extracted from the HRV analysis (Shaffer and Ginsberg 2017 ). The main HRV measures are summarized in Table 1 . However, since heart rate can be influenced by a variety of environmental stimuli and workloads, investigating HRV requires considering several aspects, such as the subject’s respiration, sampling frequency, and detection method (Laborde et al. 2017 ; Goldberger et al. 2019 ). Moreover, according to the parameters of interest, the recording period may vary from a range of a few seconds to 24 h (Laborde et al. 2017 ; Goldberger et al. 2019 ). In recent years, in addition to traditional methods such as the electrocardiogram, which remains the gold standard for HRV assessment due to its accuracy and ability to capture high-resolution R-R intervals, several portable and user-friendly technologies have emerged. These include heart rate monitor bands, chest straps, and smartphone applications that utilize photoplethysmographic sensors to estimate HRV. While these tools offer practical advantages for large-scale monitoring and daily self-assessment, particularly in non-clinical settings, it is important to consider their limitations in terms of signal quality, sampling rate, and susceptibility to motion artifacts. Therefore, their use should be tailored to the context of evaluation and the precision required (Li et al. 2023 ).

Table 1 The most common indexes of heart rate variability Variability analysis HRV parameter Variable Units Description Physiological interpretation Time domain Statistical HR max – HR min bpm Heart rates range from HR max to HR min Heart rate variability during the recording period SDNN ms Standard deviation of RR intervals Overall HRV; both sympathetic and parasympathetic activity SDANN ms Standard deviation of the averages of RR intervals in 5-min segments Long-term components of HRV RMSSD ms Root mean square of successive RR intervals differences Short-term HRV; a marker of parasympathetic activity SDNN Index ms Standard deviation of differences between adjacent RR intervals Average variability over 5-minute segments; overall HRV NN50 bpm Number of pairs of adjacent intervals differing more than 50 ms Marker of parasympathetic activity pNN50 % Percentage of successive RR intervals that differ more than 50 ms Marker of parasympathetic activity Geometric HRV triangular index - The integral of the density of the RR intervals histogram divided by its height Overall HRV TINN ms Baseline width of the RR intervals histogram Overall HRV; geometric measure Frequency domain Short-term recording Total power ms 2 The variance of all RR intervals over the temporal segment Total HRV across all frequencies ULF ms 2 Power of the ultra-low frequency Long-term regulatory mechanisms (e.g., circadian rhythms) VLF ms 2 Power of the very low frequency (0.0033–0.04 Hz) Thermoregulation, hormonal, and other slower regulatory mechanisms LF ms 2 Power of the low frequency (0.04–0.15 Hz) Sympathetic and parasympathetic activity (predominantly sympathetic) Long-term recording HF ms 2 Power of the high frequency (0.15–0.40 Hz) Parasympathetic activity LF/HF % Ratio from low to high frequency Sympathovagal balance Non-linear measures Poincare analysis S ms Area of the ellipse, representing total variability Total HRV SD1 ms Standard deviation perpendicular to the line of identity Short-term HRV; parasympathetic activity SD2 ms Standard deviation along the line of identity Both long- and short-term HRV SD1/SD2 % Ratio of SD1 to SD2 Balance between short- and long-term variability Entropy analysis ApEn - Approximate entropy, measure the regularity and complexity of a time series Complexity and irregularity of the time series SampEn - Sample entropy, measure the regularity and complexity of a time series Improved entropy estimate; complexity and irregularity Detrended fluctuation analysis DFA α 1 - Detrended fluctuation analysis that describes short-term fluctuations (< 10–11 beats) Short-term fractal scaling of HRV DFA α 2 - Detrended fluctuation analysis that describes long-term fluctuations (> 10–11 beats) Long-term fractal scaling of HRV D 2 - Correlation dimension (estimate the minimum number of variables needed to construct a model of system dynamics) Complexity; number of variables to model dynamics Recurrence quantification analysis Lmean beats Mean diagonal line length of R-R intervals Predictability and structure in HRV Lmax beats Maximal diagonal line length of R-R intervals Longest stable pattern; complexity REC % Percentage of recurrence points in the recurrence plot Overall recurrence of patterns DET % Ratio of recursive points forming a 45° diagonal structure to all recursive points in the recurrence plot Predictability and deterministic structure ShanEn - Complexity of the length distribution of diagonal structures in the recurrence plot Complexity of recurrence patterns Abbreviations : ms, milliseconds; bpm, beats per minute; %, percentage;

Causes of the autonomic dysfunction in cancer

In the oncological setting, patients are exposed to a high risk of CVD. Insults at the pericardium, myocardium, valves, cardiac innervation, and vessels, which are frequently observed in patients with cancer, resulting in an increased risk of CVD, such as heart failure, atherosclerosis, arrhythmias, hypertension, and pericarditis (Zamorano et al. 2016 ). Recently, cardiac autonomic dysfunction has been associated with increased inflammation, oxidative stress, and metastatic dissemination, leading to a negative impact on cancer progression and mortality and the development of CVDs (Martinez et al. 2024 ). Multiple factors can contribute to the development of cardiovascular autonomic dysfunction in patients with cancer, which can be classified as disease-related, lifestyle-related, and physiological variables (Fig. 2 .).

Physiological variables

Regarding physiological variables, cardiac autonomic modulation is affected by age and gender. Young subjects and females usually exhibit greater vagal activity (Koenig and Thayer 2016 ). In addition, hormonal status plays a significant role in autonomic regulation. For instance, estrogens are known to exert cardioprotective effects and are associated with enhanced parasympathetic activity and improved HRV parameters. This partially explains the higher vagal tone observed in premenopausal women compared to men of the same age, as well as the decline in HRV following menopause (Ramesh et al. 2022 ). Circadian rhythm is another important modulator of autonomic balance. HRV follows a diurnal pattern, typically showing higher parasympathetic activity during nighttime sleep and higher sympathetic dominance during the day. Disruptions in circadian rhythms, which are common in patients with cancer due to treatment schedules, hospitalizations, or psychological distress, may contribute to autonomic imbalance (Touitou et al. 2017 ).

Disease-related variables

Among the disease-related factors, the inflammation associated with cancer, as well as its progression and severity (Magnon 2015 ), and comorbidities (e.g., diabetes) (Yu and Lee 2021 ), may predispose patients to develop autonomic dysfunction. Additionally, different cancer treatments, such as some types of chemotherapy and radiation therapy, may expose patients to neuro- and cardiac toxicity (Clark et al. 2019 ; Montisci et al. 2021 ). Chemotherapy agents, such as platinum-based compounds, vinca alkaloids, and taxanes, are associated with dose-dependent neurotoxicity and, for this reason, might exert a negative effect on cardiovascular autonomic modulation, even though the evidence is currently limited to small studies reporting mixed results (Coumbe and Groarke 2018 ). Anthracyclines have a recognized negative impact dose-dependent on cardiac function, which can cause irreversible heart failure (Larsen et al. 2023 ) and, additionally, may have a toxic effect on autonomic modulation. In this sense, changes in HRV indexes were observed after the first dose of anthracycline, and some preliminary evidence is that this relationship may be dose-dependent (Coumbe and Groarke 2018 ; Stachowiak et al. 2018 ). Whereas preclinical studies have suggested toxicity of the autonomic nervous system deriving from bevacizumab, an angiogenetic agent (Storkebaum et al. 2010 ), a small investigation conducted on patients with cancer did not detect any significant change in HRV parameters (McIntyre et al. 2016 ). Radiotherapy, especially targeting the cranium, neck, and mediastinum, may damage components of the autonomous nervous system. Indeed, there are several reports of impairments in the regulation of the autonomic function of the heart after irradiation, and it seems that the risk increases with dose of radiotherapy (Teng et al. 2021 ).

Lifestyle-related variables

Regarding lifestyle, it is well established that unhealthy behaviors such as chronic psychological stress, physical inactivity, poor sleep quality, tobacco use, excessive alcohol consumption, and a high body mass index (BMI) are associated with autonomic imbalance, generally characterized by reduced vagal activity and heightened sympathetic output, ultimately leading to lower HRV. These lifestyle-related factors not only contribute to the onset and progression of cardiovascular diseases but also represent modifiable determinants of autonomic dysfunction in both healthy and clinical populations, including patients with cancer.

Cancer diagnosis and treatments may significantly impact several lifestyle habits. Daily alcohol consumption and smoking decrease only slightly after a diagnosis, indicating that a relevant proportion of patients still remain alcohol drinkers and/or smokers (Williams et al. 2013 ). Additionally, patients with cancer often exhibit low levels of physical activity (Avancini et al. 2023 ), which tend to decrease even further after the diagnosis and, at the same time, increase their sedentary behavior (Williams et al. 2013 ). Psychological impairments are also frequently observed in patients with cancer, with 19.0% and 12.9% of them reporting clinical levels of anxiety and depression, respectively, (Linden et al. 2012 ), and 55% experiencing significant distress (Carlson et al. 2019 ). Sleep disruption is common during anticancer treatment, with 36.6% and 43% of patients having insomnia symptoms and meeting the criteria for symptoms of insomnia during chemotherapy (Palesh et al. 2010 ). Another issue to keep in mind regards the variation of body composition. On one side, weight increments, particularly in fat mass, are common for some types of cancers and treatments, such as breast and prostate cancer treated with hormone therapy; additionally, other drugs, such as corticosteroids, frequently prescribed in oncology may contribute to increasing adipose tissue (Bradshaw 2024 ). Moreover, a progressive loss of muscle mass, contributing to the development of sarcopenia or cachexia, is another feature of body composition, more prevalent in patients affected by pancreatic, lung, or head/neck cancers (Avancini et al. 2021 ). All these impairments in lifestyle-related features are recognized factors that may negatively affect autonomic function through an increase in the activation of the sympathetic nervous system and a decrease in the activation of the parasympathetic nervous system (Martinez et al. 2024 ).

Heart rate variability and clinical implications in cancer

Heart rate variability, cancer survival, and progression

Several investigations explored the correlation between HRV parameters and clinical outcomes (Table 2 .). Most of the studies (14), focused on overall survival (OS)(Kim et al. 2010 ; De Couck et al. 2013 ; Wang et al. 2013 ; Gidron 2014 ; Giese-Davis et al. 2015 ; Guo et al. 2015 ; De Couck et al. 2016 ; Strous et al. 2020 ; Ciurea et al. 2021 ; Cherifi et al. 2022 ; Li, Wu et al. 2022 ; Wu et al. 2022 ; McGovern et al. 2023 ; Wu et al. 2023 ), three on progression-free survival (PFS)(Strous et al. 2020 ; Cherifi et al. 2022 ; Atar et al. 2023 ), two examined the duration until death(Chiang et al. 2010 ; Masel et al. 2014 ), and one explored the 7-day survival time(Chiang et al. 2013 ).

Table 2 Main studies investigating the association between HRV with survival in patients with cancer Author, year, and study design Patients Domain Cut - off Cardiac Patients Main Findings Ciurea et al., 2021 (Ciurea et al. 2021 ) Retrospective study 231 patients with hepatocellular carcinoma, stage ND 20–30 h ECG ▪ Time domain : SDNN; rMSSD; MSD; pNN50 ▪ Frequency domain : ULF; VLF; LF; HF ▪ SDNN: 110 ms ▪ MSD: 49.2 ms ▪ rMSSD: 91 ms ▪ ULF: 860.3 ms 2 ▪ VLF: 2438 ms 2 ▪ LF: 911 ms 2 No ▪ SDNN < 110 ms predicts worse OS (HR = 1.32, 95% CI: 1.24–1.41; p < 0.001) and low 3-years survival (HR = 3.43, 95% CI: 2.45–4.81; p < 0.001); ▪ ULF < 860.3 ms 2 predicts worse OS (HR = 3.46, 95% CI: 2.06–5.75; p < 0.001) and low 3-years survival (HR = 3.41, 95% CI: 2.45–4.75; p < 0.000); ▪ VLF < 2438 ms 2 predicts worse OS (HR = 3.23, 95% CI: 1.94–5.37; p < 0.001); ▪ LF < 911.2 ms 2 predicts worse OS (HR = 2.83, 95% CI: 1.75–4.57; p < 0.001); ▪ HF < 805.2 ms 2 predicts worse OS (HR = 1.44, 95% CI: 1.01–2.05; p = 0.043); ▪ MSD > 49.2 ms predicts better 3-year survival (HR = 1.73, 95% CI: 1.26–2.38; p = 0.01); Chiang et al. 2010 , (Chiang et al. 2010 ) Prospective study 33 patients with hepatocellular carcinoma, stage ND 5 min ECG ▪ Frequency domain : LF; HF; TP; LF/HF ▪ ND No ▪ TP is significantly correlated with TTD ( r = 0.55; p = 0.001); ▪ HF is significantly correlated with TTD ( r = 0.44; p = 0.010); ▪ LF/HF was not significantly correlated with TTD ( p = 0.390); Chiang et al. 2013 , (Chiang et al. 2013 ) Prospective study 138 patients with mixed cancer, stage advanced 5 min ECG ▪ Frequency domain : LF; HF; TP; LF/HF; ▪ logHF: 2 No ▪ logHF power < 2 predicts a higher 7-day survival (OR = 3.8, 95% CI: 1.49–11.12; p = 0.008); ▪ logTP was inversely associated with a survival of 7 days or less ( p = 0.021); De Couck et al. 2013 , (De Couck et al. 2013 ) Historical prospective study 113 patients with prostate and 133 with NSCLC, stage II-IV 10 s ECG ▪ Time domain : SDNN; rMSSD ▪ SDNN: 20 ms ▪ rMSSD: 20 ms No ▪ SDNN is related to PSA levels ( r =-0.434; p = 0.004) at 6 months from diagnosis in prostate cancer; ▪ RMSSD is related to PSA levels at 6 months ( r =-0.437; p = 0.004) and at 2 years ( r =-0.381; p = 0.013) from diagnosis in prostate cancer; ▪ No significant correlation in patients with prostate cancer stage II-III between SDNN, rMSSD, and PSA level at 6 months and 2 years ( p > 0.05); ▪ SDNN ( r =-0.895; p < 0.05) and rMSSD ( r =-0.804; p < 0.05) are correlated with PSA levels at 6 months ( r =-0.804; p < 0.05), but not at 2 years ( p > 0.05) in patients with prostate cancer stage IV; ▪ No significant correlation between stage and SDNN with OS (B=-0.068; p = 0.737) in patients with NSCLC; ▪ SDNN, rMSSD are not correlated with OS ( p = 0.357; p = 0.364) and survival time ( p = 0.435; p = 0,340) in patients with NSCLC; ▪ SDNN ( r = 0.278; p = 0.032) and rMSSD ( r = 0.282; p = 0.029) are correlated with survival time in patients with NSCLC, age < 65 years; ▪ SDNN ( r =-0.174; p = 0.247) and rMSSD ( r =-0.144; p = 0.340) are correlated with survival time in patients with NSCLC, age ≥ 65 years; De Couck et al. 2016 , (De Couck et al. 2016 ) Historical prospective study 272 pts with pancreatic cancer, stage locally advanced and metastatic 10 s ECG ▪ Time domain : SDNN; rMSSD ▪ SDNN: 20 ms Yes ▪ SDNN is significantly associated with OS (B=-0.301; p = 0.047) in the multivariate analysis; ▪ SDNN is inversely correlated with CRP ( r =-0.15; p = 0.007) and positively to survival time ( r = 0.18; p = 0.003); ▪ Adding CRP in the multivariate regression model, SDNN is no longer associated with OS (B = 0.26; p = 0.116) ▪ SDNN is unrelated to CRP ( r =-0.07; p = 0.55) in patients surviving up to one month; ▪ SDNN is inversely correlated to CRP ( r =-0.17; p = 0.04), in patients surviving longer than one month; Fadul et al., 2010 (Fadul et al. 2010 ) Historical prospective study 47 male patients with mixed cancer, stage locally advanced or metastatic 20 min ECG ▪ Time domain : SDNN ▪ Frequency Domain : VLF; LF; HF ▪ ND Yes ▪ SDNN is not associated with survival in days ( p = 0.056); ▪ HF ( p = 0.12), LF ( p = 0.73) and VLF ( p = 0.23) are not associated with survival in days; Gidron et al. 2018 , (Gidron 2014 ) Historical prospective study 202 patients with pancreatic cancer and 71 patients with NSCLC, stage advanced 10 s ECG ▪ Time domain : rMSSD ▪ ND Yes ▪ NIM index predicts OS in patients with pancreatic cancer (RR = 0.68; 95% CI: 0.51–0.92; p = 0.011) and with NSCLC (RR = 0.53; 95% CI: 0.31–0.88; p = 0.010); ▪ NIM index scores are significantly correlated with survival time ( r = 0.31; p = 0.010); Giese-Davis et al. 2015 , (Giese-Davis et al. 2015 ) Prospective study 87 patients with metastatic or recurrent breast cancer 5 min ECG ▪ Frequency domain : HF ▪ ND No ▪ Higher baseline HF-HRV predicted longer survival (HR = 0.75, 95% CI: 0.60 to 0.92; p = 0.006); ▪ A combination of HF and HR (HF/HR) improved survival prediction (HR = 0.64, 95% CI: 0.58–0.85; p = 0.002) Gou et al., 2015 (Guo et al. 2015 ) Retrospective study 651 patients with mixed solid and hematological tumors, stage I-IV 20–24 h ECG ▪ Time domain : SDNN; rMSSD; SDANN; pNN50 ▪ SDNN: 70 ms No ▪ SDNN < 70 ms predicts a lower survival (HR = 1.9, 95% CI: 1.4–2.5; p < 0.0001) Kim et al., 2010 (Kim et al. 2010 ) Retrospective study 68 patients with mixed cancer, stage ND 5 min BFM-5000 Plus (Medi-Core Co. Ltd., Seoul, Korea) ▪ Time domain : SDNN; rMSSD ▪ Frequency domain : TP; LFP; HFP; LFP/HFP ▪ SDNN: 21.3 ms ▪ RMSSD: 16.975 ms ▪ TP: 358.425 ms 2 ▪ LFP: 100.3 ms 2 ▪ HFP: 62.4 ms 2 ▪ LFP/HFP: 3.345 No ▪ SDNN predicts survival (HR = 0.062; 95% CI: 0.006 to 0.673; p = 0.022); ▪ RMSSD, TP, LFP, HFP, and LFP/HFP do not predict survival ( p > 0.05); Mouton et al. 2012 , (Mouton et al. 2012 ) Historical Prospective study 38 patients with colon cancer, stage I-IV 10 s ECG ▪ Time domain : SDNN; rMSSD ▪ SDNN: 20 ms No ▪ SDNN is correlated with CEA at 12 months from diagnosis ( r =-0.435; p = 0.006) ▪ Patients with low SDNN have significantly higher CEA levels at 12 months ( p = 0.006); ▪ SDNN is correlated with CEA in patients receiving palliative treatments ( r =-0.58; p = 0.018); Wang et al., 2013 (Wang et al. 2013 ) Prospective study 40 patients with metastatic brain cancer, stage IV 5 min ECG ▪ Time domain : SDNN; rMSSD ▪ SDNN: 10 ms ▪ rMSSD: 7 ms No ▪ Low SDNN predicts worse OS (HR = 2.204, 95% CI: 1.046–4.733; p = 0.039); ▪ RMSSD does not predict OS ( p = 0.868); Strous et al. , 2020 ( Strous et al. 2020 ) Retrospective study 428 patients with colorectal cancer, stage I-III 10 s ECG ▪ Time domain : SDNN; rMSSD ▪ SDNN: 20 ms ▪ rMSSD: 19 ms No ▪ SDNN does not predict OS ( p = 0.829) and cancer-free survival ( p = 0.924); ▪ RMSSD does not predict OS ( p = 0.274) and cancer-free survival ( p = 0.511); ▪ No significant association between SDNN and CEA-levels (OR = 1.342, 95% CI: 0.679–2.653; p = 0.397) and rMSSD and CEA-levels (OR = 1.207, 95% CI: 0.608–2.394; p = 0.590) Li et al. 2022 (Li, Wu et al. 2022 ) Prospective study 56 patients with lung cancer, stage ND 5 min ECG ▪ Non-linear domain : Lmean; Lmax; REC; DET; ShanEn ▪ Lmax: 376 ▪ REC (%): 42.8 ▪ DET (%): 98,2 ▪ ShanEn: 3.7 No ▪ Lmax predicts survival time (HR = 0.318, 95% CI: 0.151–0.669; p = 0.003); ▪ Lmean ( p > 0.05), REC % ( p = 0.147), DET % ( p = 0.139), and ShanEn ( p = 0.354) do not predict OS ( p > 0.05); Cherifi et al., 2022 (Cherifi et al. 2022 ) Retrospective study 202 patients with ovarian cancer, stage II-IV 10 s ECG ▪ Time domain : SDNN; rMSSD ▪ SDNN: 10 ms ▪ rMSSD: 10 ms No ▪ Low SDNN predicts worse OS (HR = 2.03; 95% CI:1.35–3.06; p < 0.001); ▪ Low rMSSD predicts worse OS (HR = 2.05, 95% CI:1.37–3.06; p < 0.001); ▪ SDNN and rMSSD are not associated with PFS; McGovern et al., 2023 (McGovern et al. 2023 ) Retrospective study 439 patients with colorectal cancer, stage I-III 10 s ECG ▪ Time domain : SDNN; rMSSD ▪ SDNN: 24 ms ▪ rMSSD: 29.8 ms No ▪ SDNN is not associated with OS ( p = 0.329); ▪ RMSSD is not associated with OS ( p = 0.148); Wu et al., 2023 (Wu et al. 2023 ) Prospective study 78 patients with advanced NSCLC, stage III-IV 5 min ECG ▪ Time domain : SDNN; rMSSD ▪ Frequency domain : TP; HF; LF; LF/HF ▪ Non-linear domain : ApEn; SampEn; Lmean; Lmax; REC; DET; ShanEn ▪ SDNN: 23.5 ms ▪ rMSSD: 8.9 ms ▪ TP: 67 ms 2 ▪ LF: 31 ms 2 ▪ HF: 5 ms 2 ▪ LF/HF: 4.950 ▪ ApEn: 1.140 ▪ SampEn: 1.620 ▪ Lmean: 10.74 beats ▪ Lmax: 195.0 beats ▪ REC: 33.3% ▪ DET: 97.93% ▪ ShanEn: 3.121 No ▪ HF predicts OS (HR = 2.108, 95% CI: 1.035–4.291; p = 0.040); ▪ REC predicts survival (HR = 0.415, 95% CI: 0.192–0.896; p = 0.025); ▪ DET predicts OS (HR = 0.432, 95% CI: 0.200-0.935; p = 0.033); ▪ Lmax, SDNN, rMSSD, LF, LF/HF do not predict OS ( p > 0.05); Wang et al., 2021 (Wang et al. 2021 ) Prospective study 46 patients with breast cancer, stage ND 5 min ECG ▪ Time domain : SDNN; rMSSD ▪ Frequency domain : HF, LF; LF/HF ▪ ND No ▪ RMSSD is correlated with prothrombin time ( r = 0.331; p = 0.025) ▪ HF is correlated with prothrombin time ( r = 0.292, p = 0.049); ▪ LF is correlated with prothrombin time ( r =-0.395, p = 0.007); ▪ HF is correlated with prothrombin time ( r = 0.397, p = 0.006); ▪ LF/HF is correlated with prothrombin time ( r =-0.368, p = 0.012); ▪ All HRV parameters are not correlated with thrombin time; Wu et al., 2022 (Wu et al. 2022 ) Prospective study 56 patients with lung cancer with brain metastases, stage IV 5 min ECG ▪ Time domain : SDNN; rMSSD ▪ SDNN: 13 ms ▪ rMSSD: 4.8 ms No ▪ RMSSD predicts survival (HR = 3.457, 95% CI: 1.303–9.171; p = 0.013); ▪ SDNN does not predict survival ( p = 0.062); Masel et al., 2014 (Masel et al. 2014 ) Prospective study 60 patients with advanced cancer, stage IV 24 h ECG ▪ Time domain : pNN50 ▪ Frequency domain : TP; HF; LF; logHF/LF ▪ ND No ▪ HRV was not correlated with the number of days until death Hu et al., 2018 (Hu et al. 2018 ) Retrospective Study 383 patients with cervical cancer, stage I-IV 20 min ECG ▪ Time domain : SDNN; rMSSD ▪ SDNN: 20 ms No ▪ Low SDNN predicts high CRP ( p = 0.031); Liu et al., 2021 (Liu et al. 2021 ) Cohort Study 56 patients with cervical cancer, stage ND 5 min ECG ▪ Frequency domain : HF; LF; LF/HF ▪ Non-linear domain : SD1; SD2; SD2/SD1 ▪ ND No ▪ SD2 is significantly correlated with platelet to lymphocyte ratio ( p = 0.09); ▪ LF/HF significantly correlated with neutrophil to lymphocyte ratio ( p = 0.036); Atar et al., 2023 (Atar et al. 2023 ) Retrospective study 29 patients with B-cell lymphoma and 37 patients with multiple myeloma, stage ND 10 s ECG ▪ Time domain : SDNN; rMSSD ▪ SDNN: 12 ms ▪ rMSSD: 30 ms No ▪ SDNN predicts survival (HR = 0.2, 95% CI: 0.06–0.69; p = 0.01) in diffused large B-cell lymphoma; ▪ RMSSD predicts PFS in multiple myeloma (HR = 0.191, 95% CI:0.04–0.9; p = 0.03); ▪ SDNN does not predict PFS in multiple myeloma ( p > 0.05); ▪ RMSSD is not correlated with CRP in multiple myeloma; Abbreviations: ND , not defined; HR , heart rate; SDNN , standard deviation of NN intervals; MSD , mean successive difference in normalized R-R intervals; rMSSD , root mean square of successive differences; SDANN , 24-h standard deviation of average NN intervals; pNN50 , percentages of differences between adjacent normal NN intervals > 50 ms; LF , low- frequency power (0.04–0.15 Hz); HF , high-frequency power (0.15–0.4 Hz); LF/HF , low to high-frequency power ratio; TP , total power; VLF , very low frequency (0.0033–0.04 Hz); SD1 , standard deviation of instantaneous beat-to-beat variability; SD2 , long-term standard deviation of continuous RR intervals; RRtri , RR triangular; ApEn , approximate entropy; SampEn , sample entropy; OS , overall survival; TTD , time to death; CEA , carcinoembryonic antigen; PSA , prostate-specific antigen; NSCLC , non-small cell lung cancer; Lmax , maximal diagonal line length; Lmean , mean diagonal line length; PFS , progression free survival; NIM index , neuroimmunomodulation index (HRV/CRP)

A significant correlation between time domain values of HRV and survival was reported in the majority of the studies (10/14) (Kim et al. 2010 ; De Couck et al. 2013 , 2016 ; Wang et al. 2013 ; Guo et al. 2015 ; Gidron et al. 2018 ; Ciurea et al. 2021 ; Cherifi et al. 2022 ; Wu et al. 2022 ; Atar et al. 2023 ). Indeed, Cherifi et al. , in a cohort of 202 patients with ovarian cancer (stage IIIC-IV) who underwent chemotherapy and/or surgery, found that OS was shorter in patients having low HRV values than those who presented a high HRV (26.4 vs. 45.1 months p < 0.001). In the multivariate analysis, HRV remained an independent prognostic factor with a two-fold higher risk of death among patients with SDNN < 10 milliseconds (ms) (HR = 2.03; 95% CI: 1.35–3.06) (Cherifi et al. 2022 ). Similarly, in a sample of 272 patients with locally advanced or metastatic pancreatic cancer, HRV was an independent prognostic factor, even after adjusting for potential confounders, and SDNN > 20 ms was associated with longer survival (133.5 vs. 64.0 days, p = 0.001) (De Couck et al. 2016 ).

Two recent studies employed a non-linear analysis method known as recurrence quantification analysis (RQA), which is more suitable for analyzing physiological parameters such as HRV and effectively represents the complexity of heartbeat interval. RQA indexes showed the potential to evaluate prognosis in patients with lung cancer. In the prospective study of Li et al. , the Lmax parameter, which depicts the complexity of heartbeat intervals, was significantly associated with survival time independently from confounders (HR = 0.318, 95% CI: 0.151–0.669) in a cohort of 56 patients with lung cancer affected by brain metastasis (Li, Wu et al. 2022 ). Similar findings were observed in a sample of 78 patients with advanced non-small cell lung cancer after palliative treatments, in which different RQA indexes were significantly correlated with OS (Wu, Li Wu et al. 2023a , b ).

By contrast, the prognostic role of frequency domain parameters appears more debated across the research (Chiang et al. 2010 , 2013 ; Ciurea et al. 2021 ). A retrospective study on 231 patients with hepatocellular carcinoma exhibiting lower frequency domain indices, including ULF, VLF, LF, and HF (see Table 1 .), had a 3-year shorter survival compared to those who presented higher levels (23.4% vs. 38.33%, p < 0.001) (Ciurea et al. 2021 ). Conversely, two investigations conducted in patients with mixed cancer types did not detect any significant association between frequency domains and survival (Chiang et al. 2010 , 2013 ).

Regarding the possibility of predicting PFS, it has been hypothesized that an active vagus nerve could slow tumor progression and metastasis by inhibiting inflammation, oxidative stress, and the release of sympathetic neurotransmitters (De Couck et al. 2018 ). However, to date, it is yet to be determined the degree of association between HRV and PFS (Strous et al. 2020 ; Cherifi et al. 2022 ; Atar et al. 2023 ). In this regard, Atar et al. found that an RMSSD > 30 ms could be used to significantly predict PFS in a sample of 37 patients with multiple myeloma independently of confounders (HR = 0.191; 95% CI: 0.04–0.90) (Atar et al. 2023 ). Conversely, in the study of Strous et al. , preoperative HRV did not significantly predict either PFS or the severity of postoperative complications in 428 patients with colorectal cancer candidate for surgery (Strous et al. 2020 ).

Overall, it appears that HRV, expressed through time domain indexes, may have an association with survival in cancer, whereas the evidence regarding the frequency domain parameters and the ability to predict PFS remains to be defined. Beyond the study designs, which are often retrospective, other factors should be taken into account when interpreting the results. First, the heterogeneity in the study population. Indeed, several/most of the studies included a mixed cancer population in terms of cancer type and stage. It could be possible that HRV would be a prognostic factor in some malignancies and not in others, depending on the clinical stage of the disease. In addition, another issue to consider is the lack of precise cut-off for HRV values across the investigations (Wang et al. 2013 ; Guo et al. 2015 ; Ciurea et al. 2021 ; Cherifi et al. 2022 ). Future studies exploiting a well-defined study design, focusing on a specific population in terms of cancer type and stage, could help to evaluate the real influence of an impaired vagal tone.

Association between heart rate variability and tumor markers

Four studies examined the association between HRV and serum levels of tumor markers (e.g., prostate-specific antigen (PSA), carcinoembryonic antigen (CEA) (Mouton et al. 2012 ; De Couck et al. 2013 ; Gidron Y 2014 ; Strous et al. 2020 ). For instance, De Couck et al. demonstrated that SDNN and rMSSD significantly correlated with levels of PSA at 6 months and two years in patients with prostate cancer undergoing hormonal therapy, chemotherapy, or radiotherapy, even after adjusting for confounding factors. Notably, this association was found only in patients with metastatic disease, probably suggesting an interaction effect based on cancer stage (De Couck et al. 2013 ). This assumption can be further strengthened by the evidence derived from colorectal cancer. Indeed, whereas a significant association between SDNN and blood CEA levels was found in 72 patients with stage IV colorectal cancer (Gidron Y 2014 ), no significant relationship was observed in a cohort of 428 patients with early-stage disease (Strous et al. 2020 ).

Heart rate variability and systemic inflammation

It is well-established that vagus nerve stimulation can reduce systemic inflammation, mainly due to regulating the hypothalamic-pituitary axis and the cholinergic anti-inflammatory pathway. This activity of the vagal nerve may be crucial, considering that systemic inflammation is one of the main hallmarks of cancer (Singh et al. 2019 ). Five studies found a significant association between HRV and inflammation (De Couck et al. 2016 ; Hu et al. 2018 ; Liu et al. 2021 ; Atar et al. 2023 ; McGovern et al. 2023 ). For instance, in a cohort of 56 patients with cervical cancer, preoperative HRV was found to correlate with a lower postoperative platelet-lymphocyte ratio and a higher neutrophil-lymphocyte ratio (Liu et al. 2021 ). Moreover, a study found an association with C-reactive protein; in particular, Hu et al. , in a sample of 383 patients affected by gastric cancer, higher SDNN, and rMSSD were significantly correlated with lower levels of C-reactive protein (Hu et al. 2018 ).

The association between HRV and biological markers remains under investigated. Nevertheless, given the promising results, this may be an area of future research that might also explore the underlying mechanisms by which autonomic dysfunction may interact with cancer disease and treatment.

Physical exercise as intervention to improve heart rate variability in patients with cancer?

Observational studies have resulted in evidence that being physically active after a diagnosis of cancer is associated with prolonged survival (Patel et al. 2019 ; Verheijden et al. 2023 ). Additionally, randomized controlled trials have demonstrated the beneficial effects of physical exercise in improving the physical fitness components (i.e., cardiorespiratory fitness, strength, body composition, and flexibility), ameliorating cancer-related side effects, such as fatigue, anxiety, depression, lymphoedema, peripheral neuropathy, cardiotoxicity, bone impairments, leading to enhanced quality of life (Devin et al. 2018 ; Scott et al. 2018 ; Campbell et al. 2019 ; Sweegers et al. 2019 ; Avancini et al. 2021a , 2022 ). Furthermore, besides these favorable impacts, physical exercise may also positively modulate vagal nerve activity.

Physical exercise refers to a specific type of physical activity that is planned, structured, and repeatedly done to improve or maintain physical fitness and overall health, as well as treat disease or injury. (Caspersen et al. 1985 ). In the cancer context, two major subgroups of activities are often studied: aerobic and resistance training. Aerobic training is exercise using large muscle groups, repetitively over an extended period of time e.g., walking, cycling, and running with the primary aim being improvement in cardiorespiratory capacity. Resistance training is exercise performed against resistance that limits the number of repetitions due to onset of neuromuscular fatigue. The purpose is to increase muscle size, neuromuscular strength, and endurance (Hughes et al. 2018 ). Besides these “ classical ” types of training, “mind-body” exercise has also been explored in the cancer population. Mind-body activities are typically defined as those “ whose origins lie outside of the Western culture , typically combines muscle-strengthening , balance training , light-intensity aerobic activity , and flexibility together ”. Examples include yoga, Tai Chi, and Qigong.

The “classical” physical exercise interventions

Several studies have investigated the potential role of classical physical exercise in counteracting the dysfunction of the autonomic nervous system by enhancing HRV outcomes (Table 3 .) (Riesenberg and Lubbe 2010 ; Niederer et al. 2013 ; Hyeng-Cheol Shin 2016 ; Dias Reis et al. 2017 ; Mostarda et al. 2017 ; Grote et al. 2020 ; Toohey et al. 2020 ; Fournie et al. 2022 ; Lavin-Perez et al. 2023 ; Lavín-Pérez et al. 2023 ). Through this review we found seven studies investigated a combined aerobic and resistance training program (Hyeng-Cheol Shin 2016 ; Dias Reis et al. 2017 ; Mostarda et al. 2017 ; Grote et al. 2020 ; Fournie et al. 2022 ; Lavin-Perez et al. 2023 ; Lavín-Pérez et al. 2023 ), while three examined aerobic training only (Riesenberg and Lubbe 2010 ; Niederer et al. 2013 ; Toohey et al. 2020 ).

Table 3 Main studies investigating traditional physical exercise and mind-body intervention in patients with cancer on HRV Author (year) Study design and patients Exercise intervention Feasibility and safety HRV assessment Main Findings Classical physical exercise Toohey et al. ( 2020 ) (Toohey et al. 2020 ) 3-arm RCT 17 pts with breast cancer, stage NR, after treatment 12 weeks, 3 times/week of HIIT, 7 rounds cycling of 30 s. at maximum perception interspersed by 2 min. of active recovery vs. 30 min. in total of CIMT with 20 min at 50% of maximal power vs. usual care AT: ▪ 78.7% for HIIT ▪ 79.4% for CMIT AE: No ▪ Tool: Suunto t6 ▪ Duration: 5 min ▪ ↑ VO 2 Peak in HIIT ▪ ↔ HRV variables (LnVLF, LnLF, LnHF, LnLF/HF, LnRMSSD) in any group Grote et al. ( 2020 ) (Grote et al. 2020 ) Single-arm study 76 pts with mixed cancer, stage NR, after treatments 26 weeks, 3 times/week of 20 min. aerobic exercise plus 30 min. of circuit-based resistance training AT: 59% AE: No ▪ Tool: Polar RS800X ▪ Duration: 10 min ▪ ↑ HR rest, , HF power in patients who completed treatments from at least 5 years ▪ ↔ LF power, HF power, LF/HF power ratio, VO 2 Peak Lavin-Perez et al., 2023 ) (Lavín-Pérez et al. 2023 ) Single-arm study 16 pts with breast cancer, stage NR, during treatments 4 weeks, 3 times/week of 12 min, aerobic training at 65–80% HR reserve plus resistance training, 4 sets of 8–10 reps at 55–70% 1RM AT: NR AE: NR ▪ Tool: HRV Training app ▪ Duration: 5 min ▪ ↑ lnrRMSSD, lnSDNN after 24 h from the first exercise session ▪ ↑ lnSDNN over the weeks Lavin-Perez et al., ( 2023 ) (Lavin-Perez et al. 2023 ) RCT 29 pts with breast cancer, stage NR, after treatments 16 weeks,3 times/weeks of moderate to high interval aerobic training, 4–6 intervals of 30 s. to 1 min. and rest of 30 s to 45 s at 65–95% HR reserve plus resistance training, 4 sets of 8–12 reps at 55–85% 1RM vs. usual care AT: NR AE: NR ▪ Tool: HRV Training app ▪ Duration: 5 min ▪ ↑ rMSSD, SDNN in EG vs. CG ▪ ↑ lnSDNN between months in each recovery time in exercise group ▪ ↑ lnrMSSD at after 24 h from exercise in EG Mostarda et al. (2017) (Mostarda et al. 2017 ) RCT 18 pts with breast cancer, stage I-III, during treatments 4 weeks, 3 times/week of aerobic training, 30 min. at 60% VO2 max plus resistance training, 3 sets of 8–12 reps at low-moderate intensity vs. usual care AT: 100% AE: No ▪ Tool: Tachogram ▪ Duration: 5 min ▪ ↑ HF, LF and LF/HF in EG vs. CG ▪ ↔ SDNN and rMSSD ▪ ↑ VO2max in EG vs. CG Niederer et al. ( 2013 ) (Niederer et al. 2013 ) 3-arm quasi-experimental study 45 pts with mixed cancer, stage I-III, during and after treatments 16 weeks, 3–5 times/week of home-based training at 13–14 of RPE scale plus once/week guided Nordic-Walking once/week during treatments vs. 16 weeks, 3–5 times/week of home-based training at 13–14 of RPE scale plus once/week guided Nordic-Walking after-treatments vs. usual care AT: NR AE: NR ▪ Tool: Polar S810 ▪ Duration: 5 min ▪ ↑ TP in both EGs ▪ ↔ HF, LF in any group Dias Reis et al., (2017) (Dias Reis et al. 2017 ) RCT 18 pts with breast cancer, stage I-III, during treatments 12 weeks, 3 times/week of hospital-based aerobic training, 30 min. at 60% VO2 max plus resistance exercise, 3 sets of 8–12 reps at 6 to 9 of Omni Scale vs. usual care AT: NR AE: NR ▪ Tool: Tachogram ▪ Duration: 5 min ▪ ↑ VO 2 Peak , LF/HF and HF in EG vs. CG ▪ ↓ LF in EG vs. CG ▪ ↔ SDNN, RMSSD, LF, HF ▪ 6-week of detraining restored all HRV to baseline levels Riesenberg et al., ( 2010 ) (Riesenberg and Lubbe 2010 ) Single-arm study 45 pts with lung cancer, stage ND, after treatments 28 days, 7 times/week of interval training, 30 min. of 3–5 min. rounds plus oncological rehabilitation AT: NR AE: NR ▪ Tool: Polar S810 ▪ Duration: 5 min ▪ ↑ RMSSD ▪ ↓ HR rest Shin et al. ( 2016 ) (HC 2016 ) RCT 22 pts with breast cancer, stage NR, during treatments 8 weeks, 3 times/week of circuit-based exercise, 40 min of both aerobic plus strength exercises at 11–13 RPE vs. usual care AT: NR AE: NR ▪ Tool: CANS 3000 ▪ Duration: 5 min ▪ ↑ LF in EG vs. CG ▪ ↔ LF, HF, LF/HF, SDNN, RMSSD Fournié et al. ( 2022 ) (Fournie et al. 2022 ) Single-arm study 20 pts with hematological malignancies, stage NR, after treatments 12 weeks, two times/week of aerobic training, 30 min at 70–80% HR max plus resistance circuit training, 20 min at 12–14 RPE and 10 sessions of HRVB AT: ▪ 98% for HRVB ▪ 85% for exercise AE: No ▪ Tool: SymbioLine ® ▪ Duration: 10 min ▪ ↑LF, LnLF ▪ ↔ SDNN, RMSSD, TP, VLF, LnVLF, HF, LnHF Mind-body interventions Inbaraj et al., (2023) (Inbaraj et al. 2023 ) RCT 59 pts with breast cancer Stage I-III During treatments 18 weeks, 5 times/week of yoga for 40 min both in hospital and home-based vs. usual care AT: NR AE: No ▪ Tool: lead II ECG ▪ Duration: 20 min ▪ ↑ SDNN, RMSSD, pNN50 and HF in EG vs. CG ▪ ↓ LF and LF/HF ratio in EG vs. CG ▪ ↓ RHR in EG vs. CG Fong et al., ( 2015 ) (S. 2015 ) Single-arm study 11 pts with nasopharyngeal Stage NR After treatments 5 min of Thai Chi Qigong exercise AT: NR AE: NR ▪ Tool: Polar Vantage NV ▪ Duration: 7 min ▪ ↓ in nLF ▪ ↑ in nHF ▪ ↔ in LF/HF Lee et al.( 2018 ) (Lee et al. 2018 ) Longitudinal study 80 pts with mixed cancer Stage I-III After treatments 12 weeks, once/week of Qigong Exercise for 2 h vs. 12 weeks, once/week of cognitive behavior modification and mindfulness for 90 min plus 20 min of body relaxation and meditation (Stress Management) vs. usual care with nutritional guidance AT: NR AE: NR ▪ Tool: lead II ECG ▪ Duration: 5 min ▪ ↑ SDNN, TP, HF in both QE and SM after 12 weeks ▪ ↓ SDNN, TP in both QE and SM at 3 months follow-up ▪ ↑ SDNN, TP in both QE and SM vs. CG Zhou et al., (2018) (Zhou et al. 2018a , b ) RCT 114 pts with nasopharyngeal cancer Stage III-IV During treatments 5 times/week of Thai Chi for 30 min plus 10 min of breathing and meditations plus 10 min of relaxation vs. usual care AT: NR AE: NR ▪ Tool: ECG ▪ Duration: 5 min ▪ ↑ nLF, nLF/nHF ratio in both groups ▪ ↓ nHF in both groups ▪ Lower nLF, nLF/nHF and higher nHF in EG vs. CG Lee et al., ( 2022 ) (Lee et al. 2022 ) RCT 125 pts with mixed cancer Stage NR After treatments 12 weeks, once/weeks of Qigong for 1 h vs. 12 weeks, once/weeks of Mindfulness for 1 h vs. usual care AT: NR AE: NR ▪ Tool: ECG ▪ Duration: 5 min ▪ ↑ SDNN, TP, LF, LF/HF in both Mindfulness and Qigong vs. CG ▪ ↑ HF in Mindfulness group Abbreviations : ↑, significant improvement; ↔ no significant changes; ↓, significant worsening; AT , attendance; AE , adverse events; CMIT , continuous moderate-intensity training; HIIT , high-intensity aerobic training; HRV , heart rate variability; VO 2 Peak , peak oxygen consumption; NR , not reported; EG , exercise group, CG , control group; HRVB , heart rate variability biofeedback; SDNN , standard deviation of RR intervals, rMSSD , root mean square of successive RR intervals differences; TP , total power; VLF , very low frequency; LF , low frequency; HF , high frequency; LF/HF ratio from low to high frequency; RPE , rating perceived exertion; QE , Qigong exercise; SM , stress management

Effects of aerobic training interventions

Historically, aerobic training has been considered the most beneficial type of activity for the heart, as well as for its nervous modulation. Three trials investigated the impact of aerobic training only on HRV in patients with cancer (Riesenberg and Lubbe 2010 ; Niederer et al. 2013 ; Toohey et al. 2020 ). A single-arm study, including 45 patients with lung cancer who had completed treatment, showed that 28 days of daily cycling training for 30 min plus relaxation techniques and psychological counseling significantly increased the RMSSD by 33% (Riesenberg and Lubbe 2010 ). However, a quasi-experimental investigation has matched 3 groups of patients with mixed cancer types, control ( n = 15), patients exercising during treatment ( n = 15), and patients exercising after treatment completion ( n = 15). After 16 weeks of advice to perform aerobic training 3–5 times a week plus a supervised session one a week of Nordic Walking no differences in the HRV frequency domains occurred; nevertheless, an enhancement in the total power was observed for both interventional groups (+ 11% patients during acute treatment; +16% patients who have finished the therapies) (Niederer et al. 2013 ). However, several exercise variables may influence cardiac autonomic modulation, including intensity. In line with this, a 3-arm randomized controlled trial enrolling 17 patients with breast cancer who had completed anticancer treatment were allocated to control or to perform high-intensity interval training or moderate-intensity continuous training thrice a week on a cycle ergometer. After 12 weeks of training, no changes in either frequency or time domains of HRV were found in any of the three groups, although the low sample size is a limitation in these results (Toohey et al. 2020 ).

Effects of combined aerobic and resistance exercise interventions

A combined physical exercise program, i.e., including aerobic and resistance training, currently is the most examined type of intervention across the studies (Hyeng-Cheol Shin 2016 ; Dias Reis et al. 2017 ; Mostarda et al. 2017 ; Grote et al. 2020 ; Fournie et al. 2022 ; Lavin-Perez et al. 2023 ; Lavín-Pérez et al. 2023 ). Investigations exploiting a single-arm design reported improvements in HRV parameters after a combined physical exercise program (Grote et al. 2020 ; Fournie et al. 2022 ; Lavín-Pérez et al. 2023 ), which are also supported from results observed in other randomized controlled trials (HC 2016 ; Dias Reis et al. 2017 ; Mostarda et al. 2017 ; Lavin-Perez et al. 2023a ). For instance, a randomized controlled trial explored the impact on HRV of 4-months home-based combined physical exercise in 29 patients affected by breast cancer treated with neoadjuvant/adjuvant chemotherapy or radiotherapy. The program was performed thrice a week; the aerobic component consisted of 4–6 intervals of 30 s of work at 65–95% of heart reserve rate interspersed by 30 s rest, while resistance training was comprised of 4 sets of 8–12 reps of full body exercises at 55–85% of 1 repetition maximum (1RM). Patients allocated in the intervention arm exhibited a significant increase in HRV parameters at the end of the intervention, compared to the controls, who reported a statistically significant decrease in rMMSD and SDNN domains (Lavin-Perez et al. 2023 ).

Similarly, Mostarda et al. found that compared to usual care, 4 weeks of supervised hospital-based aerobic and resistance training thrice a week was able to significantly improve the autonomic imbalance in women with stage I-III breast cancer receiving adjuvant therapies. Each session, lasting 70 min, was composed of 30 min of aerobic exercise at 60% of maximal oxygen consumption (VO 2 max) on a cycle ergometer and resistance training through 3 sets of 8–12 reps of exercises at low-moderate intensity. At postintervention, while controls did not report changes, patients in the intervention group demonstrated improvements in time and frequency domains of HRV. Additionally, the authors, through symbolic analysis (an analysis which permits to describe the dynamics of a short period in time series of HRV), also found an enhancement in vagal nerve modulation, expressed as 2LV (4.9% ± 1.0 vs. 10.0% ± 1.4; p < 0.05) and 2UV (1.0% ± 2.0 vs. 21.0% v 2.0; p < 0.05), and reduced sympathetic activity (0 V: 34.0% ± 1.5 vs. 21.0% ±2 0.3; p < 0.05) (Mostarda et al. 2017 ). Overall, a combined physical exercise intervention, composed of aerobic and resistance training, appears to positively modulate HRV in patients with cancer. Nevertheless, it seems that training should be regularly performed, as a small period of detraining, i.e., the absence of regular exercise, may be sufficient to lose the autonomic benefits. In this regard, a randomized controlled trial investigating the effect of 12-weeks of aerobic and resistance training in patients with breast cancer found improvements in HRV, especially the frequency domains such as LF (intervention: 66 ± 11 nu vs. 48 ± 9.91 nu; control: 60 ± 11 nu vs. 57 ± 9.57 nu; p < 0.05), HF (intervention: 34 ± 11 nu vs. 52 ± 9.91 nu; control: 40 ± 11 nu vs. 43 ± 10 nu; p < 0.05) and LF/HF (intervention: 2.3 ± 1.26 nu vs. 1.04 ± 0.54 nu; control: 1.6 ± 1.2 nu vs. 1.3 ± 0.94 nu; p < 0.05). Nevertheless, 8 weeks of detraining, following the intervention was sufficient to lose all improvements in levels of autonomic modulation, which returned to the baseline levels (Dias Reis et al. 2017 ).

Considerations and limitations

In conclusion, whereas the effect of aerobic training alone on cardiac autonomic modulation is still to be fully elucidated, an exercise program combining aerobic and resistance training seems more efficacious in improving HRV measures. However, different issues may limit the generalizability of these conclusions, in primis the sample size and the study population. No studies were powered to statistically detect changes in HRV measurements, and in addition, most investigations were conducted on women with breast cancer with different treatment statuses. In the future, research should be directed to expand the cancer type and stage by investigating the role of exercise on cardiac modulation, taking into account the variety of factors that may interfere with HRV, such as anticancer treatments and psychological well-being. Additionally, from an exercise prescription perspective, mode of exercise required further investigation e.g., resistance training alone, currently not investigated, and identifying the exercise dosage (i.e., volume, intensity, frequency, and duration) sufficient to drive improvements in autonomic modulation in order to better tailor physical exercise prescription to impact HRV.

Mind-body exercise interventions

As mentioned above, psychological impairments are common after a diagnosis of cancer. Nevertheless, several dysfunctional pathways embracing the nervous, endocrine, and immune systems are activated in response to chronic stress, and among them, overactivation of the sympathetic nervous system may result in an increase in autonomic dysfunction. In this context, mind-body activities, associating the positive effects of body movements with mind exercises, may theoretically provide more potent stimuli to enhance HRV. To our knowledge, only five studies have investigated the effect of mind-body exercises, such as Tai Chi, Qigong, and Yoga, in reducing autonomic impairment in patients with cancer (Table 3 .).

Effects of Tai Chi

Tai Chi is a Chinese martial art that involves “ a series of slow , gentle movements and physical postures , a meditative state of mind , and controlled breathing ” (Health 2024a , b , c ), which has been shown to produce a series of positive impacts on patients with cancer (Yang et al. 2021 ). Regarding its effect on autonomic function, a randomized controlled trial, including 114 patients with nasopharyngeal cancer, examined the impact of Tai Chi performed five times per week, one hour per session, during the chemoradiotherapy period. At postintervention evaluations, the Tai Chi group exhibited a lower increase of nLF (Tai Chi: 63.07 ± 6.99 nu vs. 67.90 ± 5.70 nu; Control: 62.54 ± 5.21 nu vs. 70.68 ± 4.90 nu; p < 0.01) and a lower decrease of nHF (Tai Chi: 36.93 ± 6.99 nu vs. 32.10 ± 5.70 nu; Control: 37.46 ± 5.21 nu vs. 29.32 ± 4.90 nu; p < 0.01) compared to the usual care; nevertheless, smaller increase in the nLF/nHF ratio (Tai Chi: 1.79 ± 0.46 vs. 2.20 ± 0.51; Control: 1.72 ± 0.36 vs. 2.51 ± 0.59; p < 0.01) was also detected, indicating a better sympathetic and parasympathetic balance (Zhou et al. 2018a , b ).

Effects of qigong

More controversial is the impact on HRV of Qigong, another discipline deriving from classical Chinese medicine, which uses exercises to “ optimize energy within the body , mind , and spirit , with the goal of improving and maintaining health and well-being ” (Health 2024a , b , c ). The quasi-experimental study of Lee et al. analyzed the effect of Qiqong with respect to a mindfulness intervention and usual care in a sample of 125 patients with mixed cancer types who had completed anticancer treatments. The Qigong and mindfulness interventions were performed two hours once a week, while the control group received usual care. After 12 weeks, the frequency domain indexes exhibited an increase in HF for the mindfulness group and a decrease for controls and Qigong, whereas LF and LF/HF ratio increased in Qigong and mindfulness interventions and reduced in the control. Although this appears to be no improvement in HRV, the total power and the SDNN increased after both Qigong (SDNN: 27.72 ± 10.94 ms vs. 29.30 ± 11.27 ms; total power: 460.95 ± 349.75 ms 2 vs. 502.55 ± 455.54 ms 2 ) and mindfulness (SDNN: 26.39 ± 9.45 ms vs. 33.36 ± 9.2 ms; total power: 413.47 ± 323.09 ms 2 vs. 618.88 ± 334.24 ms 2 ) approaches and decreased in the control (SDNN: 29.89 ± 13.78 ms vs. 29.67 ± 10.29 ms; total power: 606.70 ± 678.03 ms 2 vs. 467.61 ± 330.15 ms 2 ), suggesting an improvement in the autonomic nervous system (Lee et al. 2022 ).

Effects of yoga

Yoga, originated in India and emphasizes physical postures, breathing techniques, and meditation, and has been widely evaluated in patients with cancer (Gonzalez et al. 2021 ; Song et al. 2021 ; Health 2024a , b , c ). However, just one investigation explored the effect on HRV in a sample of 68 women affected by early-stage breast cancer undergoing adjuvant chemotherapy. The yoga program lasted 18 weeks in both hospital and home settings and consisted of 5 sessions per week conducted for 40 min, whereas patients allocated in the control group received usual care. After the intervention, all the time-domain variables, including SDRR, RMSSD, pNN50%, and the frequency-domain parameters, such as total power, LF, HF, and LF/HF ratio, significantly improved in the yoga group, and in contrast, deteriorated in the controls, indicating that this intervention may be a supportive strategy to prevent the impairment of autonomic function associated with chemotherapy treatment (Inbaraj et al. 2023 ).

To date, there is little research investigating the impact of body-mind interventions on HRV. Despite the preliminary positive evidence, further studies, following the consideration postulated for classical physical exercise, are needed to confirm and consolidate the real contribution of these alternative programs.

Mechanisms by which physical exercise May improve the autonomic modulation

Chronic physical exercise training may increase HRV by enhancing parasympathetic activity and reducing the sympathetic influence on the heart (Figueroa et al. 2007 ; Fu and Levine 2013 ). At first glance, this effect may seem paradoxical since physical exercise is a stressor stimulus for the body; nevertheless, the repeated activation of the sympathetic system at each bout of physical exercise may result in an attenuation of its influence. Interestingly, the recovery phase from each exercise session may also influence acute autonomic responses and long-term adaptations. Post-exercise recovery is typically characterized by a reactivation of parasympathetic tone and a withdrawal of sympathetic drive, and these dynamics may progressively improve with regular training. Over time, a more efficient autonomic recovery profile, marked by a faster return to baseline heart rate and HRV, can reflect improved cardiovascular resilience and reduced allostatic load. Thus, patients may adapt to training by experiencing a reduced acute autonomic perturbation after each session, which could represent a relevant physiological marker of training effectiveness.

Although the precise mechanisms by which physical exercise may modulate the cardiac autonomic system are not clearly elucidated, especially in the cancer context, several pathways, including the renin-angiotensin-aldosterone system (RAAS), nitric oxide (NO) and reactive oxygen species (ROS) are suggested as possible and direct mediators of modulation of vagal tone induced by exercise (Kingwell 2000 ; Routledge et al. 2010 ).

Dysregulation of RAAS has a well-recognized role in cancer, and it is associated with cell proliferation, metastasis, inflammation, angiogenesis, and cardiotoxicity (Hassani et al. 2023 ). Angiotensin II, a major player in the RAAS, is a hormone synthesized by the kidney that inhibits the cardiac vagal tone (Townend 1995 ; Routledge et al. 2010 ). Physical exercise may modulate the RAAS, by suppressing angiotensin II. In this regard, a recent meta-analysis, including more than 800 participants, found that chronic exercise training reduced plasma levels of angiotensin-II (SMD = − 0.71; 95% CI: −1.24 to − 0.19; p = 0.008), aldosterone (SMD = − 0.37; 95% CI: −0.65 to − 0.09; p = 0.009), as well as, norepinephrine (SMD = − 0.82; 95% CI: −1.18 to − 0.46; p < 0.001), a catecholamine linked to sympathetic nervous system activity (Baffour-Awuah et al. 2024 ). Beyond the effect on RAAS, physical exercise may also exert a positive impact on autonomic function through the upregulation of NO. NO is a free radical regulating a series of processes, such as neurotransmission in neuronal cells, vasodilation in muscle and endothelial cells, and an increase in cardiac vagal control; its dysregulation has been associated with cancer-related cardiac dysfunction in patients with breast cancer (Finkelman et al. 2017 ). Physical exercise has a prominent role in cardiovascular health and in the cancer context. Vear et al. , in their meta-analysis encompassing 171 patients with mixed cancer types, reported that compared to normal care, physical exercise significantly enhanced endothelial function, a surrogate evaluation of the NO bioavailability (SMD = 0.34, 95% CI: 0.01 to 0.67; p = 0.044) (Vear et al. 2023 ). Finally, physical exercise may be a player in oxidative stress reduction. Cancer and treatments are linked to an increase in ROS production (Perillo et al. 2020 ), which may also be implicated in the development of cardiac dysfunction (Teng et al. 2021 ). Although acute or exhaustive training was observed to promote ROS production, moderate-intensity physical exercise may attenuate ROS production towards an antioxidant status. For instance, in patients with cancer, moderate-intensity physical exercise intervention has been reported to enhance anti-oxidant markers, such as Trolox equivalent antioxidant capacity, glutathione peroxidase, and malondialdehyde, and at the same time, diminish those who had a pro-oxidative effect, including protein carbonyls and 8-hydroxy-2’-deoxyguanosine (Repka and Hayward 2016 ; Delrieu et al. 2021 ).

Beyond the direct mechanisms, physical exercise may positively regulate the cardiac autonomic function in patients with cancer in a more indirect manner, i.e., by counteracting some of the aforementioned lifestyle factors (especially chronic stress, sleep disruption, and body composition) related to its dysfunction. Indeed, physical exercise may act on psychological impairments, alleviating the levels of anxiety, depression, and distress through the regulation of the hypothalamic-pituitary-adrenal axis (Saxton et al. 2014 ). The beneficial role of physical exercise also extends to sleep disturbance. In this regard, physical exercise, especially aerobic training lasting 4–8 weeks, may enhance both subjective sleep quality and sleep onset latency in patients with cancer (Fang et al. 2019 ). Regarding body composition, physical exercise is a key modulator of adipose and muscle tissues. In overweight or obese patients with cancer, physical exercise is able to significantly decrease body mass index, of 1.37 kg/m 2 , and fat mass by 3.80% (Yang et al. 2023 ) and, at the same time, those performing resistance training produced enhanced lean mass of 0.85 kg, compared to a usual care group (Koeppel et al. 2021 ).

Future perspectives

Despite promising preliminary evidence, several knowledge gaps remain regarding the role of physical exercise in modulating autonomic function in patients with cancer. Firstly, the current literature is largely limited to small-scale studies, many of which are single-arm or pilot trials conducted predominantly in women with breast cancer. Future research should aim to include larger, adequately powered randomized controlled trials across a broader spectrum of cancer types and stages to enhance the generalizability of findings. Secondly, while combined aerobic and resistance training appears most beneficial, the independent effect of resistance training alone remains underexplored and deserves specific investigation. Additionally, mind-body interventions have shown potential to positively influence HRV, yet the heterogeneity in intervention design, duration, and outcome reporting makes it difficult to draw definitive conclusions. Moreover, the optimal exercise prescription, regarding intensity, frequency, and duration required to elicit significant changes in autonomic modulation is still unclear.

Future studies should also incorporate long-term follow-up and investigate the sustainability of HRV improvements over time, especially considering evidence that benefits may be lost after short periods of detraining. Finally, future interventions should consider a precision exercise approach, integrating baseline HRV measures, treatment-related factors, and psychological status to tailor interventions. There is also a need to better understand the underlying physiological mechanisms by which exercise influences autonomic function in the oncological setting, particularly the role of inflammation, hormonal axes, and neuroimmune interactions. Some ongoing clinical trials investigating the impact of exercise programs on HRV are expected to contribute meaningfully to filling these gaps(Table 4 ). Of particular interest, some studies are adopting a precision exercise approach by tailoring the training intensity and volume based on each patient’s baseline HRV profile, aiming to individualize intervention plans and maximize physiological adaptation. Indeed, HRV-guided training enables real-time adaptation of exercise intensity and recovery needs, potentially optimizing the effects of physical exercise while minimizing the risk of overtraining or adverse events. In this sense, an ongoing study is evaluating the possibility of mHealth solutions for collecting patient-generated health data, including also HRV, for predicting adverse health outcomes in adults people with an history of childhood cancer (Howell et al. 2024 ). Moreover, following this data-driven exercise personalization, a trial is evaluating a high-intensity training in patients with breast cancer, tailoring the exercise intensity based on individual autonomic responses (Lavin-Perez et al. 2023 ). Similarly, the APACCHE trial is exploring the effect of physical activity combined with the HRV biofeedback in patients with hematological malignancies (Fournie et al. 2020 ).

Table 4 Ongoing clinical trials evaluating the effect of exercise on HRV in patients with cancer Title Number identifier Country Study design and type of patients Intervention Prehabilitation to Improve Heart Rate Variability (PRIME) NCT06744413 Italy RCT; Patients undergoing major abdominal/thoracic surgery Supervised nutrition and exercise as part of multimodal prehabilitation Attenuating Cancer Treatment-related Toxicity in Oncology Patients With a Tailored Physical Exercise Program (ATOPE) NCT03787966 Spain RCT; Women with breast cancer before and during treatments Supervised aerobic, strength and motor control training, 18 sessions Preventing Breast Cancer Therapy-related Cardiovascular Toxicity With a Daily-adapted Program With Mhealth Support (ATOPE-PRO) NCT06518200 Spain RCT; Women with breast cancer undergoing treatments Individually adapted daily exercise using mobile technology and HRV-based feedback Adjusting the Dose of Therapeutic Exercise to Prevent Neurotoxicity Due to Anticancer Treatment (ATENTO) NCT04583124 Spain RCT; Women with breast cancer before and during treatments HRV-guided aerobic and resistance exercise, 18 sessions High-intensity exercise prescription guided by heart rate variability in breast cancer patients NCT05040867 Spain RCT; Women with breast cancer after treatments HRV-guided moderate- or high-intensity exercise, 16 weeks Cardiac Coherence Combined With Personal Physical Activity in Patients With Cancer (APACCHE) NCT03356171 France RCT; Patients with haematological malignancies Heart rate variability biofeedback + adapted physical activity, 12 weeks

Conclusions

Patients with cancer may be exposed to multiple factors, classified as disease-related, lifestyle-related, and physiological, leading to cardiac autonomic dysfunction. This impairment is associated with worse outcomes in the oncological setting, including mortality and disease progression. Physical exercise has several beneficial effects for patients and may also attenuate the sympathovagal imbalance. The current evidence is that physical exercise, especially combining aerobic and resistance training and yoga-based intervention, may improve HRV. However, evidence of the impact of physical exercise on managing autonomic modulation remains limited but certainly shows promise for benefitting people with cancer. This research topic is a relatively underexplored and novel research area.

Fig. 1 The autonomic control and its branches

Fig. 2 Factors influencing cardiovascular autonomic dysfunction in patients with cancer

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Acknowledgements

This work was supported by grants from Associazione Pietro Casagrande ONLUS. M.M. and A.A. are currently supported by PRIN (CUP B39J21037270006). S.P is supported by Associazione Italiana per la Ricerca sul Cancro (AIRC, Next Gen Clinician Scientist 2023 n° 30204).

Author contributions

All authors have made substantial contributions to the article. A.B., L.T., S.P. and A.A. designed this study (conceptualization, formal analysis, investigation and methodology) and wrote the manuscript. C.C., F.B., S.T.R, P.F., I.T., D.T., L.B., J.I., M.S., F.S. and R.U.N. helped in reviewing the manuscript and provided critical revisions. M.M., S.P. and A.A. were in charge of project administration and supervision.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Data availability

No datasets were generated or analysed during the current study.

Declarations

Ethics approval

Not applicable.

Consent to participate

Not applicable.

Consent to publish

Not applicable.

Competing interests

The authors declare no competing interests.

References

S., F. (2015) Changes in heart-rate variability of survivors of nasopharyngeal cancer during Tai Chi qigong practice. Journal of Physical Therapy Science 10.1589/jpts.27.1577 PMC4483444 26157266

Aleman BM, Moser EC, Nuver J, Suter TM, Maraldo MV, Specht L, Vrieling C, Darby SC (2014) Cardiovasc Disease after cancer Therapy EJC Suppl 12(1):18–28 10.1016/j.ejcsup.2014.03.002 PMC4250533 26217163

Allemani C Matsuda T Di Carlo V Harewood R Matz M Niksic M Bonaventure A Valkov M Johnson CJ Esteve J Ogunbiyi OJ Azevedo ESG Chen WQ Eser S Engholm G Stiller CA Monnereau A Woods RR Visser O Lim GH Aitken J Weir HK Coleman MP Group CW Global surveillance of trends in cancer survival 2000-14 (CONCORD-3): analysis of individual records for 37 513 025 patients diagnosed with one of 18 cancers from 322 population-based registries in 71 countries Lancet 2018 391 10125 1023 1075 29395269 10.1016/S0140-6736(17)33326-3 PMC5879496 Allemani C, Matsuda T, Di Carlo V, Harewood R, Matz M, Niksic M, Bonaventure A, Valkov M, Johnson CJ, Esteve J, Ogunbiyi OJ, Azevedo ESG, Chen WQ, Eser S, Engholm G, Stiller CA, Monnereau A, Woods RR, Visser O, Lim GH, Aitken J, Weir HK, Coleman MP, Group CW (2018) Global surveillance of trends in cancer survival 2000-14 (CONCORD-3): analysis of individual records for 37 513 025 patients diagnosed with one of 18 cancers from 322 population-based registries in 71 countries. Lancet 391(10125):1023–1075 29395269 10.1016/S0140-6736(17)33326-3 PMC5879496

Atar O, Ram R, Avivi I, Amit O, Vitkon R, Luttwak E, Bar-On Y, Gidron Y (2023) Vagal nerve activity predicts prognosis in diffused large B-Cell lymphoma and multiple myeloma. J Clin Med 12(3) 10.3390/jcm12030908 PMC9917757 36769556

Avancini A Belluomini L Tregnago D Trestini I Milella M Lanza M Pilotto S Exercise and anemia in cancer patients: could it make the difference? Expert Rev Hematol 2021 14 11 979 985 34784852 10.1080/17474086.2021.2007764 Avancini A, Belluomini L, Tregnago D, Trestini I, Milella M, Lanza M, Pilotto S (2021a) Exercise and anemia in cancer patients: could it make the difference? Expert Rev Hematol 14(11):979–985 34784852 10.1080/17474086.2021.2007764

Avancini A Trestini I Tregnago D Lanza M Menis J Belluomini L Milella M Pilotto S A multimodal approach to cancer-related cachexia: from theory to practice Expert Rev Anticancer Ther 2021 21 8 819 826 33971783 10.1080/14737140.2021.1927720 Avancini A, Trestini I, Tregnago D, Lanza M, Menis J, Belluomini L, Milella M, Pilotto S (2021b) A multimodal approach to cancer-related cachexia: from theory to practice. Expert Rev Anticancer Ther 21(8):819–826 33971783 10.1080/14737140.2021.1927720

Avancini A Sperduti I Borsati A Ferri T Belluomini L Insolda J Trestini I Tregnago D Schena F Bria E Milella M Pilotto S Effect of exercise on functional capacity in patients with advanced cancer: A meta-analysis of randomized controlled trials Crit Rev Oncol Hematol 2022 175 103726 35659975 10.1016/j.critrevonc.2022.103726 Avancini A, Sperduti I, Borsati A, Ferri T, Belluomini L, Insolda J, Trestini I, Tregnago D, Schena F, Bria E, Milella M, Pilotto S (2022) Effect of exercise on functional capacity in patients with advanced cancer: A meta-analysis of randomized controlled trials. Crit Rev Oncol Hematol 175:103726 35659975 10.1016/j.critrevonc.2022.103726

Avancini A Trestini I Tregnago D Belluomini L Sposito M Insolda J Schena F Milella M Pilotto S Willingness, preferences, barriers, and facilitators of a multimodal supportive care intervention including exercise, nutritional and psychological approach in patients with cancer: a cross-sectional study J Cancer Res Clin Oncol 2023 149 7 3435 3445 35943598 10.1007/s00432-022-04232-6 PMC10314831 Avancini A, Trestini I, Tregnago D, Belluomini L, Sposito M, Insolda J, Schena F, Milella M, Pilotto S (2023) Willingness, preferences, barriers, and facilitators of a multimodal supportive care intervention including exercise, nutritional and psychological approach in patients with cancer: a cross-sectional study. J Cancer Res Clin Oncol 149(7):3435–3445 35943598 10.1007/s00432-022-04232-6 PMC10314831

Baffour-Awuah B Man M Goessler KF Cornelissen VA Dieberg G Smart NA Pearson MJ Effect of exercise training on the renin-angiotensin-aldosterone system: a meta-analysis J Hum Hypertens 2024 38 2 89 101 38017087 10.1038/s41371-023-00872-4 PMC10844078 Baffour-Awuah B, Man M, Goessler KF, Cornelissen VA, Dieberg G, Smart NA, Pearson MJ (2024) Effect of exercise training on the renin-angiotensin-aldosterone system: a meta-analysis. J Hum Hypertens 38(2):89–101 38017087 10.1038/s41371-023-00872-4 PMC10844078

Bradshaw PT Body composition and cancer survival: a narrative review Br J Cancer 2024 130 2 176 183 37891197 10.1038/s41416-023-02470-0 PMC10803330 Bradshaw PT (2024) Body composition and cancer survival: a narrative review. Br J Cancer 130(2):176–183 37891197 10.1038/s41416-023-02470-0 PMC10803330

Campbell KL Winters-Stone KM Wiskemann J May AM Schwartz AL Courneya KS Zucker DS Matthews CE Ligibel JA Gerber LH Morris GS Patel AV Hue TF Perna FM Schmitz KH Exercise guidelines for Cancer survivors: consensus statement from international multidisciplinary roundtable Med Sci Sports Exerc 2019 51 11 2375 2390 31626055 10.1249/MSS.0000000000002116 PMC8576825 Campbell KL, Winters-Stone KM, Wiskemann J, May AM, Schwartz AL, Courneya KS, Zucker DS, Matthews CE, Ligibel JA, Gerber LH, Morris GS, Patel AV, Hue TF, Perna FM, Schmitz KH (2019) Exercise guidelines for Cancer survivors: consensus statement from international multidisciplinary roundtable. Med Sci Sports Exerc 51(11):2375–2390 31626055 10.1249/MSS.0000000000002116 PMC8576825

Carlson LE Zelinski EL Toivonen KI Sundstrom L Jobin CT Damaskos P Zebrack B Prevalence of psychosocial distress in cancer patients across 55 North American cancer centers J Psychosoc Oncol 2019 37 1 5 21 30592249 10.1080/07347332.2018.1521490 Carlson LE, Zelinski EL, Toivonen KI, Sundstrom L, Jobin CT, Damaskos P, Zebrack B (2019) Prevalence of psychosocial distress in cancer patients across 55 North American cancer centers. J Psychosoc Oncol 37(1):5–21 30592249 10.1080/07347332.2018.1521490

Caspersen CJ Powell KE Christenson GM Physical activity, exercise, and physical fitness: definitions and distinctions for health-related research Public Health Rep 1985 100 2 126 131 3920711 PMC1424733 Caspersen CJ, Powell KE, Christenson GM (1985) Physical activity, exercise, and physical fitness: definitions and distinctions for health-related research. Public Health Rep 100(2):126–131 3920711 PMC1424733

Cherifi F Lefevre Arbogast S Font J Abdeddaim C Becourt S Penel N Coquan E Lequesne J Gidron Y Joly F The promising prognostic value of vagal nerve activity at the initial management of ovarian cancer Front Oncol 2022 12 1049970 36523968 10.3389/fonc.2022.1049970 PMC9745166 Cherifi F, Lefevre Arbogast S, Font J, Abdeddaim C, Becourt S, Penel N, Coquan E, Lequesne J, Gidron Y, Joly F (2022) The promising prognostic value of vagal nerve activity at the initial management of ovarian cancer. Front Oncol 12:1049970 36523968 10.3389/fonc.2022.1049970 PMC9745166

Chiang JK Koo M Kuo TB Fu CH Association between cardiovascular autonomic functions and time to death in patients with terminal hepatocellular carcinoma J Pain Symptom Manage 2010 39 4 673 679 20413055 10.1016/j.jpainsymman.2009.09.014 Chiang JK, Koo M, Kuo TB, Fu CH (2010) Association between cardiovascular autonomic functions and time to death in patients with terminal hepatocellular carcinoma. J Pain Symptom Manage 39(4):673–679 20413055 10.1016/j.jpainsymman.2009.09.014

Chiang JK Kuo TB Fu CH Koo M Predicting 7-day survival using heart rate variability in hospice patients with non-lung cancers PLoS ONE 2013 8 7 e69482 23936027 10.1371/journal.pone.0069482 PMC3720672 Chiang JK, Kuo TB, Fu CH, Koo M (2013) Predicting 7-day survival using heart rate variability in hospice patients with non-lung cancers. PLoS ONE 8(7):e69482 23936027 10.1371/journal.pone.0069482 PMC3720672

Ciurea AM, Gheonea DI, Schenker M, Mehedinteanu AM, Tartea GC, Vere CC (2021) The Prognostic Correlation of Heart Rate Variability at Diagnosis with Survival of Patients with Hepatocellular Carcinoma. Diagnostics (Basel) 11(5) 10.3390/diagnostics11050890 PMC8156854 34067711

Clark RA Marin TS McCarthy AL Bradley J Grover S Peters R Karapetis CS Atherton JJ Koczwara B Cardiotoxicity after cancer treatment: a process map of the patient treatment journey Cardiooncology 2019 5 14 32154020 10.1186/s40959-019-0046-5 PMC7048085 Clark RA, Marin TS, McCarthy AL, Bradley J, Grover S, Peters R, Karapetis CS, Atherton JJ, Koczwara B (2019) Cardiotoxicity after cancer treatment: a process map of the patient treatment journey. Cardiooncology 5:14 32154020 10.1186/s40959-019-0046-5 PMC7048085

Coumbe BGT Groarke JD Cardiovascular autonomic dysfunction in patients with Cancer Curr Cardiol Rep 2018 20 8 69 29971575 10.1007/s11886-018-1010-y Coumbe BGT, Groarke JD (2018) Cardiovascular autonomic dysfunction in patients with Cancer. Curr Cardiol Rep 20(8):69 29971575 10.1007/s11886-018-1010-y

De Couck M van Brummelen D Schallier D De Greve J Gidron Y The relationship between vagal nerve activity and clinical outcomes in prostate and non-small cell lung cancer patients Oncol Rep 2013 30 5 2435 2441 24026706 10.3892/or.2013.2725 De Couck M, van Brummelen D, Schallier D, De Greve J, Gidron Y (2013) The relationship between vagal nerve activity and clinical outcomes in prostate and non-small cell lung cancer patients. Oncol Rep 30(5):2435–2441 24026706 10.3892/or.2013.2725

De Couck M Marechal R Moorthamers S Van Laethem JL Gidron Y Vagal nerve activity predicts overall survival in metastatic pancreatic cancer, mediated by inflammation Cancer Epidemiol 2016 40 47 51 26618335 10.1016/j.canep.2015.11.007 De Couck M, Marechal R, Moorthamers S, Van Laethem JL, Gidron Y (2016) Vagal nerve activity predicts overall survival in metastatic pancreatic cancer, mediated by inflammation. Cancer Epidemiol 40:47–51 26618335 10.1016/j.canep.2015.11.007

De Couck M, Caers R, Spiegel D, Gidron Y (2018) The Role of the Vagus Nerve in Cancer Prognosis: A Systematic and a Comprehensive Review. J Oncol 2018: 1236787 10.1155/2018/1236787 PMC6051067 30057605

Delrieu L, Touillaud M, Perol O, Morelle M, Martin A, Friedenreich CM, Mury P, Dufresne A, Bachelot T, Heudel PE, Fervers B, Tredan O, Pialoux V (2021) Impact of Physical Activity on Oxidative Stress Markers in Patients with Metastatic Breast Cancer. Oxid Med Cell Longev 2021: 6694594 10.1155/2021/6694594 PMC8302399 34326920

Devin JL Jenkins DG Sax AT Hughes GI Aitken JF Chambers SK Dunn JC Bolam KA Skinner TL Cardiorespiratory fitness and body composition responses to different intensities and frequencies of exercise training in colorectal Cancer survivors Clin Colorectal Cancer 2018 17 2 e269 e279 29397328 10.1016/j.clcc.2018.01.004 Devin JL, Jenkins DG, Sax AT, Hughes GI, Aitken JF, Chambers SK, Dunn JC, Bolam KA, Skinner TL (2018) Cardiorespiratory fitness and body composition responses to different intensities and frequencies of exercise training in colorectal Cancer survivors. Clin Colorectal Cancer 17(2):e269–e279 29397328 10.1016/j.clcc.2018.01.004

Dias Reis A Silva Garcia JB Rodrigues Diniz R Silva-Filho AC Dias CJ Leite RD Mostarda C Effect of exercise training and detraining in autonomic modulation and cardiorespiratory fitness in breast cancer survivors J Sports Med Phys Fit 2017 57 7–8 1062 1068 10.23736/S0022-4707.17.07012-8 28134506 Dias Reis A, Silva Garcia JB, Rodrigues Diniz R, Silva-Filho AC, Dias CJ, Leite RD, Mostarda C (2017) Effect of exercise training and detraining in autonomic modulation and cardiorespiratory fitness in breast cancer survivors. J Sports Med Phys Fit 57(7–8):1062–1068 10.23736/S0022-4707.17.07012-8 28134506

Drew RC, Sinoway LI (2012) Chapter 36 - Autonomic Control of the Heart. Primer on the Autonomic Nervous System (Third Edition). D. Robertson, I. Biaggioni, G. Burnstock, P. A. Low and J. F. R. Paton. San Diego, Academic Press: 177–180

Fadul N Strasser F Palmer JL Yusuf SW Guo Y Li Z Allo J Bruera E The association between autonomic dysfunction and survival in male patients with advanced cancer: a preliminary report J Pain Symptom Manage 2010 39 2 283 290 20152590 10.1016/j.jpainsymman.2009.06.014 Fadul N, Strasser F, Palmer JL, Yusuf SW, Guo Y, Li Z, Allo J, Bruera E (2010) The association between autonomic dysfunction and survival in male patients with advanced cancer: a preliminary report. J Pain Symptom Manage 39(2):283–290 20152590 10.1016/j.jpainsymman.2009.06.014

Fang YY Hung CT Chan JC Huang SM Lee YH Meta-analysis: exercise intervention for sleep problems in cancer patients Eur J Cancer Care (Engl) 2019 28 5 e13131 31353674 10.1111/ecc.13131 Fang YY, Hung CT, Chan JC, Huang SM, Lee YH (2019) Meta-analysis: exercise intervention for sleep problems in cancer patients. Eur J Cancer Care (Engl) 28(5):e13131 31353674 10.1111/ecc.13131

Figueroa A Baynard T Fernhall B Carhart R Kanaley JA Endurance training improves post-exercise cardiac autonomic modulation in obese women with and without type 2 diabetes Eur J Appl Physiol 2007 100 4 437 444 17406886 10.1007/s00421-007-0446-3 Figueroa A, Baynard T, Fernhall B, Carhart R, Kanaley JA (2007) Endurance training improves post-exercise cardiac autonomic modulation in obese women with and without type 2 diabetes. Eur J Appl Physiol 100(4):437–444 17406886 10.1007/s00421-007-0446-3

Finkelman BS Putt M Wang T Wang L Narayan H Domchek S DeMichele A Fox K Matro J Shah P Clark A Bradbury A Narayan V Carver JR Tang WHW Ky B Arginine-Nitric oxide metabolites and cardiac dysfunction in patients with breast Cancer J Am Coll Cardiol 2017 70 2 152 162 28683962 10.1016/j.jacc.2017.05.019 PMC5665653 Finkelman BS, Putt M, Wang T, Wang L, Narayan H, Domchek S, DeMichele A, Fox K, Matro J, Shah P, Clark A, Bradbury A, Narayan V, Carver JR, Tang WHW, Ky B (2017) Arginine-Nitric oxide metabolites and cardiac dysfunction in patients with breast Cancer. J Am Coll Cardiol 70(2):152–162 28683962 10.1016/j.jacc.2017.05.019 PMC5665653

Fournie C Bouscaren N Dalleau G Lenclume V Mohr C Zunic P Cabrera Q Verkindt C Adapted physical activity and cardiac coherence in hematologic patients (APACCHE): study protocol for a randomized controlled trial BMC Sports Sci Med Rehabil 2020 12 18 32190333 10.1186/s13102-020-00170-3 PMC7071585 Fournie C, Bouscaren N, Dalleau G, Lenclume V, Mohr C, Zunic P, Cabrera Q, Verkindt C (2020) Adapted physical activity and cardiac coherence in hematologic patients (APACCHE): study protocol for a randomized controlled trial. BMC Sports Sci Med Rehabil 12:18 32190333 10.1186/s13102-020-00170-3 PMC7071585

Fournie C Verkindt C Dalleau G Bouscaren N Mohr C Zunic P Cabrera Q Rehabilitation program combining physical exercise and heart rate variability biofeedback in hematologic patients: a feasibility study Support Care Cancer 2022 30 3 2009 2016 34636946 10.1007/s00520-021-06601-2 PMC8794932 Fournie C, Verkindt C, Dalleau G, Bouscaren N, Mohr C, Zunic P, Cabrera Q (2022) Rehabilitation program combining physical exercise and heart rate variability biofeedback in hematologic patients: a feasibility study. Support Care Cancer 30(3):2009–2016 34636946 10.1007/s00520-021-06601-2 PMC8794932

Fu Q Levine BD Exercise and the autonomic nervous system Handb Clin Neurol 2013 117 147 160 24095123 10.1016/B978-0-444-53491-0.00013-4 Fu Q, Levine BD (2013) Exercise and the autonomic nervous system. Handb Clin Neurol 117:147–160 24095123 10.1016/B978-0-444-53491-0.00013-4

Gidron Y, a. DCM D. G. J (2014) If you have an active vagal nerve, cancer stage may no longer be important. 25001652

Gidron Y De Couck M De Greve J If you have an active vagal nerve, cancer stage May no longer be important J Biol Regul Homeost Agents 2014 28 195 201 25001652 Gidron Y, De Couck M, De Greve J (2014) If you have an active vagal nerve, cancer stage May no longer be important. J Biol Regul Homeost Agents 28:195–201 25001652

Gidron Y, De Couck M, Schallier D, De Greve J, Van Laethem JL, Marechal R (2018) The Relationship between a New Biomarker of Vagal Neuroimmunomodulation and Survival in Two Fatal Cancers. J Immunol Res 2018: 4874193 10.1155/2018/4874193 PMC5964597 29854838

Giese-Davis J Wilhelm FH Tamagawa R Palesh O Neri E Taylor CB Kraemer HC Spiegel D Higher vagal activity as related to survival in patients with advanced breast cancer: an analysis of autonomic dysregulation Psychosom Med 2015 77 4 346 355 25886831 10.1097/PSY.0000000000000167 PMC5509754 Giese-Davis J, Wilhelm FH, Tamagawa R, Palesh O, Neri E, Taylor CB, Kraemer HC, Spiegel D (2015) Higher vagal activity as related to survival in patients with advanced breast cancer: an analysis of autonomic dysregulation. Psychosom Med 77(4):346–355 25886831 10.1097/PSY.0000000000000167 PMC5509754

Gilchrist SC, Barac A, Ades PA, Alfano CM, Franklin BA, Jones LW, La Gerche A, Ligibel JA, Lopez G, Madan K, Oeffinger KC, Salamone J, Scott JM, Squires RW, Thomas RJ, Treat-Jacobson DJ, Wright JS C. r. R. American Heart Association Exercise, and Secondary Prevention Committee of the Council on Clinical Cardiology, C. o. C. a. S. Nursing and a. C. o. P. V. Disease (2019). Cardio-Oncology Rehabilitation to Manage Cardiovascular Outcomes in Cancer Patients and Survivors: A Scientific Statement From the American Heart Association. Circulation 139(21): e997-e1012 10.1161/CIR.0000000000000679 PMC7603804 30955352

Goldberger JJ Arora R Buckley U Shivkumar K Autonomic nervous system dysfunction: JACC focus seminar J Am Coll Cardiol 2019 73 10 1189 1206 30871703 10.1016/j.jacc.2018.12.064 PMC6958998 Goldberger JJ, Arora R, Buckley U, Shivkumar K (2019) Autonomic nervous system dysfunction: JACC focus seminar. J Am Coll Cardiol 73(10):1189–1206 30871703 10.1016/j.jacc.2018.12.064 PMC6958998

Gonzalez M Pascoe MC Yang G de Manincor M Grant S Lacey J Firth J Sarris J Yoga for depression and anxiety symptoms in people with cancer: A systematic review and meta-analysis Psychooncology 2021 30 8 1196 1208 33763925 10.1002/pon.5671 Gonzalez M, Pascoe MC, Yang G, de Manincor M, Grant S, Lacey J, Firth J, Sarris J (2021) Yoga for depression and anxiety symptoms in people with cancer: A systematic review and meta-analysis. Psychooncology 30(8):1196–1208 33763925 10.1002/pon.5671

Grote S Ricci JM Dehom S Modeste N Sealy DA Tarleton HP Heart rate variability and cardiovascular adaptations among Cancer-Survivors following a 26-Week exercise intervention Integr Cancer Ther 2020 19 1534735420969816 33118412 10.1177/1534735420969816 PMC7605052 Grote S, Ricci JM, Dehom S, Modeste N, Sealy DA, Tarleton HP (2020) Heart rate variability and cardiovascular adaptations among Cancer-Survivors following a 26-Week exercise intervention. Integr Cancer Ther 19:1534735420969816 33118412 10.1177/1534735420969816 PMC7605052

Guo Y Koshy S Hui D Palmer JL Shin K Bozkurt M Yusuf SW Prognostic value of heart rate variability in patients with Cancer J Clin Neurophysiol 2015 32 6 516 520 26629761 10.1097/WNP.0000000000000210 PMC4668946 Guo Y, Koshy S, Hui D, Palmer JL, Shin K, Bozkurt M, Yusuf SW (2015) Prognostic value of heart rate variability in patients with Cancer. J Clin Neurophysiol 32(6):516–520 26629761 10.1097/WNP.0000000000000210 PMC4668946

Hassani B Attar Z Firouzabadi N The renin-angiotensin-aldosterone system (RAAS) signaling pathways and cancer: foes versus allies Cancer Cell Int 2023 23 1 254 37891636 10.1186/s12935-023-03080-9 PMC10604988 Hassani B, Attar Z, Firouzabadi N (2023) The renin-angiotensin-aldosterone system (RAAS) signaling pathways and cancer: foes versus allies. Cancer Cell Int 23(1):254 37891636 10.1186/s12935-023-03080-9 PMC10604988

HC S (2016) Effects of circuit exercise on autonomic nerve system of survivors after surgery of breast cancer. Journal of Physical Therapy Science 10.1589/jpts.28.2898 PMC5088149 27821958

Health NC (2024a) f. C. a. I. 2024). Qigong: What You Need To Know. Retrieved 30/07/2024, 2024, from https://www.nccih.nih.gov/health/qigong-what-you-need-to-know

Health NC (2024b) f. C. a. I. Tai Chi: What You Need To Know. Retrieved 30/07/2024, 2024, from https://www.nccih.nih.gov/health/tai-chi-what-you-need-to-know

Health NC (2024c) f. C. a. I. Yoga: What You Need To Know. Retrieved 30/07/2024, 2024, from https://www.nccih.nih.gov/health/yoga-what-you-need-to-know

Howell KE Shaw M Santucci AK Rodgers K Ortiz Rodriguez I Taha D Laclair S Wolder C Cooper C Moon W Vukadinovich C Erhardt MJ Dean SM Armstrong GT Ness KK Hudson MM Yasui Y Huang IC Using an mHealth approach to collect patient-generated health data for predicting adverse health outcomes among adult survivors of childhood cancer Front Oncol 2024 14 1374403 38800387 10.3389/fonc.2024.1374403 PMC11116558 Howell KE, Shaw M, Santucci AK, Rodgers K, Ortiz Rodriguez I, Taha D, Laclair S, Wolder C, Cooper C, Moon W, Vukadinovich C, Erhardt MJ, Dean SM, Armstrong GT, Ness KK, Hudson MM, Yasui Y, Huang IC (2024) Using an mHealth approach to collect patient-generated health data for predicting adverse health outcomes among adult survivors of childhood cancer. Front Oncol 14:1374403 38800387 10.3389/fonc.2024.1374403 PMC11116558

Hu S Lou J Zhang Y Chen P Low heart rate variability relates to the progression of gastric cancer World J Surg Oncol 2018 16 1 49 29514707 10.1186/s12957-018-1348-z PMC5842632 Hu S, Lou J, Zhang Y, Chen P (2018) Low heart rate variability relates to the progression of gastric cancer. World J Surg Oncol 16(1):49 29514707 10.1186/s12957-018-1348-z PMC5842632

Hughes DC, Ellefsen S, Baar K (2018) Adaptations to endurance and strength training. Cold Spring Harb Perspect Med 8(6) 10.1101/cshperspect.a029769 PMC5983157 28490537

Hyeng-Cheol Shin J-OY, Seung-Ryol Kim (2016) Effects of circuit exercise on autonomic nerve system of survivors after surgery of breast cancer. The Journal of Physical Therapy Science 10.1589/jpts.28.2898 PMC5088149 27821958

Inbaraj G Udupa K Raghavendra RM Ram A Patil S Rajeswaran J Nandakumar KK Belur S Arjun K Govindaraj R Bayari SK Sathyaprabha TN Effects of an 18-Week integrated yoga program on cardiac autonomic function in breast Cancer patients undergoing adjuvant chemotherapy: A randomized controlled trial Integr Cancer Ther 2023 22 15347354231168795 37594042 10.1177/15347354231168795 PMC10467170 Inbaraj G, Udupa K, Raghavendra RM, Ram A, Patil S, Rajeswaran J, Nandakumar KK, Belur S, Arjun K, Govindaraj R, Bayari SK, Sathyaprabha TN (2023) Effects of an 18-Week integrated yoga program on cardiac autonomic function in breast Cancer patients undergoing adjuvant chemotherapy: A randomized controlled trial. Integr Cancer Ther 22:15347354231168795 37594042 10.1177/15347354231168795 PMC10467170

Kim DH Kim JA Choi YS Kim SH Lee JY Kim YE Heart rate variability and length of survival in hospice cancer patients J Korean Med Sci 2010 25 8 1140 1145 20676323 10.3346/jkms.2010.25.8.1140 PMC2908781 Kim DH, Kim JA, Choi YS, Kim SH, Lee JY, Kim YE (2010) Heart rate variability and length of survival in hospice cancer patients. J Korean Med Sci 25(8):1140–1145 20676323 10.3346/jkms.2010.25.8.1140 PMC2908781

Kingwell BA (2000) NITRIC OXIDE AS A METABOLIC REGULATOR DURING EXERCISE. EFFECTS OF TRAINING IN HEALTH AND DISEASE. 10.1046/j.1440-1681.2000.03232.x 10779120

Kirkham AA Lloyd MG Claydon VE Gelmon KA McKenzie DC Campbell KL A longitudinal study of the association of clinical indices of cardiovascular autonomic function with breast Cancer treatment and exercise training Oncologist 2019 24 2 273 284 30257888 10.1634/theoncologist.2018-0049 PMC6369953 Kirkham AA, Lloyd MG, Claydon VE, Gelmon KA, McKenzie DC, Campbell KL (2019) A longitudinal study of the association of clinical indices of cardiovascular autonomic function with breast Cancer treatment and exercise training. Oncologist 24(2):273–284 30257888 10.1634/theoncologist.2018-0049 PMC6369953

Koenig J Thayer JF Sex differences in healthy human heart rate variability: A meta-analysis Neurosci Biobehav Rev 2016 64 288 310 26964804 10.1016/j.neubiorev.2016.03.007 Koenig J, Thayer JF (2016) Sex differences in healthy human heart rate variability: A meta-analysis. Neurosci Biobehav Rev 64:288–310 26964804 10.1016/j.neubiorev.2016.03.007

Koeppel M Mathis K Schmitz KH Wiskemann J Muscle hypertrophy in cancer patients and survivors via strength training. A meta-analysis and meta-regression Crit Rev Oncol Hematol 2021 163 103371 34062243 10.1016/j.critrevonc.2021.103371 Koeppel M, Mathis K, Schmitz KH, Wiskemann J (2021) Muscle hypertrophy in cancer patients and survivors via strength training. A meta-analysis and meta-regression. Crit Rev Oncol Hematol 163:103371 34062243 10.1016/j.critrevonc.2021.103371

Laborde S Mosley E Thayer JF Heart rate variability and cardiac vagal tone in Psychophysiological Research - Recommendations for experiment planning, data analysis, and data reporting Front Psychol 2017 8 213 28265249 10.3389/fpsyg.2017.00213 PMC5316555 Laborde S, Mosley E, Thayer JF (2017) Heart rate variability and cardiac vagal tone in Psychophysiological Research - Recommendations for experiment planning, data analysis, and data reporting. Front Psychol 8:213 28265249 10.3389/fpsyg.2017.00213 PMC5316555

Larsen CM Garcia Arango M Dasari H Arciniegas Calle M Adjei E Rico Mesa J Scott CG Thompson CA Cerhan JR Haddad TC Goetz MP Herrmann J Villarraga HR Association of anthracycline with heart failure in patients treated for breast Cancer or lymphoma, 1985–2010 JAMA Netw Open 2023 6 2 e2254669 36735254 10.1001/jamanetworkopen.2022.54669 PMC9898820 Larsen CM, Garcia Arango M, Dasari H, Arciniegas Calle M, Adjei E, Rico Mesa J, Scott CG, Thompson CA, Cerhan JR, Haddad TC, Goetz MP, Herrmann J, Villarraga HR (2023) Association of anthracycline with heart failure in patients treated for breast Cancer or lymphoma, 1985–2010. JAMA Netw Open 6(2):e2254669 36735254 10.1001/jamanetworkopen.2022.54669 PMC9898820

Lavin-Perez AM Collado-Mateo D Hinojo Gonzalez C Batista M Mayo X Ruisanchez Villar C Jimenez A An online home-based exercise program improves autonomic dysfunction in breast cancer survivors Front Physiol 2023 14 1256644 37841312 10.3389/fphys.2023.1256644 PMC10570414 Lavin-Perez AM, Collado-Mateo D, Hinojo Gonzalez C, Batista M, Mayo X, Ruisanchez Villar C, Jimenez A (2023a) An online home-based exercise program improves autonomic dysfunction in breast cancer survivors. Front Physiol 14:1256644 37841312 10.3389/fphys.2023.1256644 PMC10570414

Lavin-Perez AM Collado-Mateo D Hinojo Gonzalez C de Juan Ferre A Ruisanchez Villar C Mayo X Jimenez A High-intensity exercise prescription guided by heart rate variability in breast cancer patients: a study protocol for a randomized controlled trial BMC Sports Sci Med Rehabil 2023 15 1 28 36890601 10.1186/s13102-023-00634-2 PMC9993392 >Lavin-Perez AM, Collado-Mateo D, Hinojo Gonzalez C, de Juan Ferre A, Ruisanchez Villar C, Mayo X, Jimenez A (2023b) High-intensity exercise prescription guided by heart rate variability in breast cancer patients: a study protocol for a randomized controlled trial. BMC Sports Sci Med Rehabil 15(1):28 36890601 10.1186/s13102-023-00634-2 PMC9993392

Lavín-Pérez AM, Collado-Mateo D, Hinojo González C, de Juan Ferré A, Ruisánchez C, Villar X, Mayo, Jiménez A (2023) Exploring autonomic modulation: day-to-day recovery after exercise sessions in breast cancer survivors. Front Oncol 13 10.3389/fonc.2023.1231683 PMC10442838 37614512

Lee YH Lai GM Lee DC Tsai Lai LJ Chang YP Promoting physical and psychological rehabilitation activities and evaluating potential links among Cancer-Related fatigue, fear of recurrence, quality of life, and physiological indicators in Cancer survivors Integr Cancer Ther 2018 17 4 1183 1194 30354701 10.1177/1534735418805149 PMC6247550 Lee YH, Lai GM, Lee DC, Tsai Lai LJ, Chang YP (2018) Promoting physical and psychological rehabilitation activities and evaluating potential links among Cancer-Related fatigue, fear of recurrence, quality of life, and physiological indicators in Cancer survivors. Integr Cancer Ther 17(4):1183–1194 30354701 10.1177/1534735418805149 PMC6247550

Lee YH Chang YP Lee JT Lee DC Huang EY Lai LT Heart rate variability as an indicator of the beneficial effects of qigong and mindfulness training on the mind-body well-being of cancer survivors Support Care Cancer 2022 31 1 59 36534354 10.1007/s00520-022-07476-7 PMC9761690 Lee YH, Chang YP, Lee JT, Lee DC, Huang EY, Lai LT (2022) Heart rate variability as an indicator of the beneficial effects of qigong and mindfulness training on the mind-body well-being of cancer survivors. Support Care Cancer 31(1):59 36534354 10.1007/s00520-022-07476-7 PMC9761690

Li G Wu S Zhao H Guan W Zhou Y Shi B Non-invasive prognostic biomarker of lung cancer patients with brain metastases: recurrence quantification analysis of heart rate variability Front Physiol 2022 13 987835 36148296 10.3389/fphys.2022.987835 PMC9486009 Li G, Wu S, Zhao H, Guan W, Zhou Y, Shi B (2022) Non-invasive prognostic biomarker of lung cancer patients with brain metastases: recurrence quantification analysis of heart rate variability. Front Physiol 13:987835 36148296 10.3389/fphys.2022.987835 PMC9486009

Li K Cardoso C Moctezuma-Ramirez A Elgalad A Perin E Heart rate variability measurement through a smart wearable device: another breakthrough for personal health monitoring?? Int J Environ Res Public Health 2023 20 24 7146 38131698 10.3390/ijerph20247146 PMC10742885 Li K, Cardoso C, Moctezuma-Ramirez A, Elgalad A, Perin E (2023) Heart rate variability measurement through a smart wearable device: another breakthrough for personal health monitoring?? Int J Environ Res Public Health 20(24):7146 38131698 10.3390/ijerph20247146 PMC10742885

Linden W Vodermaier A Mackenzie R Greig D Anxiety and depression after cancer diagnosis: prevalence rates by cancer type, gender, and age J Affect Disord 2012 141 2–3 343 351 22727334 10.1016/j.jad.2012.03.025 Linden W, Vodermaier A, Mackenzie R, Greig D (2012) Anxiety and depression after cancer diagnosis: prevalence rates by cancer type, gender, and age. J Affect Disord 141(2–3):343–351 22727334 10.1016/j.jad.2012.03.025

Liu J Liu S Gao L Li G Xu J Sun Y Wang J Shi B Predicting Post-operative blood inflammatory biomarkers using Pre-operative heart rate variability in patients with cervical Cancer Front Physiol 2021 12 696208 34803724 10.3389/fphys.2021.696208 PMC8599823 Liu J, Liu S, Gao L, Li G, Xu J, Sun Y, Wang J, Shi B (2021) Predicting Post-operative blood inflammatory biomarkers using Pre-operative heart rate variability in patients with cervical Cancer. Front Physiol 12:696208 34803724 10.3389/fphys.2021.696208 PMC8599823

Magnon C Role of the autonomic nervous system in tumorigenesis and metastasis Mol Cell Oncol 2015 2 2 e975643 27308436 10.4161/23723556.2014.975643 PMC4904882 Magnon C (2015) Role of the autonomic nervous system in tumorigenesis and metastasis. Mol Cell Oncol 2(2):e975643 27308436 10.4161/23723556.2014.975643 PMC4904882

Martinez P Grinand M Cheggour S Taieb J Gourjon G How to properly evaluate cardiac vagal tone in oncology studies: a state-of-the-art review J Natl Cancer Cent 2024 4 1 36 46 39036385 10.1016/j.jncc.2024.02.002 PMC11256691 Martinez P, Grinand M, Cheggour S, Taieb J, Gourjon G (2024) How to properly evaluate cardiac vagal tone in oncology studies: a state-of-the-art review. J Natl Cancer Cent 4(1):36–46 39036385 10.1016/j.jncc.2024.02.002 PMC11256691

Masel EK Huber P Schur S Kierner KA Nemecek R Watzke HH Predicting discharge of palliative care inpatients by measuring their heart rate variability Ann Palliat Med 2014 3 4 244 249 25841904 10.3978/j.issn.2224-5820.2014.08.01 Masel EK, Huber P, Schur S, Kierner KA, Nemecek R, Watzke HH (2014) Predicting discharge of palliative care inpatients by measuring their heart rate variability. Ann Palliat Med 3(4):244–249 25841904 10.3978/j.issn.2224-5820.2014.08.01

McGovern J Leadbitter S Miller G Hounat A Kamande I Dolan RD Horgan PG Chang DK Jamieson NB McMillan DC The relationship between heart rate variability and TNM stage, co-morbidity, systemic inflammation and survival in patients with primary operable colorectal cancer Sci Rep 2023 13 1 8157 37208421 10.1038/s41598-023-35396-x PMC10198985 McGovern J, Leadbitter S, Miller G, Hounat A, Kamande I, Dolan RD, Horgan PG, Chang DK, Jamieson NB, McMillan DC (2023) The relationship between heart rate variability and TNM stage, co-morbidity, systemic inflammation and survival in patients with primary operable colorectal cancer. Sci Rep 13(1):8157 37208421 10.1038/s41598-023-35396-x PMC10198985

McIntyre WF Oqab Z Seaborn GE Hopman WM Hammad N Baranchuk A Changes in plasma hormones and heart rate variability in patients receiving the cardiotoxic anti-cancer agent bevacizumab Int J Cardiol 2016 219 25 26 27257852 10.1016/j.ijcard.2016.05.061 McIntyre WF, Oqab Z, Seaborn GE, Hopman WM, Hammad N, Baranchuk A (2016) Changes in plasma hormones and heart rate variability in patients receiving the cardiotoxic anti-cancer agent bevacizumab. Int J Cardiol 219:25–26 27257852 10.1016/j.ijcard.2016.05.061

Montisci A Palmieri V Liu JE Vietri MT Cirri S Donatelli F Napoli C Severe cardiac toxicity induced by Cancer therapies requiring intensive care unit admission Front Cardiovasc Med 2021 8 713694 34540917 10.3389/fcvm.2021.713694 PMC8446380 Montisci A, Palmieri V, Liu JE, Vietri MT, Cirri S, Donatelli F, Napoli C (2021) Severe cardiac toxicity induced by Cancer therapies requiring intensive care unit admission. Front Cardiovasc Med 8:713694 34540917 10.3389/fcvm.2021.713694 PMC8446380

Mostarda C, Castro-Filha J, Reis AD, Sevilio M Jr., Dias CJ, Silva-Filho AC, Garcia JBS, Nascimento M, Coelho-Junior HJ, Rodrigues B (2017) Short-term combined exercise training improves cardiorespiratory fitness and autonomic modulation in cancer patients receiving adjuvant therapy. J Exerc Rehabil 13(5): 599–607 10.12965/jer.1735048.524 PMC5667608 29114536

Mouton C Ronson A Razavi D Delhaye F Kupper N Paesmans M Moreau M Nogaret JM Hendlisz A Gidron Y The relationship between heart rate variability and time-course of carcinoembryonic antigen in colorectal cancer Auton Neurosci 2012 166 1–2 96 99 22070982 10.1016/j.autneu.2011.10.002 Mouton C, Ronson A, Razavi D, Delhaye F, Kupper N, Paesmans M, Moreau M, Nogaret JM, Hendlisz A, Gidron Y (2012) The relationship between heart rate variability and time-course of carcinoembryonic antigen in colorectal cancer. Auton Neurosci 166(1–2):96–99 22070982 10.1016/j.autneu.2011.10.002

Niederer D Vogt L Thiel C Schmidt K Bernhorster M Lungwitz A Jager E Banzer W Exercise effects on HRV in cancer patients Int J Sports Med 2013 34 1 68 73 22895874 10.1055/s-0032-1314816 Niederer D, Vogt L, Thiel C, Schmidt K, Bernhorster M, Lungwitz A, Jager E, Banzer W (2013) Exercise effects on HRV in cancer patients. Int J Sports Med 34(1):68–73 22895874 10.1055/s-0032-1314816

Palesh OG Roscoe JA Mustian KM Roth T Savard J Ancoli-Israel S Heckler C Purnell JQ Janelsins MC Morrow GR Prevalence, demographics, and psychological associations of sleep disruption in patients with cancer: university of Rochester Cancer Center-Community clinical oncology program J Clin Oncol 2010 28 2 292 298 19933917 10.1200/JCO.2009.22.5011 PMC2815717 Palesh OG, Roscoe JA, Mustian KM, Roth T, Savard J, Ancoli-Israel S, Heckler C, Purnell JQ, Janelsins MC, Morrow GR (2010) Prevalence, demographics, and psychological associations of sleep disruption in patients with cancer: university of Rochester Cancer Center-Community clinical oncology program. J Clin Oncol 28(2):292–298 19933917 10.1200/JCO.2009.22.5011 PMC2815717

Patel AV Friedenreich CM Moore SC Hayes SC Silver JK Campbell KL Winters-Stone K Gerber LH George SM Fulton JE Denlinger C Morris GS Hue T Schmitz KH Matthews CE American college of sports medicine roundtable report on physical activity, sedentary behavior, and Cancer prevention and control Med Sci Sports Exerc 2019 51 11 2391 2402 31626056 10.1249/MSS.0000000000002117 PMC6814265 Patel AV, Friedenreich CM, Moore SC, Hayes SC, Silver JK, Campbell KL, Winters-Stone K, Gerber LH, George SM, Fulton JE, Denlinger C, Morris GS, Hue T, Schmitz KH, Matthews CE (2019) American college of sports medicine roundtable report on physical activity, sedentary behavior, and Cancer prevention and control. Med Sci Sports Exerc 51(11):2391–2402 31626056 10.1249/MSS.0000000000002117 PMC6814265

Perillo B Di Donato M Pezone A Di Zazzo E Giovannelli P Galasso G Castoria G Migliaccio A ROS in cancer therapy: the bright side of the Moon Exp Mol Med 2020 52 2 192 203 32060354 10.1038/s12276-020-0384-2 PMC7062874 Perillo B, Di Donato M, Pezone A, Di Zazzo E, Giovannelli P, Galasso G, Castoria G, Migliaccio A (2020) ROS in cancer therapy: the bright side of the Moon. Exp Mol Med 52(2):192–203 32060354 10.1038/s12276-020-0384-2 PMC7062874

Ramesh S James MT Holroyd-Leduc JM Wilton SB Sola DY Ahmed SB Heart rate variability as a function of menopausal status, menstrual cycle phase, and estradiol level Physiol Rep 2022 10 10 e15298 35608101 10.14814/phy2.15298 PMC9127980 Ramesh S, James MT, Holroyd-Leduc JM, Wilton SB, Sola DY, Ahmed SB (2022) Heart rate variability as a function of menopausal status, menstrual cycle phase, and estradiol level. Physiol Rep 10(10):e15298 35608101 10.14814/phy2.15298 PMC9127980

Repka CP Hayward R Oxidative stress and fitness changes in Cancer patients after exercise training Med Sci Sports Exerc 2016 48 4 607 614 26587845 10.1249/MSS.0000000000000821 PMC4979000 Repka CP, Hayward R (2016) Oxidative stress and fitness changes in Cancer patients after exercise training. Med Sci Sports Exerc 48(4):607–614 26587845 10.1249/MSS.0000000000000821 PMC4979000

Riesenberg H Lubbe AS In-patient rehabilitation of lung cancer patients–a prospective study Support Care Cancer 2010 18 7 877 882 19714371 10.1007/s00520-009-0727-y Riesenberg H, Lubbe AS (2010) In-patient rehabilitation of lung cancer patients–a prospective study. Support Care Cancer 18(7):877–882 19714371 10.1007/s00520-009-0727-y

Routledge FS Campbell TS McFetridge-Durdle JA Bacon SL Improvements in heart rate variability with exercise therapy Can J Cardiol 2010 26 6 303 312 20548976 10.1016/s0828-282x(10)70395-0 PMC2903986 Routledge FS, Campbell TS, McFetridge-Durdle JA, Bacon SL (2010) Improvements in heart rate variability with exercise therapy. Can J Cardiol 26(6):303–312 20548976 10.1016/s0828-282x(10)70395-0 PMC2903986

Saxton JM Scott EJ Daley AJ Woodroofe M Mutrie N Crank H Powers HJ Coleman RE Effects of an exercise and hypocaloric healthy eating intervention on indices of psychological health status, hypothalamic-pituitary-adrenal axis regulation and immune function after early-stage breast cancer: a randomised controlled trial Breast Cancer Res 2014 16 2 R39 24731917 10.1186/bcr3643 PMC4052984 Saxton JM, Scott EJ, Daley AJ, Woodroofe M, Mutrie N, Crank H, Powers HJ, Coleman RE (2014) Effects of an exercise and hypocaloric healthy eating intervention on indices of psychological health status, hypothalamic-pituitary-adrenal axis regulation and immune function after early-stage breast cancer: a randomised controlled trial. Breast Cancer Res 16(2):R39 24731917 10.1186/bcr3643 PMC4052984

Scott JM Zabor EC Schwitzer E Koelwyn GJ Adams SC Nilsen TS Moskowitz CS Matsoukas K Iyengar NM Dang CT Jones LW Efficacy of exercise therapy on cardiorespiratory fitness in patients with cancer: A systematic review and Meta-Analysis J Clin Oncol 2018 36 22 2297 2305 29894274 10.1200/JCO.2017.77.5809 PMC6804903 Scott JM, Zabor EC, Schwitzer E, Koelwyn GJ, Adams SC, Nilsen TS, Moskowitz CS, Matsoukas K, Iyengar NM, Dang CT, Jones LW (2018) Efficacy of exercise therapy on cardiorespiratory fitness in patients with cancer: A systematic review and Meta-Analysis. J Clin Oncol 36(22):2297–2305 29894274 10.1200/JCO.2017.77.5809 PMC6804903

Shaffer F Ginsberg JP An overview of heart rate variability metrics and norms Front Public Health 2017 5 258 29034226 10.3389/fpubh.2017.00258 PMC5624990 Shaffer F, Ginsberg JP (2017) An overview of heart rate variability metrics and norms. Front Public Health 5:258 29034226 10.3389/fpubh.2017.00258 PMC5624990

Singh N Baby D Rajguru JP Patil PB Thakkannavar SS Pujari VB Inflammation and cancer Ann Afr Med 2019 18 3 121 126 31417011 10.4103/aam.aam_56_18 PMC6704802 Singh N, Baby D, Rajguru JP, Patil PB, Thakkannavar SS, Pujari VB (2019) Inflammation and cancer. Ann Afr Med 18(3):121–126 31417011 10.4103/aam.aam_56_18 PMC6704802

Song J Wang T Wang Y Li R Niu S Zhuo L Guo Q Li X The effectiveness of yoga on Cancer-Related fatigue: A systematic review and Meta-Analysis Oncol Nurs Forum 2021 48 2 207 228 33600394 10.1188/21.ONF.207-228 Song J, Wang T, Wang Y, Li R, Niu S, Zhuo L, Guo Q, Li X (2021) The effectiveness of yoga on Cancer-Related fatigue: A systematic review and Meta-Analysis. Oncol Nurs Forum 48(2):207–228 33600394 10.1188/21.ONF.207-228

Stachowiak P Milchert-Leszczynska M Falco M Wojtarowicz A Kaliszczak R Safranow K Kornacewicz-Jach Z Heart rate variability during and after chemotherapy with anthracycline in patients with breast cancer Kardiol Pol 2018 76 5 914 916 29756192 10.5603/KP.2018.0098 Stachowiak P, Milchert-Leszczynska M, Falco M, Wojtarowicz A, Kaliszczak R, Safranow K, Kornacewicz-Jach Z (2018) Heart rate variability during and after chemotherapy with anthracycline in patients with breast cancer. Kardiol Pol 76(5):914–916 29756192 10.5603/KP.2018.0098

Storkebaum E, Ruiz de Almodovar C, Meens M, Zacchigna S, Mazzone M, Vanhoutte G, Vinckier S, Miskiewicz K, Poesen K, Lambrechts D, Janssen GM, Fazzi GE, Verstreken P, Haigh J, Schiffers PM, Rohrer H, Van der Linden A, De Mey JG, Carmeliet P (2010) Impaired autonomic regulation of resistance arteries in mice with low vascular endothelial growth factor or upon vascular endothelial growth factor trap delivery. Circulation 122(3): 273–281 10.1161/CIRCULATIONAHA.109.929364 20606119

Strous MTA Daniels AM Zimmermann FM van Erning FN Gidron Y Vogelaar FJ Is pre-operative heart rate variability a prognostic indicator for overall survival and cancer recurrence in patients with primary colorectal cancer? PLoS ONE 2020 15 8 e0237244 32817663 10.1371/journal.pone.0237244 PMC7440652 Strous MTA, Daniels AM, Zimmermann FM, van Erning FN, Gidron Y, Vogelaar FJ (2020) Is pre-operative heart rate variability a prognostic indicator for overall survival and cancer recurrence in patients with primary colorectal cancer? PLoS ONE 15(8):e0237244 32817663 10.1371/journal.pone.0237244 PMC7440652

Sturgeon KM Deng L Bluethmann SM Zhou S Trifiletti DM Jiang C Kelly SP Zaorsky NG A population-based study of cardiovascular disease mortality risk in US cancer patients Eur Heart J 2019 40 48 3889 3897 31761945 10.1093/eurheartj/ehz766 PMC6925383 Sturgeon KM, Deng L, Bluethmann SM, Zhou S, Trifiletti DM, Jiang C, Kelly SP, Zaorsky NG (2019) A population-based study of cardiovascular disease mortality risk in US cancer patients. Eur Heart J 40(48):3889–3897 31761945 10.1093/eurheartj/ehz766 PMC6925383

Sweegers MG Altenburg TM Brug J May AM van Vulpen JK Aaronson NK Arbane G Bohus M Courneya KS Daley AJ Galvao DA Garrod R Griffith KA Van Harten WH Hayes SC Herrero-Roman F Kersten MJ Lucia A McConnachie A van Mechelen W Mutrie N Newton RU Nollet F Potthoff K Schmidt ME Schmitz KH Schulz KH Sonke G Steindorf K Stuiver MM Taaffe DR Thorsen L Twisk JW Velthuis MJ Wenzel J Winters-Stone KM Wiskemann J Chin APMJ Buffart LM Effects and moderators of exercise on muscle strength, muscle function and aerobic fitness in patients with cancer: a meta-analysis of individual patient data Br J Sports Med 2019 53 13 812 30181323 10.1136/bjsports-2018-099191 Sweegers MG, Altenburg TM, Brug J, May AM, van Vulpen JK, Aaronson NK, Arbane G, Bohus M, Courneya KS, Daley AJ, Galvao DA, Garrod R, Griffith KA, Van Harten WH, Hayes SC, Herrero-Roman F, Kersten MJ, Lucia A, McConnachie A, van Mechelen W, Mutrie N, Newton RU, Nollet F, Potthoff K, Schmidt ME, Schmitz KH, Schulz KH, Sonke G, Steindorf K, Stuiver MM, Taaffe DR, Thorsen L, Twisk JW, Velthuis MJ, Wenzel J, Winters-Stone KM, Wiskemann J, Chin APMJ, Buffart LM (2019) Effects and moderators of exercise on muscle strength, muscle function and aerobic fitness in patients with cancer: a meta-analysis of individual patient data. Br J Sports Med 53(13):812 30181323 10.1136/bjsports-2018-099191

Teng AE Noor B Ajijola OA Yang EH Chemotherapy and Radiation-Associated cardiac autonomic dysfunction Curr Oncol Rep 2021 23 2 14 33417078 10.1007/s11912-020-01013-7 Teng AE, Noor B, Ajijola OA, Yang EH (2021) Chemotherapy and Radiation-Associated cardiac autonomic dysfunction. Curr Oncol Rep 23(2):14 33417078 10.1007/s11912-020-01013-7

Toohey K Pumpa K McKune A Cooke J Welvaert M Northey J Quinlan C Semple S The impact of high-intensity interval training exercise on breast cancer survivors: a pilot study to explore fitness, cardiac regulation and biomarkers of the stress systems BMC Cancer 2020 20 1 787 32819304 10.1186/s12885-020-07295-1 PMC7441660 Toohey K, Pumpa K, McKune A, Cooke J, Welvaert M, Northey J, Quinlan C, Semple S (2020) The impact of high-intensity interval training exercise on breast cancer survivors: a pilot study to explore fitness, cardiac regulation and biomarkers of the stress systems. BMC Cancer 20(1):787 32819304 10.1186/s12885-020-07295-1 PMC7441660

Touitou Y, Reinberg A, Touitou D (2017) Association between light at night, melatonin secretion, sleep deprivation, and the internal clock: health impacts and mechanisms of circadian disruption. Life Sci 173:94–106. 10.1016/j.lfs.2017.02.008 10.1016/j.lfs.2017.02.008 28214594

Townend A-A, West C (1995) Modulation of Cardiac Autonomic Control in Humans by Angiotensin II. Hypertension 10.1161/01.hyp.25.6.1270 7768573

Vear NK, Moon Y, Mielke GI, Skinner TL, Coombes JS, McCarthy AL, Abbott CR, Bailey TG (2023) Efficacy of exercise training for improving vascular dysfunction in people with cancer: a systematic review with meta-analyses. J Cancer surviv 10.1007/s11764-023-01372-7 PMC11324680 37079184

Verheijden RJ, Cabane Ballester A, Smit KC, van Eijs MJM, Bruijnen CP, van Lindert ASR, Suijkerbuijk KPM, May AM (2023) Physical activity and checkpoint Inhibition: association with toxicity and survival. J Natl Cancer Inst 10.1093/jnci/djad245 PMC10995850 38001030

Wang YM, Wu HT, Huang EY, Kou YR, Hseu SS (2013) Heart rate variability is associated with survival in patients with brain metastasis: a preliminary report. Biomed Res Int 2013: 503421 10.1155/2013/503421 PMC3786541 24102056

Wang L Wang J Li P Wang X Wu S Shi B Association between short-term heart rate variability and blood coagulation in patients with breast cancer Sci Rep 2021 11 1 15414 34326419 10.1038/s41598-021-94931-w PMC8322388 Wang L, Wang J, Li P, Wang X, Wu S, Shi B (2021) Association between short-term heart rate variability and blood coagulation in patients with breast cancer. Sci Rep 11(1):15414 34326419 10.1038/s41598-021-94931-w PMC8322388

WHO (2021) Cancer. from https://www.who.int/news-room/fact-sheets/detail/cancer

Williams K Steptoe A Wardle J Is a cancer diagnosis a trigger for health behaviour change? Findings from a prospective, population-based study Br J Cancer 2013 108 11 2407 2412 23695026 10.1038/bjc.2013.254 PMC3681023 Williams K, Steptoe A, Wardle J (2013) Is a cancer diagnosis a trigger for health behaviour change? Findings from a prospective, population-based study. Br J Cancer 108(11):2407–2412 23695026 10.1038/bjc.2013.254 PMC3681023

Wu S Li G Guan W Zhao H Wang J Zhou Y Zhou Y Shi B Low heart rate variability predicts poor overall survival of lung Cancer patients with brain metastases Front Neurosci 2022 16 839874 35250470 10.3389/fnins.2022.839874 PMC8891474 Wu S, Li G, Guan W, Zhao H, Wang J, Zhou Y, Zhou Y, Shi B (2022) Low heart rate variability predicts poor overall survival of lung Cancer patients with brain metastases. Front Neurosci 16:839874 35250470 10.3389/fnins.2022.839874 PMC8891474

Wu S Guan W Zhao H Li G Zhou Y Shi B Zhang X Prognostic role of short-term heart rate variability and deceleration/acceleration capacities of heart rate in extensive-stage small cell lung cancer Front Physiol 2023 14 1277383 38028778 10.3389/fphys.2023.1277383 PMC10663334 Wu S, Guan W, Zhao H, Li G, Zhou Y, Shi B, Zhang X (2023a) Prognostic role of short-term heart rate variability and deceleration/acceleration capacities of heart rate in extensive-stage small cell lung cancer. Front Physiol 14:1277383 38028778 10.3389/fphys.2023.1277383 PMC10663334

Wu S Li G Chen M Zhang S Zhou Y Shi B Zhang X Association of heartbeat complexity with survival in advanced non-small cell lung cancer patients Front Neurosci 2023 17 1113225 37123354 10.3389/fnins.2023.1113225 PMC10130527 Wu S, Li G, Chen M, Zhang S, Zhou Y, Shi B, Zhang X (2023b) Association of heartbeat complexity with survival in advanced non-small cell lung cancer patients. Front Neurosci 17:1113225 37123354 10.3389/fnins.2023.1113225 PMC10130527

Yang L Winters-Stone K Rana B Cao C Carlson LE Courneya KS Friedenreich CM Schmitz KH Tai Chi for cancer survivors: A systematic review toward consensus-based guidelines Cancer Med 2021 10 21 7447 7456 34533284 10.1002/cam4.4273 PMC8559497 Yang L, Winters-Stone K, Rana B, Cao C, Carlson LE, Courneya KS, Friedenreich CM, Schmitz KH (2021) Tai Chi for cancer survivors: A systematic review toward consensus-based guidelines. Cancer Med 10(21):7447–7456 34533284 10.1002/cam4.4273 PMC8559497

Yang H Liu L Zhang X Exercise interventions on body composition and quality of life of overweight/obese breast cancer survivors: a meta-analysis BMC Womens Health 2023 23 1 484 37700300 10.1186/s12905-023-02627-2 PMC10498647 Yang H, Liu L, Zhang X (2023) Exercise interventions on body composition and quality of life of overweight/obese breast cancer survivors: a meta-analysis. BMC Womens Health 23(1):484 37700300 10.1186/s12905-023-02627-2 PMC10498647

Yu TY Lee MK Autonomic dysfunction, diabetes and metabolic syndrome J Diabetes Investig 2021 12 12 2108 2111 34622579 10.1111/jdi.13691 PMC8668070 Yu TY, Lee MK (2021) Autonomic dysfunction, diabetes and metabolic syndrome. J Diabetes Investig 12(12):2108–2111 34622579 10.1111/jdi.13691 PMC8668070

Zamorano JL Lancellotti P Rodriguez Muñoz D Aboyans V Asteggiano R Galderisi M Habib G Lenihan DJ Lip GYH Lyon AR Lopez Fernandez T Mohty D Piepoli MF Tamargo J Torbicki A Suter TM Group ESD 2016 ESC position paper on cancer treatments and cardiovascular toxicity developed under the auspices of the ESC committee for practice guidelines: the task force for cancer treatments and cardiovascular toxicity of the European society of cardiology (ESC) Eur Heart J 2016 37 36 2768 2801 27567406 10.1093/eurheartj/ehw211 Zamorano JL, Lancellotti P, Rodriguez Muñoz D, Aboyans V, Asteggiano R, Galderisi M, Habib G, Lenihan DJ, Lip GYH, Lyon AR, Lopez Fernandez T, Mohty D, Piepoli MF, Tamargo J, Torbicki A, Suter TM, Group ESD (2016) 2016 ESC position paper on cancer treatments and cardiovascular toxicity developed under the auspices of the ESC committee for practice guidelines: the task force for cancer treatments and cardiovascular toxicity of the European society of cardiology (ESC). Eur Heart J 37(36):2768–2801 27567406 10.1093/eurheartj/ehw211

Zhou W Wan Y-H Chen Q Qiu Y-R Luo X-M Effects of Tai Chi exercise on Cancer-Related fatigue in patients with nasopharyngeal carcinoma undergoing chemoradiotherapy: A randomized controlled trial J Pain Symptom Manag 2018 55 3 737 744 10.1016/j.jpainsymman.2017.10.021 29122618 Zhou W, Wan Y-H, Chen Q, Qiu Y-R, Luo X-M (2018a) Effects of Tai Chi exercise on Cancer-Related fatigue in patients with nasopharyngeal carcinoma undergoing chemoradiotherapy: A randomized controlled trial. J Pain Symptom Manag 55(3):737–744 10.1016/j.jpainsymman.2017.10.021 29122618

Zhou W Wan YH Chen Q Qiu YR Luo XM Effects of Tai Chi exercise on Cancer-Related fatigue in patients with nasopharyngeal carcinoma undergoing chemoradiotherapy: A randomized controlled trial J Pain Symptom Manage 2018 55 3 737 744 29122618 10.1016/j.jpainsymman.2017.10.021 Zhou W, Wan YH, Chen Q, Qiu YR, Luo XM (2018b) Effects of Tai Chi exercise on Cancer-Related fatigue in patients with nasopharyngeal carcinoma undergoing chemoradiotherapy: A randomized controlled trial. J Pain Symptom Manage 55(3):737–744 29122618 10.1016/j.jpainsymman.2017.10.021