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Impact of cancer and chemotherapy on autonomic nervous system function and cardiovascular reactivity in young adults with cancer: a case-controlled feasibility study


Impact of cancer and chemotherapy on autonomic nervous system function and cardiovascular reactivity in young adults with cancer: a case-controlled feasibility study

Adams, Scott C., Schondorf, Ronald, Benoit, Julie and Kilgour, Robert D. (2015) Impact of cancer and chemotherapy on autonomic nervous system function and cardiovascular reactivity in young adults with cancer: a case-controlled feasibility study. BMC Cancer, 15 (1). ISSN 1471-2407

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Official URL: http://dx.doi.org/10.1186/s12885-015-1418-3


Preliminary evidence suggests cancer- and chemotherapy-related autonomic nervous system (ANS) dysfunction may contribute to the increased cardiovascular (CV) morbidity- and mortality-risks in cancer survivors. However, the reliability of these findings may have been jeopardized by inconsistent participant screening and assessment methods. Therefore, good laboratory practices must be established before the presence and nature of cancer-related autonomic dysfunction can be characterized. The purpose of this study was to assess the feasibility of conducting concurrent ANS and cardiovascular evaluations in young adult cancer patients, according to the following criteria: i) identifying methodological pitfalls and proposing good laboratory practice criteria for ANS testing in cancer, and ii) providing initial physiologic evidence of autonomic perturbations in cancer patients using the composite autonomic scoring scale (CASS).

Thirteen patients (mixed diagnoses) were assessed immediately before and after 4 cycles of chemotherapy. Their results were compared to 12 sex- and age-matched controls. ANS function was assessed using standardized tests of resting CV (tilt-table, respiratory sinus arrhythmia and Valsalva maneuver) and sudomotor (quantitative sudomotor axon reflex test) reactivity. Cardiovascular reactivity during exercise was assessed using a modified Astrand-Ryhming cycle ergometer protocol. Our feasibility criteria addressed: i) recruitment potential, ii) retention rates, iii) pre-chemotherapy assessment potential, iv) test performance/tolerability, and v) identification and minimizing the influence of potentially confounding medication. T-tests and repeated measures ANOVAs were used to assess between- and within-group differences at baseline and follow-up.

The overall success rate in achieving our feasibility criteria was 98.4 %. According to the CASS, there was evidence of ANS impairment at baseline in 30.8 % of patients, which persisted in 18.2 % of patients at follow-up, compared to 0 % of controls at baseline or follow-up.

Results from our feasibility assessment suggest that the investigation of ANS function in young adult cancer patients undergoing chemotherapy is possible. To the best of our knowledge, this is the first study to report CASS-based evidence of ANS impairment and sudomotor dysfunction in any cancer population. Moreover, we provide evidence of cancer- and chemotherapy-related parasympathetic dysfunction – as a possible contributor to the pathogenesis of CV disease in cancer survivors.

Divisions:Concordia University > Faculty of Arts and Science > Exercise Science
Item Type:Article
Authors:Adams, Scott C. and Schondorf, Ronald and Benoit, Julie and Kilgour, Robert D.
Journal or Publication:BMC Cancer
  • Concordia Open Access Author Fund
Digital Object Identifier (DOI):10.1186/s12885-015-1418-3
Keywords:Cancer, Autonomic nervous system, Composite autonomic scoring scale, Cardiovascular disease, Young adults
ID Code:982239
Deposited On:17 Mar 2017 20:37
Last Modified:18 Jan 2018 17:54


Monsuez JJ, Charniot JC, Vignat N, Artigou JY. Cardiac side-effects of cancer chemotherapy. Int J Cardiol. 2010;144(1):3–15.

Senkus E, Jassem J. Cardiovascular effects of systemic cancer treatment. Cancer Treat Rev. 2011;37(4):300–11.

Thayer JF, Lane RD. The role of vagal function in the risk for cardiovascular disease and mortality. Biol Psychol. 2007;74(2):224–42.

Habib GB. Reappraisal of heart rate as a risk factor in the general population. Eur Heart J Suppl. 1999;1(H):2–10.

Brook RD, Julius S. Autonomic imbalance, hypertension, and cardiovascular risk. Am J Hypertens. 2000;13(S4):112S–22.

Hirvonen HE, Salmi TT, Heinonen E, Antila KJ, Valimaki IA. Vincristine treatment of acute lymphoblastic leukemia induces transient autonomic cardioneuropathy. Cancer. 1989;64(4):801–5.

Hrushesky WJ, Fader DJ, Berestka JS, Sommer M, Hayes J, Cope FO. Diminishment of respiratory sinus arrhythmia foreshadows doxorubicin-induced cardiomyopathy. Circulation. 1991;84(2):697–707.

Hansen SW. Autonomic neuropathy after treatment with cisplatin, vinblastine, and bleomycin for germ cell cancer. BMJ. 1990;300(6723):511–2.

Turner ML, Boland OM, Parker AC, Ewing DJ. Subclinical autonomic dysfunction in patients with Hodgkin's disease and non-Hodgkin's lymphoma. Br J Haematol. 1993;84(4):623–6.

Ekholm E, Salminen E, Huikuri H, Jalonen J, Antila K, Salmi T, et al. Impairment of heart rate variability during paclitaxel therapy. Cancer. 2000;88(9):2149–53.

Ekholm E, Rantanen V, Syvänen K, Jalonen J, Antila K, Salminen E. Docetaxel does not impair cardiac autonomic function in breast cancer patients previously treated with anthracyclines. Anticancer Drugs. 2002;13(4):425–9.

Ekholm E, Rantanen V, Antila K, Salminen E. Paclitaxel changes sympathetic control of blood pressure. Eur J Cancer. 1997;33(9):1419–24.

Jerian SM, Sarosy GA, Link Jr CJ, Fingert HJ, Reed E, Kohn EC. Incapacitating autonomic neuropathy precipitated by taxol. Gynecol Oncol. 1993;51(2):277–80.

Quasthoff S, Hartung HP. Chemotherapy-induced peripheral neuropathy. J Neurol. 2002;249(1):9–17.

Ekholm E, Rantanen V, Bergman M, Vesalainen R, Antila K, Salminen E. Docetaxel and autonomic cardiovascular control in anthracycline treated breast cancer patients. Anticancer Res. 1999;20(3B):2045–8.

European Heart Failure Training Group. Experience from controlled trials of physical training in chronic heart failure. Protocol and patient factors in effectiveness in the improvement in exercise tolerance. European Heart Failure Training Group. Eur Heart J. 1998;19(3):466–75.

Iellamo F, Legramante JM, Massaro M, Raimondi G, Galante A. Effects of a residential exercise training on baroreflex sensitivity and heart rate variability in patients with coronary artery disease : a randomized, controlled study. Circulation. 2000;102(21):2588–92.

Kiilavuori K, Toivonen L, Naveri H, Leinonen H. Reversal of autonomic derangements by physical training in chronic heart failure assessed by heart rate variability. Eur Heart J. 1995;16(4):490–5.

Malfatto G, Facchini M, Bragato R, Branzi G, Sala L, Leonetti G. Short and long term effects of exercise training on the tonic autonomic modulation of heart rate variability after myocardial infarction. Eur Heart J. 1996;17(4):532–8.

Oya M, Itoh H, Kato K, Tanabe K, Murayama M. Effects of exercise training on the recovery of the autonomic nervous system and exercise capacity after acute myocardial infarction. Jpn Circ J. 1999;63(11):843–8.

Low PA. Clinical autonomic disorders. 3rd ed. Philadelphia, PA: Lippincot Raven; 2008.

Cancer Care Ontario. Cancer in young adults in Canada. Toronto: Canadian Cancer Society; 2006. p. 120.

CANSIM, table 102–0512 [http://www.statcan.gc.ca/tables-tableaux/sum-som/l01/cst01/health26-eng.htm]

Thabane L, Ma J, Chu R, Cheng J, Ismaila A, Rios LP, et al. A tutorial on pilot studies: the what, why and how. BMC Med Res Methodol. 2010;10:1.

Jones LW, Eves ND, Haykowsky M, Joy AA, Douglas PS. Cardiorespiratory exercise testing in clinical oncology research: systematic review and practice recommendations. Lancet Oncol. 2008;9(8):757–65.

Mendoza TR, Wang XS, Cleeland CS, Morrissey M, Johnson BA, Wendt JK, et al. The rapid assessment of fatigue severity in cancer patients. Cancer. 1999;85(5):1186–96.

Low PA. Composite autonomic scoring scale for laboratory quantification of generalized autonomic failure. Mayo Clin Proc. 1993;68(8):748–52.

Low PA. Autonomic nervous system function. J Clin Neurophysiol. 1993;10(1):14–27.

Astrand PO, Ryhming I. A nomogram for calculation of aerobic capacity (physical fitness) from pulse rate during submaximal work. J Appl Physiol. 1954;7(2):218–21.

Argyriou AA, Koutras A, Polychronopoulos P, Papapetropoulos S, Iconomou G, Katsoulas G, et al. The impact of paclitaxel or cisplatin-based chemotherapy on sympathetic skin response: a prospective study. Eur J Neurol. 2005;12(11):858–61.

Boogerd W, ten Bokkel Huinink W, Dalesio O, Hoppenbrouwers W, van der Sande J. Cisplatin induced neuropathy: central, peripheral and autonomic nerve involvement. J Neurooncol. 1990;9(3):255–63.

Fagundes CP, Murray DM, Hwang BS, Gouin JP, Thayer JF, Sollers 3rd JJ, et al. Sympathetic and parasympathetic activity in cancer-related fatigue: more evidence for a physiological substrate in cancer survivors. Psychoneuroendocrino. 2011;36(8):1137–47.

Viniegra M, Marchetti M, Losso M, Navigante A, Litovska S, Senderowicz A, et al. Cardiovascular autonomic function in anthracycline-treated breast cancer patients. Cancer Chemother Pharmacol. 1990;26(3):227–31.

Adamsen L, Quist M, Andersen C, Moller T, Herrstedt J, Kronborg D, et al. Effect of a multimodal high intensity exercise intervention in cancer patients undergoing chemotherapy: randomised controlled trial. BMJ. 2009;339:b3410.

Courneya KS, Segal RJ, Mackey JR, Gelmon K, Reid RD, Friedenreich CM, et al. Effects of aerobic and resistance exercise in breast cancer patients receiving adjuvant chemotherapy: a multicenter randomized controlled trial. J Clin Oncol. 2007;25(28):4396–404.

Courneya KS, Sellar CM, Stevinson C, McNeely ML, Peddle CJ, Friedenreich CM, et al. Randomized controlled trial of the effects of aerobic exercise on physical functioning and quality of life in lymphoma patients. J Clin Oncol. 2009;27(27):4605–12.

Mock V, Frangakis C, Davidson NE, Ropka ME, Pickett M, Poniatowski B, et al. Exercise manages fatigue during breast cancer treatment: a randomized controlled trial. Psychooncology. 2005;14(6):464–77.

Novak V, Novak P, deMarchie M, Schondorf R. The effect of severe brainstem injury on heart rate and blood pressure oscillations. Clin Auton Res. 1995;5(1):24–30.

Novak V, Novak P, Schondorf R. Accuracy of beat-to-beat noninvasive measurement of finger arterial pressure using the Finapres: a spectral analysis approach. J Clin Monitor Comp. 1993;10(2):118–26.

Schondorf R. New investigations of autonomic nervous system function. J Clin Neurophysiol. 1993;10(1):28–38.

Hughson RL, Quintin L, Annat G, Yamamoto Y, Gharib C. Spontaneous baroreflex by sequence and power spectral methods in humans. Clin Physiol. 1993;13(6):663–76.

Low PA, Benrud-Larson LM, Sletten DM, Opfer-Gehrking TL, Weigand SD, O'Brien PC, et al. Autonomic symptoms and diabetic neuropathy: a population-based study. Diabetes Care. 2004;27(12):2942–7.

Fadul N, Strasser F, Palmer JL, Yusuf SW, Guo Y, Li Z, et al. The association between autonomic dysfunction and survival in male patients with advanced cancer: a preliminary report. J Pain Symptom Manage. 2010;39(2):283–90.

Morrow GR, Andrews PL, Hickok JT, Stern R. Vagal changes following cancer chemotherapy: implications for the development of nausea. Psychophysiology. 2000;37(3):378–84.

Morrow GR, Hickok JT, DuBeshter B, Lipshultz SE. Changes in clinical measures of autonomic nervous system function related to cancer chemotherapy-induced nausea. J Auton Nerv Syst. 1999;78(1):57–63.

Nuver J, Smit AJ, Sleijfer DT, van Gessel AI, van Roon AM, van der Meer J, et al. Left ventricular and cardiac autonomic function in survivors of testicular cancer. Eur J Clin Invest. 2005;35(2):99–103.

Strasser F, Palmer JL, Schover LR, Yusuf SW, Pisters K, Vassilopoulou-Sellin R, et al. The impact of hypogonadism and autonomic dysfunction on fatigue, emotional function, and sexual desire in male patients with advanced cancer: a pilot study. Cancer. 2006;107(12):2949–57.

Walsh TJ, Clark AW, Parhad IM, Green WR. Neurotoxic effects of cisplatin therapy. Arch Neurol. 1982;39(11):719.

Rosenwinkel ET, Bloomfield DM, Arwady MA, Goldsmith RL. Exercise and autonomic function in health and cardiovascular disease. Cardiol Clin. 2001;19(3):369–87.

Darnell RB, Posner JB. Paraneoplastic syndromes involving the nervous system. N Engl J Med. 2003;349(16):1543–54.

Stein PK, Ehsani AA, Domitrovich PP, Kleiger RE, Rottman JN. Effect of exercise training on heart rate variability in healthy older adults. Am Heart J. 1999;138(3 Pt 1):567–76.

Barney JA, Ebert TJ, Groban L, Farrell PA, Hughes CV, Smith JJ. Carotid baroreflex responsiveness in high-fit and sedentary young men. J Appl Physiol. 1988;65(5):2190–4.

Davy KP, Miniclier NL, Taylor JA, Stevenson ET, Seals DR. Elevated heart rate variability in physically active postmenopausal women: a cardioprotective effect? Am J Physiol. 1996;271(2 Pt 2):H455–60.

De Meersman RE. Heart rate variability and aerobic fitness. Am Heart J. 1993;125(3):726–31.

Dixon EM, Kamath MV, McCartney N, Fallen EL. Neural regulation of heart rate variability in endurance athletes and sedentary controls. Cardiovasc Res. 1992;26(7):713–9.

Goldsmith RL, Bigger Jr JT, Steinman RC, Fleiss JL. Comparison of 24-hour parasympathetic activity in endurance-trained and untrained young men. J Am Coll Cardiol. 1992;20(3):552–8.

Levy WC, Cerqueira MD, Harp GD, Johannessen KA, Abrass IB, Schwartz RS, et al. Effect of endurance exercise training on heart rate variability at rest in healthy young and older men. Am J Cardiol. 1998;82(10):1236–41.

Seals DR, Chase PB. Influence of physical training on heart rate variability and baroreflex circulatory control. J Appl Physiol. 1989;66(4):1886–95.

Arai Y, Saul JP, Albrecht P, Hartley LH, Lilly LS, Cohen RJ, et al. Modulation of cardiac autonomic activity during and immediately after exercise. Am J Physiol. 1989;256(1 Pt 2):H132–41.

Seals DR. The Autonomic Nervous System. In: Tipton CM, editor. Advanced Cardiovascular Exercise Physiology. Baltimore, MD: Human Kinetics; 2011. p. 197–245.

Ohuchi H, Suzuki H, Yasuda K, Arakaki Y, Echigo S, Kamiya T. Heart rate recovery after exercise and cardiac autonomic nervous activity in children. Pediatr Res. 2000;47(3):329–35.

Pierpont GL, Stolpman DR, Gornick CC. Heart rate recovery post-exercise as an index of parasympathetic activity. J Autonom Nerv Syst. 2000;80(3):169–74.

Orizio C, Perini R, Comande A, Castellano M, Beschi M, Veicsteinas A. Plasma-catecholamines and heart-rate at the beginning of muscular exercise in man. Eur J Appl Physiol O. 1988;57(5):644–51.

Robinson BF, Epstein SE, Beiser GD, Braunwald E. Control of heart rate by the autonomic nervous system: studies in man on the interrelation between baroreceptor mechanisms and exercise. Circ Res. 1966;19(2):400–11.

Bannister R, Ardill L, Fentem P. Defective autonomic control of blood vessels in idiopathic orthostatic hypotension. Brain. 1967;90(4):725–46.

Sletten DM, Grandinetti A, Weigand SD, Gehrking TL, Gehrking JA, Low PA, et al. Quantitative sudomotor axon reflex test using QSWEAT - normative values. Puerto Rico: American Autonomic Society; 2014. p. 2014.

Novak P. Quantitative autonomic testing. J Vis Exp. 2011;53.
Bleyer A. Older adolescents with cancer in North America deficits in outcome and research. Pediatr Clin North Am. 2002;49(5):1027–42.

Bleyer A. Young adult oncology: the patients and their survival challenges. CA Cancer J Clin. 2007;57(4):242–55.
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