Abstract
BackgroundPreliminary 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).MethodsThirteen 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.ResultsThe 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.ConclusionsResults 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.
Highlights
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
Various anti-cancer chemotherapies may further affect the function of the autonomic and CV systems. Using both short duration and 24 h recordings, diminished heart rate (HR) variability has been reported in patients treated with vincristine [6], doxorubicin [7], various combination therapies [8, 9], and in some [10], but not all [11], patients treated with paclitaxel
Secondary results: exploratory self-report and physiology outcomes Baseline demographic and self-report results Thirteen cancer patients and 12 sex-and age-matched controls were tested at Baseline testing (T1) (Fig. 2)
Summary
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. Aberrant blood pressure variability and maladaptive orthostatic responses have been observed in patients treated with paclitaxel, taxanes, vinca alkaloids and cisplatin [12,13,14,15] – the mechanisms were not always clear These studies lacked consistency in their selection/execution of autonomic challenges, application of their eligibility and testing criteria. Many failed to include key methodological details required to compare between trials As such, they provide very little clinical relevance, and there remains insufficient evidence to make any conclusions regarding the presence or nature of cancer-related autonomic dysfunction
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