Tailored Exercise Interventions to Reduce Fatigue in Cancer Survivors

Cancer-related fatigue (CRF) is a common and distressing symptom of cancer and/or cancer treatment that can persist for months or years in cancer survivors. Exercise is beneficial for the management of CRF, and general exercise guidelines for cancer survivors are available. However, exercise interventions have not been tailored to alleviate CRF in fatigued cancer survivors, and thus the potential to alleviate CRF may not have been realized. The primary aim of this research is to investigate the effect of a traditional vs. tailored 12-week exercise intervention on self-reported CRF severity.

Background and Rationale Approximately one-third of cancer survivors experience severe and persistent fatigue for a number of years post-treatment, but this distressing symptom is often under-treated by healthcare professionals due to a lack of mechanism-targeted interventions. The assessment of cancer-related fatigue (CRF) is reliant on subjective fatigue measurements such as self-report questionnaires. Less attention has been given to objective physiological measurements. However, there are well-established techniques which allow the assessment of neuromuscular fatigue and its peripheral and central origins which could be utilized in the study of CRF. Very few studies have considered these objective measures alongside self-report scales in the study of CRF and only two have used such techniques in cancer survivors. To date, no studies have investigated neuromuscular fatigue in whole body, dynamic activity as relevant to daily tasks (and involving the lower limb due to its functional relevance to locomotion). Novel testing developed in our laboratory could be used as part of a wider screening to develop individualized interventions to alleviate CRF. It is well accepted in the field that CRF is multidimensional and in addition to a potential neuromuscular component, the role of sleep disturbance may also be implicated. Interventions targeted at improving sleep quality are therefore warranted, and there is sound evidence for the efficacy of exercise interventions in particular for improving CRF in cancer survivors. As a non-pharmacological intervention, physical activity has the strongest evidence base for treating CRF. However, the mechanisms explaining the reduction of CRF with exercise are not understood. Due to the complex and multi-factorial nature of CRF, it would be of benefit to tailor exercise interventions to the specific deficits (in regards to neuromuscular mechanisms) or difficulties (for example sleep disturbance) experienced by the individual. Ultimately, mechanism-targeted exercise interventions could be translated to clinical rehabilitation programs and lead to an improved quality of for cancer survivors. Research Question & Objectives The primary aim of this research is to investigate the effect of a traditional vs. tailored 12-week exercise intervention on self-reported CRF severity. Methods Fatigued cancer survivors who have completed primary treatment ≥ 3 months and ≤ 5 years from enrollment will be randomly allocated to one of two treatment arms: traditional (active control) and tailored exercise. Participants in the traditional exercise group will engage in aerobic and resistance exercise that is consistent with published recommendations. The tailored exercise group will be prescribed an intervention designed to address individual deficits (identified at baseline) that may be related to CRF. Participants will be assessed before and after the intervention for patient-reported outcomes, neuromuscular function and fatigue in response to whole-body exercise, sleep quantity and quality, physical activity levels, cardiorespiratory fitness and blood biomarkers.

A tailored and individualized exercise intervention based on the results of pre-intervention testing.

The traditional exercise group will undertake a supervised exercise intervention involving aerobic exercise and light resistance training, in line with published guidelines for exercise in cancer survivors.

The tailored training group will be prescribed an individualized exercise intervention designed specifically to counteract deficits (e.g. neuromuscular) of difficulties (e.g. sleep disturbance) identified during pre-intervention testing.

Assessment of change in the Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-Fatigue) Scale

Self-report questionnaire for the assessment of of nine common symptoms experienced by cancer patients.

A reduction in maximal isometric force in the knee extensors measured before, during and after an intermittent cycling test.

A reduction voluntary activation (using transcranial magnetic stimulation) measured measured before, during and after an intermittent cycling test.

A reduction voluntary activation (using femoral nerve stimulation) measured before, during and after an intermittent cycling test.

A reduction in potentiated quadriceps twitch force (from a high frequency doublet at 100 Hz) measured before, before, during and after an intermittent cycling test.

Evoked from supra-maximal stimulation of the femoral nerve and measured before, during and after an intermittent cycling test.

Evoked from supra-maximal stimulation of the femoral nerve and measured before, during and after an intermittent cycling test.

Evoked from supra-maximal stimulation of the femoral nerve and measured before, during and after an intermittent cycling test.

Evoked from TMS and measured (from stimulation artifact to the continuous resumption of EMG) before, during and after an intermittent cycling test.

Root mean square of the EMG signal during an MVC, measured before, during and after an intermittent cycling test.

the degree of regularity of the rest-activity patterns on individual days in the 24 h environment, recorded with actigraphy.

The mean activity counts in the least active 5 h period in the average 24 h pattern) recorded with actigraphy.

The central time of the L5 period, usually referring to the through of the activity period), recorded with actigraphy.

Time spent between the moment subject turn off the light to sleep and the moment he gets up, recorded with actigraphy.

Ratio between the time spent asleep and the total duration of sleep period, recorded with actigraphy.

Blood count, catecholamines, serotonin, cortisol, inflammatory markers and markers of oxidative stress.

Assessment of change in the Centre for Epidemiological Studies Depression Scale (CES-D) questionnaire.

Self-report questionnaire for the assessment of health-related quality of life, specific to cancer type.

Inclusion Criteria: Aged between 18 and 75 years; Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) score ≤ 34; Completion of treatment in ≥ 3 months and ≤ 5 years preceding enrollment; Approval received from personal physician and/or a Canadian Society for Exercise Physiology-Clinical Exercise Physiologist (CSEP-CEP); Command of the English language. Exclusion Criteria: Contraindication to experimental procedures including transcranial magnetic stimulation (TMS); Diagnosed as having obstructive sleep apnea or anemia; Currently participating in a structured exercise intervention; Participant is pregnant.

Twomey R, Martin T, Temesi J, Culos-Reed SN, Millet GY. Tailored exercise interventions to reduce fatigue in cancer survivors: study protocol of a randomized controlled trial. BMC Cancer. 2018 Jul 24;18(1):757. doi: 10.1186/s12885-018-4668-z.