Effect of aerobic exercise on cancer-associated cognitive impairment: A proof-of-concept RCT

Journal Paper
Campbell KL, Kam JWY, Liu Ambrose T, Handy TC, Lim H, Hayden S, Hsu L, Neil-Sztramko SE, Kirkham AA, Gotay CC, McKenzie DC, Boyd LA
Psycho-Oncology, in press

Background

Change in cognitive ability is a commonly reported side effect by breast cancer survivors (BCS). The underlying etiology of cognitive complaints is unclear and to date there is limited evidence for effective intervention strategies. Exercise has been shown to improve cognitive function in older adults and animal models treated with chemotherapy. This proof-of-concept randomized controlled trial (RCT) tested the effect of aerobic exercise versus usual lifestyle on cognitive function in postmenopausal BCS.

Methods

Women, age 40-65 years, postmenopausal, stage I-IIIA breast cancer, and who self-reported cognitive dysfunction following chemotherapy treatment were recruited and randomized to a 24-week aerobic exercise intervention (EX; n = 10) or usual lifestyle control (CON; n = 9). Participants completed self-report measures of the impact of cognitive issues on quality of life (FACT-Cog), objective neuropsychological testing and functional magnetic resonance imaging (fMRI) at baseline and 24-weeks.

Results

Compared to CON, EX had a reduced time to complete a processing speed test (Trail Making Task-A) (-14.2 seconds, p < 0.01; effect size [ES] 0.35). Compared to CON, there was no improvement in self-reported cognitive function and effect sizes were small Interestingly, lack of between-group differences in Stroop behavioral performance were accompanied by functional changes in several brain regions of interest in EX compared to CON at 24-weeks.

Conclusion

These findings provide preliminary proof-of-concept results for the potential of aerobic exercise to improve cancer-related cognitive impairment, and will serve to inform the development of future trials.

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Fee-for-service cancer rehabilitation programs improve health-related quality of life

Journal Paper
A.A. Kirkham, S.E. Neil-Sztramko, J. Morgan, S. Hodson, S. Weller, T. McRae, K.L. Campbell
Current Oncology, 2016;23(4):233-40.

Background Rigorously applied exercise interventions undertaken in a research setting result in improved health- related quality of life (HRQoL) in cancer survivors, but research to demonstrate effective translation of that research to practice is needed. The objective of the present study was to determine the effect of fee-for-service cancer rehabilitation programs in the community on HRQoL and on self-reported physical activity and its correlates.

Methods After enrolment and 17 ± 4 weeks later, new clients (n = 48) to two fee-for-service cancer rehabilitation programs completed the 36-Item Short Form Health Survey (RAND-36: RAND Corporation, Santa Monica, CA, U.S.A.), the Godin Leisure-Time Exercise Questionnaire, and questions about physical activity correlates. Normal fee-for-service operations were maintained, including a fitness assessment and individualized exercise programs supervised in a group or one-on-one setting, with no minimum attendance required. Fees were associated with the assessment and with each exercise session.

Results Of the 48 participants, 36 (75%) completed both questionnaires. Improvements in the physical functioning, role physical, pain, and energy/fatigue scales on the RAND-36 exceeded minimally important differences and were of a magnitude similar to improvements reported in structured, rigorously applied, and free research interventions. Self-reported levels of vigorous-intensity (p = 0.021), but not moderate-intensity (p = 0.831) physical activity increased. The number of perceived barriers to exercise (p = 0.035) and the prevalence of fatigue as a barrier (p = 0.003) decreased. Exercise self-efficacy improved only in participants who attended 11 or more sessions (p = 0.002). Exercise enjoyment did not change (p = 0.629).

Conclusions Enrolment in fee-for-service cancer rehabilitation programs results in meaningful improvements in HRQoL comparable to those reported by research interventions, among other benefits. The fee-for-service model could be an effective model for delivery of exercise to more cancer survivors.

Effective translation of research to practice: Hospital-based rehabilitation program improves health-related physical fitness and quality of life of cancer survivors

Journal Paper
Kirkham AA, Klika RJ, Ballard TM, Downey P, Campbell KL
Journal of the National Comprehensive Cancer Network 2016;14(12):1555-62

Clinically Relevant Physical Benefits of Exercise Interventions in Breast Cancer Survivors

Journal Paper
Kirkham AA, Bland K, Sayyari S, Campbell KL, Davis M
Current Oncology Reports 2016;18(2):12

Evidence is currently limited for the effect of exercise on breast cancer clinical outcomes. However, several of the reported physical benefits of exercise, including peak oxygen consumption, functional capacity, muscle strength and lean mass, cardiovascular risk factors, and bone health, have established associations with disability, cardiovascular disease risk, morbidity, and mortality. This review will summarize the clinically relevant physical benefits of exercise interventions in breast cancer survivors and discuss recommendations for achieving these benefits. It will also describe potential differences in intervention delivery that may impact outcomes and, lastly, describe current physical activity guidelines for cancer survivors.

Utility of equations to estimate peak oxygen uptake and work rate from a sixminute walk test in patients with COPD in a clinical setting.

Journal Paper
Kirkham AA, Pauhl KE, Elliot RM, Scott JA, Doria SC, Davidson HK, Campbell KL, Camp PG
Journal of Cardiopulmonary Rehabilitation and Prevention 2015;35(6):431-8.

PURPOSE:

To determine the utility of equations that use the 6-minute walk test (6MWT) results to estimate peak oxygen uptake ((Equation is included in full-text article.)o2) and peak work rate with chronic obstructive pulmonary disease (COPD) patients in a clinical setting.

METHODS:

This study included a systematic review to identify published equations estimating peak (Equation is included in full-text article.)o2 and peak work rate in watts in COPD patients and a retrospective chart review of data from a hospital-based pulmonary rehabilitation program. The following variables were abstracted from the records of 42 consecutively enrolled COPD patients: measured peak (Equation is included in full-text article.)o2 and peak work rate achieved during a cycle ergometer cardiopulmonary exercise test, 6MWT distance, age, sex, weight, height, forced expiratory volume in 1 second, forced vital capacity, and lung diffusion capacity. Estimated peak (Equation is included in full-text article.)o2 and peak work rate were estimated from 6MWT distance using published equations. The error associated with using estimated peak (Equation is included in full-text article.)o2 or peak work to prescribe aerobic exercise intensities of 60% and 80% was calculated.

RESULTS:

Eleven equations from 6 studies were identified. Agreement between estimated and measured values was poor to moderate (intraclass correlation coefficients = 0.11-0.63). The error associated with using estimated peak (Equation is included in full-text article.)o2 or peak work rate to prescribe exercise intensities of 60% and 80% of measured values ranged from mean differences of 12 to 35 and 16 to 47 percentage points, respectively.

CONCLUSIONS:

There is poor to moderate agreement between measured peak (Equation is included in full-text article.)o2 and peak work rate and estimations from equations that use 6MWT distance, and the use of the estimated values for prescription of aerobic exercise intensity would result in large error. Equations estimating peak (Equation is included in full-text article.)o2 and peak work rate are of low utility for prescribing exercise intensity in pulmonary rehabilitation programs.

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The utility of cardiac stress testing for detection of cardiovascular disease in breast cancer survivors: A systematic review

Journal Paper
Kirkham AA, Virani SA, Campbell KL
International Journal of Women’s Health 2015;7:127-140.

Abstract

BACKGROUND:

Heart function tests performed with myocardial stress, or “cardiac stress tests”, may be beneficial for detection of cardiovascular disease. Women who have been diagnosed with breast cancer are more likely to develop cardiovascular diseases than the general population, in part due to the direct toxic effects of cancer treatment on the cardiovascular system. The aim of this review was to determine the utility of cardiac stress tests for the detection of cardiovascular disease after cardiotoxic breast cancer treatment.

DESIGN:

Systematic review.

METHODS:

Medline and Embase were searched for studies utilizing heart function tests in breast cancer survivors. Studies utilizing a cardiac stress test and a heart function test performed at rest were included to determine whether stress provided added benefit to identifying cardiac abnormalities that were undetected at rest within each study.

RESULTS:

Fourteen studies were identified. Overall, there was a benefit to utilizing stress tests over tests at rest in identifying evidence of cardiovascular disease in five studies, a possible benefit in five studies, and no benefit in four studies. The most common type of stress test was myocardial perfusion imaging, where reversible perfusion defects were detected under stress in individuals who had no defects at rest, in five of seven studies of long-term follow-up. Two studies demonstrated the benefit of stress echocardiography over resting echocardiography for detecting left ventricular dysfunction in anthracycline-treated breast cancer survivors. There was no benefit of stress cardiac magnetic resonance imaging in one study. Two studies showed a potential benefit of stress electrocardiography, whereas three others did not.

CONCLUSION:

The use of cardiac stress with myocardial perfusion imaging and echocardiography may provide added benefit to tests performed at rest for detection of cardiovascular disease in breast cancer survivors, and merits further research.

Assessment of health-related physical fitness in community-based cancer rehabilitation

Journal Paper
Kirkham AA, Neil SE, Morgan J, Hodson S, McRae T, Campbell KL
Supportive Care in Cancer 2015; in press doi:10.1007/s00520-014-2599-z

ABSTRACT Assessment of physical fitness is important in order to set goals, appropriately prescribe exercise, and monitor change over time. This study aimed to determine the utility of a standardized physical fitness assessment for use in cancer-specific, community-based exercise programs.
Tests anticipated to be feasible and suitable for a community setting and a wide range of ages and physical function were chosen to measure body composition, aerobic fitness, strength, flexibility, and balance. Cancer Exercise Trainers/Specialists at cancer-specific, community-based exercise programs assessed new clients (n = 60) at enrollment, designed individualized exercise programs, and then performed a re-assessment 3-6 months later (n = 34).
Resting heart rate, blood pressure, body mass index, waist circumference, handgrip strength, chair stands, sit-and-reach, back scratch, single-leg standing, and timed up-and-go tests were considered suitable and feasible tests/measures, as they were performed in most (≥88 %) participants. The ability to capture change was also noted for resting blood pressure (-7/-5 mmHg, p = 0.02), chair stands (+4, p < 0.01), handgrip strength (+2 kg, p < 0.01), and sit-and-reach (+3 cm, p = 0.03). While the submaximal treadmill test captured a meaningful improvement in aerobic fitness (+62 s, p = 0.17), it was not completed in 33 % of participants. Change in mobility, using the timed up-and-go was nominal and was not performed in 27 %.
Submaximal treadmill testing, handgrip dynamometry, chair stands, and sit-and-reach tests were feasible, suitable, and provided meaningful physical fitness information in a cancer-specific, community-based, exercise program setting. However, a shorter treadmill protocol and more sensitive balance and upper body flexibility tests should be investigated.

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Exercise prevention of cardiovascular disease in breast cancer survivors

Journal Paper
Kirkham AA, Davis MK
Journal of Oncology special issue: “Cancer and Cardiovascular Disease: The Complex Labyrinth” 2015; Article ID 917606, in press


ABSTRACT
Thanks to increasingly effective treatment, breast cancer mortality rates have significantly declined over the past few decades. Following the increase in life expectancy of women diagnosed with breast cancer, it has been recognized that these women are at an elevated risk for cardiovascular disease due in part to the cardiotoxic side effects of treatment. This paper reviews evidence for the role of exercise in prevention of cardiovascular toxicity associated with chemotherapy used in breast cancer, and in modifying cardiovascular risk factors in breast cancer survivors. There is growing evidence indicating that the primary mechanism for this protective effect appears to be improved antioxidant capacity in the heart and vasculature and subsequent reduction of treatment-related oxidative stress in these structures. Further clinical research is needed to determine whether exercise is a feasible and effective nonpharmacological treatment to reduce cardiovascular morbidity and mortality in breast cancer survivors, to identify the cancer therapies for which it is effective, and to determine the optimal exercise dose. Safe and noninvasive measures that are sensitive to changes in cardiovascular function are required to answer these questions in patient populations. Cardiac strain, endothelial function, and cardiac biomarkers are suggested outcome measures for clinical research in this field.

Lateral trunk lean gait modification increases the energy cost of treadmill walking in those with knee osteoarthritis

Journal Paper
• Takacs J, Kirkham AA, Brown J, Marriot E, Monkman D, Havey J, Hung S, Campbell KL, Hunt MH
Osteoarthritis and Cartilage 2014;22(2):203-9

Objective: To compare the energy expenditure of increased lateral trunk lean walking e a suggested method of reducing medial compartment knee joint load e compared to normal walking in a population of older adults with medial knee osteoarthritis (OA).
Method: Participants completed two randomly-presented treadmill walking conditions: 15 min of normal walking or walking with ten degrees of peak lateral trunk lean. Lateral trunk lean angle was displayed in front of the participant in real-time during treadmill conditions. Energy expenditure (VO2 and METs), heart rate (HR), peak lateral trunk lean angle, knee pain and perceived exertion were measured and differences between conditions were compared using paired t-tests.

Results: Twelve participants (five males, mean (standard deviation (SD)) age 64.1 (9.4) years, body mass index (BMI) 28.3 (4.9) kg/m2) participated. All measures were significantly elevated in the lateral trunk lean condition (P < 0.008), except for knee pain (P  0.22). Oxygen consumption (VO2) was, on average 9.5% (95% CI 4.2e14.7%) higher, and HR was on average 5.3 beats per minute (95% CI 1.7e9.0 bpm) higher during increased lateral trunk lean walking.

Conclusion: Increased lateral trunk lean walking on a treadmill resulted in significantly higher levels of steady-state energy expenditure, HR, and perceived exertion, but no difference in knee pain. While increased lateral trunk lean has been shown to reduce biomechanical measures of joint loading relevant to OA progression, it should be prescribed with caution given the potential increase in energy expen- diture experienced when it is employed.

Aerobic capacity and upper limb strength are reduced in women diagnosed with breast cancer: A systematic review

Journal Paper
• Neil SE, Kirkham AA, Hung SH, Niksirat N, Nishikawa K, Campbell KL
Journal of Physiotherapy 2014;60(4):189-200

Question: What are typical values of physical function for women diagnosed with breast cancer and how do these compare to normative data? Design: Systematic review with meta-analysis. Participants: Women diagnosed with breast cancer who were before, during or after treatment. Outcome measures: Physical function was divided into three categories: aerobic capacity, upper and lower extremity muscular fitness, and mobility. Measures of aerobic capacity included field tests (6-minute walk test, 12- minute walk tests, Rockport 1-mile test, and 2-km walk time) and submaximal/maximal exercise tests on a treadmill or cycle ergometer. Measures of upper and lower extremity muscular fitness included grip strength, one repetition maximum (bench, chest or leg press), muscle endurance tests, and chair stands. The only measure of mobility was the Timed Up and Go test. Results: Of the 1978 studies identified, 85 were eligible for inclusion. Wide ranges of values were reported, reflecting the range of ages, disease severity, treatment type and time since treatment of participants. Aerobic fitness values were generally below average, although 6-minute walk time was closer to population norms. Upper and lower extremity strength was lower than population norms for women who were currently receiving cancer treatment. Lower extremity strength was above population norms for women who had completed treatment. Conclusion: Aerobic capacity and upper extremity strength in women diagnosed with breast cancer are generally lower than population norms. Assessment of values for lower extremity strength is less conclusive. As more research is published, expected values for sub-groups by age, treatment, and co- morbidities should be developed.

Comparison of aerobic exercise intensity prescription methods in breast cancer

Journal Paper
• Kirkham AA, Campbell KL, McKenzie DC
Medicine & Science in Sports & Exercise 2013;45(8):1443-50

Introduction: Exercise plays an important role in cancer rehabilitation, but a precise prescription of exercise intensity is required to maximize the benefits of this intervention. It is unknown whether different methods of prescribing aerobic exercise intensity achieve the same intensity. Breast cancer treatments may alter exercise response and thereby may affect the accuracy of these methods. Purpose: The purpose of this study was to compare the accuracy and achieved intensity of four common methods of prescribing exercise intensity within and between breast cancer patients recently finished chemotherapy (n = 10), survivors finished treatment (n = 10), and healthy controls (n = 10). Methods: The methods compared were as follows: the American College of Sports Medicine’s metabolic equation for treadmill walking (METW), heart rate reserve (HRR), direct heart rate (DIRECT HR), and RPE. The methods were used to prescribe 60% oxygen consumption reserve (V ̇ O2R) in four randomly assigned 10-min periods of treadmill walking with expired gas collection to evaluate 1) achieved intensity (measured % V ̇ O2R) and 2) accuracy (defined as: [60% V ̇ O2R–achieved intensity]). Results: The accuracy of the methods was not equivalent across groups (P = 0.04). HRR and METW did not differ across groups and were most accurate in patients. HRR, METW, and DIRECT HR were all more accurate than RPE in survivors (P e 0.01). RPE was the least accurate in all groups. The accuracy of DIRECT HR was much lower in patients than that in survivors and controls (P e 0.01). Conclusions: The four methods of exercise intensity prescription varied in accuracy in prescribing 60% V ̇O2R and did not achieve equivalent exercise intensities within breast cancer patients, survivors, and healthy controls. HRR and METW were the most accurate methods for exercise intensity prescription in breast cancer patients and survivors.

Feasibility of a lifestyle intervention on body weight and serum biomarkers in breast cancer survivors with overweight and obesity

Journal Paper
• Campbell KL, Van Patten CL, Neil SE, Kirkham AA, Gotay CC, Gelmon KA, McKenzie DC
Journal of the Academy of Nutrition and Dietetics, 2012;112(4), 559-67.

Physical inactivity and being overweight or obese are lifestyle factors that put breast cancer survivors at a higher risk for a cancer recurrence and/or development of other chronic diseases. Despite this, there is limited research that has identified effective lifestyle interventions aimed specifically at weight loss in breast cancer survivors. This pilot study is a single-arm experimental pre–post test design, conducted from Novem- ber 2009 to July 2010, that tested the efficacy of a 24-week group-based lifestyle inter- vention modeled on the Diabetes Prevention Program in early stage breast cancer sur- vivors (N􏰁14). The intervention included 16 diet sessions led by a registered dietitian and 150 min/wk of moderate-to-vigorous exercise. Study outcome measures were com- pleted at baseline, 24, and 36 weeks (nonintervention follow-up). The primary outcome was change in body weight, and secondary outcomes were change in body composition, aerobic fitness, dietary intake, and blood biomarkers. Overall, participants were post- menopausal women aged 54.6􏰂8.3 years with obesity (body mass index 30.1􏰂3.6), and had completed adjuvant cancer treatment 2 years prior. Results showed an average weight loss of 3.8􏰂5.0 kg and a decrease in body mass index, percent body fat, and waist and hip circumferences at 24 weeks and an additional mean weight loss of 0.8􏰂1.2 kg at 36 weeks. In exploratory analysis, participants who lost 􏰃7% body weight were older and attended a greater percentage of diet and supervised exercise sessions. There were no significant changes in any of the blood biomarkers at 24 and 36 weeks; however, the results provide a measure of expected effect size for future research studies. This pilot study demonstrated the efficacy of a lifestyle intervention based on the Diabetes Pre- vention Program in early stage breast cancer survivors and represents an innovative clinical intervention for dietetics practitioners to address the unmet need for programs.