Recent Publications & Abstracts

Recent Publications

Hydock DS, Schneider CM, Hayward R. Exercise Preconditioning Provides Long-Term Protection Against Chronic Doxorubicin Cardiotoxicity. Integrative Cancer Therapies (in press).
Sprod LK, Hsieh CC, Hayward R, Schneider CM. Three vs. Six Months of Exercise Training in Cancer Survivors. Breast Cancer Research and Treatment 121:412-419, 2010.
Hydock DS, Schneider CM, Hayward R. Voluntary Wheel Running in Rats Receiving Doxorubicin: Effects on Running Activity and Cardiac Myosin Heavy Chain. Anticancer Research 29: 4401-4407, 2009.
Wonders KY, Hydock DS, Greufe SE, Schneider CM, Hayward R. Endurance Exercise Training Preserves Cardiac Function in Rats Receiving Doxorubicin and the HER-2 Inhibitor GW2974. Cancer Chemotherapy and Pharmacology 64:1105–1113, 2009.
Hydock DS, Lien CY, Hayward R. Anandamide Preserves Cardiac Function and Geometry in an Acute Doxorubicin Cardiotoxicity Rat Model. Journal of Cardiovascular Pharmacology and Therapeutics 14: 59-67, 2009.
Hydock DS, Iwaniec UT, Turner RT, Lien CY, Jensen BT, Parry TL, Schneider CM, Hayward R. Effects of Voluntary Wheel Running on Goserelin Acetate-Induced Bone Degeneration. Pathophysiology 15: 253-259, 2008.
Hsieh CC, Sprod LK, Hydock DS, Carter SD, Hayward R, Schneider CM. Effects of a Supervised Exercise Intervention on Recovery from Treatment Regimens in Breast Cancer Survivors. Oncology Nursing Forum 35: 909-915, 2008.
Wonders KY, Hydock DS, Schneider CM, Hayward R. Acute Exercise Protects Against Doxorubicin Cardiotoxicity. Integrative Cancer Therapies 7: 147-154, 2008.
Hydock DS, Lien C-Y, Schneider CM, Hayward R. Exercise Preconditioning Protects Against Doxorubicin-Induced Cardiac Dysfunction. Medicine and Science in Sports and Exercise 40: 808-817, 2008.

Recent Abstracts

Cancer-Related Fatigue and the Impact of Psychological and Physiological Variables

Brent M. Peterson1, Chris P. Repka1, Kurt Dallow1,2 FACSM, Reid Hayward1, Carole M. Schneider1 FACSM. 1Rocky Mountain Cancer Rehabilitation Institute, University of Northern Colorado, Greeley, CO. 2 North Colorado Family Medicine, Greeley, CO.

Fatigue has a negative impact on individuals during and following cancer therapy. Fatigue appears to be manifested early in the disease process and often worsens with treatment. There is minimal information on what psychological and physiological parameters contribute to cancer-related fatigue.

PURPOSE: To assess potential psychological and physiological variables that may contribute to cancer-related fatigue.
METHODS: A total of 593 cancer survivors, including 127 males (62.0 ± 13.7 yrs) and 466 females (55.0 ± 11.8 yrs) that had undergone radiation and/or chemotherapy were eligible for this study. Participants completed Piper fatigue and Beck depression inventories. Additionally, a comprehensive physical assessment was performed prior to the exercise intervention. Physical performance was determined during an initial assessment including VO2 peak (multistage treadmill protocol), muscular endurance (paced submaximal protocol to fatigue), body composition (skinfolds), and body weight. A multiple imputation regression analysis ascertained the effects of multiple variables on fatigue.
RESULTS: Depression, body weight, lower body endurance, and age were significantly (P<.05) associated with cancer-related total fatigue. VO2 peak approached significance (P=.07) while upper body endurance and body fat percentage were not significantly associated with total fatigue.
CONCLUSION: The results of this study imply that activities of daily living may be more difficult in cancer survivors with greater body weight and poor body strength ultimately increasing total fatigue. Therefore, cancer rehabilitation programs need to include interventions addressing decrements in cancer survivors’ ability to complete activities of daily living as opposed to improving athletic performance.

Rocky Mountain Cancer Rehabilitation Institute: A Satisfaction Survey Pilot Study

Brent M. Peterson1, Chris P. Repka1, Kurt Dallow1,2 FACSM, Jessica Weiderspon1, Dan Shackleford1, Reid Hayward1, Carole M. Schneider1 FACSM. 1Rocky Mountain Cancer Rehabilitation Institute, University of Northern Colorado, Greeley, CO. 2 North Colorado Family Medicine, Greeley, CO.

As a measure of high quality care, satisfaction survey research is an important indicator in program evaluation in clinical and rehabilitation settings. Currently, there is minimal information on client satisfaction in cancer rehabilitation.

PURPOSE: To evaluate satisfaction levels of Rocky Mountain Cancer Rehabilitation Institute (RMCRI) active clients.
METHODS: A total of 24 oncologist referred cancer survivors currently training at the RMCRI (62.38 ± 10.17 yrs) completed satisfaction surveys regarding various aspects of their experiences with their trainers and management.
RESULTS: The trainer subscale and management composite subscale elicited Chronbach alpha scores greater than .91. There was no significant (p>.05) difference or association (R= .28, R2= .08) between trainer skills, interpersonal, and management overall composite scales. However, there were significant (p<.05) correlations between the trainer skills composite scale and client weight, trainer confidence and application of knowledge, management’s attention to clients’ needs and the overall satisfaction composite score.
CONCLUSION: The results of this study imply that satisfaction with post treatment rehabilitation was increased as managements’ attention to clients’ needs increased. Additionally, clients perceived their trainers to have greater levels of knowledge applied as more client weight was lost. In addition, trainers were better able to apply knowledge as their confidence increased. Therefore, cancer rehabilitation programs need to focus on clients’ needs and empower undergraduate trainers to be confident in the application of their knowledge.

The Effect of Cancer Stage on Physiological and Psychological Parameters Following Supervised Exercise Training

Stephanie E. Greufe, Hung-Wei Cheng, Chris P. Repka, Reid Hayward, David S. Hydock, Carole M. Schneider, FACSM Rocky Mountain Cancer Rehabilitation Institute, University of Northern Colorado

Cancer treatments lead to a variety of adverse physiological and psychological effects which may be attenuated with exercise. However, minimal research has been conducted to elucidate the effect cancer stage has on the outcomes of exercise training.

PURPOSE: To examine the effect cancer stage has on baseline physiological and psychological parameters, as well as absolute change with exercise training.
METHODS: Two hundred cancer survivors were grouped according to their cancer stage, stage 1 (n=69), stage 2 (n=69), stage 3 (n=41), and stage 4 (n=21). An assessment was conducted to measure baseline data. An individualized supervised exercise intervention was implemented followed by a reassessment three months later. The assessment consisted of cardiovascular endurance, pulmonary function, depression, fatigue, and quality of life. Confidence intervals were used to determine significance between cancer stages in both baseline and post exercise data as well as absolute change following the exercise intervention. A family alpha level of 0.10 was used to determine significance.
RESULTS: No significant differences were found between cancer stages at baseline and following the exercise intervention, however, all stages improved in at least 3 parameters following the exercise intervention. Results are reported as mean change (post minus pre) and the lower and upper limits to the 98.75% confidence interval. Stage 1 showed significant improvements in FEV1 (6.2 percent of predicted [1.9, 10.4]), treadmill time (1.2 min [0.1, 2.3]), and VO2peak (3.5 ml.kg-1.min-1 [1.6, 5.5]). Stage 2 significantly improved in FEV1 (5.6 [1.3, 9.8]), treadmill time (1.4 [0.3, 2.5]), VO2peak (4.0 [2.1, 5.9]), fatigue (-1.8 [-3.2, -0.5]), and depression (-2.6 [4.6, -0.6]). Treadmill time (1.8 [0.6, 3.1]), VO2peak (4.4, [2.2, 6.6]), fatigue (-1.7 [-3.2, -0.1]), and depression (-4.1 [-6.4, -1.7]) significantly improved following the exercise intervention for cancer survivors in stage 3. Survivors in stage 4 showed significant improvements in treadmill time (2.1 [0.6, 3.6]) and VO2peak (6.9 [4.2, 9.5]).
CONCLUSION: Although stage is not a predictor of baseline physiological and psychological status or exercise response, exercise provides significant benefits for cancer survivors across all stages.

Endurance Exercise Attenuates Cardiotoxicity Induced by Androgen Deprivation and Doxorubicin

Traci L. Parry, David S. Hydock, Brock T. Jensen, Chia-Ying Lien, Carole M. Schneider, FACSM, Reid Hayward. School of Sport and Exercise Science and the Rocky Mountain Cancer Rehabilitation Institute, University of Northern Colorado, Greeley, CO, 80639

Besides doxorubicin’s (DOX) well known cardiotoxic effects, it is associated with irreversible testicular damage. In an attempt to preserve testicular function during DOX treatment, androgen deprivation therapy (ADT) using goserelin acetate is gaining clinical popularity as it temporarily suppresses gonadal function thereby minimizing DOX’s gonadal damage. However, DOX’s cardiac dysfunction is a major clinical concern as well, and evidence suggests that ADT may exacerbate DOX-induced cardiac dysfunction. Exercise has been shown to protect against DOX-induced cardiac dysfunction, but the effects of exercise on cardiac function during combined ADT and DOX treatment are currently unknown.

PURPOSE: To determine whether exercise training can attenuate the combined cardiotoxic effects of ADT and DOX.
METHODS: Male Sprague Dawley rats were randomly assigned to experimental groups: control implants (CON), androgen deprivation therapy (ADT), doxorubicin (DOX), or (ADT+DOX). Animals received ADT or control implants on day 1 and 29 of the 56 day protocol. Animals were then assigned to either sedentary activity (SED) or forced treadmill endurance exercise (TM). Exercise commenced on day 1 of the protocol. On day 15, animals received DOX at 1.5 mg/kg/d i.p. for 10 consecutive days or an equivalent volume of 0.9% SAL. On day 57, cardiac function was assessed in vivo (echocardiography) and ex vivo (isolated perfused working heart).
RESULTS: DOX alone as well as ADT+DOX treated animals possessed significantly (P < 0.05) depressed left ventricular developed pressure (-21% vs. -27%), maximal rate of pressure development (-29% vs. -32%), and minimal rate of pressure development (25% vs. 31%) respectively compared to sedentary control animals. Endurance exercise training attenuated (P > 0.05) all cardiotoxic effects of ADT+DOX treatment.
CONCLUSIONS: Treadmill training protected against combined ADT+DOX dysfunction, suggesting that cardiac function can be preserved in the clinical setting if cancer survivors concurrently endurance train while undergoing ADT and DOX treatment.

Oxidative Stress and Hematological Responses to Multimodal Exercise in a Cancer Survivor Receiving High-Dose Chemotherapy

Chris P Repka, Lauren E Dinsmore, Carole M Schneider, FACSM.
Rocky Mountain Cancer Rehabilitation Institute, University of Northern Colorado, Greeley, CO

Email: Chris.Repka@unco.edu

Despite evidence from animal models indicating that oxidative stress and hematological responses mediate the side effects of many cancer chemotherapy regimens, no clinical studies to date have examined oxidative stress and hematological dynamics in cancer survivors during chemotherapy, and potential modulation with exercise.

PURPOSE: To determine the effects of exercise on reactive carbonyl derivatives (RCD), a marker of oxidative stress, and hematological parameters in a cancer patient receiving chemotherapy. Additionally, to evaluate alterations in functional parameters.
METHODS: The case study was a 60-yr-old female, diagnosed with stage IIIC1 endometrial cancer, receiving chemotherapy (paclitaxel, carboplatin). Assessments evaluating functional parameters (muscular strength, VO2peak, fatigue) were performed one day prior to the first chemotherapy cycle and again at 3- and 6-months. Exercise was performed three times per week for one hour and consisted of treadmill walking and total body strength exercises. Plasma RCD concentrations were measured only at nadir time points, while white blood cells (WBC), red blood cells (RBC), hemoglobin (HGB), and platelets (PLT), were collected prior to each treatment and at nadir.
RESULTS: The subject had high baseline plasma RCD (6.13 nmol·mg-1), likely associated with her tumor burden. Following the exercise intervention, RCD levels dropped to 24% of baseline (1.47 nmol·mg-1). VO2peak improved 16% between baseline and 6-months (23.0 to 27.3 mL∙kg-1∙min-1). Combined upper body strength increased 21%, while combined lower body strength improved by 9%. Both WBC and PLT concentrations dropped during the course of chemotherapy (-66.5% and -55.8%, respectively), but rebounded to within normal ranges following each nadir period.
CONCLUSION: Even during a chemotherapy regimen which reduced WBC and PLT concentrations, a prescriptive exercise intervention mediated an increase in VO2 peak and muscular strength with a concomitant decrease in oxidative stress.

Center of Pressure Frequency Measures For Assessing Postural Steadiness in Cancer Survivors

Jeremy D. Smith, Abigail L. Carpenter, Gary D. Heise, Chris P. Repka, Carole M. Schneider, FASCM.
Rocky Mountain Cancer Rehabilitation Institute, University of Northern Colorado, Greeley, CO

Many cancer treatments result in peripheral neuropathies and vestibular dysfunction. Peripheral receptors and vestibular function are both important contributors to a person’s ability to maintain posture and balance.

PURPOSE: To determine whether frequency based measures of center of pressure (COP) during quiet standing were sensitive to changes in surface conditions and visual input in cancer survivors.
METHODS: Quiet standing in cancer survivors (n=11; mass = 75.6 ± 22.1 kg; height = 1.60 ± 0.05 m ; age = 56 ± 14 yr) was assessed while survivors stood on a: a) rigid surface with eyes open, b) rigid surface with eyes closed, c) compliant surface with eyes open, and d) compliant surface with eyes closed. COP data were collected for 30 s (1000 Hz). Based on previous literature focusing on postural steadiness in young and old populations, the following frequency measures were included: mean frequencies of the resultant distance (RD), anterior-posterior (AP), and medial-lateral (ML) COP; total power of the RD, AP, and ML COP; 95% power frequencies of the RD, AP, and ML COP; and fractal dimension of the confidence ellipse (CE). Two-way ANOVAs (p<0.05) with repeated measures were used to test main effects and interaction effects of surface and vision conditions.
RESULTS: Mean frequency of the ML COP increased when standing with eyes closed (0.47 to 0.57 Hz; p<0.05), but ML mean frequency decreased when standing on a compliant surface (0.64 to 0.45 Hz; p<0.01). Fractal dimension of the CE increased when the eyes were closed (1.43 to 1.49; p<0.01), but was not altered by surface condition. Total power of RD and ML increased with the eyes closed (2.8 to 8.9 Hz and 1.5 to 3.9 Hz, respectively; p<0.05) and when standing on the compliant surface (4.9 to 6.8 and 1.9 to 3.6 Hz, respectively; p<0.05). In addition, total power of the AP COP increased when the eyes were closed (5.8 to 20.7 Hz; p<0.01). No interactions were found.
CONCLUSION: Frequency measures of the COP were sensitive to changes in vision, but were less sensitive to changes in surface conditions. ML measures were more sensitive than AP measures to both conditions, which is inconsistent with results from healthy populations in the literature. Thus, in cancer survivors both ML and AP COP frequency measures should be used to assess postural steadiness.

Postural Steadiness in Cancer Survivors Based on Time Domain Measures of Center of Pressure

Abigail L. Carpenter, Jeremy D. Smith, Gary D. Heise, Chris P. Repka, Carole M. Schneider, FASCM.
Rocky Mountain Cancer Rehabilitation Institute, University of Northern Colorado, Greeley, CO

A common side-effect of cancer treatments is a loss of balance. Unfortunately, the literature related to balance in cancer patients is very descriptive with limited quantitative assessments of posture and balance in this population.

PURPOSE: To determine whether time-domain measures of center of pressure (COP) during quiet standing were sensitive to changes in surface conditions and visual input in cancer survivors.
METHODS: Quiet standing in cancer survivors (n=11; mass = 75.6 ± 22.1 kg; height = 1.60 ± 0.05 m; age = 56 ± 14 yr) was assessed while survivors stood on a: a) rigid surface with eyes open, b) rigid surface with eyes closed, c) compliant surface with eyes open, and d) compliant surface with eyes closed. COP data were collected for 30 s (1000 Hz). Based on previous literature focusing on postural steadiness in young and old populations, these time-domain measures were included: root-mean squares (RMS) of the resultant distance (RD), anterior-posterior (AP), and medial-lateral (ML) COP; total excursions of the RD, AP, and ML COP; mean velocities of RD, AP, and ML COP; and total sway area. Two-way ANOVAs (p<0.05) with repeated measures were used to test main effects and interactions of surface and vision conditions.
RESULTS: RMS values of RD and AP COP increased with eyes closed (4.6 to 6.5 and 3.9 to 6.0 mm, respectively; p<0.01). RMS values of ML COP increased with the compliant surface (1.7 to 3.1 mm; p<0.01). Total excursions of RD and AP COP increased with eyes closed (22.5 to 33.4 and 19.6 to 30.8 mm, respectively; p<0.01), and total excursions of RD and ML COP were increased with the compliant surface (24.1 to 31.9 and 8.7 to 14.4 mm, respectively; p<0.05). Mean velocity of RD, AP, and ML COP increased with eyes closed (10.6 to 20.0, 9.0 to 18.0, and 3.9 to 6.1 mm/s, respectively; p<0.05). Total sway area of AP COP increased with eyes closed (13.7 to 30.8 mm2/s; p<0.05). No interaction effects were found.
CONCLUSION: AP COP measures increased when survivors stood with eyes closed, but AP COP measures were not altered by changes in surface. AP COP measures might be beneficial in initial assessments of cancer survivors. Surface changes may be a useful perturbation in cancer survivors so that lateral stability problems may be detected, given the sensitivity of ML COP measures to surface changes.

Effects of In Vivo Doxorubicin Treatment on Skeletal Muscle Function

David S. Hydock, Chia-Ying Lien, Brock T. Jensen, Traci L. Parry, Carole M. Schneider, FACSM, Reid Hayward. University of Northern Colorado, Greeley, CO.

It is well known that the chemotherapy drug doxorubicin (DOX) is associated with a dose dependent cardiotoxicity, and thus the primary focus of DOX-induced side effects has been the heart. However, there is evidence that DOX also imparts a negative effect on skeletal muscle, but at this point, the nature of this DOX-induced myotoxicity is currently unknown.

PURPOSE: To investigate the effects of varying in vivo DOX doses on skeletal muscle function.
METHODS: Male rats were randomly assigned to receive 10 mg/kg DOX (DOX1), 12.5 mg/kg DOX (DOX2), 15 mg/kg DOX (DOX3), or control vehicle (CON). Five days following injections, animals were anesthetized and the soleus and extensor digitorum longus (EDL) muscles were excised for ex vivo muscle function analysis. Muscles were maintained in 37°C oxygenated Krebs buffer, and the proximal end of the muscle was mounted to a stationary glass hook while the distal end was affixed to an isometric force transducer. Maximal twitch contraction properties and fatigue rates were determined for all muscles using field stimulating platinum electrodes.
RESULTS: Maximal twitch force was significantly reduced in solei from DOX2 and DOX3 when compared to controls (-60% and -72%, respectively, p<0.05). Likewise, DOX2 and DOX3 solei possessed a significantly lower maximal rate of force production (-64% and -72%, respectively, p<0.05) and maximal rate of force decline (-52% and -59%, respectively, p<0.05) when compared to CON. Only EDL muscles from DOX3 possessed significantly different maximal twitch force, maximal rate of force production, and maximal rate of force decline when compared to CON (-67%, -72%, and -60%, respectively, p<0.05). Using a 100 s fatigue protocol, fatigue rate pattern differences were observed in the solei only. Whereas CON solei produced less force than baseline at 70 seconds, DOX1, DOX2, and DOX3 all produced less force than baseline at 30 seconds.
CONCLUSIONS: DOX treatment altered muscle function in a dose-dependent manner, and the effects were more profound in the soleus than the EDL. Skeletal muscle dysfunction may, therefore, be contributing to the fatigue experienced by cancer patients receiving DOX which suggests that approaches aimed at minimizing DOX-induced side effects should also target skeletal muscle.

Recent Publications & Abstracts