Annals of Oncology Advance Access originally published online on September 5, 2007
Annals of Oncology 2007 18(12):1957-1962; doi:10.1093/annonc/mdm364
© 2007 European Society for Medical Oncology
quality of life |
Cancer treatment-induced alterations in muscular fitness and quality of life: the role of exercise training
1 Rocky Mountain Cancer Rehabilitation Institute, University of Northern Colorado, Greeley, Colorado, USA
2 National Hsin Chu University of Education, Hsinchu, Taiwan
3 Regional Breast Center of Northern Colorado, Greeley, Colorado, USA
* Correspondence to: Dr Carole M. Schneider, Rocky Mountain Cancer Rehabilitation Institute, University of Northern Colorado, Campus Box 6, Greeley, CO 80639, USA. Tel: +1-970-351-2676; Fax: +1-970-351-1720; E-mail: carole.schneider{at}unco.edu
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Abstract |
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Background: Cancer survivors experience muscular weakness and reduced mobility, thereby compromising quality of life. This investigation utilized moderate prescriptive exercise to improve upper- and lower-body muscular fitness, flexibility, depression and quality of life in cancer patients.
Patients and methods: One hundred and thirty-five breast and prostate cancer survivors received cancer and medical history screening and a medical examination, as well as assessments of muscular strength (handgrip dynamometer) and endurance (bench press, lateral pull-down, leg press, shoulder press and curl-up crunch test), flexibility (Modified Sit and Reach), depression (Beck Depression Inventory) and quality of life (Quality of Life Index). Following the exercise assessments, cancer survivors trained in resistance exercise for 6 months during treatment or following treatment based on their results from the assessments and health status.
Results: Cancer survivors following treatment showed significant (P = 0.006) improvements in upper-body muscular endurance (+46.8%), lower-body muscular endurance (+67.1%), core muscular endurance (+32.5%) and flexibility (+6.2%), with concomitant improvements (P = 0.013) in depression (–25.6%) and total quality of life (+7.2%). Cancer survivors during treatment showed significant (P = 0.012) improvements in upper-body muscular endurance (+79.1%) and lower-body muscular endurance (+49.7%) while maintaining core endurance and flexibility in conjunction with improvements (P = 0.022) in depression (–43.0%) and quality of life (+11.5%).
Conclusions: Moderate-intensity individualized prescriptive exercise is a safe and efficacious means to augment muscular function and improve the quality of life of cancer survivors.
Key words: breast cancer, depression, muscular endurance, prostate cancer, survivorship
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introduction |
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TopAbstractintroductionpatients and methodsresultsdiscussionReferences |
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The mortality rate following cancer diagnosis has decreased significantly; however, cancer survivors can experience many debilitating side effects following cancer treatments. Surgery, radiation therapy, chemotherapy and hormonal therapy have acute and chronic effects on physiological systems such as the muscular system. Cancer and cancer treatments can potentially induce lean tissue degradation and abnormalities in the metabolic system in cardiac and skeletal muscle [1, 2], resulting in loss of muscular strength in cancer survivors. Multiple factors appear to contribute to muscle wasting, such as cytokines (tumor necrosis factor-
, interleukin 1, interleukin 6, interferon-
) and fatty acid-derived eicosanoids. Another potential factor involved is proteolysis-inducing factor (PIF). PIF activates the ubiquitin–proteasome proteolytic pathway, which may be the proteolytic pathway for muscle breakdown in cancer patients. The interaction of the aforesaid tumor products, hormones and inflammatory mediators promotes gluconeogenesis, limits anabolism and increases catabolism, which contributes to the poor performance status of cancer survivors and threatens cancer survival [1, 3–5]. The loss of lean muscle mass occurs due to a decline in protein synthesis in conjunction with enhanced protein catabolism. Cancer survivors experience the decline in protein synthesis due to physical inactivity (deconditioning) coupled with a possible reduction in the supply of amino acids in protein production, while protein degradation appears to be due to an increased expression of components in the ubiquitin–proteasome proteolytic pathway. The major adaptations that occur as a result of a decline in protein synthesis and protein degradation include (a) a reduction in muscle and muscle fiber cross-sectional area as a result of a loss of myofibrils and myofilaments; (b) a loss of muscle extensibility; and (c) a decrease in proteins necessary for metabolism, especially the oxidative enzymes in the Krebs cycle and electron transport chain, leading to a reduction in the muscles’ oxidative potential [1, 3]. The contractile and metabolic proteins that are lost are responsible for muscle contraction, force generation, extensibility and the production of energy (ATP). Cancer survivors with reduced protein synthesis and muscle degradation experience muscle weakness, decreased functional work capacity, decreased flexibility, reduced mobility and diminished quality of life.
In a healthy population, researchers [6–8] have found decreases in muscular endurance after only 2 weeks of physical inactivity and reductions (–60%) in oxidative enzymatic activity within 3 months of physical inactivity. Physical inactivity in chronic diseases would result in similar or exacerbated physiological reductions. Therefore, physical activity (exercise) has been used as a therapeutic aid in the treatment of various pathophysiological conditions such as cardiovascular disease. A growing body of research is showing that exercise interventions can help cancer survivors during treatment or following treatment. Studies [9–12] on the benefits of exercise have used aerobic exercise, weight training or combination exercises either during treatment or following cancer treatment. These studies have shown improvements in functional (work) capacity, upper-body fitness and lower-body fitness with concomitant decreases in fatigue in cancer survivors during or following various types of cancer therapies. Thus far, research investigating the effects of exercise on cancer survivors has reported results during treatment or following treatment utilizing different assessment criteria, yet has compared exercise outcomes across investigations. Additionally, a vast majority of studies [13–15] implement generalized exercise interventions that are not based on the health of each cancer survivor. Generalized exercise interventions have the potential to exacerbate the negative side effects of cancer treatments [16]. Therefore, the purpose of this investigation was to determine the effects of an individualized prescriptive exercise training program, performed either during or after cancer treatment, on upper-body and lower-body muscular fitness, flexibility, depression and quality of life in breast and prostate cancer survivors. It was hypothesized that cancer survivors would show improved performance on the assessed physiological and psychological parameters following a 6-month exercise intervention and that exercise would prove to be a safe and effective therapeutic aid whether cancer patients were in treatment or had finished treatment.
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patients and methods |
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patients
The study included 135 cancer survivors, 114 of breast cancer and 21 of prostate cancer. Of these, 114 patients (mean age 59 ± 10 years) had completed treatment, while 21 patients (mean age 57 ± 11 years) were undergoing cancer treatment concurrently with the exercise intervention. The types of cancer treatments that the following-treatment group had experienced included 93% surgery, 47% chemotherapy and 40% radiation. The during-treatment group had 81% undergoing chemotherapy and 67% undergoing radiation during the exercise intervention. Cancer patients participated in an established cancer rehabilitation program that was individualized for each patient according to his/her assessment results and health status. Sample fluctuations occurred for various reasons; for example, some patients were not able to perform some of the tests because our medical director felt that they had medical limitations that prohibited them from doing so. The university's Institutional Review Board approved all study procedures.
assessment and reassessment
Patients received comprehensive cancer and medical history screening followed by a medical examination [16]. Muscular strength and endurance, flexibility, depression and quality of life were assessed, leading to the development of individualized exercise prescriptions. Throughout the assessments, resting and exercise heart rates were monitored (Polar Inc., Lake Success, NY) along with blood pressure and oxygen saturation. Reassessments were obtained following a 6-month exercise intervention utilizing identical protocols to assess program effectiveness. Thus the study was a pre-/post-study design, with measures obtained at baseline and after 6 months of exercise.
Muscular handgrip strength was assessed using a Takei TKK 5101 handgrip dynamometer (Takei Scientific Instruments, Tokyo, Japan). Participants held the dynamometer parallel to their side with the dial facing away from the body and performed three trials with each hand. Testing was performed with the patient alternating between the right and left hand, allowing at least 1 minute of rest between trials. The best score for each hand was used as the measure of static strength.
Muscular endurance was assessed using the bench press, lateral pull-down, leg press and shoulder press exercises as well as the curl-up crunch test. The initial amount of weight lifted for the bench press, lateral pull-down, leg press and shoulder press exercises was based on a muscular endurance test battery for cancer patients developed by Schneider et al. [16]. Repetitions were performed at a rate of 12.5 repetitions per minute until volitional fatigue.
bench press.
The participant lay flat on the bench with feet up on the end of the bench (this helps to ensure that the back remains flat on the bench throughout the entire test). The participant's hands were placed where they were comfortable, but in a position in which the pectoral muscles were emphasized throughout the lift (hand placement may be dependent on body size). The handles of the bar were positioned at approximately the middle of the chest. A full repetition was employed as follows. Up: training arm is raised until arms are extended but not locked. Down: training arm is lowered until weight touches the top of the weight stack.
lateral pull-down.
The participant sat on the bench seat with thighs positioned comfortably underneath the roller pads (adjusted if needed). The participant's hands were positioned on the bar slightly outside shoulder width. Palms must face the participant (supinated). The participant's torso remained upright throughout the lift (no leaning forward or backward). A full repetition was employed as follows. Down: training arm is pulled down until it is approximately even with the middle of the chest (pull down in front). Up: training arm is allowed to rise until arms are extended but not locked.
leg press.
The participant sat on the leg press seat with back flat against the backrest and with buttocks tucked as far back as possible. The backrest was adjusted forward or backward until the upper leg was approximately perpendicular to the floor. There was a 90o bend in the participant's legs. The participant placed feet on the platform approximately shoulder width apart and in a position in which the quadriceps and hamstrings were exercised as evenly as possible (the participant should do a few repetitions with no weight in order to determine this position). A full repetition was employed as follows. Up: the platform is pushed out until legs are fully extended (legs should not be completely locked). Down: the platform is allowed to move back in until weight touches the top of the weight stack.
shoulder press.
The back of the seat is adjusted so that it is in the upright position (making sure that the seat is locked). The participant sat on the seat with back and buttocks against the backrest. The participant's hands were placed on the lower handles at a comfortable width (this depends on body size). Feet were placed flat on the floor approximately shoulder width apart. A full repetition was employed as follows. Up: training arm is raised until arms are extended but not locked. Down: training arm is lowered until weight touches the top of the weight stack.
curl-up crunch.
The participant assumed a supine position on a mat with knees at 90°. The arms were at the side, with fingers touching a piece of tape. A second piece of tape was placed 8 cm (for participants >45 years old) or 12 cm (for participants <45 years old) beyond the first piece of tape. A metronome was used to establish a rate of 20 crunches per minute. Participants performed crunches until they could no longer touch the line or could not maintain the repetition rate, or until they reached volitional fatigue. The participant had to lift the shoulder blades off the mat (trunk makes a 30° angle with the mat) with fingers touching the second piece of tape. The low back should be flattened before curling up. The participant must touch both pieces of tape (the start and the finish tape).
modified sit and reach.
The Modified Sit and Reach test was used to assess flexibility of the hamstrings and low back. Participants sat on the floor with shoulders, head and buttocks against the wall and legs straight in front. A 12-inch sit-and-reach box was placed against the soles of the feet with the zero end of the measuring device toward the participants. Participants maintained head and shoulder contact with the wall while holding arms straight in front of the body to establish the starting position. Bending forward at the waist and maintaining straight legs, participants performed three trials by sliding their fingertips along the top of the measuring device. The best of the three trials was used as the final score.
depression.
The Beck Depression Inventory was given to assess depression before and after exercise intervention to determine if physical activity contributed to the overall reduction in depression due to cancer diagnosis. This inventory has been shown to be reliable and valid for the assessment of depression. The inventory is a 21-question index with scores on the Beck Depression Inventory ranging from 0 to 63. Higher scores indicate greater depression [17] with 0 being no depression and >40 being extreme depression.
The Ferrans and Powers Quality of Life Index Cancer Version III [18] is a 66-question index that was used to assess social, psychological, family and health life satisfaction. This inventory was given to assess quality of life alterations before and after exercise intervention to determine if alterations in physical functioning contribute to an enhanced quality of life in cancer survivors. A higher total score and higher scores on the social, psychological, family and health subscales indicate greater satisfaction. The internal consistency reliability of this instrument is = 0.95 with a validity of r = 0.80.
exercise intervention.
The exercise trainers working with our cancer survivors had to be certified cancer exercise specialists. Cancer exercise specialists hold a Bachelors degree in a health/fitness profession, have completed coursework in cancer rehabilitation and have successfully passed a certification examination. The exercise specialists develop the individualized exercise prescriptions and exercise interventions to meet the specific needs of each cancer patient, based on results from the medical and cancer history, medical examination and initial physiological and psychological assessments. The general criteria for the exercise intervention included: (a) exercise frequency, 2–3 days per week; (b) exercise duration, 60 minutes of exercise; (c) exercise mode, resistance training (resistance tubing, Cybex variable weight machines, dumbbells) and aerobic training (outdoor or treadmill walking, stationary cycling, recumbent stepping); and (d) exercise intensity, based on health and fitness status. Intensity was determined using heart rate reserve (HRR) which is calculated as (exercise target heart rate = [(220 – age) – HRrest] x % exercise intensity + HRrest, where HRrest = resting heart rate), rating of perceived exertion (RPE) (Borg Scale: 0–10 version with 10 = very, very hard, 0 = no exertion) and increased number of repetitions (Table 1).
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Even though there are general criteria for the exercise intervention, patients’ exercise programs should be individualized for each patient based on the screening and assessment results. Specifically for this study, patients attended individualized, supervised exercise sessions 2 or 3 days per week for 6 months. The exercise sessions lasted 60 minutes, based on a ‘whole-body’ approach [16]. Each exercise session was individualized for the cancer survivor but generally included a 10–15-minute warm-up, 40 minutes of aerobic exercise and resistance and flexibility training and concluded with a 10-minute cool-down. Aerobic exercise involved outdoor or treadmill walking, stationary cycling, recumbent stepping and walking on an AquaCiser® II underwater treadmill system (Ferno-Washington, Wilmington, OH).
Resistance training followed the aerobic portion of the exercise session. Patients progressed from resistance tubing to weight machines to free weights. Stability balls, balance pads and BosuTM balls were integrated into resistance training exercises to increase proprioception and balance. The larger muscle groups were targeted first (chest and back) and then the smaller muscle groups (biceps and triceps). For example, throughout the course of the 6-month exercise intervention, the chest muscles would be trained by having the patient use the resistance tubing while seated in a chair, doing a chest press movement. The patient would then be progressed to the chest press machine. Once the patient was comfortable with the movement on the chest press machine, the cancer exercise specialist would have the patient progress to the chest press using a barbell on a flat bench. Next, the patient would perform the chest press with dumbbells on the flat bench. The stability ball would then be used instead of the flat bench to incorporate the core of the body into the exercise for balance and stability. Progression was similar for upper-body and lower-body resistance exercises. Patients performed 2–3 sets of each exercise with 8–12 repetitions per set. Resistance was based on heart rate response to the exercise and RPE. The ideal weight and number of repetitions elicited an RPE ranging from 1 to 5. Patients trained on nonconsecutive days, which allowed the cancer exercise specialists to include exercises that targeted all of the major muscle groups in each exercise session.
The exercise sessions concluded with an extremely low-intensity cool-down (i.e., heart rate = 10% HRR; RPE = 1; low repetitions using walking and light weights) targeting all of the major muscle groups.
statistical analyses
Data are presented as means ± standard deviations (SD). Patients’ characteristics in the two groups (during-treatment versus following-treatment) were compared using independent t-tests. The main effect of supervised exercise training was determined comparing before and after exercise intervention using repeated-measures analysis of variance (ANOVA). Following main effects significance, Tukey HSD post hoc tests were used to determine where significance occurred. The primary analyses compared changes before and after exercise intervention and between treatment groups using univariate analyses of covariance (ANCOVA) procedures in which the post-intervention value was the dependent variable, the pre-intervention value of the same variable was the covariate and the treatment group was the grouping variable. A Pearson correlation analysis was used between strength improvement and time out of therapy to determine spontaneous strength and endurance improvement. Statistical analyses were performed using the Statistical Package for the Social Sciences (SPSS) software package (SPSS, Chicago, IL). Significance was set at P 
0.05.
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results |
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A total of 135 breast and prostate cancer survivors were referred by their oncologists for participation in this study. Of these, 114 patients had completed surgery, radiation and/or chemotherapy treatment (average 25 months post-treatment), while 21 survivors were undergoing cancer treatment during the exercise intervention. Follow-up examinations revealed that patients’ adherence to the exercise intervention was 81.9%. The cancer survivors’ initial characteristics were similar between groups.
Table 2 shows the changes in muscular fitness for during-treatment and following-treatment groups before and after exercise intervention. The during-treatment group had significant improvements in the lateral pull-down (P = 0.008) and leg press (P = 0.16) after the supervised exercise intervention. However, there was a significant reduction of right handgrip strength in the during-treatment group (P = 0.013). The following-treatment group showed significant improvement in bench press (P = 0.000), lateral pull-down (P = 0.000), leg press (P = 0.000), shoulder press (P = 0.022), curl-up crunch (P = 0.001) and sit and reach (P = 0.011) after the supervised exercise intervention.
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Table 3 displays alterations in depression and quality of life before and after exercise intervention for during-treatment and following-treatment groups. The exercise intervention resulted in significant reductions in depression for both groups. Cancer survivors in the during-treatment group showed significant improvements in depression (P = 0.001), total quality of life (P = 0.043) and social quality of life (P = 0.004), while the following-treatment group showed significant improvement in depression (P = 0.000), total quality of life (P = 0.025) and health quality of life (P = 0.042) after the exercise training intervention. Additionally, the during-treatment group showed greater improvement (P = 0.004) in social quality of life compared to the following-treatment group.
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A correlation analysis between strength improvement and time out of therapy showed no significant relationships between strength and time out of therapy, thus implying that spontaneous strength improvement did not occur as a result of having completed treatment. The during-treatment and following-treatment participants were extremely sedentary, which was evident from their responses during screening.
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discussion |
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TopAbstractintroductionpatients and methodsresultsdiscussionReferences |
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The present study used exercise as a countermeasure to attenuate the negative side effects experienced by cancer survivors. As stated earlier, the major adaptations that occur as a result of lean tissue loss (decline in protein synthesis and an increase in protein degradation) include a reduction in muscle fiber cross-sectional area as a result of a loss of myofibrils and myofilaments, a loss of muscle extensibility and a decrease in the oxidative enzymes in the Krebs cycle and electron transport chain. The resulting decrements manifest as a loss of muscular strength and endurance with significant muscle weakness, reduced mobility and reduced quality of life in cancer survivors [1, 3–5].
The muscular endurance exercise training employed in this study has been shown to enhance work capacity in a healthy population within a 2-month period. It is well documented [6–8] that endurance exercise increases the concentration of the oxidative enzymes in the Krebs cycle and electron transport chain and increases the size and volume of muscle mitochondria. The oxidative adaptations that occur boost the capacity of the muscles to resynthesize ATP for enhanced muscular work. Exercise endurance training also increases the myoglobin content within the muscle; thus, oxygen becomes more readily available for the production of ATP. Additionally, endurance exercise increases the size of the muscle fibers as a result of increased synthesis of proteins. The increase in the muscle fiber cross-sectional area is a result of synthesis of myofibrils and myofilaments, which enhance muscle contraction and force generation. Likewise, the uptake of fatty acids by the muscle from the plasma is enhanced because of the increased number of capillaries serving the muscle fibers. This enhanced uptake provides extensive amounts of energy for improved functional work capacity [6].
Utilizing moderate individualized prescriptive exercise assessments and exercise interventions, the current investigation found improvements and/or maintenance in muscular fitness. Our findings suggest that moderate-intensity exercise can provide a sufficient physiological stimulus to improve muscular performance in cancer survivors, whether the exercise is performed during or after cancer treatment. Given that all tissues and systems in the human body are affected by physical exercise, and seeing that exercise in this study improved physical performance, it seems that regular exercise is a useful complementary strategy to improve the quality of life physically and psychologically for cancer survivors. Moderate-intensity individualized prescriptive exercise is a safe and efficacious means to improve muscular function in cancer survivors.
Taking into account the limitations of this study, such as unequal groups and lack of randomization, the readiness for the implementation of exercise in clinical practice must be approached with caution. However, it appears as if exercise, a non-pharmacological treatment, may have profound beneficial effects for cancer patients. Many of the primary benefits of exercise in healthy populations could, in essence, treat specific problems associated with cancer toxicities. The clinical relevance of this investigation involves the significant exercise outcomes found for cancer survivors during and following treatment. To date, the only definitive way to prevent toxicities associated with cancer treatments has been to limit the cumulative dose or modify the time course of cancer therapy, which could potentially lead to ineffective treatment of the cancer. Exercise-induced adaptations may attenuate cancer toxicities, which in turn could augment cure rate, increase long-term survival and improve the quality of life for cancer survivors.
Received for publication March 15, 2007. Revision received May 9, 2007. Revision received June 21, 2007. Accepted for publication June 22, 2007.
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References |
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1. DeVita VT, Hellman S, Rosenberg SA. Cancer Principles and Practice of Oncology (2005) 7th edition. Philadelphia: Lippincott Williams & Wilkins.
2. Hayward R, Ruangthai R, Schneider CM, et al. Training enhances vascular relaxation after chemotherapy-induced vasoconstriction. Med Sci Sports Exerc (2004) 36:428–434.
3. Tisdale MJ. Cachexia in cancer patients. Nature Reviews Cancer (2002) 2:862–871.[CrossRef][Web of Science][Medline]
4. Argiles JM, Costelli P, Carbo N, et al. Tumor growth and nitrogen metabolism in the host. Int J Oncol (1999) 14:479–486.[Web of Science][Medline]
5. Todorov PT, McDevitt TM, Cariuk P, et al. Induction of muscle protein degradation and weight loss by a tumor product. Cancer Res (1996) 56:1256–1261.
6. Wilmore JH, Costill DL. Physiology of Sport and Exercise (1994) 1st edition. Champaign, IL: Human Kinetics.
7. Coyle EF, Martin WH, Sinacore DR, et al. Time course of loss of adaptations after stopping prolonged intense endurance training. J Appl Physiol (1984) 57:1857–1864.
8. Haddad R, Roy RR, Zhong H, et al. Atrophy responses to muscle inactivity: I. Cellular markers of protein deficits. J Appl Physiol (2003) 95:781–790.
9. Visovsky C. Muscle strength, body composition, and physical activity in women receiving chemotherapy for breast cancer. Integ Cancer Ther (2006) 5:183–191.[CrossRef]
10. Fairey AS, Courneya KS, Field CJ, et al. Randomized controlled trial of exercise and blood immune function in postmenopausal breast cancer survivors. J Appl Physiol (2005) 98:1534–1540.
11. Hutnick NA, Williams NI, Williams WJ, et al. Exercise and lymphocyte activation following chemotherapy for breast cancer. Med Sci Sports Exerc (2005) 37:1827–1835.
12. Segal RJ, Reid RD, Courneya KS, et al. Resistance exercise in men receiving androgen deprivation therapy for prostate cancer. J Clin Oncol (2003) 21:1651–1652.
13. Dimeo F, Bertz H, Finde J, et al. An aerobic exercise program for patients with haematological malignancies after bone marrow transplantation. Bone Marrow Transp (1996) 18:1157–1160.
14. Dimeo F, Stieglitz R, Fischer-Novelli U, et al. Effects of activity on fatigue and psychologic status of cancer patients during chemotherapy. Cancer (1999) 85:2273–2277.[CrossRef][Web of Science][Medline]
15. Thorsen L, Skovlund E, Stromme SB, et al. Effectiveness of physical activity on cardiorespiratory fitness and health-related quality of life in young and middle-aged cancer patients shortly after chemotherapy. J Clin Oncol (2005) 23:2378–2388.
16. Schneider CM, Dennehy CA, Carter SD. Exercise and Cancer Recovery (2003) 1st edition. Champaign, IL: Human Kinetics.
17. Salkind MR. Beck depression inventory in general practice. J R Coll Gen Pract (1969) 18:267–271.[Medline]
18. Ferrans CE, Powers MJ. Quality of life index: development and psychometric properties. ANS Adv Nurs Sci (1985) 8:15–24.[Medline]
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