Older individuals who have survived cancer and the commensurate treatment often experience a reduced quality of life due, in part, to functional limitations, impaired muscular abilities, and deficits in mobility. Long-term cancer survivors have been characterized as having significantly higher rates of functional deficits as well as restricted levels of social participation compared with those with no cancer history.1–3 Older (70 years or older) cancer survivors are 7 to 10 times more likely to report decreased functional levels2 and are 25% to 50% more likely to report limitations in activities requiring strength and mobility (such as prolonged walking or standing, doing heavy work, or whole-body movements) than controls who have never experienced cancer.2,3
Deficits in muscle strength and mobility resulting from the dual influence of age-related muscle wasting (sarcopenia) and having survived cancer can accelerate functional decline. Cancer-related skeletal muscle wasting likely contributes to this decline and is attributable in large part to increased muscle protein degradation.4 Several proteolytic systems may be involved in a cancer survivor's decline in muscle function including the adenosine triphosphate—dependent ubiquitin-proteasome system.5 Other contributing factors include proinflammatory cytokines and the tumor-released proteolysis-inducing factor.4,6 Adverse effects on muscle from past or continued management of cancer can also affect function. For example, androgen deprivation therapy can negatively impact skeletal muscle function by acting at multiple sites, namely, the androgen receptor, the neuromuscular junction, and second messenger systems, including insulin-like growth factor-1.7 Effects at all of these sites lead to skeletal muscle wasting with weakness and contribute to cancer-related fatigue and a diminished quality of life.7,8 Decreased physical activity and decreased nutritional intake may also play a role.4 Collectively, a degradation of muscle coupled with decreased function can lead to a positive feedback loop whereby muscular abilities become more deficient, functional deficits worsen, and the older cancer survivor suffers from a unique and compounding set of adverse sequelae associated with having survived cancer, aging, and an increasing level of sedentary behaviors. The worst-case scenario is that increasing levels of functional deficits ultimately lead to premature disability. In an effort to mitigate this deteriorating condition, countermeasures designed to reverse deficits in muscular abilities and improve mobility are essential. Perhaps, even more critical is that these countermeasures must be feasible for the fatigued older cancer survivor.
A consistent effect of resistance exercise (eg, strength training) with older individuals who have not experienced cancer is an improvement in function and enhanced muscle activity and mobility.9–13 Similarly, cancer survivors 50 years or older who participated in resistance exercise have benefited. Exercise intervention studies incorporating resistance exercise have reported increases in lean muscle mass, muscular strength, cardiopulmonary function, and quality of life as well as decreases in body fat composition and fatigue.14–18
A recent meta-analysis19 highlights the greater potential for positive muscle responses with eccentric training versus concentric training in younger individuals. Resistance exercises that employ eccentric muscle contractions also have recently been incorporated in strength training regimens with older individuals.20–22 Eccentric exercise may be ideally suited to older, fatigued, and weak individuals because muscles operating eccentrically can produce high forces to help muscle grow, yet the energetic cost associated with this type of exercise is trivial compared with other exercise modes.20–22 Resistance exercise via negative, eccentrically induced work (RENEW) has been demonstrated as safe and feasible in older individuals without cancer, though this has not yet been demonstrated in cancer survivors. Previous studies 19-21,23–30 have shown that RENEW results in greater changes in quadriceps muscle size, strength, and mobility than more traditional resistance exercise that employs a combination of concentric and eccentric muscle activity. High-intensity resistance exercise is also capable of promoting longer-lasting improvements.20,21 The novelty of RENEW as a potential physical exercise countermeasure for cancer survivors is that only low levels of exertion are required to produce relatively high muscle forces and commensurate positive changes in muscle and mobility. This may be especially important for older individuals who have limited energy to put toward exercise due to the combination of aging and having survived cancer and its treatment. It is unclear however, whether older cancer survivors can feasibly tolerate the potentially high eccentric muscle forces or experience the benefits resulting from RENEW.
Therefore, the purpose of this study was to determine the feasibility and preliminary efficacy of 12 weeks of RENEW in older cancer survivors.
Male and female cancer survivors 60 years or older were recruited via the Radiation Therapy Department and the Oncology Clinic at the Huntsman Cancer Institute at the University of Utah, Salt Lake City, from clinical databases at the University of Utah, and from local newspaper advertisements as well as word-of-mouth referral. Additional inclusion criteria were being at least 6 months posttreatment, that is, localized treatment (surgery or radiation therapy or both) or systemic treatment (chemotherapy) and having no evidence of disease nor pursuing any active cancer-related treatment other than hormonal therapy. Participants were included if they had a minimum of “moderate” levels (≥4 on a Likert scale from 0 to 10; 0 = lack of perception, 10 = worst possible perception) of fatigue (combined group's mean = 4.8 [1.9]) and/or weakness (combined group's mean = 4.3 [1.9]) as measured by the General Fatigue Scale and General Weakness Scale, respectively.31 Further criteria included a Folstein Mini-Mental State Examination score of 23 or more, having the ability to ambulate in the community, and having been medically cleared to participate in an exercise program. Participants were excluded if they had a central nervous system disorder, neurological insult that manifests in a mobility disorder, myopathic disease that affects skeletal muscle structure/function, rheumatologic disease that has an effect on muscle and/or mobility; diagnosed chronic fatigue syndrome/disorder; impaired knee flexion of less than 90°, extreme claustrophobia, and/or had been a participant in regular (2-3 times per week) aerobic or resistance exercise over the previous 6 months. The Institutional Review Board at the University of Utah approved the study and written acknowledgment of informed consent was obtained from all participants before participating in the study.
Resistance Exercise via Negative, Eccentrically Induced Work Protocol
The RENEW was performed on a recumbent high-force eccentric ergometer, described previously,21 3 days a week for 12 weeks. The recumbent eccentric stepper (Figure 1) is powered by a 3-horsepower motor that drives the foot pedals in a “backwards” direction, that is, toward the individual. Eccentric muscle contractions occur when the individual attempts to resist this motion by pushing on the pedals (with verbal instructions to “try to slow down the pedals”) as they move toward him or her. Because the magnitude of the force produced by the stepper exceeds that of the individual, the pedals continue to move toward the participant at a constant velocity, resulting in eccentric contractions of the knee and hip extensors, including the quadriceps muscles.
The progression of RENEW was dictated by the exercise protocol as a function of the rating of perceived exertion based on a Borg Perceived Exertion Scale33 (Table 1). A “target” negative work, at the prescribed rating of perceived exertion level, was visible to the participant on a computer monitor and the goal was to achieve ever-increasing total amounts of negative work per session. The protocol dictated the duration and perceived exertion during exercise. The participants began with a 3- to 5-minute session on the stepper at a “very, very light” and “very light” exertion level for the first 1 to 2 weeks and progressed to a maximum of 15 minutes at a “fairly light” to “somewhat hard” exertion level during week 3 to 4. Thereafter, attempts were made to perform RENEW on the stepper at a “fairly light” to “somewhat hard” exertion level for 16 to 20 minutes for the last 8 weeks. It is our experience that during any form of exercise this population will exert to a level consistent with the perception of exercising “somewhat hard.” Therefore, once a rating of perceived exertion of “somewhat hard” was achieved, participants were instructed to maintain that exertion level throughout the remaining weeks of training. Participants exercised at a self-selected range of 15 to 25 steps per minute. Immediately after each training session, the total negative work in kilojoules was recorded and averaged over the number of exercise sessions per week.
Measures of Feasibility and Preliminary Efficacy
The measures of feasibility included (1) the ability to participate and progress the total amount of negative work output (kJ) of RENEW over a 12-week period; (2) whether RENEW induced leg “thigh” muscle pain as measured on a visual analog scale (VAS) with 0 cm = no pain, 10 cm = worst pain possible; and (3) whether peak knee extension force production (N) produced on a dynamometer became impaired.
The number of completed sessions (out of a total of 36 possible) was recorded, and overall compliance was calculated as a percentage of sessions completed. Each session, the participant's total negative work (kJ) was recorded and then averaged for the week. The program was considered feasible if older cancer survivors participated in more than 74% of the available sessions and the average total work per week continually increased over the 12 weeks. Thigh pain was assessed prior to each training session using a 10-cm VAS. Participants were asked to mark on the VAS how much pain they experienced in the muscles of their thigh since the last training session. The scale is anchored at the left end (0 cm) with the descriptor “no pain” and at the right end (10 cm) with the descriptor “worst possible pain.” VAS scores of 1 or less are considered clinically insignificant.34,35 The weekly averages were used for statistical analysis. Peak knee extension force (N) production was measured on a Kin Com dynamometer (Chattecx, Chattanooga, Tennessee) 2 to 3 days before training started in week 1 and 2 to 3 days after the last session in week 12. Knee extension force was measured with the participants seated with their hips and knees flexed at 90° and the upper body strapped to the seat of the dynamometer. The testing arm of the dynamometer is equipped with a force plate that is attached to the shin above the ankle joint. The participant completed 3 warm-up trials at 50%, 75%, and 100% of their maximal effort before scores were recorded. Participants then completed 3 trials at 100% maximal effort. The peak force (N) of each trial was recorded. This procedure was repeated for each leg. The average score of both legs over the 3 trials was used for statistical analysis.36
The measure of efficacy was the performance on the timed up-and-go (TUG) mobility test (s).37 Participants were asked to rise from a chair without using their arms, walk around a cone 3 m away, and sit back in the chair as quickly and safely as possible. Participants were given 1 practice trial and 3 test trials. The average score of the 3 test trials was used for statistical analysis.
Data were analyzed with Sigma Stat Version 3.5 (Chicago, Illinois). Descriptive statistics were calculated for baseline demographic characteristics. In the analyses, we evaluated the training effect of RENEW on the total amount of work output over each of the 12 weeks of training and whether RENEW induced leg thigh muscle pain as measured on a VAS each of the 12 weeks of training with a 1 factor (time in weeks) repeated-measures analysis of variance. Because peak knee extension torque production and the TUG mobility test were measured only at the pre- and posttraining time points, a paired t test was employed to determine whether changes occurred. With all analytical procedures, the level of significance was set at P = .05.
The participants included a total of 20 individuals (13 female, 7 male) with a mean age of 75 (7) years and a body mass index of 28 (4). The cohort's mean survival was 8.5 (9) years since their cancer diagnosis (50% breast, 25% prostate, 20% colorectal, and 5% lymphoma). Local treatment (surgery ± radiation therapy) characterized 75% of the cohort and systemic treatment (chemotherapy) or combined local and systemic treatment characterized the remaining 25% of the cohort.
The participants completed an average of 34 of the potential 36 sessions over 12 weeks of RENEW, resulting in a compliance rate of 95%. The participants significantly (P < .001) increased the total average work per week over the 12 weeks of RENEW (Figure 2). Following the first 2 weeks of acclimatization and ramping up of the work in a progressive fashion, participants increased their work approximately 3-fold from week 3 (7.6 [5.1] kJ) to week 12 (22.1 [14.8] kJ) without a statistically significant (P = .10) change in the perception of thigh pain over the 12-week RENEW training period (Figure 2). Knee extension peak force production did not become impaired. Rather, it improved significantly (P = 0.02) (pretest: 248  N; posttest: 275  N) after 12 weeks of RENEW.
The effect of RENEW on mobility was clinically positive because the time to perform the TUG test improved significantly (P < .001) (pretest: 8.4 [2.7]; posttest: 7.2 [2.3] s) after 12 weeks of RENEW.
The older individuals who have survived cancer and participated in this preliminary study were compliant with RENEW and experienced an increase in the total negative work (approximately 3-fold), with a clinical equivalent of a “no muscle injury” response. Collectively, this signifies a feasible response to the eccentric resistance exercise training. When coupled with the improvements in strength (14%) and mobility (11%) following RENEW, it also suggests a preliminary level of efficacy that is worthy of further investigation.
Resistance exercise trials (n = 24), performed 2 to 3 times per week for a median of 12 weeks, were recently reviewed in a systematic fashion.14 The consensus findings from this systematic review were that general improvements in muscle function, lean body mass, and cardiopulmonary function can occur with resistance training in cancer survivors. Less than half of the studies reported exercise intensities, but of those that did, the range of 1 repetition maximum exercise intensities was moderate to high (eg, 60%-85%) with no adverse events reported. More specifically, composite hip and knee muscle strength improves, but specific mobility tasks are infrequently reported.14 Furthermore, the systematic review generated “no evidence” for the ability of resistance training to specifically improve knee extension (aka quadriceps) strength, a muscle function closely associated with mobility-related tasks in older individuals.38–40 It is not possible to discern, however, whether the outcomes of these studies can be attributed to resistance training alone or to a combination of resistance and aerobic exercise since most studies employed both modes of exercise.
Resistance training—only studies (2 in women who were receiving or had recently completed adjuvant therapy for breast cancer16,41 and 2 in men receiving androgen-deprivation therapy for prostate cancer)15,42 demonstrated increases in strength associated with increases in various measures of physical performance and quality of life. Women having survived breast cancer did increase strength and lean body mass, although changes in quality of life were equivocal following 2 to 3 times per week sessions (at approximately 60%-70% of 1 repetition maximum) for 4 to 6 months.16,41 Men having survived prostate cancer did improve their quality of life,15 and likewise did increase muscle function15,42 as well as their performance on mobility tasks such as stair climbing, gait speed, and chair rises.42
High-intensity exercise, such as eccentric muscle exercise, may be another possible mode of resistance exercise for this population because not only can it amplify gains in muscle strength and mobility20,21,23,25–28,30 but it may also maintain these gains over a longer period of time.43 Therefore, the feasibility and utility of a high-force eccentric exercise were explored as an exercise option for increasing muscle strength and mobility in older survivors. The early findings from this preliminary study are similar to those following a more traditional resistance exercise program14 but were blunted compared with previous eccentric trials in older individuals who never experienced cancer or its treatment.21,23 Specifically, older (65 years or older) individuals have previously demonstrated 3-fold greater responses with eccentric exercise;30 with frail individuals demonstrating 20% to 60% improvements in mobility and strength, respectively, following RENEW.21 In older individuals performing RENEW 3 times per week, for 10 to 12 weeks, superior improvements in muscle size,23,27 muscle strength,21,27,30 mobility,21,24,27 and quality of life24 have consistently been demonstrated when compared with more traditional resistance exercises.
The potential of the high forces and low-energetic costs of RENEW for older cancer survivors who are weak or suffering from mobility impairments, however, remains alluring. Earlier work by Meyer et al44 and Vallejo et al45 demonstrated that older individuals require less cardiopulmonary demand during eccentric exercise than during equivalent amounts of traditional (ie, concentric) exercise. With that, older individuals with impaired exercise tolerance have the ability to tolerate 3-fold greater negative workloads at central and hemodynamic levels that are considered safe. Here we report a first attempt at having an older heterogeneous group of cancer survivors progressively increase (approximately 3-fold) their negative work at perceived exertion levels that are feasible for them and can produce efficacious outcomes. Since the older cancer survivor has numerous barriers to initiating and adhering to exercise, which ultimately interferes with improved function, exercise modes with high participation rates (70% or greater) that focus on muscle strengthening and improved mobility are a high priority.41 Furthermore, cancer-related fatigue is ubiquitous across most cancer types following diagnosis and lingers from months to years8; therefore, efficacious exercise at low-perceived exertions might be ideally suited to the cancer-survivor population.
The relatively small number of participants in this pilot study suggests that caution must be exerted when interpreting these preliminary, though statistically significant, changes. Similarly, the inclusion of individuals who experienced a range of cancers, and both local and systemic treatments, may underlie the somewhat blunted (11%-14% improvements) muscle and mobility responses to RENEW relative to older individuals who have not experienced cancer. Because this study included only those individuals who have survived cancer with residual levels of fatigue and(or weakness, it is possible that the biological mechanisms (reviewed in Al-Majid and Waters4) underlying cancer-related fatigue and(or cachexia, that is, increased levels of proinflammatory cytokines, may be responsible (in part) for the blunted response. Nevertheless, the muscle and mobility responses reported here, coupled with no cytokine upregulation following RENEW previously reported,46 highlight the need for a larger clinical trial that would incorporate fatigue-related clinical measures of efficacy, along with biological(biochemical indices that may help to substantiate the findings. That is, biomarkers of muscle injury, or lack thereof, in tandem with muscle structural findings (whole muscle via an imaging modality or muscle fibers via percutaneous biopsies) would provide more insights into the older cancer survivor's response to RENEW. Furthermore, more demanding mobility-related tasks, such as negotiating stairs, may be more revealing since the TUG test constituted a low-level mobility challenge for this cohort. The fact that the TUG measure of mobility improved in parallel with strength, however, indicates that nondamaging eccentric exercise is possible and it may be of benefit to this patient population. Finally, because cardiopulmonary function also improves following resistance exercise, commensurate measures of oxygen uptake during mobility-related tasks would also be informative.
In general, this was a rather heterogeneous cohort, although all of the participants had moderate levels of weakness and fatigue and had not participated in regular exercise during the preceding 6 months. This provided a homogeneity to the group and a reasonable test of the preliminary efficacy of RENEW. A larger, randomized controlled study that includes a greater number of older survivors of breast, colorectal, and prostate cancer would be better suited to control for these potential confounding variables.
RENEW is a resistance exercise countermeasure that appears feasible for older cancer survivors and induces improvements in muscle strength and mobility.
One or more of the authors (PCL) has received funding (R21 CA114523) from the National Cancer Institute at the National Institutes of Health. All authors were involved in the design, implementation, analyses, and write-up of this report. Each author certifies that his or her institution has approved the human protocol for this investigation, all investigations were conducted in conformity with ethical principles of research, and informed consent for participation in the study was obtained.
1. Hewitt M, Rowland JH, Yancik R. Cancer survivors in the United States: age, health, and disability. J Gerontol A Biol Sci Med Sci. 2003; 58:82–91.
2. Ness KK, Wall MM, Oakes JM, Robison LL, Gurney JG. Physical performance limitations and particip-ation restrictions among cancer survivors: a population-based study. Ann Epidemiol. 2006; 16:197–205.
3. Sweeney C, Schmitz KH, Lazovich D, Virnig BA, Wallace RB, Folsom AR. Functional limitations in elderly female cancer survivors. J Natl Cancer Inst. 2006; 98:521–529.
4. Al-Majid S, Waters H. The biological mechanisms of cancer-related skeletal muscle wasting: the role of progressive resistance exercise. Biol Res Nurs. 2008; 10:7–20.
5. Combaret L, Adegoke OA, Bedard N, Baracos V, Attaix D, Wing SS. USP19 is a ubiquitin-specific protease regulated in rat skeletal muscle during catabolic states. Am J Physiol Endocrinol Metab. 2005; 288:E693–E700.
6. Costelli P, Carbo N, Tessitore L, et al. Tumor necrosis factor-alpha mediates changes in tissue protein turnover in a rat cancer cachexia model. J Clin Invest. 1993; 92:2783–2789.
7. Williams MB, Hernandez J, Thompson I. Luteinizing hormone-releasing hormone agonist effects on skeletal muscle: how hormonal therapy in prostate cancer affects muscular strength. J Urol. 2005; 173:1067–1071.
8. Al-Majid S, Gray DP. A biobehavioral model for the study of exercise interventions in cancer-related fatigue. Biol Res Nurs. 2009; 10:381–391.
9. Treuth MS, Ryan AS, Pratley RE, et al. Effects of strength training on total and regional body composition in older men. J Appl Physiol. 1994; 77:614–620.
10. Pyka G, Lindenberger E, Charette S, Marcus R. Muscle strength and fiber adaptations to a year-long resistance training program in elderly men and women. J Gerontol. 1994; 49:M22–M27.
11. McCartney N, Hicks AL, Martin J, Webber CE. Long-term resistance training in the elderly: effects on dynamic strength, exercise capacity, muscle, and bone. J Gerontol A Biol Sci Med Sci. 1995; 50:B97–B104.
12. Hruda KV, Hicks AL, McCartney N. Training for muscle power in older adults: effects on functional abilities. Can J Appl Physiol. 2003; 28:178–189.
13. Fiatarone MA, O'Neill EF, Ryan ND, et al. Exercise training and nutritional supplementation for physical frailty in very elderly people. N Engl J Med. 1994; 330:1769–1775.
14. De Backer IC, Schep G, Backx FJ, Vreugdenhil G, Kuipers H. Resistance training in cancer survivors: a systematic review. Int J Sports Med. 2009; 30:703–712.
15. Segal RJ, Reid RD, Courneya KS, et al. Resistance exercise in men receiving androgen deprivation therapy for prostate cancer. J Clin Oncol. 2003; 21:1653–1659.
16. Schmitz KH, Ahmed RL, Hannan PJ, Yee D. Safety and efficacy of weight training in recent breast cancer survivors to alter body composition, insulin, and insulin-like growth factor axis proteins. Cancer Epidemiol Biomarkers Prev. 2005; 14:1672–1680.
17. Schneider CM, Hsieh CC, Sprod LK, Carter SD, Hayward R. Cancer treatment-induced alterations in muscular fitness and quality of life: the role of exercise training. Ann Oncol. 2007; 18:1957–1962.
18. Baker F, Haffer SC, Denniston M. Health-related quality of life of cancer and noncancer patients in Medicare managed care. Cancer. 2003; 97:674–681.
19. Roig M, O'Brien K, Kirk G, et al. The effects of eccentric versus concentric resistance training on muscle strength and mass in healthy adults: a systematic review with meta-analysis. Br J Sports Med. 2009; 43:556–568.
20. Hortobagyi T, DeVita P. Favorable neuromuscular and cardiovascular responses to 7 days of exercise with an eccentric overload in elderly women. J Gerontol A Biol Sci Med Sci. 2000; 55:B401–B410.
21. LaStayo PC, Ewy GA, Pierotti DD, Johns RK, Lindstedt S. The positive effects of negative work: increased muscle strength and decreased fall risk in a frail elderly population. J Gerontol A Biol Sci Med Sci. 2003; 58:M419–M424.
22. Krishnathasan D, Vandervoort AA. Eccentric strength training prescription for older adults. Top Geriatr Rehabil. 2000; 15:29–40.
23. Dibble LE, Hale TF, Marcus RL, Droge J, Gerber JP, LaStayo PC. High-intensity resistance training amplifies muscle hypertrophy and functional gains in persons with Parkinson's disease. Mov Disord. 2006; 21:1444–1452.
24. Dibble LE, Hale TF, Marcus RL, Gerber JP, Lastayo PC. High intensity eccentric resistance training decreases bradykinesia and improves quality of life in persons with Parkinson's disease: a preliminary study. Parkinsonism Relat Disord. 2009; 15:752–757.
25. Gerber JP, Marcus RL, Dibble LE, Greis PE, Burks RT, LaStayo PC. Effects of early progressive eccentric exercise on muscle structure after anterior cruciate ligament reconstruction. J Bone Jt Surg Am. 2007; 89:559–570.
26. Gerber JP, Marcus RL, Dibble LE, Greis PE, Burks RT, LaStayo PC. Effects of early progressive eccentric exercise on muscle size and function after anterior cruciate ligament reconstruction: a 1-year follow-up study of a randomized clinical trial. Phys Ther. 2009; 89:51–59.
27. LaStayo PC, Meier W, Marcus RL, Mizner R, Dibble L, Peters C. Reversing muscle and mobility deficits 1 to 4 years after TKA: a pilot study. Clin Orthop Relat Res. 2009; 467:1493–1500.
28. LaStayo PC, Pierotti DJ, Pifer J, Hoppeler H, Lindstedt SL. Eccentric ergometry: increases in locomotor muscle size and strength at low training intensities. Am J Physiol Regul Integr Comp Physiol. 2000; 278:R1282–R1288.
29. Lastayo PC, Reich TE, Urquhart M, Hoppeler H, Lindstedt SL. Chronic eccentric exercise: improvements in muscle strength can occur with little demand for oxygen. Am J Physiol. 1999; 276:R611–R615.
30. Mueller M, Breil FA, Vogt M, et al. Different response to eccentric and concentric training in older men and women. Eur J Appl Physiol. 2009; 107:145–153.
31. Salkind MR. Beck depression inventory in general practice. J R Coll Gen Pract. 1969; 18:267–271.
32. Marcus RL, Smith S, Morrell G, et al. Comparison of combined aerobic and high-force eccentric resistance exercise with aerobic exercise only for people with type 2 diabetes mellitus. Physical Therapy. 2008; 88(11):1345–1354.
33. Noble BJ, Borg GA, Jacobs I, Ceci R, Kaiser P. A category-ratio perceived exertion scale: relationship to blood and muscle lactates and heart rate. Med Sci Sports Exerc. 1983; 15:523–528.
34. Gallagher EJ, Liebman M, Bijur PE. Prospective validation of clinically important changes in pain severity measured on a visual analog scale. Ann Emerg Med. 2001; 38:633–638.
35. Todd KH, Funk KG, Funk JP, Bonacci R. Clinical significance of reported changes in pain severity. Ann Emerg Med. 1996; 27:485–489.
36. Schaubert KL, Bohannon RW. Reliability and validity of three strength measures obtained from community-dwelling elderly persons. J Strength Cond Res. 2005; 19:717–720.
37. Bischoff HA, Stahelin HB, Monsch AU, et al. Identifying a cut-off point for normal mobility: a comparison of the timed “up and go” test in community-dwelling and institutionalised elderly women. Age Ageing. 2003; 32:315–320.
38. Valtonen A, Poyhonen T, Heinonen A, Sipila S. Muscle deficits persist after unilateral knee replacement and have implications for rehabilitation. Phys Ther. 2009; 89:1072–1079.
39. Manini TM, Visser M, Won-Park S, et al. Knee extension strength cutpoints for maintaining mobility. J Am Geriatr Soc. 2007; 55:451–457.
40. Kristensen MT, Bandholm T, Bencke J, Ekdahl C, Kehlet H. Knee-extension strength, postural control and function are related to fracture type and thigh edema in patients with hip fracture. Clin Biomech. 2009; 24:218–224.
41. Courneya KS, Segal RJ, Mackey JR, et al. Effects of aerobic and resistance exercise in breast cancer patients receiving adjuvant chemotherapy: a multicenter randomized controlled trial. J Clin Oncol. 2007; 25:4396–4404.
42. Galvao DA, Nosaka K, Taaffe DR, et al. Resistance training and reduction of treatment side effects in prostate cancer patients. Med Sci Sports Exerc. 2006; 38:2045–2052.
43. De Backer IC, Vreugdenhil G, Nijziel MR, Kester AD, van Breda E, Schep G. Long-term follow-up after cancer rehabilitation using high-intensity resistance training: persistent improvement of physical performance and quality of life. Br J Cancer. 2008; 99:30–36.
44. Meyer K, Steiner R, Lastayo P, et al. Eccentric exercise in coronary patients: central hemodynamic and metabolic responses. Med Sci Sports Exerc. 2003; 35:1076–1082.
45. Vallejo AF, Schroeder ET, Zheng L, Jensky NE, Sattler FR. Cardiopulmonary responses to eccentric and concentric resistance exercise in older adults. Age Ageing. 2006; 35:291–297.
46. LaStayo P, McDonagh P, Lipovic D, et al. Elderly patients and high force resistance exercise—a descriptive report: can an anabolic, muscle growth response occur without muscle damage or inflammation? J Geriatr Phys Ther. 2007; 30:128–134.
cancer; eccentric; exercise; survivor