Impact of Resistance Training in Cancer Survivors

A Meta-analysis

Barbara Strasser; Karen Steindorf; Joachim Wiskemann; Cornelia M. Ulrich

Med Sci Sports Exerc. 2013;45(11):2080-2090.

Abstract and Introduction

Abstract

Purpose: Current evidence suggests many health benefits from physical activity during and after cancer treatment. However, the optimal exercise program for cancer survivors has not yet been established. The purpose of this meta-analysis was to summarize evidence for the efficacy of resistance training (RT) interventions to improve muscle strength and body composition among adult cancer survivors. We also investigate potential dose–response relationships between intensity, duration, and frequency of RT and assessed outcomes.

Methods: A systematic literature review of the Clinical Trial Register, Cochrane Trial Register, MEDLINE, and EMBASE literature databases was undertaken. Studies were included if they were randomized controlled trials (RCT) comparing RT with an exercise or nonexercise control group in cancer survivors during and after treatment. Thirteen articles from 11 RCT met our inclusion criteria. We performed a random-effects meta-analysis to determine weighted mean differences (WMD) with 95% confidence intervals using the Cochrane Review Manager 5.0.25. A random-effects metaregression model was performed to examine dose–response relationships between RT variables and assessed outcomes.

Results: Quantitative evidence shows a large effect of RT on lower-limb and upper-limb muscle strength (WMD: +14.57 kg, P = 0.0005 and +6.90 kg, P < 0.00001, respectively) and moderate effects on lean body mass and percentage of body fat (WMD: +1.07 kg, P < 0.0001 and -2.08%, P = 0.003, respectively). A small positive effect of RT was noted on Functional Assessment of Cancer Therapy–Fatigue (P = 0.05). Upper-limb muscle strength and percentage of body fat improved to a greater extent when RT interventions were of low to moderate intensity (<=75% one-repetition maximum, P = 0.042).

Conclusions: RT was shown to be associated with clinically important positive effects on muscular function and body composition in patients during treatment or in long-term follow-up.

Introduction

Cancer is the second leading cause of death in the United States, with breast and prostate cancer being the most frequently diagnosed cancers for women and men, respectively,.^[66] There are numerous side effects to cancer treatment, which often include muscle wasting or atrophy, reduced physical functioning, unfavorable changes in body composition, and depression and fatigue.^[17] A decrease in physical activity levels associated with other side effects, such as loss of appetite, can intensify muscular wasting and consequently loss of overall body strength, leading patients to experience a negative spiraling effect that further exacerbates the sense of fatigue. This loss of muscular strength together with a reduction in aerobic fitness makes it difficult to perform simple daily activities, significantly compromising the quality of life in cancer patients^[37] as well as contributing to increased rates of mortality.^[27,28] Recent systematic reviews have shown that resistance training (RT) has the power to combat many of the side effects of cancer treatment and, thus, can be of significant benefit to patients in the short and long term.^[10,15,16] Benefits include improved muscle strength and physical functioning^[73] and reduced fatigue,^[56] all potentially leading to improved quality of life.^[40] However, this has so far only been investigated for very few cancer types.

Normal aging is associated with a decline in muscle mass between 5% and 10% each decade after age 50 yr, averaging approximately 0.4 kg of lean weight loss per year after the fifth decade of life.^[33] Although weight loss occurs in roughly half of cancer patients, in cachexia, the weight loss represents a marked loss of predominantly skeletal muscle.^[58] In cachectic patients, a loss of 25% of body weight represents an approximately 75% reduction in skeletal muscle protein. Approximately 20% of cancer deaths are attributed to cachexia.^[65]

Numerous studies have demonstrated that relatively brief sessions of regular RT can increase muscle mass in adults of all ages through the 10th decade of life.^[71] Effects of RT are more pronounced if exercises are muscle site specific, high intensity, and when combined with calcium and vitamin D intake.^[8,31] Furthermore, RT can provide functional benefits and improvements in overall health and well-being, including increased bone mineral density (BMD),^[38] improved physical performance,^[25,71] and cardiovascular health.^[63] Therefore, RT may have beneficial effects in cancer patients in terms of reducing muscle wasting or regaining lost muscle mass as well as improving muscle function and a diversity of biomarkers. In turn, this may lead to reduced fatigue levels and an overall enhancement in mental health.

The current systematic review was undertaken 1) to perform a meta-analysis of randomized controlled trials (RCT) regarding the effect of RT on muscle function, body composition, and fatigue both during and after cancer treatment and (2) to investigate the potential for a dose–response relationship between intensity, duration, and frequency of RT and assessed outcomes.

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Abstract and Introduction
Methods
Results
Discussion
Conclusions
References

Table 1. Summary of articles included in the meta-analysis.
Study ID	Aim	Sample Size RT/Control	RT Intervention	Main Outcomes	Main Results RT Group
Winters-Stone et al. (73)	To evaluate the effects of RT on muscle strength and physical function	N = 67(RT =36, control = 31) breast cancer survivors	3times per week for 52 wk. 10 RT exercises, 1–3 sets of 8–12 reps at 80% 1RM + impact exercise program with weighted vests	Max muscle strength: 1RM bench press/leg press; fatigue (CFS); physical function	Significant improvements in maximalmuscle strengthin the RTgroup comparedwith controls at52 wk. RTdidnot improve fatigue
Winters-Stone et al. (74)	To evaluate the effects of RT on BMD, body composition	N = 67(RT =36, control = 31) breast cancer survivors	3times per week for 52 wk. 10 RT exercises, 1–3 sets of 8–12 reps at 80% 1RM + impact exercise program with weighted vests	BMD: lumbar spine, total hip, trochanter, femoral neck; body comp: BF%, FM, LBM	Women in the RT group preserved BMD at the lumbar spine compared with controls at 52 wk. RT significantly increased LBM among women currently taking AI compared with controls not on this therapy
Schmitz et al. (50)	To evaluate the effects of RT on lymphedema onset, muscle strength, and body composition	N = 133 (RT = 60, UC = 63 for muscle strength; RT = 65, UC = 68for body mass) survivors at risk for BCRL	2times per week for 52 wk. 10 RT exercises, 3 sets of 10 reps; weight gradually increased	BCRL: >5% increase arm swelling; muscle strength: 1RM bench press/leg press; body comp: BF%, FM, LBM	RTdidnotresultin increasedincidence ofBCRLcompared withcontrols at 52 wk. Significant improvements in muscle strength andbody fat compared with controls at 52 wk
Schmitz et al. (51)	To evaluate the effects of RT on limb swelling, muscle strength, and body composition	N = 129 (RT = 58, UC = 63for muscle strength; RT = 65, UC = 64for body mass) survivors with BCRL	2times per week for 52 wk. 10 RT exercises, 3 sets of 10 reps; weight increased gradually	BCRL: >5% increase arm swelling; muscle strength: 1RM bench press/leg press; body comp: BF%, FM, LBM	RT had no significant effect on limb swelling and resulted in a decreasedincidence of exacerbations oflymphedema at 52 wk. Further, significant improvements in muscle strength compared with controls
Schwartz et al. (55)	To evaluate the effects of RT or AET on aerobic capacity, muscle strength, and body composition	N = 101 (RT = 34, AET = 34, UC = 33) cancer survivors during/after CHT	4times per week for 52 wk. 6RT exercises, 3 sets of 12 reps or 2sets of 18–20 reps; weight increased gradually	Max muscle strength: 1RM leg extension/seated row; 12-MWT; body comp: BF%	Significant improvements in muscle strength and aerobic capacity in the RT and AET group compared with UC. BF% significantly increased in the UC group compared with AET and RT at 52 wk
Segal et al. (57)	To evaluate the effects of RT or AET on fatigue, QOL, physical fitness, body composition, PSA, testosterone, lipids, and hemoglobin	N = 121 (RT = 40, AET = 40, UC = 41) prostate cancer patients receiving RAT	3times per week for 24 wk. 10 RT exercises, 2 sets of 8–12 reps at 60%–70% 1RM	Muscle strength: 8-RM leg press/8-RM chest press; V̇O_2maxbody comp: BF%; QOL; fatigue (FACT)	RT significantly improved muscle strength, aerobic fitness, QOL, fatigue, and prevented body fat increases compared with usual care at 24 wk
McNeely et al. (35)	To evaluate the effects of RT on upper extremity pain and dysfunction	N = 52(RT =27, UC = 25) head and neck cancer survivors	2times per week for 12 wk. 5–8 RT exercises, 2 sets of 10–15 reps, starting at 25%–30% 1RM progressing to 60%–70% 1RM	Max muscle strength: 1RM chest press/seated row; QOL; shoulder pain, ROM; fatigue (FACT)	Shoulder pain and muscle strength significantly improved after RT compared with usual care at 12 wk. QOL and fatigue showed nonsignificant improvements with RT
Battaglini et al. (5)	To evaluate the effects of RT on body composition	N = 20(RT =10, control = 10) breast cancer patients during treatment	2times per week for 21 wk. 8–12 RT exercises, 3 sets of 6–12 reps at 40%–60% 1RM	Body composition: BF%, LBM%; muscle strength	Significant improvements in percent body fat, lean body mass, and muscle strength in the RT group compared with controls
Courneya et al. (12)	To evaluate the effects of RT or AET on physical fitness, body composition, QOL, and fatigue	N = 242 (RT = 82, AET = 78, UC = 82) breast cancer patients receiving CHT	3times per week for the duration of CHT (9–24 wk). 9RTexercises, 2 sets of 8–12 reps at 60%–70% 1RM	Max muscle strength: 1RM bench press/leg press; V̇O_2maxbody comp: BF%, FM, LBM; QOL; fatigue (FACT)	RT was superior to usual care for improving muscular strength, LBM, and CHT completion rate. RT did not significantly improve cancer-specific QOL and fatigue
Schwartz et al. (54)	To evaluate the effects of RT or AET on BMD	N = 66(RT =21, AET = 22, UC = 23) breast cancer patients receiving CHT	4times per week for 24 wk. 8RT exercises, 2 sets of 8–10 reps weight increased gradually	Max muscle strength: 1RM leg extension/seated row; 12-MWT; BMD	Significant improvements in muscle strength and aerobic capacity in the RT and AET group compared with UC. Weight-bearing AET preserved BMD significantly better compared with RT and UC at 24 wk
Ahmed et al. (2)	To evaluate the effects of RT on lymphedema onset or exacerbation and muscle strength	N = 45(RT =23, control = 22) breast cancer survivors	2times per week for 24 wk. 9RT exercises, 3 sets of 8–10 reps weight increased gradually	BCRL: 92% increase arm circumferences; max muscle strength: 1RM bench press/leg press	RT didnot increase the riskfor symptoms of lymphedema and resultedin significant improvements in muscle strength compared with controls at24 wk
Schmitz et al. (49)	To evaluate the effects of RT on body size andbiomarkers (glucose, insulin, IGFaxis variables)	N = 81(RT =40, control = 41) breast cancer survivors	2times per week for 24 wk. 9RT exercises, 3 sets of 8–10 reps weight increased gradually	Body composition: BF%, FM, LBM; biomarkers: glucose, insulin, HOMA, IGF axis variables.	Significant improvements in LBM, BF% and IGF-II compared with controls at 24 wk
Segal et al. (56)	To evaluate the effects of RT on QOL and fatigue	N = 155 (RT = 82, control = 73) prostate cancer patients receiving ADT	3times per week for 12 wk. 9RT exercises, 2 sets of 8–12 reps at 60%–70% 1RM	QOL; fatigue (FACT); muscular fitness (rep)	Significant improvements in QOL, fatigue, and muscular fitness in the RTgroup compared with controls at 12 wk

ADT, androgen deprivation therapy; AET, aerobic endurance training; AI, aromatase inhibitor; BCRL, breast cancer–related lymphedema; BF%, % body fat; BMD, bone mineral density; CFS, Schwartz cancer fatigue scale; CHT, chemotherapy; FACT, Functional Assessment of Cancer Therapy; FM, fat mass; HOMA, homeostatic model assessment; IGF, insulin-like growth factor; LBM, lean body mass; RAT, radiation therapy; RM, repetition maximum; ROM, range of motion; RT, resistance training; UC, usual care; V̇O_2max, peak oxygen uptake; QOL, quality of life; 12-MWT, 12-min walk test.

Table 2. Pooled estimates of effect size (95% CI) expressed as WMD for the effect of RT on muscle strength, aerobic capacity, body composition, and fatigue in cancer patients.
Outcomes	No. Studies	Sample Size	WMD	95% CI	P	Heterogeneity I ² (%)
Muscle strength
Upper limb (kg)	9	752	6.90	4.78 to 9.03	<0.00001	79
Lower limb (kg)	9	719	14.57	6.34 to 22.80	0.0005	91
Aerobic capacity
V̇O_2max (mL·kg⁻¹·min⁻¹)	2	231	0.97	−0.53 to 2.47	0.20	0
12-MWT (m)	2	111	143.65	70.46 to 216.83	0.0001	0
Bodycomposition
Body fat (%)	8	713	−2.08	−3.46 to −0.70	0.003	74
Body fat mass (kg)	5	545	−0.83	−1.87 to 0.21	0.12	12
Lean body mass (kg)	6	565	1.07	0.76 to 1.37	<0.00001	0
Fatigue
FACT (points)	4	437	1.86	−0.03 to 3.75	0.05	0