The purpose of this review is to summarize literature that describes the impact of exercise on health and physical function among children during and after treatment for cancer. Relevant studies were identified by entering the following search terms into Pubmed: aerobic training; resistance training; stretching; pediatric; children; AND cancer. Reference lists in retrieved manuscripts were also reviewed to identify additional trials. We include fifteen intervention trials published between 1993 and 2011 that included children younger than age 21 years with cancer diagnoses. Nine included children with an acute lymphoblastic leukemia (ALL) diagnosis, and six children with mixed cancer diagnoses. Generally, interventions tested were either in-hospital supervised exercise training or home based programs designed to promote physical activity. Early evidence from small studies indicates that the effects of exercise include increased cardiopulmonary fitness, improved muscle strength and flexibility, reduced fatigue and improved physical function. Generalizations to the entire childhood cancer and childhood cancer survivor populations are difficult as most of the work has been done in children during treatment for and among survivors of ALL. Additional randomized studies are needed to confirm these benefits in larger populations of children with ALL, and in populations with cancer diagnoses other than ALL.
Progress in treatments for childhood cancer have greatly improved cure rates, with 5-year survival now approaching 80% [
Impaired physical fitness has been reported during and after childhood cancer treatment [
Another factor that may be associated with impaired physical fitness among childhood cancer survivors is cancer-related fatigue. Fatigue during and after treatment has the potential to have a negative impact on physical activity and on psychosocial well-being. A recent study reported that the prevalence of cancer-related fatigue was over three times higher in long-term survivors of childhood cancer when compared to the general population (OR: 3.29; 95% CI: 1.9–5.70) [
This review of the literature indicates that there is growing evidence for the positive effects of physical training on organ system function, fatigue and physical well-being in children during and after treatment for cancer [
This paper summarizes exercise intervention studies among children with cancer and is limited to studies that tested or described exercise intervention in children diagnosed with a primary pediatric cancer when younger than 21 years of age, and, includes only manuscripts available as full-text in the English language. Studies were identified by searching the PUBMED database with the terms exercise; aerobic training; resistance training; stretching; pediatric; children; cancer. Reference lists of retrieved studies were also assessed to identify additional trials. The search of the Pubmed database initially resulted in a total of 48 citations. Of these, we excluded 31 citations (3 review only, 5 not available in English, 17 no exercise intervention, and 6 adult-cancer survivors only). We include 17 published manuscripts documenting 15 studies published by June of 2011. A review of the reference lists from the retrieved manuscripts did not identify any additional papers. When reporting the outcomes of each study, if numerical results were available, effect sizes were converted to Cohen’s
A summary of the 15 published studies included in this review examining exercise intervention for children with cancer is shown in Tables
Description of non-randomized exercise trials in children with cancer.
First author | Design | Demographics | Exercise intervention (type of training, frequency, and duration) | *Main outcomes |
---|---|---|---|---|
Sharkey, 1993 [ | Pretest/posttest trial | Intervention: aerobic training with home exercise twice per week (week 1-2 started with 15 minutes of warm-up, 15 minutes of exercise at 60% of HRmax and 15 minutes of cool-down, week 3–6 30 minutes of exercise at 70–80% HRmax, and week 7–12 30 minutes of aerobic exercise at 70–80% HRmax plus home exercise once per week). | Body fat (−), spirometry (−), peak heart rate (−), peak oxygen uptake (−), anaerobic threshold (−), peak cardiac index (−), peak stroke volume index (−), or vascular resistance (−). Exercise time (+13%). | |
Ladha, 2006 [ | Nonrandomized safety assessment with both a cancer and a healthy | Cancer group: | Intervention: one session (5 minutes of warm-up, 20 minutes of moderate- to high-intensity exercise, and 5 minutes of cool-down) of intermittent run-walk on a treadmill at 70% to 85% of VO2 peak. | An acute bout of exercise did not elicit any significant negative effects on neutrophil count. |
San Juan, 2007 [ | Pretest/posttest trial | Intervention: three weekly sessions (90–120 minutes) of supervised resistance training (bench press, shoulder press, leg extension, leg curl, leg press, abdominal crunch, lower-back extension, arm curl, elbow extension, seated row, and lateral pull-down; 8–15 repetitions) and aerobic exercise (started with 10 minutes of exercises at 50% of age-predicted HRmax and progressed to 30 minutes of continuous exercise at ≥70% HRmax by the end of the program). | VO2 peak (+), VT (+), functional mobility (+) (TUDs, 3- and 10-meter TUG) and strength tests (+) (seated bench press, seated row, and seated leg press) from before training to after training. Only increased strength remained significant after detraining. | |
Keats and Culos-Reed, 2008 [ | Pretest/posttest trial. | Intervention: physical activity and educational intervention (30 minutes of educational session, 45 minutes of aerobic training, and 15 minutes of core strength and flexibility training in the first 8 weeks; a variety of noncompetitive physical activities in the final 8 weeks) | Upper body strength (+), flexibility (+), total PA (+), QOL (+), and general fatigue (+). Participants failed to maintain their postintervention PA levels at both 3- and 12-month follow-up time points. | |
San Juan, 2008 [ | Pretest/posttest trial. | Intervention: three weekly sessions (90–120 minutes) of supervised resistance training (bench press, shoulder press, leg extension, leg curl, leg press, abdominal crunch, lower-back extension, arm curl, elbow extension, seated row, and lateral pull-down; 11 repetitions) and aerobic exercise (started with 10 minutes of exercises at 50% of age-predicted HRmax and progressed to 30 minutes of continuous exercise at ≥70% HRmax by the end of the program) | Muscle strength (+), VO2 peak (+), functional mobility (+) (TUDs, 3- and 10-meter TUG) and self-reported health status (+). | |
Takken, 2009 [ | Pretest/posttest trial. | Intervention: two weekly sessions (45 minutes) of supervised resistance training (sit-ups, push-ups, head and leg raises; 30-second repetition maximum and squats 60-second repetition maximum), aerobic exercise (66–77% of HRmax in first 4 weeks, 77–90% HRmax in the following 4 weeks, and ≥90% HRmax in the last 4 weeks) and a home-based exercise program (strength, flexibility, and aerobic fitness). | Seventy percent of trainers were satisfied with the program. BMI (−), muscle strength (−), exercise capacity (−), functional mobility (−), or fatigue levels (−). | |
Blaauwbroek, 2009 [ | Pretest/posttest trial. | Intervention: enhanced physical activity (such as walking, cycling, housekeeping, and gardening) counseling. The counselor encouraged the survivors to change their lifestyle and enhance daily physical activity to meet published exercise guidelines (i.e., at least 150 minutes of moderate-to-vigorous exercise/week) and phoned the survivors at three weeks, six weeks, and nice weeks to check goals. Feedback from a pedometer. | Significant improvements in fatigue and daily steps after intervention. There was a low correlation (0.12) between increase in daily steps and the decrease in fatigue. | |
Speyer, 2010 [ | Cross-over, single study design. | Intervention: three weekly sessions (30 minutes) of adapted physical activity (ball games, circus arts, throwing games, shooting games, racket sports, video games, and body building). | QOL scores in physical and psychological dimensions were higher for the children who practiced than for those who did not practice adapted physical activity during hospitalization. | |
Chamorro-Vina, 2010 [ | Nonrandomized controlled trial. | Intervention group: | Intervention: Five weekly sessions (~50 minutes) of supervised resistance training (arm curl, elbow extension, bench press, log extension, half squat, abdominal crunch, supine bridge, and rowing; 12–15 repetitions) (stretching exercise involving all major muscle groups) and aerobic exercise (10–40 minutes of cycle ergometry at 50% to 70% of HRmax). | Fitness levels (+) (half squat) or body mass (+). Exercise intervention during inpatient stay for HCT did not affect immune cell recovery in young children with high-risk cancer. |
Yeh, 2011 [ | Nonrandomized controlled trial. | Intervention group: | Intervention: three weekly sessions (30 minutes) of individualized home-based aerobic exercise program (exercise intensity: 40%–60% of HRR) | General fatigue (+). |
Gohar, 2011 [ | Pretest/posttest trial. | Intervention: individualized home-based exercise program (stretching exercise: ankle dorsiflexion; 5 days/week, strengthening exercise: lower- and upper-extremity exercise; 10 repetitions 5 days/week, and aerobic exercise: walking, bike riding, and dancing 10–30 minutes; 5 days/week). | Gross motor function (+) and QOL measures (+) throughout the study (at diagnosis, induction, consolidation, interim maintenance, and delayed intensification). However, QOL scores decreased from interim maintenance to delayed intensification. The parents reported being satisfied with the PT program. |
*(+) to indicate a significant effect; (−) to indicate no significant effect/change.
ALL: acute lymphoblastic leukemia; AML: acute myeloid leukemia; BMD: bone mineral density; BMI: body mass index; CNS: central nervous system; HRR: heart rate reserve; HCT: hematopoietic stem cell transplant; PA: physical activity; PT: physical therapy; QOL: quality of life; VO2 peak: peak aerobic fitness; HRmax: maximum of heart rate; TUDs: time up and down stair test; TUG: timed up and go test; VT: ventilatory threshold.
Description of the randomized exercise trials in children with cancer.
First author | Demographics | Exercise intervention (type of training, frequency, and duration) | *Main outcomes |
---|---|---|---|
Marchese, 2004 [ | Intervention group: | Intervention: five sessions (20 to 60 minutes immediately after initial testing, and 2, 4, 8, and 12 weeks later) of PT (stretching and strengthening exercises, supervised) and an individualized home-based exercise program (bilateral ankle dorsiflexion stretching for 30 sec 5 days per week, bilateral lower extremity strengthening 3 sets, 3 days per week, and aerobic exercises). | Hemoglobin level (−), ankle dorsiflexion strength (−), TUDs (−), 9-minute walk-run (−), and QOL (−). Ankle dorsiflexion range of motion (active) and knee extension strength increased in intervention group from before to after test. |
Hinds, 2007 [ | Intervention group: | Intervention: enhanced physical activity (pedaling a stationary bike-style exerciser, 30 minutes, twice daily during brief hospitalization). | Sleep efficiency (+). |
Moyer-Mileur, 2009 [ | Intervention group: | Intervention: an individualized exercise program (three 15–20-minute sessions of moderate-to-vigorous activity per week) and nutritional education. | Nutrient intake (−), height (−), weight (−), or BMI (−) between intervention and control groups. No intervention effect for upper body strength (push-up completed) or flexibility (sit and reach distance). |
Hartman, 2009 [ | Intervention group: | Intervention: preventive PT program (weekly strengthening and stretching exercise and short-burst high-intensity exercise in BMD twice per week). | Percentage of body fat (−) or less body mass (−). BMD decreased significantly in both groups between the start and end of treatment. |
*(+) to indicate a significant effect; (−) to indicate no significant effect/change.
ALL: acute lymphoblastic leukemia; BMD: bone mineral density; BMI: body mass index; PA: physical activity; PT: physical therapy; QOL: quality of life; TUDs: time up and down stair test.
Chemotherapy treatment for pediatric cancer suppresses the immune system and may interfere with normal growth, increasing susceptibility to infection and stunting or delaying musculoskeletal development during treatment [
Cardiopulmonary fitness is impaired in children during treatment and among survivors of childhood cancer [
It appears that hospital type supervised exercise interventions have better cardiopulmonary outcomes than do those that are home or community based. San Juan et al. [
Supervised exercise training also appears to have promise for childhood cancer survivors with long-term cardiopulmonary compromise. A study by Sharkey et al. [
Cancer therapy in children also impacts the musculoskeletal system. Limited range of motion, loss of muscle mass, and reduced muscle strength are common among children with cancer and among survivors [
Fatigue is a common symptom in children during and following cancer treatment [
Suppressed immune system function, poor cardiopulmonary fitness, reduced muscle strength, and fatigue may decrease the ability of a child with cancer or a childhood cancer survivor to participate comfortably in regular physical activity. Implementation of a program of exercise or EPA, on the other hand, may improve their strength and fitness and, if it alleviates fatigue, may increase ease of movement and enable activities that have a physical component. The evidence for efficacy of exercise and EPA programs to improve overall physical functioning and mobility in survivors of pediatric cancer is mixed. Among children with ALL, four different exercise intervention studies have documented the beneficial effects of a supervised training program or home-based exercise [
Six of the studies we reviewed reported a health-related quality of life outcome (HRQOL) in response to exercise training or EPA [
It appears that exercise training can be safely undertaken during treatment for ALL and HCT with no major effects on the immune system and that exercise does not have a deleterious effect on growth factors during treatment for ALL. The published evidence is positive for the impact of exercise on muscle strength and flexibility and mixed for the impact of exercise intervention on cardiopulmonary fitness among children with ALL during maintenance therapy, among children following HCT, and among survivors exposed to cardiotoxic agents. Fatigue and general physical function are enhanced if the intervention generates a cardiopulmonary training effect. The evidence for the effects of exercise training on HRQOL in the childhood cancer population is mixed and difficult to disentangle from the effects of disease recovery and normal maturation. The early evidence suggests that supervised hospital training is effective, likely because compliance and training intensity are assured. Home- or community-based programs appear to be less effective. Unfortunately, supervised training is expensive and often unrealistic for families who may have to travel long distances to a center that specializes in cancer care.
Even though early results are promising, specific limitations in the existing literature do not allow us to yet be able to state with confidence that exercise interventions offer clear benefits during or after treatment for childhood cancer. There have only been four randomized trials, sample sizes have been small, and diagnosis groups included in the trials have been very limited (mostly ALL). Intent to treat type of analysis has not always been completed, and mechanisms to characterize the effects of participant dropout have not been employed. In addition, inconsistencies in exercise type, duration, and frequency, and outcome measurement prohibit conclusions that might guide how an individual clinician might prescribe exercise in practice.
Further research is needed. Studies designed to identify and characterize the type and intensity of exercise necessary to achieve clinically meaningful positive cardiopulmonary, musculoskeletal, symptom limiting, physical function, and quality of life outcomes in children with a variety of diagnoses are necessary. These interventions must be not only safe but also realistic and portable so that children, families, and long-term survivors can adopt and incorporate exercise and physical activity into their everyday lives when they are not near the specialized center that provides care for children with cancer. Additionally, larger well-designed randomized studies that employ strong statistical methodology and that evaluate the effects of participant dropout on the outcomes are important to see if the early results from these multiple small, mostly observational trials remain positive in larger populations of children with varied cancer diagnoses.