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Study Overview
Objective. To systematically review randomized controlled trials (RCTs) examining the effects of exercise interventions on cancer-related fatigue (CRF) in patients during and after treatment to determine differential effects.
Design. Meta-analysis.
Data. 70 RCTs with a combined sample of 4881 oncology patients during active treatment (eg, chemotherapy, radiation therapy, hormone therapy) or after completion of treatment published before August 2011 that analyzed the effect on CRF of an exercise program compared with a non-exercise control. Excluded from analysis were RCTs that compared exercise with other types of interventions (ie, education, pharmacotherapy, different methods of exercise). 43 studies examined exercise during treatment while 27 studied the effects after treatment.
Measurement. Effect size was calculated to determine the magnitude of the effect of exercise on improving CRF.
Main results. The effect size (Δ = 0.34, P < 0.001) for the total sample of 70 RCTs indicated that exercise has a moderate effect on CRF regardless of treatment status. When effect sizes were calculated for the 43 RCTs that examined patients during treatment, exercise was found to significantly decrease CRF (Δ = 0.32, P < 0.001). Based on calculated effect size for the 27 RCTs that examined exercise after treatment completion, exercise continues to significantly decrease CRF (Δ = 0.38, P < 0.001). The effect of exercise on CRF was consistent not only during or after treatment, but also across cancer diagnosis, patient age, and sex.
Exercise reduces CRF both during and after treatment. In patients who exercise, CRF severity decreases by 4.9% compared to a 29.1% increase in CRF in patients who do not exercise. After treatment, exercise decreases CRF by 20.5% compared to a decrease of 1.3% in patients who do not exercise.
Both during and after treatment, patients with higher exercise adherence experienced the most improvement (P < 0.001). Patients in active treatment with less severe baseline CRF demonstrated greater adherence to the exercise program and saw greater improvements in CRF. Patients who were further from active treatment saw greater CRF severity reduction than patients closer to active treatment. After treatment, the longer the exercise program, the more effective it was in decreasing CRF. No specific type of exercise program (eg, home-based, supervised, vigorous, moderate) was shown to be more effective than another.
Conclusion. Exercise decreases CRF in patients during and after treatment. The type of exercise does not change the positive effect of exercise, so it is important to encourage patients to be active.
Commentary
Cancer-related fatigue (CRF) is the most disturbing symptom associated with cancer diagnosis and its treatment [1]. Defined as a persistent, subjective sense of tiredness that is not proportional to activity and not relieved by rest, CRF is reported in over 80% of oncology patients during active treatment [1]. This symptom is not limited to the active treatment phase, with over 30% of cancer survivors reporting CRF lasting at least 5 years [2]. CRF is associated with decreased quality of life (QOL), decreased functional status, and decreased participation in social activities [1]. The pathogenesis of CRF is not fully understood [3,4]. Disruptions in biochemical pathways [5], genome expression [6] chemotherapy or radiation treatments [7,8], cancer pathogenesis [4], or a combination of factors [9] are hypothesized as contributing to the development and severity of CRF. The complexity of CRF pathogenesis makes clinical management difficult.
The current meta-analysis suggests that exercise is an effective nonpharmacologic intervention to ameliorate the impact of this devastating symptom and improve patients’ QOL [10–12]. The meta-analysis demonstrated strong rigor, using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines [13]. Multiple electronic databases were accessed and additional evidence was obtained by review of the retrieved article reference lists. No language limitations were placed on the search, adding to the potential generalizability of the results. The procedures to extract data and evaluate the quality of each retrieved article are detailed providing evidence of the rigor of the authors’ methodology.
The limitations of the meta-analysis are related to the difficulties extracting data from multiple studies without consistent reporting of exercise mode, duration or evaluation methods. Inconsistent CRF assessment methods across studies limits the validity of the results quantifying the magnitude of CRF change identified. Despite the limitations, this is the first known meta-analysis of the effect of exercise on CRF during and after treatment synthesizing current research to provide clinical reccomendations.
As with all exercise prescriptions for any patient, the patient’s level of adherence is a moderating factor for its effectiveness. A recent study describes an interesting exercise intervention that utilizes a resource some cancer patients may already have in their homes. Seven patients with early-stage non-small cell lung cancer performed light-intensity walking and balance exercises in a virtual reality environment with the Nintendo Wii Fit Plus for 6 weeks after thora-cotomy [14]. Exercise started the first week after hospitalization and continued for 6 weeks. Outcomes seen included a decrease in CRF severity, a high level of satisfaction, high adherence rate, and an increase in self-efficacy for managing their CRF [14]. While the small sample size and homogeneous cancer diagnosis and stage limit generalizability, the study describes a promising approach to supporting patient adherence to exercise.
Applications for Clinical Practice
The results of this meta-analysis support exercise as an effective intervention to decrease CRF in oncology patients during and after treatment. Based on the results, exercise should be prescribed as a nonpharmacologic intervention to decrease CRF. Patients’ adherence to the exercise intervention is needed for effective CRF reduction. Thus, exercise prescription should be tailored to patients individual preferences, abilities, and available resources.
—Fay Wright, MSN, APRN, and Allison Squires, PhD, RN
1. Berger AM, Abernethy A, Atkinson A, et al. NCCN guidelines: cancer-related fatigue. Version 1. National Comprehensive Cancer Network; 2013.
2. Cella D, Lai J-S, Chang C-H, et al. Fatigue in cancer patients compared with fatigue in the general United States population. Cancer 2002;94:528–38.
3. Mustian K, Morrow G, Carroll J, et al. Integrative nonpharmacologic behavioral interventions for the management of cancer-related fatigue. Oncologist 2007;12 Suppl 1:52–67.
4. Ryan J, Carroll J, Ryan E, et al. Mechanisms of cancer-related fatigue. Oncologist 2007;12 Suppl 1:22–34.
5. Hoffman AJ, Given B, von Eye A, et al. Relationships among pain, fatigue, insomnia, and gender in persons with lung cancer. Oncol Nurs Forum 2007;34:785–92.
6. Miaskowski C, Dodd MJ, Lee KA, et al. Preliminary evidence of an association between a functional interleukin-6 polymorphism and fatigue and sleep disturbance in oncology patients and their family caregivers. J Pain Symptom Manage 2010;40:531–44.
7. Hwang SY, Chang V, Rue M, Kasimis B. Multidimensional independent predictors of cancer-related fatigue. J Pain Symptom Manage 2003;26:604–14.
8. Cleeland C, Mendoza T, Wang X, et al. Levels of symptom burden during chemotherapy for advanced lung cancer: Differences between public hospitals and a tertiary cancer center. J Clin Oncol 2011;29:2859–65.
9. Cleeland C, Bennett G, Dantzer R, et al. Are the symptoms of cancer and cancer treatment due to a shared biologic mechanism? A cytokine-immunologic model of cancer symptoms. Cancer 2003;97:2919–25.
10. Al Majid S, Gray DP. A biobehavioral model for the study of exercise interventions in cancer-related fatigue. Biol Res Nurs 2009;10:381–91.
11. Cramp F, Byron-Daniel J. Exercise for the management of cancer-related fatigue in adults. Cochrane Database Syst Rev 2012;11:CD006145.
12. Puetz TW, Herring MP. Differential effects of exercise on cancer-related fatigue during and following treatment: a meta-analysis. Am J Prev Med 2012;43:e1–24.
13. Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med 2009;6(7):e1000097.
14. Hoffman AJ, Brintnall RA, Brown JK, et al. Too sick not to exercise: Using a 6-week, home-based exercise intervention for cancer-related fatigue self-management for postsurgical non-small cell lung cancer patients. Cancer Nurs 2013;36:175–88.
Study Overview
Objective. To systematically review randomized controlled trials (RCTs) examining the effects of exercise interventions on cancer-related fatigue (CRF) in patients during and after treatment to determine differential effects.
Design. Meta-analysis.
Data. 70 RCTs with a combined sample of 4881 oncology patients during active treatment (eg, chemotherapy, radiation therapy, hormone therapy) or after completion of treatment published before August 2011 that analyzed the effect on CRF of an exercise program compared with a non-exercise control. Excluded from analysis were RCTs that compared exercise with other types of interventions (ie, education, pharmacotherapy, different methods of exercise). 43 studies examined exercise during treatment while 27 studied the effects after treatment.
Measurement. Effect size was calculated to determine the magnitude of the effect of exercise on improving CRF.
Main results. The effect size (Δ = 0.34, P < 0.001) for the total sample of 70 RCTs indicated that exercise has a moderate effect on CRF regardless of treatment status. When effect sizes were calculated for the 43 RCTs that examined patients during treatment, exercise was found to significantly decrease CRF (Δ = 0.32, P < 0.001). Based on calculated effect size for the 27 RCTs that examined exercise after treatment completion, exercise continues to significantly decrease CRF (Δ = 0.38, P < 0.001). The effect of exercise on CRF was consistent not only during or after treatment, but also across cancer diagnosis, patient age, and sex.
Exercise reduces CRF both during and after treatment. In patients who exercise, CRF severity decreases by 4.9% compared to a 29.1% increase in CRF in patients who do not exercise. After treatment, exercise decreases CRF by 20.5% compared to a decrease of 1.3% in patients who do not exercise.
Both during and after treatment, patients with higher exercise adherence experienced the most improvement (P < 0.001). Patients in active treatment with less severe baseline CRF demonstrated greater adherence to the exercise program and saw greater improvements in CRF. Patients who were further from active treatment saw greater CRF severity reduction than patients closer to active treatment. After treatment, the longer the exercise program, the more effective it was in decreasing CRF. No specific type of exercise program (eg, home-based, supervised, vigorous, moderate) was shown to be more effective than another.
Conclusion. Exercise decreases CRF in patients during and after treatment. The type of exercise does not change the positive effect of exercise, so it is important to encourage patients to be active.
Commentary
Cancer-related fatigue (CRF) is the most disturbing symptom associated with cancer diagnosis and its treatment [1]. Defined as a persistent, subjective sense of tiredness that is not proportional to activity and not relieved by rest, CRF is reported in over 80% of oncology patients during active treatment [1]. This symptom is not limited to the active treatment phase, with over 30% of cancer survivors reporting CRF lasting at least 5 years [2]. CRF is associated with decreased quality of life (QOL), decreased functional status, and decreased participation in social activities [1]. The pathogenesis of CRF is not fully understood [3,4]. Disruptions in biochemical pathways [5], genome expression [6] chemotherapy or radiation treatments [7,8], cancer pathogenesis [4], or a combination of factors [9] are hypothesized as contributing to the development and severity of CRF. The complexity of CRF pathogenesis makes clinical management difficult.
The current meta-analysis suggests that exercise is an effective nonpharmacologic intervention to ameliorate the impact of this devastating symptom and improve patients’ QOL [10–12]. The meta-analysis demonstrated strong rigor, using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines [13]. Multiple electronic databases were accessed and additional evidence was obtained by review of the retrieved article reference lists. No language limitations were placed on the search, adding to the potential generalizability of the results. The procedures to extract data and evaluate the quality of each retrieved article are detailed providing evidence of the rigor of the authors’ methodology.
The limitations of the meta-analysis are related to the difficulties extracting data from multiple studies without consistent reporting of exercise mode, duration or evaluation methods. Inconsistent CRF assessment methods across studies limits the validity of the results quantifying the magnitude of CRF change identified. Despite the limitations, this is the first known meta-analysis of the effect of exercise on CRF during and after treatment synthesizing current research to provide clinical reccomendations.
As with all exercise prescriptions for any patient, the patient’s level of adherence is a moderating factor for its effectiveness. A recent study describes an interesting exercise intervention that utilizes a resource some cancer patients may already have in their homes. Seven patients with early-stage non-small cell lung cancer performed light-intensity walking and balance exercises in a virtual reality environment with the Nintendo Wii Fit Plus for 6 weeks after thora-cotomy [14]. Exercise started the first week after hospitalization and continued for 6 weeks. Outcomes seen included a decrease in CRF severity, a high level of satisfaction, high adherence rate, and an increase in self-efficacy for managing their CRF [14]. While the small sample size and homogeneous cancer diagnosis and stage limit generalizability, the study describes a promising approach to supporting patient adherence to exercise.
Applications for Clinical Practice
The results of this meta-analysis support exercise as an effective intervention to decrease CRF in oncology patients during and after treatment. Based on the results, exercise should be prescribed as a nonpharmacologic intervention to decrease CRF. Patients’ adherence to the exercise intervention is needed for effective CRF reduction. Thus, exercise prescription should be tailored to patients individual preferences, abilities, and available resources.
—Fay Wright, MSN, APRN, and Allison Squires, PhD, RN
Study Overview
Objective. To systematically review randomized controlled trials (RCTs) examining the effects of exercise interventions on cancer-related fatigue (CRF) in patients during and after treatment to determine differential effects.
Design. Meta-analysis.
Data. 70 RCTs with a combined sample of 4881 oncology patients during active treatment (eg, chemotherapy, radiation therapy, hormone therapy) or after completion of treatment published before August 2011 that analyzed the effect on CRF of an exercise program compared with a non-exercise control. Excluded from analysis were RCTs that compared exercise with other types of interventions (ie, education, pharmacotherapy, different methods of exercise). 43 studies examined exercise during treatment while 27 studied the effects after treatment.
Measurement. Effect size was calculated to determine the magnitude of the effect of exercise on improving CRF.
Main results. The effect size (Δ = 0.34, P < 0.001) for the total sample of 70 RCTs indicated that exercise has a moderate effect on CRF regardless of treatment status. When effect sizes were calculated for the 43 RCTs that examined patients during treatment, exercise was found to significantly decrease CRF (Δ = 0.32, P < 0.001). Based on calculated effect size for the 27 RCTs that examined exercise after treatment completion, exercise continues to significantly decrease CRF (Δ = 0.38, P < 0.001). The effect of exercise on CRF was consistent not only during or after treatment, but also across cancer diagnosis, patient age, and sex.
Exercise reduces CRF both during and after treatment. In patients who exercise, CRF severity decreases by 4.9% compared to a 29.1% increase in CRF in patients who do not exercise. After treatment, exercise decreases CRF by 20.5% compared to a decrease of 1.3% in patients who do not exercise.
Both during and after treatment, patients with higher exercise adherence experienced the most improvement (P < 0.001). Patients in active treatment with less severe baseline CRF demonstrated greater adherence to the exercise program and saw greater improvements in CRF. Patients who were further from active treatment saw greater CRF severity reduction than patients closer to active treatment. After treatment, the longer the exercise program, the more effective it was in decreasing CRF. No specific type of exercise program (eg, home-based, supervised, vigorous, moderate) was shown to be more effective than another.
Conclusion. Exercise decreases CRF in patients during and after treatment. The type of exercise does not change the positive effect of exercise, so it is important to encourage patients to be active.
Commentary
Cancer-related fatigue (CRF) is the most disturbing symptom associated with cancer diagnosis and its treatment [1]. Defined as a persistent, subjective sense of tiredness that is not proportional to activity and not relieved by rest, CRF is reported in over 80% of oncology patients during active treatment [1]. This symptom is not limited to the active treatment phase, with over 30% of cancer survivors reporting CRF lasting at least 5 years [2]. CRF is associated with decreased quality of life (QOL), decreased functional status, and decreased participation in social activities [1]. The pathogenesis of CRF is not fully understood [3,4]. Disruptions in biochemical pathways [5], genome expression [6] chemotherapy or radiation treatments [7,8], cancer pathogenesis [4], or a combination of factors [9] are hypothesized as contributing to the development and severity of CRF. The complexity of CRF pathogenesis makes clinical management difficult.
The current meta-analysis suggests that exercise is an effective nonpharmacologic intervention to ameliorate the impact of this devastating symptom and improve patients’ QOL [10–12]. The meta-analysis demonstrated strong rigor, using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines [13]. Multiple electronic databases were accessed and additional evidence was obtained by review of the retrieved article reference lists. No language limitations were placed on the search, adding to the potential generalizability of the results. The procedures to extract data and evaluate the quality of each retrieved article are detailed providing evidence of the rigor of the authors’ methodology.
The limitations of the meta-analysis are related to the difficulties extracting data from multiple studies without consistent reporting of exercise mode, duration or evaluation methods. Inconsistent CRF assessment methods across studies limits the validity of the results quantifying the magnitude of CRF change identified. Despite the limitations, this is the first known meta-analysis of the effect of exercise on CRF during and after treatment synthesizing current research to provide clinical reccomendations.
As with all exercise prescriptions for any patient, the patient’s level of adherence is a moderating factor for its effectiveness. A recent study describes an interesting exercise intervention that utilizes a resource some cancer patients may already have in their homes. Seven patients with early-stage non-small cell lung cancer performed light-intensity walking and balance exercises in a virtual reality environment with the Nintendo Wii Fit Plus for 6 weeks after thora-cotomy [14]. Exercise started the first week after hospitalization and continued for 6 weeks. Outcomes seen included a decrease in CRF severity, a high level of satisfaction, high adherence rate, and an increase in self-efficacy for managing their CRF [14]. While the small sample size and homogeneous cancer diagnosis and stage limit generalizability, the study describes a promising approach to supporting patient adherence to exercise.
Applications for Clinical Practice
The results of this meta-analysis support exercise as an effective intervention to decrease CRF in oncology patients during and after treatment. Based on the results, exercise should be prescribed as a nonpharmacologic intervention to decrease CRF. Patients’ adherence to the exercise intervention is needed for effective CRF reduction. Thus, exercise prescription should be tailored to patients individual preferences, abilities, and available resources.
—Fay Wright, MSN, APRN, and Allison Squires, PhD, RN
1. Berger AM, Abernethy A, Atkinson A, et al. NCCN guidelines: cancer-related fatigue. Version 1. National Comprehensive Cancer Network; 2013.
2. Cella D, Lai J-S, Chang C-H, et al. Fatigue in cancer patients compared with fatigue in the general United States population. Cancer 2002;94:528–38.
3. Mustian K, Morrow G, Carroll J, et al. Integrative nonpharmacologic behavioral interventions for the management of cancer-related fatigue. Oncologist 2007;12 Suppl 1:52–67.
4. Ryan J, Carroll J, Ryan E, et al. Mechanisms of cancer-related fatigue. Oncologist 2007;12 Suppl 1:22–34.
5. Hoffman AJ, Given B, von Eye A, et al. Relationships among pain, fatigue, insomnia, and gender in persons with lung cancer. Oncol Nurs Forum 2007;34:785–92.
6. Miaskowski C, Dodd MJ, Lee KA, et al. Preliminary evidence of an association between a functional interleukin-6 polymorphism and fatigue and sleep disturbance in oncology patients and their family caregivers. J Pain Symptom Manage 2010;40:531–44.
7. Hwang SY, Chang V, Rue M, Kasimis B. Multidimensional independent predictors of cancer-related fatigue. J Pain Symptom Manage 2003;26:604–14.
8. Cleeland C, Mendoza T, Wang X, et al. Levels of symptom burden during chemotherapy for advanced lung cancer: Differences between public hospitals and a tertiary cancer center. J Clin Oncol 2011;29:2859–65.
9. Cleeland C, Bennett G, Dantzer R, et al. Are the symptoms of cancer and cancer treatment due to a shared biologic mechanism? A cytokine-immunologic model of cancer symptoms. Cancer 2003;97:2919–25.
10. Al Majid S, Gray DP. A biobehavioral model for the study of exercise interventions in cancer-related fatigue. Biol Res Nurs 2009;10:381–91.
11. Cramp F, Byron-Daniel J. Exercise for the management of cancer-related fatigue in adults. Cochrane Database Syst Rev 2012;11:CD006145.
12. Puetz TW, Herring MP. Differential effects of exercise on cancer-related fatigue during and following treatment: a meta-analysis. Am J Prev Med 2012;43:e1–24.
13. Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med 2009;6(7):e1000097.
14. Hoffman AJ, Brintnall RA, Brown JK, et al. Too sick not to exercise: Using a 6-week, home-based exercise intervention for cancer-related fatigue self-management for postsurgical non-small cell lung cancer patients. Cancer Nurs 2013;36:175–88.
1. Berger AM, Abernethy A, Atkinson A, et al. NCCN guidelines: cancer-related fatigue. Version 1. National Comprehensive Cancer Network; 2013.
2. Cella D, Lai J-S, Chang C-H, et al. Fatigue in cancer patients compared with fatigue in the general United States population. Cancer 2002;94:528–38.
3. Mustian K, Morrow G, Carroll J, et al. Integrative nonpharmacologic behavioral interventions for the management of cancer-related fatigue. Oncologist 2007;12 Suppl 1:52–67.
4. Ryan J, Carroll J, Ryan E, et al. Mechanisms of cancer-related fatigue. Oncologist 2007;12 Suppl 1:22–34.
5. Hoffman AJ, Given B, von Eye A, et al. Relationships among pain, fatigue, insomnia, and gender in persons with lung cancer. Oncol Nurs Forum 2007;34:785–92.
6. Miaskowski C, Dodd MJ, Lee KA, et al. Preliminary evidence of an association between a functional interleukin-6 polymorphism and fatigue and sleep disturbance in oncology patients and their family caregivers. J Pain Symptom Manage 2010;40:531–44.
7. Hwang SY, Chang V, Rue M, Kasimis B. Multidimensional independent predictors of cancer-related fatigue. J Pain Symptom Manage 2003;26:604–14.
8. Cleeland C, Mendoza T, Wang X, et al. Levels of symptom burden during chemotherapy for advanced lung cancer: Differences between public hospitals and a tertiary cancer center. J Clin Oncol 2011;29:2859–65.
9. Cleeland C, Bennett G, Dantzer R, et al. Are the symptoms of cancer and cancer treatment due to a shared biologic mechanism? A cytokine-immunologic model of cancer symptoms. Cancer 2003;97:2919–25.
10. Al Majid S, Gray DP. A biobehavioral model for the study of exercise interventions in cancer-related fatigue. Biol Res Nurs 2009;10:381–91.
11. Cramp F, Byron-Daniel J. Exercise for the management of cancer-related fatigue in adults. Cochrane Database Syst Rev 2012;11:CD006145.
12. Puetz TW, Herring MP. Differential effects of exercise on cancer-related fatigue during and following treatment: a meta-analysis. Am J Prev Med 2012;43:e1–24.
13. Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med 2009;6(7):e1000097.
14. Hoffman AJ, Brintnall RA, Brown JK, et al. Too sick not to exercise: Using a 6-week, home-based exercise intervention for cancer-related fatigue self-management for postsurgical non-small cell lung cancer patients. Cancer Nurs 2013;36:175–88.