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The Oncologist, Vol. 12, No. suppl_1, 52-67, May 2007; doi:10.1634/theoncologist.12-S1-52
© 2007 AlphaMed Press

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Integrative Nonpharmacologic Behavioral Interventions for the Management of Cancer-Related Fatigue

Karen M. Mustiana, Gary R. Morrowa,b, Jennifer K. Carrolla,c, Colmar D. Figueroa-Moseleya,d, Pascal Jean-Pierrea,c, Geoffrey C. Williamse

aDepartment of Radiation Oncology, bDepartment of Psychiatry, cDepartment of Family Medicine, dDepartment of Medicine, and eDepartment of Internal Medicine, University of Rochester School of Medicine and Destistry, James P. Wilmot Cancer Center, Rochester, New York, USA

Key Words. Cancer • Fatigue • Behavioral medicine • Exercise • Nutrition

Correspondence: Karen M. Mustian, Ph.D., University of Rochester School of Medicine, James P. Wilmot Cancer Center, 601 Elmwood Avenue, Box 704, Rochester, New York 14642, USA. Telephone: 585-275-5513; Fax: 585-461-5601; e-mail: karen_mustian{at}urmc.rochester.edu

Received December 5, 2006; accepted for publication January 4, 2007.


   ABSTRACT
Top
 Abstract
Introduction
 Current Approaches to the...
 Integrative Nonpharmacologic...
 Recommendations for Future...
 Conclusions
 Acknowledgments
 Disclosure of Potential...
 References
 
Cancer-related fatigue (CRF) is a debilitating, multi-faceted biopsychosocial symptom experienced by the majority of cancer survivors during and after treatment. CRF begins after diagnosis and frequently persists long after treatments end, even when the cancer is in remission. The etiological pathopsychophysiology underlying CRF is multifactorial and not well delineated. Mechanisms may include abnormal accumulation of muscle metabolites, dysregulation of the homeostatic status of cytokines, irregularities in neuromuscular function, abnormal gene expression, inadequate ATP synthesis, serotonin dysregulation, abnormal vagal afferent nerve activation, as well as an array of psychosocial mechanisms, including self-efficacy, causal attributions, expectancy, coping, and social support. An important first step in the management of CRF is the identification and treatment of associated comorbidities, such as anemia, hypothyroidism, pain, emotional distress, insomnia, malnutrition, and other comorbid conditions. However, even effective clinical management of these conditions will not necessarily alleviate CRF for a significant proportion of cancer survivors. For these individuals, intervention with additional therapeutic modalities may be required. The National Comprehensive Cancer Network guidelines recommend that integrative nonpharmacologic behavioral interventions be implemented for the effective management of CRF. These types of interventions may include exercise, psychosocial support, stress management, energy conservation, nutritional therapy, sleep therapy, and restorative therapy. A growing body of scientific evidence supports the use of exercise and psychosocial interventions for the management of CRF. Research on these interventions has yielded positive outcomes in cancer survivors with different diagnoses undergoing a variety of cancer treatments. The data from trials investigating the efficacy of other types of integrative nonpharmacologic behavioral therapies for the management of CRF, though limited, are also encouraging. This article provides an overview of current research on the relative merits of integrative nonpharmacologic behavioral interventions for the effective clinical management of CRF and makes recommendations for future research.

Disclosure of potential conflicts of interest is found at the end of this article.


   INTRODUCTION
Top
 Abstract
 Introduction
Current Approaches to the...
 Integrative Nonpharmacologic...
 Recommendations for Future...
 Conclusions
 Acknowledgments
 Disclosure of Potential...
 References
 
Cancer treatments, such as surgery, chemotherapy, radiation therapy, and hormone therapy, cause suffering and distress that lead to impaired quality of life (QoL) for many cancer survivors. The most common problem reported by cancer survivors is cancer-related fatigue (CRF) [1–19]. Cancer survivors frequently report that CRF begins with diagnosis, worsens during the course of treatment, and persists for months, and even years, after treatment is complete [1–22]. Furthermore, CRF often continues even when the survivor's cancer is undetectable or in remission 1–19,23–25]. Survivors with varying cancer diagnoses and receiving different types of treatment report a frequency of CRF in the range of 60%–100%, with 41% or more indicating severe CRF (a score >7 on an 11-point Likert scale where 0 = no CRF and 10 = CRF as bad as you can imagine) during treatment [3–5,16,26,27]. Moreover, as many as 81% of survivors report persistent CRF, with 17%–38% indicating persistent severe CRF 6 months or longer after completing treatment [11,27–31].

CRF is a multifaceted, subjective, physiological state characterized by persistent, overwhelming exhaustion and a decreased capacity for physical and mental work (Fig. 1) [1–4,6–19,23–25,32]. The nature of CRF makes it a symptom that is difficult to define fully. In general, however, CRF is differentiated from the fatigue experienced by healthy individuals by its severity, its impact on the QoL of cancer survivors, and the fact that CRF is not alleviated by rest or sleep [1–4,6–19,23–25,32]. The impact of CRF is far reaching. CRF is detrimental to recovery and has a significant negative effect on QoL on a day-to-day basis. The lack of effective remedies adds to the distress cancer survivors must endure because of the inability to alleviate this debilitating symptom [1–4,6–19,23–25,32–36].


Figure 1
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  		Figure 1. Multiple biopsychosocial dimensions of cancer-related fatigue.

 
The experience of CRF by cancer survivors involves multiple biopsychosocial signs and symptoms (Fig. 1) that are usually reported by patients as concurrent cancer-or treatment-related side effects [1–19,23–25,37–44]. Physiological signs and symptoms often include anemia, hypothyroidism, shortness of breath, muscle atrophy, physical weakness, decreased aerobic capacity, sleep disruption, pain, and self-reported tiredness [1,2,16,32]. Mood symptoms include depression and anxiety [1,2,16,32]. Motivational symptoms generally appear as hopelessness or negative outcome expectancies. Cognitive symptoms manifest as impaired memory and the inability to concentrate [1,2,16,32]. Social symptoms generally include a reduction in patients' ability to participate in leisure activities [1,2,16,32,45], their capacity to sustain meaningful relationships and activities with their families [1,2,16,32,46], their ability to work, and their capacity to engage in social and other activities during and after treatment [1,2,16,32,47,48]. No two individuals experience CRF in exactly the same way, making it difficult to develop effective treatments and, most likely, impossible to develop an effective intervention targeted at a single pathopsychological or patho-physiological mechanism that will provide relief for the majority of patients with cancer.

CRF often means that survivors must depend on others for home management, transportation, and even simple self-care activities, such as preparing food or bathing [1,2,16,32,48–50]. These changes in daily activity and self-sufficiency may be demoralizing and discouraging. Furthermore, CRF forces patients to engage in unwanted activities in an attempt to cope with their fatigue, such as lying down or taking naps [1,2,16,32,51]. Importantly, CRF is considered more distressing and has a greater negative impact on patients' daily activities and QoL than other cancer-related symptoms, including vomiting, nausea, pain, and depression [1,2,16,32,52]. With the improvements and advances in cancer therapy seen in recent years, the impact of CRF is magnified because life expectancy has increased in cancer survivors [1,2,11,16,24,32,53–56].


   CURRENT APPROACHES TO THE TREATMENT OF CRF
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 Abstract
 Introduction
 Current Approaches to the...
Integrative Nonpharmacologic...
 Recommendations for Future...
 Conclusions
 Acknowledgments
 Disclosure of Potential...
 References
 
The etiology of CRF is complex and multidimensional. The causal contributions of numerous biopsychosocial domains hypothesized to influence CRF are poorly understood and encompass a vast array of potential contributing factors and dynamic psychophysiological pathways. These possible causes are outlined by Ryan and colleagues [57]. CRF remains underrecognized and undertreated because it is not clearly understood. Indeed, it was not until 1998 that CRF was acknowledged as an official diagnosis in the International Classification of Disease (ICD-10). Subsequently, in 2000, the National Comprehensive Cancer Network (NCCN) published the first set of guidelines synthesizing available research and clinical experience in oncology to provide recommendations for supportive patient care [58]. Since that time, the NCCN Fatigue Practice Guidelines have been updated annually to provide concise, up-to-date recommendations for the management of CRF based on the current understanding of the symptom and the development of new therapies [32].

The guidelines for the management of CRF currently proposed by the NCCN [32] suggest that clinicians frequently screen for CRF in patients with cancer and, when present, screen for possible contributing factors (e.g., pain, emotional distress, sleep disruption, anemia, nutrition), including comorbid conditions (e.g., infection, cardiac dysfunction, pulmonary dysfunction, renal dysfunction, hepatic dysfunction, neurologic dysfunction, endocrine dysfunction, hypothyroidism). Identifying CRF and its contributing factors does not mean the problem will be alleviated. Clinicians usually treat contributing factors via pharmacologic means (e.g., colony-stimulating factors, antidepressants, steroids, benzodiazepines, benzodiazepine-receptor agonists, thyroid hormones, and psycho-stimulants) and expect that the CRF will also be resolved [1,2,13,14,16,32]. Unfortunately, many patients with cancer continue to experience CRF even after successful clinical treatment of these contributing factors [1,2,16,32,59,60], Additionally, clinicians often encourage patients experiencing CRF to rest and conserve energy, although CRF is not alleviated by periods of rest, as is the case with other types of fatigue [1,2,16,51]. Patients may also experience CRF in the absence of any clinically discernable contributing factors [1,2,8,9,12–14,16]. In instances where no specific causal factors can be identified or when the patient continues to have moderate-to-severe fatigue after addressing these factors, the NCCN guidelines [32] recommend that physicians consider both pharmacologic interventions and integrative nonpharmacologic behavioral interventions.

The NCCN guidelines recommend the use of a variety of integrative nonpharmacologic behavioral interventions, including exercise, psychosocial interventions, and other integrative therapies for the effective management of CRF. This article provides an overview of the scientific evidence for the efficacy of integrative nonpharmacologic behavioral interventions in the management of CRF and makes recommendations for future research.


   INTEGRATIVE NONPHARMACOLOGIC BEHAVIORAL INTERVENTIONS
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 Abstract
 Introduction
 Current Approaches to the...
 Integrative Nonpharmacologic...
Recommendations for Future...
 Conclusions
 Acknowledgments
 Disclosure of Potential...
 References
 
Nonpharmacologic behavioral interventions encompass a wide array of therapeutic modalities with varying levels of scientific evidence supporting their use in the clinical management of CRF. These types of therapeutic interventions are historically referred to as alternative, complementary, traditional, Eastern, or integrative therapies, depending on cultural context and professional discipline. Since the primary focus of this article is to summarize the evidence regarding the merits of supportive care interventions to be used in conjunction with treatments for cancer, all nonpharmacologic behavioral therapies discussed hereafter are generally referred to as integrative therapies. The integrative nonpharmacologic behavioral interventions discussed in this article are organized into three main categories: (a) exercise, (b) psychosocial interventions, and (c) other integrative therapies (Fig. 2).


Figure 2
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  		Figure 2. Nonpharmacologic interventions for the management of cancer-related fatigue.

 
Exercise Interventions
Physical activity is defined as any skeletal muscle movement that causes an increase in energy expenditure above a resting basal metabolic rate and encompasses a wide variety of lifestyle and occupational activities [61]. Exercise is more specifically defined as physical activity performed in a systematically dosed manner (e.g., a specific frequency, intensity, duration, and mode) with the intention of improving health-related outcomes, such as cardiovascular fitness, muscular strength, body composition, depression, anxiety, sleep, cognition, and fatigue [61]. In the current article, the term exercise or physical exercise is used to describe any physical activity intervention designed and delivered with the intention of improving CRF.

Physical exercise is an integrative nonpharmacologic behavioral intervention that shows great promise in mitigating the acute CRF experienced by cancer patients during treatment, as well as the persistent CRF they experience after treatments are complete. Galvao and Newton [62], Knols and colleagues [63], Stevinson and colleagues [64], Schmidtz and colleagues [65], and McNeely and colleagues [66] recently summarized the evidence from over 45 studies, reported in 64 published papers [67–130], demonstrating positive benefits from physical exercise interventions implemented with cancer survivors during and after treatment. Eight additional published studies [131–138], not included in these reviews, also demonstrated positive effects from physical exercise interventions during and after treatments for cancer. The main outcomes examined included CRF, emotional distress (e.g., depression, anxiety), QoL, aerobic capacity, muscular strength, flexibility, body composition, functional capacity, and immunological parameters. Twelve of these studies assessed CRF as a primary or secondary outcome and employed a randomized, controlled clinical trial experimental design. The current article restricts discussion of studies involving exercise interventions to these 12 randomized controlled clinical trials (Table 1Go) [74,81,89,104–107,117,124,128,131,132].


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  		Table 1. Randomized controlled trials investigating exercise for the management of cancer-related fatigue

 


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  		Table 1. (Continued)

 
Collectively, the results of these 12 studies provide preliminary evidence that exercise is safe and well tolerated by cancer survivors with various cancer diagnoses. The studies also suggest the results are similar for patients throughout the cancer care continuum, postsurgery or post-transplant, as well as during and after chemotherapy, radiation therapy, and/or hormone therapy. One study also suggests that low-intensity seated exercise is safe and well tolerated even by women with metastatic breast cancer. Additionally, this research suggests that exercise interventions involving moderately intense (55%–75% of heart rate maximum) aerobic exercise (e.g., walking and cycling) ranging from 10–90 minutes in duration, 3–7 days/week are consistently effective at either reducing or halting the progression of CRF in cancer patients during and after treatment. Furthermore, one study showed that progressive resistance training (three times per week, 85%–90% of one-repetition maximum, progressively increasing sets and repetitions) was effective in reducing CRF in cancer patients receiving hormone therapy. Lastly, a recent meta-analysis by Schmitz and colleagues [65] suggests that the evidence for exercise as an effectivetherapy for managing CRF is indeed consistently positive, although the effect size (ES) is small (weighted mean ES = 0.13, 95% confidence interval [CI], –0.06 to 0.33 during treatment; weighted mean ES = 0.16, 95% CI, –0.23 to 0.54 post-treatment), indicating the need for developing more effective exercise interventions.

Although the extant exercise and cancer control literature provides consistent support for the efficacy of exercise interventions in managing CRF during and after treatment, this body of literature is preliminary. The studies have small sample sizes and lack consistency in the type and amounts of exercise used. These limitations make it impossible to apply the results effectively as specifically tailored exercise prescriptions that best meet the needs of the patient. There are also methodologic concerns. The measures used to assess CRF and control groups are inconsistent, making interpretations and conclusions across studies difficult. Appropriate statistical and follow-up analyses were not commonly used (e.g., intent-to-treat analyses in randomized controlled trials), making comparisons based on regimen and methods of exercise intervention difficult to ascertain [62–64].

Despite these limitations, this growing body of research provides consistent preliminary support for the safety of exercise interventions for cancer survivors across the entire cancer care continuum.

Psychosocial Interventions
During the last 20 years the body of knowledge regarding the benefits of psychosocial interventions for cancer survivors has grown substantially. Psychosocial interventions include activities such as support interventions (either individually or in groups), education, stress management, coping strategy training, and behavioral interventions designed to assist survivors with managing their CRF. Psychosocial interventions may be particularly useful for cancer survivors in whom exercise is contraindicated, or as an adjunct to exercise programs. As with exercise interventions, a growing body of empiric data supports the use of psychosocial interventions for the management of CRF. Randomized, controlled clinical trials have examined a variety of psychosocial interventions in cancer survivors during and after treatment (Table 2Go) [139–153].


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  		Table 2. Randomized controlled trials investigating psycho socialinterventions for the management of cancer-related fatigue

 


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  		Table 2. (Continued)

 
Taken together, the results of these studies suggest that psychosocial support therapy portends lower levels of CRF among patients undergoing treatment and cancer survivors with different cancer diagnoses. Additionally, this research suggests that psychosocial interventions are effective in helping to manage CRF whether delivered individually or in a group setting, orally or written, and, interestingly, by a licensed professional or a trained nonprofessional. Furthermore, the benefits may continue for many months following cessation of the interventions [141]. However, interventions that are too lengthy and that require too many sessions during the time when patients are receiving treatments for their cancer, such as radiation, may in fact exacerbate CRF [153].

Unfortunately, the wide variety of psychosocial interventions and the lack of detailed descriptions of the interventions limit the ability to make a differential or overall assessment of the efficacy of psychosocial interventions. As is evident from Table 2Go, studies used varying combinations of psychosocial intervention techniques and investigated the effects on CRF using a wide range of assessment tools. Despite the diverse array of psychosocial interventions, in general, the results from these studies suggest that psychosocial interventions benefit patients with cancer both during and after the completion of treatments by improving CRF. However, further research is needed to delineate the optimal mode of delivery, as well as the optimal content for psychosocial interventions targeted at managing CRF.

Other Integrative Interventions
In an attempt to mitigate the unpleasantness of treatment side effects, including CRF, patients with cancer and survivors are increasingly turning to integrative nonpharmacologic behavioral interventions that have not typically been considered part of western European medicine [154–157]. The most common forms of integrative modalities used by cancer survivors across the U.S. include prayer, relaxation, and exercise [157]. A brief summary follows of the evidence for the merits of yoga, mindfulness-based stress reduction (MBSR), nutrition, sleep, polarity, and restorative therapies for managing CRF.

Yoga
One particular type of exercise intervention, collectively known as yoga, is based on Eastern traditions from India (i.e., classical, Advaita Vedanta, Tantra), Tibet (i.e., Tibetan), and China (i.e., Chi Kung, Tai Chi) [158,159]. The word yoga is derived from its Sanskrit root, "yuj," which literally means "to yoke" or join together. In this case, yoga refers to a joining of the mind and the body. The earliest forms of yoga were firmly rooted in introspective and meditative practices based on Vedic, Upanishad, and Sutra texts. These early forms ultimately led to what is known today as classical yoga. The system of classical yoga, based largely on the yoga sutras, combines physical exercise with mindfulness, and is the most common style of yoga taught today in the West [158–160]. In an effort to alleviate side effects, such as CRF, and improve QoL, patients with cancer are turning to yoga with promising results.

Cohen [158] demonstrated no increase in CRF among 39 patients with lymphoma actively receiving treatment, or within 12 months post-treatment, who participated in a Tibetan yoga stress reduction program once a week for 7 weeks. The program included yoga postures, visualization, breathing, and mindfulness. Participants in the wait-list control demonstrated increases in CRF. This is the first published study to report the effect of yoga on CRF using a validated measure (Brief Fatigue Inventory). While results of the study are very encouraging and suggest that yoga may be a viable therapeutic intervention for improving CRF, the evidence remains preliminary. However, this study strongly suggests the need for appropriately powered, randomized controlled trials with CRF as a primary outcome in order to develop a scientific evidence base supporting the use of yoga for the clinical management of CRF [161,162].

MBSR
Mindfulness-based stress reduction (MBSR) is a multimodal program focused on improving well-being and health [163]. The most widely recognized MBSR program was developed by Kabat-Zinn [163] at the Massachusetts Medical Center. The program includes one 90-minute session per week for 8 weeks, along with a 3-hour silent retreat between weeks 6 and 7. The curriculum consists of three major components: (a) experiential practice of gentle Hatha yoga (including yoga stretches, poses, and breathing and meditation exercises) performed once a week during the 90-minute sessions and at home; (b) educational materials related to mindfulness, relaxation, meditation, and yoga; and (c) group processing and discussion.

Speca and colleagues [164] demonstrated greater reductions in CRF among 109 early-or late-stage cancer patients participating in an MBSR program compared with participants in a wait-list control group. Additionally, Carlson and colleagues [165,166] reported improvements in CRF from preintervention to postintervention among 59 patients with breast or prostate cancer participating in an 8-week MBSR program. Both intervention programs were modeled after the Massachusetts Medical Center program headed by Kabat-Zinn [163]. The yoga portion of the intervention included gentle Hatha yoga stretches and poses and breathing and meditation exercises performed once a week as part of the 90-minute class. These are the first two published studies to report on the effect of MBSR on CRF. Again, while results of these studies are positive and suggest that MBSR may be a useful therapeutic intervention for improving CRF, the evidence is preliminary. There is a need for appropriately powered, randomized controlled trials with CRF as a primary outcome to create an informed scientific evidence base upon which to base clinical care.

Nutritional Therapy
Patients with cancer are at risk for malnutrition and other nutrition-related problems as a result of the cancer itself, the body's response to the cancer, and the treatment prescribed. Many factors may contribute to malnutrition, including nausea, vomiting, mucositis, diarrhea, and malabsorption of food. Clinical manifestations of malnutrition include fatigue, anorexia, weight loss, and muscle wasting, resulting in poor patient outcomes, including a negative effect on recovery and survival. Importantly, malnutrition and other nutrition-related problems may contribute to the development and exacerbation of CRF. In a recent randomized controlled trial in 111 patients with colorectal cancer undergoing radiation therapy, Ravasco and colleagues [167] reported lower CRF among participants assigned to the individualized dietary counseling group and those assigned to the protein-supplement group compared with individuals in the ad libitum food intake group. Patients who received protein supplements did not experience the same reduction in CRF as those receiving dietary counseling who were consuming ordinary foods. The results from this trial are encouraging and they represent the first preliminary evidence that concurrent individualized dietary counseling, based on regular foods, is an effective means of improving patients' nutritional intake and CRF. However, further research is needed to establish a solid scientific evidence base regarding the benefits of nutritional therapy on CRF.

Sleep Therapy
Although patients with CRF frequently report disruptions in their sleep patterns, the relationship between sleep patterns and CRF is not well understood [168,169]. Health-care professionals frequently recommend rest and sleep for the management of CRF [168]. One approach that is recommended for the management of sleep disorders is improved sleep hygiene [170]. The rationale behind this approach is that the often self-perpetuating nature of sleep problems means they can be a continuing cause of fatigue. Patients who sleep poorly often extend their overall period of sleep by taking naps, going to bed earlier, or getting up later. This extended "sleep opportunity" can be problematic, however, if it exceeds the basal ability of the body to generate sleep. The resulting reduction in nocturnal sleep quality increases the likelihood that patients will feel fatigue during the day and the cycle continues to repeat itself. Sleep interventions provide patients with guidance on good sleep hygiene (e.g., encouraging patients to go to sleep at the same time each evening and to rise at a similar time every morning). Other sleep interventions limit the overall time spent in bed, the duration of daytime naps, and evening stimulation [171].

Support for the utility of sleep hygiene in the management of CRF is limited by the lack of randomized controlled investigations in this area, although some preliminary positive evidence exists from nonrandomized, noncontrolled studies. Graydon and colleagues [172] observed improvements in CRF among cancer survivors who practiced rest and sleep to manage their symptoms. However, a wide variety of sleep scores were measured among patients adopting similar strategies, suggesting involvement of other factors. More recently, Berger and colleagues [171] reported that a sleep-management intervention in patients undergoing breast cancer chemotherapy resulted in improvements in CRF during the first three chemotherapy cycles, but not during the fourth cycle. Additionally, Savard and colleagues [173] reported significant differences in CRF from pre-to postintervention among breast cancer survivors receiving cognitive behavioral therapy for insomnia compared with survivors in a wait-list control condition. While these results may seem promising, they do not provide sufficient evidence to support the efficacy of sleep therapy for mitigating CRF and further research is needed.

Polarity Therapy
Polarity therapy is an energy therapy, developed by Dr. Randolph Stone in 1947, that employs gentle human touch in an effort to balance the electrical energy fields of living organisms and, thus, portend a state of well-being and health [174]. This "energy therapy" is based in historical Greek, Indian, Egyptian, and Chinese medical traditions. Roscoe and colleagues [174] published the first randomized, controlled pilot study investigating the efficacy of polarity therapy for improving CRF. This study reported that breast cancer survivors receiving one 75-minute session or two 75-minute sessions (a week apart) of polarity therapy during the course of radiation therapy demonstrated significant reductions in CRF compared with survivors receiving standard radiation therapy alone [174]. These results are very encouraging, especially considering this is an integrative nonpharmacologic behavioral intervention that does not require substantial lifestyle change on the part of the cancer survivor. However, this is the only published study to investigate the efficacy of polarity therapy for improving CRF and the study was conducted with a very small sample (n = 15). As such, further randomized controlled trials are needed to establish the efficacy of polarity therapy for improving CRF and create a solid evidence base upon which to inform clinical practice.

Restorative Therapy
Decreased attention capacity, or attentional fatigue, represents one aspect of the sensory dimension of CRF that has been documented in patients with cancer [175]. The aim of restorative therapy is to maintain or restore attentional capacity and decrease attentional fatigue, thereby decreasing CRF. This is accomplished through involvement in activities that engage patients' fascination or have other restorative properties that improve attentional capacity. Though limited, existing data indicate that restorative therapy provides benefits for the sensory dimension of CRF in patients newly diagnosed with cancer and in patients with cancer after surgery. For example, Cimprich [176] observed improvements in attentional fatigue in a randomized controlled trial involving 32 women during the 3 months after surgery for stage I or II breast cancer. More recently, Cimprich and Ronis [177], in a randomized study of 157 women with newly diagnosed breast cancer, reported that regular exposure to the natural environment was demonstrated to improve attentional fatigue. Research in this field is preliminary and a number of questions remain unanswered, particularly, the relationship between and specific role of mental fatigue and somatic fatigue in CRF. Additionally, since the studies conducted by Cimprich and colleagues did not use standard multidimensional CRF measures, it is not possible to establish whether the improvements in attentional fatigue actually resulted in improvements in CRF or more specific benefits, such as increased ability to perform activities of daily living or social activities. Further rigorous research is needed to develop scientific knowledge regarding the efficacy of restorative therapy for the management of CRF.


   RECOMMENDATIONS FOR FUTURE RESEARCH
Top
 Abstract
 Introduction
 Current Approaches to the...
 Integrative Nonpharmacologic...
 Recommendations for Future...
Conclusions
 Acknowledgments
 Disclosure of Potential...
 References
 
Clearly, some progress has been made in establishing clear scientific evidence for the use of several integrative nonpharmacologic behavioral interventions for the clinical management of CRF, but a great deal of research is still needed. Future research on integrative nonpharmacologic behavioral interventions should focus on discerning: (a) what physical exercise dose (mode, frequency, intensity, duration) is most effective for treating CRF; (b) how the safe and effective physical exercise dose for treating CRF varies with different cancer diagnoses (e.g., solid tumors, leukemias, and lymphomas, varying stages 0–IV); (c) how the safe and effective physical exercise dose for treating CRF varies throughout the cancer care continuum from diagnosis to many years post-treatment; (d) what the negative side effects of physical exercise for cancer survivors are and at what time points and doses they occur (e.g., interference with chemotherapy, radiation, hormone therapy, immune compromise); (e) what the optimum delivery method is for a physical exercise intervention (e.g., home-based, community, Internet) to achieve acceptable levels of adherence and compliance to produce improvements in CRF; (f) what the specific content of psychosocial therapy should include; (g) what the optimal delivery method is for psychosocial therapy interventions (e.g., individual, group, oral, written, licensed psychologist, or nonlicensed professional); (h) which other promising integrative nonpharmacologic behavioral interventions, such as yoga, MBSR, nutrition, sleep, polarity, and restorative therapies, are effective in treating CRF; and (i) which single intervention or combination of interventions provides the most effective means of treating CRF. Future research on integrative nonpharmacologic behavioral interventions for the management of CRF should also follow rigorous scientific research methodology. Clinical trials should follow the Consolidated Standards of Reporting Trials (CONSORT) guidelines [178]; experimental designs and statistical analyses should include CRF as a primary study outcome; research programs promoting specific interventions should include and be clearly reported as phase I, phase II, phase III, and phase IV clinical trials; and statistical analyses should use intent-to-treat analyses, as appropriate.


   CONCLUSIONS
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 Abstract
 Introduction
 Current Approaches to the...
 Integrative Nonpharmacologic...
 Recommendations for Future...
 Conclusions
Acknowledgments
 Disclosure of Potential...
 References
 
In line with guidelines from the NCCN, integrative nonpharmacologic behavioral treatment should be implemented for the effective management of CRF. A wide range of these interventions is available, including physical exercise, psychosocial therapy, yoga, MBSR, and nutritional, sleep, polarity, and restorative therapies. Physical exercise and psychosocial therapeutic interventions currently have the strongest scientific evidence base to support their use. Unfortunately, the most effective exercise prescription or psychosocial therapy remains unclear and the effect sizes are small. This means that while oncologists can and should encourage their patients to exercise and participate in psychosocial therapy to improve their symptoms and side effects, they cannot provide specific exercise or psychosocial prescriptions for the effective treatment of CRF, and hence, even with exercise and psychosocial therapy, the improvements in CRF may be small. As a result, exercise and psychosocial interventions as part of clinical care for symptom and side-effect management in oncology are not as effective or efficient as they should be. There is also promising, but very limited, evidence to support the use of other integrative nonpharmacologic behavioral interventions for the management of CRF, including yoga, MBSR, and nutritional, sleep, polarity, and restorative therapies. However, the scientific evidence underlying these interventions is very preliminary and the use of these modalities as part of standard clinical care in oncology for the management of CRF is premature.

Integrative nonpharmacologic behavioral interventions are already sought and used by many patients with cancer to aid in the management of their cancer-and treatment-related symptoms and side effects, such as CRF. The scientific community must continue conducting and funding research to provide the detailed scientific evidence and resources necessary for oncologists to prescribe these types of integrative nonpharmacologic behavioral interventions effectively as part of standard care and to assist cancer survivors in choosing which intervention will best suit their needs. While much is still to be discovered, integrative nonpharmacologic behavioral interventions show great promise in the battle against CRF and its life-altering effects.


   ACKNOWLEDGMENTS
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The authors are recipients of National Cancer Institute grants 1R25-CA102618-01A1 and 2U10 CA037420-20 and American Cancer Society grant RSG01071-01-PBP. Publication of this article was supported by a grant from Cephalon, Inc., Frazer, PA.


   DISCLOSURE OF POTENTIAL CONFLICTS OF INTEREST
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 Conclusions
 Acknowledgments
 Disclosure of Potential...
References
 
G.R.M. has acted as a consultant for MGI Pharma and Cephalon.


   REFERENCES
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  1. Morrow GR, Andrews PL, Hickok JT et al. Fatigue associated with cancer and its treatment. Support Care Cancer 2002;10:389–398.[CrossRef][Medline]
  2. Morrow GR, Shelke AR, Roscoe JA et al. Management of cancer-related fatigue. Cancer Invest 2005;23:229–239.[Medline]
  3. Hickok JT, Roscoe JA, Morrow GR et al. Frequency, severity, clinical course, and correlates of fatigue in 372 patients during 5 weeks of radio-therapy for cancer. Cancer 2005;104:1772–1778.[CrossRef][Medline]
  4. Hickok JT, Morrow GR, Roscoe JA et al. Occurrence, severity, and longitudinal course of twelve common symptoms in 1129 consecutive patients during radiotherapy for cancer. J Pain Symptom Manage 2005;30:433–442.[CrossRef][Medline]
  5. Hofman M, Morrow GR, Roscoe JA et al. Cancer patients' expectations of experiencing treatment-related side effects: A University of Rochester Cancer Center–Community Clinical Oncology Program study of 938 patients from community practices. Cancer 2004;101:851–857.[CrossRef][Medline]
  6. Cella D. Factors influencing quality of life in cancer patients: Anemia and fatigue. Semin Oncol 1998;25(suppl 7):43–46.[Medline]
  7. Cella D, Peterman A, Passik S et al. Progress toward guidelines for the management of fatigue. Oncology (Williston Park) 1998;12:369–377.[Medline]
  8. Cella D, Davis K, Breitbart W et al. Cancer-related fatigue: Prevalence of proposed diagnostic criteria in a United States sample of cancer survivors. J Clin Oncol 2001;19:3385–3391.[Abstract/Free Full Text]
  9. Cella D, Lai JS, Chang CH et al. Fatigue in cancer patients compared with fatigue in the general United States population. Cancer 2002;94:528–538.[CrossRef][Medline]
  10. Curt GA, Breitbart W, Cella D et al. Impact of cancer-related fatigue on the lives of patients: New findings from the Fatigue Coalition. The Oncologist 2000;5:353–360.[Abstract/Free Full Text]
  11. Barton-Burke M. Cancer-related fatigue and sleep disturbances. Further research on the prevalence of these two symptoms in long-term cancer survivors can inform education, policy, and clinical practice. Am J Nurs 2006;106;(3) (suppl):72–77.[Medline]
  12. Escalante CP. Treatment of cancer-related fatigue: An update. Support Care Cancer 2003;11:79–83.[Medline]
  13. Jereczek-Fossa BA, Marsiglia HR, Orecchia R. Radiotherapy-related fatigue: How to assess and how to treat the symptom. A commentary. Tumori 2001;87:147–151.[Medline]
  14. Ahlberg K, Ekman T, Gaston-Johansson F et al. Assessment and management of cancer-related fatigue in adults. Lancet 2003;362:640–650.[CrossRef][Medline]
  15. Mock V, Olsen M. Current management of fatigue and anemia in patients with cancer. Semin Oncol Nurs 2003;19(suppl 2):36–41.[CrossRef][Medline]
  16. Mock V. Evidence-based treatment for cancer-related fatigue. J Natl Cancer Inst Monogr 2004;32:112–118.[Abstract/Free Full Text]
  17. Irvine DM, Vincent L, Bubela N et al. A critical appraisal of the research literature investigating fatigue in the individual with cancer. Cancer Nurs 1991;14:188–199.[Medline]
  18. Kroenke K, Wood DR, Mangelsdorff AD et al. Chronic fatigue in primary care. Prevalence, patient characteristics, and outcome. JAMA 1988;260:929–934.[Abstract/Free Full Text]
  19. Piper BF, Lindsey AM, Dodd MJ. Fatigue mechanisms in cancer patients: Developing nursing theory. Oncol Nurs Forum 1987;14:17–23.[Medline]
  20. Blesch KS, Paice JA, Wickham R et al. Correlates of fatigue in people with breast or lung cancer. Oncol Nurs Forum 1991;18:81–87.[Medline]
  21. Fobair P, Hoppe RT, Bloom J et al. Psychosocial problems among survivors of Hodgkin's disease. J Clin Oncol 1986;4:805–814.[Abstract/Free Full Text]
  22. King KB, Nail LM, Kreamer K et al. Patients' descriptions of the experience of receiving radiation therapy. Oncol Nurs Forum 1985;12:55–61.[Medline]
  23. Berger AM. Patterns of fatigue and activity and rest during adjuvant breast cancer chemotherapy. Oncol Nurs Forum 1998;25:51–62.[Medline]
  24. Broeckel JA, Jacobsen PB, Horton J et al. Characteristics and correlates of fatigue after adjuvant chemotherapy for breast cancer. J Clin Oncol 1998;16:1689–1696.[Abstract]
  25. Portenoy RK, Itri LM. Cancer-related fatigue: Guidelines for evaluation and management. The Oncologist 1999;4:1–10.[Abstract/Free Full Text]
  26. Cassileth BR, Lusk EJ, Bodenheimer BJ et al. Chemotherapeutic toxicity–the relationship between patients— pretreatment expectations and posttreatment results. Am J Clin Oncol 1985;8:419–425.[Medline]
  27. Mustian KM, Hofman M, Morrow GR et al. Cancer-related fatigue and shortness of breath among cancer survivors: A prospective URCC CCOP Study. NCI Cancer Survivorship Research Conference; October 4–6, 2006; Bethesda, Maryland.
  28. Frank-Stromborg M, Wright P. Ambulatory cancer patients' perception of the physical and psychosocial changes in their lives since the diagnosis of cancer. Cancer Nurs 1984;7:117–130.[Medline]
  29. Meyerowitz BE, Watkins IK, Sparks FC. Quality of life for breast cancer patients receiving adjuvant chemotherapy. Am J Nurs 1983;83:232–235.[CrossRef][Medline]
  30. Padilla GV, Grant MM. Quality of life as a cancer nursing outcome variable. ANS Adv Nurs Sci 1985;8:45–60.[Medline]
  31. Prue G, Rankin J, Allen J et al. Cancer-related fatigue: A critical appraisal. Eur J Cancer 2006;42:846–863.[CrossRef][Medline]
  32. National Comprehensive Cancer Network (NCCN). Clinical practice guidelines in oncology: Cancer-related fatigue, v1.2006. Available at: http://www.nccn.org/professionals/physician_glf/PDF/fatigue.pdf. October 2006.
  33. Ferrell BR, Grant M, Funk B et al. Quality of life in breast cancer. Cancer Pract 1996;4:331–340.[Medline]
  34. Janda M, Gerstner N, Obermair A et al. Quality of life changes during conformal radiation therapy for prostate carcinoma. Cancer 2000;89:1322–1328.[CrossRef][Medline]
  35. Hofman M, Ryan JL, Figueroa-Moseley CD et al. Cancer-related fatigue: The scale of the problem. The Oncologist 2007;12(suppl 1):4–10.[Abstract/Free Full Text]
  36. Carroll JK, Kohli S, Mustian KM et al. Pharmacologic treatment of cancer-related fatigue. The Oncologist 2007;12(suppl 1):43–51.[Abstract/Free Full Text]
  37. Armstrong TS, Cohen MZ, Eriksen LR et al. Symptom clusters in oncology patients and implications for symptom research in people with primary brain tumors. J Nurs Scholarsh 2004;36:197–206.[CrossRef][Medline]
  38. Beck SL, Dudley WN, Barsevick A. Pain, sleep disturbance, and fatigue in patients with cancer: Using a mediation model to test a symptom cluster. Oncol Nurs Forum 2005;32:542.[Medline]
  39. Dodd MJ, Miaskowski C, Paul SM. Symptom clusters and their effect on the functional status of patients with cancer. Oncol Nurs Forum 2001;28:465–470.[Medline]
  40. Given B, Given C, Azzouz F et al. Physical functioning of elderly cancer patients prior to diagnosis and following initial treatment. Nurs Res 2001;50:222–232.[CrossRef][Medline]
  41. Hwang SS, Chang VT, Rue M et al. Multidimensional independent predictors of cancer-related fatigue. J Pain Symptom Manage 2003;26:604–614.[CrossRef][Medline]
  42. Paice JA. Assessment of symptom clusters in people with cancer. J Natl Cancer Inst Monogr 2004;32:98–102.[Abstract/Free Full Text]
  43. Savard J, Simard S, Blanchet J et al. Prevalence, clinical characteristics, and risk factors for insomnia in the context of breast cancer. Sleep 2001;24:583–590.[Medline]
  44. Tchekmedyian NS, Kallich J, McDermott A et al. The relationship between psychologic distress and cancer-related fatigue. Cancer 2003;98:198–203.[CrossRef][Medline]
  45. Bloom JR, Gorsky RD, Fobair P et al. Physical performance at work and at leisure: Validation of a measure of biological energy in survivors of Hodgkin's disease. J Psychosoc Oncol 1990;8:49–63.[CrossRef]
  46. Piper BF. Anonymous Monograph on Nursing Management of Common Problems: State of the Art. Fatigue in cancer patients: Current perspectives on measurement and management. Fifth annual conference on cancer nursing. New York: American Cancer Society, 1988:92-107.
  47. Meyerowitz BE, Sparks FC, Spears IK. Adjuvant chemotherapy for breast carcinoma: Psychosocial implications. Cancer 1979;43:1613–1618.[CrossRef][Medline]
  48. Rhodes VA, Watson PM, Hanson BM. Patients' descriptions of the influence of tiredness and weakness on self-care abilities. Cancer Nurs 1988;11:186–194.[Medline]
  49. Devlen J, Maguire P, Phillips P et al. Psychological problems associated with diagnosis and treatment of lymphomas. I: Retrospective study. Br Med J (Clin Res Ed) 1987;295:953–954.[Medline]
  50. Devlen J, Maguire P, Phillips P et al. Psychological problems associated with diagnosis and treatment of lymphomas. II: Prospective study. Br Med J (Clin Res Ed) 1987;295:955–957.[Medline]
  51. Piper BF. Subjective fatigue in women receiving six cycles of adjuvant chemotherapy for breast cancer. Doctoral Dissertation. San Francisco: University of California, 1992
  52. Curt GA, Breitbart W, Cella D et al. In: Marty M, Pecorelli S, eds. Fatigue and Cancer. Impact of cancer-related fatigue on the lives of patients: New findings from the Fatigue Coalition. Amsterdam: Elsevier, 2001:3-16.
  53. Andrykowski MA, Curran SL, Lightner R. Off-treatment fatigue in breast cancer survivors: A controlled comparison. J Behav Med 1998;21:1–18.[CrossRef][Medline]
  54. Loge JH, Abrahamsen AF, Ekeberg O et al. Fatigue and psychiatric morbidity among Hodgkin_s disease survivors. J Pain Symptom Manage 2000;19:91–99.[CrossRef][Medline]
  55. Smets EM, Visser MR, Willems-Groot AF et al. Fatigue and radio-therapy: (A) Experience in patients undergoing treatment. Br J Cancer 1998;78:899–906.[Medline]
  56. Smets EM, Visser MR, Willems-Groot AF et al. Fatigue and radiotherapy: (B) Experience in patients 9 months following treatment. Br J Cancer 1998;78:907–912.[Medline]
  57. Ryan JL, Carroll JK, Ryan EP et al. Mechanisms of cancer-related fatigue. The Oncologist 2007;12(suppl 1):22–34.[Abstract/Free Full Text]
  58. Mock V, Atkinson A, Barsevick A et al. NCCN Practice Guidelines for Cancer-Related Fatigue. Oncology (Williston Park) 2000;14:151–161.[Medline]
  59. Morrow GR, Hickok JT, Roscoe JA et al. Differential effects of paroxetine on fatigue and depression: A randomized, double-blind trial from the University of Rochester Cancer Center Community Clinical Oncology Program. J Clin Oncol 2003;21:4635–4641.[Abstract/Free Full Text]
  60. Roscoe JA, Morrow GR, Hickok JT et al. Effect of paroxetine hydro-chloride (Paxil®) on fatigue and depression in breast cancer patients receiving chemotherapy. Breast Cancer Res Treat 2005;89:243–249.[CrossRef][Medline]
  61. American College of Sports Medicine. ACSM's Guidelines for exercise testing and prescription. Baltimore: Lippincott, Williams, & Wilkins, 2006.
  62. Galvao DA, Newton RU. Review of exercise intervention studies in cancer patients. J Clin Oncol 2005;23:899–909.[Abstract/Free Full Text]
  63. Knols R, Aaronson NK, Uebelhart D et al. Physical exercise in cancer patients during and after medical treatment: A systematic review of randomized and controlled clinical trials. J Clin Oncol 2005;23:3830–3842.[Abstract/Free Full Text]
  64. Stevinson C, Lawlor DA, Fox KR. Exercise interventions for cancer patients: Systematic review of controlled trials. Cancer Causes Control 2004;15:1035–1056.[CrossRef][Medline]
  65. Schmitz KH, Holtzman J, Courneya KS et al. Controlled physical activity trials in cancer survivors: A systematic review and meta-analysis. Cancer Epidemiol Biomarkers Prev 2005;14:1588–1595.[Abstract/Free Full Text]
  66. McNeely ML, Campbell KL, Rowe BH et al. Effects of exercise on breast cancer patients and survivors: A systematic review and meta-analysis. CMAJ 2006;175:34–41.[Abstract/Free Full Text]
  67. Adamsen L, Midtgaard J, Rorth M et al. Feasibility, physical capacity, and health benefits of a multidimensional exercise program for cancer patients undergoing chemotherapy. Support Care Cancer 2003;11:707–716.[CrossRef][Medline]
  68. Allgayer H, Nicolaus S, Schreiber S et al. Decreased interleukin-1 receptor antagonist response following moderate exercise in patients with colorectal carcinoma after primary treatment. Cancer Detect Prev 2004;28:208–213.[CrossRef][Medline]
  69. Berglund G, Bolund C, Gustavsson UL et al. Starting again—a comparison study of a group rehabilitation program for cancer patients. Acta Oncol 1993;32:15–21.[Medline]
  70. Berglund G, Bolund C, Gustafsson UL et al. One-year follow-up of the ‘Starting Again’ group rehabilitation programme for cancer patients. Eur J Cancer 1994;30A:1744–1751.[CrossRef]
  71. Berglund G, Bolund C, Gustafsson UL et al. A randomized study of a rehabilitation program for cancer patients: The starting again group. Psychooncology 1994;3:109–120.[CrossRef]
  72. Berglund G, Petersson LM, Eriksson KR et al. "Between men": Patient perceptions and priorities in a rehabilitation program for men with prostate cancer. Patient Educ Couns 2003;49:285–92.[CrossRef][Medline]
  73. Burnham T, Wilcox A. Effects of exercise on physiological and psychological variables in cancer survivors. Med Sci Sports Exerc 2002;34:1863–1867.
  74. Campbell A, Mutrie N, White F et al. A pilot study of a supervised group exercise programme as a rehabilitation treatment for women with breast cancer receiving adjuvant treatment. Eur J Oncol Nurs 2005;9:56–63.[CrossRef][Medline]
  75. Coleman EA, Coon S, Hall-Barrow J et al. Feasibility of exercise during treatment for multiple myeloma. Cancer Nurs 2003;26:410–419.[Medline]
  76. Coleman EA, Hall-Barrow J, Coon S et al. Facilitating exercise adherence for patients with multiple myeloma. Clin J Oncol Nurs 2003;7:529–534, 540.[Medline]
  77. Courneya KS, Keats MR, Turner AR. Physical exercise and quality of life in cancer patients following high dose chemotherapy and autologous bone marrow transplantation. Psychooncology 2000;9:127–136.[CrossRef][Medline]
  78. Courneya KS, Friedenreich CM, Sela RA et al. Correlates of adherence and contamination in a randomized controlled trial of exercise in cancer survivors: An application of the theory of planned behavior and the five factor model of personality. Ann Behav Med 2002;24:257–268.[CrossRef][Medline]
  79. Courneya KS, Friedenreich CM, Sela RA et al. The group psychotherapy and home-based physical exercise (group-hope) trial in cancer survivors: Physical fitness and quality of life outcomes. Psychooncology 2003;12:357–374.[CrossRef][Medline]
  80. Courneya KS, Mackey JR, Bell GJ et al. Randomized controlled trial of exercise training in postmenopausal breast cancer survivors: Cardiopulmonary and quality of life outcomes. J Clin Oncol 2003;21:1660–1668.[Abstract/Free Full Text]
  81. Courneya KS, Friedenreich CM, Quinney HA et al. A randomized trial of exercise and quality of life in colorectal cancer survivors. Eur J Cancer Care (Engl) 2003;12:347–357.[CrossRef][Medline]
  82. Cunningham AJ, Edmonds CV, Jenkins GP et al. A randomized controlled trial of the effects of group psychological therapy on survival in women with metastatic breast cancer. Psychooncology 1998;7:508–517.[CrossRef][Medline]
  83. Cunningham BA, Morris G, Cheney CL et al. Effects of resistive exercise on skeletal muscle in marrow transplant recipients receiving total parenteral nutrition. JPEN J Parenter Enteral Nutr 1986;10:558–563.[Abstract/Free Full Text]
  84. Dimeo F, Stieglitz RD, Novelli-Fischer U et al. Correlation between physical performance and fatigue in cancer patients. Ann Oncol 1997;8:1251–1255.[Abstract/Free Full Text]
  85. Dimeo F, Fetscher S, Lange W et al. Effects of aerobic exercise on the physical performance and incidence of treatment-related complications after high-dose chemotherapy. Blood 1997;90:3390–3394.[Abstract/Free Full Text]
  86. Dimeo F, Rumberger BG, Keul J. Aerobic exercise as therapy for cancer fatigue. Med Sci Sports Exerc 1998;30:475–478.
  87. Dimeo F, Schwartz S, Fietz T et al. Effects of endurance training on the physical performance of patients with hematological malignancies during chemotherapy. Support Care Cancer 2003;11:623–628.[CrossRef][Medline]
  88. Dimeo FC, Tilmann MH, Bertz H et al. Aerobic exercise in the rehabilitation of cancer patients after high dose chemotherapy and autologous peripheral stem cell transplantation. Cancer 1997;79:1717–1722.[CrossRef][Medline]
  89. Dimeo FC, Stieglitz RD, Novelli-Fischer U et al. Effects of physical activity on the fatigue and psychologic status of cancer patients during chemotherapy. Cancer 1999;85:2273–2277.[CrossRef][Medline]
  90. Durak E, Lilly P. The application of an exercise and wellness program for cancer patients: A preliminary outcomes report. J Strength Cond Res 1998;12:3–6.[Medline]
  91. Durak E, Lilly P, Hackworth J. Physical and psychosocial responses to exercise in cancer patients: A two-year follow-up survey with prostate, leukemia, and general carcinoma. J Exercise Physiol Online 1999;2.
  92. Fairey AS, Courneya KS, Field CJ et al. Effects of exercise training on fasting insulin, insulin resistance, insulin-like growth factors, and insulin-like growth factor binding proteins in postmenopausal breast cancer survivors: A randomized controlled trial. Cancer Epidemiol Biomarkers Prev 2003;12:721–727.[Abstract/Free Full Text]
  93. Galantino ML, Capito L, Kane RJ et al. The effects of Tai Chi and walking on fatigue and body mass index in women living with breast cancer: A pilot study. Rehabil Oncol 2003;21:22.
  94. Hayes S, Davies PS, Parker T et al. Total energy expenditure and body composition changes following peripheral blood stem cell transplantation and participation in an exercise programme. Bone Marrow Trans-plant 2003;31:331–338.[CrossRef][Medline]
  95. Hayes S, Davies PS, Parker T et al. Quality of life changes following peripheral blood stem cell transplantation and participation in a mixed-type, moderate-intensity, exercise program. Bone Marrow Transplant 2004;33:553–558.[CrossRef][Medline]
  96. Hayes SC, Davies PS, Parker TW et al. The role of a mixed type, moderate intensity exercise programme after peripheral blood stem cell transplantation. Br J Sports Med 2004;38:304–309; discussion 309.[Abstract/Free Full Text]
  97. Hayes SC, Rowbottom D, Davies PS et al. Immunological changes after cancer treatment and participation in an exercise program. Med Sci Sports Exerc 2003;35:2–9.
  98. Kolden GG, Strauman TJ, Ward A et al. A pilot study of group exercise training (GET) for women with primary breast cancer: Feasibility and health benefits. Psychooncology 2002;11:447–456.[CrossRef][Medline]
  99. MacVicar MG, Winningham ML. Promoting the functional capacity of cancer patients. Cancer Bull 1986;38:235–239.
  100. MacVicar MG, Winningham ML, Nickel JL. Effects of aerobic interval training on cancer patients' functional capacity. Nurs Res 1989;38:348–351.[Medline]
  101. McKenzie DC, Kalda AL. Effect of upper extremity exercise on secondary lymphedema in breast cancer patients: A pilot study. J Clin Oncol 2003;21:463–466.[Abstract/Free Full Text]
  102. McNeely ML, Parliament M, Courneya KS et al. A pilot study of a randomized controlled trial to evaluate the effects of progressive resistance exercise training on shoulder dysfunction caused by spinal accessory neurapraxia/neurectomy in head and neck cancer survivors. Head Neck 2004;26:518–530.[CrossRef][Medline]
  103. Mello M, Tanaka C, Dulley FL. Effects of an exercise program on muscle performance in patients undergoing allogeneic bone marrow trans-plantation. Bone Marrow Transplant 2003;32:723–728.[CrossRef][Medline]
  104. Mock V, Burke MB, Sheehan P et al. A nursing rehabilitation program for women with breast cancer receiving adjuvant chemotherapy. Oncol Nurs Forum 1994;21:899–907; discussion 908.[Medline]
  105. Mock V, Pickett M, Ropka ME et al. Fatigue and quality of life outcomes of exercise during cancer treatment. Cancer Pract 2001;9:119–127.[CrossRef][Medline]
  106. Mock V, Dow KH, Meares CJ et al. Effects of exercise on fatigue, physical functioning, and emotional distress during radiation therapy for breast cancer. Oncol Nurs Forum 1997;24:991–1000.[Medline]
  107. Mock V, Frangakis C, Davidson NE et al. Exercise manages fatigue during breast cancer treatment: A randomized controlled trial. Psychooncology 2005;14:464–477.[CrossRef][Medline]
  108. Mustian KM, Katula JA, Gill DL et al. Tai Chi Chuan, health-related quality of life and self-esteem: A randomized trial with breast cancer survivors. Support Care Cancer 2004;12:871–876.[CrossRef][Medline]
  109. Na YM, Kim MY, Kim YK et al. Exercise therapy effect on natural killer cell cytotoxic activity in stomach cancer patients after curative surgery. Arch Phys Med Rehabil 2000;81:777–779.[Medline]
  110. Nieman DC, Cook VD, Henson DA et al. Moderate exercise training and natural killer cell cytotoxic activity in breast cancer patients. Int J Sports Med 1995;16:334–337.[Medline]
  111. Oldervoll LM, Kaasa S, Knobel H et al. Exercise reduces fatigue in chronic fatigued Hodgkin's disease survivors—results from a pilot study. Eur J Cancer 2003;39:57–63.[CrossRef][Medline]
  112. Peters C, Lotzerich H, Niemeier B et al. Influence of a moderate exercise training on natural killer cytotoxicity and personality traits in cancer patients. Anticancer Res 1994;14:1033–1036.[Medline]
  113. Peters C, Lotzerich H, Niemeir B et al. Exercise, cancer and the immune response of monocytes. Anticancer Res 1995;15:175–179.[Medline]
  114. Petersson LM, Nordin K, Glimelius B et al. Differential effects of cancer rehabilitation depending on diagnosis and patients' cognitive coping style. Psychosom Med 2002;64:971–980.[Abstract/Free Full Text]
  115. Pickett M, Mock V, Ropka ME et al. Adherence to moderate-intensity exercise during breast cancer therapy. Cancer Pract 2002;10:284–292.[CrossRef][Medline]
  116. Pinto BM, Clark MM, Maruyama NC et al. Psychological and fitness changes associated with exercise participation among women with breast cancer. Psychooncology 2003;12:118–126.[CrossRef][Medline]
  117. Pinto BM, Goldstein MG, Ashba J et al. Randomized controlled trial of physical activity counseling for older primary care patients. Am J Prev Med 2005;29:247–255.[Medline]
  118. Porock D, Kristjanson LJ, Tinnelly K et al. An exercise intervention for advanced cancer patients experiencing fatigue: A pilot study. J Palliat Care 2000;16:30–36.[Medline]
  119. Schwartz AL. Fatigue mediates the effects of exercise on quality of life. Qual Life Res 1999;8:529–538.[CrossRef][Medline]
  120. Schwartz AL, Nail LM, Chen S et al. Fatigue patterns observed in patients receiving chemotherapy and radiotherapy. Cancer Invest 2000;18:11–9.[Medline]
  121. Schwartz AL, Mori M, Gao R et al. Exercise reduces daily fatigue in women with breast cancer receiving chemotherapy. Med Sci Sports Exerc 2001;33:718–723.
  122. Schmitz K, Ahmed RL, Hannan PJ et al. 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.[Abstract/Free Full Text]
  123. Segal R, Evans W, Johnson D et al. Structured exercise improves physical functioning in women with stages I and II breast cancer: Results of a randomized controlled trial. J Clin Oncol 2001;19:657–665.[Abstract/Free Full Text]
  124. 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.[Abstract/Free Full Text]
  125. Segar ML, Katch VL, Roth RS et al. The effect of aerobic exercise on self-esteem and depressive and anxiety symptoms among breast cancer survivors. Oncol Nurs Forum 1998;25:107–113.[Medline]
  126. Sharkey AM, Carey AB, Heise CT et al. Cardiac rehabilitation after cancer therapy in children and young adults. Am J Cardiol 1993;71:1488–1490.[CrossRef][Medline]
  127. Wall LM. Changes in hope and power in lung cancer patients who exercise. Nurs Sci Q 2000;13:234–242.[Abstract/Free Full Text]
  128. Windsor PM, Nicol KF, Potter J. A randomized, controlled trial of aerobic exercise for treatment-related fatigue in men receiving radical external beam radiotherapy for localized prostate carcinoma. Cancer 2004;101:550–557.[CrossRef][Medline]
  129. Winningham ML, MacVicar MG. The effect of aerobic exercise on patient reports of nausea. Oncol Nurs Forum 1988;15:447–450.[Medline]
  130. Winningham ML, MacVicar MG, Bondoc M et al. Effect of aerobic exercise on body weight and composition in patients with breast cancer on adjuvant chemotherapy. Oncol Nurs Forum 1989;16:683–689.[Medline]
  131. Dimeo FC, Thomas F, Raabe-Menssen C et al. Effect of aerobic exercise and relaxation training on fatigue and physical performance of cancer patients after surgery. A randomised controlled trial. Support Care Cancer 2004;12:774–779.[CrossRef][Medline]
  132. Headley JA, Ownby KK, John LD. The effect of seated exercise on fatigue and quality of life in women with advanced breast cancer. Oncol Nurs Forum 2004;31:977–983.[Medline]
  133. Mustian KM, Katula JA, Zhao H. A pilot study to assess the influence of tai chi chuan on functional capacity among breast cancer survivors. J Support Oncol 2006;4:139–145.[Medline]
  134. Turner J, Hayes S, Reul-Hirche H. Improving the physical status and quality of life of women treated for breast cancer: A pilot study of a structured exercise intervention. J Surg Oncol 2004;86:141–146.[CrossRef][Medline]
  135. Adamsen L, Midtgaard J, Andersen C et al. Transforming the nature of fatigue through exercise: Qualitative findings from a multidimensional exercise programme in cancer patients undergoing chemotherapy. Eur J Cancer Care (Engl) 2004;13:362–370.[CrossRef][Medline]
  136. Crevenna R, Schmidinger M, Keilani M et al. Aerobic exercise for a patient suffering from metastatic bone disease. Support Care Cancer 2003;11:120–122.[Medline]
  137. Dahn JR, Penedo FJ, Molton I et al. Physical activity and sexual functioning after radiotherapy for prostate cancer: Beneficial effects for patients undergoing external beam radiotherapy. Urology 2005;65:953–958.[CrossRef][Medline]
  138. 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.[Abstract/Free Full Text]
  139. Spiegel D, Bloom JR, Yalom I. Group support for patients with meta-static cancer. A randomized outcome study. Arch Gen Psychiatry 1981;38:527–533.[Abstract/Free Full Text]
  140. Forester B, Kornfeld DS, Fleiss JL. Psychotherapy during radio-therapy: Effects on emotional and physical distress. Am J Psychiatry 1985;142:22–27.[Abstract/Free Full Text]
  141. Fawzy FI, Cousins N, Fawzy NW et al. A structured psychiatric intervention for cancer patients. I. Changes over time in methods of coping and affective disturbance. Arch Gen Psychiatry 1990;47:720–725.[Abstract/Free Full Text]
  142. Fawzy NW. A psychoeducational nursing intervention to enhance coping and affective state in newly diagnosed malignant melanoma patients. Cancer Nurs 1995;18:427–438.[Medline]
  143. Gaston-Johansson F, Fall-Dickson JM, Nanda J et al. The effectiveness of the comprehensive coping strategy program on clinical outcomes in breast cancer autologous bone marrow transplantation. Cancer Nurs 2000;23:277–285.[CrossRef][Medline]
  144. Given B, Given CW, McCorkle R et al. Pain and fatigue management: Results of a nursing randomized clinical trial. Oncol Nurs Forum 2002;29:949–956.[Medline]
  145. Jacobsen PB, Meade CD, Stein KD et al. Efficacy and costs of two forms of stress management training for cancer patients undergoing chemo-therapy. J Clin Oncol 2002;20:2851–2862.[Abstract/Free Full Text]
  146. Given C, Given B, Rahbar M et al. Effect of a cognitive behavioral intervention on reducing symptom severity during chemotherapy. J Clin Oncol 2004;22:507–516.[Abstract/Free Full Text]
  147. Barsevick AM, Dudley W, Beck S et al. A randomized clinical trial of energy conservation for patients with cancer-related fatigue. Cancer 2004;100:1302–1310.[CrossRef][Medline]
  148. Sherwood P, Given BA, Given CW et al. A cognitive behavioral intervention for symptom management in patients with advanced cancer. Oncol Nurs Forum 2005;32:1190–1198.[CrossRef][Medline]
  149. Given BA, Given CW, Jeon S et al. Effect of neutropenia on the impact of a cognitive-behavioral intervention for symptom management. Cancer 2005;104:869–878.[CrossRef][Medline]
  150. Stanton AL, Ganz PA, Kwan L et al. Outcomes from the Moving Beyond Cancer psychoeducational, randomized, controlled trial with breast cancer patients. J Clin Oncol 2005;23:6009–6018.[Abstract/Free Full Text]
  151. Boesen EH, Ross L, Frederiksen K et al. Psychoeducational intervention for patients with cutaneous malignant melanoma: A replication study. J Clin Oncol 2005;23:1270–1277.[Abstract/Free Full Text]
  152. Williams SA, Schreier AM. The role of education in managing fatigue, anxiety, and sleep disorders in women undergoing chemotherapy for breast cancer. Appl Nurs Res 2005;18:138–147.[CrossRef][Medline]
  153. Brown P, Clark MM, Atherton P et al. Will improvement in quality of life (QOL) impact fatigue in patients receiving radiation therapy for advanced cancer? Am J Clin Oncol 2006;29:52–58.[CrossRef][Medline]
  154. Richardson MA, Straus SE. Complementary and alternative medicine: Opportunities and challenges for cancer management and research. Semin Oncol 2002;29:531–545.[CrossRef][Medline]
  155. Richardson MA, Sanders T, Palmer JL et al. Complementary/alternative medicine use in a comprehensive cancer center and the implications for oncology. J Clin Oncol 2000;18:2505–2514.[Abstract/Free Full Text]
  156. Lee MM, Lin SS, Wrensch MR et al. Alternative therapies used by women with breast cancer in four ethnic populations. J Natl Cancer Inst 2000;92:42–47.[Abstract/Free Full Text]
  157. Yates JS, Mustian KM, Morrow GR et al. Prevalence of complementary and alternative medicine use in cancer patients during treatment. Support Care Cancer 2005;13:806–811.[CrossRef][Medline]
  158. Cohen LW. Psychological adjustment and sleep quality in a randomized trial of the effects of a Tibetan yoga intervention in patients with lymphoma. Cancer 2004;100:2253–2260.[CrossRef][Medline]
  159. Kirk M, Boon B. Hatha Yoga for Greater Strength, Flexibility, and Focus. Champaign, IL: Human Kinetics, 2003.
  160. Saper RB, Eisenberg DM, Davis RB et al. Prevalence and patterns of adult yoga use in the United States: Results of a national survey. Altern Ther Health Med 2004;10:44–49.[Medline]
  161. Bower JE, Woolery A, Sternlieb B et al. Yoga for cancer patients and survivors. Cancer Control 2005;12:165–171.[Medline]
  162. Cohen L, Warneke C, Fouladi RT et al. Psychological adjustment and sleep quality in a randomized trial of the effects of a Tibetan yoga intervention in patients with lymphoma. Cancer 2004;100:2253–2260.[CrossRef][Medline]
  163. Kabat-Zinn J. An outpatient program in behavioral medicine for chronic pain patients based on the practice of mindfulness meditation: Theoretical considerations and preliminary results. Gen Hosp Psychiatry 1982;4:33–47.[CrossRef][Medline]
  164. Speca M, Carlson LE, Goodey E et al. A randomized wait-list controlled clinical trial: The effect of a mindfulness meditation-based stress reduction program on mood and symptoms of stress in cancer outpatients. Psychosom Med 2000;62:613–622.[Abstract/Free Full Text]
  165. Carlson LE, Speca M, Patel KD et al. Mindfulness-based stress reduction in relation to quality of life, mood, symptoms of stress and levels of cortisol, dehydroepiandrosterone sulfate (DHEAS) and melatonin in breast and prostate cancer outpatients. Psychoneuroendocrinology 2004;29:448–474.[CrossRef][Medline]
  166. Carlson WJ, Williams WB, Davol H. A factor structure of child home observation data. J Abnorm Child Psychol 1984;12:245–260.[CrossRef][Medline]
  167. Ravasco P, Monteiro-Grillo I, Vidal PM et al. Dietary counseling improves patient outcomes: A prospective, randomized, controlled trial in colorectal cancer patients undergoing radiotherapy. J Clin Oncol 2005;23:1431–1438.[Abstract/Free Full Text]
  168. Berger AM, Parker KP, Young-McCaughan S et al. Sleep wake disturbances in people with cancer and their caregivers: State of the science. Oncol Nurs Forum 2005;32:E98–E126.[CrossRef][Medline]
  169. Roscoe JA, Kaufman ME, Matteson-Rusby SE et al. Cancer-related fatigue and sleep disorders. The Oncologist 2007;12(suppl 1):35–42.[Abstract/Free Full Text]
  170. Berger A. Treating fatigue in cancer patients. The Oncologist 2003;8:10–14.[Abstract/Free Full Text]
  171. Berger AM, VonEssen S, Khun BR et al. Feasibility of a sleep intervention during adjuvant breast cancer chemotherapy. Oncol Nurs Forum 2002;29:1431–1441.[Medline]
  172. Graydon JE, Bubela N, Irvine D et al. Fatigue-reducing strategies used by patients receiving treatment for cancer. Cancer Nurs 1995;18:23–28.[Medline]
  173. Savard J, Simard S, Ivers H et al. Randomized study on the efficacy of cognitive-behavioral therapy for insomnia secondary to breast cancer, part I: Sleep and psychological effects. J Clin Oncol 2005;23:6083–6096.[Abstract/Free Full Text]
  174. Roscoe JA, Matteson SE, Mustian KM et al. Treatment of radiotherapy-induced fatigue through a nonpharmacological approach. Integr Cancer Ther 2005;4:8–13.[Abstract/Free Full Text]
  175. Cimprich B. Attentional fatigue following breast cancer surgery. Res Nurs Health 1992;15:199–207.[Medline]
  176. Cimprich B. Development of an intervention to restore attention in cancer patients. Cancer Nurs 1993;16:83–92.[Medline]
  177. Cimprich B, Ronis DL. An environmental intervention to restore attention in women with newly diagnosed breast cancer. Cancer Nurs 2003;26:284–294.[CrossRef][Medline]
  178. Moher D, Schulz KF, Altman DG. The CONSORT Statement: Revised recommendations for improving the quality of reports of parallel-group randomised trials. Lancet 2001;357:1191–1194.[CrossRef][Medline]



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