Multicomponent Rehabilitative Intervention

To conduct a systematic review to identify which nursing interventions are used to reduce fatigue caused by cancer treatment and to identify the level of evidence for those interventions.

Databases searched were PubMed and CINAHL (1995–February 2005).

Search keywords were cancer, cancer treatment, chemotherapy, distraction, education, exercise, fatigue, nursing intervention, radiotherapy, and sleep promotion.

Studies were included in the review if 

• The intervention was performed by nurses
• The study was conducted by nurses
• The intervention was performed with adults
• The intervention was performed during cancer treatment.

An initial search was performed to find systematic reviews. No reviews of studies meeting the inclusion criteria were found. A second search to locate intervention studies yielded 192 studies in CINAHL and 78 in PubMed. Screening for inclusion criteria resulted in the identification of 18 studies that were then included in the review. Ten studies reported the effects of exercise, five reported education and counseling, two reported distraction and relaxation, and one reported sleep promotion.

The sample was comprised of 904 patients across 18 studies.

Exercise Studies

• Sample sizes varied from 22 to 119 patients.
• Kind of exercise varied from a seated video exercise program to an aerobic program at home or in a supervised clinic.
• Intensity of exercise varied.
• Patient adherence to exercise programs was a problem, and not all studies accounted for this factor.
• Only five studies divided patients into exercisers and nonexercisers based on usual activity. 
• Five studies demonstrated significant effects in the intervention group.
• One qualitative study was found in which fatigue changed from a negative to a positive experience with exercise, and patients experienced increased physical activity and increased level of energy.

Education and Counseling

• Three studies were randomized, controlled trials (RCTs), one used a pre-/posttest design, and one was longitudinal.
• Information was provided on tape, by telephone, or in person.
• Information was given in 3 to 10 sessions and included information about other symptoms in addition to fatigue in four out of the five studies.
• In two studies, fatigue increased with the intervention, and in three studies, a decrease was found in the experimental group.
• Talking to someone was an important aspect, a trend associated with group interaction was found, and one study found a significant effect over time.

Distraction and Relaxation

• One RCT used relaxation breathing every day for six weeks in patients who received stem cell transplantation. The intervention group experienced significantly less fatigue.
• One crossover design study used virtual reality during intravenous chemotherapy treatment. There was a significant effect, but the posttest was performed immediately after treatment.

Sleep Promotion

• One study used a pre-/posttest design using an individualized sleep promotion plan. No significant effects were found.

Sleep promotion was identified as a promising intervention despite the single study results because other studies have shown a relationship between fatigue and sleep disorders. More research is warranted in this area. Lack of effect seen with education and counseling studies may be due to small sample sizes, lack of equivalent control groups, and lack of sensitivity in fatigue measurement. It is also possible that education alone is not enough to change patient behavior. Exercise is shown to be effective, but nothing is known about the long-term effects of exercise after treatment and whether exercise can prevent the beginning of fatigue. Adherence to exercise programs is an area that requires attention. No data were available regarding the level of activity prior to cancer treatment, which might influence the findings in this area.

• None of the studies used a theoretical framework, likely explained by the fact that no satisfactory theory has been formulated to explain fatigue in this population. Some studies did not even use a definition of fatigue.
• Fatigue was measured differently, and three different measures were used.
• In two-thirds of the studies, the sample was breast cancer patients receiving chemotherapy, limiting the external validity of the findings.
• Half of the studies had very small sample sizes of less than 30 patients.
• Study of distraction and relaxation was limited by the timing of fatigue measurement.
• No long-term effects or ongoing intervention was studied.

There are several promising interventions that can be provided by nurses. It is likely that a combination of interventions may be most helpful for patients. More research is specifically needed on the effects of interventions that enhance the quality of sleep, education, and counseling related to fatigue management and prevention.

STUDY PURPOSE: To summarize evidence regarding rehabilitation interventions to address problems of cancer survivors

TYPE OF STUDY: Systematic review

DATABASES USED: PubMed, EMBASE, CINAHL, Scopus, Google Scholar

INCLUSION CRITERIA: Effectiveness of treatment that could be provided by rehab professionals, subjects 18 years or older, cancer survivors (defined as having completed primary treatment). Reports on only systematic reviews and RCTs, though these were not identified as criteria.  

EXCLUSION CRITERIA: Pharmaceutical, surgical, or radiological interventions

TOTAL REFERENCES RETRIEVED: Not stated

EVALUATION METHOD AND COMMENTS ON LITERATURE USED: No quality rating applied. Appears to have very few studies in multiple areas.

• FINAL NUMBER STUDIES INCLUDED =  56
• SAMPLE RANGE ACROSS STUDIES, TOTAL PATIENTS INCLUDED IN REVIEW: Not provided
• KEY SAMPLE CHARACTERISTICS: Not provided

PHASE OF CARE: Transition phase after active treatment

• Reviews seven systematic reviews and six RCTs regarding impact of exercise on fatigue
• States that results confirm a positive effect on fatigue for rehab therapies
• Some of these studies included acupuncture, counseling, and mindfulness-based stress reduction therapy

Evidence supports the effectiveness of exercise-based interventions in managing fatigue among cancer survivors.

• No quality rating of studies
• Limited studies included, and it is not clear how these were selected
• Study findings are grouped by problem, rather than synthesizing evidence related to specific interventions (for example, combining effects of exercise and acupuncture interventions)

The review provides limited information to assess efficacy of specific interventions. Studies reviewed here do not add further to the body of knowledge overall, and the report is aimed at identifying interventions that can be provided by rehabilitation professionals rather than synthesis of intervention evidence.

STUDY PURPOSE: To conduct a systematic review of studies examining the impact of multidimensional rehab programs

TYPE OF STUDY: Meta-analysis and systematic review

DATABASES USED: MEDLINE, EMBASE, CINAHL through February 2012, Cochrane Register of Controlled Trials (CENTRAL)

KEYWORDS: Extensive listing of search terms per database is provided.

INCLUSION CRITERIA: RCT or quasi RCT, interventions included a physical and psychological component, sample is adults who have completed cancer treatment, at least two treatments of the intervention were provided

EXCLUSION CRITERIA: Not specified

TOTAL REFERENCES RETRIEVED: 25,824

EVALUATION METHOD AND COMMENTS ON LITERATURE USED: Used a checklist of study characteristics for risk of bias. Nine studies had insufficient information to evaluate risk of bias.

• FINAL NUMBER STUDIES INCLUDED = 12 (6 studies that used the SF36 for outcome measures were included in meta-analysis)
• SAMPLE RANGE ACROSS STUDIES: 24–543
• TOTAL PATIENTS INCLUDED IN REVIEW = 1,669
• KEY SAMPLE CHARACTERISTICS: Prostate and breast cancer were most prevalent patient types. One study involved head and neck, and four studies included multiple cancer types.

Two studies showed no benefit of the intervention, seven showed benefit in one domain, and three reported significant improvement in physical and psychosocial domains. Three studies specifically reported fatigue outcomes with combinations of CBT or psychoeducational and exercise interventions. All of these had moderate-to-high risk of bias. Duration of interventions that was longer than 12 weeks showed no additional improvement over interventions delivered up to 12 weeks. Interventions delivered face-to-face appeared to be more effective, and additional telephone follow-up “boosters\" improved results. Meta-analysis of physical and mental components of SF36 measures showed no statistically significant overall effect of the intervention. The nature, timing, and duration of interventions varied substantially across studies.

There is insufficient evidence to assess the efficacy of multidimensional rehab programs to improve fatigue in individuals with cancer. Programs with a single focus may be more successful in improving outcomes that are the focus of the intervention. Face-to-face delivery with follow-up boosters appear to be most effective.  Beneficial effects seen appear to plateau after about six months.

Meta-analysis was possible on only a few studies. Few studies used objective measures of physical component outcomes. Program adherence by patients was not often reported in studies.

Findings here do not show sufficient evidence to fully evaluate the effectiveness of multidimensional rehab programs to improve fatigue or physical and psychological outcomes for cancer survivors. Such programs may have short-term benefit for some patients, and it appears that interventions delivered face-to-face with follow-up may be more effective.

To evaluate whether a six-week supervised multimodal exercise intervention can reduce cancer-related fatigue levels.

The intervention involved having patients exercise for 2.25 hours for four days per week for a total of six weeks in a group session of dynamic exercises using heavy resistance, cardiovascular training, relaxation techniques, body awareness (i.e., stretching, breathing, yoga, and Pilates), and massage.  The study was wait-list controlled.

• The sample was comprised of 213 patients.
• Mean age was 47.5 years (range 20–65).
• In the control, 28% of patients were male and 72% were female. In the intervention, 20.8% of patients were male and 79.2% were female. 
• Mean days since diagnosis was 82/86.5, and 52% to 58% of patients had no evidence of disease at baseline.
• Of the patients, 103 had breast cancer and 29 had bowel cancer.
• Of the patients, 83.7% of the control and 82.7% of the intervention reported some kind of exercise at baseline.

• Single site 
• Outpatient 
• Copenhagen

Patients were undergoing the active antitumor treatment phase of care. 

This was a randomized, controlled trial.

Functional Assessment of Cancer Therapy-Anaemia Questionnaire (FACT-An) 

Improvement occurred in fatigue score in the intervention compared to the control (p = 0.002; effect size = 0.44).  FACT-An subscale score (13 items were related to fatigue, and seven were indirectly related) was also improved in the intervention compared to the control (p = 0.015). FACT-An improved (p = 0.009), and Anemia-ANS improved (p = 0.002). Well-being scores of Quality of Life (QOL) scores showed no difference.

Supervised exercise can have an effect on fatigue levels for patients during chemotherapy. Specific diagnoses and fatigue after treatment were not evaluated.

• There were risks of bias due to no blinding, lack of an appropriate attentional control condition, and sample characteristics [patients were self-referred to the program, suggesting a highly motivated group]).
• Participant withdrawals were 10% or greater.

 Patients experiencing fatigue during active treatment may benefit from supervised multimodal exercise.

To assess feasibility and effects of an inpatient rehabilitation program on symptoms and physical function

Participants attended three weeks of inpatient rehabilitation and a follow-up five-day stay 8–12 weeks later. All attended group programs, which included physical training and education following cognitive behavioral approaches. Physical training was done twice a day for 60–120 minutes.

• N = 131
• AGE: 14% were 25–44 years old, 86% were greater than or equal to 45
• MALES: 23%, FEMALES: 77%
• KEY DISEASE CHARACTERISTICS: Participants had multiple tumor types, although breast and GI were most common.
• OTHER KEY SAMPLE CHARACTERISTICS: All had high school education, and 66% had some college education. Time since diagnosis was less than two years in 72%. Thirty percent were working full-time or part-time.

• SITE: Single site  
• SETTING TYPE: Inpatient  
• LOCATION: Norway

• PHASE OF CARE: Multiple phases of care

• Quasiexperimental

• EORTC Cancer Quality of Life Core 30 (EORTC–QLQ-C30) questionnaire
• Fatigue questionnaire
• Physical activity questionnaire
• Maximal oxygen consumption test (Vo₂ max test)
• Sit-to-Stand Test (SST)
• Maximum step length

Multiple symptoms showed decline. These were statistically significant; however, the degree of change seen from the end of the initial three weeks to the final measure was less than that which the authors identified as clinically relevant. Fatigue scores increased from baseline to postintervention measures (8.9–9.3 for physical fatigue and 4.9 for mental fatigue at both time points). All symptoms declined from baseline over time.

Findings suggest that a multicomponent rehabilitation program can improve multiple symptoms for patients with cancer.

• Risk of bias (no control group)
• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• Risk of bias (sample characteristics)
• Subject withdrawals of 10% or greater 
• Dropouts tended to be those with lower education levels, and significantly more males dropped out.
• The sample was self-selected.
• Lack of a control group does not enable determination if changes seen were due only to time, as it is known that many symptoms decline over time. 
• Authors noted that the three-week program was very resource intensive.  

Findings showed improvement of multiple symptoms after a three-week inpatient rehabilitation program. This was resource intensive and had many dropouts, causing one to question the practicality and cost-effectiveness of this approach. This study is limited by its design, with lack of a control group.

To describe the feasibility of delivering a structured physical therapy (PT) program as part of a multidisciplinary intervention to patients undergoing outpatient radiotherapy for advanced cancer.

Patients were randomly assigned to receive the structured intervention or standard care using a stratified approach based on Eastern Cooperative Oncology Group (ECOG) performance status, age, sex, and tumor type. The structured multidisciplinary intervention consisted of eight sessions delivered by a PT and a psychiatrist or a psychologist with facilitation provided by an advanced practice nurse, licensed social worker, or certified hospital chaplain depending on the theme. Cognitive, emotional, social, and spiritual dimensions of the intervention centered on specific topics and coping strategies related to patients' goal setting, challenging negative thoughts, communication, and hope. PT sessions incorporated education and provision of printed material, truncal and upper-limb strengthening exercises, and lower-limb strengthening alternating between standing and seated exercises. These were performed with resistance provided by elastic bands. Aerobic conditioning was not included, although patients were encouraged to engage in regular physical activity. Standard care consisted of regular assessment of treatment toxicities. Patients were not counseled regarding the potential benefits of exercise.

This report focused on the PT and interdisciplinary structured intervention aspects of a previously reported study (Rummans et al. 2006).

• The study was comprised of 103 patients (59%–69% male) receiving radiotherapy for two weeks or longer who received no more than one treatment at the time of study entry.
• Age was 59.4–59.7 years. 
• The highest percentage of patients had gastrointestinal cancer; the sample also included head and neck, lung, brain, and other cancers
• Of the patients, 59%–63% were also receiving chemotherapy, 78%–89% were married, 32% were fully active performance status, and 55% were currently employed.
• Patients were included if they had an ECOG performance status of three or greater and had recurrent disease following a six-month disease-free survival.
• Radiation doses ranged from 3000 to 7200 cGy.

• Single site
• Mayo Clinic

The study was a single-blind, randomized, controlled trial.

• Spitzer Uniscale used for quality of life (QOL) measurement
• Linear analog scales (0–10) for self-assessment of physical well-being and fatigue. These scores were subsequently converted to a 100-point scale.
• Profile of Mood States (POMS) Short Form Vigor and Fatigue subscales
• 30-minute walk

• Six patients were not eligible for analysis due to missing more than four PT sessions.
• Attendance rates for the entire cohort were 89.3%.
• Mean scores after approximately one week of the intervention differed significantly between the intervention and control groups only in overall physical well-being (p = 0.02).
• Changes from baseline were not different between the two groups in any measure at weeks 8 and 27.
• Approximately half of the intervention group declined functionally despite participation in the structured program.

The structured intervention appeared to provide short-term improvement in overall perception of well-being; however, this effect was not sustained over the duration of the trial.

• No commonly used fatigue measures were reported.
• The authors reported improvement in fatigue; however, the measure was actually patient perception of overall well-being.
• There was no attentional control group for comparison.
• The 50% decline in function for patients in the intervention group points to the need to determine which patients might benefit the most from such an intervention and what type of exercise or combined intervention is most effective.
• The study assessed subjective physical well-being rather than objective performance or the specific phenomenon of fatigue.

To assess feasibility and effectiveness of aquatic-based exercise in the form of deep water running as part of a multimodal physiotherapy program for breast cancer survivors in an effort to decrease cancer-related fatigue

Eight week program of one hour sessions, three times per week, of multimodal physiotherapy program combined with deep water running delivered by physiotherapists in groups of 8–10 participants. Each session included 30 minutes of land-based exercise, followed by 20 minutes of deep water running.

• N = 42  
• MEAN AGE = 47.27 years for the intervention group and 48.67 years for the control group
• FEMALES:100%
• KEY DISEASE CHARACTERISTICS: Patients were within one year of breast cancer diagnosis, were aged 25–65 years, and post-cancer treatment within past six months.
• OTHER KEY SAMPLE CHARACTERISTICS: Patients were excluded if they had a fear of aquatic exercise.

• SITE: Multi-site  
• SETTING TYPE: Outpatient  
• LOCATION: Two primary care centers in Andalusia, Spain

• PHASE OF CARE: Transition phase after active treatment

• Non-randomized study with a wait-list control group 
• Outcomes were measured/evaluated by one assessor who was blinded to participant group allocation.

• Piper Fatigue Scale–Revised
• SF-12 Health Survey
• European Quality of Life (five dimensions)
• European Visual Analog Scale

Statistically significant differences in fatigue were found between groups after eight weeks, with the intervention group reporting greater improvement in behavioral severity, affective/meaning, and sensory fatigue.

Demonstrated positive effects of exercise on cancer-related fatigue. Supports prior studies that demonstrated greater improvement combining educational and exercise programs

• Small sample (< 100)
• Risk of bias (no random assignment)
• Intervention expensive, impractical, or training needs existed
• No long-term follow-up

This is a difficult program to replicate, but it appears that it is likely to be effective in reducing cancer-related fatigue.

To investigate the effects of a physical activity intervention for men receiving androgen deprivation therapy (ADT) on physical activity behavior, quality of life (QOL), and fitness.

Patients were randomly assigned to either the intervention or a wait-list control group. Assessments were performed in both groups at baseline, after completion of the 16-week activity intervention, and two and six months postintervention. The exercise program included a home-based portion and weekly group sessions of an individualized program provided by a certified fitness professional. Exercises were tailored to ability but consisted mostly of walking, stretching, and resistance exercises with a Thera-Band. A physioball and Thera-Band were provided to each patient for use in the home-based activity. Home exercise was suggested three to five times per week. Group sessions were conducted weekly for 16 weeks and monthly thereafter until completion of all follow-up measures. These included a group-based workout with individualized feedback, education, and group discussion. Discussion focused on common concerns, goal setting, monitoring behavior, overcoming barriers, role of a positive attitude, social support, relapse prevention, and nutrition.

• One hundred patients were randomized, and 66 completed the study.
• Mean age was 67.6 years (standard deviation = 8.6 years). 
• Patients had any stage of prostate cancer and were expected to receive ADT for at least six months.
• Patients with a high risk of osteoporosis were excluded (long-term steroid use or a T-score less than –2.5 on bone mineral densitometry).
• Of the patients, 88% were married and 61% were retired.
• Patients were recruited between 2004 and 2006 and had physician clearance to participate in the exercise program.

• Single site
• Calgary, Canada

The study used a randomized, controlled, repeated measures design.

• European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30)
• Expanded Prostate Cancer Index Composite (EPIC):  This instrument assesses function and bother in three organ systems:  sexual, urinary, and bowel, and has recently expanded to include possible effects of ADT. The test retest reliability and internal consistency is reported to be high for the urinary, bowel, sexual, and hormonal domain summary scores (r ≥ 0.80; α ≥ 0.82).
• Fatigue Severity Scale (FSS)
• Center for Epidemiologic Studies Depression scale (CESD)
• Godins’ leasure score index (LSI) of Godin’s leisure time exercise questionnaire:  a three-item measure assessment of frequency of exercise
• Fitness assessment, including resting heart rate, blood pressure, six-minute walk, grip dynamometer, and flexibility by testing modified sit and reach
• Body mass index (BMI)
• Baseline bone densitometry
• Variety of bloodwork

• Of the patients, 34% dropped out.
• LSI scores pre- to postintervention showed a significant interaction effect (p = 0.004) with the intervention group reporting increased physical activity and the controls reporting decreased levels.
• No significant changes were seen in QOL measurements.
• Of the patients who dropped out, 67% were in the wait-list control group. In the intervention group, 10 patients withdrew; five of these withdrew for medical reasons.
• Attendance for group sessions was 77.8%, with attendance on average at 12 of 16 sessions.
• At baseline, both groups had similar BMI measures and were considered in the overweight category. After the program, the intervention group had a very slight decrease in average BMI (change of –0.23), whereas the controls showed an average increase to 29.04 (change of 0.75), just below the level that differentiates overweight from obesity.
• In the intervention group, there were nonsignificant improvements seen in depression over time; however, the intervention group had a higher level of depression at baseline than the control group.
• There were no significant changes in fatigue scores over time or between groups.

The physical activity intervention was associated with an overall increase in reported physical activity. There were no significant effects seen in QOL or fatigue.

• The high drop-out rate reduced the statistical power of the study, which may have resulted in an inability to detect significant differences between groups.
• No mechanism was used to evaluate patient adherence to the home-based part of the program.
• The study lacked an attentional control.
• There may have been sample selection bias because individuals interested in or already having a more active lifestyle may be more likely to participate in this type of program, so any results seen cannot be attributed to solely to the program.
• The duration of the intervention may not have been sufficient to see significant changes in the outcome measures.
• The study demonstrated that maintaining involvement and adherence to exercise in this patient population is challenging.
• The findings showed that additional studies of the use of exercise in various patient types should continue because effects and issues seen in this study differ somewhat from those in other patient groups.

The primary aim was to evaluate the effectiveness of a home-based exercise training intervention called the Pro-self:  Fatigue Control Program on the management of cancer-related fatigue (CRF). The secondary aim was to study the effects of the intervention on sleep disturbance, depression, and pain.

Patients were randomized to one of three groups. Two groups received a home-based prescription for exercise called the Pro-self:  Fatigue Control Program (during and after cancer treatment). One of these groups had follow-up. The third group received usual care. All patients completed four valid and reliable tools at baseline, the week before the second chemotherapy treatment, at the end of cancer treatment, and at the end of the study (about one year after the start of the study). The tools measured fatigue, sleep disturbance, depression, and pain and were analyzed to compare how fatigue and other study variables had changed over time and by groups. It was a randomized, single-blind, three-arm, controlled trial design.

• The sample was comprised of 119 women.
• Patients had to be 18 years or older to enroll.
• Mean age was 50.5 years.
• Patients had colon (n = 1), ovarian (n = 6), and breast (n = 112) cancer.
• Patients had a mean education of 16.1 years. 
• Mean Karnofsky Performance Status (KPS) was 87.63. 
• A mean of 94 patients were employed.

• Setting Type1:  Multisite
• Setting Type2:  Outpatient setting
• San Francisco Bay Area

The study was a randomized, controlled trial (RCT).

• Piper Fatigue Scale (PFS) (α range .96–.97)
• General Sleep Disturbance Scale (GSDS) (α range .83–.86)
• Center for Epidemiologic Studies Depression Inventory (CESD) (α range .80–.89)
• Worst of Pain Intensity Scale
• KPS
• Intervention Framework:  Pro-self:  Fatigue Control Program based on self-care and adult learning theory
• Data Analysis used SPSS version 15, two-tailed tests and multilevel regression analysis. 

Change in fatigue did not change over time. No significant change in fatigue occurred among groups.

The home-based exercise intervention had no effect on fatigue or related symptoms associated with cancer treatment. The optimal timing of exercise remains to be determined.

When the study was conducted, the benefits of exercise were being reported in the literature and patients could not be asked to stop their regular exercise. The PFS was administered only three times a year, which might not be frequent enough to capture the true effect of exercise on CRF. The self-report of exercise behaviors was obtained with no objective measures.

CRF is a common problem. Some physical activity is better than none, and there is no harm in exercise as tolerated during cancer treatment. More frequent assessments of fatigue, sleep disturbance, depression, and pain may capture the effect of exercise.

To evaluate the degree to which a multi-component rehabilitation program improves symptom control and quality of life in patients with advanced cancer

The intervention was a 10-12 week program offered by a multidisciplinary team, consisting of nutritional counseling, a collaborative care plan based on patient goals, a palliative care physician specialist focused on symptom-related medical interventions, a pivot nurse for care coordination and case management, and an exercise component with semi-weekly exercise sessions with a physical therapist and a home exercise plan. Occupational therapy was provided and focused on self care, leisure, and productivity. Patients were assessed at baseline and during their final clinic visit at the end of the study.

• N = 131  
• MEAN AGE = 59.9 years (SD = 13.0 years)
• MALES: 50.4%, FEMALES: 49.6%
• KEY DISEASE CHARACTERISTICS: All had stage III and IV disease with a variety of primary tumor types including both hematologic and sold tumors.
• OTHER KEY SAMPLE CHARACTERISTICS: 38% were on current chemotherapy; most had ECOG performance status of 1 or 2.

SITE: Single site  

SETTING TYPE: Outpatient  

LOCATION: McGill University Cancer Center, Montreal, Canada

Quasi-experimental

Change in symptom severity was analyzed and Cohen’s d was used to calculate effect size. Severity of depression from ESAS declined (p <. 0001, d = 0.7); anorexia declined (p < .0001, d = .4);  pain declined (p < .0001, d = .4); physical and general fatigue declined (p < .0001, d = .7); mental fatigue declined (p < .0005, d = .4); and level of distress and difficulty coping declined (p < .0001).

The multi-component rehabilitation program provided here resulted in a significant improvement in multiple symptoms and a reduction in distress and difficulty coping.

• Risk of bias (no control group)
• Risk of bias (no blinding)
• Risk of bias (no random assignment) 
• Risk of bias (no appropriate attentional control condition)  
• Unintended interventions or applicable interventions not described that would influence results
• Subject withdrawals ≥ 10%
• Other limitations/explanation: 30% of patients withdrew from the study–the majority of these were due to death or disease progression. No information is provided about medication changes over the course of the study that might affect outcomes measured. The report states some different results in the body of the article versus tables provided.

A multi-component, multi-disciplinary rehabilitation and palliative care program can provide effective improvement of multiple symptoms in patients with advanced disease.

To explore the effects of a prostate-specific program on physical activity, fatigue, mental distress, and quality of life (QOL).

Courses were conducted by a multidisciplinary team, including lectures, physical activity, and group sessions, lasting for six days. Activity was performed in groups of six to nine patients twice daily, including water gymnastics, walking, Nordic walking, resistance training, pelvic floor training, stretching, and relaxation for 60 to 90 minutes. Group sessions met for one hour daily and were led by a nurse with experience in group counseling. Lectures involved presentation of medical facts, treatment modalities, late effects, and social and other benefits of physical activity. Study measurements were obtained at baseline and at three-month follow-up.

• Sixty-eight patients (100% male) were included, and 51 completed the entire program. 
• Mean age was 67.4 years (range 48.5–81.2).
• All patients had prostate cancer.
• Of the patients, 14% had metastatic disease, 43% had undergone surgery and radiotherapy, 20% had received radiotherapy, and 16% had received hormonal therapy.
• Median time since diagnosis was 18.2 months.
• Most patients were retired, 50% had completed college education, and 86% were married or cohabitating.

• Single site
• Inpatient
• Norway

Patients were undergoing the active treatment phase of care.

This was a prospective, observational study.

• Godin Leisure-Time Exercise Questionnaire
• Fatigue Questionnaire (physical score range 0–21; mental score range 0–12)
• Memorial Anxiety Scale for Prostate Cancer (MAX-PC)
• Hospital Anxiety and Depression Scale (HADS)
• European Organization for Research and Treatment of Cancer Quality of Life (EORTC QLC-C30 QOL) scale

Total fatigue scores declined from 16.1 to 14.0 (p = 0.001), and physical fatigue declined from 11.1 to 9.2 (p = 0.001). Those who did not complete the entire program had higher baseline fatigue scores. Anxiety results were mixed:  anxiety declined on the prostate specific measure (p = 0.001), but there was no change on the HADS scale. QOL measures did not change significantly.

Although there was a significant reduction in fatigue, the degree of change was small (2 of 33 points possible). The study did not provide strong support for the effectiveness of this program.

• The study had a small sample size, with less than 100 patients.
• No control or comparison group was used.
• The sample was highly variable in terms of the age range, and the rehabilitative needs of younger patients who may have undergone curative surgery can be expected to be different than those of older patients; this was not analyzed.
• Use of an inpatient setting for six days for this type of program can be expected to be expensive.
• Time from surgery to study entry varied, and final measures were three months after the program, with no interim assessment; it is not clear what the best timing of such interventions are in the disease trajectory.
• There was no information regarding continued activity prior to the final study measures being obtained.

The results suggested a small effect of this type of program on fatigue and no significant impact on overall anxiety or QOL.

To evaluate the effectiveness of a comprehensive exercise program consisting of low-to-moderate intensity aerobic and resistance exercise twice a week for 16 sessions to assess improvements in physical function, fatigue, and mood.

Patients received low-to-moderate aerobic and resistance exercise, education, and support twice weekly. At the start of each session, a specialist obtained blood pressure, oxygen saturation, and heart rate for each patient. Patients performed aerobic exercise on a seated machine or treadmill. Progression was obtained through increased exercise duration by adding small increments of three to five minutes per session as tolerated. All patients were able to progress to 40 minutes of aerobic exercise before the end of 16 sessions. Education included various topics focused on symptom management, coping, and wellness, including support groups, survivorship, resources, spirituality, stress management, chemotherapy, radiation, nutrition, energy conservation, relaxation and imagery, drugs and herbs, fatigue and pain, humor therapy, exercise safety and benefits, diagnostic testing, communication issues, financial issues, complementary therapy, and infection control. Average attendance per month was 12 sessions. Support included peer support, exercise environment conducive to discussion within the group, and facilitation of relationships of sharing and encouragement. The specialist inquired about how patients were coping with their disease, side effects, and treatments.

• The sample was comprised of 39 patients (77% female) in active treatment and cancer survivors beyond treatment.
• Patients were older than 18 years. Mean age was 63 years (range 42–87 years; standard deviation = 10.61 years).
• Patients had 13 different cancer types, with the majority being breast cancer (39%). The most common diagnosed stage was stage III (26%); patients also had stage I (23%), stage II (21%), and stage IV (14%) cancer. One patient had ductal carcinoma in situ (DCIS) of the breast. 
• Of the patients, 24% stated that exercise was new to them and 30% indicated that exercise was not at all new to them.

• Single site
• Cancer Center in a 350-bed teaching hospital in east central Indiana

The study was a retrospective analysis of archived data. Patients were eligible if they had a diagnosis of cancer; type and age of diagnosis were not factors.

• Six-minute walk test
• Profile of Mood States (POMS) Questionnaire to evaluate personal and social integrity
• Piper Fatigue Scale (PFS) Questionnaire to measure conservation of energy pre- and postprogram
• The main variables were physical function, fatigue, and mood.

• Pre- and postprogram outcome measures had significant differences (p < 0.05). Patients had significant improvements in physical function, fatigue, and mood.
• Change in fatigue:  On average, patients reported less fatigue on the PFS compared to before the program. Of the sample, 75% improved and 25% stayed the same.
• The study had a small sample size.
• No control comparison was used.

A comprehensive exercise program consisting of low-to-moderate intensity aerobic and resistance exercise, education, and support twice a week for eight weeks resulted in significant improvements in physical function, fatigue, and mood in patients in active treatment and in cancer survivors beyond treatment.

• The study lacked a control group and uniformity. However, the heterogenicity of the group demonstrated that, regardless of diagnosis and stage, improvements can be achieved.
• Of the patients, 69% had a break in exercise consistency.
• Educational sessions were optional, and not all patients attended educational sessions regularly; therefore, the direct role of education on outcome is unknown.

Further studies may need to be conducted comparing the degree of benefit achieved by patients in a comprehensive program versus a single-component exercise or support group program. The study encouraged the use of low-to-moderate intensity exercise to benefit people with all types of cancer. Further studies need to be completed to determine the best mode, duration, and intensity of exercise for survivors. The authors can say with some certainty that low-to moderate intensity exercise produces significant benefits for people with cancer without causing participant overload or drop-out.

To evaluate the effects of a rehabilitation program on quality of life (QOL), fatigue, fear of movement (kinesiophobia), distress, anxiety, depression, and physical condition.

The intervention consisted of a 12-week comprehensive rehabilitation program based on Herstel and Balans’s 12-week program. The program combined physical exercise, psychoeducation, and individual counseling. Each component consisted of 

• Physical training to enhance cardiorespiratory and muscular capacity. Physical training occurred three times a week for 60 minutes and was led by an expert physiotherapist.
• Psychoeducation to enhance self-confidence, autonomy, and coping skills. Psychoeducation occurred eight times. Each session lasted 90 minutes.
• Individual counseling to improve patients' follow-up and provide an individualized program. Individual counseling consisted of a 10-minute session at the start of the program, at the beginning of every exercise session, and at the end of the program.

The intervention was provided at no cost to patients.

• The sample was comprised of 36 patients (83% female, 17% male).  
• Mean age was 50 years (standard deviation [SD] = 12 years; range 28–75 years).
• The majority of patients (n = 27) had breast cancer.
• Patients had completed all cancer treatments, except long-term hormone treatment. Patients had received diverse treatments (i.e., chemotherapy, radiotherapy, surgery, and biotherapy) before the intervention.
• Time lapse since the last treatment varied, with a mean of nine months (SD = 14 months; range 0–60 months).
• Twenty patients were on hormone treatment during the intervention.

• Single site
• Outpatient
• University hospital in Belgium

• Patients were undergoing the transition after initial treatment phase of care.
• The study has clinical applicability for late effects and survivorship.

The study used a prospective, one-group pre-/posttest design.

• European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30), to measure global QOL and physical functioning and condition
• Functional Assessment of Cancer Therapy–Fatigue (FACT-F), to measure fatigue
• Hospital Anxiety and Depression Scale (HADS), to measure depression and anxiety
• RAND 36-Item Health Survey (RAND-36), to measure general health-related QOL
• Tampa Scale of Kinesiophobia, to measure fear of movement or injury
• Distress Barometer, to measure distress
• Tecumseh Step Test, to measure cardiorespiratory fitness

• The authors noted significant improvements in QOL (p < 0.001), physical condition (p = 0.007), fatigue (p = 0.01), and depression (p = 0.012).
• Kinesiophobia (p = 0.229), distress (p = 0.344), and anxiety (p = 0.101) did not change significantly.
• In regard to depression, HADS scores changed from 5.71 (SD = 4.7) to 4.13 (SD = 4.36). This change was statistically significant.

The rehabilitation program was associated with a positive effect on depression, fatigue, and QOL; however, weaknesses in study design may preclude making a definitive conclusion based on the study. Prospective randomized studies must determine the long-term impact and the relative contribution of the program versus spontaneous recovery. Future research should also consider the cost-effectiveness of the rehabilitation program.

• The small sample size and nature of the sample (i.e., patients with early stage breast cancer) threaten the external validity of the study.
• The study did not include an appropriate control group. The lack of control group threatens the internal validity of the study. Thus, statistically significant effects may be placebo effects or time effects.
• The study did not include information regarding the scale and range of scores and method of score computation; therefore, the credibility of analysis based on the scores is unknown.
• The authors did not report whether patients were clinically depressed and if the improvement in the depression score indicates a clinically significant change.
• For various reasons, more than half (51%) of the patients who had an intake interview did not participate in the study. This may generate problems associated with the applicability of the program to patients with cancer.

Multidisciplinary rehabilitation can be one way to manage depression and fatigue in patients with cancer.

Intervention consisted of physiotherapy, group exercises, and psycho-oncologic interventions. Patients received a brochure with instructions for nine muscle strength and nine stretching exercises for large muscle groups. Outcomes were assessed at baseline, start of intervention (T1), end of intervention (T2), and at a three-month follow-up (T3).

• N = 63
• AGE: In the intervention group, 56% were aged 51–70 years
• KEY DISEASE CHARACTERISTICS: Patients with breast cancer with cancer-related chronic fatigue
• OTHER KEY SAMPLE CHARACTERISTICS: Control group patients were slightly younger, but otherwise both groups were well balanced. Intervention group: 56% married, 59% working, most patients had received chemotherapy (66%) and radiation therapy (81%), and 78% received hormonal therapy
• EXCLUSION CRITERIA: Evidence of psychiatric disease or patients who were less than six weeks to preceding surgery or chemotherapy

• PHASE OF CARE: Active treatment, inpatient rehabilitation

• Randomized controlled trial
  • Structured physical training intervention (N = 32)
  • Control (N = 31)

• Linear analogue scale (LASA)
• Multidimensional Fatigue Inventory (MFI)
• Functional Assessment of Cancer Treatment (FACT)

Trial outcome index for fatigue in the FACT-F questionnaire showed improvement in fatigue from T1–T3. The interaction of time and group were statistically significant (p = 0.003). For MFI measures, interaction between group and time effects was significant for physical fatigue between T2–T3 (p = 0.028). The mean MFI total score was higher for both the control and intervention group in comparison to the mean MFI total score for healthy women in the age group of 40–50 years at the three-month follow-up.

• Small sample size

Future research should incorporate better measures for the intensity of the exercise.

To evaluate whether pre- and postoperative physical exercise affect quality of life and symptoms in patients undergoing radical cystectomy

Patients were randomized to a standard care or intervention group. Standard care included preoperative nutritional screening counseling and the use of oral supplements as needed, patient education, and standard mobilization postoperatively by walking during each shift with supervision once daily. The intervention included all aspects of standard care plus a preoperative exercise program and a more comprehensive postoperative exercise program with related patient education 14 days prior to surgery. Prior to surgery, a phone call after one week was done to promote adherence to the program. Postsurgery, the intervention group had physical therapy sessions two times per day including progressive muscle strength and endurance training. The difference between groups at four months after the intervention were reported.

• N = 100
• MEAN AGE = 70 years (range = 46–91 years)
• MALES: 66%, FEMALES: 34%
• KEY DISEASE CHARACTERISTICS: All had surgery for urinary diversion
• OTHER KEY SAMPLE CHARACTERISTICS: 57% married and living with a partner

• SITE: Single-site  
• SETTING TYPE: Multiple settings  
• LOCATION: Denmark

• PHASE OF CARE: Active antitumor treatment

Randomized, controlled trial

• European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ)
• Charlson Comorbidity Index (CCI)
• Nutritional risk screening tool

Those in the intervention group reported reduced symptoms of constipation and flatulence. Compared to the intervention group, those in the standard care group reported reduced insomnia (p = 0.04) and a clinically relevant, but not statistically significant, reduction in fatigue. There were no other differences between groups in symptoms.

The perioperative multicomponent rehabilitation program studied here did not result in reduced fatigue or improvement in overall quality of life compared to those who received standard care.

• Risk of bias (no blinding)
• Risk of bias (no appropriate attentional control condition)
• Subject withdrawals ≥ 10%
• Other limitations/explanation: Patient adherence to exercises preoperatively was not described.

A more intensive exercise and educational counseling program provided perioperatively did not result in better patient outcomes related to fatigue four months after surgery for this group of patients. The lack of information about patients’ adherence to both pre- and postoperative exercise recommendations is a limitation of this report. Additional research on the impact of perioperative rehabilitation therapies in various patient groups would be of benefit.

This was a twelve-week outpatient rehabilitation program combining physical exercise and psycho-education and delivered in a group setting (12–16 participants per group). Physical training was led by two physiotherapists for two hours twice a week. Sessions aims included improving movement skills, improving strength and endurance, coping with fatigue, enhancing feelings of control, and reducing stress. Each session consisted of individual strength and endurance training (one hour) or a group sports activity (one hour), paired with 30 minutes of aqua aerobics. Each session of the group sports activity had a central theme (i.e., capability and cooperation, coordination, throwing and catching, social contact, winning and losing, relaxation). Psychoeducation sessions were led by oncology health professionals and aimed at providing support in coping with cancer and enhancing self-confidence and autonomy. Participants were provided with information on cancer-related subjects and encouraged to share their experiences as cancer survivors. Patient outcomes were assessed at baseline, week 6, and week 12.

• N = 658
• MEAN AGE =50.6 years
• AGE RANGE = 18–75 years
• FEMALES: 77.8%
• KEY DISEASE CHARACTERISTICS: Participants with mixed solid tumors and hematologic malignancies. Approximately 50% of the sample had the diagnosis of breast cancer.
• OTHER KEY SAMPLE CHARACTERISTICS: The majority was married or lived together (77.7%), most had children (76.9%), about half were employed at the time of diagnosis (48.3%). At the start of rehabilitation, only one-fifth (15.8%) was actually at work. The sample was a mean of 1.3 years from the conclusion of treatment, with a range of 0–14 years following treatment.
• EXCLUSION CRITERIA: Physically at risk owing to cancer or serious comorbidity, serious cognitive disturbances, restricting side effects of medication, or if needing more complex rehabilitation

• Longitudinal single-arm cohort design
  • No comparison group

• EORTC QLQ-C30

After six weeks, participants in the intervention group experienced a significant decline in fatigue (p < 0.001) in comparison to baseline measurements. After 12 weeks, participants experienced an even greater decline in fatigue (p < 0.0001) in comparison to baseline measurements.

• Unable to determine the benefits of exercise and psychoeducation components of intervention separately
• Lack of a neutral comparison group; therefore, unable to determine whether improvements in quality of life were a direct result of the rehabilitative program
• Long-term effects were not assessed in the study

Future research should incorporate objective physical strength and endurance tests and validated measurement instruments for more specific psychosocial parameters.

To investigate the feasibility and effects of a multimodal intervention for fatigue compared to home-based aerobic exercise

Individuals selected which intervention they wanted—home exercise or the multimodal intervention. The multimodal intervention included psychoeducation, including mindfulness-based techniques, sleep education regarding sleep hygiene, restriction and stimulus control, eurythmy therapy involving mind-body exercises, and medicine-oriented painting therapy. Those in the exercise group were asked to carry out 30-minute sessions three to five times weekly. Those in the multimodal group had 225 minutes of activity once weekly over 10 weeks, led by specialists in that therapy. Baseline and follow-up study measures were obtained within three weeks prior to starting the study and within three weeks after completion.

• N = 28 
• MEAN AGE = 57 years
• MALES: 0.5%, FEMALES: 99.5%
• KEY DISEASE CHARACTERISTICS: All had breast cancer. On average, patients were three years out from initial diagnosis and treatment.
• OTHER KEY SAMPLE CHARACTERISTICS: Approximately half were employed. All had a fatigue score of at least four and had fatigue for at least six months.

• SITE: Single site 
• SETTING TYPE: Outpatient 
• LOCATION: Germany

• PHASE OF CARE: Late effects and survivorship

• Observational two-group pilot study

• Cancer Fatigue Scale (CFS-D) (scale of affective, physical, and cognitive fatigue)
• Pittsburgh Sleep Quality Index (PSQI)
• Satisfaction with intervention on five-point Likert scale

Those in the multimodal group showed a significant reduction in physical fatigue (p = .0342, mean change = -2.1). Those in the multimodal group had a significant improvement in global sleep quality (p = .041, mean change = -2.0).

A multicomponent intervention was seen to be feasible and had a positive impact on rating of physical fatigue and global sleep quality.

• Small sample (< 30)
• Risk of bias (no control group)
• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• Risk of bias (no appropriate attentional control condition)
• Other limitations/explanation: Adherence to home-based exercise is not known.

A holistic multicomponent approach to manage patient fatigue and sleep disruption may have greater benefit than interventions that only incorporate exercise. Further research is needed to determine what type and intervention components are most effective.

To test the hypothesis that a home-based exercise intervention would improve fitness and physical activity and to determine the intervention effects on fatigue, self-reported physical functioning, and quality of life (QOL).

Those randomized to the exercise program received in-person instructions on how to exercise at a moderate intensity level, monitoring heart rate and how to warm-up and cool-down with exercise. Patients in the exercise group were asked to keep activity logs and were encouraged to exercise at least 10 minutes two days per week, increasing to 30 minutes per day, at least five days per week. Each received a weekly telephone call for the 12-week study to identify problems and reinforce participation, using cognitive-behavioral processes of change tailored to each patient. Patients in the control condition received weekly calls for 12 weeks for the administration of a symptom questionnaire and problem monitoring. Patients then received monthly telephone calls for three months. Telephone calls were audiotaped, and 25% of the tapes were reviewed for content to ensure fidelity to the study protocol. Study measures were obtained at baseline and at 3, 6, and 12 months.

• The sample was comprised of 46 patients (56.5% female, 43.5% male). 
• Mean age was 55.6 years (standard deviation [SD] = 8.24 years) in the control group and 59.5 years (SD = 11.2 years) in the exercise group. 
• All patients had colorectal cancer, with an average of three years since diagnosis.
• All patients had undergone surgery, and most did not receive radiation or chemotherapy treatment. 
• A majority of the patients had attended college and had a median income of greater than $60,000.

• Single site
• Home
• Rhode Island

Patients were undergoing multiple phases of care.

The study was a randomized, controlled trial.

• Seven-day Physical Activity Recall (7-day PAR)
• Treadwalk maximal fitness test
• Community Health Activities Model Program for Seniors (CHAMPS) questionnaire
• Functional Assessment of Cancer Therapy–Fatigue and Colorectal subscales (FACT-F and FACT-C)
• Short Form 36 (SF-36) physical functioning subscale

Both groups showed improvement in fitness and physical functioning over time, as well as increased physical activity. The exercise group showed a greater increase in physical activity at three months, but there was no difference from the control group at 6 or 12 months. During the first three months, the exercise group also showed significant improvement from baseline in CHAMPS energy expenditure and motivational readiness; however, these effects declined after three months. The intervention group demonstrated better submaximal aerobic fitness than the control group at all time points (p < 0.02). There were no significant intervention effects on fatigue, physical functioning, or QOL. These outcomes improved in all patients, and these improvements were sustained throughout the 12 months of follow-up. The authors speculated that the lack of apparent impact on fatigue may be associated with the fact that patients were highly functioning, although their baseline fatigue levels were lower than those seen in other studies in which exercise was effective.

The home-based exercise program improved patients’ physical activity, motivation, and fitness; however, it did not demonstrate an impact on fatigue or QOL. Activity and motivation were most improved during the first three months, when they received weekly telephone calls, suggesting that frequent contact may have been important in these results.

• The study had a small sample size, wth less than 100 patients.
• No information was provided regarding patient adherence to the recommended exercise program from patient logs.
• The lack of differences in CHAMPS between groups suggests that their actual activity levels were not substantially different.
• The majority of patients were highly educated and in a higher socioeconomic status and almost 100% were white, suggesting that these findings may not be applicable to other types of patients.

The findings suggest that a home-based exercise program can improve physical activity and aerobic fitness, but it did not appear that these improvements translated into reduced fatigue. Further research in the area of exercise and fatigue are needed to determine if exercise may be most effective in patients with greater fatigue at baseline.

To assess the feasibility, acceptability, and preliminary effects of a 12-week combined physical activity and relaxation intervention for breast cancer survivors.

Participants met with an intervention coordinator to complete baseline questionnaires and an activity assessment. They were then provided with exercise education about types of exercise and stretches, using a pedometer, setting activity goals, progressive muscle relaxation, and how to record these activities. Participants were then called weekly for 12 weeks during the intervention to provide further counseling.

• The sample was comprised of 19 women.
• Mean age was 52.5 years.
• Participants had breast cancer stage 0 to II.
• Participants had completed cancer therapy and were considered sedentary (moderate activity less than twice weekly or vigorous activity less than once weekly).
• Of the participants, 95.7% were white.

• Multisite
• Oncology clinics

• Participants were undergoing the long-term follow-up phase of care.
• The study has clinical applicability for late effects and survivorship.

The study used a pre-/post design.

• Intervention feasibility was assessed using single-item, 1-to-5 scale, not a standard instrument.
• Seven-day Physical Activity Recall (7-day PAR)
• The Stage of Motivational Readiness for Physical Activity
• IM Systems–three accelerometers (objective measure of physical activity) 
• Profile of Mood States (POMS)
• Pittsburgh Sleep Quality Index (PSQI)

Fatigue was statistically reduced from baseline to weeks 12 (p < 0.05) and 24 (p < 0.01). Sleep quality was also improved from baseline to weeks 12 (p < 0.01) and 24 (p < 0.05).

Participants found the intervention feasible without interrupting their levels of physical activity. Fatigue and sleep quality were improved significantly from baseline, suggesting a benefit from physical activity and relaxation as a combined practice. Further research is needed with control groups.

• The study lacked an appropriate control group.
• The study had a small sample size, with less than 30 participants.

Behavioral interventions for breast cancer survivors are a feasible and safe practice and may improve quality of life in participants. These interventions can be taught by nurses to patients.

To determine the efficacy of a 28-day inpatient rehabilitation program for patients with lung cancer

The program involved physical training with a bicycle ergometer to achieve a target heart rate. No other components of the program were described. Study measures were obtained at baseline and at the end of the program at 28 days.

• N = 44
• AGE = Not provided
• MALES: Not provided, FEMALES: Not provided
• KEY DISEASE CHARACTERISTICS: All had lung cancer and related surgery
• OTHER KEY SAMPLE CHARACTERISTICS: None provided

• SITE: Single site  
• SETTING TYPE: Inpatient  
• LOCATION: Germany

PHASE OF CARE: Transition phase after active treatment

Quasi-experimental

• Short Form 36 (SF-36)
• Multidimensional Fatigue Scale (MFS)

There were significant reductions in all components of the fatigue scale after the intervention (p < 0.001).

This inpatient exercise program was associated with reduced fatigue.

• Small sample (< 100)
• Risk of bias (no control group)
• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• Measurement/methods not well described
• Other limitations/explanation: There was no clear identification of all the study measures used. There was no demographic information provided to describe the sample.

This study adds to the already large body of evidence supporting the efficacy of exercise for managing fatigue in patients with cancer. The practicality of 28 days of inpatient exercise is questionable.

To evaluate a multimodal mind-body program (MMMT) compared to walking effect on fatigue in women with stage I–IIIA breast cancer

Participants in the intervention group underwent six hours of training in meditation, whole-food cooking, naturopathic strategies, and mindfulness by a multidisciplinary team. A sports therapist supervised a walking program in weeks 1, 3, and 10. Participants were encouraged to walk at home three times per week for 30 minutes. Participants in the control group also underwent a sports therapist-supervised walking program in weeks 1, 3, and 10. They also were encouraged to walk at home three times per week for 30 minutes.

• N = 55   
• AGE: Control mean: 55.3 years; MMMT mean: 58.1 years
• MALES: 0%, FEMALES: 100%
• KEY DISEASE CHARACTERISTICS: Average time first diagnosis: 39.7 months control, 61.9 months MMMT; stage I disease: 48% control, 30% MMMT; stage II disease: 44% control, 56.7% MMMT; stage IIIA disease: 0% control, 6.7% MMMT
• OTHER KEY SAMPLE CHARACTERISTICS: 20% smokers in MMMT group, 0 in control; mean fatigue in last month: MMMT 6.5, control 6.7

• SITE: Single site 
• SETTING TYPE: Outpatient 
• LOCATION: University of Duisburg-Essen, Germany

• PHASE OF CARE: Late effects and survivorship

• RCT

• German Fatigue Assessment Questionnaire with visual analog scale
• European Organization for Research and Treatment of Cancer EORTC QLQ-30
• Multidimensional Fatigue Inventory (MFI)
• Hospital Anxiety and Depression Scale (HADS)
• Menopausal Rating Scale

Unusual fatigue in the last week and last month was improved in both groups with no group differences. Anxiety in the MMMT group was improved compared to the control group (p = .043) during treatment but was not maintained in follow-up (p = .422). Both groups showed overall anxiety improvement. Reported pain between groups was improved in MMMT at follow-up compared to control (p = .031).  Menopausal symptoms decreased in both groups. No significant side effects were seen.

A home-based exercise program showed improvement in reported fatigue. The addition of a mind-body component showed no additional benefit.

• Small sample (< 100)
• Risk of bias (no control group)
• Unintended interventions or applicable interventions not described that would influence results
• Key sample group differences that could influence results
• Questionable protocol fidelity
• Subject withdrawals ≥ 10%

Home-based exercise is a reasonable and safe option for patients experiencing cancer-related fatigue.

The three-week inpatient rehabilitation included exercise, manual lymph drainage, and massage; some patients also received group counseling, progressive muscle relaxation, and balneotherapy (carbon dioxide bath and mud therapy). The aim of carbon dioxide baths is to increase peripheral blood flow while mud packs increase tissue temperature. Measures were obtained two weeks preadmission, at the end of treatment, and six months later.

• The sample was comprised of 149 women with breast cancer who were 3 to 72 months postsurgery.
• Mean age was 57 years (standard deviation = 10.5 years; range 32–82 years).
• Of the patients, 70% had lymphedema.

Rehabilitation center and spa in Austria

The study used a pre-/posttest design.

• European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) 
• Hospital Anxiety and Depression Scale (HADS)
• CA15-3 tumor markers
• German Illness-Coping Questionnaire

Patients received a median of 61 treatments. Of the patients, 22% dropped out at follow-up. There was a significant decrease in fatigue (p < 0.001) from pre- to posttest (effect size [ES] = .38) and pretest to six-month follow-up (ES = .38).

Fatigue improvement was greater for those with greater lymphedema.

• The study lacked a control group.
• The measure of fatigue was limited.
• The study was very heterogeneous in terms of type of treatment and time since treatment.
• No data were provided regarding cost or whether service was free.

To evaluate the effects of a supervised outpatient physical therapy strengthening and conditioning program on symptoms and quality of life

The program included aerobic exercise and strength training. The first two sessions were individualized under the supervision of a physical therapist. Patients who needed additional assistance walking, transferring, or using equipment continued to attend one-hour individual sessions. Patients were placed into 90-minute group sessions. The program consisted of intensive work for eight weeks, then six months of maintenance training was offered for those who were interested. Study assessments were done at baseline and after eight weeks.

• N = 75
• MEAN AGE = 62.6 years (SD = 11.9 years)
• MALES: 34.7%, FEMALES: 65.3%
• KEY DISEASE CHARACTERISTICS: Various tumor types (breast and lung were most prevalent)
• OTHER KEY SAMPLE CHARACTERISTICS: 34.7% metastatic disease; 15.3% in active treatment; 26.7% working full- or part-time

• SITE: Single-site  
• SETTING TYPE: Outpatient  
• LOCATION: Minnesota, United States

• PHASE OF CARE: Multiple phases of care

Quasi-experimental

• Short Form 36 (SF-36)
• Six-Minute Walk Test (6MWT)
• MD Anderson Symptom Inventory (MDASI)

The results of the 6MWt were better on average at the end of eight weeks (p < 0.0001). Physical component scores on the SF-36 improved (p < 0.001) as did mental component scores after eight weeks (p < 0.005). At the end of six months, only physical component scores remained higher than reported at baseline. Fatigue (p = 0.003) and dyspnea (p = 0.007) were improved at eight weeks. After six months, fatigue (p = 0.0077), shortness of breath (p = 0.0005), and disturbed sleep (p = 0.045) were improved from baseline. Patients still in active treatment showed significantly less improvement. Those who showed the worst performance at baseline showed the greatest improvement.

The eight-week strengthening and conditioning program improved physical function, fatigue, dyspnea, and sleep disturbance in this study. Improvement was greatest among those who had the worst symptoms and physical performance statuses at baseline and among those who were not in active treatment.

• Small sample (< 100)
• Risk of bias (no control group)
• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• Subject withdrawals ≥ 10%  
• Other limitations/explanation: Greater than 30% of participants withdrew from the study. There were significant differences for individuals still in treatment; however, the sample was too small to adequately analyze study sample subgroups. No information was provided about other relevant interventions that may have occurred during the six months of follow-up.

The findings of this study demonstrated the effectiveness of an exercise program on symptoms of fatigue, shortness of breath, and sleep disturbance among a variety of patients with cancer. These findings add to the large body of evidence about the efficacy of exercise.

The 15-week, multidimensional rehabilitation program included aerobic bicycle training plus general muscle force training, supervised sports sessions, psychoeducational sessions, and informational classes.

• The sample was comprised of 72 patients (85% female) who were posttreatment.
• Mean age was 51.4 years (standard deviation = 9.6 years).
• Of the patients, 61% were women with breast cancer.
• Patients were included if they
  • Were 18 years or older
  • Had their last cancer treatment greater than three months previously
  • Had an estimated life expectancy of one year or greater 
  • Had an indication for rehabilitation.

• Outpatient
• Center for Rehabilitation in The Netherlands

The study used a pre-/posttest design with measures before and after completion of the program. No control group was used.

• Multidimensional Fatigue Inventory (MFI)
• Rotterdam Symptom Checklist (RSCL)
• Exercise capacity and muscle force
• Short Form 36 Health Survey (SF-36)

• Of the patients, 77.8% completed the program and were posttest drop-outs.
• Drop-outs had more recurrences.
• There was significant improvement in every dimension of the MFI.
• The greatest effect was on physical fatigue.
• Effect sizes ranged from –0.35 to –0.78.
• There were no differences based on time since treatment.

• The intervention was delivered by an interdisciplinary team, including physical therapists and a psychosocial specialist.
• The role of nursing is unclear and atheoretical.
• Consequences were used as predictors.
• There was no control for overlap in the tools.
• It is not possible to determine which aspects of the intervention were effective.

To determine the effect of a combined rehabilitation program (physical training [PT] and cognitive-behavioral training [CBT]) and PT alone on cancer-related fatigue (CRF) compared with a control group receiving no intervention.

Two groups of cancer survivors were randomly assigned to 12 weeks of PT or to 12 weeks of PT plus CBT. The control group was not randomized. PT included aerobic training combined with progressive resistance exercise (twice weekly for two hours). CBT included self-management skills based on problem-solving (once weekly for two hours). In the analysis, fatigue scores were also compared to a general Dutch population of similar age.

• The sample was comprised of 147 patients (44% male, 56% female).   
• Mean age was 46 years.
• Breast cancer was predominant in all three groups.
• Patients were cancer survivors one to two years posttreatment.

• Multisite  
• Four rehabilitation centers in The Netherlands

The study was a randomized, controlled trial.

Multidimensional Fatigue Inventory (MFI) was used preintervention (Cronbach α range 0.73–0.83) and postintervention (Cronbach α range 0.84–0.88) to measure five domains:  general fatigue, physical fatigue, reduced activity, reduced motivation, and mental fatigue.

Levels of fatigue significantly decreased in all domains in all groups (p < 0.05; effect size across domains range –0.38 to –1.36), except in mental fatigue in the control group. No significant differences were found in decline of fatigue between the intervention groups. Patients completed 82.4% of PT and CBT sessions and 83.5% of PT sessions. In the post hoc analysis, patients with lower educational levels reported less decline in physical fatigue, reduced motivation, and reduced activation.

PT combined with CBT was equally effective in reducing fatigue, suggesting that CBT had no benefit beyond PT. Patients in the control group also showed a significant decline in fatigue, suggesting that time alone is also effective related to fatigue reduction.

• The study lacked an appropriate control group.
• There was an overrepresentation of patients with breast cancer.
• The study lacked a group receiving CBT only.
• The study duration was limited (12 weeks). 

The study supported the effectiveness of PT in the treatment of CRF.

To examine the effectiveness of an exercise program on quality of life (QOL), fatigue, sleep disturbances, exercise self-efficacy, exercise behavior, and exercise capacity in women with breast cancer.

Patients were randomly assigned to an exercise or usual care group. The exercise intervention was a six-week walking program based on modified exercise guidelines of the American Cancer Society and American College of Sports Medicine. This program included use of a heart rate ring monitor, pedometer, weekly telephone call, weekly meetings, and use of an exercise diary. Exercise was of low to moderate intensity (40%–60% maximum heart rate). In this program, patients performed weekly goal setting and were provided advice and information, and several specific strategies were described that were intended to boost self-efficacy. Patients were oriented to the exercise program prior to surgery, and exercise was begun within a few days after surgery. Data were collected at 24 hours prior to surgery and at 24 hours prior to the first cycle of chemotherapy, seven to 10 days after chemotherapy, and at the end of six weeks.

• Sixty-two patients were included.
• Mean age was 50.42 years (standard deviation = 9.64 years).
• All patients were female.
• All patients had stage I or II disease and were newly diagnosed.
• All patients had undergone mastectomy, 36% had at least a college education, 80.6% were married, and 51.4% were working full-time.

• Single site  
• Outpatient
• Taiwan

Patients were undergoing the active treatment phase of care.

The study used an experimental, longitudinal repeated measures design.

• Functional Assessment of Cancer Treatment – General and Fatigue scales (FACT-G, FACT-F) 
• Pittsburgh Sleep Quality Index (PSQI)
• Exercise Self-Efficacy Scale (EXSE)
• Godin Leisure-Time Exercise Questionnaire (GLTEQ)
• Six-minute walk test

The pattern of change in QOL over time showed significant consistent improvement among those in the exercise group compared to usual care controls (p < 0.001). Patterns of change in and overall sleep disturbance also showed significant improvement over time compared to controls (p < 0.006). The pattern of fatigue showed higher fatigue levels in the exercise group at all study time points. Average fatigue scores went from 40.5 to 45.8 at week 6 in the exercise group and from 40.1 to 40 with usual care. Patients in the exercise group had significantly better exercise self-efficacy (p ≤ 0.001) and higher levels of exercise behavior (p < 0.001) than those receiving usual care. Patients in the exercise group walked farther in the six-minute walk test than controls after the intervention (p ≤ 0.001).

Findings showed that a self-managed home exercise program, along with intervention strategies aimed at boosting self-efficacy, had a positive effect on QOL and exercise behavior among women newly diagnosed with breast cancer.

• The study had a small sample size, with less than 100 patients.
• It is not clear what type of relevant patient information and education was provided in the usual care group. 
• The duration of the study was relatively short at six weeks. 
• The sample was only very slightly underpowered.
• Lack of any blinding suggests the potential of bias.
• It is not clear if both patient groups received weekly telephone calls so that attentional control was provided. 
• The authors noted that there was a 30% contamination rate, with 30% of control group patients also exercising at least three times per week.

Findings of this study did not show a positive impact of a home-based exercise and self-efficacy interventions on fatigue in the first six weeks after surgery in newly diagnosed patients. However, over a longer period of time, patients in the exercise group did better. These findings suggest that nurses may need to educate patients that adherence to an exercise program may not show results in the short term and that effects may take some time to be felt. Nurses can educate and encourage patients to exercise at home and support activities to boost a patient's sense of efficacy may improve patient adherence to an exercise prescription.

To examine the effects of a multidisciplinary intervention on fatigue

The intervention group received training in individual sessions at week one, three, and six. A physical therapist provided education in deep breathing and designed a program of physical exercises to do at home. A nutritionist assessed needs and educated patients in nutrition during therapy. A nurse met with the patient, providing general psychoeducational intervention. All specialists had sessions with the patient at all study time points.

• N = 60   
• MEAN AGE = 56.1 years
• AGE RANGE: 45–65 years
• MALES: 68.3%, FEMALES: 31.7%
• KEY DISEASE CHARACTERISTICS: Lung cancer, undergoing chemotherapy
• OTHER KEY SAMPLE CHARACTERISTICS: Fatigue, pain, and peripheral neuropathy were the most frequent symptoms at baseline.

• SITE: Single site 
• SETTING TYPE: Outpatient 
• LOCATION: Thailand

• PHASE OF CARE: Active antitumor treatment

• RCT

• Piper Fatigue Scale

At the end of the study, the trial group had a lower fatigue score than controls (p = .036).

A multidisciplinary intervention to promote self-care may reduce symptoms of fatigue.

• Risk of bias (no blinding)
• Risk of bias (no appropriate attentional control condition)
• Other limitations/explanation: No information about patients' actual practice of exercise and other recommendations is provided. No baseline fatigue levels are provided.

Education provided by a multidisciplinary group may be beneficial and positively impact fatigue during cancer therapy.

For patients to evaluate the usefulness of the information provided.

Patients starting a course of radiotherapy or chemotherapy (inpatient and outpatient) at Tayside Cancer Centre in the United Kingdom were given a “Fatigue Initiative” folder containing information on fatigue together with advice on starting aerobic walking exercise during treatment. Patients were also encouraged to attend workshops on fatigue management as listed on flyers included in the folder. Materials included home exercise information, walking information, and a guide for good sleep.

• The sample was comprised of 146 patients (90 women and 115 men). 
• Mean age was 63.4 years.
• Patients had genitourinary (n = 119), gynecologic (n = 37), breast (n = 46), and other (n = 3) cancers.
• The study included four treatment groups:  radical radiotherapy, postoperative radiotherapy, palliative radiotherapy, and chemotherapy.

• Single site
• United Kingdom

This was an observational cohort study.

• Brief Fatigue Inventory (BFI) to assess level of fatigue before and after cancer treatment. The tool was administered four times:  baseline, end of treatment, and the first and second follow-up visits.
• Two study evaluation questionnaires were used:  one rated the information usefulness, and one provided information regarding exercise. No questions or scores were provided.

Overall, patients reported an increase in fatigue from baseline to the end of cancer treatment and from baseline to the first follow-up visit. Of the patients, 70% to 78% rated the information on fatigue helpful. Patients who said they used the information were more likely to exercise (odds ratio [OR] 3.71; 95% confidence interval [CI] [1.19, 11.56]; p = 0.024). Patients who received radiotherapy were more likely to exercise than those receiving chemotherapy (OR 14.9; 95% CI [2.43, 81.53]; p = 0.003). Higher levels of fatigue were reported by patients who used the information provided. Patients who exercised (p < 0.001), were older (p = 0.001), had cancers other than breast (p = 0.018), and were not receiving chemotherapy (p < 0.05) reported lower fatigue scores on the BFI. Ten patients participated in a fatigue workshop.

The findings supported the positive effect of exercise on fatigue during cancer treatment and identified that age, breast cancer, and treatment with chemotherapy rather than radiotherapy are associated with the level of fatigue experienced. The findings suggest that the provision of written educational/informational materials can be helpful in encouraging patients to exercise.

• The study lacked an appropriate control group.
• Time intervals varied between baseline and end of treatment for those receiving palliative radiotherapy (one to two weeks), radical or postoperative radiotherapy (four weeks), and chemotherapy (four months). Workshops were held in palliative care centers.

Fatigue did not decrease in any group. The study demonstrated the importance of providing information on fatigue and encouraging a walking/home exercise program. Patients who were able to exercise during treatment had lower fatigue levels. The finding that those who used the information had higher levels of fatigue may suggest that patients who have the most fatigue are more likely to use information to help them cope with it.