Exercise

STUDY PURPOSE: To assess the effects of aerobic and resistance exercise on treatment-related side effects during adjuvant treatment for breast cancer

TYPE OF STUDY: Meta-analysis and systematic review

• FINAL NUMBER STUDIES INCLUDED = 32 in review, 26 in meta-analysis
• TOTAL PATIENTS INCLUDED IN REVIEW = 2,626
• SAMPLE RANGE ACROSS STUDIES: 20–242 patients
• KEY SAMPLE CHARACTERISTICS: All were receiving adjuvant treatment for breast cancer

PHASE OF CARE: Active antitumor treatment

• Fatigue: SMD for in favor of exercise was –0.28 (95% confidence interval [CI] [–0.41, –0.16]) with moderate quality evidence (19 studies including 1,698 women).
• Depression: The difference with exercise was not significant, and evidence quality was moderate (5 studies including 674 women).
• Cognitive function assessed with Trail Making Test: MD –11.55 (95% CI [–22.06, –1.05]) with low quality evidence (2 studies including 213 women)
• Anxiety: Three studies assessed anxiety. A meta-analysis of two studies found no significant difference with exercise.
• A variety of other outcomes were assessed and reported, such as physical fitness, quality of life, and mood.

The findings show a moderate effect of exercise on fatigue among women receiving adjuvant treatment for breast cancer. No significant effects were seen for depression or anxiety. A statistically significant effect for cognitive function was found; however, the evidence was deemed to be of low quality.

• High heterogeneity
• The authors reported lack of sufficient information in reports to make clear judgments about potential bias.

Exercise probably reduces fatigue and improves physical fitness among women during treatment for breast cancer. Adherence to exercise can be a challenge, and implementation of exercise recommendations or programs will need to address factors to foster exercise participation to be successful.

• FINAL NUMBER STUDIES INCLUDED = 12
• TOTAL PATIENTS INCLUDED IN REVIEW = 442
• SAMPLE RANGE ACROSS STUDIES = 12–107 patients
• KEY SAMPLE CHARACTERISTICS: Although education status may influence neuropsychological test results, only half of the studies provided this information. Likewise, menopausal status may affect cognition, and this was only reported by two thirds of the studies.

PHASE OF CARE: Late effects and survivorship

Studies of pharmacologic interventions were not found to be effective in improving cognitive function. Medications reviewed included d-methylphenidate (n = 1), epoetin alfa (n = 2), and ginkgo biloba (n = 1). Evidence for nonpharmacologic interventions was mixed. No improvements in cognitive function were found with Tibetan sound meditation (n = 1). Natural restorative therapy (n = 1) improved attention only when comparing the baseline with the final 90-day evaluation (p = 0.01). Exercise (n = 1) improved attention (p = 0.019) and verbal memory (p = 0.048) but not working memory. Cognitive rehabilitation (n = 1) improved four out of six measures of information processing speed (p < 0.05) but not attention, verbal memory, or executive function. Cognitive behavioral training (n = 2) improved verbal memory (p < 0.05) in both studies and was effective in improving in information processing speed when compared to baseline scores in one study (p ≤ 0.01) but not the other. Computerized cognitive training was effective in one study in improving processing speed (p = 0.009), executive function (p = 0.008), and a measure of executive function and language (p = 0.003) but not verbal memory. However, in another study, there was no difference in verbal memory or information processing speed between the intervention and control groups.

Nonpharmacologic interventions, especially cognitive training, may have a role for improving attention, information processing speed, and verbal memory. Exercise and computerized cognitive training may be effective for improving executive function. However, additional research validating these findings with larger sample sizes and evaluating other cognitive domains is needed. In addition, studies determining the dose or duration of interventions is required for a durable response.

• A small number of studies (n = 12) were included in the review for multiple types of interventions.
• Only one study had a sample size greater than 100 (range = 12–107).
• Studies of low quality were included. 

These findings suggest that nonpharmacologic, not pharmacologic, interventions may be helpful in managing chemotherapy-induced cognitive impairment in patients with breast cancer. However, these findings were based on a small number of studies per intervention. Additional research validating which interventions might be useful in improving cognitive impairments in women receiving chemotherapy for breast cancer is needed. 

STUDY PURPOSE: To determine the effectiveness of exercise for minimizing cognitive impairment related to cancer and/or cancer-treatment.

TYPE OF STUDY: Systematic integrative review

DATABASES USED: PsycINFO, PubMed, CINAHL

YEARS INCLUDED: (Overall for all databases) though January 2016

INCLUSION CRITERIA: Quantitative studies evaluating effectiveness of exercise for maintaining cognitive functioning in adult patients with cancer with objective and/or subjective assessments 

EXCLUSION CRITERIA: Studies published in a language other than English.

TOTAL REFERENCES RETRIEVED: 232 citations screened, but only 26 met study eligibility criteria.

EVALUATION METHOD AND COMMENTS ON LITERATURE USED: The Grading of Recommendations Assessment, Development and Evaluating tool was used to appraise the quality of evidence for study outcomes.

FINAL NUMBER STUDIES INCLUDED: 26

TOTAL PATIENTS INCLUDED IN REVIEW: 2,145 

SAMPLE RANGE ACROSS STUDIES: 4 to 658 participants.

KEY SAMPLE CHARACTERISTICS: 85% of studies included breast cancer survivors, 77% of all participants received chemotherapy and 31% received radiation therapy.

PHASE OF CARE: Late effects and survivorship

Twenty-six studies evaluated the effectiveness of exercise on improving various cognitive functions (CF) (i.e., memory [M], attention/concentration [AC], executive function [EF], information processing speed [IPS], language [L]) or perceived cognitive function (PCF). Forty-two percent of the studies were randomized controlled trials (n = 11), 42% were quasiexperimental (n = 11), 11.5% were observational (n = 3), and one case study. Interventions included aerobic exercise (n = 4), resistance exercise (n = 3), combination of aerobic and resistance exercise (n = 7), aerobic exercise with another modality (e.g., methylphenidate, psycho-education, behavioral intervention) (n = 4), and mindfulness-based exercise (i.e., yoga, Tai chi, Qigong) (n = 8). Of note, 15% of studies did not have an intervention but, rather, relied on patient self-report regarding exercise.  

Eighty-one percent of studies used subjective measures, but only 35% included objective measures of CF. In addition, there was a great deal of variability between instruments used as well the frequency or timing of evaluation. Eighty-eight percent of studies were longitudinal and assessed patients at baseline until less than three months (26%), three months (52%), or six months (22%). While some studies found significant improvements in PCF and/or various cognitive domains (e.g., IPS, AC, EF, L, M), these results were not consistent across studies.

Findings from this study revealed that there is insufficient good quality evidence to determine whether exercise may improve cognitive functioning in cancer survivors.  Although exercise may be beneficial in improving cognitive functioning, there is insufficient evidence to determine the type of exercise, including duration and frequency, that would be recommended. Additional research, including multi-site studies with large sample sizes and higher quality evidence, are needed to determine the effectiveness that specific types of exercise might have a role in alleviating cognitive impairment.

• Limited search
• Mostly low quality/high risk of bias studies

Study findings do not support recommending exercise for improving cognitive impairment in cancer survivors. However additional research using these interventions are recommended to further determine their effectiveness.

STUDY PURPOSE: To evaluate the effectiveness of an exercise intervention and physical activity behavior on cancer-related cognitive impairment

TYPE OF STUDY: Systematic review

• FINAL NUMBER STUDIES INCLUDED = 19 (5 animal studies and 14 human studies) 
• TOTAL PATIENTS INCLUDED IN REVIEW = 1,560 patients and 226 rodents
• SAMPLE RANGE ACROSS STUDIES: 4–447 patients
• KEY SAMPLE CHARACTERISTICS: Although educational status may influence neuropsychologic test results, this information was not provided. Likewise, menopausal status may affect cognition; because 14 studies primarily consisted of patients with breast cancer (four studies included other tumor types), this was not reported.

PHASE OF CARE: Late effects and survivorship

In patients, studies of exercise interventions had mixed results regarding their effectiveness in improving cognitive function. Interventions reviewed included an undefined physical activity (n = 3), cardiovascular fitness (n = 1), home-based walking and resistance band training (n = 1), yoga (n = 3), speed-feedback therapy on a bicycle ergometer (n = 1), medical qigong (n = 1), physical activity behavior change program (n = 1), Tai chi (n = 1), progressive aerobic endurance training on a treadmill (n = 1), and strength training (n = 1). Although the review reported cross-sectional studies that revealed correlations between physical activity with visual memory (n = 1), executive function (n = 1), attention (n = 1), and information processing (n = 1), the strength of these correlations was not reported. Randomized, controlled trial studies reported improved perceived cognitive functioning with walking, yoga, and medical qigong but not with the physical activity behavior change program. In addition, improvements were found for executive function with speed-feedback therapy, attention and verbal memory (but not working memory with strength training), and memory with yoga. However, in each of these results, the significance of these findings was not reported. These results are further complicated by the lack of consistency in regard to the cognitive functioning measures used.

Exercise may improve perceived cognitive function. However, further research is needed to validate if specific types of exercise affect cognitive functioning and to determine the dose or duration required for a durable response. Longitudinal studies with larger sample sizes that incorporate both objective and subjective measures of evaluating cognitive function are needed before recommendations for exercise can be made as a means to counteract chemotherapy-related cognitive impairment.

• High heterogeneity
• Low sample sizes
• A small number of studies with humans (n = 14) was included in the review for multiple types of exercise and physical activity interventions.  
• Studies of low quality were included.

The findings suggest that some forms of exercise or physical activity interventions may be helpful in improving patients’ perception of chemotherapy-induced cognitive impairment; however, these findings are based on a small number of studies per intervention. Recommendations cannot be made based on this review.

 To evaluate the effectiveness of resistance training on cognitive abilities in patients with breast cancer undergoing neoadjuvant chemotherapy   

The intervention group (IG) participated in 60 minutes of resistance training (three sets of 8–12 reps for 10 different exercises at 55%–75% maximum effort) twice a week for 12 weeks. The control group (CG) did not receive any information. Cognitive evaluations were performed in the IG prior to them receiving the intervention and at study conclusion (one to two weeks after end of chemotherapy) for both groups.

• The total number of participants was 17 (9 in intervention group, and 8 in thecontrol group). 
• The mean age for the IG was 46.6 years (+/- 6.9 years). The mean age for the CG was 52 years (+/- 5.5 years).
• The percentage of males and females was not provided.
• Participants had been diagnosed with stage I–III breast cancer and were receiving neo-adjuvant chemotherapy.

• Site was not specified.
• Patients were recruited from the Breast Center of the University Hospital of Cologne, Germany.

Patients were undergoing active treatment.

Prospective, non-randomized controlled trial

• Memo memory test (verbal memory)     
• Wilde Intelligence subtest (working memory)
• d2 Test of Attention (focused attention and concentration)

The IG's d2 Test of Attention scores improved (p = 0.049), but no significant differences were observed in comparison to the CG. The IG d2 error rate decreased from baseline by 1.12 points (p = 0.017) but was significantly different from the CG at baseline (p = 0.040) and post-intervention (p = 0.019). The IG short-term verbal memory was marginally improved from baseline (p = NS) but was significantly better than CG scores (p = 0.048). IG Wilde test scores for working memory showed significant improvement from baseline (p= 0.049), but no significant difference existed between IG and CG scores.

Improvements were seen in focused attention and concentration, working memory, and verbal memory for the IG. Although no differences were observed in verbal memory and attention between the IG and CG, the CG did not have baseline evaluations performed for adequate group comparisons.  

• The sample size was less than 30.
• The sample was not randomized.
• No pre-test was conducted for the CG.
• No comparative demographics were collected (e.g., education, occupation, information on treatment, previous treatment modalities). 
• No actual scores or data were presented in the research brief. 

Benefits of physical activity, predominately aerobic exercise, have improved symptoms of fatigue, sleep disturbances, affect, and cognitive function. Using resistance training may improve short-term verbal memory, working memory, attention, and concentration. Further study is warranted.

Assess the preliminary effectiveness of moderate-intensity walking, compared to usual care, on cognitive function during chemotherapy for non-metastatic, invasive breast cancer.

The intervention included two groups: moderate-intensity walking (targeting a self-managed goal of 150 minutes over 12 weeks) versus usual care.

Participants randomly assigned to the moderate-intensity walking group were given a booklet promoting reaching of the goal through self-management, starting with at least 10 minutes of walking and moving up to 30 minutes 5 days per week over 12 weeks. Participants were given a pedometer and were asked to record daily steps and complete the Borg Rating of Perceived Exertion Scale in a daily diary. Participants were also asked to log their weekly goals. 

Participants assigned to the usual care group received no intervention.

Study assessments were done pre-chemotherapy (familiarization, no data collected); midway through chemotherapy (pre-randomization); and after chemotherapy (i.e., postintervention).

• N = 50
• MEAN AGE: 52 years (SD = 10.4) 
• FEMALES: 100%
• CURRENT TREATMENT: Chemotherapy
• KEY DISEASE CHARACTERISTICS: Initial diagnosis of non-metastatic, invasive breast cancer (stage I-III)
• OTHER KEY SAMPLE CHARACTERISTICS: Undergoing neo-adjuvant (18%) or adjuvant (82%) chemotherapy with FEC with or without taxotere, reported less than 150 minutes of moderate-intensity activity per week, aged 18-75, 62% postmenopausal, race/ethnicity not reported, 44% completed college

• SITE: Single site   
• SETTING TYPE: Home    
• LOCATION: England, UK

PHASE OF CARE: Active anti-tumor treatment

Unblinded randomized controlled trial of moderate-intensity walking versus usual care with pre-/post- assessments

• Objective cognitive function: Battery of tests of executive function, working memory, attention, visuospatial skills
• Self-reported cognitive function: Cognitive Failures Questionnaire
• Other measures: Physical activity (accelerometer [data not usable], pedometer, perceived exertion), psychosocial patient-reported outcomes (results reported elsewhere)

• Feasibility: 79% completed the study, 80% in intervention group met goal of 150 minutes per week of moderate-intensity walking (no significant difference in minutes walked between week 1 and week 12); adverse events not reported
• Cognitive impairment: Self-reported cognitive failures were lower in the intervention group at baseline and did not worsen during the walking intervention, while the usual care group started with more self-reported cognitive failures that worsened with time (p = 0.05). Greater levels of physical activity were associated with fewer cognitive failures (p = 0.05). No group x time effects were found for any domain of objective cognitive function. The physical activity group had better working memory overall than the control group (p < 0.001), and all participants improved in working memory over time (p = 0.03). 
• Other outcomes: No associations were found between psychosocial patient-reported outcomes and cognitive function.

This  study provides evidence that a self-managed, home-based walking program of moderate-intensity is feasible during chemotherapy and may reduce declines in self-reported cognitive function during treatment.

• Small sample (< 100)
• Baseline sample/group differences of import
• Risk of bias (no blinding)
• Risk of bias (no appropriate attentional control condition)
• Findings not generalizable
• Subject withdrawals ≥ 10%  
• Other limitations/explanation: The participants in the intervention group reported fewer cognitive failures at baseline than the control group (potential ceiling effect for self-reported cognitive function). Generalizability unclear with no attention control and limited to women with stage I-III breast cancer.

This study provides preliminary evidence that self-managed, moderate-intensity walking might improve self-reported cognitive function, which is commonly reported to be impaired by breast cancer survivors. The findings support future well-powered studies evaluating walking to improve cognitive function.

Examine the preliminary efficacy of a moderate-intensity aerobic exercise intervention, compared with a waitlist/attention control, on cognitive function among sedentary breast cancer survivors who reported cognitive problems.

The intervention included two groups: aerobic physical activity (targeting a goal of at least 150 minutes of moderate-to-vigorous physical activity over 12 weeks)  versus waitlist/attention control (i.e., matching email contact frequency for intervention group with women’s health topics).

Participants randomly assigned to the aerobic physical activity group completed an in-person walking assessment, after which study staff used motivational interviewing to set physical activity targets to reach the target goal for the study. Participants were given a Fitbit, which was used by staff to provide feedback on increasing physical activity during calls at two and six weeks. Motivational emails were sent every three days.

Participants assigned to the control group received women’s health topic emails every three days.

Study assessments were done before and at the end of the intervention (i.e., approximately 12 weeks post-baseline).

• N = 87
• MEAN AGE: 57 years (SD = 10.4)
• FEMALES: 100%
• CURRENT TREATMENT: Other
• KEY DISEASE CHARACTERISTICS: Initial diagnosis of non-metastatic, invasive breast cancer (stage I-III)
• OTHER KEY SAMPLE CHARACTERISTICS: Self-reported as sedentary at baseline, diagnosed less than 5 years before enrollment, no recurrence or other cancers within 10 years, 82% White, 71% completed college, 53% received chemotherapy (analysis stratified by receipt), 70% currently on endocrine therapy

• SITE: Single site   
• SETTING TYPE: Home    
• LOCATION: California, USA

PHASE OF CARE: Late effects and survivorship

Unblinded randomized controlled trial of moderate-to-vigorous physical activity versus waitlist/attention control with repeated measures

• Objective cognitive function: NIH Toolbox
• Self-reported cognitive function: PROMIS cognitive abilities, cognitive concerns
• Other measures: Accelerometer, BMI

• Feasibility: 98% completed the study, 60% in intervention group met goal of 150 minutes per week of moderate-to-vigorous physical activity measured by actigraphy (compared to 19% at baseline; p = 0.006); adverse events not reported
• Cognitive impairment: Self-reported cognitive concerns were lower in the physical activity group at baseline (p = 0.04). The physical activity group had greater improvements in processing speed (p = 0.049) than the control group. No group differences were found for other cognitive domains or for self-reported cognitive function.
• Other outcomes: No group differences were found at baseline or over time in BMI.

This pilot study provides evidence that moderate-to-vigorous physical activity shows preliminary efficacy to improve a specific domain of objectively-measured cognitive function, processing speed.

• Small sample (< 100)
• Baseline sample/group differences of import
• Risk of bias (no blinding)
• Risk of bias (no appropriate attentional control condition)
• Findings not generalizable
• Other limitations/explanation: The participants in the intervention group reported fewer cognitive concerns at baseline than the control group (potential ceiling effect for self-reported cognitive function). The waitlist/attention control condition only partially controlled for the attention received by the intervention group.

This study provides preliminary evidence that moderate-to-vigorous aerobic physical activity might improve the speed of doing mental tasks (i.e., processing speed), which is found to be impaired among some breast cancer survivors. The findings support future well-powered studies using aerobic physical activity to improve processing speed.

This 12-week physical fitness and psychoeducational rehabilitation program was conducted to enhance quality of life and recovery among cancer survivors of all types of cancer. Its physical fitness component was aimed at improving movement skills, strength, and endurance; helping participants cope with physical complaints (e.g., fatigue); and enhancing feelings of control and stress reduction. Its psychoeducational component was aimed at providing support in coping with cancer and enhancing self-confidence and autonomy.

 The intervention had three components.  

1. A physical fitness program involving two hours of training twice weekly with guidance from two expert physiotherapists. Each session consisted of

• One hour of individual training for endurance and strength or one hour of group sports and games
• 30 minutes of aqua-aerobics in an indoor pool.

2. A psychoeducational program consisting of seven two-hour sessions aimed at providing support in coping with cancer and enhancing self-confidence and autonomy.

3. Information on cancer-related subjects.

Subjective measures were completed prior to the intervention, 6 weeks into the intervention, and at 12 weeks at the intervention's end. 

• The number of enrolled participants was 665. Of the enrolled participants, 658 initiated the program, 634 completed 6 weeks of the program, and 579 completed the program's full 12 weeks. 
• The average age of the participants was 50.6 ± 9.5 years, with a range of 18–75 years.
• 54% of the participants had breast cancer. Other cancers included were lymphoma, digestive tract, gynecologic, and lung cancer.
• 77.8% of the participants were female and 21% were male. Gender was unknown for 1.2% of the participants. 
• The average time since diagnosis was 2.1 years, with a range of 0–25 years.
• The average time since end of treatment was 1.3 years, with a range 0–14 years.

This was a single-site study. 

This was a prospective trial. 

The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-30 (EORTC QLQ-C30) was used to measured global and functional quality of life using 6 subscales (global, physical, role, cognitive, emotional, social functioning) and one symptom scale on fatigue. Scores range from 0–100, with higher scores indicating higher quality of life for the global and functional scales. Higher symptom scores indicate greater fatigue.

The Tampa Kinesophobia Scale was used to measure excessive, irrational and debilitating fear of physical movement and activity resulting from a feeling of vulnerability to painful injury or re-injury. Two subscales were used to measure avoidance of activities (7 items) and pathologic somatic focus (4 items).

As measured by two items on the EORTC QLQ–C30, cognitive function improved at 12 weeks, but not at 6 weeks. There were significant improvements for all quality-of-life domains and fatigue for all cancer patients after 12 weeks (p < 0.05).

The authors suggest that exercise may improve cognitive functioning as well as other quality-of-life domains.

• Although subjective cognitive function improved over 12 weeks, this finding was not confirmed by objective cognitive-specific measures.
• A wide range of ages was included in the sample, but no age breakdown was recorded for the two cohorts; ge-related changes in cognitive function may influence the results between the two cohorts.
• The authors were unable to determine whether changes in quality of life were a result of the exercise versus the psychoeducational intervention or the combination of both.
• There was no control group as a comparison. 

To determine the feasibility and effectiveness of speed-feedback therapy on improving cognitive function in elderly patients with cancer

The intervention consisted of subjects pedaling for five minutes on a bicycle ergometer once per week for four weeks compared to usual daily life activities. The bicycle ergometer was linked to a computer with the screen displaying the target speed, revolutions per minute, and a changing path for the subjects to follow. Subject’s actual speed and revolutions were displayed as the subject tried to match the target speed and revolutions on the path on the screen. The exercise load was set at 20 W, and the maximum number of rotations was set at 80 revolutions per minute. Demographic data were collected at baseline. Cognitive function and other assessments were obtained at baseline and at week 4.

• N = 78 (38 intervention, 40 control)
• MEAN AGE = 74.24 years
• MALES: 45%, FEMALES: 55% 
• KEY DISEASE CHARACTERISTICS: All participants were diagnosed with either breast or prostate cancer irrespective of stage or treatment modalities. Most subjects were undergoing treatment (53% intervention, 70% control).
• OTHER KEY SAMPLE CHARACTERISTICS: Average education = 12.11 years

• SITE: Single-site    
• SETTING TYPE: Outpatient    
• LOCATION: Hiroshima University Hospital rehabilitation center, Japan

• PHASE OF CARE: Multiple phases of care
• APPLICATIONS: Elder care  

Randomized, controlled trial design; outcomes evaluator blinded to group assignment

• Frontal Assessment Battery (FAB)
• Barthel Index (BI)
• Lawton and Brody Instrumental Activities of Daily Living (IADL)
• Functional Assessment of Cancer Therapy-General (FACT-G) version 4

There were more subjects who underwent radiation therapy in the intervention than the control group (p = .01). There were significant differences between groups in the FAB change score for time effect (F = 24.39, p < .001, partial ɳ² = .247), group effect (F = 9.26, p = .003, partial ɳ² = .109), and interaction (F = 7.88, p = .006, partial ɳ² = .094). Younger age was an independent factor associated with greater improvement in FAB scores (p = .018, β = -.264). There were no differences between groups for BI, IADL, or FACT-G scores at baseline or over time.

Findings from this study suggest that speed-feedback therapy may improve cognitive function. However, this intervention required a bicycle ergometer associated with a computer and training by professionals in a hospital setting, which may impact accessibility and costs. Additional studies in other cancer diagnoses with longitudinal follow-ups to demonstrate sustained cognitive improvements is warranted.

• Small sample (< 100)
• Intervention expensive, impractical, or training needs

Speed-feedback therapy with a bicycle ergometer may be a potential intervention to improve cognitive function, particularly sustained attention. Additional research with larger sample sizes and a longer follow-up period is needed to determine the effectiveness and the sustainability of any improvements in cognitive function.

To examine the effects of tai chi on neuropsychological, psychological, and physical health of female cancer survivors  

Women participated in an hour-long, twice-weekly Yang-style tai chi course for 10 weeks. They underwent testing prior to the course and then one month following the test.

• A total of 23 participants enrolled in the study.  
• The women's average age was 62.3 years (SD = 10.8 years).
• The sample was 100% female.
• The women had been diagnosed with breast (n = 16), ovarian (n = 3), or endometrial (n = 1) cancer; NHL (n = 2); or CLL (n = 1).
• All had received chemotherapy at least 12 months prior.
• On average, the women had complete 16.4 years (SD = 2.1 years) of education.
   

• Mutli-site 
• Mid-Western city
   

Patients were undergoing long-term follow-up.

Pilot study

• Rey Auditory Verbal Learning Test (memory)    
• Trail Making Test A
• Trail Making Test B (executive functioning)
• Stroop Test (executive functioning)
• Oral Word Association Test
• Wechsler Adult Intelligence Scale Third Edition (WAIS-III) Digit Span and Digit Symbol
• Multiple Abilities Self-Report Questionnaire (MASQ)

Statistical significant changes were seen in the scores of immediate memory (Rey trial 1, Rey trials 1–5, Logical Memory), delayed memory (logical memory II), verbal fluency (COWAT), attention (Trails A, Digit Symbol) and executive functioning (Trails B, Stroop Test). The Reliable Change Index analyses did not meet the criteria for reliable change as a group. Self-reported cognitive functioning improved for verbal and visual memory in the MASQ (p < 0.05). No significant changes were seen in fatigue. Significant improvements were seen in multiple measures of balance (p < 0.002).

Tai chi may promote gains in cognitive and physical functioning in cancer survivors.

• The sample was small at less than 30 participants.
• It was a well-educated group, all female, with a range of treatment and length from last treatment)
• No control group was included.
• Classes were taught in a group setting, so the group support and interaction may have influenced the findings, rather than the tai chi itself.

This is a small pilot study, but it suggests that tai chi may be helpful in improving neurocognitive functioning. Tai chi is a relatively easy exercise to perform for most patients and is readily available in most areas. Further research is needed to verify the benefits of tai chi on cognitive dysfunction.

To evaluate the effects of a 12-week resistance training intervention in patients with breast cancer during adjuvant chemotherapy

Patients were randomly assigned to the intervention or attention control group. The control group received a supervised group muscle relaxation program with the same session schedule as the intervention group. The exercise intervention involved the use of eight different machine-based progressive resistance exercises without an aerobic component. Both interventions were provided in group settings for 60 minutes twice weekly. Study measures were obtained at baseline and at the end of the intervention period.

• N = 95
• MEAN AGE = 52.7 years (range = 30–71 years)
• FEMALES: 100%
• KEY DISEASE CHARACTERISTICS: All participants had breast cancer. The majority of participants had stage 1 or 2 disease. The mean number of days since surgery was 56. All participants were receiving adjuvant chemotherapy.
• OTHER KEY SAMPLE CHARACTERISTICS: 18% had baseline depression 

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

• PHASE OF CARE: Active antitumor treatment

Randomized, controlled trial

• Fatigue Assessment Questionnaire (FAQ)
• European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30)
• Center for Epidemiologic Studies (CES-D) for depression
• Trail Making Test (TMT)

The overall between-group difference in fatigue was –5.8. This difference was not statistically significant. There was no overall effect of the intervention on the affective or cognitive dimensions in the fatigue measure. In a subgroup analysis of women who were not depressed at baseline, the between-group difference was –8.1 (p = –0.039). Fatigue increased in the relaxation group. Cognitive performance on the TMT improved in the exercise group compared to the control group, but the difference was not significant. Depression remained unchanged in both groups.

The findings of this study show that resistance exercise can be helpful in reducing fatigue during adjuvant chemotherapy, particularly in patients who have depressive symptoms. There were no apparent effects of the resistance exercise program on fatigue or cognitive function.

• Small sample (< 100)
• Risk of bias (no blinding)
• Key sample group differences that could influence results
• Other limitations/explanation: A significantly larger proportion of patients in the exercise group had higher depression scores at baseline (p = 0.0098). This difference may have affected overall findings.

Findings showed that resistance exercise reduced fatigue during adjuvant chemotherapy. These effects were more pronounced in women who did not have depressive symptoms at baseline. This points to the potential influence of depression on fatigue and the efficacy of interventions for fatigue. These results suggest the need to ensure the effective management of depressive symptoms to manage fatigue during treatment. The interventions studied here did not show an effect on depression or cognitive function.

This study was conducted to examine the effect of exercise and methylphenidate (MPH) on fatigue, functional ability, and cognitive function in patients with melanoma. It also aimed to determine the percentage of patients who adhered to interferon-alfa, MPH, and exercise treatment.

The intervention group was given 20 mg of long-acting MPH every morning for four months and took part in at least 15–20 minutes of aerobic exercise four days per week. The duration and intensity of exercise gradually increased over the study's four months.

Assessments were completed prior to the first dose of interferon-alfa. Subsequent assessments of functional ability and cognition function (using Trail Making Test forms) and quality of life were repeated at one and four months after baseline. Subsequent assessments of fatigue scale, body weight, daily activity, and medication logs were submitted monthly.

• The total number of individuals involved in the study was 28.
• There were 12 participants and 16 historic controls. 
• The average age of the treatment group was 44, with a range of 20–64. Age information for the historic group was not provided.
• Gender information was not provided.
• 92% of the participants were Caucasian.
• The treatment group tended to have completed more years of formal education.
• Participants had newly diagnosed melanoma with surgical intervention, no prior treatment, and were actively undergoing treatment with interferon-alfa.

The study took place at a university-based cancer center.

This was a longitudinal pilot study with descriptive/exploratory design. It made use of a historic control group for comparison.

• The Trail Making Test (TMT) Parts A and B measured visual attention, motor speed, and cognitive flexibility.
• The Schwartz Cancer Fatigue Scale measured fatigue with 6 items. Scores range from 6–36, with higher scores indicating greater fatigue.
• The Medical Outcomes Study Short Form (SF-36) measured quality-of-life and global function with physical and mental health subscales. Scores range from 0–100, with higher scores indicating higher functioning.
• Adherence was measured with daily activity and medication logs.
• Body weight was measured to the nearest 0.1 kg and obtained monthly.

Functional ability increased an average of 6% for all participants and 9% for the treatment group. A percent change in a 12-minute walk was negatively related to TMT-A (p = 0.04) and TMT-B (p = 0.05), suggesting a relationship between higher exercise and improved cognitive functioning (indicated by lower scores on TMT). Taking MPH was correlated with improved TMT-B performance at 4 months (r = -0.85, p < 0.001). 

All participants' cognitive function scores were within normal ranges at baseline. Sixty-six percent of participants adhered to MPH at four months; all subjects continued to exercise at four months.

The combination of exercise and MPH has positive effects on cognitive function, functional ability, and fatigue over time. The authors suggest that MPH may have contributed to better exercise adherence.

• The study had a small sample size.
• One-third of the participants stopped taking MPH within the first week; for one participant, this was due to significant side effects related to anxiety.
• Two participants regularly exercised prior to enrollment, but the study did not address which group they were assigned to, potentially influencing outcomes.

A uniform NCCN consensus determined that recommendations were appropriate (NCCN Category of Evidence and Consensus = 2A).

Some interventions that may be useful to improve or maintain cognitive function might not be included in these guidelines because this manuscript did not detail search strategies, inclusions and exclusions, or the number of articles included in the recommendations.

The NCCN cognitive function algorithm aids healthcare professionals considering the assessment and treatment of cancer-related cognitive function. Nonpharmacologic interventions should be recommended to oncology survivors experiencing cognitive issues. Pharmacologic interventions may be considered when medical conditions permit and potential contributing factors are ruled out or managed.

PHASE OF CARE: Late effects and survivorship

All recommendations were based on lower level evidence and consensus.

Physical activity and memory aids were recommended for cognitive impairment. SSRIs and SNRIs were recommended for depression as first-line treatment, and benzodiazepines were recommended as first-line treatment for anxiety. Physical activity, cognitive behavioral therapy, psychoeducation, and the consideration of psychostimulants were recommended for fatigue.

• Mainly consensus for most recommendations
• Limited database use  
• Full results of search not provided

This guideline gave numerous recommendations and suggestions for various aspects of patient needs. Most recommendations were consensus-based.