The intervention consisted of structured sessions that began with 20 minutes of conditioning exercises conducted by a physical therapist, followed by an educational session with cognitive-behavioral strategies for coping with cancer, and an open discussion with group leaders and other participants. Sessions were balanced with didactic material, a question and answer period, sharing, reflecting, relaxation, and physical activity. Participants attended eight sessions throughout the four weeks following enrollment. The intervention was delivered three days per week. After the fourth week, patients completed quality of life (QOL) questionnaires, and the questionnaires were collected at eight and 27 weeks after enrollment via mail.

• In total, 103 patients (66 male, 37 female) were included.
• Mean age was 59.6 years (range 31–85); 85.7% of patients were older than 50 years.
• The most common dominant disease status was gastrointestinal (36.7%).
• Of the participants, 59.2% were undergoing current chemotherapy, 77.6% were married, and 57.1% were currently employed.

Patients were included if they

• Were diagnosed within the past year
• Had an expected survival time of at least six months
• Had a treatment recommendation of radiation therapy of at least two weeks.

Patients were excluded if they had undergone previous radiation therapy, had recurrent disease after a disease-free period longer than 6 months, or had psychiatric disorders or active suicidality.

Division of Radiation Oncology, Mayo Clinic, Rochester, Minnesota

Patients were undergoing the active treatment phase of care.

The study was a randomized, stratified, two-group, controlled clinical trial and included a structured intervention arm (n = 49) and a standard medical care arm (n = 54).

• Linear Analogue Self Assessment (LASA)
• Profile of Mood States (POMS)
• Spielberger’s State-Trait Anxiety Inventory (STAI)
• Symptom Distress Scale (SDS)

The intervention had no significant impact on any fatigue measures between the groups. No significant differences were observed at baseline between the groups for fatigue. There were no significant differences in mean fatigue scores between the groups at any week.

The compliance of the patients after the sessions were completed is unknown.

To evaluate the effect of types of exercise on cancer-related fatigue.

Only randomized, controlled trials studying the outcome variable of cancer-related fatigue were included.

Seven thousand two hundred forty-five articles met the initial selection criteria. A final sample of 44 studies was included. Two independent raters collected data, and the intensity of exercise was estimated using metabolic equivalent units (METs).  MET values for a given exercise were coded from the Compendium of Physical Activity.

• The total number of participants across all studies was 3,245.
• Twenty-five studies exclusively reported breast cancer survivors.
• Mean age was 53.8 years.
• Forty-six percent of patients were undergoing active cancer treatment.

Characteristics of the Interventions

• Average length of exercise was 11.5 weeks (standard deviation [SD] = 5.2 weeks), and average intensity was 5.6 MET.
• Twenty-four studies included only aerobic exercise, six included only resistance exercise, 11 included a combination of resistance and aerobics, and six used neuromuscular exercise, such as yoga or tai chi.
• Ten studies used a theoretical base:  transtheoretical model of behavior change, self-efficacy, Roy adaptation model, Payne adaptation model, and the Levine conservation model.

Fatigue Measurement

• Fatigue was measured in 30% of patients with the Functional Assessment of Cancer Therapy (FACT) questionnaire, 20% with the Piper Fatigue Scale, 13% with the Profile of Mood States (POMS), 11% with the Brief Fatigue Inventory (BFI), 11% with the European Organisation for Research and Treatment of Cancer Quality of Life questionnaire (EORTC QOL-C30), and 4% with the linear analog scale.

Regression analysis was used to identify factors that were related to the degree of fatigue modulation.  Significant factors were

• Adherence to a theoretical model (p < 0.001)
• Sample of older cancer survivors (p = 0.04)
• Moderate intensity resistance exercise use (3–6 MET) (p = 0.01).

Session length and number of exercise sessions were not significantly related to effects on fatigue.

Overall effect size of fatigue modulation was 0.31 (95% confidence interval [0.22, 0.4]).  Effect size was 0.39 among survivors of breast cancer and 0.42 among survivors of prostate cancer.  In other cancer types, there were few studies and very small effects, but analysis demonstrated a consistent effect in favor of exercise.

Resistance exercise of moderate intensity appears to be the most effective in reducing cancer-related fatigue. This finding can be useful in planning exercise interventions as well as further research. The report stated a dose response effect on fatigue with exercise; however, the number and length of sessions was not a predictor of the degree of change in fatigue. These two findings seem to be contradictory. This aspect was not discussed by the authors.

The finding that resistance exercise interventions of moderate intensity were more effective than low-intensity or aerobic exercise is contrary to current National Comprehensive Cancer Network (NCCN) and American Cancer Society (ACS) guidelines, which do not mention resistance exercise and emphasize aerobic exercise. Moderate resistance exercise, such as weight machines, resistance bands, or free weights, may be a type that patients can maintain more easily. Use of theoretical models that incorporate issues of exercise behavior and behavior change may be more effective in providing support for the psychological components of adhering to an exercise program.

To perform a meta-analysis and systematic review to determine the efficacy of exercise in reducing the symptoms of depression among cancer survivors

• Databases searched were PubMed, PsycINFO, CINAHL Plus, SPORTDiscus, and ProQuest medical databases. In addition, investigators searched reference lists for relevant studies.
• Search keywords were cancer (and related terms), depression OR anxiety (and similar terms) AND exercise (and associated terms).
• Included studies were RCTs involving exercise, adults who had survived some form of cancer, and at least one measure of depression.
• Authors excluded studies involving children.

• The sample was composed of 14,702 participants.
• Except for noting the general method of collecting data, authors did not report the evaluation method.

• The number of studies included in the sample was 37; the number of participants was 2,929. Authors did not provide the sample range across studies.
• The sample included patients with breast, prostate, and colorectal cancers as well as patients with leukemia and lymphoma.

Late effects and survivorship

• The intensity of exercise was low to moderate, according to calculations of metabolic equivalent of task (MET).
• Exercise interventions most often occurred during curative treatment. 
• Compared to standard care, exercise provided a small reduction in measures of depression symptoms. Subgroup analysis showed this effect among breast cancer patients only (d = –0.19, 95% CI –0.28, –0.09). Moderators of the effect were increases in the amount of aerobic exercise per week: Aerobic exercise reduced depression in dose-response fashion. 
• Effects were greatest when exercise sessions were supervised.

Findings support the conclusion that exercise has a small positive effect on symptoms of depression among women with breast cancer.

• Studies were highly heterogeneous, even just those studies of patients with breast cancer.
• Authors state that included studies were limited by sample size and quality issues, but they do not describe how they assessed study quality.
• In most studies, depression symptoms were at a very low level at baseline.
• Effect sizes were very small.

Findings suggest that supervised aerobic exercise may be helpful in reducing mild symptoms of depression among women with breast cancer. Applicability of the findings to patients with other diagnoses is unclear.

To determine the protective effects of memantine on cognitive function in patients receiving whole brain radiotherapy (WBRT)

Patients received a total of 37.5 Gy WBRT over 15 fractions. Patients were randomized to receive escalating doses of memantine or placebo orally for 24 weeks beginning within three days of WBRT initiation. Weekly escalation was: Week 1: 5 mg every morning; Week 2: 5 mg twice daily; Week 3: 10 mg every morning, 5 mg every evening; Weeks 4–24: 10 mg twice daily.  Five neuropsychological assessments were performed at baseline, 8 weeks, 16 weeks, 24 weeks, and 52 weeks.

• N = 256 (study drug arm) and 252 (placebo arm)    
• MEDIAN AGE = 59 years
• MALES: 44%, FEMALES: 56%
• KEY DISEASE CHARACTERISTICS:
  • Adults with a pathologically proven solid malignancy and visible brain metastases on MRI or CT scan: lung = 355, breast = 75, colon = 5, other sites = 73 
  • Neurologic function: fully active, no symptoms = 40%; some symptoms, fully active = 53%; not active with symptom = 7% 
  • 71% had no prior radiosurgery or surgical resection for brain lesions; 45% had received prior chemotherapy; 65% were receiving steroid therapy at baseline assessment; and 27% were receiving WBRT at time of baseline assessment.
• OTHER KEY SAMPLE CHARACTERISTICS:
  • Primarily Caucasian = 84%, non-Hispanic/Latino = 93% 
  • Education status: grades 0–12 = 65%, some college/technical school = 18%, bachelor’s degree = 17%

• SITE: Multi-site (143 centers participating in Radiation Therapy Oncology Group studies)  
• SETTING TYPE: Outpatient    
• LOCATION: United States of America and Canada

• PHASE OF CARE: Multiple phases of care

• Longitudinal randomized double-blind placebo-controlled clinical trial; pre-post test design involving multiple longitudinal neuropsychological assessments (baseline up to one-year post intervention)

• Hopkins Verbal Learning Test (HVLT)-Revised Total Recall, Delayed Recall, and Delayed Recognition subscales: memory
• Trails Making Test Part A (TMT-A): speed of processing
• Trails Making Test Part B (TMT-B): executive control function 
• Controlled Oral Word Association Test (COWA): verbal fluency
• Clinical Trials Battery Composite (mean of the z scores of all the instruments)
• Mini-Mental Status Examination (MMSE): global cognitive function

Overall, trends of less cognitive decline were observed over time for those receiving memantine versus those receiving placebo. Significant differences (p < 0.05) between groups for cognitive decline were (1) raw scores and standardized scores for memory recognition (HVLT-Recognition) at 24 weeks, (2) raw scores for global cognitive function (MMSE) at 24 weeks, and (3) fewer individuals experiencing a change of 2 SD in verbal fluency (COWA) at eight weeks. The probability of cognitive failure was greater for the memantine arm (53.5%) than for the placebo arm (64.9%). Likewise, the time to cognitive failure was significantly longer in the memantine arm. Significant differences (p < 0.05) were observed in the memantine arm for COWA scores at 8 weeks and 16 weeks and for TMT-A and MMSE at 24 weeks. There were no differences between groups in progression-free survival, overall survival, use of steroids, or side effects experienced for memantine or placebo.

Use of memantine during and after WBRT was well tolerated and resulted in trends of better cognitive function over time, delays in cognitive failure, and reduced rates of decline for specific cognitive functions involving memory, executive control function, and processing speed. However, generalization of these results is limited due to the small sample size at study conclusion, which resulted in a lack of statistically significant findings.

• Subject withdrawals ≥ 10%  
• Other limitations/explanation: Number of subjects completing intervention and longitudinal assessments did not meet power analysis quota.

This study demonstrates the potential application of administering prophylactic memantine during WBRT to reduce cognitive decline observed in individuals with brain metastasis. These results are limited and warrant further study with a larger sample size enrolled throughout study conclusion.

To review the studies regarding cancer-related anorexia and cachexia symptom management and to make recommendations for future directions

A literature search was conducted using the Cochrane Library, MEDLINE, CancerLit, CINAHL, Embase, CRISP, EBM Reviews: Best Evidence, and dissertation abstracts.

All studies focused on increasing food intake. Studies evaluated included:

• Seven nonpharmacologic randomized controlled trials (RCTs) that examined the effects of nutritional counseling and/or commercial oral liquid supplements. Sample sizes ranged from 26 to 180 patients. Clinical trials were included if the major focus was increasing food intake, decreasing energy usage, or minimizing weight loss. 
• Four topical research reviews on pharmacologic and exercise interventions.
• Three overviews of the problem from 1998 to 2000.
• One meta-analysis on oncology nursing symptom-management interventions.
• Twenty-eight RCTs testing cancer symptom management interventions from published and unpublished studies from 1981 to 1990. Only one study focused on anorexia and cachexia.

Weight, appetite, and well-being were improved with progestational agents, with megestrol acetate having the most supporting evidence. All nonpharmacologic RCTs reported improved caloric intake resulting from nutritional counseling and oral liquid supplements. The meta-analysis concluded that insufficient evidence existed at the time to recommend any of the nursing interventions.

Patients with cancer should be screened at diagnosis and reevaluated at regular intervals for current and potential nutritional problems. If nutritional screening identifies an at-risk patient, a comprehensive nutritional assessment should be completed. A valid screening tool is needed.

STUDY PURPOSE: To summarize epidermal growth factor receptor inhibitor (EGFRI)–induced rash management recommendations and evaluate the scientific evidence of these recommendations

TYPE OF STUDY: Systematic review

• FINAL NUMBER STUDIES INCLUDED = 59 
• TOTAL PATIENTS INCLUDED IN REVIEW = Not noted
• SAMPLE RANGE ACROSS STUDIES: Not noted
• KEY SAMPLE CHARACTERISTICS: Most articles reviewed were expert opinion. No patient demographics were noted in the article.

PHASE OF CARE: Active antitumor treatment

INTERVENTIONS: Most articles identified in their search recommended both topical and oral antibiotic treatments. All three randomized, controlled trials and five of seven studies with prospective designs supported their use. Other common drug interventions included topical corticosteroids and antihistamines.

EVIDENCE: In the 59 articles, a range of evidence sources were cited for rash management recommendations. The most common basis of evidence for recommendations was expert opinion.  

RASH SEVERITY: Data demonstrated a pattern of escalating rash management interventions by rash severity: Topical treatments are mostly recommended for grade 1 rash, oral treatments are recommended for grade 2 rash, and delay or dose interruptions are almost exclusively recommended for grade 3 rash.

VARIATION: Data also revealed that substantial variation exists in the recommendations for rash management. Twenty rash management interventions were reviewed, including oral and topical retinoids, benzoyl peroxide, salicylic acid, and vitamin K cream. Recommended treatments, including oral and topical antibiotics, may be indicated for various grades of rash.

PREVENTION: Three randomized, controlled trials evaluated the prevention of onset of EGFRI-induced rash by using oral antibiotic prior to rash onset. All studies found that preemptive oral antibiotics were well tolerated and showed signs of reducing severe skin toxicities; however, future studies are needed.

Most recommendations for EGFRI-associated rash management relied on expert opinion. Although differences in the rash management recommendations existed, it was generally agreed that interventions for the rash management was dependent on the rash severity. For mild (grade 1) rash, topical treatments were recommended. For grade 2 rash, oral antibiotics or corticosteroids were recommended. For severe (grades 3 and 4) rash, treatment with oral corticosteroids and dose interruptions and delays were recommended. Additional randomized, controlled studies are needed to evaluate preemptive versus reactive treatments for EGFRI-induced rash.

• No quality evaluation
• Most common source cited for recommendations was expert opinion

Various interventions are available for managing mild, moderate, and severe EGFRI-induced rash. Nurses need to assess patients who are receiving EGFR inhibitors for severity of skin rash. Also, nurses need to understand the variety of options for managing EGFRI-induced rash and collaborate with physicians to select an appropriate intervention.

To evaluate the effectiveness of a combined biobehavioral intervention (CBI) and cognitive behavior therapy (CBT) for depressed patients coping with the stresses of cancer

12–20 individual 75-minute CBI and CBT sessions

Topics: Stress, coping, communication, seeking information

• N = 36
• MEAN AGE: 49 years
• MALES: 0%, FEMALES: 100%
• KEY DISEASE CHARACTERISTICS: Breast and gynecologic

• SITE: Single site   
• SETTING TYPE: Outpatient   
• LOCATION: Cancer Center in Northeast United States

PHASE OF CARE: Late effects and survivorship

Single group pre-post design

• Hamilton Rating Scale for Depression (HRSD)
• Beck Depression Inventory (BDI)
• Fatigue Symptom Inventory (FSI)
• Brief Pain Questionnaire
• Quality of Life

Depressive symptoms, fatigue, and mental health significantly improved following intervention.

CBI and CBT showed significant improvement in depression, fatigue, and quality of life and reduced cancer stress.

• Small sample (< 100)
• Risk of bias (no control group)
• Risk of bias (no random assignment)
• Subject withdrawals ≥ 10%

Cancer survivors who display depressive symptoms may benefit from CBI and CBT.

To assess efficacy of patient-controlled intrathecal analgesia for management of cancer-related pain, emphasizing impact on breakthrough pain control and other symptoms

After patients had placement of an intrathecal pump, patient-controlled analgesia was begun immediately. Usually, the starting PCIA dose was 10% of the daily opioid dose, administered every 2–4 hours as needed. Patients used PCIA in addition to previous breakthrough medications as needed. After hospital discharge, patients were instructed to use PCAI and NSAIDs for any residual incisional pain. Patients completed symptom inventory assessment and were asked to respond to questions about breakthrough pain.

• N = 58   
• MEAN AGE = 56.8 years (SD = 14.6 years)
• MALES: 68.9%, FEMALES: 22.1%
• CURRENT TREATMENT: Not applicable
• KEY DISEASE CHARACTERISTICS: Various tumor types. Prostate and colorectal were most prevalent.
• OTHER KEY SAMPLE CHARACTERISTICS: All patients had planned implantation of an intrathecal pump due to either poorly controlled pain or intolerance of opioids from sedation, nausea, or constipation. Of the patients, 40% had opioid monotherapy via the intrathecal pump, and 42% received opioid and bupivacaine.

• SITE: Single site   
• SETTING TYPE: Multiple settings    
• LOCATION: Utah

• Prospective observational

• MD Anderson Symptoms Inventory
• Breakthrough pain survey

The follow-up period ranged from 12–82 days. On average, worst pain scores were 8.32 prior to the intervention and 4.98 postintervention (p < 0.001). Of the patients, 8% reported worse pain and 12% reported no change. Of the remaining patients, 56% reported at least a 30% reduction in pain, and 44% reported a 50% reduction. The percentage of patients reporting breakthrough pain after the intervention was reduced by 20% (p < 0.013), and efficacy of PCIA was reported to be better than the efficacy of prior breakthrough medications (p < 0.0001). Sixty-five percent had discontinued all nonintrathecal opioid medications at follow-up. Of a total of 98 pumps inserted, there was infection in one case requiring pump removal and antibiotics, and three patients developed postdural puncture headache that resolved in two to three weeks with use of an epidural blood patch.

Patient-controlled intrathecal analgesia was effective for improved chronic and breakthrough pain control.

• Small sample (< 100)
• Risk of bias (no control group)
• Risk of bias (no blinding)
• Risk of bias (no random assignment) 
• Key sample group differences that could influence results 
• Measurement/methods not well described
• Measurement validity/reliability questionable
• Various patients were receiving multiple different adjunct medications for pain. Measurement of breakthrough pain was not well described. High variability existed in the follow-up time frame for measurement.

Findings of this study showed that intrathecal patient-controlled analgesia was associated with improved pain control in patients with refractory and breakthrough cancer-related pain, and this intervention was associated with few complications. These findings are limited by the study design. These results are promising, and further well-designed research to establish the appropriate role of patient-controlled intrathecal analgesia in cancer-related pain control is warranted.

To evaluate the feasibility and efficacy of an eight-week, supervised exercise program in deconditioned cancer survivors within two to six months of chemotherapy completion

Twice-weekly, aerobically-based group sessions in a hospital setting for a duration of eight weeks plus a home exercise program.

• SITE: Single-site    
• SETTING TYPE: Other    
• LOCATION: Ireland

• PHASE OF CARE: Late effects and survivorship

Prospective, two-arm, randomized controlled trial

• Feasibility: Demand and recruitment rates
• Adherence: Heart rate monitor, diaries, observation, and attendance
• Acceptability: Exit participant interviews
• Fitness: Modified Bruce Protocol (MBP)
• Quality of Life: Functional Assessment of Cancer Therapy–General (FACT-G)
• Fatigue: Functional Assessment of Chronic Illness Therapy–Fatigue (FACIT-F)
• Physical Health: Physical Function Scale (PFS) of the Short Form (SF) 36
• Physical Activity (PA): RT3 triaxial accelerometer and self-report using the Godin Leisure Time Exercise Questionnaire

Feasibility: 81% eligible patients were recruited to the study. Conflicting data on drop-outs were presented. Exercise intervention was positively received as noted in exit interviews with subjects. Adherence to supervised and home-based exercise intervention was good (76% to 105%, respectively). There were no statistically significant differences between the groups for any health-related fitness outcomes. Total FACIT and fatigue subscale scores were better in the exercise group at three months (mean difference = 6.2, 95%, CI 1.4–11.0).

• Small sample size (< 100)
• Baseline sample/group differences of import: Gender, treatment, and stage of cancer
• Risk of bias (sample characteristics): Gender, treatment, and stage of cancer
• Key sample group differences that could influence results: Majority of sample was female; there was a disproportionate distribution of radiation/chemotherapy-treated patients and patients with late/early-stage in exercise and control groups.
• Findings not generalizable
• Intervention expensive, impractical, or training needs
• Subject withdrawals ≥ 10%: The explanation of withdrawals and reasons do not match the number of subjects that completed assessments at each phase.
• Other limitations/explanation: Variability of activities for home exercise program.

Data support the benefit of exercise to address cancer-related fatigue in the early survivorship period. However, sample was “healthy” with few co-morbidities and, although deconditioned, did not include older adults (> 65 years of age), which raises questions about safety and which type and dose of exercise should be recommended to the large group of cancer survivors who continue to experience cancer-related fatigue.

STUDY PURPOSE: To synthesize the evidence regarding the effect of rapid diagnostic approaches on anxiety in patients with cancer

TYPE OF STUDY: Systematic review

• FINAL NUMBER STUDIES INCLUDED: 23
• TOTAL PATIENTS INCLUDED IN REVIEW: 3,663
• SAMPLE RANGE ACROSS STUDIES: 27-583 patients
• KEY SAMPLE CHARACTERISTICS: Most (16) studies involved patients with breast cancer.

PHASE OF CARE: Diagnostic

Patients receiving a benign diagnosis showed significant decreases in anxiety. Women eventually diagnosed with breast cancer had either increased or sustained anxiety levels; however, increases were not statistically significant in all but one study. Findings were mixed in this regard across studies involving prostate and ovarian cancer and melanoma. Among suspected breast cancer cases, 46%-73% had anxiety scores (Hospital Anxiety and Depression Scale [HADS] instrument) that were ≥ 8, indicating at least borderline clinically relevant anxiety. In studies using the State-Trait Anxiety Inventory (STAI) tool, suspected patients with breast cancer had mean STAI scores between 40.1 and 60, with a score of 44 being considered high anxiety. Three studies examined the effect of rapid diagnostic evaluation in breast cancer. One study found significantly larger reduction in anxiety after 24 hours in a one-stop evaluation versus two-stop evaluation; however, this difference disappeared after three weeks. In all studies, anxiety declined significantly among those who had benign result when results were obtained more quickly. In all studies, there were small numbers of patients who were diagnosed with benign disease.

Rapid diagnostic pathways reduce anxiety in patients with benign disease.

No evaluation of the quality of studies was included.

Findings that anxiety declines in patients with benign disease are not surprising. Findings confirm that the more quickly one receives a benign diagnosis, the more quickly related anxiety is reduced. The emotional impact during the diagnostic phase related to cancer can be substantial. Use of one-stop rapid diagnosis can result in a shorter period of uncertainty and related anxiety.