To assist the health care practitioner by summarizing research studies that have examined the use of nonpharmacologic adjunctive therapies (NATs) for symptom management in pediatric oncology patients

• Databases searched were Cochrane Library, PubMed, CINAHL, and PsycINFO.
• Authors included an extensive list of search keywords. Of particular relevance to the pediatric oncology setting were pain, cancer, oncology, self-care, nausea, vomiting, fatigue, and coping.
• Studies were included if they dealt with nonpharmacologic therapies to help alleviate symptoms associated with cancer treatment in children.

Investigators retrieved and reviewed 41 studies. Their review related to symptoms studied, modalities used, study design, sample size, and study results. The analysis included all 41 studies. The studies pertained to multiple modalities, including hypnosis, imagery, breathing, distraction, relaxation, cognitive behavioral therapy, art therapy, and music therapy.

• Sample sizes ranged from N – 1 to 122 patients.
• Across studies, participants included in the samples were pediatric patients receiving chemotherapy, needlesticks, radiation, lumbar punctures, bone marrow aspiration, IV insertion, MRI, or port placement for the treatment of unspecified disease.

Over all the studies, the results are mixed in regard to the effect of NATs on procedural pain. Some studies indicated that hypnosis produced promising results in reducing procedural pain. Cognitive behavioral therapy and distraction showed both an effect and no effect on pain. One study (based on observation and self-reporting) indicated that NATs had no effect on procedural pain. In a few studies, hypnosis (along with distraction and relaxation and cognitive behavioral therapy) produced significant pain reduction. Studies found that music therapy had little to no effect on the pain of bone marrow aspiration.

This review of NATs produced mixed results.

• The samples studied were inconsistent in regard to modality.
• Some terms (e.g., anxiety and distress) were found to be interchangeable; on the other hand, hypnosis encompassed several definitions.
• The sample size of some of the studies was small.
• In the pediatric populations studied, the intervention provider (patient, professional, or parent) was unclear.

More research needs to be done in this area. Health care practitioners, patients, and families need education about NATs and their application to pediatric oncology.

In the control group, one of the researchers visited caregivers for about 10 minutes twice a week for three weeks and asked, “How are you doing?”

In the massage therapy and Healing Touch groups, caregivers were provided with six 30-minute sessions. A certified massage therapist administered massage therapy, and a certified therapist provided Healing Touch treatments.

• The sample (N = 36) was comprised of family caregivers of patients undergoing hematopoietic stem cell transplantation.
• Caregivers did not have an acute health problem.

Outpatient oncology clinic

• The study was a well-designed quasi-experimental trial without randomization (control group [n = 13], massage therapy group [n = 13], Healing Touch group [n = 10]).
• The sample size was determined by power analysis.

• Subjective Burden Scale
• Beck Anxiety Inventory
• Center for Epidemiologic Studies–Depression
• Multidimensional Fatigue Inventory–20

• No significant difference was found in burden.
• Anxiety scores declined significantly for the massage therapy group only.
• Although depression scores declined for both treatment groups, only the massage therapy group achieved significance on post-hoc analysis.
• Significant differences in general fatigue, reduced motivation fatigue, and emotional fatigue were found between the control and massage therapy groups, but no differences were found in physical fatigue and activity.

• The study had a small sample and no randomization.
• Special training was needed for the intervention.

STUDY PURPOSE: To evaluate evidence regarding effects of psychoeducational interventions for preoperative anxiety

• FINAL NUMBER STUDIES INCLUDED  =  13
• TOTAL PATIENTS INCLUDED IN REVIEW: Not provided
• SAMPLE RANGE ACROSS STUDIES: Not provided
• KEY SAMPLE CHARACTERISTICS: Not provided, although report does state inclusion of patients with cancer

PHASE OF CARE: Active antitumor treatment

The report suggests that nursing interventions of a psychoeducational nature can reduce preoperative anxiety, based on findings of six randomized, controlled trials conducted from 1985 to 2005. Samples in these studies were self-selected, and the review identifies a number of study design aspects that would create risk of bias, inappropriate statistical analysis, and high volume of missing data and elimination of patients from data analysis. The review also stated that patients benefit from individualized information and have associated reduction in anxiety; however, review of these studies also suggested multiple design flaws, and this finding appears to be based on various authors’ recommendations rather than actual study findings.

There are multiple limitations of this review, and it does not provide strong support for effectiveness of various nursing interventions to reduce preoperative anxiety.

No information is provided about study sample types or actual quality of studies included. Findings stated in the article are not clearly derived from actual research results.

Due to study limitations, this review does not provide strong support for the efficacy of psychoeducational and informational interventions to reduce preoperative anxiety. Provision of preoperative patient education is a necessary component of care, but it may not be sufficient to alleviate anxiety.

The purpose of this meta-analysis and systematic review was to examine the effects of prophylactic colony-stimulating factors (CSFs) related to reduction in incidence and duration of febrile neutropenia as well as “all-cause” and infection-related mortality in patients with breast cancer undergoing chemotherapy.

Various national and international databases were examined.

Articles were examined if they were randomized, controlled trials (RCTs) comparing CSFs with placebo or no treatment for patients with breast cancer and all stages identified as at-risk for developing febrile neutropenia during chemotherapy

Articles were excluded if they reported on trials for secondary prophylaxis with G-CSF or GM-CSF or primary prophylaxis with G-CSF.

1,023 total references were retrieved

Quality of the evidence was evaluated using the guidelines from the Cochrane Handbook for Systematic Reviews of Interventions for risk of bias. The GRADES levels of evidence were applied to study outcome areas.

• Eight studies were included in the final analysis.
• The sample range across all eight studies was 20–928
• Patients were aged 18-78 years, with a mean age of 50. 
• Patients had a diagnosis of breast cancer and were receiving chemotherapy (any regimen).

• The phase of care was active antitumor treatment  
• Application was for elder care

Effect of primary prophylactic CSF use on rate of febrile neutropenia showed a risk ratio (RR) of 0.27 (95% CI [0.11, 0.7]) in favor of CSF prophylaxis. Evidence in this area was graded as moderate.
Early mortality risk was significantly lower in the intervention group (RR = 0.32; 95% CI [0.13, 0.77].  When one large study was taken out of analysis, accounting for five deaths in the control course and 14 in the control group, the significance was not realized (RR = 0.19; 95% CI [0.03, 1.24]) The grade of evidence in this area was deemed to be low. There was minimal size of effect on the outcome of rate of infection related mortality with (RR = 0.14; 95% CI [0.02, 1.20]). Evidence in this area was graded as low.

Conclusions are difficult to summarize because the studies did not use standard definition of febrile neutropenia, subjects were not homogenous for breast cancer (stage, pathology, treatment, and risk for FN).
No recommendations can be made based on quality and limitations of studies.

Six of the studies identified risk of bias, three of these six had more than one bias risk.  Forty percent of patients included in summary are from one study. Overall, studies were of low to only moderate level of quality. This review includes only studies conducted on patients with breast cancer.

This report does not strengthen evidence already available from guidelines for prophylactic use of CSFs in breast cancer.

To assess whether urea-based cream (UBC) has prophylactic benefits on sorafenib-induced hand-foot skin reaction (HFSR) in patients with advanced hepatocellular carcinoma (HCC)

Patients were randomized to the intervention or control group. Patients in the intervention group received 10% UBC three times a day plus best supportive care (BSC), and those in the control group received BSC alone starting on day 1 of sorafenib treatment for up to 12 weeks. Once HFS developed, patients were allowed to use any creams per the treating physician. HFSR was evaluated every two weeks for 12 weeks, and an additional follow-up assessment was conducted at 14 weeks.

• N = 699
• AGE = 20–86 years
• MALES: 86%, FEMALES: 14%
• KEY DISEASE CHARACTERISTICS: Advanced HCC
• OTHER KEY SAMPLE CHARACTERISTICS: Performance status, previous anticancer therapy, history of disease

• SITE: Multi-site    
• SETTING TYPE: Not specified  
• LOCATION: 64 centers throughout China

• PHASE OF CARE: Active antitumor treatment
• APPLICATIONS: Elder care, palliative care 

• Investigator-initiated, randomized, open-label, phase-III, multicenter clinical trial

• Patient-reported questionnaire
• HFSR evaluated by physician at each visit with Common Terminology Criteria of Adverse Events (CTCAE), version 3, every two weeks for 12 weeks

During the 12-week study, the patients receiving prophylactic UBC plus BSC had a significantly lower incidence and severity of HFSR than those receiving only BSC at each study visit (p < 0.001) for the entire 12-week study period (p < 0.001). At each study visit, the incidence of any grade HFSR was lower in the study group (p < 0.001). The time to first occurrence was significantly longer in the UBC group (p < 0.001). The rates of grade II and grade III HFSR were lower in the experimental group compared to the controls (p = 0.004).

UBC prophylaxis in patients with advanced HCC starting sorafenib reduced HFSR rates, extended the time to first occurrence of HFSR, and improved patient quality of life compared to BSC.

• Risk of bias (no blinding)
• Unintended interventions or applicable interventions not described that would influence results
• Findings not generalizable
• “Blinded, randomized, placebo-controlled trials to determine the role of UBC on the incidence and severity of HSFR are warranted.”
• The UBC and BSC group had 85 nonevaluable patients resulting in 354 patients evaluable for time to first HFSR. The BSC group had 87 nonevaluable patients resulting in 345 patients evaluable for time to first HFSR.

UBC plus BSC appears to be of benefit in this particular population of patients receiving sorafenib for advanced HCC. Although this cannot be generalized to other populations, it is worth suggesting to patients as they begin this therapy. Understanding the limitations of this study allows nurses to educate patients appropriately and supports their decisions to add UBC to their care.

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 compare a 12-week Nia-based exercise program to usual care on cancer-related fatigue, quality of life, aerobic capacity, and shoulder flexibility in women receiving radiation therapy for breast cancer

Participants randomized to the intervention were instructed in Nia techniques as well as given a DVD for home use. They were instructed to perform the exercises for 20–60 minutes at least three times a week and maintain a log. The control group were instructed to maintain their usual exercise regime and maintain a log. The principle investigator met individually with both groups at the beginning and at 6 and 12 weeks. At the end of the 12 weeks, control group participants were given the opportunity to take part in a Nia group.

• N = 41  
• MEAN AGE = 56 (range = 34–85)
• KEY DISEASE CHARACTERISTICS: Patients with breast cancer receiving radiation therapy

• SITE: Single site  
• SETTING TYPE: Outpatient    
• LOCATION: Northern Ohio

• PHASE OF CARE: Active anti-tumor treatment

• Randomized, controlled study stratified by stage or disease and age

• Fatigue and quality of fife were measured by the Functional Assessment of Chronic Illness Therapy–Fatigue (FACIT-F).
• Aerobic capacity measured by a six-minute walk test
• Shoulder flexibility assessed using a goniometer

Both groups reported increased fatigue at week 6 (completing therapy) with improvement at week 12. Repeated measures of covariance noted statistically significant differences in the Nia and control groups between weeks 6 and 12; the Nia group had a greater increase in FACIT-F scores (p = 0.05).

Sample size and study limitations make it difficult to draw conclusions; however, Nia exercise can be beneficial to women with breast cancer receiving radiation therapy to reduce cancer-related fatigue.

• Small sample (< 100)
• Baseline sample/group differences of import
• Risk of bias (no blinding)
• Risk of bias(sample characteristics)
• Selective outcomes reporting
• Findings were not generalizable
• Intervention expensive, impractical, or training needs
• Questionable protocol fidelity
• Subject withdrawals ≥ 10% 
• Other limitations/explanation: Control group had less fatigue at baseline; both groups reported that keeping a diary reminded them to exercise

Nia exercise can be beneficial to women with breast cancer receiving radiation therapy, particularly those who favor a holistic or complementary approach.

To evaluate the efficacy and acceptability of acupuncture in pediatric oncology patients receiving highly emetogenic chemotherapy (HEC) as an adjunct to standard antiemetic therapy

Prior to the initiation of HEC, pediatric patients were randomized to either antiemetic medications alone or antiemetic medications with acupuncture. Patients received standard antiemetics for all cycles (5HT3 with or without dexamethasone and IV phenothiazine). Acupuncture was given on day 1 of chemotherapy and on subsequent days on demand. The first two courses of chemotherapy were included in the study.

• N = 5
• MEDIAN AGE = 14.5 years (range = 15–16.8)
• MALES: 20%, FEMALES: 80%
• KEY DISEASE CHARACTERISTICS: Treated for sarcoma

• SITE: Multi-site    
• SETTING TYPE: Not specified  
• LOCATION: Witten, Germany

• PHASE OF CARE: Active antitumor treatment
• APPLICATIONS: Pediatrics

Quasi-experimental, crossover design

• Patients' diaries noted why they chose to continue the intervention (acupuncture).
• Determined if patients were able to reduce the amount of antiemetic medication taken during subsequent courses of chemotherapy without breakthrough chemotherapy-induced nausea and vomiting

Patients receiving acupuncture perceived that they had reduced chemotherapy-related side effects and higher levels of mental alertness.

Episodes of nausea and vomiting were not statistically different with or without acupuncture. One patient experienced pain during needling.

• Small sample (< 30)
• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• Measurement/methods not well described
• Measurement validity/reliability questionable
• Subject withdrawals ≥ 10%  
• Other limitations/explanation: Extremely small number of patients

Pediatric patients receiving HEC may be open to acupuncture to reduce chemotherapy-induced nausea and vomiting in addition to standard antiemetic therapy. More research needs to be done to validate its benefit.

To evaluate a patient education program aimed at reducing fatigue.

Patients were randomly assigned to intervention or wait-list control groups. The intervention consisted of group education and support sessions for 90 minutes once weekly for six weeks. Data were collected at baseline and at six weeks and six months postintervention. Patients were encouraged to keep a diary at home, perform exercises, and implement lifestyle changes.

• In total, 234 patients (2.6% male, 97.4% female) were included.
• Mean age was 57.5 years.
• Patients had breast, colon, and prostate cancers.
• Greater than 90% of the patients had fatigue for longer than six months. Baseline fatigue scores from multiple tools showed that patients were highly fatigued and had significant fatigue interference with daily activities.

• Multisite 
• Outpatient 
• Germany

Patients were undergoing the late effects and survivorship phase of care.

The study was a randomized, controlled trial.

• Fatigue Assessment Questionnaire
• European Organisation for Research and Treatment of Cancer Quality of Life (EORTC-QOL)
• General Self Efficacy (GSE) Scale
• Exercise Self Efficacy (EXSE) Scale
• Frieburg Questionnaire on Physical Activity
• Hospital Anxiety and Depression Scale (HADS)
• Fatigue Knowledge Scale (developed by the investigator)
   

Analysis showed that, over time, fatigue was significantly reduced in the intervention group (effect size of partial eta² = 0.248; p < 0.001). GSE and EXSE improved over time in the intervention group but declined in the control group.

Findings demonstrated that the psychoeducational intervention was effective in reducing cancer-related fatigue.

• The study had risks of bias due to no appropriate attentional control condition and no blinding.
• Unintended interventions or applicable interventions were not described that would have influenced the results (no information was provided about the use of medications or other interventions that could have influenced the outcomes).

The study adds to the body of evidence that supports the effectiveness of psychoeducational interventions for the management of cancer-related fatigue. This group of patients was very fatigued at baseline, and the effect size of the intervention was substantial, suggesting that the psychoeducational approach effect was clinically meaningful in a challenging group of patients.

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.