STUDY PURPOSE: To evaluate evidence for psychological interventions in women with breast cancer

TYPE OF STUDY: Meta analysis and systematic review

PHASE OF CARE:  Multiple phases of care

In 24 of 28 trials, cognitive behavioral therapy was the basis of the intervention. Most studies had unclear risk of bias, and for studies aimed at anxiety and depression, quality of the evidence was graded as low. Comparison of CBT versus control across multiple studies for depression showed an overall standard mean difference (SMD) of -1.01 (p = 0.02) in favor of the CBT intervention. Only two studies examined CBT delivered individually, showing no significant benefit and high heterogeneity. Examined separately, group CBT also did not consistently show significant benefit for depression. Eight studies looked at change in anxiety. Both individual- and group-delivered CBT showed significant benefit, with an overall SMD -10.48 (p = 0.0006). CBT showed a significant positive effect for stress, and only marginal effect on quality of life.

Findings showed overall benefit of CBT for anxiety and depression in women with early-stage breast cancer

Although studies have shown that psychological interventions are more effective for individuals with psychological problems, the studies included here excluded women with psychological morbidity.  There was high heterogeneity, and most studies were of low quality.

CBT delivered in a group or individual setting has been shown to have a positive effect on depression and anxiety among women with early-stage breast cancer. The strength of these results is limited by the relatively low quality of studies included in this review.

• The author described strategies to prevent or minimize symptoms of palmar-plantar erythrodysesthesia (PPE).
  • Dose reduction or interruption of therapy often is necessary.
  • Use a systemic strategy.
  • Pyridoxine has been found beneficial as therapy (doses of 50–150 mg per day).
  • High-potency corticosteroids and a wet disinfectant treatment of blisters and erosions have been effective as local topical therapy. For grade 1 PPE, avoiding mechanical irritation of the skin on the palms and soles and mild emollient creams are sufficient. Cooling the affected areas with a cooling battery or hand and foot baths (without extensive washing) may relieve the symptoms.

Multiple interventions can be implemented to prevent or minimize PPE, including teaching patients to avoid mechanical irritation of the skin, use topical emollient creams, and use regional cooling.

• Patients received 910 mg/m² IV amifostine as a 15-minute infusion prior to 200 mg/m² melphalan.
• Ten consecutive patients who were treated within the same protocol without amifostine were used as controls.
• Patients received granulocyte colony-stimulating factor (G-CSF) from day +4 to neutrophil recovery.

• The study reported on a sample of 20 patients.
• All patients were receiving 200 mg/m² high-dose melphalan and autologous stem-cell transplant (ASCT).
• Patients were given cytoxan, mesna and G-CSF for mobilization.

The study was conducted between November 1998 and February 2000.

This was a pilot, feasibility study.

The National Cancer Institute (NCI) Common Toxicity Criteria for Oral Mucositis was used to assess oral mucositis daily.

Most of the patients (9 out of 10) received the full dose of amifostine. One patient received only 780 mg/m² because of recurrent hypotension. Significant nausea, as well as hypotension and vomiting, occurred.

Amifostine did not show a benefit for gastrointestinal toxicity or mucositis of more than grade 2.

• This was a feasibility study.
• The sample size was small.

To evaluate the efficacy of ramosetron, aprepitant, and dexamethasone in preventing chemotherapy-induced nausea and vomiting (CINV) in patients receiving cisplatin-based chemotherapy

On day 1, all patients received intravenous 0.6 mg ramosetron and oral 12 mg dexamethasone 30 minutes before chemotherapy, and they received 125 mg aprepitant orally one hour before chemotherapy. On days 2 and 3, patients received 80 mg aprepitant and 8 mg dexamethasone orally in the morning. On day 4, patients only received 8 mg dexamethasone. Patients could take rescue antiemetic medications at any time for vomiting or severe nausea. Antiemetic rescue medications were determined by treating physicians.

• N = 39  
• MEDIAN AGE = 59 years (range = 43–74 years)
• MALES: 75.6%, FEMALES: 24.4%
• KEY DISEASE CHARACTERISTICS: Multiple types of cancer
• OTHER KEY SAMPLE CHARACTERISTICS: Both adjuvant and palliative chemotherapy (primarily palliative)

• SITE: Multi-site    
• SETTING TYPE: Outpatient    
• LOCATION: Korea

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

Prospective, open-label study

• Complete response (no vomiting and no rescue medications divided into acute phase [0–24 hours], delayed phase [24–120 hours], and overall phase)
• Absolute complete response (no vomiting, no rescue medications, and no nausea) 
• Multinational Association of Supportive Care in Cancer Visual Analog Scale (MASCC VAS)
• Common Toxicity Criteria for Adverse Events (CTCAE) clinical and laboratory adverse events

Complete response (CR) was achieved by 94.9% of patients in the acute phase, 92.3% in the delayed phase, and 92.3% in the overall phase. Absolute CR was achieved by 74.4% in the acute phase, 51.3% in the delayed phase, and 46.2% in the overall phase. The median nausea score during the acute phase was 0 (interquartile range [IQR] 0–1), 0 in the delayed phase (IQR 0–4), and 2 during the overall phase (IQR 0–4). On the VAS, mild nausea was observed in 10% of patients in the acute phase and 13% of patients in the delayed phase. Moderate to severe nausea was observed in 15% of patients in the acute phase and 36% of patients in the delayed phase.

The combination of ramosetron, aprepitant, and dexamethasone is an effective CINV regimen. The overwhelming majority of patients in this study achieved a complete response and experienced no nausea or vomiting in both the acute and delayed phase after chemotherapy.

• Small sample (< 100)
• Risk of bias (no control group)
• Risk of bias (no blinding)
• Risk of bias (no random assignment)

Ramosetron, aprepitant, and dexamethasone is an effective regimen to prevent CINV in patients receiving cisplatin-based therapy. Almost all of the patients were able to achieve a complete response in both the acute and delayed phase after administration of chemotherapy. In this study, the majority of patients were receiving palliative care, therefore this combination of drugs should be considered for palliative care patients.

To investigate the effect of a combined hatha and restorative yoga intervention on memory in cancer survivors and to explore relationships between memory and sleep

YOCAS^©® (Yoga for Cancer Survivors) is an instructor-guided standardized program that incorporates movement emphasizing restorative poses, breathing exercises, and mindfulness exercises. The intervention was offered twice a week in the late afternoon or evening over 75 minutes for a total of eight sessions. Although all the group trainers were Registered Yoga Alliance Teachers, they were also required to complete a training session, reviewing a detailed YOCAS^©® manual to facilitate standardization across sites.

• N = 328   
• MEAN AGE = 54.62 years
• AGE RANGE = 26–72 years
• MALES: 4%, FEMALES: 96%
• CURRENT TREATMENT: Hormonal therapy in 53% of sample
• KEY DISEASE CHARACTERISTICS: Various cancers but predominantly breast cancer (77%)
• OTHER KEY SAMPLE CHARACTERISTICS: Of the sample, 82% had a partial college education or more. Seventy-four percent of women were postmenopausal.

• SITE: Multi-site  
• SETTING TYPE: Outpatient    
• LOCATION: 12 cities within the United States

PHASE OF CARE: Late effects and survivorship

Secondary analysis of a randomized, clinical trial

• MD Anderson Symptom Inventory (MDASI)—primary outcome was one item regarding perceived memory.
• Pittsburgh Sleep Quality Index (PSQI)—primary outcome was global sleep quality.

At baseline, the average score on the MDASI indicated only a mild level of perceived memory problems overall. Although both groups continued to report memory problems as being mild, a significant decrease (p < 0.05) was observed in patients who completed the intervention. This difference continued to be significant when controlling for differences in age, gender, educational level, past treatment regimen, current hormonal therapy, baseline memory, and baseline sleep scores. Of note, those who received the intervention also had improved sleep (p < 0.05), which accounted for approximately 26% of the improvement in memory (p = 0.039).

Although yoga appeared to decrease perceived memory problems, this outcome was based on a single item of the MDASI. Further longitudinal studies designed specifically to measure the effect of yoga on cognitive function as measured by both objective and subjective measures are warranted.

• Risk of bias (no blinding)
• Measurement validity/reliability questionable

Although this study suggested that yoga may improve patients’ perception of memory problems, some of the benefit was because of better sleep.

To compare the efficacy of massage therapy to a social attention condition in Taiwanese patients with cancer with bone metastases

• A five-day, two-group trial with a pre/post-test design was used.
• The experimental intervention was 45 minutes of massage; condition control was caring therapist for a comparable amount of time.

• The sample was 72 patients with cancer with bone metastasis.
• Mean patient age was 50 years.
• The sample was 42% male and 58% female.
• The sample was Taiwanese, age 18 or older, oriented x3 (alert and normal), Chinese-speaking and reading, radiologically diagnosed with bone metastasis via bone scan, and reporting moderate bone pain of at least 4 on a 0–10 scale.
• Patients were excluded if they were regularly receiving massage therapy, were undergoing surgeries or procedures during admission, or had allodynia, thrombocytopenia, spinal cord compression syndrome, deep vein thrombosis, or other contraindications to massage therapy.

• Single site
• Inpatient setting
• Five hospital oncology units

• Patients were undergoing the active treatment phase of care.
• The study has clinical applicability for end-of-life and palliative care.

The study was a randomized, controlled clinical trial.

• Present Pain Intensity (PPI) – Visual Analog Scale (VAS)     
• Mood VAS
• Relaxation VAS
• Sleep VAS
• Symptom Distress Scale
• Demographic and medical profiles

• Pre- to postintervention effects: No statistical significance was shown in individual patients.
• Results from MANCOVAs showed statistically significant intervention effects on pain, mood, and relaxation VASs, but not the sleep VAS.
• There was a significant linear group by time effect on relaxation VAS in both groups: F (1, 69) = 10.39, p = 0.002, indicating a different pattern of change in relaxation VAS change scores between the groups.

This trial documented therapeutic effects of massage on improving pain intensity, mood status, and muscle relaxation in patients with metastatic bone pain. The study has clinical implications supporting massage therapy and other medical modalities for optimal improvement in patients with cancer with bone metastases.

• The study had a small sample, with less than 100 participants.
• The patient population was heterogeneous.
• The study involved a short course of therapy.
• The study lacked multidimensional measurement of pain and patient binding.

Massage therapy may play an important role in cancer bone pain, sleep, and, mood.

• FINAL NUMBER STUDIES INCLUDED = 5
• TOTAL PATIENTS INCLUDED IN REVIEW = 415
• SAMPLE RANGE ACROSS STUDIES: 66–93 patients
• KEY SAMPLE CHARACTERISTICS: Mean age = 54.5 years; mean weight = 73.9 kg; mean height = 169 cm; predominantly Caucasian

PHASE OF CARE: Multiple phases of care (not reported)
 
APPLICATIONS: Palliative care

No head to head trials between products existed. FBT produced a greater improvement in PID in the first 60 minutes after dosing (66% more probable than ODT and 68% more than OTFC). ODT and OTFC showed similar benefits, and ODT had a slightly higher benefit with a 53% probability of pain relief at 60 minutes. The two agents compared with morphine sulfate immediate-release, FBT and ODT, were compared, and benefits were significant within 15 minutes after dosing.

FBT may be advantageous as a fentanyl product, as it showed an advantage over ODT and OTFC.

Two of the trials compared FBT to a placebo, so more paitents received FBT. Therefore, cell sizes were not similar, resulting in an unequal comparison. Seven transmucosal immediate-release fentanyl (TIRF) studies existed. Only three were used in the comparison. Limited databases were searched.

Some TIRF products may have better efficacy compared to others. This analysis showed that FBT had an advantage. All products were shown to be superior to morphine in achieving pain relief one hour after dosing. Additional head to head comparison studies are needed.

STUDY PURPOSE: To evaluate the efficacy of oral fentanyl combinations for breakthrough cancer-related pain

TYPE OF STUDY: Meta-analysis and systematic review

DATABASES USED: PubMed

KEYWORDS: breakthrough cancer pain; incident pain; pain flare; morphine; fentanyl

INCLUSION CRITERIA: RCT

EXCLUSION CRITERIA: Not specified

TOTAL REFERENCES RETRIEVED: Not stated

EVALUATION METHOD AND COMMENTS ON LITERATURE USED: Not stated

• FINAL NUMBER STUDIES INCLUDED = 5
• SAMPLE RANGE ACROSS STUDIES, TOTAL PATIENTS INCLUDED IN REVIEW: Not provided
• KEY SAMPLE CHARACTERISTICS: Not provided

APPLICATIONS: Palliative care

The probability of superior relief of breakthrough pain by differences in pain intensity scores at 15- and 60-minute intervals was calculated for immediate-release morphine and fentanyl preparations, versus placebo and versus each other. There was a 61% probability that morphine would produce a better outcome than placebo. Corresponding results versus placebo for fentanyl buccal tablet (FBT) was 97%, for orally disintegrating tablet (ODT) was 72%, and for transmucosal oral fentanyl (OTF) tablet was 81%. The probability of superiority of fentanyl over morphine during the first 60 minutes was 68% for FBT, 57% for ODT, and 66% for OTF. Pain intensity differences were larger for fentanyl preparations than for morphine when compared to placebo.

Findings suggest that oral fentanyl preparations may provide better relief of breakthrough pain during the first 60 minutes than immediate-release oral morphine.

• Small number of studies
• Only one study directly compared fentanyl preparations to morphine.

Findings suggest that oral fentanyl preparations may be more effective for management of breakthrough pain than oral immediate-release morphine. It should be noted however, that the duration of effect with morphine could be longer because of differences in half-life. Onset, intensity, and duration of relief of breakthrough pain with various approaches need to be evaluated to determine the best approach for individual patients.

To examine, within a blinded, randomized, controlled trial design, whether biofield therapy (hands-on healing) would significantly reduce fatigue in survivors with persistent cancer-related fatigue compared to mock healing and a wait-list control group.   

Energy chelation (hands-on-healing with standard hand positions focusing for five to seven minutes over each body part, i.e., feet, hips, knees, bladder, stomach, hands, elbows, shoulders, heart, throat, head, and heart) for one hour, two times each week for four weeks in the intervention group; mock biofield therapy for one hour, two times each week for four weeks; and a wait-list with no specific intervention. All participants submitted saliva samples at four time points. Timing of self-reported measures of quality of life (QOL) and depression were not reported.

• In total, 76 participants (100% female) with breast cancer were included. 
• Age ranged from 31 to 75 years. Mean age was 52 years in the healing group, 52 years in the mock group, and 50 years in the wait-list control group.
• Patients were included if they
  • Were aged 18 to 70 years
  • Were stage I to IIIA
  • Were one month to 10 years post completion of adjuvant or neoadjuvant therapy
  • Scored less than 50 on the RAND SF-36 vigor-fatigue subscale
  • Had no current use of biofield therapy.

• Single site  
• Outpatient
• University of San Diego, San Diego, California

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

The study used a blinded, randomized, controlled design.

• RAND SF-36 vigor-fatigue subscale    
• Multidimensional Fatigue Symptom Inventory-Short Form (MFSI-SF)
• Center for Epidemiologic Studies Depression (CESD) Scale
• Functional Assessment of Cancer Therapy-Breast (FACT-B)
• Biofield Therapies Use and Expectations Questionnaire
   

• Overall attrition was 9%, with no differential attrition between groups. 
• No adverse events were reported.
• Previous use of biofield therapy was 49% prior to the study.
• The passage of time predicted changes for the overall sample for fatigue and QOL but not depression.
• There were no significant differences between biofield healing and mock healing on belief.
• Of the participants, 75% thought they received biofield healing.
• Compared with controls, biofield healing significantly decreased total fatigue (p < 0.0005; Cohen's d = 1.04), as did mock healing (p = 0.02; Cohen's d = 0.68), with no significant differences between biofield healing and mock healing.
• Cortisol slope significantly decreased for biofield healing versus both mock healing and control (p < 0.04 for both; Cohen's d = 0.58).
• Belief predicted changes in QOL over and above group (p = 0.004; Cohen's d = 0.84).
• Belief did not affect fatigue or cortisol variability.

Nonspecific factors are important in responses to biofield interventions for fatigue. Belief predicts QOL responses but not fatigue or cortisol variability. Biofield therapies increase cortisol variability independent of belief and other nonspecific factors. A need exists to further examine the effects of specific processes of biofield healing on outcomes for cancer populations.

• The study had a small sample size, with less than 100 participants.
• The study lacked follow-up assessment.
• The study lacked generalizability.
• Participants older than 70 years of age were included, which was determined to be an exclusion criterion.
   

Use of a hands-on healing intervention takes time and a skill set not traditionally taught in undergraduate or graduate nursing programs. Few clinical nurses have the time or skills to practice hands-on healing as described in the study. The intervention is noninvasive and a potentially effective independent nursing intervention with a minimal side effect profile.

To determine whether biofield therapies affect positive health outcomes and reduce disease symptoms.

Databases searched were PubMed, CINAHL, PyscINFO, and Allied and Complementary Medicine (AMED).

Search keywords were spiritual healing, subtle energy, energy healing, biofield healing, external qi therapy, emitted chi, emitted qi, qi therapy, Johrei, pranic healing, polarity therapy, Reiki, therapeutic touch, and healing touch. Investigators also manually searched the reference sections of studies and review papers.

Studies were included if they

• Were published in a peer-reviewed journal in the English language
• Used a proximally practiced (that is, practiced with the practitioner and client in the same room) biofield-based modality and included quantitative endpoints
• Were randomized, controlled trials (RCTs) with a within-subject design.

Studies were excluded if they related to distant healing or intercessory prayer; integrated modalities that were not biofield-based modalities with biofield-based modalities in such a way that the interventions could not be separated; were animal, plant, and/or in vitro studies; were clinical studies with group assignment but without randomization; were purely descriptive studies; or were unpublished dissertations.
 

• The number of references retrieved was 88.
• Investigators evaluated studies by means of an evaluation quorum that used a checklist of guidelines.
• Ten studies examined the outcomes associated with the use of biofield therapies for patients with cancer.
   

• The number of studies analyzed was 66.  
• The authors did not report the total sample size or the sample size range across studies.
• The sample included patients with pain; hospitalized and postoperative patients; and patients with dementia, cardiovascular issues, and cancer.
   

Patients were undergoing the active treatment phase of care.

The authors presented results according to type of patient and levels of evidence.

• Pain:  The analysis revealed Level I evidence to support biofield therapies as a means of reducing the intensity of pain; Level 4 evidence of affecting comprehensive pain assessment; and Level 4 evidence on affecting anxiety and depression. The analysis also revealed that biofield therapies could have positive effects on health-related quality of life.
• Cancer:  The analysis revealed Level 2 evidence to support biofield therapies as a means of reducing acute pain in patients with cancer; Level 4 of reducing chronic pain; Level 4 of affecting fatigue; Level 4 of affecting quality of life; and Level 4 of affecting physiological measures of relaxation response.
• Hospitalized and Postoperative Patients:  The analysis revealed Level 2 evidence to support biofield therapies as a means of reducing anxiety and Level 2 of reducing pain. The evidence that the analysis revealed about the effect of biofield therapies on depression and functional or autonomic outcomes was insufficient to allow conclusions.
• Dementia:  The analysis revealed Level 2 evidence to support biofield therapies as a means of reducing negative behavioral symptoms associated with dementia.
• Patients with Cardiovascular Issues:  The analysis revealed Level 4 evidence to support biofield therapies as a means of reducing anxiety and Level 4 of reducing diastolic blood pressure. Study quality and duration of each treatment session were not associated with the number of positive outcomes; however, the total number of treatment sessions was positively associated with the number of positive psychological outcomes.

Proximally practiced biofield therapies are promising complementary interventions as means of reducing pain intensity in multiple populations, reducing anxiety in hospitalized populations, and reducing agitated behaviors in patients with dementia. The long-term effects of the therapies on fatigue and autonomic nervous system activity are unclear.

• The review was systematic but not a meta-analysis.
• The authors relied on p-values versus effect size.
• Nonquantitative studies were not included.

Future research should compare biofield therapies with empirically supported treatments for specific conditions.