To identify the long-term effect of complete decongestive therapy (CDT) to decrease lymphedema and enhance quality of life in patients after radical mastectomy with unilateral upper extremity lymphedema

• N = 45   
• AGE = 48.44 (SD = 6.5 years)
• FEMALES: 100%
• CURRENT TREATMENT: Immunotherapy
• KEY DISEASE CHARACTERISTICS: Breast cancer survivors after radical mastectomy
• OTHER KEY SAMPLE CHARACTERISTICS: History of unilateral post mastectomy lymphedema with more than 2 cm circumference than the normal side, aged older than 19 years, no neurological disorders, no untreated or unstable medical conditions, no edema in lower extremities

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

• PHASE OF CARE: Late effects and survivorship
• APPLICATIONS: Palliative care

• Pre-post design

• Modified truncated cone method
• European Organization of Research and Treatment of Cancer Core Quality of Life (EORTC QLQ-C30) questionnaire
• Upper limb lymphedema quality of life (ULL-QOL) questionnaire

Volume of the affected limb was decreased by 80.22 (95% confidence interval [CI] [–96.71, –63.73]) from baseline to the third month (p < 0.0001). Mean change in quality of life at the second month as compared to baseline was significant (69.95, 95% CI [66.49, 73.42], p < 0.0001).

CDT may be effective in reducing the volume in the lymphedema limb and in enhancing breast cancer survivors’ quality of life.

• Small sample (< 100)
• Risk of bias (no control group)
• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• Measurement validity/reliability questionable
• Findings not generalizable
• Intervention expensive, impractical, or training needs
• Single-site study

More rigorously designed studies are needed to examine the effectiveness of CDT in patients with lymphedema. Note that patients who underwent lumpectomy also developed lymphedema.

PHASE OF CARE: End of life care, various stages of diseases (dementia, advanced disease including cancer, children chronic illness) care  
 
APPLICATIONS: Pediatrics, Elder care, Palliative care

• Reported only on the arm that involved informal caregivers
• Eight of 15 ICG studies provided self-reported data on stress and anxiety. Seven of the 15 studies reported statistically significant improvements with informal caregiver use of meditative interventions. 
• Twelve of 15 studies measured ICGs' mood or mental health. Eight of those reported statistically significant improvements in caregiver mental health after a mindfulness intervention.
• Heterogeneity Q statistics were statistically significant for controlled trials of anxiety and for pre- and postintervention studies of ICG depression. 
• The combined effect for controlled trial studies involving ICGs on depression, anxiety, stress, self-reported efficacy, and quality of life and mental health showed benefits from meditation. 
• The combined effect for pre- and postintervention studies on depression, anxiety, stress, and caregiver burden showed meditation benefits.
• An insufficient number of studies existed to examine combined effect for caregiver fatigue, sleep quality, confusion and grief, personal growth, hope, energy, and life satisfaction was included.  
• Three out of the six studies that examined self-efficacy (a positive outcome) showed significant caregiver improvement, but the combined effect of the controlled trials suggested a meditation benefit but not for a reduction of caregiver burden. 
• Six of the seven studies of ICGs that assessed physiological measures of stress showed a statistically significant change postintervention. 

Focusing on the outcomes for ICGs, the combined evidence from the controlled trials supports use of meditative interventions to minimize ICG’s depression, anxiety, and stress. Combined evidence from the pre- and postmeditative intervention studies supported their use in alleviating ICG burden. However, the insufficient study rigor and number prevent ed conclusions about the meditative interventions' effects on caregiver energy, fatigue, hope, confusion, and grief or life satisfaction. The insufficient number of studies prevents assessment of effect of meditation on caregivers’ capacity for decision making, patient advocacy, or resilience.

• Review of the ICGs of mostly patients without cancer limits the applicability for patients with cancer and their caregivers  
• Insufficient studies exist to make conclusions about several caregiver-related outcomes (e.g., energy, fatigue, hope, confusion, grief or life satisfaction, capacity for decision making, patient advocacy or resilience).
• The majority of female study participants minimized the generalizability of findings to male ICGs.
• Many studies relied on self-report with a wide variability of assessed study qualities (Downs and Black criteria).
• Study reviewed only English language studies

The effect of a meditative intervention on caregivers of patients with cancer should be explored with more studies using rigorous designs possessing higher statistical power. The initial data from this study indicate that a meditative intervention may benefit the ICGs of patients with various illnesses.

To determine the effect of manual lymph drainage (MLD) in addition to exercise compared to exercise alone for management of lymphedema in patients with breast cancer

After surgery, patients with axillary node dissection were recruited to the study and randomized to receive exercise, guidelines for self-care and MLD, or exercise and guidelines alone. MLD was begun one week after removal of axillary drains and 5 weeks after surgery and was provided for 20 weeks. All patients received the same guidelines and 30-minute individual exercise sessions. Standardized MLD sessions took half an hour, and patients received 40 treatments during the study period. Patient assessments were done at 1, 3, 6, and 12 months after surgery.

• The study sample was comprised of 158 patients who followed for the first six months and 154 who completed the study after 12 months.
• Most patients in the study were female (99%).
• Mean age was 55.15 years.
• Sixty-eight percent of the sample had breast conserving surgery, 85% also had radiotherapy, 67% had chemotherapy, and 76% had endocrine treatment.
• Median increase in arm volume before allocated treatment was 8 ml in both study groups.

The study took place at a singe outpatient site in the Netherlands.

Patients were undergoing multiple phases of care.

The study used a single-blind randomized controlled trial design.

• Arm volume was measured using water displacement.
• Arm circumference was measured.
• Lymphedema was defined as increase of 200 ml or more.
   

There were no differences between groups in incidence of arm lymphedema, time to lymphedema development, or maximal increase in arm circumference.

 The addition of MLD to a program of patient guidelines and education and exercise did not have an effect on prevention of arm lymphedema in patients with breast cancer after axillary node dissection.

• Key sample group differences could influence results.
• No analysis of group baseline differences was provided, and patients in the intervention group had higher percentage with level 1–3 axillary surgery. 
• The maximum percentage of patients who developed lymphedema by month 12 was 24%, so not all patients were at risk in the sample. 
• It is not known if there were substantial differences in surgeries performed that could have affected results.

Findings show that the addition of MLD to a program of exercise and patient guidelines for self-management had no benefit to prevent lymphedema development.

To obtain estimates of the effect of selected psychoeducational interventions on pain in patients with cancer

• Databases searched were PubMed, CINAHL, Dissertation Abstracts, PsycLIT, and the Cochrane Database of Systematic Reviews.
• Keywords searched were cancer, neoplasms, patient education, counseling, behavioral therapy, guided imagery, hypnosis, relaxation therapy, music, and pain.
• Studies were included if they
  • Were experimental, quasi-experimental, or employed a pre/post-test single-group design.
  • Included outcome measurement for which an effect size could be calculated.
• Studies were excluded if they compared psychoeducational therapy to pharmacologic treatment for pain, involved fewer than five subjects in each treatment condition, and included treatment and control groups from different settings.

The search retrieved 50 studies. Authors eliminated 25 studies on the basis of inclusion and exclusion criteria. Authors did not describe the method of evaluation.

• Across all studies, the sample included 1,354 patients with various types of cancer. The sample range was 7–206 patients.
• Authors included 25 studies in meta-analysis. 

• Types of interventions: Interventions included listening to music, hypnosis, progressive muscle relaxation and imagery, cognitive-behavioral counseling, distraction, and support groups.
• Effects on pain:
  • Relaxation, guided imagery music, or hypnosis interventions: Twelve studies used an intervention of this type, demonstrating an average weighted effect size of 0.65 (p < 0.05).
  • Education interventions: Six studies included this type of intervention.  Overall average effect size was 0.36 (p < 0.05).
  • Support plus other content: Five studies were included in this group.  Average effect size was 0.44 (p < 0.05).
  • Relaxation plus other content: Six studies showed an effect size of 0.07.

Most studies demonstrated that psychoeducational interventions had at least a small positive effect on pain in patients with cancer.

• This analysis included a broad variety of interventions, a fact that raises questions about the generalizability of conclusions from the analysis.
• Authors identified a number of methodologic and reporting issues, which raises concerns about the validity and utility of study findings.
• Several studies had very small sample sizes and reported very high attrition rates.
• Differences among educational interventions, cognitive behavioral therapy interventions, and usual care are unclear.
• Most of the education studied in this research was aimed at enhancing patient use of prescribed analgesic regimens.

Further well-designed research in this area is needed. The complexity of cancer-related pain presents a number of challenges inherent in this research; authors outline these challenges. Psychoeducational interventions may be more acceptable to some patients than others, as high attrition rates suggest. In addition, rating pain is a subjective activity. The efficacy of an intervention may differ with cancer phase and with different pain severity. These factors should affect selection of intervention type.

To review the literature on the use of appetite stimulants in oncology by a multidisciplinary group established by the French National Federation of Cancer Centers

The group conducted a literature search of four databases (MEDLINE, CancerLit, Embase, and the Cochrane Library) using search phrases: appetite stimulants, anorexia/drug therapy, cachexia/drug, or appetite associated with neoplasms. The search yielded 55 reports of randomized controlled trials (RCTs) published between 1990–1999 that evaluated the appetite-stimulating effect of corticosteroids, synthetic progestogens, or other drugs. 

The group defined standards, options, and recommendations for the use of appetite stimulants.

• Standards: Clinical situations for which there exist strong indications or contraindications for a particular intervention.
• Options: Situations for which there are several alternatives without clear superiority of one choice over another.
• Recommendations: Additional information to enable the available options to be ranked using explicit criteria with an indication of the level of evidence.

They also defined the level of evidence. 

• A: High-standard, meta-analysis, or several high-standard RCTs with consistent results.
• B: Good-quality evidence from randomized trials or prospective or retrospective studies with consistent results.
• C: Weak methodology of studies or inconsistent results.
• D: Lack of scientific data or case study reports only.
• Expert Agreement: Data do not exist for the method concerned, but the experts are unanimous in their judgment.

The primary outcome used in analysis of study results was anorexia. Secondary outcomes were improved quality of life, increase in body weight, increased food consumption, decrease in nausea and/or vomiting, and improvement in anthropometric and biologic parameters.

Corticosteroids

Corticosteroids were found to be effective appetite stimulants. Their level of evidence was B1 (good-quality evidence from randomized trials), but optimal dose and scheduling information was lacking.

Synthetic Progestogens

Megesterol acetate: Effective appetite stimulant (level B1) and beneficial effect on body weight (level B1). Minimum effective dose is 160 mg/day (level B1). Optimal dose is 480 mg/day (level C). No greater efficacy was seen with doses higher than 480 mg/day (level B1).*

Medroxyprogesterone acetate: Effective appetite stimulant (level B1). Effect on weight was not confirmed (level C). The group recommended more clinical trials to establish optimal dose and duration of therapy.

Cyproheptadine: May be an appetite stimulant, but adverse effects were reported (level C).

Dronabinol, metoclopramide, nandrolone, pentoxifylline: No appetite-stimulating effects were shown (level C). These should be used only in the setting of RCTs.

Hydrazine sulfate: Not an appetite stimulant (level A).

Corticosteroids and progestogens can be used in the treatment of anorexia in patients with cancer, especially in patients with advanced disease and with any type of cancer. Hydrazine sulfate should not be used.

* Data from trials completed after 1999 establish the safety and efficacy of higher doses of megesterol acetate.

Patients were randomized to two groups. Group A received the placebo for the first phase of the study and then switched to receiving multivitamins for the second phase. Group B received multivitamins for the first phase of the study and then switched to receiving placebo for the second phase. The multivitamins provided for patients were Centrum Silver tablets. To keep patients and researchers blinded, Centrum Silver tablets were crushed and offered to patients within capsules identical to those containing placebo. Randomization was centralized by a pharmacist to maintain the blinding of patients and investigators. Patient outcomes were assessed at baseline (phase I), at the time of switching (phase II), and right before the start of the last radiation treatment (phase III).

• The sample was comprised of 40 women with breast cancer who were to receive radiation therapy to the breast after breast-conserving surgery or after mastectomy.
• Group A included 19 patients (mean age = 57.47 years); 63.2% were living with a companion, 78.9% were White, 89.5% were not working outside the home, 84.3% had children in elementary school or younger, 26.3% were in each stage (I, II, and III), 73.6% had breast-conserving surgery, 47.4% had hypertension, and 68.5% had prior chemotherapy.
• Group B included 16 patients (mean age = 57.56 years); 56.3% were living with a companion, 56.3% were White, 93.7% were not working outside the home, 81.2% had children in elementary school or younger, 37.5% had an unknown tumor stage, 75% had breast-conserving surgery, 25% had hypertension, and 75% had prior chemotherapy.
• Patients were excluded if they had a previous history of radiation therapy, chronic anemia, depression, or serious psychiatric disorders.

Patients were undergoing the active treatment phase of care.

This was a double-blind, randomized, crossover trial with two groups:  multivitamin and placebo.

• Chalder Fatigue Scale
• European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30)

No significant changes were elicited in fatigue outcomes by the multivitamin intervention. When groups were compared at phase I, no significant differences were found in fatigue. At phase II, group A had a significantly lower rate of general and physical fatigue than group B (p = 0.035). The Chalder Fatigue Scale scores of both general and physical fatigue reflected a trend in the same direction (p = 0.048).

To assess the effectiveness of a combination of Ayurvedic drugs in alleviating cancer- and treatment-related symptoms

Patients initially were divided into two groups. Group 1 did not receive any Ayurvedic drugs. Patients in group 2 received Ayurvedic herbal combinations at various time points during chemotherapy. Within group 2, arm 1 received the same drugs and a full course of chemotherapy while arm 2 received the same drugs at the start of the sixth chemotherapy cycle and arm 3 received them after completing the sixth cycle. Treatment was continued for 16 weeks. Drugs used were maukitkyukta kamdudha (MKD) and mauktikyukta praval panchamruta (MPP) in all treatment arms. Arm 3 also received suvarnabhasmadi (SBD) according to clinician preference based on Eastern Cooperative Oncology Group scores. MKD and MPP at 250 mg each were given orally twice daily. SBD was given orally at a dose of 395 mg twice daily in cow’s ghee. Patients were followed for six months. Outcomes were measured after the first cycle of chemotherapy, after the sixth cycle of chemotherapy, and one month after the sixth cycle.

• N = 64
• AGE: Not provided
• MALES (%): Not provided, FEMALES (%): Not provided
• KEY DISEASE CHARACTERISTICS: Patients with various tumor types receiving different chemotherapy agents including highly emetogenic agents
• OTHER KEY SAMPLE CHARACTERISTICS: None were receiving radiation therapy 

• SITE: Single site 
• SETTING TYPE: Not specified
• LOCATION: India

• PHASE OF CARE: Active antitumor treatment
• APPLICATIONS: Palliative care 

Prospective study

• European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30)
• National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE)
• Eastern Cooperative Oncology Group (ECOG) score to reflect symptoms such as pain

Patients in arm 1 of the treatment group showed the least symptom severity of all groups. However, there were no statistically significant differences between the groups in any outcome measure. Symptoms declined in all patients after the first chemotherapy cycle. There were no significant differences in other chemotherapy-related toxicities.

This study showed some interesting but insignificant differences in chemotherapy-associated symptoms between patients receiving Ayurvedic drugs throughout chemotherapy, patients receiving the experimental drugs at difference time points, and patients who did not receive any of these drugs. This study's findings did not show that Ayurvedic drugs were effective in reducing symptoms compared to controls overall. This report had numerous design and reporting limitations.

• Small sample (< 100)
• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• Unintended interventions or applicable interventions not described that would influence results
• Measurement validity/reliability questionable
• Other limitations/explanation: The report states that patients who were lost to follow-up were not included in the analysis, but it provides no information on those patients or how many there were. There was no ITT analysis. Measurements such as ECOG scores were insufficient as measures of symptom severity. This report does not provide demographic information about participants and those lost to follow-up. Some interventions were at the physician's discretion, and there was no related subgroup analysis. There was no information about any other interventions for symptom management. No information was provided regarding the actual contents of the drugs used.

Little research has been done on the effects of Ayurvedic drug combinations among patients with cancer as a form of complementary and alternative medicine to manage treatment-related symptoms. This study did not demonstrate the efficacy of the particullar combination tested, and the study had several design and reporting flaws. Additional well-designed and clearly reported research for this type of intervention is needed to determine what role, if any, Ayurvedic drugs have for symptom management in cancer care.

The intervention was a 12-minute cancer orientation program video and an orientation booklet. The video provided an overview of the cancer center, a welcome statement, an introduction to the clinic’s philosophy of care, locations of treatment centers, and identified staff members. The orientation booklet provided more detail and information about various resources and services:

• Welcome statement
• Clinic philosophy
• Introduction to the cancer care center
• What is cancer
• Preparing for your visit
• Cancer center resources and services
• Clinical trials
• Frequently asked questions
• Summary
• Glossary of cancer terms
• Telephone numbers

Measurements done at baseline included questionnaires regarding awareness of cancer resources and services, demographic information, and state and trait anxiety. Postintervention questionnaires three weeks later measured awareness, use of and satisfaction with services and resources, and state and trait anxiety. Before their first MD appointment, patients were consented and randomized to one of four arms:

• Arm 1: Class—A facilitator showed the video and provided the booklet in class (n = 6).
• Arm 2: Drop-in—Patients were invited to view the video at their convenience and pick up a booklet, without staff teaching (n = 7).
• Arm 3: Mailed home—An orientation package containing the video and booklet was mailed to patients’ homes, without staff teaching (n = 23).
• Arm 4: Control group—An invitation was mailed with preintervention questionnaires and instructions. No video or booklet was provided. Information provided to patients and caregivers was part of routine care (n = 18).

• The study reported on a sample of 54 newly diagnosed patients with cancer and their caregivers.
• Patients were receiving care at a medical oncology clinic.
• Most participants were Caucasian, male, and married.
• Patients had a variety of cancer types; 30% had lung cancers.

Medical oncology clinic

A randomized controlled trial design was used.

• Profile of Mood States (POMS)
• State-Trait Anxiety Inventory (STAI)
• Three tools created by the authors and pilot tested: (a) Awareness and Use of Resources, (b) Coping, and (c) Understanding of the Cancer Center
• T test and Fisher exact tests
• 10% difference to determine clinical significance

• The class arm and drop-in arm had less than 10 participants, and their results were not reported.
• Analyses of effect size (partial eta squared) were conducted to further determine the magnitude of associations rather than only relying on null hypothesis significance testing.
• Exact p values reported: The mailed intervention arm was successful in improving patient outcomes, which was most helpful with high trait anxiety (p = 0.005). Baseline state anxiety of the mail arm was p = 0.003, with follow-up of p = 0.18. Baseline state anxiety of the control group was p = 0.02, with follow-up of p = 0.005.
• Fewer benefits for caregivers were noted.

The study had a small sample size.

STUDY PURPOSE: To evaluate the safety and effectiveness of adjunctive or alternative agents to platelet transfusions in patients with hematologic malignancies undergoing intensive chemotherapy or stem cell transplantation to prevent bleeding

TYPE OF STUDY: Systematic review

• FINAL NUMBER STUDIES INCLUDED = 10 trials
• TOTAL PATIENTS INCLUDED IN REVIEW = 554
• SAMPLE RANGE ACROSS STUDIES: Sample size ranged from 18 to 120.
• KEY SAMPLE CHARACTERISTICS: Six trials (n = 336) included patients with acute myeloid leukemia (AML) receiving intensive chemotherapy; two trials (n = 38) included patients with lymphoma undergoing chemotherapy; two trials (n = 180) included participants undergoing allogeneic stem cell transplantation. In nine trials, a thrombopoetin (TPO) mimetic was compared to placebo or standard of care; in one trial, platelet-poor plasma was compared to platelet transfusion. All trials were conducted in high-income countries, and were equally well represented by men and women.

PHASE OF CARE: Active antitumor treatment

The authors concluded that the available evidence does not allow a determination of the effect of TPO or platelet-poor plasma on the prevention of bleeding in patients with hematologic malignancies undergoing intensive chemotherapy or stem cell transplantation. This conclusion is attributed to the quality of evidence (very low quality) and the lack of adequate power to detect a clinically significant decrease in bleeding. No trials identified which evaluated agents, such as artificial platelet substitutes, fibrinogen concentrate, recombinant activated factor VII, or desmopressin, in this population.

Sufficient, high quality evidence does not exist with which to determine the safety or efficacy of adjunctive or alternative agents to platelet transfusions in patients with hematologic malignancies undergoing intensive chemotherapy or stem cell transplantation in the prevention of bleeding.

• Mostly low quality/high risk of bias studies
• Low sample sizes
• Studies were underpowered to detect a clinically significant difference in bleeding; in addition, eight trials were funded by the manufacturer of the agent being studied.

Additional studies are needed to evaluate adjunctive or alternative agents in the prevention of bleeding. Neither TPO nor plasma-poor platelets can be substituted for platelet transfusions given the current state of knowledge.

• RESOURCE TYPE: Evidence-based guideline

• PHASE OF CARE: Active antitumor treatment

No information is provided regarding the volume of evidence retrieved or quality ratings of studies included.

• Oral hygiene
• Pretreatment control of preexisting periodontal and dental disease with professional cleaning
• Routine use of palifermin is not recommended.

• Regular oral care with use of nonalcohol-containing mouthwashes
• At least weekly assessment

All specific interventions had either recommendations against use or no ability to provide a recommendation. Cryotherapy even with bolus 5-FU was not recommended due to lack of evidence in the setting of RT for patients with head and neck cancer. The guideline provides a listing of numerous interventions that have been examined with no recommendations for use.

• Limited search and no clear study quality rating
• Unclear if the panel reviewed all the evidence or just statements created by an individual facilitator

This review provides a comprehensive list of interventions, none of which can be recommended for practice. This article does provide a good overview of assessment instruments and provides some information on probable risk factors.