To analyze factors associated with treatment failure and success in lymphedema

All patients underwent complete decongestive therapy (CDT) with manual drainage, multilayer low-stretch bandages and specific exercises and skin care as recommended in international consensus guidelines. Patients were followed at 6 and 12 months and then yearly.  At each patients were questioned about actual treatments used and responses were recorded

• The sample (N = 682) was comprised of female patients with lymphedema.
• Of the sample, 47.8% had mastectomy and 97.4% had radiation therapy.
• Median time to lymphedema onset was 22 months and duration was 32 months.
• All patients had initial lymphedema volume of more than 250 ml. 

The study used a descriptive design.

• Arm circumference was measured.
• Treatment failure was defined as a lymphedema volume increase of more than or equal to 50% of total reduction obtained during the first intensive CDT.
   

• Median lymphedema volume was 936 ml prior to therapy and 335 ml after CDT (p < 0.0001).
• Median duration of follow up was 28 months.
• Volume increased after initial intensive phase CDT throughout the first year.
• Analysis gave hazard ratios of: MLD alone = 1.91, p = 0.03; elastic sleeve alone = 0.65, p = 0.1; MLD and elastic sleeve = 1.09, p = 0.73; bandage and elastic sleeve = 0.53, p = 0.004; MLD, bandage, and elastic sleeve = 0.73, p = 0.14. 
• Lymphedema volume mainly reflected treatment compliance.
• MLD alone was associated with increased risk of failure and adding MLD did not reduce the risk of failure. 
• Being overweight was associated with increased risk of failure.
• Compression therapy with an elastic sleeve during the day and bandaging at night were the main means to stabilize lymphedema volume. 
• Body mass index was associated with higher risk of treatment failure.

MLD did not appear to reduce the risk of treatment failure for lymphedema. Compression therapy appears to be the main factor in stabilizing lymphedema volume.

• The study did not have a control group, blinding, or random assignment. 
• Measurement and methods were not well described.
• It is unclear if multiple people did measurement.
• Measurement validity and reliability were questionable.
• Patient self-report of compliance is not well described.
• How relevant data was coded for analysis is not described.

Findings add to the growing body of evidence pointing to the critical nature of patient compliance with compression sleeves and bandaging over time for ongoing effective management of lymphedema. Findings suggested that being overweight may also contribute to potential for treatment failure. Nursing measures to provide support for treatment adherence and weight control are important areas for patient care.  Interventions to facilitate adherence to compression therapy should be researched.

To retrospectively evaluate the efficacy of the addition of olanzapine in adults experiencing refractory chemotherapy-induced nausea and vomiting (CINV) stratified by chemotherapy emetogenicity

This was a retrospective chart review of adults receiving chemotherapy between January 2008 and January 2012. Inclusion criteria required that patients received one or more daily doses of olanzapine 10 mg per dose for the indication of refractory CINV during the same admission. Each patient must have received antiemetic prophylaxis and first-line rescue antiemetics appropriate for the emetogenicity level of the chemotherapy regimen according to National Comprehensive Cancer Network guidelines at the time of chemotherapy administration. Patients were excluded if olanzapine was used for anything other than refractory CINV.

• N = 33
• MEDIAN AGE = 49 years (range = 19–77 years)
• MALES: 20, FEMALES: 13
• KEY DISEASE CHARACTERISTICS: The most common oncologic diagnoses were advanced melanoma (36%) and Hodgkin lymphoma (34%).
• OTHER KEY SAMPLE CHARACTERISTICS: Most subjects were Caucasian (58%) or Hispanic (24%).

• SITE: Single site  
• SETTING TYPE: Inpatient  
• LOCATION: Southwest United States

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

• Retrospective chart review

Researchers measured the number of rescue antiemetics received following the first dose of olanzapine. Patients were stratified by chemotherapy emetogenicity level, age, gender, and number of prophylactic antiemetics received.

Thirteen women and 10 men were included in this study, the majority of whom were Caucasian (58%) and were most frequently being treated for advanced melanoma (36%) and non-Hodgkin lymphoma (24%). The addition of olanzapine was successful for 65% of patients receiving regimens with low to moderate emetogenicity (n = 23) and 70% of patients receiving regimens with high emetogenicity (n = 10). For these cohorts, olanzapine 5–10 mg was administered for one to eight days (median four days). More women (85%) than men (55%) were successfully treated with the addition of olanzapine. For patients receiving a serotonin antagonist, glucocorticoid, and aprepitant as prophylaxis, the addition of olanzapine was successful for controlling breakthrough nausea 68% of the time. Patients who received a prophylactic serotonin antagonist alone were treated successfully 63% of the time for breakthrough nausea with olanzapine. Cohorts 18 to 50 years old (n = 12) and over 50 years (n = 15) received relief with the addition of olanzapine 67% of the time.

Adding olanzapine contributed to the success of CINV management, particularly for women more often than men. Findings suggest that the addition of olanzapine for refractory to prophylactic and breakthrough antiemetic regimens in all levels of emetogenicity may be beneficial.

• Small sample (< 100)
• Risk of bias (no random assignment)
• Risk of bias (no appropriate attentional control condition)
• Unintended interventions or applicable interventions not described that would influence results
• Findings not generalizable
• Retrospective design

Nurses who assess and administer chemotherapy with low to moderate or high levels of emetogenicity should consider the addition of olanzapine for refractory CINV.

To evaluate the effect of oral glutamine on the prevalence and severity of acute radiation-induced oral and esophageal mucositis

Data were collected retrospectively for patients receiving radiation therapy. Findings were compared between those who did and did not receive glutamine. Outcomes between those who were given glutamine early (prior to radiation therapy) versus late (after radiation therapy was begun) in the course of radiation therapy were compared. Data on nutritional status and interruptions in treatment were evaluated.

• The sample was composed of 117 patients, including 79 cases with oral mucositis.
• Mean patient age was 62.2 years (SD = 13.6 years) in the experimental group.
• The sample was 81.2% male and 10.8% female.
• Diagnoses were head and neck, lung, esophageal, and lymphoma.
• The majority of patients (73.5%) were also receiving chemotherapy.

The study was conducted at a single site outpatient setting in Spain.

Patients were undergoing the active antitumor treatment phase of care.

This was a retrospective study.

The World Health Oragnization (WHO) mucositis grading scale was used.

• In the final sample, 27.4% of patients received early glutamine, 49.5% received glutamine late, and 23.1% of patients did not receive glutamine.
• Analysis showed that prevalence of mucositis was lower among patients who received early glutamine compared to those who either did not receive glutamine or were given glutamine late (p ≤ 0.02).
• After correction for sex, age, chemotherapy, radiation dose, and previous surgery, only glutamine use was predictive of risk for development of oral mucositis (risk difference = -9.0%; 95% CI = -18%, -1%).
• For patients receiving radiation to the head and neck region, severity of oral mucositis was higher among those who did not receive early glutamine (p = 0.039).

Provision of oral glutamine prior to the beginning radiation therapy may be of benefit in the prevention of oral mucositis. Firm conclusions cannot be made because of multiple study limitations.

• Differences in the baseline sample group and variations in chemotherapy regimens, which could have affected the development of mucositis, could have influenced results.
• A risk of bias exists because of the lack of a control group, blinding, and random assignment.
• Unintended interventions or applicable interventions that were not described could have influenced results.
• Measurement and methods were not well described.
• No information about the oral care used was provided.
• The timing of mucositis evaluation and how evaluations were done was not reported. 

This study has numerous limitations and risks of bias, and it attempted to draw conclusions across a very heterogenous population of patients. Findings suggest that oral glutamine may be helpful in preventing oral mucositis in patients receiving radiation to the head and neck area, and it appears that glutamine treatment may be most beneficial if treatment is begun prior to the initiation of radiation therapy.

Traditional Chinese acupuncture was performed twice per week for four weeks or once per week for six weeks. The acupuncturists used points commonly used for fatigue.

• Thirty-seven adults (68% female) were included.
• Mean age was 61 years (range 43–78).
• Patients were ambulatory.
• Patients were at least three weeks posttreatment.
• Patients had a Brief Fatigue Inventory (BFI) score of 4 or greater. 
• Race/ethnicity were not reported.
• Patients were excluded if they had severe anemia, a Karnofsky Performance Status (KPS) score of less than 70, or an anticipated survival of less than 3 months.

Acupuncture was delivered in an Integrative Medicine clinic.

The study used a single-arm, phase II, pilot design.

• BFI was measured at baseline pretreatment and one and two weeks posttreatment.
• Anxiety and depression were covariates, not outcomes.

Mean improvement was 31.1% (confidence interval [CI] [20.6%, 41.5%]); 39% of patients improved by greater than 40%. Younger and less depressed patients showed a greater response.

Acupuncture may affect serotonin pathways. No adverse events occurred.

• No control group or randomization was used.
• There was no control for exercise.
• Travel to the site was a barrier.

Certified acupuncturists are needed. Once weekly treatment was preferable. The intervention seemed to show benefits that suggest it is worthy of further study.

Treatment consisted of two phases: acupuncture and acupressure. Patients were randomized to receive a single session of true or placebo acupuncture. Semi-permanent acupuncture studs then were inserted, and patients applied pressure to the studs twice a day to provide ongoing stimulation to acupuncture points.

• N = 47 (25 randomized to acupuncture and 22 to placebo)
• KEY DISEASE CHARACTERISTICS: Patients with lung or breast cancer presenting with dyspnea 

• SETTING TYPE: Inpatient and outpatient
• LOCATION: Memorial Sloan-Kettering Cancer Center

• Randomized, placebo-controlled pilot trial

• Dyspnea was assessed with a 0–10 numerical rating scale immediately before and after acupuncture treatment and daily for a week thereafter.

Dyspnea scores were slightly higher for patients receiving true versus placebo acupuncture immediately after and for the one week daily follow-up, but the difference was not statistically significant.

Acupuncture technique as used in this trial is unlikely to have an effect on dyspnea. 

• Two modifications of the trial existed: the first was to only include patients with non-zero dyspnea scores and the second changed one acupoint on the wrist, which caused pain in several patients. Protocol changes are problematic to the conclusion about the intervention.
• Patients only received one acupuncture treatment as opposed to several, which may be more effective.
• Accrual to the study was slow and limited by refusal by patients who deemed themselves too ill to participate.

200 mcg of misoprostol or placebo was dissolved in 15 ml of water. Patients swished in oral cavity for two minutes, then swallowed. Patients were advised to gargle before swallowing.

The study was comprised of 83 patients with squamous cell carcinoma of the head and neck, older than 18 with a total radiation dose higher than 50 Gy.
Misoprostol arm: n = 42
Placebo arm: n = 41
 

1999–2002

Double-blind, placebo-controlled, randomized trial

Extent of RTOG grade 3 mucositis (incidence and duration).

Secondary endpoints were time to development of mucositis, extent of grade 2 mucositis, patient weight, general well-being using VAS, and oropharyngeal or oral soreness.

RTOG, VAS
 

No significant differences were found for endpoints. More patients in the misoprostol arm reported increased levels of oral or oropharyngeal soreness.

Did not accrue adequate patients according to statistical analysis.

12% patient withdrawals

To evaluate short- and long-term effects of different exercise parameters during adjuvant treatment on cancer-related fatigue.

Databases searched were CINAHL, EMBASE, MEDLINE, Scopus, PEDro, and Cochrane Library to 2008. Hand searching was performed using reference lists from articles obtained.

Search keywords were cancer (and related terms), chemotherapy, radiotherapy, hormone*, exercise, cycle, train*, walk, and fatigue.

Studies were included in the review if 

• They were randomized, controlled trials
• They studied effects of exercise on cancer-related fatigue in adults receiving adjuvant therapy
• There was overlap of 50% or more of the exercise intervention with the cancer treatment period
• The study compared exercise with a no exercise usual care group
• Patient-reported fatigue was the outcome.

No exclusion criteria were specified.

Initally, 1,097 articles were identified. A final set of 18 articles met the inclusion criteria. The PEDro scale was used to rate the methodological quality of the research. Fifteen studies were considered to be of high quality, with a score 4 or greater (range 2–8).

• The final sample of 18 studies involved 1,109 patients.
• Study sample sizes ranged from 14 to 174 patients.
• Twelve of the 18 studies were performed in patients with breast cancer.

Overall Findings in Breast Cancer

• Pooled results in patients with breast cancer (n = 654) showed a small significant reduction in fatigue with exercise (standardized mean difference [SMD] = 0.22; 95% confidence interval [CI] [0.06, 0.37]; Z = 2.46; p = 0.01).

Home-Based Exercise

Exercise was home-based and self-monitored in seven studies. Interventions consisted of walking for 10 to 45 minutes per week and for three to six times per week. In one study, the participants also performed resistance exercises. Cancer treatments and timing of the programs varied. Adherence ranged from 70% to 100%.

• Pooled results of 2 high-quality studies (n = 128) showed a small nonsignificant reduction in fatigue (SMD = 0.10; 95% CI [-0.25, 0.45]).

Supervised Exercise Programs

Supervised programs were used in five studies. Three involved aerobic exercises, and the others included groups with stretching and/or resistance exercises. Most were performed for 10 to 30 minutes three times per week. Programs were completed by 39% to 100% of partcipants.

• Pooled analysis of three high-quality studies (n = 340) showed a medium significant reduction in fatigue with exercise (SMD = 0.30; 95% CI [0.09, 0.51]).

Overall Findings in Prostate Cancer

Four studies were performed in patients with prostate cancer; three were supervised and one was home-based.

• Pooled results in these five studies showed a medium significant reduction in fatigue with exercise (SMD = 0.32; 95% CI [0.05, 0.59]).
• Subgroup analysis of home-based and supervised programs showed small nonsignificant effects, with these approaches analyzed individually.

Findings in Multiple Myeloma and Acute Myeloid Leukemia

One study was performed in each of these patient groups. One was of low quality. Both had nonsignificant reductions in fatigue.

Only short-term effects could be analyzed because only one study described any longer-term effects of physical exercise. No significant adverse effects overall were seen. Supervised aerobic exercise programs were more effective in reducing fatigue than home-based programs. There were significant positive effects during breast cancer treatment, with small to moderate effect sizes. The most effective frequency intensity or duration of exercise could not be determined. Reported adherence to the exercise program varied widely.

• There was an overall beneficial effect of exercise in patients with prostate cancer when all findings were pooled; however, the effectiveness of home-based and supervised programs could not be demonstrated separately.
• The limited number of studies and available data in this area may have influenced these results.
• The clinical relevance of findings could not be determined due to the wide range of measurement instruments used in the research and the lack of associated data that establish clinically important differences.

Findings showed that exercise had at least a small beneficial effect in reducing fatigue for patients during adjuvant treatment. Supervised programs may be more effective than self-managed home-based programs. More research on the effects of resistance exercise, home-based exercise, and most effective exercise parameters are needed. Longer-term outcomes and patient adherence need to be examined further. Research on the effects of exercise in other patient types is also needed.

To compare the effectiveness of two antifungal prophylaxis regimens in the setting of hematopoietic cell transplantation (HCT)

The study compared patient outcomes between patients undergoing HCT who received only 200 mg posaconazolel three times daily for 100 days to those who also received intermittent IV micafungin at 50–100 mg. Micafungin was provided for patients who were unable to take the oral medication for any reason. The decision to switch to micafungin was at the physician’s discretion.

• N = 212
• MEAN AGE = 46.7 years
• MALES: 58%, FEMALES: 42%
• KEY DISEASE CHARACTERISTICS: Most patients undergoing HCT had acute leukemia or lymphoma.

• SITE: Multi-site  
• SETTING TYPE: Multiple settings    
• LOCATION: Germany

PHASE OF CARE: Active antitumor treatment

• Retrospective

• Incidence of proven or probable invasive fungal infection (IFI) defined according to European Organization for Research and Treatment of Cancer and the Mycoses Study Group (EORTC/MSG)
• Febrile neutropenia defined as incidence of fever not responsive to antibiotics for at least 72 hours.
• Pneumonia—fever with positive diagnostic imaging

Mean number of febrile days was 5.9 in the posaconzole group and 4.3 in the group also receiving micafungin (p = 0.051). The number of possible IFI in the group receiving micafungin bridging was significantly lower (16% versus 3.8%, p = 0.005). Those receiving micafungin bridging had higher fungal-free survival at 100 days post-HCT (p = 0.009). There was no difference in overall survival between groups.

Use of IV micafungin in patients unable to take oral posaconazole was effective in reducing fungal infections.

• Risk of bias (no random assignment)

This study shows that intermittent use of IV micafungin was effective for patients unable to take oral posaconazole for antifungal prophylaxis following HCT. Both of these regimens were shown to be feasible and effective. Further research in this area is warranted to determine most effective drug combinations and timing to prevent breakthrough IFI.

To compare caspofungin and itraconazole as secondary prophylaxis in patients with hematological malignancies.

Physicians completed case report forms via the intranet for data collection and analysis.  Physicians did not follow any specific protocol, drug selection was based upon individual discretion and timing, and dosages of medications used varied. Outcomes were assessed at the end of neutropenia.

• Seventy-seven patients (64% male, 36% female) were included.
• Average age was 48.5 years (range 16–72).
• Seventy percent of patients did not undergo transplantation.  Most of the remaining patients underwent allogeneic stem cell transplantation.

• Multi-site  
• Inpatient 
• Germany

Patients were undergoing the active antitumor treatment phase of care.

This study was observational.

• European Organization for Research and Treatment of Cancer (EORTC)/Mycoses Study Group (MSG) criteria for diagnosis and assessment of first and breakthrough invasive fungal disease (IFD)
• Complete response (defined as a disappearance of all clinical, microbiological, and radiographic evidence of infection)
• Partial response (defined as >50% radiographic signs of infection).

Incidence of breakthrough IFD was similar in both groups of patients (31.9%–32.1%). There were no significant differences between groups in any other outcome measures.  Death attributable to IFD ranged from 3.6% to 4.3%. Aspergillosis was the most frequent infection, followed by candidiasis.  Overall mortality was 16%.
 

No differences were found in efficacy between these two medications; however, no conclusions could be drawn due to multiple study limitations and significant differences between patient groups in the sample.

• Small sample (<100)     
• Baseline sample/group differences of import   
• Risk of bias (no control group, no blinding, no random assignment, sample characteristics*) 
• Key sample group differences that could influence results*
• Measurement validity/reliability questionable*

*Substantial variability in patient characteristics that would influence findings, variability in methods of treatment, other measures used for infection prevention, etc.

This study provided no evidence to differentiate the efficacy between these two medications for secondary antifungal prophylaxis.

To compare the effects—on quality of life and symptoms of depression—of an intervention consisting of a psychotherapeutic intervention, narrative therapy, plus escitalopram to the effects of usual care plus escitalopram

The initial sample was composed of 1,026 patients, between March 2006 and June 2008, with a diagnosis of breast, lung, or colorectal nonmetastatic cancer, three months after cancer diagnosis and no later than two years after diagnosis. Investigators used the Hospital and Anxiety Depression Scale (HADS) to screen participants for depression. A total of 150 had depressive disorder according to DSM-IV-TR criteria. The study contained 72 participants, 33 in usual care and 39 in combined care. Escitalopram was administered on a fixed-flexible schedule in both groups, beginning with 10 mg per day and adjusted up to 20 mg per day by week 8. A minimum of six months treatment was established for both groups. The narrative intervention was carried out individually during 12 weekly sessions, each 45 minutes long, and was guided by a treatment manual. Of the sessions, 10% were videotaped to help ensure adherence. Usual care consisted of oncologist-adminstered antidepressant. The oncologist followed a protocol and reported side effects of the medication. The follow-up of patients in the usual-care group was similar to that of patients in the treatment group. Investigators assessed depression-related outcome at weeks 12 and 24.

• The sample was composed of 72 participants. At the 12-week assessment, the sample contained 68 participants. At the 24-week assessment, the sample contained 56 participants.
• Mean patient age was 54.6 years (SD = 10.4 years). The age range was 35–75 years.
• The sample contained 19.4% males and 80.6% females.
• Participants had lung, breast, or colorectal nonmetastatic cancer and major depressive disorder, single-episode or major recurrent depressive disorder, or adjustment disorder with depressed mood, or adjustment disorder with mixed anxiety and depressed mood.
• Participants had a life expectancy longer than one year and a Karnofsky Performance Status Score of 70 or higher. Participants were receiving ambulatory care and had depressive disorder according to DSM-IV-TR criteria.
   

• Multisite
• Outpatient
• Madrid, Spain

• Phases of care: multiple
• Clinical applications: late effects and survivorship

Two-center randomized controlled trial

• European Organization for Research and Treatment Cancer Core Quality of Life C30 (EORTC QLQ-C30), a self-rating scale that measures quality of life. Thirty items evaluate five functional domains and three scales of symptoms. Five items assess common physical symptoms of cancer. Other items assess global health, global quality of life, and the perceived financial impact of disease and treatment. Scores are 0–100. The EORTC QLQ-C30 has been validated for use by Spanish patients with cancer.    
• Hospital anxiety and depression scale (HADS). Investigators used this scale at baseline, for screening, and at 12 and 24 weeks. HADS is a 14-item self-rating scale that measures anxiety and depression and is designed specifically for patients with physical illness. A score of 11 or more indicates probable psychological morbidity; a score of 8–10 indicates possible psychological morbidity. The scale has been validated for use by Spanish patients.

Demographic variables did not differ significantly between the two groups. Gender and age were unbalanced because of cancer types. At 12 and 24 weeks, the combined-therapy group showed significantly greater improvement in all the dimensions of function (p < 0.01), pain scale (p = 0.02), global health (p = 0.02), and global quality of life (p = 0.007). Between groups there were no statistically significant differences in symptoms of depression. From week 12 to 24, study retention was higher in the combined-treatment group (p = 0.01).

Using combined therapy for major depression in patients with cancer results in significant improvements in quality of life but does not result in a significant reduction in symptoms of depression. Narrative therapy is an integrative intervention designed to address components of critical importance in patients with depression. The therapy may have a positive impact on patient’s fears and worries about medication interactions and side effects.

• The study had a small sample size, with fewer than 100 participants.
• Types of cancer were not evenly distributed between groups.
• The study used interim analysis to estimate statistical power and sample size.
• A different specialist administered the drug.
   

The interventions proved to be acceptable to patients. The intervention shows good potential for dissemination, is relatively easy to implement, and improved compliance. The intervention may be a low-cost means of improving the quality of life of patients with cancer.