To examine the use of oral platelet gel supernatant with supportive medical treatment versus supportive medical treatment alone in the management of radiation-induced oral mucositis (OM) in patients with head and neck cancer

The intervention group was a prospective sample of patients receiving treatment for head and neck cancer, and controls were historical controls. The intervention and control groups received supportive measures maintaining adequate hydration, nutritional status, and oral hygiene, including mild-flavored toothpaste, saline peroxide mouthwash three to four times a day, and an antifungal agent. The intervention group also received platelet gel supernatant (PGS) three times per day one hour before breakfast, lunch, and dinner. PGS treatment was started on the first day of radiation or chemoradiation treatment and stopped at the end of the radiation course. Patients were monitored during treatment and as many as seven weeks after treatment completion. OM was assessed by two radiation oncologists.

• N = 80
• AGE RANGE = 47–65 years (intervention), 51–63 years (control)
• MALES: 62%, FEMALES: 38%
• KEY DISEASE CHARACTERISTICS: Radiation-induced mucositis
• OTHER KEY SAMPLE CHARACTERISTICS: Patients with nonmetastatic head and neck cancer treated with radiation with or without chemotherapy

• SITE: Single site    
• SETTING TYPE: Not specified    
• LOCATION: San Salvatore Hospital

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

Quasi-experimental

• The World Health Organization (WHO) score of OM was used to grade the severity of oral mucositis.
• The ​Oral Mucositis Questionnaire Head and Neck (OMQ-HN) was used to assess quality of life.

The intervention group experienced a decrease in the severity of WHO grade 3 and 4 toxicity that was statistically significant (p = 0.0074). The intervention group also showed a later onset of mucositis based on the WHO grade toxicity and higher quality of life as measured by OMQ-HN (p = 0.001). A greater decrease in the use of opioid analgesics was found in the intervention group (p = 0.0021) compared to the control group.

A decrease in WHO grades 3 and 4 toxicity and a slower symptom onset was demonstrated with PGS administration.

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

PGS in combination with supportive therapy is potentially beneficial in the management of radiation-induced OM. The intervention was aimed at affecting OM. Using the WHO grading scale, a delay in OM development was seen; however, some patients did not receive chemotherapy, and certain drugs exacerbate OM. Additional studies in in populations receiving radiation and chemotherapy are needed.

To evaluate lymphedema rates when axillary reverse mapping (ARM) is added to lymphadenectomy

After sentinel lymph node localization, ARM was performed by injecting blue dye subcutaneously to localize lymphatics draining the arm. Standard level I and II lymph node dissection was done to include blue lymph nodes as appropriate. Otherwise, blue nodes were preserved. Average follow-up was 14.6 ± 9.4 months.

• The study reported on 148 patients.
• Mean age was 56.9 years with a range of 44.4–69.4 years.
• The sample was 100% female.
• The majority of patients (95%) had stage I or II disease.

This was a single-site study conducted in Arkansas.

Patients were undergoing the active antitumor treatment phase of care.

This was an bservational, descriptive study.

Arm volume was measured; the method of measurement was not described.

Almost a third (30%) of patients had axillary staging done prior to neoadjuvant chemotherapy; the remaining patients had the ARM procedure done during their definitive surgical treatment. Overall incidence of lymphedema when the ARM node was preserved was 2.9% compared to 18.7%  in patients who had ARM lymphatics resected.

Findings suggest that ARM with preservation of lymph nodes when possible can result in lower incidence of lymphedema.

• A risk of bias exists because there was no control group, no blinding, and no random assignment. The sample characteristics also present potential bias.
• Unintended interventions or applicable interventions that were not described could have influenced results.
• Measurement methods were not well described.
• This was a descriptive type of design only.
• The follow-up duration was shorter than the length of time it takes some patients to develop lymphedema. 
• No information was provided regarding whether other preventive measures for lymphedema were done and if these were consistent among patients.

Findings suggest that the addition of ARM to standard surgical procedures might enable preservation of some lymph nodes with resulting lowered prevalence of lymphedema in patients with breast cancer. This study provides minimal support because of study design and limitations.  Long-term effects of lymph node preservation need to be explored.

To develop practice guidelines answering two questions:

1. What are the optimal methods to prevent acute skin reactions related to radiation therapy (RT) within the first six months of irradiation?
2. What are the optimal methods to manage acute skin reactions related to RT?

Databases searched were PreMEDLINE, MEDLINE, CANCERLIT, and Cochrane Library between January 1980 and April 2004. The name of the initiative was the Cancer Care Ontario’s Program in Evidence-Based Care. The method used was the practice guidelines development cycle. Articles were included based on rigorous inclusion criteria (meta-analysis, systematic reviews, evidence-based practice guidelines, comparative studies, prospectively collected data in at least one trial arm, studies with reported outcomes—degree of skin reaction [using a validated skin reaction tool] and other outcomes reported and articles available as published articles or abstract reports). Exclusion criteria were also identified.

The systematic review included interprofessional members from the Supportive Care Guidelines Group of Cancer Care Ontario and the Program in Evidence-Based Care, an internationally recognized program at McMaster University, Hamilton, Ontario, Canada.

No conflict of interest was identified.

A systematic review of 28 clinical trials was included in analyses; 23 pertained to prevention and 5 addressed management of skin reactions. Two practice guides were reviewed:  Oncology Nursing Society and British Columbia Cancer Agency (expert opinion and consensus).

A table of clinical studies presented study descriptions and outcomes of the trials on prevention and management of skin reactions, pain, and itching.

The largest randomized trial compared calendula versus Biafine and was significant (p = 0.03) in reducing the severity of RT dermatitis.

• Gentle skin washing with water alone or mild soap (unscented, lanolin-free) and water
• Gentle shampooing of the scalp with mild shampoo if receiving RT to the head
• Encourage personal hygiene habits to avoid psychosocial distress. Limiting personal hygiene practices is not recommended.
• Patients who received breast irradiation may use calendula ointment to decrease the occurrence of a grade 2 or higher skin reaction.

Insufficient evidence existed to support or refute the use of

•Topical agents (corticosteroids, sucralfate cream, Biafine® (Ortho Dermatologics), ascorbic acid, aloe vera, chamomile cream, almond ointment, or polymer adhesive skin sealant)
•Oral agents (enzymes, sucralfate)
•Intravenous agents (amifostine)

Gentle skin and hair washing should be unrestricted in patients receiving RT. No barrier exists to using mild soap.

No trials answered the question on management.

Future Research:

• Outcome assessment tools are required, including quality of life tools.
• Trials to assess oral enzymes are needed to confirm studies showing potential for prevention benefit.
• Randomized trials are needed (double-blinded, randomized, controlled trials) about the benefits of moisturizing cream as a preventive measure.
• Randomized trials are needed that address moist desquamation management with the use of dressings as an intervention.
• Trials are needed that explore sites with different risk factors and possible differing management.

Opinions of This Group:

• Use plain, unscented, lanolin-free hydrophilic cream, but discontinue with skin breakdown.
• Low-dose corticosteroid cream may be helpful with itching and irritation, but caution patients about overuse. More evidence is required to make firm recommendations.

To investigate the therapeutic effect of acupuncture on hot flashes and disturbed sleep in patients with breast cancer, the possible side effects of this treatment, and the effect on plasma estradiol levels

Two experienced acupuncturists provided either true acupuncture or sham acupuncture in the predetermined points. Group 1 had manual acupuncture in pre-determined bilateral points for 15–20 minutes once a week for five consecutive weeks. These points were Hc6, Ki3, Sp6, and Lr3, which are located on the wrist, ankle, and foot. Group 2 had sham acupuncture in four predetermined bilateral non-acupuncture points outside the meridian but within the same region as the true points. The treatment was given once a week for five weeks. Group 3 received no acupuncture. All groups completed a log book. Plasma estradiol levels were measured in blood samples obtained just prior to the first treatment and 30 minutes after. It was measured again at five weeks later and 30 minutes after the final treatment. Group 3 had plasma estradiol levels obtained at allocation and five weeks later.

• N = 94
• MEAN AGE = 61 years (45–76 years)
• FEMALES: 100%
• KEY DISEASE CHARACTERISTICS: Breast cancer
• OTHER KEY SAMPLE CHARACTERISTICS: Self-estimation of troublesome hot flashes and disturbed night sleep

• SITE: Single site    
• SETTING TYPE: Outpatient area   
• LOCATION: Denmark

• PHASE OF CARE: Post-surgical and survivorship
• APPLICATIONS: Elder care

• Double-blinded, randomized (double-blind only applied to Groups 1 and 2 for the investigator and participants)

• Completion of a logbook using a subjective visual analog scale to rate extent of symptoms
• Obtained plasma estradiol levels prior to first treatment, 30 minutes after that treatment, at five weeks and 30 minutes after final treatment
• The control group had the levels drawn at allocation and five weeks later.
• Analysis performed using Roche Modular Immunochemistry, Electrochemical Luminescent Immuno Assay

The researchers reported that a significant relief occurred in the acupuncture group after the second treatment, lasting until 6 weeks post-treatment (p < 0.05), as compared to the sham acupuncture and no treatment groups, which lasted for at least 12 weeks. A decrease in sleep disturbance also was noted in the same group as compared to the others. Side effects were reported as mild and temporary. Reported side effects included fatigue, pruritus, and nausea. No effect on the plasma estradiol levels in all groups occurred. Eleven women from all groups reported using concurrent treatments including clonidine and/or venlafaxine, mirtazapine with clonidine, and hormone replacement.

The acupuncture group reported a decrease in hot flashes versus the other groups. No formal validation of the visual analog scale occurred. The concurrent use of other therapies may influence the reported outcomes. Restrictions of concurrent therapies for hot flashes during participation and validation of the self-reporting tool were needed.

• Small sample (< 100)
• Baseline sample/group differences of import
• Unintended interventions or applicable interventions not described that would influence results
• Other limitations/explanation: 11 participants used other forms of treatment in conjunction with their study participation to control hot flashes. Participants were Caucasian. No other groups were included in the sample.

A large randomized trial exploring acupuncture versus placebo is needed that restricts concurrent therapy usage during trial participation and includes women with breast cancer having similar hot flash interventions such as tamoxifen or aromatase inhibitors with hot flash occurrence. True acupuncture may benefit, but further study is indicated.

The purpose of this study was to determine the effectiveness of G-CSF and GM-CSF in patients with malignant lymphomas for improving overall survival (OS) and freedom from treatment failure (FFTF). Secondary goals were to to decrease the risk and duration of neutropenia and febrile neutropenia, infection and mortality during chemotherapy; improve received dose intensity, tumor response, and quality of life; and examine adverse effects.

Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CancerLit, Medikat, Russmed Articles, SOMED, Toxline, BIOSIS Previews, and LILACS databases were used.

In addition, Internet databases of grey literature (SIGLE) and ongoing trials were reviewed, as were conference proceedings. Experts and pharmaceutical companies also were contacted for unpublished or ongoing trials. Citations of identified trials also were searched.

Key words included granulocyte–colony-stimulate factor (G-CSF), granulocyte-macrophage–colony-stimulating factor (GM-CSF), malignant lymphoma
 
Studies were included if they were randomized, controlled trials (RTCs) conducted from January 1980 to April, 2008 comparing G-CSF or GM-CSF prophylaxis with placebo or no prophylaxis; studies on long-lasting G-CSFs (e.g., filgrastim) also were included. Abstracts and unpublished data were included if enough data were available on study design, patient characteristics, interventions, and outcomes.
 

Studies were excluded if they were crossover studies, quasi-randomisedand, or nonrandomised comparative studies.

306 total abstracts were reviewed. Of these, 90 studies were evaluated and 74 excluded for not meeting inclusion criteria. The remaining 16 RTCs met inclusion criteria, but three of these were later excluded due to not fulfilling all criteria.

Subgroup analysis and investigation of heterogeneity (drug type: G-CSF versus GM-CSF; Hodgkin disease versus non-Hodgkin lymphoma; age [trials that included all ages 16 and older versus those restricted to older than age 60 years]; administration of prophylactic antibiotics during chemotherapy; different toxicity of chemotherapies); sensitivity analysis (placebo-controlled versus open label; concealment of allocation; size of studies [less than 100 versus 100 or greater]; published versus unpublished, unreported, or abstract based; and duration of follow-up). Statistical analyses included hazard ratios (OS and FFTF) (missing patient data analyzed using published survival curve methods); relative risk and 95% confidence interval (CI) (binary data) using the Mantel-Haenszel method for pooling (pooled using a fixed effect model); continuous data calculated as weighted mean differences with 95% CI; heterogeneity of treatment effect via chi-squared (p < 0.05); robustness of overall results and causes of heterogeneity assessed by sensitivity and subgroup analyses; funnel plots and linear regression (for bias; 0.1 = significant) used for meta-analyses of four or more trials; all data based on intention-to-treat or full set analysis.

• The final sample size included 13 RTCs.
• Total subjects across reviewed studies ranged from 25–784.
• 2,607 randomized patients were included in the review.
• Patients were aged 16 years and older with malignant lymphomas (Hodgkin disease or non-Hodgkin lymphoma) with the histological classifications of Working Formulation, Kiel, REAL, and WHO.
• All participants received standard nonmyeloablative chemotherapeutic agents and either G-CSF or GM-CSF within 72 hours of receiving the chemotherapy and prior to onset of neutropenia in the first or second line treatment of their malignant lymphoma.
• The control groups had to receive the same chemotherapies and same supportive care.

• The phase of care was active treatment
• Application was for elderly care

The prophylactic use of G-CSF or GM-CSF in patients aged 16 years and older with malignant lymphomas who underwent standard chemotherapy treatment had a reduced risk of neutropenia, febrile neutropenia, and infections. The prophylactic use of G-CSF or GM-CSF in this patient population does not increase overall survival or freedom from treatment failure.

Since neutropenia, febrile neutropenia, and infections are prevalent among patients with malignant lymphomas being treated with chemotherapeutic agents, the prophylactic use of G-CSF and GM-CSF is warranted to decrease the risk of these deleterious treatment effects.

Implications for nursing practice include knowledge about the efficacy of using these growth factors, advocating for their use, and close patient monitoring.

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

Societies in the United States and Europe continue to have different recommendations regarding the use of ESAs during cancer treatment; for QoL in palliative settings, the harmful effects of ESAs should be balanced against potential benefits. There is no evidence to support their use in managing cancer-related fatigue.

Greater than 90% of the studies were funded by pharmaceutical companies.

For patients receiving palliative care, there may be a role for ESAs in reducing transfusion use; there does not appear to be any role for ESAs in managing cancer-related fatigue.

A psychoeducational intervention was offered between three weeks and four months postsurgery for malignant melanoma to groups of 8 to 10 patients. The intervention was organized into six sessions lasting approximately 2.5 hours each and was performed over a six-week period. The intervention consisted of health education about malignant melanoma and follow-up routines, the importance of limiting sun exposure, stress awareness, and stress management (relaxation and guided imagery). Patients were given a workbook and a CD with relaxation and imagery exercises. Psychological support was provided via the presence of a group therapist throughout all sessions and through peer support in the group setting.

• In total, 262 patients with T1-4, N1a-2a, M0 malignant melanoma were recruited between 3 and 12 weeks postsurgery.
• No follow-up data on these patients were available.
• There were no significant differences between the treatment and control groups relative to any demographic or medical variables.
• The majority of the patients in both groups were married and between ages 40 and 60 years.

• Multisite
• Outpatient oncology clinics in eastern Denmark

Patients were undergoing the long-term follow-up phase of care.

The study was a randomized, controlled trial with a usual care control group. Fatigue was evaluated at baseline prior to the intervention and at 6 and 12 months postintervention.

Profile of Mood States (POMS)

Controlling for baseline levels of fatigue, there was a statistically significant effect of the intervention on fatigue six months postintervention. This effect was not sustained at 12-month follow-up. Sixteen patients dropped out of the intervention before it started or after one session. All patients who dropped out cited that they dropped out due to the time or the distance involved or that they felt no need for support.

• The study lacked an attentional control group.
• Sixteen patients dropped out of the intervention.
• The direction of the bias on the intervention effect on fatigue (i.e., overestimation of the effect versus underestimation of the effect) created by these drop-outs was not examined/reported.
• Professional training was required to deliver the intervention.

Efficiencies of treatment were achieved through the group intervention modality.

To test the effects of a group cognitive behavioral therapy (CBT) intervention on psychosocial symptoms in women with breast cancer

One to two weeks after surgery, women who agreed to participate were randomly assigned to a psychosocial intervention or a usual-care control group. The intervention consisted of 12 hours of education over a two-week period. Education provided information about treatment modalities, side effects, social rights, healthful diet, stress management, cognitive reframing, and sexuality issues. The intervention then involved meetings of eight women. Each group met weekly, in a 2.5-hour session, for eight weeks. In the sessions, the women shared experiences to reveal negative thinking and integrate the elements of cognitive therapy. Follow-up was up at 1, 6, and 12 months.

• The sample consisted of 176 women with breast cancer.
• In the intervention group, 61% were older than age 50; in the control group, 76% were older than age 50. Mean age and range were not stated.
• The majority of patients had received treatment with chemotherapy plus radiation therapy plus hormonal therapy.
• 74% of the women were married or cohabiting.

• Single site
• Outpatient setting
• Denmark

 Randomized controlled trial

• Profile of Mood States questionnaire
• Mental Adjustment to Cancer Scale
• EORT Quality of Life questionnaire
• Barrett-Lennard Relationship Inventory

At no time in the study did differences exist between groups in regard to mood disturbances, quality of life, or marital relationships.

The psychosocial intervention, consisting of cognitive behavioral techniques, had no effect on depression, anxiety, quality of life, or marital relationship.

• The study included baseline sample and group differences.
• The study presents risk of bias because it did not include blinding or an appropriate attentional control condition.
• Patients in the control group were older than patients in the intervention group. 
• The study does not make clear whether women were actively receiving adjuvant treatment during the study.

The CBT intervention tested had no observable effect on depression or anxiety in women with breast cancer.

To investigate the effects of modafinil on fatigue, depression, cognitive impairment, and health-related quality of life in patients with primary brain tumors

The intervention consisted of subjects receiving modafinil versus a placebo over six weeks. The week 1 dosage was 100 mg twice daily and the weeks 2–6 dosages were 200 mg twice daily. The cross-over occurred after the completion of week 6; thus, subjects who initially received the placebo followed the same dosing schedule over the next six weeks while those who had taken modafinil previously were given a placebo. Neuropsychological assessments and self-report measures were completed at baseline, six weeks, and 12 weeks.

• N = 37  
• AVERAGE AGE = 48.16 years (SD = 12.02 years)
• MALES: 37.8%, FEMALES: 62.8%
• KEY DISEASE CHARACTERISTICS: Gliomas and meningiomas with stable tumor status for six months
• OTHER KEY SAMPLE CHARACTERISTICS: Subjects had to score > 27 on the Checklist Individual Strength Test indicating the presence of fatigue. Exclusions include psychiatric disease or depressive disorders and medication interactions with modafinil.  

• SITE: Multi-site    
• SETTING TYPE: Outpatient    
• LOCATION: VU University Medical Center (Amsterdam), Academic Medical Center (Amsterdam), and Medical Center Haaglanden (Hague)

PHASE OF CARE: Multiple phases of care

Randomized, controlled, double-blinded clinical trial using a cross-over design. Measurements were performed at baseline, six weeks, and 12 weeks.

• Rey Auditory Verbal Learning Test (RAVLT)
• Memory Comparison Test
• Stroop Color and Word Test (Stroop)
• Letter Digit Substitution Test
• Concept Shifting Test (CST)
• Categorical Word Fluency Test
• Checklist Individual Strength (CIS)
• Center for Epidemiologic Studies Depression Scale (CES-D)
• Medical Outcomes Study Short-Form Health Survey (MOS SF-36)
• Medical Outcomes Study Subjective Cognitive Functioning Scale (MOS)

The CIS severity and reduced motivation scores for fatigue were lower after treatment with both modafinil (p = 0.01, p = 0.021) and placebo arms (p < 0.001, p = 0.027), but there was no difference in scores between trial arms. Significant improvements in working memory (p = 0.04, p = 0.043), information-processing (p = 0.036, p = 0.04), and attention (p = 0.015, p = 0.013) were found after treatment with modafinil and the placebo, respectively. There were no differences in scores between trial arms. Health-related quality of life measured by the physical component summary of the SF-36 was significantly improved for both modafinil (p = 0.001) and placebo arms (p = 0.008). There were no differences in depressive symptoms following modafinil or placebo.

The results indicate that there were no significant differences observed in fatigue, cognitive functioning, health-related quality of life, and mood between modafinil and a placebo. These findings may be related to the study design, duration of treatment, low study accrual, subject withdrawals, and lack of longitudinal follow-up.

• Small sample (< 100)
• Subject withdrawals ≥ 10%

Findings do not support the use of modafinil to improve fatigue, cognitive functioning, mood, and health-related quality of life in patients with brain tumors.

To determine factors that impact health-related quality of life (HRQOL) and mastery of caregivers of patients with high-grade glioma, and to investigate if a structured intervention consisting of psycho-education and cognitive behavioral therapy (CBT) leads to an improvement in the mental component of HRQOL and mastery of caregivers

Caregiver dyads randomly were assigned to the intervention group or care as usual group. The intervention group consisted of six one-hour sessions with a psychologist for CBT and psycho-education regarding disease-specific symptoms. Participants completed questionnaires concerning their perception of the patients' HRQOL, neurologic functioning, cognitive functioning, their own HRQOL perceptions, and feelings of caregiver mastery at baseline (prior to randomization) and every two months thereafter until eight months later, five times total.

• N = 56 caregiver dyads  
• MEAN AGE = 50 years
• MALES: Intervention group = 26%, control group = 48%; FEMALES: Intervention group = 74%, control group = 52%
• KEY DISEASE CHARACTERISTICS: High-grade glioma stage III/IV
• OTHER KEY SAMPLE CHARACTERISTICS: Participants were informal caregivers (defined as a spouse or significant other providing at least 21 hours of care per week); aged 18 years or older; 57% were receiving active treatment during the study 

• SITE: Multi-site    
• SETTING TYPE: Outpatient  
•  LOCATION: VU University Medical Center (Amsterdam)/Academic Medical Center (Amsterdam), and Medical Center Haaglanden (Netherlands)

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

• Randomized, controlled trial

• MOS 36-item short form survey (SF-36)
• Caregiver mastery scale
• MOS Cognitive Functioning Scale
• Brain cancer module

Caregivers' HRQOL and caregiver mastery were associated with patient-related factors at baseline. A positive correlation was found between a positive mental functioning (MCS) of the patient and a positive MCS of the caregiver. Feelings of mastery in the intervention group increased over time, while feelings of mastery in the control group showed the opposite pattern. Those who received the intervention maintained a more stable level of mental functioning and showed modest improvement in feelings of mastery in comparison to the control group. Patients' HRQOL and neurologic functioning were found to be related to HRQOL and feelings of mastery of the informal caregiver at baseline. The intervention helped caregivers in maintaining a stable level of HRQOL and improved feelings of mastery over an eight-month period.

The findings from this RCT suggest that informal caregivers can benefit from a psychological CBT intervention because it is a helpful tool in maintaining a stable level of mental functioning and caregiver mastery.

• Small sample (less than 100)
• Risk of bias (no blinding)
• Risk of bias (no appropriate attentional control condition)
• Findings not generalizable as a result of high attrition
• Intervention expensive, impractical, or training needs—significant time/burden for the caregiver (burdensome)
• Subject withdrawals 10% or greater
• Other limitations/explanation: Approximately 24% died prior to study conclusion

Future nursing practice should focus on offering supportive interventions to patients with high-grade glioma and their informal caregivers. Further research should continue to look at the effects of a psychological intervention on HRQOL and feelings of mastery of informal caregivers of the high-grade glioma patient population. Findings suggest that CBT interventions can be of benefit to caregivers.