RESOURCE TYPE: Expert opinion  

PROCESS OF DEVELOPMENT: The SWG was a multidisciplinary team of experts in the field who were closely involved in the sorafenib clinical development program. The group was established with the objective of developing recommendations to allow the early detection, prevention, and management of cutaneous adverse events in everyday clinical practice.

PHASE OF CARE: Active antitumor treatment

The SWG aims to collect the experience of each clinician in order to develop detailed, practical guidelines for the prevention and management of dermatological adverse events associated with sorafenib.

For grade 1 HFSR on the hands, apply zinc oxide and magnesium silicate lenitive cream without Vaseline. For feet, wear comfortable shoes with a latex insole if possible. Wash with non-foaming cleansing creams, apply same cream as hands, and wear perspiring socks without seams. For grades 2–3 HFSR, aspirate fluid inside blister and then medicate with a PEG-based cicatrizing ointment. Avoid antibiotics. General erythema should be treated also with zinc oxide and magnesium silicate lenitive cream. For follicular rash, apply a cold compress of potassium permanganate 0.0125% solution followed by 2% sulfosalicylic cream without Vaseline. No antibiotics recommended.

• Unknown

Nurses should consider these recommendations, especially for HFSR. Certainly, the preventative measures are worthy. However, one also needs to be familiar with any trials using the products that are recommended from this expert group.

Report results from using prophylactic outpatient use of teicoplanin or vancomycin for hospitalized patients on febrile neutropenia and bacterial sepsis for cases from 2005–2015. Prior to 2008, no routine antibiotic prophylaxis was used and antibiotics for prophylaxis when used varied. In 2009, a regimen with teicoplanin 15–20 mg/kg IV was instituted, starting at the onset of severe neutropenia on alternate days until the absolute neutrophil count was more than 400/mcl. In hospitalized cases, vancomycin was used. All patients received Pneumocystis jirovecii and systemic antifungal prophylaxis. Colony-stimulating factors were not used.

Data were collected from retrospective chart review for the use of antibiotics and the incidence and severity of infection.

• N = 50   
• AGE: Not provided
• MALES: Not provided  
• FEMALES: Not provided
• CURRENT TREATMENT: Chemotherapy
• KEY DISEASE CHARACTERISTICS: All had acute myeloid leukemia. Cases of relapse after hematopoietic cell transplantation were not included.

• SITE: Single site   
• SETTING TYPE: Multiple settings    
• LOCATION: Vienna

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

Retrospective cohort comparison

• Febrile neutropenia defined as a temperature greater than 38 degrees C with neutropenia that lasted for an hour, or a single temperature of at least 38.5.
• Bacterial blood cultures were obtained for patients with fever or other signs of infection.

In 98 chemotherapy cycles with teicoplanin or vancomycin prophylaxis, no patients developed viridians sepsis compared to 12 cases of viridians sepsis in patients without prophylaxis (p < 0.0001). Episodes of febrile neutropenia were also fewer in the teicoplanin/vancomycin group (44% versus 82%, p < 0.0001). No appreciable rise in vancomycin-resistant enterococci (VRE) incidence was observed since the regimen had begun.

The findings showed improved outcomes with antibiotic prophylaxis and no apparent rise in VRE isolates with the use of teicoplanin/vancomycin for prophylaxis.

• Small sample (< 100)
• Risk of bias (no control group)
• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• Key sample group differences that could influence results
• The efficacy of the regimen studies was compared to no prophylaxis.
• There were few cases in which different antibiotics were used.

The findings provide support for the benefit of antibiotic prophylaxis in general. Additional research is needed to determine the effects of routine vancomcin/teicoplanin use on the emergence of resistant organisms. Although no such increase was observed in this study, it has been identified in others.

To compare the effects of decongestive therapy in patients who did and did not receive previous treatment for lymphedema

Data were obtained retrospectively from medical records. Patient were grouped according to having received lymphedema treatment or not. Patients had undergoing assessment and 4–12 lymphedema treatments for four to six weeks. Consecutive patients referred for lymphedema treatment were included in the analysis. The intervention included MLD and compression, as well as teaching about good skin care, limb exercises, and deep breathing.

• N = 72   
• MEAN AGE = 53
• FEMALES: 100%
• KEY DISEASE CHARACTERISTICS: Patients with breast cancer with unilateral arm lymphedema who had standard axillary lymph node dissection
• OTHER KEY SAMPLE CHARACTERISTICS: Two to three years postsurgery for breast cancer

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

Retrospective cohort comparison

• Lymphedema defined as a volume increase of greater than 150 ml compared to the ipsilateral arm.
• Perometer measurement

Both groups had a reduction in limb volume.

Complete decongestive therapy was effective in reducing lymphedema for both patients who had prior treatment for lymphedema and those who did not.

• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• Unclear what types of previous treatment were involved

The findings add to the body of knowledge that complete decongestive therapy is effective in reducing lymphedema volume whether or not patients had undergone previous treatment for lymphedema.

Patients were exposed to the same kind of music played from a music set located within the chemotherapy unit while their chemotherapies were administered. Music included pieces from the album “Love Songs” by James Galway, distributed by BMG music, 2001 of which were instrumental pieces of international classical music. Patient outcomes were evaluated before and after a baseline cycle of chemotherapy and before and after a chemotherapy cycle with the musical intervention.

• The sample was comprised of 18 patients with breast cancer receiving adriamycin-containing adjuvant chemotherapy after undergoing modified radical mastectomy (median age = 45.5 years [range 28–60]).
• The majority of patients had stage II disease (77.8%), and five patients (27.7%) had associated comorbidities (e.g., hypertension, type 2 diabetes mellitus, coronary heart disease).

Outpatient clinics

This was a pilot study.

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

The music intervention did not demonstrate improvement in fatigue outcomes.

• The study had a small sample size.
• The study lacked a control group.

Future studies may want to account for personal preferences of the patients for the type of music listened to during chemotherapy.

STUDY PURPOSE: To complete a thorough systematic review of the evidence available in the literature regarding the use of nebulized medications in the treatment of dyspnea in chronic obstructive pulmonary disease (COPD), cancer, interstitial lung disease (ILD), and cystic fibrosis

TYPE OF STUDY: Systematic review

• FINAL NUMBER STUDIES INCLUDED = 39
• TOTAL PATIENTS INCLUDED IN REVIEW = Not combined for evaluation, not quantified
• SAMPLE RANGE ACROSS STUDIES: 1–100, also included literature reviews
• KEY SAMPLE CHARACTERISTICS: Studies varied widely, including studies examining medications, examining medication delivery (jet nebulizers), and reviewed literature reviews. Studies on children as well as adults with a variety of lung illnesses were included.

PHASE OF CARE: Multiple phases of care
 
APPLICATIONS: Pediatrics, elder care, palliative care

Results delineated by disease populations.

• Cancer: Findings were mixed with 12 publications supporting use, 8 inconclusive/insignificant, and one recommendation against use. Studied drugs included morphine, fentanyl, hydromorphone, and furosemide. Mixed results existed with both.
• For COPD: Medications reviewed included opioids and furosemide, again with mixed results. Favorable results were observed with jet nebulizers and fentanyl and furosemide. All morphine studies were negative.
• IPF: Of seven studies, three were high quality, and all of these were studies that included subjects with multiple diseases, one of which was IPF. Results were mixed (two inconclusive and one positive).
• Cystic fibrosis: Four studies were included. All were positive, but all had low-quality evidence (case reports).  
• Healthy: These were studies in which dyspnea was induced experimentally—two reviews; four double-blind, randomized trials of furosemide; and three positive.
• Terminal/end-stage populations: Three looked at cystic fibrosis, two looked at end-stage ILD/IPF, one at end-stage COPD, and eight at end-stage cancer. None was high-quality. Positive results with various agents existed, but, again, no high-quality studies existed.
• In all studies, results with morphine were mixed, and there were more positive studies with hydromorphone, fentanyl, and furosemide, but these were not of high quality.

Although many studies evaluated nebulized medications, this review included a wide variety of studies with varied goals, including systemic reviews, evaluation of opioids and furosemide, and delivery via ultrasound versus jet nebulizer across many disease processes and populations. The authors of this review suggested considering the use of nebulized medications on a case-by-case basis. No broader recommendations can be made at this point.

• Mostly low quality/high risk of bias studies
• High heterogeneity
• Low sample sizes

The oncology nurse should be aware of the use of nebulized medications as a delivery method for dyspnea but that there has not been any high-quality evidence to support the use of any specific medication. Although the delivery method may be more acceptable, the increased cost and lack of evidence do not support its use at this time.

To assess the effect of regularly administered extended-release morphine for dyspnea in patients receiving standard hospice care

• Regular administration of extended-release oral morphine 10 mg twice daily or 30% dose increase for those already on morphine
• Patients received 15 mg twice-daily metoclopramide for the first five days and a laxative.

• N = 15 (13 completed 48-hour assessment, 9 completed final assessment)
• MEAN AGE = 73 years
• MALES: 7, FEMALES: 8
• KEY DISEASE CHARACTERISTICS: Patients with cancer in hospice; mixed diagnoses—mostly lung primary or lung metastases, but four also had chronic obstructive pulmonary disease; patients with dyspnea from irreversible causes
• OTHER KEY SAMPLE CHARACTERISTICS: 13 were opioid-naive, and 2 were opioid-tolerant

• Eight patients were at home, and seven were hospice inpatients.

• Open, nonrandomized, uncontrolled

• Dyspnea visual analog scale (VAS)
• Support Team Assessment Schedule
• Borg Scale
• Respiratory rate
• Sedation VAS
• State-Trait Anxiety Inventory
• Pain (0–10)
• Assessments at baseline, 48 hours, and 7–10 days

Decline in dyspnea VAS scores for six patients was not statistically significant (p = 0.06). No clinically significant decline was found in respiratory function. No change was seen in anxiety, but actual scores were not reported. The authors stated that the high incidence of sedation and dizziness was of concern and indicated a need to monitor patients carefully. The authors also stated that the use of immediate-release morphine on an as-needed basis might be effective and cause less sedation.

Although the authors claimed that morphine should be trialed in patients, the evidence from this study does not support that. The problem may be the use of modified-release morphine 10 mg opposed to immediate release.

• The study had a small sample size with attrition.
• Three patients died, and three asked to withdraw because of side effects.
• Sedation at 48 hours was the main problem.
• Two patients who withdrew and two who died reported excessive drowsiness.

To evaluate a liposuction surgery and multidisciplinary rehabilitation approach for advanced lymphedema of the upper and lower extremities

Liposuction was performed under general anesthesia following limb exsanguination and tourniquet application. Using specialized Helixed Tri-Port III cannulas (22 and 30 cm long, 4–5 mm wide) connected to a vacuum pump, subcutaneous tissue was removed through multiple small incisions along the limb. Presurgical limb volume determined how much tissue was removed to equalize volume relative to the unaffected limb. Compression garments were applied to the affected limb immediately postsurgery prior to tourniquet release (custom-made 30 mmHg JOBST^® Elvarex for arms, or Ready Wraps^® [Solaris] for legs). From one week postsurgery, all leg patients wore JOBST Elvarex custom-made compression garments 50–80 mmHg. Initial postsurgical garments were measured using the circumference of the unaffected limb. Subsequent measurements were obtained from the operated limb by a trained garment fitter. Every order consisted of two garments, allowing one to be worn while the other was washed. Throughout follow-up, compression garments alone were used in areas where liposuction was performed. However, decongestive lymphatic therapy was used when indicated in areas where liposuction was not performed (hands or feet) or areas that could not be adequately compressed (shoulder or hip).

• N = 21 (15 arm and six leg)
• MEAN AGE = 57.8 years (range = 25–69 years) in arm group; 50.7 years (range = 18–66 years)
• FEMALES: 100%
• KEY DISEASE CHARACTERISTICS: Cancer-related secondary lymphedema
• OTHER KEY SAMPLE CHARACTERISTICS: Cancer-related secondary lymphedema was a more common reason for liposuction (85.7%) than primary (congenital) lymphedema (14.3%) with breast cancer treatment being the most common underlying cause (66.7%). The mean time of longstanding lymphedema was 9.1 years (range = 2–29 years) in the arm group versus 15.5 years (range = 3–42 years) in the leg group. 

• SITE: Single site    
• SETTING TYPE: Multiple settings
• LOCATION: Australia

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

Prospective clinical study, one arm, pre and post measures

• Limb volume by tape was calculated using 4 cm truncated cone circumferential measurements
• Lymph fluid measured by bioimpedance spectroscopy (L-Dex^®) measurement
• Functional and emotional impairment was assessed using the Patient-Specific Functional Scale (PSFS). PSFS is reliable and valid across contexts and sensitive to change in breast cancer survivors, but it was not previously validated for lymphedema.

Liposuction was safe and may be an effective option for carefully selected patients with advanced lymphedema. Assessment, treatment, and follow-up by a multidisciplinary team is essential.

• Small sample (< 30)
• Baseline sample/group differences of import 
• Risk of bias (no control group)
• Risk of bias (no blinding)
• Risk of bias (no random assignment) 
• Risk of bias (no appropriate attentional control condition)  
• isk of bias (sample characteristics)

Liposuction is a surgical approach to lymphedema. It should be noted that even with continuous compression therapy, postliposuction, patients’ lymph fluid level was elevated beyond normal. Nurses should continue observing the impact of liposuction on patients’ physiological, functional, and emotional aspects. Nurses should also advise patients according to current evidence.

The purpose of the study was to evaluate the incidence of lymphedema after axillary dissection to determine the effects of prospective monitoring and early physiotherapy intervention

The study sample (N = 65) was comprised of a treatment group and a control group.

The study used a randomized controlled trial design.

Both arms of patients were measured for circumference, volumetry, and multi-frequency bioimpedance analysis preoperatively and 5 days and 1, 3, 6, 12, and 24 months postoperatively.

A small number of women detected with clinically significant lymphedema (n =12); 91% of women completed measures at two years after surgery. Two women had bilateral surgeries within the first month after enrollment. At 24 months, three times as many women in the control group compared to treatment group showed secondary lymphedema (except for volume criteria). Using volume criteria, a trend toward increased lymphedema in patients with mastectomy complete with breast conservation therapy existed. Hand or arm dominance did not influence lymphedema by these measurements. Logistic regression used to determine risk factors for development of lymphedema included

• Axillary dissection by level
• Number of lymph nodes removed
• Number of lymph nodes affected with disease
• Wound infection
• Body mass index
• Total wound drainage
• Seroma
• Age
• RT
• Occupation
• Clinical.

Clinical incidence of lymphedema in the study was 21% at two years.

The study was very well done and well designed.

• The sample size was small; however, the data are useful in that they suggest a preventative approach with ongoing monitoring to prevent and minimize risk in a population with high-risk criteria for development of symptoms.
• Anecdotal evidence of some specific cases.

Nurses should advocate ongoing measurement to detect changes early and intervene.

To examine, relative to a health education control, the feasibility and efficacy of an Iyengar yoga intervention for breast cancer survivors with persistent posttreatment fatigue.

Outcome assessors of the performance tasks were blinded to group assignment. The intervention was briefly but fully described, and then participants were randomly assigned to a group that received a 12-week, Iyengar-based yoga intervention or a group that received 12 weeks of a health education (control group).

• The sample was comprised of 31 women.
• Mean age was 54.4 years (standard deviation [SD] = 5.7 years) in the intervention group and 53.3 years (SD = 4 years) in the control group.
• All participants had stage 0 to II breast cancer.
• Most participants were white.
• The range of education was high school completion through graduate degree.
• Twenty-four participants were completing radiotherapy, 17 were completing chemotherapy, and 22 were receiving hormone therapy.
• In the intervention group, median time posttreatment was 1.7 years (range 0.7–4.1).
• Breast cancer survivors with posttreatment fatigue were recruited through multiple mechanisms. Inclusion and exclusion criteria were applied.
• The original enrollment target was 72 participants; researchers assumed a 20% loss to follow-up. Because of the stringent enrollment plan, the sample size was smaller than expected.
   

• Single site
• Outpatient
• University of California, Los Angeles
   

• Patients were undergoing the posttreatment phase of care.
• The study has clinical applicability for survivorship and late effects and survivorship.

The study was a randomized, controlled trial.

• Fatigue Symptom Inventory (FSI)
• Multidimensional Fatigue Symptom Inventory (MFSI), to assess vigor
• Beck Depression Inventory II (BDI-II)
• Pittsburgh Sleep Quality Index (PSQI)
• Perceived Stress Scale (PSS)
• Timed chair stands and functional reach test, to assess physical performance
• Medical Outcomes Study (MOS)
   

Relative to the control group, fatigue severity in the intervention group declined significantly (p = 0.032) from baseline to posttreatment and over the three-month follow-up. In addition, relative to the control group, the yoga group had significant (p = 0.011) increases in vigor. Both groups had positive changes in symptoms of depression and perceived stress (p < 0.05). The authors noted no significant changes in sleep or physical performance. 

One adverse protocol-related event occurred:  a participant with a history of back problems experienced a back spasm in yoga class. After evaluation by her physician, she returned to class.

A targeted yoga intervention led to a significant reduction in fatigue and improvement in vigor among breast cancer survivors with persistent fatigue symptoms. This conclusion should be understood in the context of the study:  participants were relatively healthy and without comorbid conditions found in the general population.

• The study had a small sample size, with less than 100 participants.
• Some participants had been living with cancer for more than five years, which was longer than most in the study had been living with cancer.
• Because of the context of the study, researchers were unable to use a double-blind design.
• The study included multiple conditions.
• The results were not generalizable.

This study offered minimal conclusive data in support of the intervention. Preliminary findings indicated that the yoga intervention is feasible and safe and has a positive effect on fatigue. A larger trial that includes participants with common comorbid conditions—a study more representative of the general population of women with breast cancer posttreatment—is warranted. Secondary outcomes included vigor, symptoms of depression, sleep, perceived stress, and physical performance.

PHASE OF CARE: Late effects and survivorship

Adapted from three guidelines by multidisciplinary experts using supplementary evidence and clinical experience. Most recommendations listed verbatim but some modified to include updated evidence or current practice beliefs.

Recommendations focused on patients who have completed active treatment or are considered in clinical remission. Treat underlying causes, moderate physical activity after cancer treatment with PT and lymphedema referrals as needed (meta-analysis, systematic review, [randomized controlled trial [RCT]; 10 cited), cognitive behavioral therapy (meta-analysis, RCT, systematic reviews; 6 cited), psychoeducational therapies (systematic, RCT; 3 cited), psychosocial services, mindfulness-based interventions (RCT; 3 cited), yoga (RCT; 2 cited), acupuncture (RCT; 2 cited), psychostimulants/wakefulness agents (limited evidence in patients who are post-treatment disease-free). Additional areas in which research needed include biofield therapies, massage, music therapy, relaxation, Reiki, Qigong, ginseng, and vitamin D.

Guidelines were tailored to survivors with current evidence as not all evidence done is survivors.

Screening, assessment, and treatment guidelines summarized for use in cancer survivors.