STUDY PURPOSE: To analyze the effects of low-level laser therapy (LLLT) on lymphedema secondary to breast cancer surgery

TYPE OF STUDY: Systematic review

• FINAL NUMBER STUDIES INCLUDED = 5 
• TOTAL PATIENTS INCLUDED IN REVIEW = 189
• SAMPLE RANGE ACROSS STUDIES: 11–61
• KEY SAMPLE CHARACTERISTICS: All had breast cancer–related lymphedema (BCRL).

PHASE OF CARE: Late effects and survivorship

All studies showed positive results of LLLT compared to control groups, which was most evidenced in studies with longer time frames.

The findings suggest that LLLT may be a treatment option for upper limb lymphedema in women with breast cancer; however, more well designed research is needed.

• Limited number of studies included
• Low sample sizes

More research with larger samples and comparisons to other effective interventions are needed to determine the role of LLLT for lymphedema treatment. LLLT may be a useful adjunct for lymphedema treatment.

To examine infection measures to reduce the transmission of vancomycin-resistant enterococci (VRE).

VRE cultures were obtained from all 259 patients (100%) in 404 admissions to the unit during the use of enhanced infection control strategies and 167 of 184 patients (91%) in 210 admissions to the unit during the use of standard infection control practices.

Enhanced Infection Control

1. Inpatient surveillance: perianal cultures on admission and weekly
2. Hand washing before and after patient contact
3. Contact isolation for VRE-colonized and VRE-infected patients
4. Gown and glove use on entry of rooms of VRE-colonized and ​VRE-infected patients
5. Consultation with infectious disease specialists when infection is first suspected
6. Systematic recommendation by infectious disease specialists to discontinue empirical vancomycin use after 72 hours
7. Systematic recommendation by infectious disease specialists to use oral metronidazole rather than oral vancomycin for Clostridium difficile colitis
8. Spatial separation of patients into three cohorts: VRE-positive, VRE-negative, and VRE-unknown patients
9. Surveillance of perianal cultures taken for inpatients with cancer housed off the oncology unit
10. Gown and glove use on entry of rooms of VRE-unknown patients
11. Assignment of staff cohorts; nurses and nursing assistants assigned to VRE-positive patients or VRE-negative and VRE-unknown patients
12. Patient orientation about VRE with an explanatory brochure
13. Monitoring compliance by observational studies
14. Environmental cultures taken in VRE-positive patient rooms before and after patient discharge and room disinfection

Patients were evaluated during the use of enhanced infection control strategies (n = 259) and standard infection control practices (n = 184).

Eleven-room, 22-bed adult oncology unit in a 650-bed tertiary care hospital

This was a prospective cohort study.

Standard infection control versus enhanced infection control:

• VRE infection rates
• Colonization
• Changes in antimicrobial use.

• VRE colonization was significantly reduced: 8.6 patients per 1,000 days versus 13.2 patients per 1,000 days
• Compliance with enhanced strategies: 91.7% of individuals who entered rooms wore gowns and gloves
• Enhanced infection control strategies: The incidence of VRE bloodstream infections decreased significantly (1.4 patients per 1,000 days versus 3.2 patients per 1,000 days for the standard group).

• No conceptual model was described.
• Single unit where patients were not transferred
• No randomization
• Fifteen infection control measures were implemented simultaneously; therefore, the influence of each intervention is unknown.

To compare the effects of fentanyl and ketamine as premedication before painful procedures in children

Participants scheduled for invasive procedures requiring sedation were randomized to receive either fentanyl or ketamine pre-medication before lumbar puncture for intrathecal chemotherapy or bone marrow biopsy. The treatment was reversed prior to the next procedure each child received. Pain was measured two hours after the procedure when patients fully recovered from sedation, and patients were monitored for 24 hours after the procedure. The average washout period was 5.8 weeks.

• N = 55   
• AGE = 16% were younger than 4, 43.6 % were 4–8 years, and 40% were older than 8
• MALES: 49.1%, FEMALES: 50.9%
• KEY DISEASE CHARACTERISTICS: All had hematologic cancers

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

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

• Controlled, randomized, crossover trial

• FLACC scale (Faces, Legs, Activity, Cry, Consolability) for those younger than four years
• Wong-Baker FACES pain rating scale for 4–8 year olds
• Visual Analog Scale for Pain (VAS-Pain) for those older than eight years

Pain severity was lower with fentanyl (median 2 versus median 2.44 with ketamine) (p = 0.002). When receiving fentanyl, patients also had less nausea and vomiting post-procedure. Ketamine was associated with side effects of hallucination, nausea, vomiting, and increased salivation. Side effects seen with fentanyl were nausea (9%) and vomiting (3.64%) within 24 hours post-procedure.

Premedication with fentanyl in children prior to invasive procedures was associated with less severe pain and fewer side effects compared to ketamine.

It is unclear if the specific procedures were the same for both study conditions in the crossover. Validity of determination of side effects such as hallucination in the youngest children is questionable—behavioral changes were included in the author's definition of this side effect.

Fentanyl premedication for invasive procedures requiring sedation in children was associated with lower severity of pain after the procedures and fewer side effects compared to ketamine.

• Cohort A: Six patients received docetaxel (43 mg/m²) weekly for six weeks every eight weeks.
• Cohort B: Six patients received docetaxel weekly combined with etanercept (25 mg subcutaneously) twice weekly in addition to the docetaxel dosing schedule observed in Cohort A.
• Cohort C: Six patients received docetaxel at a higher dose (52 mg/m²) weekly combined with etanercept (25 mg subcutaneously) twice a week for six weeks.
• Cohort D: Eight patients received docetaxel (52 mg/m²) weekly combined with etanercept (25 mg subcutaneously) twice a week and G-CSF (5 ug/kg per day for four consecutive days starting the day after each docetaxel administration).
• Outcomes were assessed at baseline and each week.

N = 28

MEDIAN AGE = 56 years

AGE RANGE = 25–83 years

MALES = 17

KEY DISEASE CHARACTERISTICS: Most had received previous chemotherapy and/or radiotherapy and had multiple disease sites. The most common disease site was non-small-cell lung.

EXCLUSION CRITERIA: Patients were excluded if they were scheduled for major surgery, radiotherapy, or chemotherapy within 28 days of study entry or had brain metastases, serious infections, or psychiatric disorders that would interfere with consent or follow-up; pre-existing moderate-to-severe peripheral neuropathy; or cardiac disease. Pregnant or lactating women also were excluded.

• PHASE OF CARE: Active treatment

• Pilot feasibility study

• National Cancer Institute (NCI) fatigue grade assessment
• Fatigue Symptom Inventory (FSI)

Patients randomly were selected to receive etanercept/docetaxel. Less fatigue was self-reported in comparison to patients who received docetaxel only (p < 0.001). The FSI Interference score of Cohort A was significantly greater than the score of Cohort B (p < 0.001). Patients receiving additional cycles for treatment (Cohorts B,C, and D) did not experience worsening fatigue.

• Pilot study and therefore lacking a neutral comparison group
• Small sample size
• Fatigue assessment endpoints were not predetermined

To investigate whether moist skin care with 3% urea lotion will reduce acute radiation (RT) skin toxicity.

Irradiated skin of inpatients was treated with 3% urea lotion (Eucerin^® 3%, Beiersdorf).

Outpatients were treated with either urea lotion or powder, depending randomly on the date when they started RT (Azulon^®, Baxter Oncology GmbH, formerly ASTA Medical AWD).

They were instructed to avoid mechanical, chemical, or thermal irritations of the skin, to wear light clothes, and to omit jewelry. Men were told to use an electric shaver.

Starting with the first day of irradiation, irradiated skin was treated with lotion or powder twice daily. At the occurrence of a skin reaction grade I or II, the lotion or powder was given at least five times per day. If skin lesions grade III or IV occurred, treatment with lotion or powder was stopped and the patient received appropriate wound care programs (povidone-iodine and zinc ointments). Findings were compared to those of historical controls.

• The sample was comprised of 88 patients (63 urea lotion, 25 historical controls).
• Age was not reported.
• Of the patients, 85% were male and 15% were female.
• Patients had carcinomas of the head and neck and were undergoing RT with curative intent.
• Mean total dose was 60 Gy (range 50–74 Gy).

Multiple sites in Germany

The study was a single-arm clinical trial with a historical control comparison.

Patients were evaluated weekly for acute skin reactions according to the Radiation Therapy Oncology Group (RTOG) score.

To exclude sampling errors and scoring differences between different observers, all skin evaluations were performed by the same physician.

Results showed that controls had a higher prevalence of skin toxicities at all grades, at lower radiation doses (p < 0.05).

Moist skin care with 3% urea lotion may delay the occurrence of acute RT-induced skin reactions.

• The sample of patients with head and neck cancers was very diverse, and treatment plans varied substantially. A 6-mev machine tends to have more skin toxicity than an accelerator with the ability to perform multienergy.
• A larger proportion of controls were also receiving chemotherapy, which may have skewed the results.
• The study had a relatively small sample and was not randomized.

To evaluate the effectiveness of regional cooling on palmar-plantar erythrodysesthesia (PPE).

Patients received pegylated liposomal doxorubicin (PLD) every 28 days, with dosages ranging from 30 mg/m² to 50 mg/m².

Group 1 (n = 17) used regional cooling. The regional cooling protocol (RCP) included administration of ice packs to the wrists and ankles, and iced liquids were available for consumption during PLD infusion. In addition, patients were encouraged to use the ice packs for up to 24 hours after completion of the PLD infusion.

Group 2 (n = 3) did not use RCP. Patients were instructed to avoid ingestion of hot foods or liquids, avoid contact with hot water and direct sunlight, and minimize friction to the hands and feet for 72 hours post-PLD treatment.

• The study reported on a sample of 20 female patients with recurrent epithelial ovarian cancer who received PLD.
• The median number of PLD cycles was five.

University of Nebraska Medical Center in Omaha

This was a retrospective analysis of 20 patients’ records.

PPE was graded from 1 to 4; however, the authors did not specify what grading system was used.

The frequency and severity of PPE was reduced in 17 women who used the RCP, compared to three women who did not use those measures (p = 0.047).

Regional cooling around the wrists and ankles was well tolerated and had a high degree of compliance during chemotherapy administration.

• This was a retrospective review of records.
• The sample size was small.
• The description of the measurement method used to grade PPE symptoms was insufficient; reliability and validity were unclear.

To evaluate the feasibility and effectiveness of a patient-performed daily spirometry as an early warning tool and the use of a positive expiratory pressure (PEP) flute device to prevent pneumonia among outpatients undergoing treatment for acute myeloid leukemia (AML)

All patients received a 45-minute face-to-face educational session about pneumonia prevention and assessing for early signs, plus instructions on how to use a spirometer and record findings daily. The intervention group received PEP flutes and instructions for use. All patients received instructions for contacting a healthcare provider if symptoms occurred. The primary outcome was occurrences of pneumonia.

• N = 80 (40 per group)   
• MEAN AGE = 56 years (both groups)
• MALES: 63.75%, FEMALES: 36.25%
• CURRENT TREATMENT: Chemotherapy
• KEY DISEASE CHARACTERISTICS: AML

• SITE: Multi-site   
• SETTING TYPE: Multiple settings    
• LOCATION: Copenhagen, Denmark

• PHASE OF CARE: Active antitumor treatment

• Randomized, controlled trial

• Adherence to the PEP flute was measured by patient feedback at weekly meetings (unclear if verbal or written).
• Pneumonia was measured by x-ray verification of infiltrates, bronchoalveolar lavage or sputum cultures, and electronic transfer of data from the spirometer to show adherence.

The use of FEV1 to monitor for early onset pneumonia can be effective. The use of the PEP flute significantly decreases the occurrence of pneumonia.

• Small sample (< 100)
• The findings were reported on a total of 80 patients, although three dropped out in the beginning of the study, seven during induction chemotherapy, and another eight because of distress.
• Table II reported on pneumonia findings in all 80 patients.
• Statistical considerations for missing data were unclear.
• An adjustment was made for the FEV1 analysis (10 patients removed because of comorbidities and/or very poor lung capacity, 4 of whom had cases of pneumonia).

Direct patient education on the use of spirometry to evaluate FEV1 and PEP flutes is effective. FEV1 findings can potentially aid with early pneumonia diagnosis, and the use of the PEP flutes can help prevent pneumonia.

To evaluate the effectiveness of systemic antibiotic treatments (oral doxycycline) and local treatment for skin rash in patients receiving cetuximab.

Patients were prospectively evaluated by dermatologists from two phase 2 trials between October 2003 and May 2004. Dermatologists determined they would treat four patients with oral doxycycline; in three of those patients, a topical treatment (retinoid) was given as well. Other patients were treated with benzoyl peroxide (n = 1) or fusidic acid (n = 1).

• The study reported on a sample of 13 patients with metastatic colorectal cancer who were receiving cetuximab once per week (400 mg/m² on week 1 and 250 mg/m² thereafter).
• The cetuximab treatment was associated with oxaliplatin, 5-fluorouracil, and fusidic acid, or irinotecan.

Service de Dermatologie et Service d’Oncologie, Hôpital Tenon, in Paris, France

This was a prospective trial.

Rash intensity was graded as mild, moderate, or severe.

• Eleven patients treated with cetuximab (85%) developed skin lesions.
• The six treated patients responded to classical modalities of doxycycline (n = 4), benzoyl peroxide (n = 1), and fusidic acid (n = 1). Skin lesions resolved in four weeks.
• Five patients were not treated because the acneform rash was mild. In those patients, the rash resolved spontaneously, although cetuximab was continued at the same dose.

Antibiotic treatments (oral doxycycline) and local treatments given to six patients receiving cetuximab were effective in resolving skin lesions.

• This was a very small, nonrandomized trial.
• The description of the measurement tool or method used to grade rash symptoms was inadequate, with no reliability and validity.
• Treatment was determined by the dermatologist.
• A combination of interventions was used; therefore, determining the effectiveness of the individual interventions is difficult.

To evaluate the effectiveness of systemic antibiotic treatments (oral doxycycline) and local treatment for skin rash in patients receiving cetuximab.

Patients were prospectively evaluated by dermatologists from two phase 2 trials between October 2003 and May 2004. Dermatologists determined they would treat four patients with oral doxycycline; in three of those patients, a topical treatment (retinoid) was given as well. Other patients were treated with benzoyl peroxide (n = 1) or fusidic acid (n = 1).

• The study reported on a sample of 13 patients with metastatic colorectal cancer who were receiving cetuximab once per week (400 mg/m² on week 1 and 250 mg/m² thereafter).
• The cetuximab treatment was associated with oxaliplatin, 5-fluorouracil, and fusidic acid, or irinotecan.

Service de Dermatologie et Service d’Oncologie, Hôpital Tenon, in Paris, France

This was a prospective trial.

Rash intensity was graded as mild, moderate, or severe.

• Eleven patients treated with cetuximab (85%) developed skin lesions.
• The six treated patients responded to classical modalities of doxycycline (n = 4), benzoyl peroxide (n = 1), and fusidic acid (n = 1). Skin lesions resolved in four weeks.
• Five patients were not treated because the acneform rash was mild. In those patients, the rash resolved spontaneously, although cetuximab was continued at the same dose.

Antibiotic treatments (oral doxycycline) and local treatments given to six patients receiving cetuximab were effective in resolving skin lesions.

• This was a very small, nonrandomized trial.
• The description of the measurement tool or method used to grade rash symptoms was inadequate, with no reliability and validity.
• Treatment was determined by the dermatologist.
• A combination of interventions was used; therefore, determining the effectiveness of the individual interventions is difficult.

To assess the feasibility of inspiratory muscle training (IMT) in the lung cancer population and to explore changes in outcomes

Patients were randomized to either the standard care group or the intervention group, which received standard care and intervention of IMT, consisting of two supervised sessions, then home self-delivery of IMT with provided device (pressure threshold device) in five sessions weekly for 12 weeks of 30 minutes per day divided over two sessions. Assessments were completed at 4, 8, and 12 weeks.

• N = 46  
• MEAN AGE = 69.5 years 
• AGE RANGE = 51–85 years
• MALES: 80.4%, FEMALES: 19.6%
• KEY DISEASE CHARACTERISTICS: The study included patients with primary lung cancer or mesothelioma, refractory dyspnea, prognosis of less than three months as judged by a clinician, and an O₂ saturation less than 85% at rest.
• OTHER KEY SAMPLE CHARACTERISTICS: The study excluded patients who had received radiation to the chest within four weeks or chemotherapy within two weeks. It generally included patients with stable disease who were off treatment.

• SITE: Multi-site   
• SETTING TYPE: Multiple settings—large cancer centers, but participants completed intervention in their homes
• LOCATION: Two sites in the UK and one in Cyprus

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

• Randomized, controlled trial

• Spirometry assessment (physiologic data)—forced vital capactiy (FVC), forced expiratory volume (FEV1), FEV1%, and peak expiratory flow (PEF)
• Severity of breathlessness, distress caused by breathlessness, ability to cope with breathlessness, and satisfaction with management of breathlessness all assessed by patient self-report on a 0–10 numeric rating scale
• Modified Borg Breathlessness Scale (MBBS) 
• Short Form Chronic Respiratory Disease Questionnaire (SF-CRDQ)
• Hospital Anxiety and Depression Scale (HADS)
• Clinician assessement and patient self-report or hypercapnia (safety) 
• Compliance measured with patient-maintained training diary
• Chronic Respiratory Disease Questionnaire (CRDQ)

This trial showed that IMT is feasible and acceptable for patients with lung cancer. In comparison of IMT group and control group, several outcomes, including worst breathlessness, average breathlessness, distress from breathlessness, ability to cope with breathlessness, satisfaction with management of breathlessness, fatigue, and depression and anxiety had improved for the IMT group over the control group. No differences were seen in spirometry and breathlessness between groups.

IMT is feasible and acceptable for patients with lung cancer and improved outcomes were seen for patients receiving IMT. However, this trial had a small sample size, so it cannot adequately draw solid conclusions regarding outcomes for patients with lung cancer undergoing IMT for breathlessness. Larger trials should be conducted to evaluate this.

• Small sample (< 100)
• Findings not generalizable
• This study included only patients with lung cancer.
• Does not include those with breathlessness from metastasis
• Does not quantify number of patients with other underlying lung disorders that may contribute to breathlessness
• Excludes only those with unstable COPD

IMT may be of benefit for the treatment of breathlessness, but data are too weak due to the small sample size to strongly recommend IMT. In addition, the study included only patients with lung cancer. This study is inadequately powered to draw conclusions about outcomes and does not address any patients experiencing breathlessness from nonthoracic malignancies.