STUDY PURPOSE: To discuss the treatment of breast cancer-related lymphedema with low-level laser therapy (LLLT), its usefulness, and safety

TYPE OF STUDY: General review/\"semi\" systematic review

• FINAL NUMBER STUDIES INCLUDED = 4
• TOTAL PATIENTS INCLUDED IN REVIEW = 149 (n = 75 treatment, n = 74 control)
• SAMPLE RANGE ACROSS STUDIES: 12–66
• KEY SAMPLE CHARACTERISTICS: All treatment groups received LLLT, and all subjects were breast cancer survivors with BCRL. Ages in both groups were similar, ranging from 45–63 years in the treatment group and 49–65 years in the control group. Baseline excess limb volumes were also similar between the treatment and control groups, although varied measures were used.

PHASE OF CARE: Late effects and survivorship

Three of four studies were able to show statistical significance in limb volume after treatment; however, follow-up times varied. Carati et al. reported a significance of 0.017 (89.7 ml versus 32.1 ml) three-months post-treatment, Kaviani et al. reported a greater reduction in all weeks except one (no statistical reference), Kozanoglu et al. reported a greater reduction with LLLT (p = 0.04 at post-treatment and p = 0.02 at 12 months), and Lau et al. reported a statistically significant reduction at four weeks post-treatment (448.2 to 320.9 ml, p = 0). Two studies reported significance in a decrease in tissue hardness. No improvement in subjective symptoms were reported (pain, range of motion [ROM], heaviness, grip strength); however, Lau et al. reported significantly decreased mean scores on the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire in the treatment group (p = 0.04) post-treatment, but they were not statistically significant at four weeks follow-up.

• Limited search
• Low sample sizes
• Control group protocols, treatment protocols, and lymphedema assessment measures were dissimilar in all four studies.
• Quality was assigned to articles; however, evidence levels were not assigned (the authors address this in the article).
• Lack of operational definitions and comparison with standard therapy (CDT) were also limitations.

Nurses need to be knowledgeable of clinical trials involving LLLT and stay current with lymphedema management, as well as educate patients on LLLT.

• Patients were randomly assigned to use either ice chips or room-temperature normal saline (NS) rinses before, during, and after melphalan infusion, two days before peripheral blood stem cell transplantation (PBSCT).
• Patients in the ice chips group were instructed to place approximately 1 oz of crushed ice in the mouth. Ice was allowed to melt and was replenished as soon as it was completely melted. Patients were instructed to start 30 minutes before and continue for 6 hours after the end of the 30-minute melphalan infusion.
• Patients in the saline rinse group were instructed to swish 1 oz of room-temperature normal saline in the mouth and spit it out every 30 minutes.   
• Patients were instructed not to eat or drink anything extremely hot or cold during this period.
• The sample size was set at 40 to provide 91% power at a 0.05 significance level.

• The study reported on 41 randomized patients with 21 assigned to receive ice chips and 20 assigned to receive NS. One patient in the NS group withdrew because the patient wanted ice chips. Therefore, data was collected for 21 patients in the ice chips group and 19 in the NS group.
• Patients had to be 18 years or older with multiple myeloma scheduled to receive single-agent melphalan at 200 mg/m² followed by autologous PBSCT.
• Patients were stratified by age less than or greater than 60 years.

This was a randomized trial.

• Patients completed questionnaires that addressed overall health as well as mouth and throat soreness.
• Patients rated difficulties swallowing, drinking, eating, talking, sleeping, and tasting on a 0–4 scale with 0 = no difficulty and 4 = unable to perform.
• Patients rated mouth and throat soreness on a 0–10 scale.  
• Clinical providers and nurses conducted oral assessments as part of routine care using National Cancer Institute (NCI) common toxicity criteria.

• Fewer patients in the ice chips group (14%) experienced grade 3–4 mucositis than in the NS group (75%) (p = 0.0005).
• Patients in the ice chips group required fewer days of total parenteral nutrition (TPN) than the NS group (2 versus 5.5; p = 0.04).
• Patients in the ice chips group also required fewer days of IV narcotics than the NS group (0 versus 5.5; p = 0.0003).
• No significant difference was found in days of hospitalization.
• Patients in the ice chips group experienced significantly less difficulty with activities of eating, talking, sleeping, and tasting.

• The sample size was small.  
• Some inconsistencies occurred with protocol compliance such as variations in the length of time that ice was used and lack of reporting how long ice was used. Some patients complained of coldness and stopped using the ice chips. Additionally, four patients did not fill out any pain reports or record other activities.

Cryotherapy was associated with improved outcomes. Research is needed to determine the required length of cryotherapy.

The study evaluated the value of true acupuncture in management of hot flashes in women with breast cancer receiving tamoxifen.

Patients  on tamoxifen who experienced vasomotor symptoms were randomly assigned to true acupuncture or control acupuncture groups.  All patients were treated for 20 minutes twice weekly for 5 weeks in an outpatient clinic.  In the true acupuncture group, 8 needles were inserted at defined points.  In the control group, needles did not penetrate the skin, but were rotated until the patient felt a superficial sensation on the skin.  In the control group, the needles were placed at 8 sites, as well.   Study data were collected at baseline, week 6, and week 18.

The study enrolled 74 women with a mean age of 58 years. 

• KEY DISEASE CHARACTERISTICS: All had breast cancer  and were receiving tamoxifen.
• OTHER KEY SAMPLE CHARACTERISTICS:
  • 70% were post menopausal
  • 69% had received previous estrogen replacement therapy
  • 22% were also receiving SSRIs
  • 41% in the treatment group and 38% in the control group had received previous acupuncture therapy

The study was conducted in an outpatient clinic in Sweden.

PHASE OF CARE: Transition phase after active treatment

The study was a single-blind, randomized, sham-controlled trial.

Instruments/measures included:

• Vasomotor symptom intensity – 5 point self-report scale
• Hot flush diary

There were no significant differences between groups in frequency of hot flushes and sweating over time.  The acupuncture group reported less severity of symptoms of sweating at night ( p = .03).    Both groups demonstrated significant improvement in symptoms over time.  Of those who received true acupuncture, 69.4% thought they had receiving true acupuncture, while 63.9% of those in the control group thought they had received true acupuncture, suggesting that patient blinding was accomplished.  One adverse event of bleeding and bruising was reported in 1 control patient.

Findings suggest little difference in symptoms between those who received acupuncture versus those who received sham acupuncture.  Acupuncture may have some benefit, but it is unclear if this also reflects a placebo effect from the intervention.

Study limitations included:

• Small sample (< 100)
• Risk of bias (no blinding)
• Measurement/methods not well described 
• Measurement validity/reliability questionable 
• It is unclear how a control patient could have experienced the adverse event of bleeding at a sham acupuncture site when the sham needles did not puncture the skin.  This raises questions about fidelity to the sham procedure used. 
• Investigators who collected the data were not blinded. 
• It is unclear how the frequency of night sweatings was actually measured and what was used for the analysis – the measurement method described does not specify frequency of episodes and does not specify time of day of episodes. There was no analysis of significance of  baseline symptom differences between groups, or correction of changes over time with baseline symptom levels

This study provides limited evidence regarding the effect of acupuncture for vasomotor symptoms in women with breast cancer treated with tamoxifen.  It does demonstrate questions regarding potential placebo effects of acupuncture or placebo effects of sham acupuncture procedures that complicate research design in this area. Appropriate placebo or comparison control groups for this type of research need to be identified.

To evaluate the effectiveness and adverse effects of palonosetron in prevention of chemotherapy-induced nausea and vomiting (CINV)

Databases searched were Medline, Embase, Chinese VIP database, Evidence-Based Medicine Review, Cochran Central Register, Current Controlled Trials, National Research Register, and Clinicaltrials.gov.

Search keywords were palonosetron, chemotherapy-induced nausea and/or vomiting, CINV.

Studies were included if they were randomized, controlled trials (RCTs) that compared palonosetron with first generation 5-HT₃ receptor antagonists (RAs).

Studies were excluded if they involved pediatric patients.

An initial 235 references were identified. Eight RCTs were identified for inclusion. Studies were evaluated in terms of randomization, blinding, allocation concealment, crossover design, and intention to treat analysis.

The final sample included eight RCTs involving 3,592 patients receiving highly or moderately emetogenic chemotherapy.

In comparing the effectiveness of palonosetron with first-generation 5-HT₃ RAs for acute CINV

• Palonosetron reduced the risk of acute CINV by 24% (p = 0.0003)
• No difference was found between 0.25-mg and 0.75-mg palonosetron doses.

In comparing the effectiveness of palonosetron with first-generation 5-HT₃ RAs for delayed CINV, both the 0.25-mg and 0.75-mg palonosetron doses yielded better prevention of delayed CINV (p < 0.00001).

Studies that included dexamethasone (two trials) reported that dexamethasone plus palonosetron reduced the risk of CINV by 38%–40% (p < 0.00001).

The 0.75-mg palonosetron dose was associated with a higher risk of constipation than lower-dose palonosetron or first-generation medications (p = 0.01).

Meta-analysis demonstrated that palonosetron was more effective in risk reduction for both acute and delayed CINV than first-generation 5-HT₃ RAs. This effect was seen with both 0.25- and 0.75-mg dosages, and with or without concomitant use of dexamethasone. A 0.75-mg dose of palonosetron was associated with more constipation.

A limited number of studies were used in some subgroup analysis, and no studies looked at lower-dose palonosetron and dexamethasone compared to first-generation drugs. This research is warranted, because lower dosages are associated with less constipation.

Palonosetron is a safe and effective alternative for prevention of CINV. Nurses need to be aware of the potential for constipation with higher dosages, particularly in patients with other treatments that affect bowel function.

To review the evidence regarding spinal cord stimulation for pain management in cancer

This study is a systematic review.

Databases searched were the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Chinese Biomedical Database (up to July 2012), National Cancer Institute trial registry, World Health Organization International Clinical Trials Registry Platform, and clinicaltrials.gov, supported by the National Institutes of Health. The authors also hand-searched relevant articles.

Search terms were text words combined with medical subject headings (MeSH) terms for electrostimulation and cancer.

Studies were included in the review if they were randomized controlled trials (RCTs) or nonrandomized trials comparing spinal cord stimulation with another intervention for cancer pain.

All studies had to report on adult patients.

A total of 430 references were retrieved.

The authors assessed risk of bias from sequence assignment and allocation concealment. No specific rating scale is mentioned. The STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) checklist was used for observational studies, as no RCTs were found.

• A final number of four pre-post case reviews were included.
• The sample range across studies was 11–454 patients. The large study was a retrospective review.
• Key sample characteristics were not specified.

The study has clinical applicability for palliative care.

There were very few studies, and prospective studies were pre-post case series reports. More than 80% of patients reported at least a 50% reduction in pain severity, and more than 50% reported reduction in opioid use. Minor complications included headache, asthenia, dizziness, and muscle twitches. Major complications included infection, cerebrospinal fluid leak, pain at electrode sites, and system failure. Follow-up ranged from one week to one year. All studies were of low quality.

There is insufficient evidence to evaluate the potential role of spinal cord stimulation for cancer-related pain control.

Limitations included few publications and low-quality research.

Effectiveness of spinal cord stimulation for management of cancer-related pain cannot be determined. There is a need for high-quality research in this area.

To determine if prophylactic use of hyaluronic acid cream postpones acute radiodermatitis or reduces its severity and to evaluate the efficacy of hyaluronic acid to delay the onset of necrosis or to accelerate recovery in case of ulceration

Hyaluronic or placebo cream was applied to irradiated skin area twice daily. The first application was one-to-two hours after the radiation therapy session and the second was in the evening. The topic treatment was continued over a six-week period.

• The study sample (N = 134) was comprised of male (n = 74) and female (n = 60) patients with head and neck (n = 90), breast (n = 30), or pelvic cancer (n = 14).
• Mean age was 59.9 years in the treatment group and 55.7 years in the placebo group.

The study took place at Ospedale San Giovanni and Centre Hospitlier Universitaire, both in Switzerland.

The study used a randomized placebo-controlled double-blind trial design.

• Skin was evaluated using a scale of 0–5 (0 = normal skin, 1 = light epidermal irritation, 2 = erythema with dry desquamation, 3 = exudate less than 50%, 4 = exudate more than 50%, 5 = ulcer).
• Healing was reported using a 1–4 scale (1 = minimum and maximum lesion diameters, 2 = lesion cleaning, 3 = beginning of proliferation process and proliferation of tissue granulation, 4 = re-epithelialization).
• Physician global judgment on therapeutic efficacy was evaluated using a 0–3 verbal scale (0 = poor, 1 = fair, 2 = good, 3 = excellent).

• Acute radiodermatitis scores were significantly higher in the placebo group (p < 0.01 at 3–7 weeks and p < 0.05 at 8–10 weeks).
• Global efficacy judgment by both physician and patient showed a significant difference in favor of the intervention (p < 0.01 to p < 0.05).
• A statistically significant difference in skin reactions was reported in favor of the intervention group based on global efficacy (p < 0.01).
• A significant difference was reported for the head and neck group in favor of the intervention following observation at week 3 (p = 0.0003), week 4 (p = 0.0001), and week 5 (p = 0.0035).

The prophylactic use of hyaluronic acid cream is shown to reduce the incidence of high-grade radiodermatitis.

• Very small numbers for evaluation of healing.
• Did not allow statistical evaluation to be carried out for this aspect of the study.
• No discussion of evaluation tools or the reliability or validity of tool.

To determine the incidence of visceral pain and to evaluate the efficacy of oxycodone in the context of visceral pain

Patients with visceral pain stopped existing drug treatment and instead used controlled-release oxycodone for 15 days. Conversion was according to international guidelines. Dosage of the study drug was individualized. If by day 7 a patient did not achieve a pain-score reduction of at least 50% or if he or she experienced a severe adverse event, clinicians administered an alternative opioid. Investigators gathered pain scores at baseline and after 3, 7, and 15 days of treatment. The regimen permitted use of rescue medication, morphine sulfate.

• The sample was composed of 340 patients.
• Mean patient age was 64.1 years. Age range was 25–100 years.
• Of all patients, 46.5% were female and 53.5% were male.
• Of all patients, 94.9% had oncologic disease. The types of cancer that occurred most often in the sample were cancer of the colon (which 21% of patients had), pancreatic cancer (14%), and gastric cancer (10%). Of all patients, 57% had experienced pain, at levels that made them eligible for the study, for 0–3 months. Data reflect patients screened, not those included in the study.
• Of patients with visceral pain, 97.1% rated their pain as uncontrolled—that is, as 4–10 on the rating scale. More than two-thirds of patients rated their pain in the 7–10 range on the scale.
• At baseline, 65.5% of patients were taking strong opioids.

• Multisite
• Outpatient
• Pain centers in Italy

Prospective observational single-group trial

• Numeric rating scale, 0–10, to measure pain
• Four-point verbal rating scale, to measure patient's assessment of pain management effectiveness
• SF-12 Health Survey

All patients who entered the study completed the study. None had to switch to another opioid. Mean dose after titration was 50.1 mg/day controlled-release (CR) oxycodone. At all time points, pain scores had decreased from a baseline mean of 7.04. At day 15, the mean pain score was 2.37 (p < 0.00001). Authors noted some improvement in all domains of the SF-12, but these changes were not statistically significant. Few patients experienced more than mild adverse evens. The most frequent adverse events were nausea, constipation, and sleepiness.

In this study, use of CR oxycodone was associated with significant reduction in mean pain scores over a 15-day period, with minimal adverse events.

• The study had a risk of bias due to no appropriate control group.
• Individual physicians determined their own definitions of visceral pain.
• Authors did not provide data regarding rescue medication use or breakthrough episodes.
• The study was of short duration.
• Authors did not specify whether patients reported current, average, least, or worst pain levels.

This study showed CR oxycodone to be effective in producing significant pain reduction within three days and over 15 days. This finding warrants a study of long-term effect. CR oxycodone is one medication in the armamentarium of opioid formulations for pain management. The side effects of CR oxycodone are those to be expected with opioid use.

To determine the efficacy of oral sucralfate in reducing radiation (RT)-induced acute complications in the treatment of patients with head and neck cancer. This study looked at mucositis and dermatitis.

Patients were given oral sucralfate at a dose of 1 gm six times a day from the onset of RT and continued during the entire treatment.

• The sample was comprised of 83 patients.
• Age and gender were not provided.
• Patients had head and neck cancer.
• Patients were treated to 55 Gy in five weeks.

Two sites in Belgium

The study was a randomized, placebo-controlled, double-blind trial.

Dermatitis scoring scale:

• 0 = none
• 1 = slight erythema
• 2 = deep erythema
• 3 = dry desquamation
• 4 = spotted epidermolysis
• 5 = confluent epidermolysis
• 6 = necrosis

Other variables analyzed were weight, tumor site, and stage; subjective tolerance; dysphagia; nausea and vomiting; dermatitis; mucositis; total dose; and daily fractionation schedule.

Of the initial 102 patients randomized, only 83 were evaluable due to issues of patient nonadherence to the protocol. Compliance was worse in the sucralfate group. There were no differences in mean scores for dermatitis or other symptoms measured between the two study groups.

No clinical evidence indicated that sucralfate reduces acute RT-induced side effects.

• Patients were given local anesthetics and systemic painkillers when needed, so it would be difficult to determine what actually worked.
• Patients were not evaluated at the end of treatment.
• Many participants did not follow protocol.
• Use of a nonstandard tool makes comparison to other studies difficult.
• No data were provided on gender and age.
• No data were shown regarding total RT dose and fractionation schedule.

• N = 79
• KEY DISEASE CHARACTERISTICS: Eighteen patients had breast cancer and 61 had prostate cancer.
• OTHER KEY SAMPLE CHARACTERISTICS:
  • In patients with bone metastasis, patients were already using long-term analgesics and had measurable pain symptoms, a positive bone scan with at least three lesions, and sufficient bone marrow and renal function.
  • Patients were excluded for bone fractures, spinal cord compression, and soft tissue tumors causing nerve compression.
  • Participants entered study at different levels of the World Health Organization (WHO) three-step ladder.
  • Bisphosphonates were stopped four weeks before treatment. Eighty-nine percent of patients had been treated with bisphosphonates for at least six months.
  • Nineteen percent of patients had chemotherapy, 27% had external beam therapy, and all stopped at least five months before treatment.
  • Patients with prostate cancer received hormone treatment for at least six months before treatment and also resumed treatment after postobservation or an orchiectomy.

• LOCATION: Germany

Prospective, nonrandomized study

• Weekly interviews including a Visual Analog Scale (VAS, 0–10) to assess pain relief, use of analgesics
• Karnofsky Performance Status (KPS), blood work, and bone scan before study and after 12 weeks
• Primary endpoint of pain relief was defined as at least two points on the VAS in two consecutive weeks without increase in analgesic use.

• Ten percent of patients had grade 1 thrombocytopenia, and 2% had grade 2.
• There were two patients with grade 1 leucopenia and one with grade 2.
• Most patients had grade 1 anemia.
• No statistical difference existed in the decrease of platelets or leukocytes between the four radiopharmaceuticals.
• For most patients, toxicity resolved 12 weeks after treatment.
• No evidence of local or systemic intolerance existed. However, 19% of patients had a flare reaction with a reversible increase of pain within 14 days after therapy.
• Pain relief (two points in two consecutive weeks without increase in analgesic use) occurred in 73% of patients and 15% were pain-free. The duration of response was greater than 12 weeks for 14 of the 24 patients who had a response. The rest of the patients had a duration of less than nine weeks.
• No significant difference was seen in response rate, pain relief, or duration between the four radiopharmaceuticals.
• KPS increased from baseline. There was no significant difference between the radiopharmaceuticals. However, the increase was significant with 188Re-HEDP (p < 0.001).
• Prostate patients: 23% showed a reduction in PSA of more than 50%.
• Bone scans were not different, although three single cases had a decrease in bone metastasis within 12 months after treatment.

• Non-randomized, unclear how authors chose which agent to receive
• Small number of breast cancer patients; did not stratify results based on disease type  
• Did not report breast cancer tumor marker response
• Did not report hormonal agents taken by breast cancer patients or oophorectomy
• In the group that received 89Sr, there were more patients with an analgesic-level 3 and a lower KPS than other groups.
• Unclear whether there a change in survival or a difference in progression-free interval
• More than one administration not noted
• Not all of these radionuclides are available for use.

These treatments produced mild and reversible side effects, and it is therefore a good option. It is usually used in palliation, but due to low side effects, there is possibility that it might be considered earlier in disease process. Future research could review concomitant treatment with chemotherapy.

To assess the impact of communication skills training programs on changes in patients’ and relatives’ anxiety following a three-person consultation

Prior to a three-person consultation (physician/patient/caregiver), physicians who had earlier completed a basic training program were randomly assigned to complete a consolidation workshop or to a wait-list for the workshop. To gain study data, patients and relatives completed an anxiety questionnaire and a physiologic distress questionnaire (depression and anxiety) the week before and repeated the anxiety questionnaire one week after the three-person consultation. Physicians chose patients with cancer and their accompanying relatives for an audiotaped consultation. Transcription of the consultations occurred to allow a measurement of quality of consultations. Trained psychologists assessed physician skills in assessment, information, and supportive skills according to a French national rating system used in three previous studies.

• The sample was comprised of 56 physicians and 56 patient/relative pairs (27 with physician basic training and consolidated workshops; 29 with physician basic training but no workshops).
• Mean physician age was 42.6 years, mean patient age was 61.2 years, and mean relative age was 58.3 years.
• No statistically significant difference was found between patient and relative groups receiving consultation from a physician with basic training or basic training with consolidation workshops.
• Females represented 24 physicians (43%), 32 patients (57%), and 30 relatives (54%); males represented 32 physicians (57%), 24 patients (43%), and 26 relatives (46%).
• Patients needed to have a cancer diagnosis to be included in the study. No identification of stage or type of cancer was given.
• Physicians had to be specialty (cancer) doctors, work either full- or part-time, and have completed the basic training program.
• Patients and relatives needed to speak French, be older than age 18, have no cognitive dysfunction, and provide informed consent.

• Inpatient setting (inferred)
• Brussels, Belgium

A pre/post-test design was used.

• Hospital Anxiety and Depression Scale (HADS): Used to assess the patient’s anxiety and depression the week before the consultation. HADS contains 14 self-report items, each scaled on a one to four value. The instrument was translated into French and validated in a sample of French patients, but no reliability or validity statistics appeared in the article.
• State Trait Anxiety Inventory–State (STAI-S): Used to measure anxiety of the relative and the patient before and after the three-person consultation. STAI-S contains 20 items and four response options to yield scores between 20 and 80. The instrument was translated into French and validated, but no reliability and validity indices appeared in the article.
• Patients and relatives completed a sociodemographic data tool preconsultation.
• Doctors completed a sociodemographic and socioprofessional questionnaire preconsultation.

No statistically significant differences were found between patients’ and relatives’ sociodemographic characteristics and disease and over time with basic training consultation and the basic training added to the consolidation workshops. A multivariate analysis of variance assessment showed significant change between time in changes in patients’ anxiety following the three-person consultation (p = 0.027). Although anxiety decreased for both patients and relatives following the consultation, none of these changes was significant. There were no significant correlations between changes in patients’ and relatives’ anxiety and physician assessment, information, and supportive skills. In further analyses (mixed-effects modeling), physician communication skills had no influence on changes in patients and relatives following a three-person consultation. Only contextual variables (e.g., type of bad news, type of information transmitted by physicians and self-reported before the consultation) had an effect on changes in anxiety and distress.

The physician training program described did not diminish patient or relative anxiety about cancer following the consultation.

• The sample was small, with less than 100 participants.
• The study had a heterogeneous nature of the types of consultations.
• Physicians chose the patients to be studied.

The concept of nurse/patient/caregiver conversations as part of routine nursing care seems appropriate in the U.S. healthcare system that seeks to increase primary care. Although relatives’ and patients’ needs may vary, nurses have strong assessment, information-gathering, and supportive skills to promote health and coping of patients, caregiver relatives, and families either in group formats or individual forums.