STUDY PURPOSE: To examine the literature regarding precautionary and lifestyle behaviors to prevent adverse effects with arm lymphedema secondary to breast cancer surgery

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

• FINAL NUMBER STUDIES INCLUDED = 26 
• TOTAL PATIENTS INCLUDED IN REVIEW = 2,992
• SAMPLE RANGE ACROSS STUDIES: 12–632 patients
• KEY SAMPLE CHARACTERISTICS: All patient sample studies were of women with breast cancer; none had lymphedema or lymph node removals.

PHASE OF CARE: Late effects and survivorship

Nine studies looked at air travel and risk of lymphedema. No consensus among studies regarding the utility of compression garment use during air travel was found, and no evidence exists to show that its use is of benefit or a risk to patients. Five studies regarding temperature extremes were included. Two studies conducted in China reported benefit from local heat therapies, and one study showed that sauna use may be associated with increased risk. Findings were insufficient to draw firm conclusions. Four studies looked at risk and the use of the affected arm for blood pressure monitoring. Two studies showed some evidence that blood pressure measurement was associated with increased lymphedema. Ten studies looked at venipuncture and lymphedema risk or outcomes. Conflicting reports were seen, and most evidence was of low quality. Eight studies involving the relationship between infection and incident worsening of lymphedema were reviewed. Of these, six suggested a significant relationship between worse lymphedema outcomes and infection, injury, or cellulitis.

Insufficient evidence exists to draw firm conclusions about the necessity of precautionary guidelines for behavior to reduce the potential for incident worsening of lymphedema and related adverse effects, although guidelines are based on sound physiological principles. Studies have shown that skin infections and inflammation are significant risk factors.

• Limited number of studies included
• Mostly low quality/high risk of bias studies
• Included recommendations from hand surgeons and studies unrelated to breast cancer–related lymphedema.
• The strongest evidence was nonrandomized, prospective, observational, or cohort designs, but these were based on patient recollection and other survey data.

This study adds to a growing body of evidence encouraging the questioning of traditional patient teaching for risk reduction behaviors aimed at reducing the risk of incident worsening of arm lymphedema after surgery for breast cancer. Insufficient evidence shows that risk reduction behaviors are effective in reducing risk; however, insufficient evidence supports that elimination of these behaviors is safe for patients. Traditional patient teaching to avoid the use of tourniquets or limb constriction, wounds or punctures, exposure to extreme temperatures, the use of compression garments with air travel, and maintain cleanliness are founded in sound physiological rationale. Such risk reduction behaviors are not overly restrictive and are sensible aspects of patient teaching for self-care.

STUDY PURPOSE: To develop an evidence-based guideline on central venous catheter (CVC) care for patients with cancer

TYPE OF STUDY: Systematic review

DATABASES USED: MEDLINE (PubMed) and the Cochrane Collaboration Library

KEYWORDS: Authors did not state which keywords were utilized.

INCLUSION CRITERIA: As long as the randomized clinical trials included a majority of patients with cancer, they were included for this review. Most recent trials were included as opposed to older trials. Authors searched from 1980–July 2012 in databases that were published in English.

EXCLUSION CRITERIA: No specific exclusion criteria were mentioned by authors. Randomized controlled trials (RCTs) were excluded if patients with CVCs were compared to patients with permanent catheters.

TOTAL REFERENCES RETRIEVED = 133, plus an unspecified number of pre-existing guidelines that were discovered during the search

EVALUATION METHOD AND COMMENTS ON LITERATURE USED: 108 RCTs of patients with cancer and 25 meta-analyses or systematic reviews were found in the search. Several pre-existing guidelines also were discovered during the literature search.

• FINAL NUMBER STUDIES INCLUDED = 133, plus an unspecified number of pre-existing guidelines that were discovered during the search, 108 RCTs, and 25 meta-analyses
• KEY SAMPLE CHARACTERISTICS: Patients with cancer; patients with cancer with CVC access

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

Not enough evidence was found to suggest only one type of CVC for patients or to suggest only one insertion site or approach for tunneled lines. A CVC bundle should be used for line insertion and maintenance. 

Evidence is insufficient to recommend one type of CVC for patients with cancer. The choice of catheter needs to be patient-specific, avoiding femoral lines because of increased risk of infection. Hand hygiene, barrier precautions during catheter insertion and utilization, and chlorhexidine skin antisepsis during insertion are recommended to prevent catheter-related infections. Cultures should be drawn prior to antibiotic administration when an infection is suspected.

• No major limitations identified in meta-analysis

Hand hygiene and maximum barrier protection should be used during any type of catheter manipulation to avoid infection. Routine flushing with normal saline is recommended for patency. Blood cultures should be collected from CVCs prior to antibiotic administration. Tissue plasminogen activator should be used for catheters with patency issues. Routine prophylaxis with anticoagulants is not recommended for catheter-associated thrombus.

To study the effect of acupuncture on hot flashes in men with prostate cancer treated with androgen deprivation

Men with hot flashes occurring at least 3 or more times per day for at least three days before enrollment were enrolled. They completed hot flash diaries with resulting hot flash scores at baseline, daily for at least 6 weeks, and then monthly for 8 months (targeted time was 36 months). Acupuncture was administered by same acupuncturist twice a week for 4 weeks to the same 10 points with electro stimulation applied to 8 of the 10 points per protocol.

• N = 14  
• AGE:  mean 68 years
• MALES (%)  100%     FEMALES (%)  0
• KEY DISEASE CHARACTERISTICS:   Locally advanced prostate cancer
• OTHER KEY SAMPLE CHARACTERISTICS:   Advanced local disease managed with androgen deprivation therapy

The study enrolled men with locally advanced prostate cancer, who had been treated with androgen deprivation therapy as an adjuvant to radiation therapy, radical prostatectomty, or brachytherapy. All men must have had hot flashes occurring at least 3 or more times per day for at least three days before enrollment. Patients could not be receiving medications for hot flashes nor have a history of acupuncture treatment.

• SITE: Single site   
• SETTING TYPE: Outpatient setting   
• LOCATION: United States

PHASE OF CARE: Active Treatment

APPLICATIONS: Late effects & survivorship; Elderly care

Prospective single arm trial

• Hot Flash Diaries    
• Hot Flash Score - calculated as frequency x severity.

Mean initial Hot Flash Score (HFS) was 28.3, which decreased to 10.3 (p= 0.0001) at 2 weeks post-treatment, 7.5 (p = 0.0001) at 6 weeks post-treatment, and 7.0 (p= 0.0001) at 8 months post-treatment. Clinical improvement for each patient was defined as the percent decrease in the mean HFS at each time point. The mean improvement at weeks 2 and 6 was 68.4% and 89.2%.

In this limited sample size, acupuncture appeared to reduce hot flash symptoms experienced by men treated with androgen deprivation for their locally advanced prostate cancer.

• Small sample <30
• The study clearly defined the participant group; however it failed to define further the acupuncture points used within the study. It also did not define which of the 8 out of  10 points had electro stimulation applied in order to determine if these were exact points used in each participant.  
   

Further research is needed in larger sample sizes to determine effectiveness, and  the reproducibility of the study when using multiple providers. The study explored the long term benefits of using acupuncture and suggested (demonstrated) an 80.3% decrease in HFS at the 8-month follow-up.

To compare if individual psychosocial support for patients with breast cancer provided by oncology nurses specially trained in cognitive behavioral techniques was as effective as that given by psychologists or standard care.

Patients received individualized psychosocial support interventions using cognitive behavioral techniques, such as relaxation, distraction, activity scheduling, and ways to improve communication. The frequency of sessions varied based on patients' perceptions of need. Patients were randomized in blocks of nine into one of three alternatives:  60 received individual psychosocial support by a specially trained oncology nurse, 60 received it from a psychologist, and 59 received standard care. Outcomes measured were quality of life (QOL), fatigue, nausea, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties.

• The study was comprised of 179 consecutive patients with breast cancer about to start adjuvant treatment.
• Mean age was 55 years (range 23–87).

The study was conducted at the Department of Oncology, Uppsala University, Sweden.

Patients were undergoing the active treatment phase of care.

This was a prospective, randomized, quasiexperimental study using repeated measures at baseline and at one, three, and six months.

• European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLC-C30)
• EORTC QLQ–Breast Cancer (EORTC QLQ-BR23)
• Hospital Anxiety and Depression Scale (HADS)
• Impact of Event Scale (IES)
• State Trait Anxiety Inventory–State (STAI-S)

The results revealed statistically significant group by time interactions for global QOL and health status, nausea and vomiting, and systemic therapy side effects. Intervention groups showed statistical differences on the insomnia, dyspnea, and financial difficulties EORTC subscales, in favor of one or both of the interventions.

• The number of sessions varied and was determined by the need and desire of individual patients.
• There was a need for special training to deliver the intervention.

Patients were randomized to two intervention groups:  Individual Psychosocial Support, provided by a trained oncology nurse (INS), and Individual Psychosocial Support, provided by a psychologist (IPS). Both interventions used the same techniques of relaxation, distraction, activity scheduling, and ways to improve communication. The number of sessions and time intervals between sessions varied according to the needs and desires of individual patients. Each session lasted 45 to 60 minutes, in which patients' problems were identified and developments were made to help manage these problems. Patients were provided with written and oral instructions on how to practice these strategies. Quality of life questionnaires were administered at baseline and at one, three, and six months.

• The study included 179 women with breast cancer about to start adjuvant treatment.
• Mean age was 55 years (range 23–87).
• Of the participants, 136 were married/cohabitant, and the majority (n = 130) were in stage T1.
• Most participants had received no preoperative chemotherapy.
• For postoperative treatment, most had received local radiation therapy only (n = 100), hormonal therapy (n = 88), or adjuvant polychemotherapy (n = 69).
• Patients were excluded if they had ongoing psychiatric illness, previous cancer diagnosis, or inability to speak and understand Swedish.

Department of Oncology, Uppsala University Hospital

Patients were undergoing the active treatment phase of care.

This was a prospective, randomized study.

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

Intervention groups had lower fatigue scores on the EORTC-QLQ-C30 at baseline, one month, and six months; these differences were minimal and not statistically significant.

• Twenty percent of the patients did not complete all three assessments.
• A significantly higher proportion of patients randomized to the INS group were diagnosed in stage N0 compared to the other groups. It is unclear whether this had a significant impact on the results.

To compare individual psychosocial support (cognitive behavioral therapy [CBT]) for patients with breast cancer provided by oncology nurses specially trained in psychologic techniques (INS), or the same support given by psychologists (IPS), versus standard care provided in Sweden.

Measures were done at one, three, and six months after inclusion in study.

The sample was comprised of 179 patients with breast cancer who were about to start adjuvant therapy.

A prospective, randomized study design was used.

• Hospital Anxiety and Depression Scale
• State-Trait Anxiety Inventory
• Impact of Event Scale (intrusion and avoidance subscales)

Results indicated that CBT offered by specially trained nurses is just as effective as CBT offered by psychologists. Statistically significant improvements in anxiety over time (p < 0.01) were shown between the INS and IPS groups versus the standard care group.

• No screening for psychological problems or treatment before inclusion into the study may flaw the results.
• Insufficient power of study may limit results.

To evaluate the effectiveness of oligon central venous catheters (CVC) and chlorhexidine biopatch to reduce CVC-related infections. Oligon catheters are impregnated with antimicrobial silver, platinum, and carbon.

Patients were randomized to receive either a standard polyurethane catheter, a standard catheter plus biopatch, or an oligon catheter. All catheters were triple lumen. Standard maximum barrier insertion techniques were used, and dressing change frequency was every three days with a transparent dressing. Those getting the biopatch had the biopatch changed with regular dressing changes. The primary study endpoint was catheter colonization. A decision to remove the catheter was made by individual physicians.

• N = 376; 465 in intention to treat analysis
• MEDIAN AGE = 59 years
• AGE RANGE = 32–73 years
• MALES: 69.7%, FEMALES: 30.3%
• CURRENT TREATMENT: Immunotherapy
• KEY DISEASE CHARACTERISTICS: Overall, 7% of the sample had cancer.
• OTHER KEY SAMPLE CHARACTERISTICS: 96% of patients were in the ICU for mechanical ventilation.

• SITE: Multi-site   
• SETTING TYPE: Inpatient    
• LOCATION: Greece

• Three-group randomized, controlled trial (RCT)

• Catheter colonization defined as 10³ or greater colony forming units ml of catheter tip
• Catheter-related infection (CRI) defined as positive colonization and clinical evidence of sepsis with the same organism and no other clinical site for infection
• Central line–associated bloodstream infection (CLABSI) defined as CRI plus one positive peripheral blood culture with the same organism as isolated from the catheter tip

There were no differences in catheter colonization rates, CRI, or CLABSI between groups. There were no differences between groups in number of catheter days, CLABSI incidence per 1,000 catheter days, or other factors potentially associated with development of CLABSI. Analysis showed that use of jugular or femoral insertion site and cancer diagnosis were significantly associated with development of catheter colonization (p < 0.05).

Findings did not support efficacy of BIOPATCH dressings or antimicrobial catheters for prevention of catheter-related colonization or infections.

• Risk of bias (no blinding)
• Risk of bias (sample characteristics)
• Key sample group differences that could influence results
• The study was underpowered. Patients receiving BIOPATCH dressing and impregnated catheters had significantly lower proportion of patients. No data regarding actual adherence to insertion and dressing change protocols existed.

Findings did not show efficacy of chlorhexidine-BIOPATCH CVC dressings or antimicrobial impregnated short-term catheters to prevent catheter colonization and related CVC-infection related outcomes.

To determine the effects of ginger on chemotherapy-induced nausea and vomiting (CINV) in women receiving adjuvant anthracycline for breast cancer

Patients were randomly assigned to control and treatment groups. Women in the intervention group consumed 500 mg of powdered ginger mixed with yogurt twice daily after an initial dose 30 minutes prior to chemotherapy. Both groups received triplet antiemetic therapy. Patients were followed for five days and were asked to record episodes of vomiting and retching and to evaluate their nausea using a numeric 10-point scale four times per day in a diary. The numeric scale also was used on the first day of chemotherapy to collect baseline data. Patient diaries were collected at the end of the five-day study period.

• N = 60  
• MEAN AGE = 48.5 years (range = 49–58 years)
• FEMALES: 100%
• KEY DISEASE CHARACTERISTICS: All patients were receiving adjuvant anthracycline, were currently receiving triplet antiemetics, and experienced grade 3 or higher CINV during the previous cycle of chemotherapy.

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

• PHASE OF CARE: Active antitumor treatment

Randomized, controlled trial

• Numeric Rating Scale (NRS) for nausea
• Patient diary 

Nausea severity was significantly lower in the experimental group after the intervention on study days 2–5 (p = 0.0001). The number of vomiting episodes also was lower in the experimental group on some study days (p < 0.05).

The use of ginger as an adjuvant to triplet antiemetics among women receiving anthracycline-based chemotherapy resulted in lower acute and delayed nausea severity.

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

Advances in antiemetic drugs have substantially improved the prevention and control vomiting in the acute and delayed phases of CINV. However, the prevention of nausea has been difficult to achieve. Findings from this study suggest that the use of ginger in combination with triplet antiemetics can be beneficial in reducing the severity of nausea.

To evaluate the effectiveness of prophylactic tetracycline on afatinib-induced skin toxicities

Afatinib was given after disease progression with chemotherapy. Patients receiving afatinib were randomly assigned to receive general dermatological recommendations (control group) or 250 mg tetracycline every 12 hours in addition to general recommendations. All were receiving 40 mg afatanib every day until disease progression or toxicity. Dosage of afatinib was reduced to 30 mg daily for grade 3 or prolonged grade 2 toxicity. General recommendations provided to all patients were brief baths with lukewarm water, use of sunscreen, emollient creams, hypoallergenic soap, and fingernail care. Study assessments were conducted at baseline, week 2, and week 4 by a blinded assessor.

• N = 90
• MEAN AGE = 57 
• MALES: 26.7%, FEMALES: 73.3%
• KEY DISEASE CHARACTERISTICS: All had lung cancer.

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

PHASE OF CARE: Active antitumor treatment

• Single-blind, randomized, controlled trial

• National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE)

Most common toxicities were rash (65.6%), pruritus,(42.2%), mucositis (41.1%), paronychia (33.3%), skin fissures (24.4%), folliculitis (24.4%), and trichomegaly (22.2%). No grade 5 toxicities existed. Rash incidence was 75.5% in the control group versus 55.5% in the tetracycline group (relative risk [RR] = 0.4, p = 0.046), and rash severity of grade 2 or higher was 15.6% in the tetracycline group compared to 35.6% among controls (RR = 0.35, p = 0.03). Incidence of paronychia was lower in the tetracycline group, but group differences were not statistically significant. No other differences existed between groups in skin effects, and no differences existed between groups in the proportion of patients who required afatinib dose reductions. Most patients developed maximum rash intensity between weeks 1 and 4 of treatment. No relationship existed between rash incidence or severity and general disease outcomes.

Prophylactic tetracycline was effective in reducing the incidence and severity of rashes associated with afatinib use.

• Small sample (< 100)

Very limited evidence exists for effective interventions to prevent or treat skin toxicities associated with epidermal growth factor receptor inhibitor (EGFRI) administration. Although the use of antibiotics has been suggested, currently little research demonstrates their efficacy. This study begins to fill that evidence gap, showing that tetracycline can be effective in reducing the incidence and severity of skin toxicity. This is a relatively low-cost and generally safe intervention to reduce adverse skin effects in patients receiving EGFRIs.

To evaluate the efficacy of low level laser therapy (LLLT) for the prevention and treatment of radiotherapy-induced oral mucositis in patients with oral cancer

Patients with primary oral cancer were randomized to the laser group or a control group. All patients had oral prophylaxis before starting radiation therapy, and all had the same oral care during treatment. All patients were evaluated daily for pain severity, functional impairment, and oral mucositis. The clinical exams were performed by a single examiner. All the laser treatments were administered by one operator. The treatment consisted of use of a laser scanner for the first eight days followed by treatment to six areas on the right and left sides of the oral cavity for 25 days.

• The study reported on 24 patients, ages 55–59 years old.
• The sample was 50% female and 50% male.
• Patients were newly diagnosed with primary oral cancer limited to the oral cavity
• Patients received 66 Gy in 33 fractions, 5 days per week for 6.5 weeks. No patients experiencing treatment delays were included in the study.

This was a single site, inpatient and outpatient study conducted at Kasturba Medical College of Manipal University in Karnataka, India.

This was a randomized controlled trial.

• A numeric rating scale was used to measure severity of oral pain.
• To evaluate patient need for supplemental analgesics, the World Health Organization (WHO) analgesic ladder, date of initiation, and  duration of analgesic use were recorded.
• Functional impairment was recorded.
• A scale was used to assess severity of dysphagia.
• Mucositis severity was assessed daily by one examiner using the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer (RTOG/EORTC) scoring system.

Pain increased gradually and was the greatest at the end of seven weeks. The laser group had a statistically significant lower level of pain than did the control group (p < 0.03). In week 3, the laser group had grade I functional impairment, while the control group progressed to grade II and III functional impairment, with one individual having grade IV impairment. Overall, the laser group had lower mucositis severity than the control group (p = 0.033).

Prophylactic laser therapy during radiation therapy can reduce the severity of mucositis, as well as the severity of functional impairment and pain.

• The control group had a small sample size of fewer than 30 patients.
• The article did not state what the control group procedure involved (e.g., sham treatment).

This form of laser therapy is effective in the prevention of severe mucositis, but it is very high tech and requires special equipment and highly trained personnel.