To examine associations between exercise and lymphedema in breast cancer survivors

The study and all protocols were approved by the University of Minnesota.

• The study sample (N = 85) was comprised of female breast cancer survivors who were recruited from October 2001–June 2002.
• Forty-two women were randomly selected for the intervention group, 23 of which had undergone axillary dissection.
• Forty-three women were randomly selected to the control group, 23 of which had also had axillary dissection.
• All participants gave signed informed consent.

The study took place in the Minneapolis-Saint Paul greater metropolitan area in Minnesota.

The study used a randomized controlled trial design.

• Arm circumference measurements were taken on both arms at the level of the metacarpophalangeal joints, just distal to the ulnar styloid process, 10 cm distal to the midpoint of the lateral epicondyle, and 10 cm proximal to the midpoint of the lateral epicondyle. During measurements, participants lay prone with their arms at their sides and elbows straight. A cloth measuring tape was placed around the arm so that there was no slack and no indentation of the tissue. Participants who wore compression sleeves removed them one hour before measurements were taken. The mean of two measurements was used. The outcome measure was the calculated difference in each circumference measure between the ipsilateral and contralateral arms.
• A validated survey measured self-report of lymphedema diagnosis, symptoms, and treatment over the past three months. The survey had a specificity of 0.90 and sensitivity of 0.86–0.92 for diagnosing lymphedema (difference in arm circumferences of 2 cm), compared with clinical assessment by a physical therapist with training in lymphedema. Symptoms of lymphedema included whether or not a patient had noticed that her hand or lower or upper arm on the side of the cancer was larger than the side of the opposite arm and if the difference was mild, moderate, or severe. Additionally, other symptoms included altered fine motor function, puffiness, swelling, or pain of the hand or arm.
• A patient was a self-reported “incident” case of lymphedema if she self-reported a clinician diagnosis of lymphedema at six months but not at baseline. A patient was a self-reported “prevalent” case if she self-reported a clinician diagnosis of lymphedema. A participant was considered to have lymphedema symptoms if she reported any lymphedema symptoms in the survey.

After dropouts and loss to follow-up, 78 women completed baseline and six-month measurements of arm circumference. A twice-a-week weight training for a period of six months did not increase arm-circumference measurements or exacerbate symptoms of lymphedema in survivors of breast cancer compared with nonintervention controls.

• Six months may not have adequately captured acute or transient changes in circumferences or symptoms that may result from exercise.
• They did not measure change in volume, which is correlated with circumference measures but may be more sensitive to change.
• Few of the women randomly selected at baseline had lymphedema.

To examine associations between exercise and lymphedema in breast cancer survivors

The study and all protocols were approved by the University of Minnesota.

• The sample was comprised of (N = 85) breast cancer survivors recruited from October 2001 to June 2002.
• The randomized intervention group (n = 42) included 23 patients who underwent axillary dissection.
• The randomized control group (n = 43) included 23 patients who underwent axillary dissection.
• All participants gave signed informed consent.

The study was conducted in the great Minneapolis-St. Paul, MN, metropolitan area.

A randomized controlled trial

Lymphedema was measured three ways: arm circumference measurements, self-reported symptoms, and symptoms of lymphedema.

Arm circumference

• Arm circumference measurements were taken on both arms at the level of the metacarpophalangeal joints, just distal to the ulnar styloid process, 10 cm distal to the midpoint of the lateral epicondyle, and 10 cm proximal to the midpoint of the lateral epicondyle.
• During arm circumference measurements, participants lay prone with their arms at their sides and elbows straight. A cloth measuring tape was placed around the arm so that there was no slack and no indentation of the tissue. Participants who wore compression sleeves removed them one hour before measurements were taken. The mean of two measurements was used. The outcome measure was the calculated difference in each circumference measure between the ipsilateral and contralateral arms.

Self-reported symptoms

• A validated survey measured self-report of lymphedema diagnosis, symptoms, and treatment over the past three months.The survey had a specificity of 0.90 and sensitivity of 0.86–0.92 for diagnosing lymphedema (difference in arm circumferences 2 cm), compared with clinical assessment by a physical therapist with training in lymphedema.
• Symptoms of lymphedema included whether or not a participant had noticed that her hand, lower or upper arm on the side of the cancer was larger than the side of the opposite arm and if the difference was mild, moderate, or severe.
• Other symptoms included altered fine motor function, puffiness, swelling, and/or pain of the hand or arm.

Symptoms of lymphedema

• A participant was a self-reported “incident” case of lymphedema if she self-reported a clinician diagnosis of lymphedema at six months but not at baseline.
• A patient was a self-reported “prevalent” case if she self-reported a clinician diagnosis of lymphedema.
• A participant was considered to have lymphedema symptoms if she reported any lymphedema symptoms in the survey.

• After dropouts and loss to follow-up, 78 women completed baseline and six-month measurements of arm circumference.
• A twice-a-week weight training for a period of six months did not increase arm circumference measurements or exacerbate symptoms of lymphedema in survivors of breast cancer compared with nonintervention controls.

• Six months may not have adequately captured acute or transient changes in circumferences or symptoms that may result from exercise.
• Researchers did not measure change in volume, which is correlated with circumference measures but may be more sensitive to change.
• Few of the women randomly selected at baseline had lymphedema.

To evaluate the effect of low-level laser therapy (LLLT) on limb volume, shoulder mobility, and grip strength

Patients were randomized to treatment and placebo control groups. The treatment group received LLLT at an average dose of 1.5 J/cm² for 20 minutes three times per week for 36 sessions. In the placebo group, the patients were set up with the same parameters of therapy but the machine was not turned on. All patients were advised to perform the same arm and shoulder exercises daily. Patients were evaluated every 4 weeks for 12 weeks.

• The study sample (N = 50) was comprised of female patients with breast cancer.
• Mean age of the sample was 54.06 years.
• All patients had axillary node dissection and unilateral arm lymphedema.
• Patients had arm circumference increases in the affected arm of 2–8 cm.
• Patients with severe lymphedema were excluded.
• Seventy-two percent of patients had modified radical mastectomy.
• Lymphedema was in the dominant arm in 78% of patients.
• Mean duration of lymphedema was 14 months and average time since surgery was 40 months.

The study took place in an outpatient setting in Egypt.

The study has clinical applicability for late effects and survivorship.

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

• Arm circumference was measured.
• Grip strength was measured with a dynamometer.
• Goniometer measured shoulder range of motion.

The laser group had greater reduction in limb volume than controls. The difference was significant at 8 and 12 weeks (p < 0.01).  At 16 weeks, total limb circumference was 31 in the laser group and 23 in the control group. Shoulder mobility was better in the laser group and significantly better than controls at 12 weeks (p < 0.01).  Grip strength improved in both groups. At 8 and 12 weeks, grip strength improvement was significantly higher in the laser treatment group (p < 0.01).

 LLLT reduces lymphedema arm volume and increased shoulder mobility and grip strength in women after mastectomy.

• The study sample was small, with less than 100 participants.
• Subject withdrawals were greater than or equal to 10%.
• The study was of short duration, so long-term efficacy is not clear.

Low-level laser therapy can reduce lymphedema volume and improve extremity strength and mobility. The study showed that 14% of patients did not adhere to receiving all treatments, which has also been shown in other studies of LLLT. The need for patients to make multiple visits for treatments may limit the practicality of the approach. Effects over the longer term are unclear.

The intervention was a Swedish/Esalen massage of shoulders, neck, and scalp lasting 20 minutes up to three times per week. Prior to hospitalization, patients were randomly assigned to massage or standard medical care conditions.

• Thirty-five adult patients with varying diagnoses admitted for autologous bone marrow transplantation were included.
• Mean age was 41 years, and the sample was predominantly female.
• Race and ethnicity were not reported.

All participants were inpatients in the bone marrow transplantation unit of a cancer center.

Patients were undergoing the active treatment phase of care. 

The study was a randomized trial comparing massage (n = 16) with a quiet time control condition (n = 18).

Fatigue was measured by a zero to 10 Numerical Rating Scale.

• Borderline significant decreases were observed in fatigue (p = 0.06) over time, although significant decreases were seen during week 1 (pretreatment) and prior to discharge.
• The most robust effects were found during the first week of treatment.

• The study had a small sample size and a lack of control for covariates.
• The analysis of time by group interaction was confusing.
• Effects may not be as great during the posttreatment phase when patients are most ill.
• Massage was performed by a trained healing arts specialist.

Patients scheduled to undergo bone marrow transplant were randomly assigned to receive either massage therapy or standard treatment. Patients in the massage therapy group received three 20-minute sessions of shoulder, neck, head, and facial massage per week. The average length of stay was three weeks, so as many as nine sessions were reported during patients’ hospital stays. Massages were performed by a trained, healing arts specialist with more than 10 years of experience.

• The sample consisted of 34 patients.
• The mean age of patients was 41 years ± 9.3.
• Race and ethnicity were not reported.
• All patients were bone marrow transplant recipients.
• The majority of the patients had breast cancer (65%); the remaining diagnoses were acute myelogenous leukemia, non-Hodgkin’s lymphoma, Hodgkin’s lymphoma, or other (ovarian cancer or acute promyelocytic leukemia).

Participants were inpatients and were scheduled for bone marrow transplant at Dartmouth-Hitchcock Medical Center in New Hampshire.

The study design was a randomized, controlled clinical trial.

• Numeric scales from 0-10 were used to evaluate nausea, with 0 representing an absence of the symptom and 10 representing an extreme level of the symptom.
• Total dosages of opioids, anxiolytics, and antiemetics were recorded because of confounding effects of the drugs on anxiety, nausea, and emotional distress.
• Data were collected prior to and following the patients’ first, fifth, and final massages (on day 7 and at mid-treatment and predischarge).

Patients in the massage group experienced significantly larger reductions in nausea than the standard group at day 7. The strongest effects were seen immediately after massage when patients experienced a reduction in diastolic blood pressure, nausea, distress, and anxiety. How long the positive effects were maintained is difficult to evaluate.

• The sample is small and from one institution.
• The timing of massage was variable.

A 30-hour infusion of adenosine 5’-triphosphate (ATP) was given every two to four weeks for 10 to 20 μg/kg/minute escalated to 75 μg/kg/minute. Regulation of biologic processes may be altered by ATP infusion to inhibit weight loss and deterioration of quality of life.

• The sample included 58 patients (ATP, n = 28; control, n = 30).
• Age and other parameters were similar.

• Outpatient
• The Netherlands

• Patients were randomized to ATP versus supportive care.
• Patients were stratified by tumor stage (IIIB or IV), prior chemotherapy versus none, and Karnofsky Performance Status (KPS) greater than 70 versus less than 70.

• Rotterdam Symptom checklist (RSCL)
• Single-item measures of tiredness and lack of energy

• A significant benefit of ATP was observed on tiredness (p = 0.0001) and lack of energy (p = 0.001).
• Mild, transient side effects were noted in the majority of patients.

• No placebo was administered, and outcome assessors were not blinded to patients' treatment arms.
• A control for concomitant steroids, which were given for brain edema, nausea, and dyspnea, did not exist.
• Ethical concerns arose about giving 10 30-hour infusions every two to four weeks (requiring hospital admissions) in patients with non-small cell lung cancer with limited expected lifespans.
• Hospitalization costs were a limitation.

To compare senna versus lactulose in relation to efficacy and adverse events in patients with terminal cancer.

Lactulose, an osmotic laxative, is a synthetic disaccharide. Senna acts mainly in the large intestine, directly stimulating the myenteric plexus and increasing water and electrolyte secretions, thus stimulating peristaltic activity. Their action extends over six to 12 hours. Side effects are abdominal pain, nausea, vomiting, and diarrhea.

Group A received senna BID starting at 0.4 ml (12 mg). Group B received lactulose BID starting at 15 ml. Based on clinical response, doses were increased in increments of 0.4 ml and 15 ml, respectively, every three days. Max doses were 1.6 ml (48 mg) for senna and 60 ml (40 g) for lactulose.

When patients reached the ceiling of their respective laxative and had three days without defecation, they were maintained on that dose and, in the absence of side effects, were started on an initial dose of another laxative, which could then be increased at three-day intervals until reaching the experimental maximum. Enema or mechanical bowel evacuation was prescribed after a three-day period without defecation (for ethical reasons), and was recorded as a failure with increase in laxative dose. If no results occurred from mechanical evacuation after six hours, patients were held on standby outside of the study until defecation. 

The randomization schedule was stratified for age and gender (limit of eight per stratum). The study period was seven days to assess laxative efficacy on defecation days and at variable opioid dosage, and 27 days to assess mean morphine dose at which a laxative was necessary. Both laxative and opioid treatments were initiated simultaneously. Prescribers were blinded (single doses of identical volume in closed opaque flasks).

• The study reported on a sample of 91 patients with terminal cancer; 43 patients were assigned to the senna arm and 48 patients were assigned to the lactulose arm. 
• Patients were aged older than 18 years and were in a palliative care program from July 1, 1993, to July 1, 1995.
• Mean patient age was 67.8 years (range 41–93). 
• All patients had clearly documented terminal disease with a life expectancy less than six months, and caregivers in the home.
• Thirty percent had lung cancer, 11% had breast cancer, and 9% had stomach cancer. 
• Patients were excluded if they had contraindications to the experimental laxatives, including colectomy, steatorrhea, or aphagia; a Karnofsky performance status lower than 10%; or taken opioids (codeine or morphine) or laxatives within 72 hours prior to initiation of the study.

The study took place at a palliative care unit (PCU) in Madrid, Spain. The PCU assists patients who are released from the local hospital and is responsible for home care follow-up protocols.

This was a comparative study with a randomized, open, parallel-group design.

• Outcome measures were defecation-free intervals of 72 hours, number of days with defecation events, and general state of health (rated on a five-point Likert-type scale).
• Defecation days as a function of opioid dose and treatment cost also were examined.
• Laxative efficacy was analyzed by t-test and ANOVA.

• Of 91 patients, 75 completed the study for at least seven days and were evaluated in the analysis.
• Sixteen patients abandoned the study within four days and were not included in the analysis. Reasons for leaving were diarrhea (n = 1), noncompliance (n = 4), dying within the first 24 hours (n = 4), permanent hospitalization (n = 5), and moving out of the jurisdiction of the home care area (n = 2).
• Opioid dose did not determine laxative efficacy.
• By the end of the study, 37.5% of patients required both laxatives.

No difference existed between senna and lactulose in efficacy as measured by defecation-free intervals, days with defecation, or adverse effects. Senna use is recommend based on its lower cost. The description of the study design was very precise and detailed.

• Patients could differentiate medications by taste and texture.
• Data were based on self-report, which is not considered reliable.
• The study was done in Spain, so results may not be transferable to a U.S. population.
• The sample size was fewer than 100 patients in the final analysis.
• Baseline effects of diet, age, tumor type, and mobility were not discussed in relation to the results.

To examine the effect of therapeutic touch (TT) on pain and fatigue in patients undergoing chemotherapy.

Patients were randomized to one of three groups:  the TT group; the placebo group, which underwent a procedure that mimicked TT; or the control group, which received standard treatment. Interventions were used for five days. Patients in the TT group received 30 minutes of TT delivered by a trained researcher. The same researcher delivered all interventions.

• The study was comprised of 90 women (30 patients in each group).
• Mean age was 36.86 years in the TT group, 42.70 years in the placebo group, and 43.30 years in the control group.
• All patients were receiving inpatient cancer treatment.

• Three inpatient units (Whether they were at one site or multiple sites is unknown.)
• Iran

• Patients were undergoing the active treatment phase of care.
• The study has clinical applicability for end of life and palliative care.

The study was a randomized, controlled trial with an intervention group and a usual care control.

• 10-point, 10-cm visual analog scale (VAS) (patient marked line for pain score)   
• Rhoten Fatigue Scale (RFS), 0 to 10 scale (0 = no fatigue, 10 = as much fatigue as I can bear)

• The pain scores of the TT group were lower than the pain scores of the placebo and control groups (p = 0.04).
• The fatigue scores of the TT group were lower than the scores of the placebo and control groups (p = 0.002).
• On some days, the scores of the placebo group were significantly lower (p < 0.05) than the scores of the control group.
• At all times, the fatigue scores of the TT group were lower than the scores of the placebo and control groups (p < 0.05).

TT was more effective at decreasing pain and fatigue than were placebo and control treatments. The placebo arm showed \"control\" that was superior to that in the control group.

• The study had a small sample size, with less than 100 patients.
• The sample was comprised of Muslim women in Iran, which may affect the applicability of the findings.
• The authors did not describe the actual intervention.

TT may decrease pain and fatigue scores in patients undergoing chemotherapy. The fact that a therapist must receive significant training to deliver TT may affect the practicality of the intervention.

STUDY PURPOSE: To review randomized, controlled trials evaluating the effect of telehealth interventions on pain, depression, and health-related quality of life outcomes in cancer care

TYPE OF STUDY: Systematic review

DATABASES USED: PubMed, EMBASE, Google Scholar, CINAHL, and PsychINFO

KEYWORDS: Neoplasms, cancer remote consultation, mHealth, connected health, text messaging, telemedicine, telehealth, ehealth, telephone therapy, teleconsultation, mobile technology, telecare, internet, digital health, mobile phone, smartphone, apps, and mobile application

INCLUSION CRITERIA: Reported the effect of telehealth on pain, depression, or quality of life in patients with cancer; randomized, controlled trials

EXCLUSION CRITERIA: Not stated

TOTAL REFERENCES RETRIEVED: 4,929

EVALUATION METHOD AND COMMENTS ON LITERATURE USED: Cochrane Collaboration’s risk of bias tool 

• FINAL NUMBER STUDIES INCLUDED = 20 
• TOTAL PATIENTS INCLUDED IN REVIEW = 3,654
• SAMPLE RANGE ACROSS STUDIES: 25–571 patients 
• KEY SAMPLE CHARACTERISTICS: Patients with cancer, access to telehealth, and smart phones; English-speaking; high-income countries; most were studies of patients with breast cancer

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

Many of the included studies were telephone-based interventions with the interventions provided by professionals or peer counselors. Five studies used a web-based delivery of the intervention. The duration of the interventions ranged from one week to 12 months with a median of 12 weeks. Three studies examined the effect on pain; two of these showed a significant positive effect of the intervention, and one showed no difference between the groups. Nine studies examined the intervention effect on depression; four of these showed positive effect on depression while five showed no significant effect. Eight studies examined quality of life, and one measured well-being.

This review showed mixed results for the effects of technology-based interventions on pain and depression among patients with cancer.

There were few included studies, and most of them were done in high-income populations that were tech-savvy. There was high heterogeneity in the outcomes. Many of the studies had a high or unclear risk of bias.

It may be worthwhile to use telehealth applications with tech-savvy, high-income patients. These types of interventions are worthy of additional study to fully determine the efficacy of these interventions for symptom management.

To evaluate the safety and efficacy of (177)Lu-EDTMP for the palliation of pain from bone metastases

Patients with documented bone metastases from prostate or breast cancer were randomly assigned to two groups. One received low-dose and one received high-dose (177)Lu-EDTMP. The radiopharmaceutical was given over one minute via an indwelling IV catheter. Patients were examined at one, two, four, six, eight, 12, and 16 weeks.

• N = 44  
• MEAN AGE = 66 years (males), 47 years (females)
• MALES: 72%, FEMALES: 28%

• PHASE OF CARE: Active antitumor treatment

Randomized, parallel-group trial

• Analgesic score (0 = no analgesic, and 4 = regular opioids)
• Visual Analog Scale (VAS) for pain severity (> 70% VAS decrease = complete response, 40%–70% decrease = partial response, 20%–40% decrease minimal response, and < 20% decrease = no response)
• Bone lesion score based on skeletal scintigraphy
• National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE)

Overall, 13% of participants experienced a complete responses to the intervention, 48% had partial responses, and 25% had minimal responses. VAS scores were significantly lower at all time points compared to baseline (p < 0.0001) with progressive decreases till four weeks. There was no change between weeks four and eight, and thereafter, pain increased significantly. There were no significant differences in responses between the high- and low-dose groups or between patients with prostate and breast cancers. Grades 3–4 toxicities were seen in 23% of patients, including anemia. The median hemoglobin nadir occurred at three weeks, and the median time to recovery was six weeks. Leukocyte and platelet nadirs occurred at four weeks and recovered to baseline after eight weeks. There was no relationship between pain responses and bone lesion scores.

The radiopharmaceutical tested here was effective in relieving pain from bone metastases in patients with prostate and breast cancers, and it was associated with few high-grade toxicities. Low- and high-dose treatments had similar efficacy.

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

This study added to the body of evidence regarding the efficacy of radiopharmaceuticals for pain relief from bone metastases. Various agents have shown different durations of pain-free periods. Nurses need to be aware that bone marrow toxicity is a major dose-limiting factor with radiopharmaceuticals, and patients who receive these agents should be monitored for toxicity. Additional research directly comparing the efficacy and duration of various radiopharmaceuticals' effects is needed.