To investigate the effects of supervised exercise training on cardiopulmonary function and fatigue in cancer survivors undergoing various clinical treatments.

Patients were divided into four groups based on specific type of treatment:  surgery alone (n = 22); surgery and chemotherapy (n = 30); surgery and radiation (n = 17); and surgery, chemotherapy, and radiation (n = 27). Following comprehensive screening and medical examination, cardiovascular endurance, pulmonary function, and fatigue were assessed. Individualized exercise prescriptions and six-month exercise interventions were developed. Participants attended supervised exercise sessions two to three days per week for six months.

• Ninety-six patients were included in the study.
• This was a convenience sample of breast cancer survivors undergoing various clinical treatments. 
• Age was 57.9 years (standard deviation = 10.4 years). 
• All patients were females with breast cancer. 
• All patients had undergone surgery.
• No significant differences were observed in age, height, or weight between groups.

• Single site
• Outpatient
• Oncology rehabilitation center

This was a pre-/posttest quasiexperimental study.

• Repeated measures ANOVA and ANCOVA were used to compare the effectiveness of the interventions and difference among treatment groups.
• Main variables were systolic and diastolic blood pressure, resting heart rate, forced vital capacity, forced expiratory volume, predicted oxygen consumption, time on treadmill, and fatigue.
• The revised Piper Fatigue Scale (PFS) was used to assess cancer-related fatigue.
• The behavioral fatigue subscale includes six questions and was used to assess the effect of fatigue on school and work, interacting with friends, and the overall interference with activities that are enjoyable.
• The affective fatigue subscale includes five questions to assess the emotional meaning attributed to fatigue.
• The sensory subscale includes five questions to assess mental, physical, and emotional symptoms of fatigue.
• The cognitive and mood fatigue scale consists of six questions.
• The average score on the 22 total questions from the subscales provided the total fatigue score.

Cardiopulmonary function (predicted maximal oxygen consumption and time on treadmill) significantly increased in all groups after exercise training. In addition, resting heart rate and forced vital capacity significantly improved in those undergoing surgery, chemotherapy, and radiation. Psychologically, the exercise intervention resulted in significant reductions in behavioral, affective, sensory, cognitive, mood, and total fatigue scale scores in all three groups who received treatment with surgery. The breast cancer survivors in the surgery alone group showed significant reductions in behavioral, affective, and total fatigue scale scores but not in sensory, cognitive, and mood fatigue scale scores.

The results suggested that moderate-intensity individualized exercise maintains or improves cardiopulmonary function with concomitant reductions in fatigue, regardless of treatment type. Moreover, cancer survivors receiving combination chemotherapy and radiotherapy following surgery appear to benefit to a greater extent as a result of an individualized exercise intervention.

• This was a convenience sample of women from one geographic location.
• The study lacked a control group.

Symptom management recommendations should be given to cancer survivors concerning the effectiveness of exercise throughout the cancer continuum, and the importance of participating in a cancer rehabilitation exercise program should be emphasized.

RESOURCE TYPE: Expert opinion

PHASE OF CARE: Active antitumor treatment

Briefly reviews the management of diarrhea related to checkpoint inhibitor adverse reactions.

Brief literature review of common checkpoint inhibitor adverse and serious adverse events. No evidence quality review was provided.

Patient education is crucial to the early reporting of adverse events that develop in patients after treatment with checkpoint inhibitors. Closely monitor patients with evidence of adverse events. Hospitalization and aggressive patient support may be required for serious adverse events.

• PHASE OF CARE: Multiple phases of care

The AGREE II and Cochrane Risk of Bias tool were used for evaluation of articles. Three practice guidelines and 12 RCTs were evaluated, and 27 supplemental supportive documents were reviewed (e.g., reviews, information summaries, consensus statements, best practice advice), which were not always cancer-focused. Results are summarized briefly with modest overall quality found in the practice guidelines and RCTs. Considerations were made for small samples, short follow-up in effectiveness trials, and lack of details on methods. Formal assessments were not conducted on supplemental articles to fill in missing gaps of knowledge.

The guideline recommends, at minimum, a brief and focused assessment for sleep disturbances in patients with cancer and cancer survivors and provides options for screening tools and self-report assessments. Strategies, algorithms for screening, assessment, and management are provided based on literature, but they also are consensus-driven. The screening should include a short two-step process using standardized tools. The focused assessment then should identify chronicity and severity of the sleep problems (parameters of symptoms of poor sleep included). This includes key questions and a sleep diary for full evaluation. Referrals for noninsomnia-related disorders (e.g., apnea, restless legs syndrome) are prompted within the algorithm. Based on the initial evaluation, nonpharmacologic and pharmacologic interventions are recommended in a step process with care pathways that match the severity of the sleep disturbance (i.e., mild, transient, insomnia syndrome) with three corresponding care pathways. Preventative and supportive educational information is provided for all patients with cancer and cancer survivors that focuses on sleep hygiene and other sleep-promoting strategies. Rationale is provided for each strategy of treatment within this algorithm.

• The guideline addresses sleep disturbances within the context of an insomnia syndrome.
• All other disorders requiring referral are not within the scope of the proposed guidelines.
• Menopause-related sleep disturbances are not addressed.
• The use of the guideline would necessitate training of healthcare providers to fully incorporate into practice. 

A basic and focused screening for sleep problems in patients with cancer is needed, with corresponding treatment and education as pertained to the scope of practice.

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

Guidelines and algorithm developed

• Limited data reviewed.
• Guidelines based on data from 2009
• Implementation and evaluation plans for translation to practice not described

Guidelines developed for clinical practice.

To determine whether modafinil could reduce fatigue related to docetaxel chemotherapy

Patients with metastatic breast or prostate cancer receiving docetaxel chemotherapy and experiencing significant fatigue were randomized to receive modafinil or placebo for 15 days beginning with their third cycle of treatment and repeated for 2–4 subsequent chemotherapy cycles.

• N = 83  
• MEAN AGE = 66.4 years in the modafinil group and 68 years in the placebo group
• MALES: 78%, FEMALES: 22%
• KEY DISEASE CHARACTERISTICS: Primarily Caucasian; metastatic breast/prostate cancer; received at least two cycles of docetaxel; MDASI fatigue score (≥ 4/10); Hgb ≥ 10

• SITE: Multi-site  
• SETTING TYPE: Not specified  
• LOCATION: Australia

• PHASE OF CARE: Active anti-tumor treatment

• Phase II randomized, double-blind, placebo-controlled.
• Eligible patients were randomized 2:1 to modafinil or placebo and stratified according to tumor type.

• MD Anderson Symptom Inventory (MDASI)
• Secondary outcomes measures included depression, sleep disturbance, exercise, cognition, and mood states.

The goal was a 10% or greater relative difference between the two treatment groups.

The primary endpoint of reduced fatigue during docetaxel chemotherapy was not statistically different between the two treatment arms.

• Small sample (< 100)
• Key sample group differences that could influence results
• Measurement validity/reliability questionable
• Questionable protocol fidelity
• Other limitations/explanation: Study had to be repowered due to limited recruitment. Unclear how secondary measures were evaluated. Use of dexamethasone premedication.

Features a trend in docetaxel-related fatigue. Effectiveness was not established for the broader cancer-related fatigue treatment.

To determine the short- and long-term effects of bone marrow stromal cells (BMSC) transplantation for breast cancer-related lymphedema and to compare and contrast BMSC transplantation with complex decongestive physiotherapy

Patients in the complex decongestive physiotherapy group underwent manual lymphatic drainage, compression therapy, remedial exercises for arm and shoulder, and deep breathing to promote venous and lymphatic flow. Patients in the BMSC transplant group underwent bone marrow aspiration from the iliac crest, were admitted, and underwent brachial plexus or general anesthesia with range of transplantation being around the axilla, chest wall, and upper arm of the affected extremity. After the intensive phase, all patients were measured for and wore custom garment during waking hours. Patients were interviewed via telephone at 3 months and 12 months after treatment.

• The study sample (N = 50) was comprised of the control group (n = 35) and the intervention group (n = 15).
• Patients on an in-patient unit were enrolled and followed for one year.
• All patients had were female and had underwent breast cancer surgery without radiation five years earlier.

The study took place in a single site in China.

The study used a controlled trial design.

• Pain was assessed on numerical scale from 0–5.
• Volume measurements were performed according to Kuhnke’s Disk Model, measuring the circumferences of the arms at 4 cm intervals beginning at the wrist and ending at the shoulder.
• The volume of edema was calculated as the difference between the affected and unaffected arms; the percentage of edema in the arm was then calculated.
• The percentage of change in the edema arm was calculated by the formula [(VT – VI)/ (VI –VN)] 100, where VT is the post-treatment volume of the edema arm, VI the initial volume of the edema arm, and VN the volume of the normal arm.

Both groups of patients experienced a reduction in pain and lymphedema volume. Patients in the BMSC transplant group had better long-term results. At three months (p = 0.0151) and at 12 months (p = 0.0001) patients in the BMSC group had significantly greater reduction in edema in the affected limb.

Autologous BMSC to treat breast cancer-related upper-extremity lymphedema was effective in the study at one year.

• The study size was small, with less than 100 participants.
• Study cites need for lymphoscintigraphy pre- and post-treatment to evaluate formulation of new lymphatic vessels.
• They study had no random assignment.

The study adds evidence to the effectiveness of complex decongestive physiotherapy in this population, which requires compliance with therapy, education, and support for patients and families.

To evaluate the use of erythropoietin (EPO) for the prevention and reduction of oral mucositis (OM) in patients undergoing autologous hematopoietic stem cell transplantation

The intervention group used EPO mouthwash (50 IU/ml, 15 ml) four times per day beginning on the day of conditioning initiation and for 14 days post transplant or until DC, whichever came first. The control group received mouthwash (15 ml) four times a day without EPO for the same period of time. The mouthwash looked, smelled, and tasted the same. All patients were evaluated daily until day 21 by the same blinded evaluator. The World Health Organization (WHO) Oral Toxicity Scale was used for assessment.

• N = 80 (40 in intervention group, 40 in control group)   
• AGE = Older than 18 years (mean age was 43.37 years in the treatment group; mean age was 45.07 years in the control group)
• MALES: 51.25% overall (55% intervention group, 47.5% placebo group); FEMALES: 48.75% (45% intervention group, 52.5% placebo group)
• CURRENT TREATMENT: Chemotherapy
• KEY DISEASE CHARACTERISTICS: Non-Hodgkin lymphoma, Hodgkin lymphoma, and multiple myeloma; active treatment
• OTHER KEY SAMPLE CHARACTERISTICS: All undergoing autologous stem cell transplantation

• SITE: Single site   
• SETTING TYPE: Inpatient    
• LOCATION: Iran

• PHASE OF CARE: Active antitumor treatment
• APPLICATIONS: Palliative care 

• Double-blinded, randomized controlled trial

• WHO Oral Toxicity Scale
• Length of stay
• Duration of neutropenia and thrombocytopenia
• Engraftment time
• Incidence and length of neutropenic fever
• Number of transfusions (platelets and packed cells)
• Use of parenteral opioid narcotics

Overall, less OM occurred in the EPO group (p < 0.001), less grade 2–4 OM occurrend in the EPO group (p = 0.003), and no significant difference existed in severe OM (grades 3–4) between groups, but the trend was less in the EPO group. Less intensity and severity of OM occurred in the EPO group (p < 0.001), shorter duration of OM occurred in the EPO group (p < 0.001), and the duration of neutropenic fever was less in the EPO group (p = 0.016). No differences in hematologic recovery, duration of neutropenia, or length of stay existed across groups. In addition, no differences in parenteral opioid use and transfusion were present across groups.

EPO mouthwash reduced the overall incidence of OM, decreased the severity and intensity of OM, and decreased the duration of OM. The duration of neutropenic fever was also decreased. A trend toward less severe OM (grades 3–4) in patients who used the EPO mouthwash was present.

• Small sample (< 100)
• Findings not generalizable
• This is the first RCT. The dose of EPO prior to this study has not been studied for the prevention of OM. The patient population studied is limited to high-dose chemotherapy and autologous stem cell transplantation.

EPO mouthwashes hold promise for preventing OM in patients undergoing autologous stem cell transplantation and receiving high-dose chemotherapy. Additional study is indicated, and the investigation of EPO mouthwash dosing will be important. The cost of EPO mouthwash may be an issue and will need to be evaluated.

To evaluate the effects of guided imagery on chemotherapy-induced nausea and vomiting (CINV) among patients with breast cancer

Women who experienced nausea and vomiting within 24 hours after the first course of chemotherapy were assessed before and after the second course of chemotherapy. For the third course of therapy, participants listened to two audio recorded guided imagery scripts. One had mixed nature sounds as background and the other track instructed listeners to imagine feeling better within a pleasant setting of their choice. Patients listened to the first track the night before the third course of treatment. Prior to chemotherapy, severity and frequency of nausea and vomiting were measured.

• N = 55   
• MEAN AGE = 57.5 years (SD = 8.43)
• FEMALES: 100%
• CURRENT TREATMENT: Chemotherapy
• KEY DISEASE CHARACTERISTICS: All had breast cancer.

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

PHASE OF CARE: Active antitumor treatment

Quasiexperimental

Morrow Assessment of Nausea and Vomiting

Pre- and post nausea and vomiting scores were lower in the third treatment cycle compared to those in the second cycle of chemotherapy (p = 0.0001).

Guided imagery may be helpful for reducing CINV.

• Small sample (< 100)
• Risk of bias (no control group)
• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• Measurement validity/reliability questionable
• The type of chemotherapy was not identified.
• No information is provided regarding any use of antiemetics.  
• Apparently, CINV was evaluated immediately pre- and postchemotherapy, so it may not have picked up actual time in which the symptoms were experienced.
• It is unclear how scores were determined based on description of the items on the instrument.  
• The article is not clearly written, making it difficult to determine exact study procedures and timing of measurement.

The findings suggest that guided imagery might be helpful to reduce CINV symptoms. This study and report do not provide strong evidence because of multiple limitations. Additional research is needed to determine efficacy. Guided imagery is a very low-risk intervention that might be helpful to some patients, but the appropriate timing of such an intervention related to timing of chemotherapy administration needs to be determined in future research.

To determine the optimal single-dose radiotherapy schedule for pain related to bone metastases

Patients were randomly assigned to receive a single dose of 8 Gy, a single dose of 4 Gy, or 12 Gy in four fractions given over two consecutive days. Additional treatment with 8 Gy was given if moderate or severe pain persisted. Analgesic use was documented at baseline and at each follow-up. Patients were assessed at baseline and at four, eight, 12, 24, and 52 weeks.

• N = 545 at week 4  
• MEDIAN AGE = 57 years (range = 25–88 years)
• MALES: Not provided, FEMALES: Not provided
• KEY DISEASE CHARACTERISTICS: Multiple tumor types; metastasis sites were spine, pelvis, hip, femur, humerus, and other sites
• OTHER KEY SAMPLE CHARACTERISTICS: About 21% of patients were not receiving any analgesics at baseline, and 34% were receiving strong opioids.

• SITE: Multi-site  
• SETTING TYPE: Outpatient  
• LOCATION: International

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

Randomized trial

• 10 cm Visual Analog Scale (VAS) for pain
• Four-point scale for pain (0 = none, and 4 = severe)
• Complete response (CR) was defined as no pain and a score of 0 on the VAS. Partial response (PR) was defined as a reduction of one point on the four-point scale or a VAS reduction of at least 10 mm.

Across all follow-up time points, the proportion of those with CR and PR was higher with radiotherapy at 8 Gy although the difference between the groups was only significant at eight weeks. More treatments were needed with 4 Gy radiotherapy (p = 0.01). The response rate with 8 Gy was 70%–80% at four weeks compared to 82% with 4 Gy.

A single dose of 8 Gy radiotherapy was associated with higher CR rates, and a dosage of 4 Gy was effective in a substantial number of patients.

• Risk of bias (no blinding)
• Measurement/methods not well described 
• Other limitations/explanation: How pain data was collected was not stated. No information was provided on any changes in analgesics or the use of bone modifying agents.

Both single-dose 4 Gy and 8 Gy radiotherapy were effective in reducing pain in the majority of patients. An 8 Gy dosing was beneficial in a higher proportion of patients, and fewer patients at this dose required additional treatment. Individual patient variables need to be considered in determining dosages based on tolerance and concerns about toxicity.

To compare a single, intravenous infusion of ibandronate with single-dose radiotherapy for metastatic bone pain

Patients referred for pain management were randomized to receive 6 mg ibandronate or a single dose of 8 Gy radiotherapy. Patients whose pain failed to respond to the treatment at four weeks were allowed to cross over to the opposite treatment within four to eight weeks. Assessments were done at baseline and at four, eight, 12, 26, and 52 weeks.

• N = 470
• MEDIAN AGE = 72.5 years (range = 47–97 years)
• MALES: 100%
• KEY DISEASE CHARACTERISTICS: All had prostate cancer
• OTHER KEY SAMPLE CHARACTERISTICS: Patients who had previous treatment with radiotherapy or bisphosphonates within the last six months were excluded. Overall, 90% were receiving hormone therapy. The baseline median pain score was 7.

• SITE: Multi-site  
• SETTING TYPE: Outpatient  
• LOCATION: United Kingdom

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

Randomized noninferiority trial

• World Health Organization (WHO) criteria for analgesia
• Morphine equivalents for analgesia use
• Brief Pain Inventory (BPI)
• Effective Analgesic Score (EAS)
• Functional Assessment of Chronic Illness Therapy (FACIT) for quality of life
• Complete response was defined as a pain score of 0 with stable or reduced analgesic use.
• Partial response was defined as a two-point reduction in pain scores or a 25% reduction in analgesia with a stable pain score.

Overall, 31% of participants who began with ibandronate were crossed over, and 24% who began with radiotherapy were crossed over. There was no difference in WHO worst pain response between the groups at any study assessment period. There were no differences between the groups in worst pain response. At four weeks, those receiving radiotherapy had better responses (p = 0.04), but there was no difference at 12 weeks. There were no differences in quality of life between groups. Twice as many patients in the radiotherapy group had diarrhea (p = 0.014), and more had nausea (p = 0.058).

Single-dose radiotherapy and a single infusion of ibandronate had similar results on pain caused by bone metastases in men with prostate cancer. Radiotherapy was associated with more short-term adverse effects.

• Risk of bias (no blinding)
• Unintended interventions or applicable interventions not described that would influence results
• Other limitations/explanation: No information was provided regarding analgesics used, and data regarding any changes in analgesia were not provided.

This study showed similar results for pain reduction with single-dose radiotherapy and a single infusion of ibandronate. Ibandronate is a newer bone modifying agent, so it is not clear if all bone modifying agents would provide equivalent results in comparison to radiotherapy. Bone modifying agents may have fewer side effects, which can be of importance depending upon the site of radiotherapy.