To examine the effect of cognitive-behavioral therapy (CBT) on fatigue and to examine whether the effect on fatigue is mediated by physical activity and/or physical fitness.

Patients referred for CBT were randomly assigned to the intervention group or to a wait-list control group. The CBT intervention was provided in six modules focusing on coping, rear of disease recurrence, dysfunctional cognitions related to fatigue, activity management, dysregulation of sleep, social support, and negative social interactions. Material was adapted to the individual patients. All patients set a baseline level of physical activity and, once set, began an activity program of cycling or walking five to 10 minutes twice daily. This was increased to a maximum of 120 minutes daily. Study measures were obtained at baseline and six-month follow-up. Physical activity was measured for two weeks prior to study entry.

• Thirty-seven patients (48.6% male and 51.4% female) were included.            
• Mean age was 49.5 years.
• Patients had various disease types of solid tumors or non-Hodgkin lymphoma.  
• All patients had completed initial antitumor therapy. 
• At baseline, average time since diagnosis was 52 months for the intervention group and 45 months for the control group.
• Patients with psychological problems or treatment and those with depression were excluded.

• Single site  
• Setting not specified    
• Netherlands

Patients were undergoing the late effects and survivorship phase of care.

This was a randomized, controlled trial.

• Checklist Individual Strength (CIS) fatigue severity subscale
• Sickness Impact Profile (SIP)
• Actigraphy:  resting and activity oxygen consumption, ventilation, respiratory quotient, and maximal oxygen consumption

Forty-six percent of patients in the intervention were lost to follow-up. The CBT group had a significantly greater improvement in fatigue scores than control patients (p < 0.001). There was significantly greater improvement in functional impairment in the CBT group compared to controls (p = 0.009). Fatigue and impairment improved over the six-month period in both groups. There were no significant differences between groups in physical activity or physical fitness measures at baseline or follow-up. Analysis showed no mediation effect of physical activity or physical fitness.

Findings suggested that CBT was effective in reducting cancer-related fatigue and sickness impact scores. Findings suggested that this effect was not mediated by physical activity or fitness.

• The study had a small sample size, with less than 100 patients.
• Baseline sample/group differences were of import. 
• The study had risks of bias due to no blinding and no appropriate attentional control condition.
• Unintended interventions or applicable interventions that would influence the results were not described.
• Key sample group differences could influence the results.
• Measurement validity/reliability was questionable.
• Patient withdrawals were 10% or greater.
• Physical activity was only measured at baseline, and activity levels in both groups over the course of the study period were not measured and reported. This suggests that findings regarding the potential mediation of CBT effects by activity were not valid. 
• More patients in the control group had a combination of surgery, chemotherapy, and radiation therapy, which may have had a greater impact on fatigue. 
• The large drop-out rate in the intervention group was a limitation of findings. 
• There was no analysis of differences between those who were lost to follow-up and others.

Findings supported the potential effectiveness of CBT for fatigue management in cancer care. These findings were in patients about four years after completion of treatment, suggesting benefits even long after active treatment. There were several study limitations that reduced the strength of this evidence.

To assess the efficacy and tolerability of MAS065D (Xclair™) compared to a vehicle control in the management of radiation dermatitis

There was a washout period of seven days for other topical medication prior to the beginning of treatment. The treatment field was divided into two sections. Participants were randomized into two groups. One received MASO65D on section one and the control vehicle on section two. The other participant group received the reverse. Participants were to apply the product three times a day upon the start of treatment and continue for two weeks after the completion of treatment.

• N = 22 patients
• MEDIAN AGE = 57 years
• FEMALES: 100%
• KEY DISEASE CHARACTERISTICS: Breast cancer
• OTHER KEY SAMPLE CHARACTERISTICS: Total dose of 50–70 Gy over four to six weeks in daily fractions, no concurrent chemotherapy

• LOCATION: Radiation facility in Italy

• Double-blind, vehicle-controlled longitudinal study
  • Quasi-experimental design with patients as their own controls

• National Cancer Institute (NCI) toxicity scale 0–4 used to grade skin toxicity
• Transepidermal water loss (TEWL) was measured with a Tewameter^®
• Erythema rating measured using the Mexameter^® MX 16
• Skin hydration measured using the Corneometer^® CM 825
• Visual numeric scale (1–10) to measure pain and itch
• Wilcoxon matched-pairs signed-rank test for skin grading and other measurements

Overall toxicity scale results across groups were

• Grade 1: 35%
• Grade 2: 35%
• Grade 3: 5%
• Grade 4: 0%

The mean scores for NCI grading in both treatment groups increased from visit 1 to visit 6 and then declined. With MASO65D, the mean NCI scores were lower in five of the assessment weeks; however, this difference was statistically significant only at week 4. The mean score for erythema with MAS065D was found to be significantly lower than that of the control (p = 0.031) only at visit 5. The mean score for TEWL/hydration observed in the breast sections treated with MAS065D was lower than in those treated with the control vehicle from visit 3 onward, but this was not statically significant Both the patients and investigators preferred the MAS065D (p = 0.007 and p = 0.035, respectively). The pain and itch scores were mainly 0 throughout the study, and there was no difference noted. No adverse events were reported with either skin product.

MAS065D is effective in the management of radiation dermatitis, but further studies are necessary.

• Small sample size
• Total dose was 20–70 Gy (mean ± SD: 65.5 ± 13.9) over one to six weeks (5.6 ± 1.4). At the low end of dosage and short duration of treatment, skin toxicity would be expected to be lower. This factor was not discussed in the study. The authors did not describe TEWL, erythema, or skin hydration measurement sufficiently, or the manner in which the instruments provided these measures.
• The way in which patient and investigator preference were measured was not clearly identified.

To evaluate types of psychosocial interventions employed in patients with cancer

To update and extend a previous review by conducting a search and reporting on recent trials

Databases searched were MEDLINE, CINAHL, PsycINFO, Social Sciences Citation Index, Social Services Abstracts, and PubMed databases from 1999–2007.

Search keywords were psychosocial care, intervention, service, support, oncology, effectiveness (effect*) and evaluation (evaluat*).

Studies were included in the review if they reported

• Any type of psychosocial intervention delivered during the treatment phase of cancer
• Primary cancer of any histological type
• A randomized controlled trial (RCT) or quasi-experimental design
• Measurements of one or more intended effects of psychosocial intervention
• An English-language samples of patients age 18 or older.

Studies were excluded if they reported on patients with metastatic disease.

A total of 1,702 studies were initially identified. After elimination of studies that did not meet inclusion criteria, 27 studies were included. Study quality was evaluated using a modified Jadad scoring approach. There were 22 final RCTs and 5 pilot studies used.

There were few studies with a high-quality rating, and the mean rating for the entire sample of studies was 2.41 on a 5-point scale. Effect sizes were calculated for only nine studies, in which statistically significant results were reported. Patient outcomes measured in this subgroup of studies varied and included general health, emotional control, social support, global adjustment to illness, relationship quality, optimism, self-esteem, and self-efficacy. Studies were conducted in the United States, Canada, Europe, Hong Kong, Australia, and New Zealand.

• Across the final set of 27 studies, sample sizes reported ranged from 17 to 260, with a total of more than 3,600 patients.
• Breast cancer was the most common diagnosis.
• Studies also included melanoma, gynecologic, head and neck, lung, colon, prostate, and other cancer types.

The mean effect size was small, at 0.28, across the varied outcomes measured in studies. 

Individual interventions: psychosocial, psychoeducational, and cognitive behavioral

• Nine studies examined the effect of psychosocial counseling.
  • Three studies demonstrated mixed results, with negative effects.
  • Two studies did not report actual statistical findings.
  • Three studies did not demonstrate statistically significant findings. 
  • One study demonstrated significantly better scores for self-administered stress reduction on some general health and depression scales compared to controls and those in a professionally led intervention.
  • One small pilot study reported significant improvement in body image perception.
• Four studies used cognitive behavioral interventions.
  • One study reported mixed results.
  • Two studies did not find statistically significant results. In one of these, there was no main effect, but symptoms improved more in a subgroup of patients who had more severe symptoms at baseline.
  • One study demonstrated significant differences in anxiety and perceived social support.

 Telephone intervention

• Four studies used telephone interventions primarily to address educational and resource needs.
• Only one of these studies showed a trend toward improvement in depression and fatigue; however, there were unadjusted differences between groups at baseline.

Group counseling

• Four studies tested group interventions. Three of these did not find significant differences between groups, and one study reported significant effects on psychological distress at 6 months, but not at 12 months.

Miscellaneous

• One study reported significant differences in relationship quality with couples counseling and psychological distress, but only at a 1 week time point in the study.
• One study examined the effect of feedback to the physician regarding patients’ distress. No significant effects were found.

Attrition was a problem in many of the studies. In a few studies, positive effects or trends were seen with individuals who had more severe problems at baseline; however, attrition was also highest among these patients.

There appears to be some evidence supporting interventions targeting stress and coping; however, there is no strong support for any one type of intervention evaluated here. Where significant findings were seen, effect sizes were small and the clinical relevance of this level of effect could not be evaluated. There do not appear to be any long-term effects with the interventions examined here.

The quality of most studies was not high.

While no long-term effects were clearly found, even short-term effects on distress for people with cancer can be important for patients and clinically useful.

Positive results in one study using self-managed approaches for stress reduction suggest that this may be a practical and cost-effective way to address short-term patient needs.

Patients with cancer are a heterogeneous group, and the nature of psychosocial interventions is such that one should expect them to be highly individualized, as is the approach in clinical practice. Further, psychosocial interventions delivered on an individual basis versus group therapy were better supported and easier to maintain. This represents one of the challenges in this area of research that should be addressed in future studies.

Given attrition levels discussed here along with findings that greater effect is seen among patients with more severe baseline problems, in future work, care needs to be taken to consider for whom psychosocial interventions is indicated and how onerous the intervention and study protocol are for participants.

Findings point to the need for higher quality research design and reporting in this field.

Psychoeducational interventions addressing patients’ informational needs about cancer, progression, treatment, and side effects were found to be beneficial.

Psychosocial interventions found to be most beneficial include cognitive adaption, coping management, and encouraging patients to practice stress management techniques at home.

To assess the effect of physical treatment programs on the volume, shape, condition, and long-term (six months) control of oedema in lymphoedematous limbs and to assess the psycho-social benefits of physical treatment

Databases included in the review were the Cochrane Breast Cancer Group Trials Register, The Cochrane Central Register of Controlled Trials, MEDLINE^©, EMBASE, CINAHL^©, the National Research Register and UnCover, PASCAL, SIGLE, reference lists produced by The British Lymphology Society, and The International Society of Lymphology Congress Proceedings. Keywords were lymphoedema, lymphedema, lymphodema, or elephantiasis; exercise; physical therapy; bandage; hosiery or hose; compression; bandages and dressings; compression garments; physical therapy modalities; intermittent pneumatic compression devices; physiotherapy; kinesiotherapy; compression stocking; pneumatic compression; limb volume; limb size; excess (limb) volume; oedema or edema volume; and quality of life measure or tool. Studies were included in the review if they were randomized controlled trials that tested physical therapies with a follow-up period of at least six months. Studies were excluded if they had a follow-up  less than six months or the trial did not use limb volume as the method of assessing change in size.

The total number of studies reviewed initially was 185. Two blinded reviewers independently assessed trial quality and extracted data. Meta-analysis was not performed because of the poor quality of the trials.

• Three studies were included in the report.
• The total sample size was 150.
• The sample range across studies was 25–33.
• All types of lymphedema were included, non cancer-related and cancer- related.
• Patients with cancer had to have completed their cancer treatment at least six months before entering the trial and could not have evidence of recurrent malignant disease when going into the trial.

Wearing a compression sleeve is beneficial. The bandage plus hosiery results in a greater reduction in excess limb volume than hosiery alone and this difference in reduction was maintained long term.

All three trials have their limitations and have yet to be replicated, so their results must be viewed with caution.

There is a clear need for well-designed, randomised trials of the whole range of physical therapies if the best approach to managing lymphedema is to be determined.

To investigate the analgesic efficacy and safety of a transdermal buprenorphine patch used by patients with chronic severe cancer pain

Eligible patients participated in an open-label two-week phase in which they stopped drug therapy with previously prescribed analgesics. In this phase patients started drug therapy that consisted of a 70 mcg buprenorphine (BUP) transdermal (TDS) patch applied every three days. Pain intensity scores and intake of rescue medication, sublingual BUP, indicated whether a patient responded to BUP TDS. At the end of two weeks, patients who responded to BUP TDS were assigned to the BUP TDS group or the placebo group for a two-week maintenance phase. Patients used rescue medication for breakthrough pain as needed. BUP and placebo patches were identical in appearance and adhesive properties. Twice daily patients reported current pain on a 10-point scale. Authors evaluated the amount of BUP rescue medication taken and patients’ global satisfaction with treatment. At each visit the patient was asked to report any new adverse event.

• Initially, 289 patients entered the trial. The analyzed sample was composed of 188 patients.
• Mean patient age was 63 years. Age range was 29–90 years.
• Of all patients, 42.9% were female and 57.1% were male.
• Of all patients, 73% had metastatic disease. The most frequent metastases were to bone, liver, and lung. More than 30% of patients were also receiving corticosteroids and/or benzodiazepines. Overall, 35% of patients were receiving adjuvant chemotherapy, 18% were receiving hormone treatment, and 9% had had radiotherapy. Eligible patients had received insufficient pain relief from opioid regimens used before the study. Patients were receiving single or combination opioid therapy. Use of adjuvant analgesics—such as tricyclic antidepressants, benzodiazepines, anticonvulsants, muscle relaxants, or corticosteroids—was allowed if doses were stable.

• Multisite
• Twenty-six cancer centers in Austria, Belgium, Croatia, France, Poland, and the Netherlands

Randomized double-blind, placebo-controlled trial following an initial two-week open-label phase

• Ten-point numeric rating scale, to measure pain
• Five-point Likert scale, to measure patients' global satisfaction with treatment

• Of the 289 subjects entered, 32% discontinued BUP TDS treatment during the initial two-week run-in phase. Of the 189 patients who responded to BUP, 15.8% discontinued the study: 7 in the BUP TDS group and 24 in the placebo group.
• Of patients in the BUP TDS group, 74% responded to the treatment, compared to 50% in the placebo group (p = 0.0003).
• The most commonly reported adverse events were nausea, vomiting, and constipation.
• Compared to patients receiving placebo, patients receiving BUP TDS had a greater degree of global satisfaction, reported lower pain scores, and used less rescue medication.

Findings suggest that, for some patients, transdermal buprenorphine may be effective in the treatment of chronic cancer pain.

• There was a substantial dropout rate after the two-week initial study.
• To be eligible for the study, all patients had to have chronic severe pain. It is not at all surprising that patients using any pain medication would respond better than patients receiving placebo.
• Authors note that European Medicines Agency guidelines regarding chronic pain recommend comparing active treatment versus placebo to prove efficacy. However, this procedure raises concerns about the relevance of such comparisons and resulting findings to actual clinical care.
• Patients entered into the placebo-controlled part of this study were only those who clearly demonstrated response to BUP TDS. Results indicated that more than 30% of initial patients did not meet this criteria and did not respond to BUP TDS.

Transdermal buprenorphine may be helpful to some patients, but in this study more than one-third of cases did not respond to the treatment. The relevance of the findings of a placebo-controlled trial such as this one are questionable; patients with chronic pain would be expected to respond better to any pain medication than to placebo. Authors provide no information about the value of transdermal buprenorphine compared to the value of other analgesics.

Databases searched were MEDLINE and CINAHL (1992 to fall 2004).

Search keywords were mucositis, stomatitis, and chemotherapy in combination with prevention, mouthwashes, antiseptic, oral infection, chlorhexidine, chamomile, povidone-iodine, and sodium bicarbonate.

Studies were included in the review if they

• Were randomized studies of the effect of mouthwashes for the prevention and amelioration of oral mucositis in adult patients undergoing chemotherapy.
• Involved mouthwashes for oral mucositis, had a controlled study design, and included an outcome measure of the severity of mucositis.

Seven studies met the criteria. Five investigated chlorhexidine, one investigated iodine mouthwash, and one investigated chamomile solution. All studies randomly allocated participants to either an intervention or a comparison group. One study assigned patients by stratified block randomization. Most studies used a placebo mouthwash or sterile water as a control.

• Patients were adults with a mean age of 53.6 years.
• Among the patients included across all studies, 72% of the patients received chemotherapy, 6% of the patient received hematopoietic stem cell transplantation, and 22% had unknown treatments.

• The five studies investigating chlorhexidine mouthwash showed no significant effect (weighted mean difference = 0.22; 95% CI = –0.20, 0.63). I
• n the chamomile study, no differences were found between the chamomile group and the control group in either incidence or severity of mucositis.
• In the povidone-iodine study, the iodine group had significantly less severe mucositis and shorter duration compared with the control group; however, the sample size (n = 40; power ≤ 80) was too small to be confident in the findings.

Povidone-iodine was the only agent to show activity for preventing mucositis. Because of the effects of chlorhexidine (e.g., teeth discoloration, bitter taste, unpleasant sensations), the authors concluded that sterile water, 0.9% saline solution, or sodium bicarbonate all are better alternatives.

To determine the feasibility of testing Reiki, a complementary therapy intervention, for women undergoing breast biopsy

A two-group study design was used: conventional care group (CCG) and Reiki intervention group (RIG). The intervention (Reiki treatment lasting 45–50 minutes) was delivered at the local complementary therapy office. The Reiki treatments were given on two occasions: one within seven days of biopsy and one within seven days following biopsy. Six trained Reiki practitioners delivered the Reiki treatments.

• The study reported on a sample of 32 participants: 17 in the RIG and 15 in the CCG.
• Mean age in the RIG was 52 years (SD = 8.86; range = 37–75 years); mean age in the CCG was 51 years (SD = 6.19; range = 39–61 years).
• The sample was 100% female.
• All women were undergoing diagnostic breast biopsy.
• The majority of the sample was Caucasian (13 [76%] in RIG and 13 [87%] in CCG); the remainder self-described as African American, Hispanic, and other.

• Multisite
• Outpatient setting
• Sample was recruited from five different ambulatory sites.

Patients were undergoing the diagnostic phase of care.

A randomized controlled trial design was used.

• Spielberger State-Trait Anxiety Inventory (STAI)
• Center for Epidemiologic Studies Depression Scale (CES-D)
• Hospital Anxiety and Depression Scale (HADS)

Neither group displayed significant amounts of distress (as operationalized by the three measures) either before or after breast biopsy. Likewise, there were not significant differences in any of the measures between groups (RIG and CCG) over time. Over time (pre to post breast biopsy), there were significant decreases for both groups in the A-state (F (2) = 4.78, p = 0.0119), HADS total (F (1) = 6.18, p = 0.0187), and HADS anxiety subscale (F (1) = 12.96, p = 0.0011).

The study did not conclude that Reiki was an effective intervention for reducing biopsy-related distress.

• The study had a small sample size, with less than 30 participants.
• The lack of investigator blinding had an associated risk of bias.
• Sampling and data collection time points were not clear from the report.
• Data collection procedures for the CCG were not explained, and it was unclear who was interviewed (both groups or only RIG) or why.
• Study is stated to be a randomized controlled trial, but it seemed to be rather a pilot to determine the feasibility of the Reiki intervention with this group.
• The small sample had insufficient power to determine group difference or efficacy on the intervention in reducing biopsy-related anxiety and depression.
• Table 2 lists the three reported measures (STAI, CES-D, and HADS) but then also reports data on anxiety and depression. However, it is not clear what this data came from.
• The intervention was provided by multiple practitioners, with possible treatment variations.

Simple complementary interventions integrated within the clinical setting (thus not requiring patients to commit to off-site interventions) should be considered. Effective ways to recruit and maintain enrollment in clinical trials of complementary therapies should continue to be investigated.

To determine the feasibility of testing a Reiki intervention, a complementary therapy, on women undergoing breast biopsy; to determine the effectiveness of a Reiki intervention in the sample

Two-group design: conventional care group (CCG) and Reiki intervention group (RIG)

• The sample was composed of 32 participants; 17 in RIG and 15 in CCG.
• Mean participant age was 52 years (SD = 8.86 years); the age range was 37–75 years.
• All participants were female.
• Of all participants, 32 were undergoing diagnostic breast biopsy.
• Most participants were Caucasian: in RIG 13, or 76%, were Caucasian; in CCG, 13, or 87%, were Caucasian.

• Multisite
• Outpatient
• United States

Diagnostic

Randomized controlled single-blind trial

• State-Trait Anxiety Inventory (STAI), by Spielberger
• Center for Epidemiological Studies Depression Scale (CESD)
• Hospital Anxiety and Depression Scale (HADS)

Neither group displayed significant distress (as operationalized by the three measures) either before or after breast biopsy. Likewise, the study showed no significant difference in any of the measures between groups (RIG and CCG) over time. Over time (pre- to post–breast biopsy), the A state did not decrease significantly in either group (F (2) = 4.78, p = 0.0119) in regard to the HADS total (F (1) = 6.18, p = 0.0187) or HADS anxiety subscale (F (1) = 12.96, p = 0.0011).

One cannot conclude that Reiki was an effective intervention for reducing biopsy-related distress.

• The study had a small sample, with fewer than 30 participants.
• The degree of blinding is unclear; the study contains contradictory information.
• Data-collection time points are not clearly described—how long exactly after biopsy, what was the range of time points for collection of T3 data? Furthermore, the author discusses postintervention telephone interviews, but neither the purpose of the interviews nor the data collected in them are reported.
• Data-collection procedures for the CCG group were not explained: Who was interviewed, both groups or only RIG participants?
• Many practitioners provided the intervention; treatment variations may have resulted.

Findings do not support the effectiveness of Reiki under the conditions of the study.

To provide interdisciplinary expert recommendations on how to treat patients with skin reactions undergoing anti–epidermal growth factor receptor (EGFR) treatment.

The task force prepared the first manuscript based on the data retrieved. All panel members were then asked to agree on a consensus statement following a period of meetings and discussions.

The search strategy included literature published until April 8, 2010, and data presented during the Annual Meeting of the American Society of Clinical Oncology (ASCO) 2008; the World Congress of Gastrointestinal (GI) Cancer, Barcelona 2008; the European Cancer Organisation–15 Congress 2008; ASCO GI 2009; and ASCO 2009.

Databases searched were MEDLINE, the Cochrane Library, Cochrane Central Register of Controlled Trials, and EMBASE: Drugs and Pharmacology.

Acneform Rash:

• Moisturize.
• Begin topical antibiotic treatment (erythromycin, metronidazole, or nadifloxacin) twice daily for early-stage skin reactions.
• Systemic treatment should be started if grade 2 or higher skin reactions occur. Oral tetracyclines (doxycycline or minocycline) are recommended.

Xerotic Skin:

• Avoid hot showers and excessive use of soaps.
• Return moisture by applying emollients.

Pruritus:

• Skin moisturizer
• Urea or polidocanol-containing lotions

Fissures:

• Treat topically with propylene glycol 50% in water for 30 minutes under plastic occlusion every night, followed by application of hydrocolloid dressing.

Paronychia:

• Daily antiseptic baths to avoid bacterial superinfection.

Dermatology Referral:

• Lesions classified as grade 3 or higher should be managed collaboratively by an oncologist and a dermatologist.

Treatment Adjustments:

• Perform if skin reaction is grade 3 or higher.

Prophylactic Treatment:

• A number of unresolved issues remain, including whether or not to give prophylactic agents, and if given, whether to use topical or systemic approaches.

To date, no evidence-based treatment algorithms exist for the management of these skin reactions. The most important conclusion from this panel is that EGFR-inhibitor–induced skin reactions can be effectively treated at all stages and grades. The panel recommends to intervene as early as possible at the first sign of dermatologic reactions. Basic skin care combined with a specific therapy adapted to the stage and grade of the skin reaction is recommended. Randomized phase 3 trials are needed to make recommendations on prophylactic treatment.

RESOURCE TYPE: Expert opinion

Unable to discern any information about scope or evidence used in this article. Expert opinion.

Recommendations for the management of mild diarrhea include oral hydration, American Dietary Association diet, and lomotil four times per day. For symptoms that persist for more than three days or increase, oral or IV corticosteroids should be used, although no dosages were noted. For severe cases in which steroids do not improve diarrhea, patients should be hospitalized for IV therapy to include hydration and steroids up to 2 mg/kg twice a day. For symptoms that still persist, infliximab 5 mg/kg once every two weeks can be used.

• Limited clinical experience with immune checkpoint inhibitors
• Only patients with melanoma were considered.

Additional studies need to be conducted to determine the best management practice for gastrointestinal side-effect management with immune-checkpoint blocking antibodies in a variety of cancer types.