Meta-analysis investigating effects of cognitive behavioral therapy (CBT) and patient education (PE) on anxiety in adult cancer survivors

The search included databases from 1993-2004: Medline, PsychINFO, and the Cochrane Database. Search words used: cancer, anxiety, depression, quality of life (QOL), fatigue, stress, pain, physical function, social, self-management, evidence-based, interventions, and random/randomized.

Inclusion Criteria: adult patient with cancer (all types of cancer and all stages), control group, randomization, measurable outcomes of interest (anxiety, depression, fatigue, QOL, physical function, and pain) and at least one follow-up assessment beyond post-treatment, which allowed for examination of duration of effects.

Quality assessed by modified version of Jadad six-item checklist (randomization, double blinding, descriptions of withdrawals and dropouts, statistical analyses, inclusion and exclusion criteria, and adverse effects). Studies were excluded if not randomized or controlled, or had score less than four on checklist, or did not report follow-up data, or did not report data on targeted outcomes. Dissertations excluded

CBT interventions on anxiety (four studies) Individual and group CBT: Large effect noted (g=1.99, p 0.01; 95% CI 0.69-3.31) Of these four studies, a sensitivity analysis revealed a large effect size for individual treatment (g=2.41, p0.01; 95% CI 1.2-3.55) and no effect for group interventions (d=0.03, p+0.82; 95% CI -0.20-0.25) Forest plots representing the effect sizes of CBT on anxiety favor the intervention.

Significance to practice: CBT is effective for short-term management (8 months) of anxiety. Individually based interventions were more effective than those delivered in a group format. Various CBT approaches provided in an individual format can assist cancer survivors in reducing the emotional distress of anxiety.

The single trial using PE to decrease anxiety resulted in no short-term effect on anxiety and did not include long-term follow up on anxiety (d= -.02, p= 0.89; CI-0.36-0.31). Analysis did not consider patient adherence to pharmacologic interventions, which is known to be modest in medical patients.

No cost-benefit implications.

DOI Link: 10.1038/sj.bmt.1705418

To determine whether itraconazole is superior to fluconazole in the prevention of invasive fungal infections, particularly invasive aspergillosis, in hematopoietic stem cell transplant (HSCT) recipients and patients with acute leukemia (AL).

Patients were stratified to either high or low risk based on type of therapy or disease.  High risk included patients undergoing allogeneic HSCT or patients with relapsed/resistant AL.  Low risk included patients undergoing autologous HSCT or newly diagnosed patients with AL receiving induction.  Patients were then randomized to receive either itraconazole or fluconazole prophylaxis in each risk stratum, using a random number generator, in blocks of four.  Intravenous (IV) preparations were used only if the patient could not tolerate oral medications and was switched back to oral as soon as the patient tolerated oral medications.  Antifungal prophylaxis was continued until the resolution of neutropenia, for a maximum of eight weeks. Antibacterial prophylaxis was not administered.  Fluconazole was given in a dose of 400 mg once daily, and itraconazole was given at 200 mg twice daily.

• One hundred ninety-five patients were included.
• Median patient age was 49 (range 18–73) in the fluconazole arm and 50 (range 17–75) in the itraconazole arm.
• In the fluconazole arm, 56% of patients were male and 43% were female.  In the intraconazole arm, 63% of patients were male and 33% were female.
• Patients received autologous HSCT (56% in the fluconazole group, 52% in the itraconazole group), allogeneic HSCT (19% in the fluconazole group, 18% in the itraconazole group), haploidentical HSCT (3% in the fluconazole group, 4% in the itraconazole group), or no transplant (21% in the fluconazole group, 22% in the itraconazole group).  Per the above criteria, patients were considered low-risk (74% in the fluconazole group, 72% in the itraconazole group) or high-risk (25% in the fluconazole group, 24% in the itraconazole group).  Mean duration of neutropenia for high-risk patients was 13.4 days (SD = 6.1) in the fluconazole arm and 15.4 days (SD = 9.7) in the itraconazole arm.  Mean duration of neutropenia in low-risk patients was 10.7 days (SD = 6.4) in the fluconazole arm and 10.8 days (SD = 7.0) in the itraconazole arm.  Patients receiving group 1 chemotherapy (consisting of standard induction and consolidation regimens for AL and chemotherapy-based conditioning regimens for autologous bone marrow transplant [BMT]) included 77% in the fluconazole arm and 76% in the itraconazole arm.  Patients receiving group 2 chemotherapy (consisting of total body irradiation-based conditioning regimens for autologous or allogeneic BMT) included 10% in the fluconazole arm and 8% in the itraconazole arm.  Patients receiving group 3 chemotherapy (consisting of reduced intensity or T cell depleted conditioning regimens, which included anti-thymocyte globulin and/or fludarabine for allogeneic or haploidentical BMT) included 12% in both groups.

• Single site  
• Inpatient 
• This study was conducted at a single hematology and BMT center, comprising a 15-bed BMT unit and an 11-bed hematology unit, on hospitalized patients in these two units, in a protected environment using a high-efficiency particulate absorption filtration system.

Patients were undergoing the active treatment phase of care.

This was a randomized trial comparing oral and IV itraconazole with oral and IV fluconazole.

Toxicity was graded from 0 to 4 according to the National Cancer Institute Common Toxicity Criteria.

Itraconazole was not found to be more effective than fluconazole in preventing invasive fungal infections (IFIs) in neutropenic patients after chemotherapy for AL or after HSCT.  Both drugs were successful in preventing invasive candidal infections.  Invasive aspergillosis (IA) was not as decreased in the itraconazole arm as expected, although the mortality from IA  was lower in the itraconazole arm.

Fungal prophylaxis is important in patients with AL and those undergoing HSCT.  Both itraconazole and fluconazole seem to be effective in preventing IFIs and IA, but neither appeared to be superior to the other in this study.  Itraconazole seems to be less well tolerated in the oral form due to gastrointestinal side effects, although none were significant.  Neither drug completely prevented IA, which causes significant morbidity and mortality; therefore, more research is needed for drugs that have better prophylaxis against IA.

This was a nonblinded study leading to bias in the assessment of efficacy and adverse events, as well as the evaluation of response and causes for adverse events.  There was a lack of itraconazole blood measurement.  Antifungal prophylaxis was only used during the early period at risk (during the neutropenic period), the high-risk patients, especially, are at risk for significantly more time than just the neutropenic period.  Antifungal prophylaxis should be continued for an extended period after engraftment, especially in patients undergoing allogeneic HSCT.  This information is useful for most hematologic malignancy but may not be generalizable for patients with solid tumors.

Education related to antifungal prophylaxis and the necessity of taking these medications is important.  Nurses can educate about the expected side effects, especially the GI side effects of itraconazole when given orally.

DOI Link: doi: 10.1186/1471-2407-12-6

STUDY PURPOSE: To examine the effectiveness of conservative treatments for lymphedema

TYPE OF STUDY: Systematic review

DATABASES USED: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, AMED, and CINAHL 1990–January 2010

KEYWORDS: Search terms provided in online file

INCLUSION CRITERIA: RCT or observational study with comparison group, pediatric and adult patients with secondary lymphedema for any reason except filariasis infection

EXCLUSION CRITERIA: Pharmacologic or surgical treatment for lymphedema

TOTAL REFERENCES RETRIEVED: 6,814 articles were evaluated.

EVALUATION METHOD AND COMMENTS ON LITERATURE USED: Jadad scale used for RCTs; Newcastle-Ottawa Scale used  for observational studies

• FINAL NUMBER STUDIES INCLUDED = 44 (32 with cancer)
• SAMPLE RANGE ACROSS STUDIES: 21–150
• KEY SAMPLE CHARACTERISTICS: Cancer evidence was in patients with breast cancer.

PHASE OF CARE: Not provided

Six RCTs involving intermittent pneumatic compression (IPC) were used. Two showed IPC had benefit over CDT or self-massage, and three did not show IPC to be any better than massage, skin care, or elastic sleeve; one compared different IPC devices. Six RCTs using massage-based treatments were used, and five showed no benefit. Four studies of low-level laser were used. Three showed low-level laser was superior to exercise, sham laser, or usual care, and one shows that low-level laser was better than sham laser at some time points in the study. Dieting yielded conflicting findings. Equivocal results were seen for ultrasound, modified manual lymph drainage, and compression stockings.

This review provides limited evidence of effects of conservative treatments for lymphedema, and no conclusions about the most effective conservative approach are possible from this review.

Most studies had “fair” quality. Follow-up time frames in studies varied considerably. The majority of studies were among breast cancer patients only. It is surprising that this review did not include any studies involving CDT.

Findings from this review showed that most interventions reduced limb volume and were not associated with any significant patient harms. Dieting alone does not appear to be particularly effective for limb volume reduction. Patients may benefit from a variety of conservative approaches to manage lymphedema. Ongoing research is needed to determine comparative effects of various approaches.

DOI Link: doi: 10.1158/1078-0432.CCR-0772-03

Women with breast cancer receiving high-dose infusional paclitaxel (725 mg/m² for 24 hours) in combination with doxorubicin (165 mg/m² for 96 hours) and cyclophosphamide (ACT) (100 mg/kg for two hours) were studied on two autologous peripheral blood stem cell transplant protocols—one with and one without amifostine (740 mg/m² administered over 10 minutes before and 12 hours after initiation of the paclitaxel infusion).

• N = 31
• KEY DISEASE CHARACTERISTICS: Women with high-risk breast cancer eligible to receive ACT with or without amifostine, and stable patients with stage IV breast cancer eligible to receive ACT with amifostine

Women in each group were evaluated before ACT and 20–40 days later with neurologic examination, a composite peripheral neuropathy score, peroneal and sural nerve conduction studies, and quantitative sensory testing. The same technologist performed all nerve conduction studies.

No significant effect was seen of amifostine on chemotherapy-induced peripheral neuropathy after high-dose paclitaxel in regard to nerve conduction parameters, quantitative sensory testing, or composite neuropathy scores.

• The study’s small sample size and lack of randomization to treatment with amifostine may bias results.

DOI Link: doi: 10.1158/1078-0432.CCR-0772-03

Women with breast cancer receiving high-dose infusional paclitaxel (725 mg/m² for 24 hours) in combination with doxorubicin (165 mg/m² for 96 hours) and cyclophosphamide (100 mg/kg for two hours; ACT) were studied on two autologous peripheral blood stem cell transplantation protocols, one with and one without amifostine (740 mg/m² administered over 10 minutes before and 12 hours after initiation of the paclitaxel infusion).

The sample consisted of 31 women with high-risk breast cancer and who were eligible to receive ACT with or without amifostine, and patients with breast cancer who were at stable stage IV and eligible to receive ACT with amifostine.

The study had a nonrandomized comparison group design.

Women in each group were evaluated before ACT and 20–40 days later with neurologic examination, a composite peripheral neuropathy score, peroneal and sural nerve conduction studies, and quantitative sensory testing. The same technologist performed all nerve conduction studies.

No significant effect was noted for amifostine on chemotherapy-induced peripheral neuropathy after high-dose paclitaxel in regard to nerve conduction parameters, quantitative sensory testing, or composite neuropathy scores.

The study’s small sample size and lack of randomization to treatment with amifostine may bias results.

DOI Link: doi: 10.3390/ijerph13090929

To evaluate the degree to which a rational emotive behavioral approach and techniques can benefit patients and family members in hospice care

A manual for the intervention approach was developed to guide the treatment process. It was based on a cognitive behavioral approach, including cognitive restructuring, confrontation, therapeutic alliance, acceptance, dialogue, reframing, use of metaphors worksheets, and motivational activities. The intervention was provided for 10 weeks in 45-minute sessions weekly, with four weeks of follow-up meetings in each household. Study assessments were conducted at baseline, after the 10-week intervention, and after the four weeks of follow-up, using self-report instruments and structured interviews. Participants randomized to the control intervention received usual care involving spiritual support, caregiving, counseling, etc., for the same amount and duration of time.

• N = 32 patients and 52 family caregivers   
• MEAN AGE = 48.33 years (SD = 6.17)
• MALES: 15.38%, FEMALES: 84.62%
• CURRENT TREATMENT: Not applicable
• KEY DISEASE CHARACTERISTICS: Breast, cervical, and prostate cancers; all patients were at terminal stage of disease. 
• OTHER KEY SAMPLE CHARACTERISTICS: The majority lived in rural settings.

• SITE: Single site   
• SETTING TYPE: Home    
• LOCATION: Nigeria

• PHASE OF CARE: End-of-life care
• APPLICATIONS: Palliative care 

Randomized, controlled trial

• Patients and Family Caregivers' Assumptions Questionnaire
• Death Anxiety Questionnaire
• Kessler Psychological Distress Scale

Overall baseline problematic assumptions and death anxiety were high, and distress scores showed severe distress. Respeated measures analysis of variance (ANOVA) showed that the intervention program had a significant effect on problematic assumptions (p = 0.00), death anxiety (p = 0.00), and distress (p = 0.00) in caregivers and patients compared to those in usual care. This difference was maintained at follow-up.

The findings show that cognitive behavioral techniques and the specific approach used here were effective in reducing problematic assumption, death anxiety, and psychological distress among patients with cancer and their family caregivers.

• Small sample (< 100)
• Risk of bias (no blinding)
• Findings not generalizable
• The study involved mainly patients and family members living in rural Nigeria; the results may not be applicable to other cultural groups.

The findings demonstrated that cognitive behavioral approach techniques are helpful in reducing stress and anxiety in patients in hospice and their informal caregivers. Nurses can incorporate these types of approaches into usual counseling and supportive interventions with caregivers and patients.

DOI Link: doi: 10.4103/0378-6323.32755

To investigate whether the prophylactic use of topical betamethasone 0.1% can prevent acute radiation dermatitis

Patients were randomly assigned to one of three groups: betamethasone, petrolatum, or no treatment. The treatment delivery protocol was the same for all groups. Education on the amount of skincare product to use was consistent.

• The study sample (N = 51) was comprised of female patients with breast cancer (stage I or II).
• Age of the sample ranged from 34–66 years.
• Patients did not undergo concurrent chemotherapy or systemic corticosteroids.
• The total radiation dose was 50 Gy to the chest wall, with patients receiving a single 2 Gy per day for five days a week.
• A cobalt-60 unit was used, which does not have the same skin-sparing abilities of the 3-D conformal or intensity-modulated radiation therapy.

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

• Patients were assessed using the Radiation Therapy Oncology Group acute radiation morbidity scoring criteria for acute radiation dermatitis.
• Statistical analysis was done using non-parametrical tests (Kruskal-Wallis test and Friedman test).

By the third week (30 Gy), 26.3% of the betamethasone group had grade 1 skin toxicity compared to 64.7% and 66.7% of the petroleum and control groups, respectively (p = 0.027). By the seventh week, 15.8% of the betamethasone patients had grade I skin toxicity, 6.7% of the control group had grade I, and 100% of the petroleum group had grade II or higher.

Acute radiation dermatitis increased over time for all groups. The betamethasone group had lower prevalence at one time point; however, at the end of treatment, acute radiation dermatitis was lower in the untreated controls.

• Skin assessment did not include the inframammary fold.
• No statement if a patient missed a treatment.
• Patient perceptions, such as pain or itching, were not addressed.
• Though the study stated the aim was to prevent acute radiation dermatitis, more than 90% of the sample had grade 2 or higher acute radiation dermatitis at the beginning of the study.
• The study had no blinding and a small sample size, with less than 100 participants.

DOI Link: doi: 10.1007/s00520-012-1546-0

To review the effect of low-level laser therapy (LLLT) in the management of breast cancer-related lymphedema

Databases searched were MEDLINE, EMBASE, CINAHL, Center for Reviews and Dissemination, PEDro, and Cochrane Database of Systematic Reviews. Search keywords were breast cancer, lymphedema, and low level laser therapy. Studies were included in the review if they

• Were randomized controlled and uncontrolled trials. 
• Had a sample of women with unilateral lymphedema secondary to breast cancer surgery
• Had a sample that experienced a limb volume increase greater than or equal to 100 ml compared to the contralateral limb. 
• Compared LLLT  to no treatment, placebo, or another therapy.

 

The total references retrieved was 10. Literature was evaluated using Sackett''s levels of evidence. The PEDro Scale was used to rate the methodological quality of trials.

• The final number of studies included was eight. 
• The total sample across studies was 210 patients, with a range of 10–64.

The study has clinical applicability for late effects and survivorship.

A variety of doses and laser wavelengths were studied with different definitions for lymphedema.  3b dual wavelength scanning was used in three studies with favorable results. Hand-held 3b lasers were used in five studies where the laser was applied directly over fibrotic or congested areas. All doses were within the therapeutic window. In most studies, treatment was three times weekly with up to 18 total sessions over three to four months. Various methods were used to measure outcomes and reliability of measures was not discussed. Sometimes laser was used in combination with other co-interventions that could have influenced results.

There is moderate to strong evidence for effectiveness of LLLT for the management of breast cancer-related lymphedema.

• The review had a limited number of studies. 
• The variation of methods of outcome measurement and variability of LLLT treatment regimens makes comparison across studies difficult. 
• Co-interventions used in studies could intervene to affect results. 
• There were substantial baseline differences in study sample groups (the duration and severity of lymphedema varied greatly).

Findings suggest moderate to strong support for use of LLLT to manage lymphedema among patients with breast cancer. Research in this area needs to incorporate reliability of lymphedema measurement and common definitions of lymphedema

DOI Link: doi: 10.1007/s00520-010-0985-8

To review the Multinational Association of Supportive Care in Cancer (MASCC) guidelines for low- or minimal-emetic potential anticancer agents

Experts from MASCC met in Perugia in 2009 to revise the MASCC consensus guideline.

Searched keywords were antiemetic, low, minimal, guidelines, chemotherapy, dexamethasone, 5-HT₃ receptor antagonists, and dopamine receptor antagonists

Studies were included in the review if they involved chemotherapeutic agents with low or minimal emetic potential.

Studies were excluded from the review if they involved agents with moderate or high emetic potential.

The guidelines apply to multiple phases of care.

This review has applications for elderly and palliative care.

For chemotherapy with minimal emetic potential, the following is recommended.

• No antiemetic prophylaxis should be given in patients with no prior history of nausea and vomiting.
• Single-agent dexamethasone, 5-HT₃, or dopamine receptor antagonists should be given for nausea and vomiting.

For chemotherapy with low emetic potential, single-agent dexamethasone, 5-HT₃, or dopamine receptor antagonists should be administered.

More data is needed on the emetic potential and outcomes related to newer agents in oncology. A lack of clinical data is available on the emetic potential of some agents (e.g., cytotoxics, newer targeted agents), and the emetic potential has not been divided into acute or delayed.

DOI Link: doi: 10.1007/s00520-012-1696-0

To determine the effectiveness of the addition of a seven-day aprepitant dose to standard triple-drug antiemetic therapy for patients receiving multiday, highly emetogenic chemotherapy (HEC)

Patients were given 125 mg of oral apreipitant on day 1 and 80 mg of apreipitant on days 2-7, a 5-HT₃ on days 1-5, and 8 mg of dexamethasone on 1-8 for each cycle of chemotherapy.  Assessment of efficacy was performed via daily diaries, and analysis of outcomes was done for each chemotherapy cycle.  Rescue medication was lorazepam, metoclopramide, haloperideol, or prochlorperazine.

• The study consisted of 50 participants.
• The median age was 30 with a range of 19-60.
• The sample was 96% male and 4% female.
• All patients had germ cell cancer.

 

The study was conducted at a single outpatient site in Austalia.

This was a prospective, observational trial.

Patients recorded the number of vomiting episodes and severity of nausea and an 11-point numeric scale in diaries.

 

• The majority of patients (96%) reported no emesis on day 1, and an average of 82% (95% CI 68-91) had no emesis on days 1-7 in cycle 1.  This was maintained over 4 cycles, with more than 80% reporting no emesis on any day.
• Nausea was not as well controlled. In cycle 1, 71% of patients experienced no nausea on day one but only 27% reported no nausea days 1-7.  The pattern of nausea was similar for all cycles.
• Authors stated that adherence was good, but they did not report actual adherence to the medications.

This study adds to the current evidence for effectiveness of triple-drug antiemetic therapy for patients receiving HEC. The findings suggested that additional days of neurokinin 1 (NK1) may improve outcomes. The findings showed that nausea continues to be poorly controlled with current regimens.

• The sample size was small with fewer than 100 participants.
• A risk of bias exists because no control group, blinding, or random assignment was included in the study design.
• The outcomes reporting was selective.
• The measurement validity and reliability was questionable.
• No information on nausea severity or use of rescue medications was provided, so it was not clear how use may have varied and influenced results. 
• No data was provided on adherence or compliance with diary documentation of symptoms and episodes of vomiting.
• Findings cannot be directly compared to others because this study did not evaluate and define outcomes in terms of complete control per phase of chemotherapy administration.

Triple-drug antiemetic therapy for patients receiving HEC is the current established recommendation for management of chemotherapy-induced nausea and vomiting (CINV).  The addition of further NK1 may improve control. Although current therapies appear to control vomiting well, nausea continues to be a problem for patients.  Ongoing research aimed at nausea control is needed.