STUDY PURPOSE: To collect, review, and report on the current evidence on behavioral and educational interventions used to support family caregivers of patients who are receiving end-of-life care

TYPE OF STUDY: Systematic review

• FINAL NUMBER STUDIES INCLUDED = 14 
• TOTAL PATIENTS INCLUDED IN REVIEW: 1,773 total—406 in educational interventions, 1,152 in cognitive behavioral therapy interventions, and 575 in psychoeducational interventions
• SAMPLE RANGE ACROSS STUDIES: Three studies had a sample of 10–50, two had 50–100, five had more than 100, two had more than 200, one hand more than 300, and one had more than 400.
• KEY SAMPLE CHARACTERISTICS: All studies were phase 2 or 3 studies. Eight of 14 studies included caregivers of patients with advanced cancer; mean age of 55–61 years; high percentage of females (70% in 10 studies), Caucasians (60%–80% in seven studies), and spouses/partners (60%–70% in six studies)

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

Educational and behavioral interventions for caregivers of patients with advanced cancer at the end of life appear to be effective. They are difficult to study because of high attrition rates, in part because of the point in the illness trajectory in which one is asked to participate. However, increasing evidence supports that these types of interventions will benefit caregiver competence and well-being. Ongoing study is needed to identify more specifics about the interventions, what makes them successful, and the methods of delivery, the timing, and the dose, as well as what outcomes should be measured and with what instruments. Perhaps some consistency should be developed. The cost-effectiveness of interventions should be considered as well.

• High heterogeneity
• High attrition rates
• About half were smaller studies of quasiexperimental design, and the types of interventions studied were clearly different and should be looked at individually.

Educational and behavioral interventions for caregivers appear to be helpful in improving caregiver outcomes, with statistical improvement seen in a variety of caregiver domains. The type of intervention strategy used seems to influence the specificity and breadth of outcomes influenced, with some showing more results on competence and knowledge and others expanding beyond competence and knowledge to include an additional impact on the emotional well-being and quality of life of the caregiver. All three types of interventions appear to have positive impact. Care must be taken when choosing an intervention, considering what outcome is desire.

STUDY PURPOSE: To evaluate the effectiveness of olanzapine compared to other antiemetic regimens for preventative and breakthrough chemotherapy-induced nausea and vomiting (CINV). A secondary objective is to evaluate the effectiveness of 5 mg compared to 10 mg olanzapine for the prevention of CINV.

TYPE OF STUDY: Meta-analysis and systematic review

• FINAL NUMBER STUDIES INCLUDED = 13 total studies, 10 for prevention and 3 for breakthrough CINV
• TOTAL PATIENTS INCLUDED IN REVIEW = 1,082 patients for prevention and 308 patients for breakthrough
• SAMPLE RANGE ACROSS STUDIES: Prevention studies: 19–241 patients; breakthrough studies: 106–109 patients
• KEY SAMPLE CHARACTERISTICS: Prevention studies: Six studies included patients with HEC, four with both HEC and MEC, and no studies with only MEC. Breakthrough studies: Two studies included patients with MEC, and one study included HEC.

PHASE OF CARE: Active antitumor treatment
 
APPLICATIONS: Elder care

Efficacy of Acute Phase: Olanzapine was statistically superior to non-olanzapine regimens for emesis (RR = 1.10, 95% CI [1.03, 1.17]) but not nausea. The 10 mg olanzapine was statistically superior to a non-olanzapine regimen for emesis and nausea.

Efficacy of Delayed Phase: Olanzapine was statistically superior to standard antiemetic regimens for emesis (RR = 1.31, 95% CI [1.14, 1.52]) and for nausea (RR = 1.50, 95% CI [1.15, 1.97]). The 10 mg olanzapine was statistically superior to a non-olanzapine regimen for emesis (RR = 1.31, 95% CI [1.11, 1.54]) and nausea (RR = 1.50, 95% CI [1.15, 1.97]).

Efficacy Overall: Olanzapine was statistically superior to standard anti-emetic regimens for emesis (RR = 1.41, 95% CI [1.18, 1.68]) and for nausea (RR 1.53, 95% CI [1.18, 1.97]). Olanzapine 5 mg and 10 mg were both statistically superior for emesis, and 10 mg strength was superior for nausea. No studies were available for nausea with 5 mg.

Efficacy of Breakthrough: Only emesis (not nausea) was available for analysis, and olanzapine showed superiority (RR = 2.09, 95% CI [1.63, 2.68]) to non-olanzapine regimens.

Olanzapine is effective in treating emesis at all time points and is effective in treating nausea in the delayed phase. More studies are needed to determine the most effective dosing.

• Limited number of studies included
• Low sample sizes
• A secondary objective was to evaluate the effectiveness of 5 mg compared to 10 mg, but no results were found to answer this objective (5 mg and 10 mg were compared only to non-olanzapine regimens).

Olanzapine should be used as an adjunct medication for the treatment of acute chemotherapy related vomiting, breakthrough vomiting, and delayed CINV.

STUDY PURPOSE: To use meta-analysis technique to examine the short-term and intermediate-term effects of acupuncture on menopause-related symptoms, particularly on hot flashes, in breast cancer survivors

TYPE OF STUDY: Meta-analysis and systematic review

• FINAL NUMBER STUDIES INCLUDED = 7 studies 
• TOTAL PATIENTS INCLUDED IN REVIEW = 391 participants were reported in the paper; 342 subjects were reported in the absract.
• SAMPLE RANGE ACROSS STUDIES: 38–72 participants
• KEY SAMPLE CHARACTERISTICS: The average age was 57.5 years (range = 45–85 years) in the acupuncture group and 57.2 years (range = 43–82 years) in the control group. The participants included women with treatment-induced menopause and natural menopause. Not all subjects had a diagnosis of breast cancer. A total of six studies addressed the impact of acupuncture on hot flash frequency; three studies addressed the impact of acupuncture on hot flash severity, and four studies addressed the impact of acupuncture on other menopausal symptoms.

PHASE OF CARE: Multiple phases of care

Acupuncture produced small-size effects on reducing hot-flash frequency and the severity of menopause-related symptoms. This effect did not persist even one to three months on hot-flash frequency and severity.

• Limited number of studies included
• Low sample sizes
• The exact years searched is unclear.  
• The exact number of subjects is conflicted.
• The exact exclusion strategy was not detailed.
• The exact duration of the sessions was variable, and the methods of assessment were different, which might result in inconsistent results.
• The follow-up was short (less than three months).

Acupuncture and sham control procedures might offer a short-term reduction in the severity and frequency of hot flashes, but more research with larger longer studies is needed.

Low-dose leuprorelin acetate (Lupron^®) 3.75 mg given subcutaneously at least 30 days prior to transplant conditioning regimen and the second injection given 28 days after the first
 

• N = 30
• FEMALES: 100%
• OTHER KEY SAMPLE CHARACTERISTICS: Premenopausal females undergoing bone marrow or peripheral blood stem cell transplantation with high-dose conditioning chemotherapy

• Menstrual bleeding and vaginal spotting during thrombocytopenia were assessed.
• Long-term outcomes related to menstrual status were assessed via measurement of luteinizing hormone, follicle-stimulating hormone, and estradiol measures, but these outcomes are not of interest to this review.

Mean duration of thrombocytopenia was 28 days; only one patient developed menstrual bleeding during this time. No side effects related to leuprorelin acetate were noted.

PHASE OF CARE: Multiple phases of care

The primary outcome was a change in a sleep parameters. The results of the meta-analysis indicated that MBIs had a medium effect size on the improvement of sleep quality, and this effect persisted up to three months after treatment. The weighted mean effect size was -0.43 (95% CI, -0.24 to -0.62), and the long-term effect size (up to three months) was -0.29 (95% CI, -0.52 to -0.06). The sensitivity analysis revealed that MBIs had a significant effect on sleep (g = -0.33, p < 0.001). The moderating effects of components of the intervention, methodologic features, subject characteristics, and the quality of the studies on the relationship between MBIs and sleep were not found (all p values > 0.05). The main interventions used in included studies in which yoga and mindfulness-based stress reduction were employed. Some studies involved the use of meditation, hypnosis, or sleep hygiene interventions. Yoga interventions yielded an effect size similar to that of other individual interventions (g = -0.40, p = 0.71).

This meta-analysis suggested that MBIs yield a medium effect size on sleep quality, and its effects are maintained for up to three months.

Although there was a comprehensive review of the literature, the selection criteria may have limited the studies included in the review, and the search strategies may have influenced the articles obtained. Only RCTs with MBIs reporting improved sleep outcomes may have been published, and studies with negative results may have been missed, causing a publication bias. Analysis was only done across all studies, which had substantially different interventions, some of which included cognitive behavioral therapy, which is shown to be effective in sleep improvement. The validity of calculating results across studies with very different interventions is questionable. Different methods of measurement were used in some studies as well. The included studies all lacked attention control.

The findings of this meta-analysis support the implementation of MBIs into multimodal approaches to managing sleep quality in patients with cancer; however, it should be recognized that this pooled analysis was done across specific interventions that were very different from each other, and there are multiple limitations that affect the strength of these conclusions.

• FINAL NUMBER STUDIES INCLUDED = 9
• TOTAL PATIENTS INCLUDED IN REVIEW = 599
• SAMPLE RANGE ACROSS STUDIES: Not provided

PHASE OF CARE: Multiple phases of care

Overall, the effect size for walking on sleep disturbance was -0.52 (Hedges' g: 95%; CI -0.79, -0.25). There was significant overall heterogeneity among the studies. Multiple subgroup analyses were conducted to explore factors that may contribute to the heterogeneity. The effect size was not associated with age, gender, the duration of the intervention, or adherence rate. An analysis demonstrated no evidence of publication bias. Studies were done before, during, or after treatment for cancer, and the overall effect sizes did not differ according to the timing of the intervention. All studies used walking of moderate intensity, and most studies were done in women with breast cancer. Some studies included additional exercise interventions such as strength training, and some also included psychoeducational interventions.

Walking exercise appears to improve sleep in patients with cancer.

There was a relatively small number of studies included with high heterogeneity. Twelve studies were excluded because they did not report sufficient data to compute an effect size or they did not use a self-reported sleep outcome. These excluded studies, which have been summarized in other PEP^® summaries, did not demonstrate the effectiveness of exercise. This suggests that effectiveness may be overestimated in this analysis.

This analysis provides some support for moderate intensity walking exercise to improve sleep. The findings need to be viewed with caution because of the high heterogeneity of the studies and the contrary findings that were excluded from this analysis. However, walking is a safe activity for patients, and it can be suggested to patients as an approach that may improve sleep. It also could be incorporated into multicomponent approaches to address sleep-wake disturbances.

STUDY PURPOSE: To evaluate the effects of acupuncture in reducing cancer-related pain associated with treatment types

TYPE OF STUDY: Meta-analysis and systematic review

• FINAL NUMBER STUDIES INCLUDED = 36
• TOTAL PATIENTS INCLUDED IN REVIEW: 2,213
• SAMPLE RANGE ACROSS STUDIES: 21–215 patients
• KEY SAMPLE CHARACTERISTICS: Various tumor types

PHASE OF CARE: Multiple phases of care
 
APPLICATIONS: Palliative care

Eleven trials focused on radiation-induced pain, and five focused on surgery-induced pain. The majority of trials (17) focused on general cancer-related pain. Overall analysis showed that acupuncture reduced cancer-related pain with a small effect size (-0.45, 95% CI [-0.63, -0.26]). There was high and significant heterogeneity. In the 17 trials regarding cancer-related pain, the weighted mean effect size was -0.71 (95% CI [-0.94, -0.48]), without significant heterogeneity. Among trials examining radiation-related pain, no effect was found. For surgical-related pain, mean effect size for five randomized, controlled trials was -0.4 (95% CI [-0.69, -0.1]) with high heterogeneity. For patients receiving hormonal therapy, no significant effect was seen.

Acupuncture may be helpful in reducing chronic cancer pain and pain associated with surgical procedures.

• Mostly low quality/high risk of bias studies
• Low sample sizes
• Various types of acupuncture were used, including auricular as well as other acupoint locations.
• Various measures were used, and some studies measured pain outcomes only in terms of patient response as to whether or not they felt better, or practitioner evaluations of the responses.
• No information regarding other interventions or medications used for patients with chronic and acute pain

Evidence regarding efficacy of acupuncture for pain is limited; however, findings from this meta-analysis suggest that it may be helpful for chronic and acute pain in patients with cancer. Effect sizes were small.

To determine if the combination of Lactobacillus acidophilus plus Bifidobacterium bifidum is effective in preventing diarrhea in patients with locally advanced cervical cancer receiving radiation therapy

Patients were randomized to receive either L. acidophilus plus Bifidobacterium bifidum or placebo capsules. Beginning 7 days before and continuing throughout the entire time of receiving radiotherapy, participants took 2 capsules, 2 times each day before breakfast and dinner. Patients needing antidiarrheal medication were given loperamide (2 mg).

• The study reported on 63 patients.
• The median age was 52 years in the placebo group and 47 years in the study group.
• The sample was 100% female.
• All patients had International Federation of Gynecology and Obstetrics (FIGO) stage IIB-IIIB squamous cell carcinoma of the cervix and were scheduled to receive standard treatment for locally advanced cervical cancer (i.e., external beam whole pelvis radiation and brachytherapy plus weekly cisplatin at 40 mg/m²).

The study was conducted in Thailand.

All patients were undergoing the active treatment phase of care.

This was a prospective, randomized, double-blind, placebo-controlled study.

The National Cancer Institute Common Toxicity Criteria, version 2, was used.

• All patients experienced diarrhea; however, the difference in the severity of the diarrhea was significant (p = 0.002). In the placebo group, 55% of patients experienced grade 1 diarrhea, 42% experienced grade 2, and 3% experienced grade 3. In the study group, 91% experienced grade 1 diarrhea, 9% experienced grade 2, and none experienced grade 3.
• The intervention group also had a significantly improved stool consistency (p < 0.001).  
• In the placebo group, 32% of patients needed antidiarrheal medication, compared with only 9% of patients in the study drug group (p = 0.03).

The prophylactic use of the combination of live L. acidophilus plus Bifidobacterium bifidum was shown to be effective in decreasing the severity of diarrhea.

• The sample size was small sample with fewer than 100 patients.
• Cultures were not performed on stool, which could have missed infectious causes of diarrhea. 
• The use of antimicrobials was not mentioned as exclusion criteria.

The prophylactic use of L. acidophilus plus Bifidobacterium bifidum may decrease the severity of diarrhea, improve stool consistency, and reduce the need for antidiarrheal medication in patients with locally advanced cervical cancer undergoing pelvic radiation with concomitant weekly cisplatin.  Further studies need to be done with larger samples.

To evaluate the effectiveness of physical activity on depression and anxiety symptoms, cognitive function, and quality of life in patients receiving androgen deprivation therapy (ADT) for prostate cancer

TYPE OF STUDY: Systematic review

DATABASES USED: MEDLINE, PsycINFO, EMBASE, Informit, Scopus, Cochrane Library, CINAHL

KEYWORDS: Prostate neoplasm, prostate cancer, prostate carcinoma, prostate adenocarcinoma, androgen deprivation therapy, androgen ablation, androgen suppression, hormone therapy, androgen antagonist, androgen agonist, gonadotropin, luteinizing hormone-releasing hormone, antiandrogen, orchidectomy, surgical castration, chemical castration, physical activity, physical exercise, exercise, sport therapy, sport, endurance, aerobic training, resistance training, cardiac training, aerobic activity, resistance activity, and motor activity

INCLUSION CRITERIA: Physical activity interventions, exercise interventions, and supervised and nonsupervised interventions. Participants who were patients with prostate cancer receiving ADT only (or separate results according to cancer and treatment type). All study designs. Pilot studies (no sample size limitations). Published in English.

EXCLUSION CRITERIA: Studies with the additional interventions of psychotherapy or nutritional consultation. Studies about physical activity behavior or motivation. Studies involving outcomes other than depression, anxiety, quality of life, or cognitive function. Studies involving the impact of physical activity on patients with prostate cancer undergoing forms of treatment other than ADT.

TOTAL REFERENCES RETRIEVED: N = 867

EVALUATION METHOD AND COMMENTS ON LITERATURE USED: Reviewed studies for inclusion and exclusion criteria. No appraisal or scoring system used.

• N (studies)  =  7
• TOTAL PATIENTS INCLUDED IN REVIEW: 420 participants with 242 participants receiving physical activity intervention
• KEY SAMPLE CHARACTERISTICS: Men with prostate carcinoma with any disease stage receiving androgen deprivation therapy at least three months after recruitment or on therapy for two months or expected to receive for six months

PHASE OF CARE: Multiple phases of care

Existing data suggest that physical activity improved quality of life. The existing evidence, however, is not sufficiently robust to determine the adequacy of physical activity as an intervention to improve depression, anxiety, and cognitive function outcomes. One study examined impact on depression and found no significant effect.

Preliminary findings support physical activity to improve quality of life in men receiving ADT for prostate cancer.

• Potential for sample selection bias with participants interested in an active lifestyle being more likely to participate
• Three studies did not report comorbidities.
• Social support bias and attention effects with structured fitness environment fostering social interaction
• Very few studies for outcomes of anxiety or depression

Evidence suggests that clinical exercise in the form of resistance and combined aerobic and resistance training programs may be important for the health status and rehabilitation of patients with prostate cancer.

To examine the effects of an online symptom reporting system on caregiver negative mood, preparedness, and perceptions of physical burden

Following recruitment, patients were randomized to either the  Comprehensive Health Enhancement Support System (CHESS) only intervention or CHESS plus clinician report (CR). The CHESS only group of patient-caregiver dyads accessed the CHESS website for coaching, information, and communication resources for advanced-stage cancer care. At baseline and weekly, dyads “checked in” to CHESS to report needs and symptoms informed by the Edmonton Symptom Assessment System (ESAS) and Eastern Cooperative Oncology Group Performance Status. “Checking in” allowed symptom tracking to evaluate patient improvement or decline. Caregivers also reported preparedness and caregiving burden and could pose questions for future clinical visits. The CHESS plus CR group would access the CHESS website as well as have access to the ePRO system (CR) that delivered dyadic tracking information and alerts to clinicians when the patient or caregiver met certain criteria of concern. The ePRO system would support clinicians’ timely response to improve caregiver management of patient symptoms and lessen burden. Intervention technical support was provided to both groups. CHESS intervention access varied from 12–24 months based on patient diagnosis, and caregivers sequentially were assessed following the intervention.

• N = 235 caregiver-patient dyads
• MEAN AGE = 56 years for caregivers
• MALES: 35.8%, FEMALES: 64.2%
• KEY DISEASE CHARACTERISTICS: Recruited patients with advanced-stage prostate, breast, or lung cancer who received usual care, including palliative or curative treatment
• OTHER KEY SAMPLE CHARACTERISTICS: The majority of caregivers were white, spousal caregivers, educated beyond high school, and had moderate comfort with Internet use

• SITE: Multi-site  
• SETTING TYPE: Home  
• LOCATION: Northeast, Midwest, and Southwest U.S. cancer centers

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

• Pooling of two randomized trials of unblinded patient-caregiver dyads
  • Data analyzed by general linear mixed modeling

• ESAS—modified for study; measured dyadic symptom distress; no reliability or validity reported but used in previous studies
• Preparedness Scale (subscale of Family Care Inventory)—used to examine caregiver task preparedness; had sustained high internal consistency (Cronbach’s alpha = 0.79–0.85)
• Physical Burden Scale (subscale of Caregiver Burden Inventory)—used to examine effect of caregiving on caregiver health; high sustained internal consistency (alpha = 0.78–0.85)
• Shortened Version of the Profile of Mood States (SV-POMS)—used to measure caregiver negative mood and depression; sustained high internal consistency (alpha = 0.92–0.96)

Caregivers in the CHESS plus CR group reported more positive moods than those in the CHESS alone group at 6 months (p = 0.009) and 12 months (p = 0.004). However, the two groups did not differ significantly on caregiver preparedness or physical burden at 6- and 12-month assessment.

Online delivery of information, communication, and coaching resources, combined with a format that supports patient and caregiver reporting of symptoms to facilitate clinician-caregiver timely communication, has the potential to improve caregiver mood and minimize distress of patients with advanced-stage cancer.

• Key sample group differences that could influence results—authors report that results may underestimate the potential impact of CHESS plus CR for those who benefit the most
• Findings not generalizable—authors report that the majority of patients in the sample are well-educated Caucasians. This may limit the ability to generalize the results to other ethnic populations. As a result of CR being integrated in CHESS, the study could not assess how CR alone would influence caregiver outcomes.
• Subject withdrawals 10% or greater
• Other limitations/explanation: Lack of blinding for caregivers, patients, and clinicians

Advances in technology offer opportunities for oncology clinicians to partner with patients and their caregivers to promote patient and caregiver health during the cancer trajectory. Issues such as clinician heavy workload and continued clinical focus on patient needs challenge oncology clinicians in redefining workplace approaches to improve outcomes for patients and their caregivers.