To evaluate the impact of mistletoe extract injections on overall survival and quality of life in patients with advanced pancreatic cancer

Escalating doses of mistletoe extract were self-administered by patients as a 1 ml subcutaneous injection three times a week for the duration of the trial (up to one year) by the patient, a family member, or the local treatment center staff. The dose was escalated as follows: 0.01 mg for two injections, 0.1 mg for two injections, 1 mg for five injections, 2 mg for five injections, 5 mg for eight injections, and 10 mg for the remainder of the injections. Patients were evaluated by completing the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-C30) at seven timepoints (at enrollment and before each visit in months 1, 2, 3, 6, 9, and 12). Patients were evaluated by the physician at each visit for the severity of symptoms of cancer (including weight loss) and undesired events.

• N = 168  
• AGE = 98 patients were aged 18–65 years, and 70 patients were aged greater than 65 years.
• MALES: 56%, FEMALES: 44%
• KEY DISEASE CHARACTERISTICS: Locally advanced or metastatic pancreatic cancer
• OTHER KEY SAMPLE CHARACTERISTICS: Not receiving any treatment other than best supportive care

• SITE: Multi-site  
• SETTING TYPE: Multiple settings    
• LOCATION: Serbia

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

Prospective, randomized trial (randomized 1:1 ratio to mistletoe injections or control after stratification for prognosis of good or poor)

• EORTC-QLQ-C30 (five functional scales, nine symptom scales, and one global quality of health scale)
• Common Terminology Criteria for Adverse Events (CTCAE)

All questionnaires were evaluated at the end of the trial. The treatment group received a median of 61.5 mistletoe injections. The treatment improved the global quality of life with statistical significance (p < 0.001) for global quality of life, appetite loss, fatigue, pain, and nausea at various follow-up time periods. The number of questionnaires received at various time points in the study ranged from 0–110 in the control group and 19–110 in the mistletoe group. The number of documented injections ranged from 3–156 per patient. No side effects were reported. The trial was terminated early because of demonstrated efficacy.

The results of the patient-completed quality of life questionnaires were reported with improvements in 13 of the 15 scales in the group treated with mistletoe. The administration of mistletoe was associated with improvements in appetite loss, fatigue, and pain.

• Risk of bias (no blinding)
• Selective outcomes reporting
• Measurement/methods not well described
• Findings not generalizable
• Subject withdrawals ≥ 10%  
• Other limitations/explanation: Patient self-reporting bias; tool scoring not described; limited to one cancer diagnosis; injections were to be self-administered by the patients and there is no information provided on degree of patient adherence to the study regimen; range of injections reported suggests that a number of patients did not receive all of the expected injections; no placebo comparison; large amount of missing data; approach regarding intent to treat analysis is unclear as the statistical methods are described

The findings of this study suggest that mistletoe may be beneficial to patients with advanced cancer for multiple symptoms. The positive findings of this study suggest that additional research in this area is warranted.

Guided imagery was added to a standard antiemetic regimen; subjects in the experimental group listened to a 20-minute audiotape during chemotherapy administration, and the control group received standard antiemetic regimen alone. The intervention was done over three cycles of chemotherapy. The 20-minute tape was listened to 60 minutes prior to cisplatin, the following morning before breakfast, and the following evening at bedtime.

• The study consisted of 28 newly diagnosed chemotherapy-naive patients with cancer who were receiving cisplatin.
• Ages ranged from 33–80 years, and the mean age was 63 years for the control and experimental groups.
• Patients with gastric cancer, malignancies in the upper gastrointestinal (GI) system, or pre-existing disease states of GI tract were excluded.

Subjects were recruited from one oncologist’s practice (inpatients and outpatients) in a large, Midwestern teaching center.

The study included a convenience sample and was nonrandomized.

• The Rhodes Index of Nausea and Vomiting, form 2 (eight-item, five-point, Likert-type, self-report tool) was used to determine each patient's total experiences score.
• The Chemotherapy Experience Survey, which was designed by the researchers, was used to evaluate overall perceptions of the chemotherapy experience. It consists of two parts. The first is a five-point, Likert-type tool with eight word pairs ranging from negative to positive; the second is a rating of overall chemotherapy experience (10 = most negative, 100 = most positive).

• No statistical significance was demonstrated with symptom occurrence and distress.
• Guided imagery did not have a statistically significant effect on patients’ perceptions of the frequency of nausea, vomiting, and retching, as well as associated distress.
• Patients who participated in the guided imagery felt significantly more in control, powerful, relaxed, and prepared than the control group.
• The guided imagery group described their overall experience more positively than the control group.

• Only adult patients receiving cisplatin were included.
• Only one physician's office was used for recruiting the sample (could control antiemetic regimen).
• The scope of the study was limited.
• The study had a small sample size.
• Other limitations include complex monitoring required over three cycles of chemotherapy, communication difficulties, and inability to control hospital setting and activities.

To determine the safety and effectiveness of TBO-filgrastim and filgrastim alone to reduce the duration of neutropenia in recipients of autologous transplantation with multiple myeloma receiving melphalan 200 mg/m²

Two groups with the same diagnosis received filgrastim alone from June 2013 to April 15, 2014, and TBO-filgrastim from April 16, 2016, to February 15, 2015, were analyzed. Three weeks before autologous transplantation, most patients underwent a mobilization process with chemotherapy regimens, including cytoxan, doxorubicin, vincristine, and dexamethasone, and few patients (less than 20%) were mobilized with TBO-filgrastim or filgrastim alone with or without plerixafor. In the conditioning period of transplantation, all patients received melphalan 200 mg/m² on day 1, followed by stem cells on day 0. Five days after transplantation infusion, patients who weighed less than 80 kg were treated with 300 microgram daily and patients weighing more than 80 kg received 480 microgram daily subcutaenous injections of TBO-filgrastim or filgrastim, which was discontinued when the absolute neutrophil count reached more than 1 x 10(9)/L. Patients were also covered with antimicrobial prophylaxis, that is, acyclovir, fluconazole, and ciprofloxacin, given on day 1, and cefepime was started with the first spike of temperature. Those with viral infections and gram-positive organisms associated with colonization were excluded from the study.

• N = 182   
• AGE = 39–71 years
• MALES: 96%, FEMALES: 4%
• CURRENT TREATMENT: Chemotherapy, other
• KEY DISEASE CHARACTERISTICS: Multiple myeloma
• OTHER KEY SAMPLE CHARACTERISTICS: Demographics

• SITE: Single site   
• SETTING TYPE: Inpatient    
• LOCATION: Northwestern Memorial Hospital, Chicago, IL

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

Retrospective cohort study

Hospital database

Significant difference seen in the post-transplantation infection complication with the use of TBO-filgrastim–treated patients (21%) versus filgrastim-treated patients (8%), respectively (p < 0.0185). No significant change was noticed in the stem cell transplantation time.

As per the findings with the use of both TBO-filgrastim and filgrastim, engraftment time was more or less the same, but, in terms of the occurrence of infection, more incidences were noticed in TBO-filgrastim group than the filgrastim group. Moreover, other highlighted views were the cost of the two medications, as TBO-filgrastim is less expensive than filgrastim and has received FDA approval only in one out of six settings.

• Risk of bias (no random assignment) 
• Risk of bias (no appropriate attentional control condition)
• Risk of bias (sample characteristics)
• Selective outcomes reporting
• Measurement/methods not well described
• Measurement validity/reliability questionable
• Findings not generalizable
• Intervention expensive, impractical, or training needs
• Differences in conditioning regimes, growth factor doses, and institution-specific clinical practices

Overall, the study was very limited to the disease and treatment protocols. More focus was on the use of cost-saving medication, which is a decent thought, but in terms of FDA approval, those medications should bring in the market that is already approved by authority and can be implemented sooner to achieve a good quality care.

To evaluate the effects of a general hospital diet (GD) and a neutropenic diet (ND) on the incidence of microbiologically confirmed infections in hematopoietic stem cell transplantation (HSCT) recipients.

In 2006, the organization replaced its ND with a GD that retained restrictions for undercooked meat, fish, and some unpasteurized dairy products but allowed fresh fruits and vegetables. Data were obtained from electronic medical records of consecutive hospitalized HSCT recipients who received the GD or the ND during neutropenia.  All patients were receiving standard antibiotic, antifungal, and antiviral prophylaxis.  The ND excluded all fresh fruits and vegetables, black pepper, raw and undercooked meats and cheeses, cold smoked fish, raw or unpasteurized dairy products, raw miso and grain products, and brewer’s yeast. The GD permitted black pepper and well-washed fresh fruits and vegetables but excluded raw tomatoes, seeds, and grains. Other diet restrictions remained in place.  All patients were placed on these particular diets around the time of neutropenia and reverted back to a GD once neutropenia resolved.

• In total, 726 patients (58.6% male, 41.4% female) were included. 
• Mean age was 57 (range 18–78).
• All patients were HSCT recipients. 
• The majority of patients had myeloma, non-Hodgkin lymphoma, or acute myeloid leukemia.
• Sixty to seventy percent of patients developed neutropenic fever.

• Single site
• Inpatient 
• Chicago

Patients were undergoing the active antitumor treatment phase of care.

This was a retrospective descriptive study.

• Neutropenic fever (defined as a temperature of >101°F or two temperatures >100.5°F with an absolute neutrophil count of <500/mm³)
• All positive microbial cultures from onset of neutropenia until hospital discharge
   

There were significantly fewer confirmed infections in the GD group (p < 0.0272). Diarrhea (p < 0.095) and urinary tract infection (p < 0.003) were more common in the ND group. Overall mortality and hospital length of stay was similar between the groups.  The ND group had a higher rate of infection after resolution of neutropenia, with more frequent Clostridium difficile and vancomycin-resistant enterococci infections (p < 0.07).

Maintaining an ND that restriced fresh fruits and vegetables did not reduce infection and was associated with an increased risk of infection after resolution of neutropenia.

• Risk of bias (no control group, no blinding, no random assignment) 
• Retrospective descriptive study design

The study findings provide further evidence that restricting fresh fruits and vegetables from the diet of patients who are neutropenic is not beneficial.  These findings suggest that such restrictions may have a negative impact.

To determine whether topically administered Caphosol, rinsed orally four times daily at the initiation of conditioning, reduces the duration of severe oral mucositis (OM) compared with placebo among children and adolescents undergoing hematopoietic cell transplantation (HCT)

Supplied Caphosol A (phosphate solution) and B (calcium solution) or sterile 0.9% sodium chloride solution were provided by two unblinded pharmacists after patients were randomized 1:1 between treatment and control groups. The nurses mixed the Caphosol in the syringes to form a pH-neutral supersaturated solution. The children and adolescents rinsed their mouths thoroughly for one minute, gargled, and spit with one-half of the mixed solution. They repeated with the remaining solution for a total rinse time of two minutes. Younger children with small mouths could rinse with a reduced volume. Participants rinsed four times per day (two rinses per episode) at approximately evenly spaced intervals. The therapy was initiated on the first day of conditioning and continued daily until after day 20 or hospital discharge, whichever occurred first. The subjects were assessed daily for OM by trained study staff until refusal by patient to participation, day +2-, or discharge home. Common Terminology Criteria for Adverse Events (CTCAE) criteria were used to assess toxicity.

• N = 220   
• MEAN AGE = 13.7 years
• MALES: 56 placebo, 62 caphosol; FEMALES: 54 placebo, 48 caphosol
• CURRENT TREATMENT: Chemotherapy, combination radiation and chemotherapy
• KEY DISEASE CHARACTERISTICS: Scheduled to undergo myeloablative autologous or allogeneic HCT for any indication
• OTHER KEY SAMPLE CHARACTERISTICS: Patients were aged 4–21 years. Graft sources included bone marrow (BM), umbilical cord blood (UCB), and peripheral blood stem cells (PBSCs). Eligible donors were HLA-matched, mismatched for a single HLA locus of A, B, or C, or DR, BM, PBSCs, or UCB. At least four of six loci matched at A, B, and DR. Patients could not have received palifermin within 30 days and could not have been previously treated with Caphosol. Patients were stratified by type of graft and type of conditioning regimen.

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

• PHASE OF CARE: Active antitumor treatment
• APPLICATIONS: Pediatrics

Phase III, international, multicenter, randomized, double-blinded, placebo-controlled, prospective clinical trial. The primary endpoint was the duration of severe OM (World Health Organization [WHO] score of 3 or greater).

• WHO Oral Toxicity Scale
• Mouth Pain Categorical Rating Scale
• Modified Oral Mucositis Daily Questionnaire
• Opoid analgesic use
• Total parenteral nutrition use
• Fever and neutropenia incidence
• Invasive bacterial infections

The mean duration of severe OM was not reduced among Caphosol (4.5, SD = 5 days) versus placebo (4.5, SD = 4.8; p = 0.99) recipients. No significant differences existed in any of the secondary endpoints between the groups.

Caphosol did not reduce severe OM compared with placebo among children and adolescents undergoing myeloablative HCT.

• Missing data
• Supportive care was not standardized.
• Pretransplantation dental evaluation or ongoing oral care was not collected.
• The study was underpowered.
• The WHO toxicity scale does not identify reasons children do not eat or drink that are unrelated to mouth pain.

Caphosol did not reduce severe OM compared with placebo among children and adolescents undergoing myeloablative HCT. Effective interventions for OM is needed in this and in other populations.

Adult cancer patients receiving moderately emetogenic chemotherapy (MEC) or highly emetogenic chemotherapy (HEC) were randomized to receive the active ReliefBand^® or an inactive device. All patients received scheduled and as-needed antiemetics. Patients wore devices continuously for five days, except during showering and hand washing.

• The study consisted of 49 patients.
• Mean age was 45 years.
• Diagnoses included leukemia, non-Hodgkin lymphoma, sarcoma, breast, head and neck, and lung cancer.
• A variety of chemotherapy regimens were reported that met criteria for MEC or HEC. Many subjects had three to four prior chemotherapy cycles. All received single- or multiday chemotherapy, including myeloablative chemotherapy, for bone marrow transplant.

All participants in this single-site study were inpatients at the University of North Carolina Hospitals.

The study design was a randomized, prospective, double-blind, placebo-controlled trial.

• Patients recorded nausea, vomiting, retching episodes, and antiemetic medications use in diaries daily.
• The Functional Living Index Emesis and tolerability survey were completed at the conclusion of the study.

Patients wearing the ReliefBand experienced less vomiting, retching, and nausea severity over the five-day period than patients wearing the inactive device. Vomiting was statistically and significantly reduced during the delayed period, and nausea was significantly reduced during the acute and delayed periods. Functional Living Index Emesis scores did not differ between the two groups.

• Differences existed in risk factors for emesis, chemotherapy, and antiemetic regimens.
• The sample size was small.
• Patients with pacemakers, low life expectancy, and poor performance status (greater than three) were excluded.

To explore the safety and efficacy of simple lymph node grafting

The lymph node grafting procedure was performed in a day-surgery setting with local anesthetic infiltration at the donor site (groin) and the two recipient sites (wrist and supratrochlear area). A small dose of intravenous ketamine or midazolam was given as sedation. The nodes were grafted into the superficial soft tissue of the affected limb. Subcuticular absorbable sutures were used to close the wounds. Patients did not use their regular compressive therapy for the first six weeks postoperatively so as not to compress the superficial vessels supplying the graft. Each patient received five days of oral flucloxacillin (250 mg every eight hours) as prophylaxis against opportunistic infection.

• N = 10
• AVERAGE GE = 64 years (range = 41–78 years)
• MALES: 10%, FEMALES: 90%
• KEY DISEASE CHARACTERISTICS: Lymphedema
• OTHER KEY SAMPLE CHARACTERISTICS: Eight patients (80%) had breast cancer-related lymphedema, one (10%) had melanoma as the primary malignancy, and one (10%) had metastatic squamous cell carcinoma requiring axillary dissection. The average duration of lymphedema was 3.5 years, and all patients had tried conservative management since onset. All 10 patients were using compressive bandaging on a daily basis prior to involvement in the study. Four patients (40%) had International Society of Lymphology (ISL) stage 3 lymphedema, and the remaining six patients (60%) had ISL stage 2 lymphedema. Nine (90%) patients reported a subjective improvement in their lymphedema. The patient who had no subjective or objective improvement had ISL stage 3 lymphedema that had been established for five years.

• SITE: Single site    
• SETTING TYPE: Outpatient    
• LOCATION: Central Health and Disability Ethics Committee, New Zealand

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

Prospective, interventional study with repeated measures at two, six, and 12 weeks

• Total circumferential volume (TCV) measurements were taken at the ulnar styloid and in 10 cm increments up the arm with patients in a seated position with arms hanging by their sides.

Lymph node grafting is was a safe procedure and should be investigated as an alternative to a microsurgical procedure as treatment for upper limb lymphedema.

• Small sample (< 30)
• Baseline sample/group differences of import
• Risk of bias (no control group)
• Risk of bias (no blinding)
• Risk of bias (no random assignment) 
• Risk of bias (no appropriate attentional control condition)
• Risk of bias (sample characteristics)
• Measurement validity/reliability questionable
• Intervention expensive, impractical, or training needs

Lymph node grafting needs to be investigated. Nurses should advise patients according to the current evidence.

To examine the effects of an 18-week exercise program on preventing an increase in fatigue. The intervention is offered early after diagnosis and incorporated into the daily clinical practice setting.

An 18-week exercise program (two 60 minute aerobic and strength exercise session per week and including cognitive behavioral principles) supervised by a physical therapist. The control arm of usual care maintained their usual physical activity pattern for 18 weeks and then could participate in an exercise program.

• N = 164  
• MEAN AGE: 49.7 years
• FEMALES: 100%
• KEY DISEASE CHARACTERISTICS: Breast cancer diagnosis less than six weeks before recruitment; scheduled for chemotherapy; stage M0; performance status > 60
• OTHER KEY SAMPLE CHARACTERISTICS: No contraindications for physical activity

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

• PHASE OF CARE: Active antitumor treatment

• Two-arm, randomized controlled trial using computer generated 1:1 randomization

• Quantitative data of outcome assessments at baseline, 18, and 36 weeks postintervention.
• Fatigue: Multidisciplinary Fatigue Inventory (MFI) and Fatigue Quality List (FQL
• Quality of Life: EORTC QOL Core-30 and SF-36®
• Anxiety/Depression: Validated Dutch language version of the 20-item Hospital Anxiety and Depression Scale
• Aerobic capacity by cardiopulmonary exercise test with continuous breathing gas analysis; thigh muscle strength by Cybex dynameter; handgrip strength by mechanical handgrip dynameter; body weight/height and physical activity level by Short Questionnaire to Assess Health Enhancing Physical Activity (SQUASH)

Effects were based on an intention-to-treat analysis using within-group and between-group differences. On the MFI, the only between-group difference seen was a lower increase in physical fatigue at 18 weeks in the intervention group. Although there were decreases in general and mental fatigue in the intervention group at 18 weeks, there was no significant between-group differences. There was no between-group difference on the FQL. The EORTC and Hospital Anxiety/Depression Scale showed decreased QOL, decreased anxiety, and increased depression in both groups at 18 weeks with no between-group difference and improvement in both groups at 36 weeks with decreased improvement in the intervention group. Aerobic capacity and muscle strength were improved in the intervention group at 18 weeks but not at 36 weeks.

An exercise program offered early in the treatment phase of breast cancer appears to positively impact physical fatigue, aerobic capacity, and muscle strength.

• Key sample group differences that could influence results
• Intervention expensive, impractical, or training needs
• Subject withdrawals of 10% or greater 
• Other limitations/explanation:  The control group may have had a high baseline activity level that continued throughout the study. Multiple measurements make interpretation difficult. Requires resources to implement exercise program.

There is an opportunity to continue to study the effect of exercise on fatigue in all patients with cancer. It may be challenging to implement a structured exercise program in clinical practice.

To evaluate the impact of dietary and social restrictions on infections among children participating in a clinical trial

Data on infectious complications were abstracted from medical records at the institutions where the patients were treated. At the same time, an international survey was conducted regarding practices in restricting social contacts, pets at home, and food diets. Analysis was conducted by linking institutional survey results with associated patient infection–related outcome data.

• N = 339   
• AGE RANGE = 0–18 years, 30% were between 1–18 years
• MALES: 50%, FEMALES: 50%
• CURRENT TREATMENT: Chemotherapy
• KEY DISEASE CHARACTERISTICS: All had acute myeloid leukemia (AML)
• OTHER KEY SAMPLE CHARACTERISTICS: 59% were deemed high risk for neutropenia

• SITE: Multi-site   
• SETTING TYPE: Multiple settings    
• LOCATION: International

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

• Cohort comparison, retrospective

Infection was defined as clinical signs and symptoms associated with the institution of antibiotics, an isolated pathogen, or an identified infection site though a physical exam or imaging study.

A wide variety of restrictions existed. Over 90% were restricted from attending kindergarten or school, and more than 80% were restricted from eating raw seafood or meat. Higher restriction of social contacts was associated with an increased incidence of bactermia (incidence rate ratio [IRR] = 1.21, p = 0.003). Higher restriction of pets at home was associated with a decreased incidence of pneumonia (IRR = 0.86, p = 0.05). No relationship was observed between food restriction and infections. When adjusted for age, risk stratification, and antibiotic prophylaxis, none of the restrictions used were associated with infections. Patients who were overweight (p = 0.002) or underweight (p = 0.028) had higher risks of infection.

The restriction of social contact, pets at home, and the use of dietary restrictions were not significantly associated with the decreased incidence of infections.

• Risk of bias (no control group)
• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• Key sample group differences that could influence results

The findings suggest that strict neutropenic diets; restrictions of social contact, such as school attendance; and restriction of pets at home do not reduce infections in pediatric patients with neutropenia. These policies need to be questioned and evaluated further for their effects on overall clinical and quality-of-life outcomes.

The goal of the study was to determine utility of substitution of pregabalin for gabapentin therapy in relief of neuropathic pain.

All patients starting on gabapentin and all patients already using gabapentin as monotherapy were offered the choice of replacing their gabapentin with pregabalin. Comparison was made between the groups switched to pregabalin and a cohort group of patients with peripheral neuropathy and pain receiving only gabapentin without a switch to pregabalin.

• The total sample consisted of 40 participants (68% female, 32% male).
• The mean age of those classified as gabapentin responders was 57.3 years (SD = 9.2).
• The mean age of those classified as nonresponders was 54.5 years (SD = 9.8).
• The mean age of those in the gabapentin cohort was 58.4 years (SD = 11.1).
• 38 patients were diabetic, 11 had MGUS, 6 had vitamin B12 deficiency, 34 had idiopathic peripheral neuropathy, 2 had autoimmune conditions, and 2 had multiple myeloma.

The study was conducted at a single site in Canada.

Cohort study

• Toronto Clinical Scoring System (TCSS) was used to measure diabetic peripheral neuropathy.
• EQ-5D: European Quality of Life–5 domains
• EQ-5D VAS: European Quality of Life–Pain Visual Analog Scale

Both gabapentin responder and nonresponders groups had additional pain relief of about 25% following substitution of pregabalin after 6 and 12 months. The percentage of improvement on the EQ-5D VAS was significant (p < 0.025).

Findings show that pregabalin may provide pain relief in this patient population.

• These patients had diabetic and/or five other possible causes of peripheral neuropathy.
• No blinding in the study sample.
• Small sample.
• Few patients had cancer.

The findings support that notion that both pregabalin and gabapentin may provide pain relief in some patients with peripheral neuropathy. The majority of cases were patients with diabetes. Application to patients with cancer is unclear.