STUDY PURPOSE: To determine whether colony-stimulating factors or antibiotic prophylaxis are optimal choices for the prevention of febrile neutropenia in patients receiving docetaxel-cyclophosphamide chemotherapy

TYPE OF STUDY: Systematic review

• FINAL NUMBER STUDIES INCLUDED = 14 
• TOTAL PATIENTS INCLUDED IN REVIEW = 2,535
• SAMPLE RANGE ACROSS STUDIES: 30–982

PHASE OF CARE: Active antitumor treatment

Hospital admission because of febrile neutropenia (FN) occurred in a median of 13% of patients, and 7.5%, on average, had delays in chemotherapy because of FN. DC chemotherapy was associated with median FN rates of 6.6% with and 31.3% without primary prophylaxis.

FN prophylaxis was associated with lower FN rates; however, the study results could not differentiate the efficacy of antibiotics versus colony-stimulating factors.

• Limited search
• Mostly low quality/high risk of bias studies
• Most studies were retrospective.

Patients receiving DC chemotherapy benefit from primary FN prophylaxis. Insufficient evidence exists to determine the comparative efficacy of prophylaxis with antibiotics versus colony-stimulating factors.

To evaluate the effect of bupivacaine-morphine patient-controlled epidural analgesia (PCEA) versus IV morphine patient-controlled analgesia (PCA) on pain at rest and during coughing and on time to potential discharge, length of hospital stay, nausea, vomiting, pruritus, and overall patient satisfaction

Control group received IV morphine PCA 1 mg/hour basal rate with rescue dose of 1 mg every 10 minutes as needed by PCA. The women in the treatment arm had thoracic epidural morphine-bupivacaine PCEA 100 mcg/ml with 0.05% bupivacaine basal rate 4 mg/hour with rescue boluses of 4 ml every 30 minutes. In both treatment arms, therapy was titrated to ensure adequate pain control with treatment of any side effects.

• The sample was composed of 135 patients.
• All patients were 18 years old or older. In the PCEA group, mean patient age was 57 years. In the PCA group, mean patient age was 55 years.
• All participants were female.
• All participants were women who had undergone abdominal surgery by laparotomy for treatment of a gynecologic disorder. More than 75 of participants had a diagnosis of gynecologic cancer.

• One site
• Inpatient cancer center
• Memorial Sloan-Kettering Cancer Center, New York City

Prospective randomized trial

Visual analog scale (VAS), a 10-point pain scale regarding side effects

• For the first three postoperative days, the mean VAS scores reflecting pain while coughing were significantly lower (P < 0.05) in the PCEA arm than were the mean VAS scores in the PCA group.
• On Day 1, the mean at-rest pain score was 3.3 in the PCEA group and 4.3 in the PCA group (P = 0.01).
• For the first six days, women treated with PCEA had significantly less pain (P < 0.003) at rest and while coughing than did women in the PCA group.
• Time to discharge did not differ significantly between the two groups.
• Compared to women in the PCEA group, significantly fewer women in the PCA group had pruritus.
• Investigators noted no significant differences in the rates of nausea during the first two days.
• Significantly more women had postoperative urinary retention in the PCEA group than did women in the PCA group.
• Over the first six postoperative days, global satisfaction scores showed that women in the PCEA group were significantly more satisfied with their pain therapy than were women in the PCA group.

For the first six postoperative days, women treated with PCEA morphine-bupivacaine had less pain at rest and during coughing than did women treated with conventional IV PCA. The incidence and severity of adverse effects were not significantly different between groups.

• This study had a risk of bias due to no blinding.
• According to calculations, the sample size should have been 120 per arm; however, the study had a sample size of 135 total. Therefore, lack of power is a limitation of the study.

Nurses must be knowledgeable about postoperative care, the complications associated with abdominal surgery, and optimization of perioperative PCEA.

To investigate the relative merits of the current guidelines advising patients to avoid ipsilateral blood draws, injections, blood pressure measurements, trauma, and wearing compression sleeve for air travel to reduce the risk of developing lymphedema

Patients with newly diagnosed breast cancer from 2009–2014 were prospectively screened for lymphedema in bilateral arms using an optoelectronic perimeter, an infrared light to measure arm circumference and volume. Participants were measured at preoperative baseline, postoperatively, and after chemotherapy and/or radiation therapy at regular follow-up oncology visits. (Regular means between three to seven months.) Patients were also measured at their request. At each measure, patients completed a questionnaire and reported on blood draws, injections, blood-pressure readings, trauma, and frequency and length of flights. A total of 3,040 measurements were made.

• N = 632   
• AGE = 52 years
• BMI: 26
• FEMALES: 100%
• CURRENT TREATMENT: Chemotherapy, radiation, immunotherapy
• KEY DISEASE CHARACTERISTICS: Patients newly diagnosed with breast cancer with six months of postsurgical follow-up; patients with axillary lymph node dissection or sentinel lymph node dissection; a history of cellulitis was okay; patients with bilateral lymphedema
• OTHER KEY SAMPLE CHARACTERISTICS: Exclusion criteria: Patients with metastases or who wore a compression sleeve when flying

• SITE: Outpatient clinic visit at Massachusetts General Hospital    
• SETTING TYPE: Outpatient
• LOCATION: Boston, MA

PHASE OF CARE: At start of breast cancer, up to six months of follow-up

A prospective screening study to assess for lymphedema in patients with newly diagnosed breast cancer from 2009 to 2014

The researchers used an optoelectronic perimeter to calculate bilateral arm volumes preoperatively, postoperatively, again after chemotherapy and/or radiation therapy, and at regular follow-up oncology visits (every three to seven months). The relative volume change (RVC) formula was used to quantify limb volume changes in unilateral limb involvement, and the weight-adjusted volume change (WAC) formula was used to quantify limb volume changes for bilateral limb involvement. Lymphedema was defined as RVC or WAC scores greater than or equal to 10%. Patients completed the questionnaire regarding limb risk behaviors, including blood draws, blood pressures, injections, and trauma.

No association of nonprecautionary limb behaviors and the development of lymphedema existed among patients with breast cancer in this prospective study. ALND, BMI greater than or equal to 25, RLND, and cellulitis were associated with increases in limb volume.

• Unintended interventions or applicable interventions not described that would influence results 
• What was said to the participants at the start of therapy is unclear.
• The discussion section clearly states that the authors provided “persistent recommendations to avoid blood draws, blood pressure reading and injections in the at-risk limb to reduce the risk of lymphedema,” which appears to be an unintended intervention.

Although most lymphedema precautionary behaviors are “expert opinion,” this study does not dismiss the need for such affected limb precautionary behaviors. Continue with all such precautionary behaviors. Just as all patients do not develop lymphedema, patients develop lymphedema from an array of activities.

To evaluate the efficacy of a brief cognitive behavioral therapy to manage chemotherapy-related cognitive dysfunction

• Participants were randomized into a memory and attention adaptation training (MAAT) group or a waitlist to receive the intervention.
• Pre- and post-intervention cognitive testing was performed.
• The intervention consisted of 30- to 50-minute biweekly individual office visits of brief cognitive behavioral therapy to enhance cancer survivor skills for self-managing and coping with cognitive failures of daily life. The sessions included how to self-awareness training and compensatory strategies.
• Follow-up contact between visits was conducted by telephone.
• The intervention lasted eight weeks, for a total of four office visits.
• Participants in the intervention arm received a workbook.
   

• The sample consisted of 40 participants whose mean age was 50.3 years (SD = 6.4).
• The sample was 100% female.
• Participants had been diagnosed with stage I and II breast cancer.
• Participants had completed a mean total of 16.38 years of education (SD = 2.4).
• All participants were postmenopausal. 
• All received chemotherapy. 
• Twenty-three participants were taking hormonal therapy during study (30% waitlist group, 27.5% MAAT group).  
   

• Single site
• Outpatient setting
• Lebanon, New Hampshire, USA
   

• Patients were in the transition phase after initial treatment.
• The clinical applications are for late effects and survivorship.
   

Randomized clinical trial

• Multiple Ability Self-Report Questionnaire (MASQ)    
• California Verbal Learning Test-2 (CVLT-II)
• Trail Making Number-Letter Trial from the Delis Kapan Executive Function System (DKEFS)
• Color-Word-Interference from the DKEFS
• Color-Word and Switching Trials from the DKEFS
• Digit Symbol-Coding form the Wechsler Adult Intelligence Scale-III (WAIS-III)
   

Participants who received the intervention experienced a significant improvement in verbal memory, as measured by the CVLT-II total score (p < 0.05). In contrast, no difference was found in either information processing speed (DKEFS scales and WAIS-III subscale) or patients’ self-report (MASQ) of their cognitive functioning.

Although the cognitive behavioral therapy intervention was formulated to assist patients in dealing with memory and attention problems, significant improvement in total score was found only in verbal memory. Because improvement was not found in information processing speed, alternative strategies may need to be developed to help patients compensate in other cognitive domains. Although patients reported high satisfaction with the intervention, self-report scores did not indicate any improvement in their cognitive functioning.

• The sample size was less than 100.
• The number of intervention sessions was limited, which limited the generalizability of results and the feasibility of the intervention.
• No attentional control condition was used.
   

Ongoing cognitive problems have been reported by many patients after completion of cancer treatment. Cognitive behavioral training has been suggested as a strategy to assist patients in dealing with the impact of these problems. However, further studies are needed to determine strategies for specific cognitive domains that are feasible in the outpatient setting.

The study was conducted to examine Memory and Attention Training (MAAT) as a possible intervention for cognitive dysfunction. MAAT consists of four cognitive-behavioral components.

1. Education on memory and attention
2. Self-awareness training
3. Self-regulation emphasizing arousal reduction through relaxation training, activity scheduling, and pacing
4. Cognitive compensatory strategies training, which consists of self-instructional training, verbal rehearsal of auditory information, schedule-making, external cueing, and outlining written material

The MAAT intervention contained

1. Workbooks with written information about chemotherapy and memory difficulty, and step-by-step guides on how to practice and apply compensatory strategies
2. Four monthly visits, lasting 30–50 minutes, that focused on knowledge of chemotherapy-associated memory problems, identification of at-risk situations where memory failures arise, and learned and rehearsed compensatory strategies relevant to participants' difficulties
3. Three interim phone calls to assist participants in applying compensatory strategies
4. Homework between phone calls to further apply the compensatory strategies.

• The number of participants was 29.
• All participants were Caucasian and female.
• All participants had breast cancer.
• The average participant age was 56.
• Participants had an average of 15.40 years of education, and their mean IQ was 112.82.
• Participants were an average of 8 years post-chemotherapy and had reported memory and attention problems.
• Telephone screenings were completed for psychiatric disorders using PRIME-MD.
• Participants who had previous central nervous system (CNS) radiation or intrathecal therapy were excluded from the study. Those who had psychiatric mental health issues or neurologic, CNS-related, or neuroehavioral risk factors were also excluded.

• Rural
• Regional academic cancer center (Dartmouth-Hitchcock Medical Center)
• Private oncology offices in Northern New England

This was a prospective, longitudinal, single-arm pilot study.

• California Verbal Learning Test-II (CVLT-II) for verbal memory
• Logical Memory I and II for memory
• Digit Symbol for graphomotor skills
• Trail Making Test (TMT), Parts A and B, for visual attention, motor speed, and cognitive flexibility
• Stroop Color-Word Interference Task for executive function
• Center for Epidemiologic Studies Depression Scale for depression
• State-Trait Anxiety Inventory for anxiety
• Quality of Life-Cancer Survivors (QOL-CS) for cancer-related quality of life
• Multiple Ability Self-Report Questionnaire (MASQ)

Participants rated the MAAT program with high levels of general satisfaction post-treatment, and reported that it was helpful with improving memory, attention, and compensatory skills.

Neuropsychological test results revealed improvement on verbal memory (p = 0.001), executive functioning (p < 0.001), and psychomotor functioning (p = 0.001). Moderate to large treatment effect sizes (0.47 to 0.67) were observed in the MASQ total score and subscales immediately post-treatment, and the visual perceptual scale (0.63) was significant at the two month follow-up. Self-report in cognitive function in participants’ daily lives improved significantly over baseline and was sustained across all follow-up periods (p = 0.001). Similar patterns of improvement were observed on MASQ subscales of attention and concentration, spatial memory, verbal memory, and language. 

MAAT is a feasible and possibly effective cognitive-behavioral, non-pharmacologic management approach to a common problem for many cancer survivors.

• The sample size was small and lacked diversity. 
• The study had no comparison control group or randomization. 
• Participants were highly educated, limiting the generalizability of study findings.
• Neuropsychiatric scores fell within normal range after conversion of the raw scores to standardized scores, despite patient complaints of cognitive issues. This may reflect the measure’s insensitivity or specificity or imply that the participants did not have mild impairments in their memory or attention.
• Measurements were not acquired before chemotherapy treatments for a true baseline measure.
• Differences in chemotherapies or other treatments for the participants were not reported.

To assess which of the three topical emollients commonly used for the skin care of patients undergoing whole breast radiation therapy minimizes the grade of dermatitis and cost of product, and to evaluate their effect on quality of life.

A total of 30 patients were randomized to three groups of 10 patients each and received one of three different skin care products to apply during radiation therapy to the whole breast (Calendula cream twice daily, RadiaPlex (hydrogel cream) twice daily, or mometasone twice weekly during the first and second weeks of radiation and daily during week three, plus Aquaphor daily). Weekly skin evaluations were conducted by a medical doctor or a nurse practitioner and RN. Another skin assessment was conducted at one week, one month, and three months post radiation therapy. Life quality index forms were completed by the patients at during visits.

• N = 30   
• FEMALES: 100%
• KEY DISEASE CHARACTERISTICS: Women with stage I–II node-negative breast cancer. Post lumpectomy or partial mastectomy with negative margins. At least two weeks post breast surgery.
• OTHER KEY SAMPLE CHARACTERISTICS: Patients who were scheduled to receive 4256 cGy to the whole breast in 16 fractions. Patients were excluded if they were undergoing concomitant chemotherapy or were less than two weeks post chemotherapy. Other exclusion criteria included patients with connective tissue disorders, such as lupus or rheumatoid arthritis.

• SITE: Single site    
• SETTING TYPE: Not specified  
• LOCATION: New York University (NYU) Clinical Cancer Center

PHASE OF CARE: Active antitumor treatment

Randomized, controlled trial using three commonly used topical emollients

Weekly skin assessment by a medical doctor or a nurse practitioner and RN at one-week follow-up, one-month follow-up, and three-month follow-up visits. Completion of a Dermatology Life Quality Index (DLQI) (visual analog survey) or DLQI upon enrollment to study, during enrollment, and after radiation.

Skin assessment findings and quality of life index scores showed no significant difference based on the product used. All patients experienced grade 1–2 (maximum) dermatitis. Patients did not report a significant decline in their quality of life scores based on the amount of radiation dermatitis they experienced. The maximum grade of dermatitis occurred the first week after completing treatment. Time to maximum skin reaction and time to resolution of the skin reaction for each of the three study arms were equal. A difference in cost existed between the three products (the Calendula cream was the least expensive at approximately $11 per 6.7 oz tube, the mometasone was approximately $48 per unknown dose size, and the RadiaPlex was the most expensive agent at $59 per 6 oz tube).

In this small pilot study, no significant difference was observed between three commonly used topical emollients on the occurrence or severity of radiation dermatitis among patients undergoing whole breast radiation. A cost difference existed between the three products.

• Small sample (< 30)
• After equivocal findings regarding skin reaction and life quality measures, is it justifiable to recommend more costly topical agents instead of the most cost-effective one?

Future research involving multicenter trials and larger sample size could support standard of care recommendations for the most cost-effective product (Calendula cream). The findings show no significant difference in the effectiveness of the three tested agents in terms of severity of radiation dermatitis or decrease in quality of life.

The study sought to assess the efficacy of relaxation training in reducing the incidence of hot flashes in women with primary breast cancer.

The intervention group received a single relaxation training session and was instructed to use practice tapes on a daily basis at home for one month; the control group received no intervention.

The study enrolled150 women from three breast cancer centers in England.

• Inclusion criteria: Postmenopausal women diagnosed with primary breast cancer and suffering from menopausal hot flashes. Any level of severity was accepted for inclusion in the trial as long as the women found the flashes to be troublesome. Postmenopausal was defined as six months without menstruation.

The study was a randomized controlled trial.

The incidence of flashes was measured using a diary, kept by the women, of every flash as it occurred over the period of one week. The women also gave a measure of the severity of each flash using four predefined categories: (a) length of flash, (b) physical manifestation, (c) emotional response, and (d) behavioral response. For each of these domains, four levels of severity (graded 1–4) were assigned, using the Hunter Menopause Scale.

Of 150 women recruited to the trial, 104 women completed it to the primary endpoint at one month, and 97 completed all three months. The incidence and severity of hot flashes, as recorded by diaries, significantly declined over one month (p < 0.001 and p < 0.01, respectively), compared with the control group. Distress caused by flashes also significantly declined in the treatment group over one month (p < 0.01), compared with the contro.l No significant differences between the treatment group and the control group at three months and no changes in anxiety or QOL were reported.

A large amount of attrition marred the trial.

To evaluate of the use of Biafine or Lipiderm to prevent radiodermatitis

Participants were randomized to one of three trial arms: Biafine, Lipiderm, or control (no prophylactic treatment). Study preparations were applied twice daily, starting 10 days prior to the beginning of radiation therapy and continuing until 10 days after treatment. Skin treatment was upgraded if necessary to steroids (grade 3 reaction), antibiotics (grade 4 reaction) or pause in therapy (grade 5 reaction).

• The study sample (N = 74) was comprised of female patients with breast cancer.
• Mean age was 69 years, with a range of 42–85 years.
• Of patients in the study, 63% were receiving concomitant tamoxifen.

The study took place at a single site.

The study used a randomized controlled trial design.

• The Radiation Therapy Oncology Group and European Organisation for the Research and Treatment of Cancer skin toxicity scale was used
• Overall treatment success was determined by maximal treatment grade, total number of radiation treatment gaps needed, the patients’ weekly impression, the radiotherapists clinical impression, and the study nurses’ impression.
• Impressions were measured by an evaluation questionnaire using the same criteria. Relevant data were reported as a grade of reaction.
• Pearson correlation, Chi-square or Fisher’s exact tests were used to analyze relationships among the three study arms.

• No objective data revealed an advantage in the Biafine or Lipiderm arm.
• The maximum skin treatment level was lower in the two intervention arms, but was not significant.
• Patients in both intervention arms reported a high level of satisfaction (Biafine 86% and Lipiderm 85%).

The study does not refute or support use of these products for an existing skin reaction and did not show a radioprotective effect.

• The study groups were too small to demonstrate any differences among study arms.
• Rubbing effects may have cause tissue damage.
• Radiation therapists, nurses, and patients were all responsible for granding, which affects the reliability of data.
• There was no mention of whether addition treatments were used as allowed.

To evaluate the use of Biafine or Lipiderm to prevent radiodermatitis.

Participants were randomized to one of three trial arms:  (a) Biafine, (b) Lipiderm, or the (c) control (no prophylactic treatment).

Study preparations were applied twice daily, staring 10 days prior to the beginning of radiation therapy (RT) and continuing until 10 days after treatment. Skin treatment was upgraded if necessary to steroids for grade 3 reaction antibiotics for grade 4 reactions or pause in therapy for grade 5 reactions.

• The sample was comprised of 74 women.
• Mean age was 69 years (range 42–85).
• Patients had T1-T2N0M0 breast cancer.
• Of the patients, 63% received concomitant tamoxifen.
• Patients with a complicated surgical wound or history of skin conditions were excluded.

Single site

The study was a randomized, controlled trial.

• The Radiation Therapy Oncology Group (RTOG) skin toxicity scale was used.
• Impressions were measured by an evaluation questionnaire using the same criteria. Relevant data were reported as a grade of reaction.
• Overall treatment success was determined by maximal treatment grade, total number of RT gaps needed, the patients’ weekly impressions, the radiotherapists' clinical impressions, and the study nurses’ impressions.
• Pearson correlation, chi-square, or Fisher exact tests were used to analyze the relationships between the three study arms.

• No objective data revealed an advantage in the Biafine or Lipiderm arms.
• Maximum skin treatment level was lower in the two intervention arms but was not significant.
• Patients in both intervention arms reported high levels of satisfaction (Biafine 86%, Lipiderm 85%).

The study neither refutes nor supports use of these products for existing reactions. These products did not show radioprotective effects.

• The study groups were too small to demonstrate any differences among study arms.
• Rubbing effects may have caused tissue damage.
• There were several responsible graders:  radiation therapist, nurses, and patients. Interrater reliability of the measurements was not addressed.

To study the effect of acupuncture on depression and insomnia in patients with malignant tumors. 

One time per day for 20 to 30 minutes, over a course of 30 days, patients in the intervention group received acupuncture on these acupoints:  Fenglon (ST-40), Yinlingquan (SP-9), Xuehai (SP-10), Sanyinjiao (SP-6), Yintant (EX-HN3), Baihui (DU-20), Sishencong (EX-HN1), Neiguan (PC-6), and Shenmen (TF-4). Patients in the control group received fluoxetine, 20 mg/day. Depression scores and sleep ratings were collected before and after the three-day treatment.

• The sample was comprised of 80 patients (66% male, 34% female) with malignant tumors:  40 patients were in the treatment group, which received acupuncture, and 40 were in the control group, which received 20 mg of fluoxetine daily.
• Mean age was 63.8 years (standard deviation [SD] = 5.47 years; range 18–75 years).
• All patients had a malignant tumor. Seven types of cancer were represented in the sample:  lung, gastric, breast, colorectal, lymphoma, cervical, and ovarian cancer. 
• Depression was assessed according to the Chinese Classification of Mental Disorders, third edition (CCMD-3).
• Patients with a functional disorder of the heart, liver, kidney, or spinal cord were excluded, as were those currently taking antidepressant medications.

• Single site
• Beijing, China

Patients were undergoing the active treatment phase of care.

The study was a randomized, controlled trial with intervention and control groups.

• Zung Self-Rating Depression Scale (SDS)    
• Hamilton Rating Scale for Depression (HRSD)
• Pittsburgh Sleep Quality Index (PSQI)

Pretreatment SDS scores of the treatment and control groups were 64.12 (SD = 5.34) and 64.24 (SD = 4.98), respectively, with no significant difference (p > 0.05). After treatment, SDS scores of the treatment and control groups were 43.64 (SD = 5.28) and 50.76 (SD = 5.42), which showed significant difference (p < 0.05). HRSD scores of both groups showed no significant difference before treatment (p > 0.05); however, after-treatment scores were 9.88 (SD = 1.27) in the treatment group and 13.72 (SD = 2.05) in the control group (p < 0.05). These results indicate that both acupuncture and fluoxetine were effective in reducing depression scores in these patients, with acupuncture showing greater effectiveness. PSQI scores of the treatment group, before and after treatment, were 14.48 (SD = 1.71) and 7.92 (SD = 1.22), respectively, with a significant difference (p < 0.001). The control group's PSQI scores, 13.92 (SD = 2.59) and 11.44 (SD = 1.89), did not reach significance (p > 0.05). Results indicate that acupuncture improved sleep quality in more patients than did fluoxetine.

Both acupuncture and fluoxetine were associated with reduced depression scores and some improvement in sleep. Due to the lack of a real control group and no control over cancer type and treatment phase, drawing a conclusion about the effectiveness of the intervention is difficult.

• The study had a small sample size, with less than 100 patients.
• The age range was small.
• The study was conducted at a single site, and the measurement tools were self-report instruments.
• Fluoxetine may take more than 30 days to reach therapeutic effectiveness.
• The study compared a fluoxetine-using group to an acupuncture-using group; the study included no real control group.
• The sample included diverse cancer types, and patients were at different phases of treatment. These factors may confound the findings.
• The authors did not analyze the differences between groups in regard to posttreatment PSQI scores. 
• The study did not include an attentional control or consider the possible placebo effect of acupuncture.
   

Acupuncture is a nonpharmacologic intervention that shows promise in reducing depression and improving sleep quality in patients with cancer and depression.