STUDY PURPOSE: To determine if prophylactic or treatment transfusion of platelets is required, and answer questions of optimal prophylactic platelet dose, platelet threshold to be used, and whether a therapeutic only strategy is as safe and effective as prophylaxis

TYPE OF STUDY: Meta-analysis and systematic review

PHASE OF CARE: Active antitumor treatment

Studies compared therapeutic only versus prophylactic platelet transfusion or placebo. The incidence of severe or life-threatening bleeding as many as 30 days from study entry was significantly different (RR = 4.91, 95% CI [0.86, 28.12]) in favor of prophylactic transfusion. Differences in other outcomes such as bleeding episodes, duration, etc., could not be estimated. There was no evidence of differences in adverse events. Patients in the therapeutic-only arm had less platelet transfusions and a shorter time to first bleeding episode. Findings regarding an appropriate platelet threshold are not provided.

Patients receiving therapeutic platelet transfusion may be at greater risk for bleeding than those given platelets prophylactically. There may not be an increased risk of adverse events or death if platelet transfusions are given only therapeutically.

• Limited number of studies included
• Mostly low quality/high risk of bias studies
• High heterogeneity
• Methods for grading of bleeding and recording of bleeding varied across studies.
• Extremely wide confidence interval

Results of this review need to be viewed with caution, as the quality of studies included was low to moderate and there was insufficient evidence to answer many questions regarding differences in outcomes. Further research would be helpful—while prophylactic platelet transfusion is the usual standard of care, and somewhat reduces risk of bleeding, there is no evidence to show any effect in terms of mortality and other disease-related outcomes. Transfusions are not risk free. Overall, there is very limited evidence for interventions to prevent bleeding.

G-CSF 230 mcg/m² given days 4–17 unless the post-nadir neutrophil count exceeded 10x10⁹/1 after day 12. Treatment repeated every 21 days for up to six cycles of chemotherapy (cyclophosphamide, doxorubicin, and etoposide).
Control was placebo injection.
Patients in the placebo group crossed over to G-CSF after episode of febrile neutropenia.

The study was comprised of 199 patients, of the 211 patients who had enrolled.
G-CSF = 95
Placebo = 101
Small-cell lung cancer

Multicenter

Randomized, prospective, control phase III trial

Febrile neutropenia was the primary endpoint. Also looked at infectious complications and oral mucositis.
WHO scale
Oral candidiasis included as mucositis incidence, severity, and time to onset.
Duration of mucositis was determined by a combination of patient reporting and clinical examination findings.
 

54% versus 72% episode of mucositis in G-CSF versus placebo group. Most episodes were grade I–II. Median duration of mucositis was the same for both groups (eight days).
First-cycle mucositis: 28% versus 47% (p = 0.041)
 

Difficult to determine some results because of cross-over nature of study. Also allowed dose reduction in treatment group, which decreased mucositis; confounding results.

Trials with nonmyelosuppressive therapy are needed to determine effect.

• Eighteen citations listed: No evaluative summary of sources or levels of evidence 
• Note provided by authors on levels of evidence (I-V) and grades of recommendation (A-D) as used by the American Society of Clinical Oncology provided in the tables of recommendations
• Statements within the guidelines without grading were considered standard clinical practice as recommended by the expert authors and the ESMO faculty

• Definition: Incidence of FN, complications, and mortality rates
• Regimens: Risk of FN > 20%
• Indication: FN primary prophylaxis with ​hematopoietic growth factors (hGFs)
• Special situations: hGFs and standard therapy
• Dose schedule: Administration of granulocyte-colony stimulating factor (G-CSF) and pegfilgrastim
• Indications: Use G-CSF and pegfilgrastim; high-risk situations
• G-CSF after autologous stem-cell transplant or allogeneic transplant
• Mobilization of peripheral blood stem cell autologous or allogeneic settings
• G-CSF treatment for radiation injury

• Data sources before 2010 may be outdated.
• Not all tumor types and treatments were represented.
• No process was provided for how these guidelines were developed.
• The inclusive resources cited were not evaluated separately with a table of evidence.
• These guidelines were established on expert opinion, consensus of ESMO faculty, and the adoption of ASCO levels of evidence and grades of recommendations.

Identifying patients at-risk for FN and the appropriate use of hGFs is critical to improve patient outcomes. Nurses must consider the strength of evidence for and the process of guideline development of treatments before using clinical practice guidelines in patient care.

To evaluate the rate of uncontrolled chemotherapy-induced nausea and vomiting (CINV) after initiation of antiemetic prophylaxis with palonosetron as compared to all other 5-HT₃ antagonists in patients diagnosed with hematologic malignancies and receiving highly emetogenic chemotherapy (HEC) or moderately emetogenic chemotherapy (MEC)

Subjects who were 18 or older, were identified from eight million cancer discharges that are part of the Premier Perspective Database, which includes data from more than 600 hospital systems. After establishing the correct diagnosis and pharmacologic treatment, data were retrospectively extracted from the database from initiation of chemotherapy to the end of eight rounds of chemotherapy treatment or for six months. 

• This study reported on 971 patients with a mean age of 61.9 years.
• The sample was 48% male and 52% female.
• Primary hematologic malignancies were defined as lymphoma (79%), myeloma (6.4%), and leukemia  (AML , CML, ALL, CLL, and other leukemia, 14%).   
• Patients were chemotherapy naïve, with no prior evidence of nausea or vomiting.
• Patients had hematologic malignancies and were initiated with single or multiday chemotherapy and antiemetic prophylaxis with palonosetron (group 1) or all other 5-HT₃ antagonists (group 2). The sample was 71.2 % white. Patients who received palonosetron represented 22% of the sample.

This was a multisite, outpatient study based on the Premier Perspective Database containing data from more than 600 hospitals.

• All patients were in active treatment.
• This study has application to late effects and survivorship.

This was a longitudinal, retrospective observational study.

The primary study outcome was rate of uncontrolled CINV events in the study follow-up period of eight cycles of chemotherapy or six months, with events operationally defined by either the need for rescue antiemetics on day two or by any of the ICD-9 codes for nausea, vomiting or volume depletion, dehydration, or hypovolemia. The unit of analysis was one cycle, defined as number of treatments in seven days.

• Of 971 subjects for whom data were extracted, 211 subjects were treated initially with palonosetron and 760 subjects were treated with other 5-HT₃ antagonists.  The groups were comparable in most aspects, including the Charlson Comorbidity Index (mean CCI = 0.2); however, group 1 had a higher percentage of patients who received HEC.
• After adjusting for baseline differences in the two groups, multivariate analysis results predicted a 20.4% lower CINV event rate per chemotherapy cycle in patients with hematologic malignancies treated with palonosetron. This difference was slightly more than one episode per cycle. No significant differences were found in the actual event rate from analysis. 
• Females were shown to have a higher CINV rate, but it was not statistically significant.
• Cycle length (total days within week) also was found to be associated with CINV, with increased days leading to more CINV.

Patients treated with palonosetron in the outpatient setting had significantly lower CINV event rates (decrease of 20%) versus patients treated with other 5-HT₃ antagonists after adjusting for baseline differences.  However, because this study did not look at the contribution of other antiemetics (e.g., aprepitant, dexamethasone), we may only conclude that in a fairly large sample of patients from the Premier Perspective Database, the group of patients who were given palonosetron on the initiation of HEC or MEC experienced less CINV.

• A retrospective study design relies on the accurate documentation of events by others; however the large sample size is definitely a plus.  
• Using a combined data set pulls patients from many practices, the researchers cannot control for variation in clinical practices. We do not know why palonosetron was chosen originally.
• The use of other antiemetics were not considered, including corticosteroids and the neurokin 1 (NK1) receptor antagonist aprepitant, which may have an impact on the study results.
• We do not know the patients' histories of previous nausea and vomiting, motion sickness, smoking history, or how much medication was given.

Palonosetron should be considered for the prevention of CINV in patients with hematologic malignancies being treated with HEC or MEC. 

The objective of the study is to determine whether the administration of oxygen therapy alleviated dyspnea in adults with chronic end-stage disease versus breathing room air or placebo air in a non-acute care setting.

Databases searched were Cochrane reviews, OVID MEDLINE, CENTRAL, CINAHL (1982-2006), Cancer Lit (1975-2006), ACP Journal Club (1991-2006), Turning Research Into Practice (TRIP) (1997-2006), Dissertation Abstracts (ProQuest Digital Dissertations) (1985-2004), LILACS (1994-2006), Australasian Medical Index (National Library of Australia) (1990-2006) via Informit, LOCATOR plus (U.S. National Library of Medicine), EMBASE (1987-2006), PubMed (1950s-2006) (National Library of Medicine).

Search keywords oxygen, dyspnea, dyspnea, palliative, terminal, breathless, end-stage, and adult as either text words or mesh headings were used to search EMBASE Excerpta Medica, Australasian Medical Index, Latin American and Caribbean Health Sciences Literature (LILACS), and American College of Physicians (ACP) Journal Club and Dissertation Abstracts.

The Cochrane Library was searched using the terms oxygen and dyspnea or dyspnea and palliative or terminal.

Studies were included if they

• Were a randomized controlled trial (blinded or unblinded) performed in a non-acute care setting
• Included participants with chronic terminal illness (excluding chronic obstructive pulmonary disease) and breathlessness at rest or on mild exertion with or without hypoxemia
• Compared usual active treatment plus palliative oxygen therapy with a control groups
• Compared mean levels of dyspnea experienced by participants with a chronic terminal illness before and after administration of oxygen gas or room air/placebo
• Used a valid instrument to measure dyspnea.

Four hundred forty-six initial articles were retrieved. Only randomized controlled trials were considered for this review, with inclusion of unblended studies. Electronic databases were searched for predefined search terms. All studies were assessed for methodologic quality using a 0-5 scale based on the Oxford Quality Scale, and Quality of Concealment of allocation was rated.

Eight studies met inclusion criteria, for a final total sample of 144. Sample sizes across studies ranged from 12-45. Oxygen for dyspnea was evaluated in four studies among patients with cancer, three studies among patients with cardiac failure (CHF), and one study among patients with kyphoscoliosis. Of the sample, 99 were males and 46 were females. All were adults with listed comorbidities, some with or without domiciliary oxygen, with moderate to severe dyspnea.

Overall oxygen was not associated with reduction in the symptom of dyspnea.

Due to small number of research studies, variation in study methodologies, and small sample sizes among studies, evidence is still inconclusive regarding the short-term or long-term benefit of oxygen therapy over air inhalation in patients with cancer with dyspnea due to end-stage malignancy.

Newer, larger, well designed, controlled, randomized studies are needed with adequate power to detect variations in breathlessness with sufficient “washout” time between test gas inhalation times. Therefore, immense caution is suggested regarding the benefits of short-term oxygen inhalation over air inhalation for dyspnea relief in terminal care patients.

• Study Design: Both randomized and nonrandomized studies were considered to acquire a complete understanding of the topic area. The key inclusion criterion was that all studies, regardless of design, had to include some form of physical exercise training for patients surgically treated for NSCLC. This review intended to include quantitative, qualitative, and mixed-method study designs.
• Participants: Studies that included participants diagnosed with resectable NSCLC were included in this review. Exercise interventions were defined as supervised or unsupervised inpatient, outpatient, community- or home-based interventions that included any type of exercise training applied to patients surgically treated for NSCLC. Some studies included additional components. Four studies included education, four included smoking cessation, and three used phone calls.
• Outcome measures: All outcomes measured were recorded in this review. 

• Study Design: All poster abstracts and non-English full-text articles were excluded.  
• Participants: Studies with < 65% of the patient population were excluded to ensure a consistent sample.

PHASE OF CARE: Multiple phases of care

• Fatigue increase was noted in studies presurgery to immediately postsurgery, yet the authors did not cite which studies.  
• Fatigue reduction was found from baseline to postintervention in three out of five studies. The authors note that in two studies, fatigue severity from baseline to postintervention was not reduced and that each of these studies were of a different type of exercise (resistance) with different intervention timing (preoperative).
• Fatigue reduction was noted to be sustained in two participants who did not receive adjuvant therapy as compared to those who underwent adjuvant treatment.

Preliminary findings from the review suggest that intervention via exercise compared with usual care pre- and postsurgery may reduce fatigue. The results from the systematic review show the infancy of this particular field of study with very few studies included for analysis, with the majority of studies being of observational methodology. In addition, studies included a wide range of exercise prescriptions.

The field of treatment for fatigue in the surgical NSCLC population is in its infancy. In one study of the reviewer’s expertise, it is noted that the article was labeled as an unsupervised intervention when the article discusses the actual supervision of subjects participating in the exercise intervention.

Additional study of the best exercise prescription for fatigue management is needed related to patients undergoing surgery. The best timing for such interventions is not clear.

To evaluate the effect of exercise on cancer-related fatigue during and after cancer treatment. This was an update of a study from 2008. A secondary objective, subject to available data, was to explore the effect of exercise in different types of cancer populations.

Databases searched were the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 1, 2011), MEDLINE (1966 to March 2011), EMBASE (1980 to March 2011), CINAHL (1982 to March 2011), British Nursing Index (January 1984 to March 2011), AMED (1985 to March 2011), SIGLE (1980 to March 2011), and Dissertation Abstracts International (1861 to March 2011).  The authors also searched references of all articles; hand searched the following journals up to April 2011: Cancer, Journal of Clinical Oncology, Psycho-Oncology, Cancer Practice, Oncology Nursing Forum; and searched unpublished literature through searches of conference proceedings up to June 2011.

Appendix 1 details the keywords searched, including expanded neoplasms, leukemia, lymphoma radiation therapy, bone marrow transplantation, exercise, movement, and fatigue.

Studies were included in the review if 

• They evaluated and reported the effect of physical exercise on cancer-related fatigue
• They compared exercise with no exercise, a usual care group (i.e., no specific exercise program prescribed), or an alternative treatment or exercise regime for fatigue associated with cancer
• The intervention took place in any setting and was delivered to a group or individual participant
• Any type of physical exercise, including aerobic exercise, strength training, and flexibility exercises, was performed
• They investigated an exercise program accompanied by attempts to promote participant engagement.

Studies were excluded if they explored multidimensional programs in which the effects of exercise alone could not be determined and if a specific exercise program was not described and participants were only given advice or education about the potential benefits of exercise.

Fifty-eight new references plus 28 from the original review were retrieved.

Two independent reviewers reached 100% consensus; they assessed the methodological quality of the studies from the previous review.

• Fifty-six total studies were included in the final review (28 new plus 28 from the original review).
• The sample sizes ranged from 10 to 242 participants; the total number of participants was 4,068.
• Participants had various cancer diagnoses and various timing since diagnosis.
• The majority of participants had breast cancer.
• There was a mix of female and male patients; however, 29 of 56 studies included only females.
• Mean age ranged from 39 to 70 years (mostly in the 50s).

Patients were undergoing multiple phases of care.

Statistically significant improvements in fatigue were identified following an exercise program performed either during cancer therapy (standardized mean difference [SMD] = -0.23; 95% confidence interval [CI] [-0.23, -0.33]) or following cancer therapy (SMD = -0.44; 95% CI [-0.79, -0.09]). Statistically significant beneficial effects were identified specific to breast cancer (n = 672) and prostate cancer (n = 239) populations, but not for those with hematological malignancies (n = 114). Statistically beneficial effects were identified following aerobic training but not following resistance training or low-intensity mind-body interventions.

Sufficient evidence exists to support the recommendation of aerobic exercise during and after treatment for patients with breast or prostate cancer. Insufficient evidence exists to support the recommendation of hematological malignancies or other solid tumors. Exercise modalities other than aerobic exercise do not have sufficient evidence to support their recommendation.

Most studies

• Had small sample sizes
• Did not blind the intervention
• Provided little information about those who refused to participate
• Included self-reports
• Had exercise programs that did not reach the current recommended amounts for adults.

Aerobic exercise is recommended for appropriate patients during and after treatment for breast or prostate cancer. Consider recommending exercise for other solid tumors. Research is needed for various cancer types and stages, including palliative care and for types and duration of exercise.

Databases searched were the Cochrane Controlled Trials Register (CCTR), MEDLINE, EMBASE, CINAHL, British Nursing Index, AMED, SIGLE, and Dissertation Abstracts International through July 2007.

Twenty-eight published randomized, controlled trials investigating the effect of exercise on cancer-related fatigue in adults were identified.

Outcomes

Fatigue was assessed using various self-report measures, including the Functional Assessment of Cancer Therapy-Fatigue (FACT-F), fatigue subscale of the POMS, the Piper Fatigue Scale, and the Brief Fatigue Inventory (BFI). Only three studies incorporated more than one fatigue outcome measure.

Treatment Evaluated

Mode, intensity, and timing of exercise differed across studies. Thirteen studies investigated home-based/unsupervised exercise programs, whereas 16 studies investigated supervised, institutionally-based exercise programs. Some studies investigating supervised exercise programs encouraged participants to undertake additional home-based exercise. The mode of aerobic exercise included walking, stationary cycling, or a range of modalities. Three studies included strength training as a component of the exercise program, and two studies investigated the outcomes of resistance training in isolation. Two studies included flexibility training as a component of the exercise program, although several studies incorporated routine stretching as part of the warm-up, cool-down, or both. Yoga was investigated in two trials and seated exercise in one. The intensity of exercise varied greatly across studies, with the comparison complicated by differences in the methods (e.g., heart rate monitoring, predicted oxygen uptake, and patient perceived effort) used to monitor intensity in each study. The length of the intervention also varied greatly, ranging from three to 32 weeks; the largest proportion of studies had an exercise intervention duration of 12 weeks.

• There were 2,083 participants. 
• Participants had various cancer diagnoses, although the majority of studies investigated breast cancer only.
• Nineteen of the 28 studies investigated participants with a specific cancer diagnosis and nine investigated participants with a range of diagnoses.
• The time since diagnosis and stage of treatment (active versus posttreatment) varied widely between studies and, in some cases, within studies.

Using posttest means and mean change scores from the pre- posttests, exercise was found to be statistically significantly more effective than the control intervention in the management of fatigue. In separate analyses, dividing studies based on whether the intervention was performed during or following cancer treatment, exercise was consistently statistically significantly found to be more effective for fatigue than the control intervention. Similarly, positive results concerning the effects of exercise for fatigue were also found when only those studies performed in women with breast cancer were examined. Quantitative comparison of fatigue intervention outcomes in other disease-specific groupings was not possible due to limitations in the available data. However, two studies of the effects of exercise on fatigue in prostate cancer populations reported mixed results. A four-week, home-based walking program had no significant effect on fatigue, whereas a 12-week supervised resistance training program produced a statistically significant improvement in the exercise group compared to the control group. No statistically significant improvements in fatigue were observed in patients with colorectal cancer who were prescribed a 16-week, home-based cardiovascular and flexibility program; in patients with lymphoma attending a weekly supervised yoga session; or in patients with multiple myeloma receiving an individualized 32-week, home-based strength and aerobic training program.  Follow-up assessment of long-term outcomes was limited, with 18 of 28 studies failing to assess outcomes beyond the end of the intervention period. From the remaining ten studies that included a follow-up assessment, three did not present the follow-up data in the original publication.

Methodologic quality of the studies was modest (the majority of the studies assigned an Oxford Quality Score of 2 or 3 on the 0–5 scale, with higher scores indicating better methodologic quality).

• All studies lost points in the scoring of methodologic quality due to the failure of the design to conceal group allocation of study participants to the exercise intervention.
• The authors also noted that observer blinding was rarely reported in the included studies.
• Several studies had methodologic flaws, such as providing incomplete descriptions of dropouts or inadequate descriptions of the methods of randomization.
• Although 20 of the 28 studies provided some data on adherence to the exercise interventions, methods for reporting adherence varied between studies, making it difficult to control for adherence when comparing results across studies.

To evaluate the effects of yoga on quality of life, anxiety, depression, and sleep in patients with colorectal cancer.

• N = 44  
• MEAN AGE = 68.26 years (range = 40-87)
• MALES: 61.1%, FEMALES: 38.9%
• KEY DISEASE CHARACTERISTICS: All had colorectal cancer and were an average of 23 months since surgery
• OTHER KEY SAMPLE CHARACTERISTICS: The majority of patients were retired and were married

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

• PHASE OF CARE: Late effects and survivorship

• Randomized, controlled trial

• Functional Assessment of Cancer Therapy (FACT) colorectal and fatigue scales
• Hospital Anxiety and Depression Scale (HADS)
• Pittsburgh Sleep Quality Index (PSQI)

At week 10, the yoga group had greater decline in anxiety (p = 0.043) and depression (p = 0.038) scores, but, at week 22, there was no difference between groups. At week 10, there were no differences between groups in PSQI scores, however, at week 22, those in the yoga group had better sleep quality (p = 0.043). There was no relationship between home practice time and outcomes. Only about half attended yoga sessions, and average home practice was about one hour per week. There were no significant differences between groups in overall quality of life scores.

Yoga may be helpful to some patients to reduce sleep disturbances.

• Small sample (less than 100)
• Baseline sample/group differences of import
• Risk of bias (no blinding)
• Risk of bias (no appropriate attentional control condition)
• Measurement validity/reliability questionable
• Subject withdrawals of 10% or greater 
• Other limitations/explanation: More than 20% were lost to follow up. Baseline anxiety and depression scores were very low, so it is not likely that reduction would be seen due to floor effects, and those reductions seen have questionable clinical relevance.

These results did not show meaningful impact of yoga on anxiety or depression. Yoga was beneficial in terms of improving sleep, although changes seen were small, and findings are limited due to study limitations. Further research in the potential role of yoga for sleep improvement is needed.

To evaluate the effects of a 12-week traditional Hatha yoga and meditation intervention on menopausal symptoms in survivors of breast cancer

• N = 40  
• MEAN AGE: 49.2 years (SD = 5.9 years)
• FEMALES: 100%
• KEY DISEASE CHARACTERISTICS: The study included survivors of breast cancer with no metastatic tumors after completing antineoplastic treatment, surgical chemotherapy, or radiotherapy. Women were aged 30-65 years, with or without antiestrogen medications.
• OTHER KEY SAMPLE CHARACTERISTICS: Patients scored 5 points or more, moderate score, on the Menopause Rating Scale (MRS). Antiestrogens, nonhormonal, and antidepressant medication were included if dose was fixed/stabilized and no changes in perspective were noted in 24 weeks.

• SITE: Single site    
• SETTING TYPE: Not specified    
• LOCATION: Department of Gynecology Certified Breast Cancer at Malteser Hospital St. Anna, Duisburg, Germany

• PHASE OF CARE: Transition phase after active treatment

Unicenter, open-labeled, randomized clinical trial with two groups: (a) the group with yoga and meditation intervention and (b) the control group with usual care

• Menopause Rating Scale (MRS)
• Quality of life was measured with Functional Assessment of Cancer Therapy-Breast (FACT-B)
• Fatigue measured with Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F)
• Depression and anxiety were measured with Hospital Anxiety and Depression Scale (HADS)

Primary outcome: At week 12 and week 24, total menopausal symptoms were lower in the yoga group than in the usual care group (week 12: p = 0.004; week 24: p = 0.023). Regarding quality of life, significant group differences were observed at week 12 for the FACT-B total score (p = 0.002), and for the social (p = 0.024), emotional (p = 0.005), and functional well-being subscales (p = 0.024). There were no group differences for anxiety or depression. Women who received antiestrogen medication (n = 36) presented total menopausal symptoms lower in yoga group at week 12 (p = 0.013) but not at week 24 (p = 0.084). At week 24, no group differences were observed for any of the MRS subscales in the subgroup analysis (p = 0.075–0.352).

Yoga combined with meditation appears to be an effective intervention to relieve menopausal symptoms in survivors of breast cancer for at least three months after the end of the active neoplastic treatments. It can help reduce fatigue, and, for women who are receiving antiestrogen medication, yoga can have at least short-lasting effects.

• Small sample (less than 100)
• Risk of bias (no blinding)
• Risk of bias (sample characteristics)
• Unintended interventions or applicable interventions not described that would influence results 
• Key sample group differences that could influence results
• Intervention expensive, impractical, or training needs
• Groups can be different, as well as anxiety and depression scores at the beginning. Groups also can be contaminated one to another if there is contact.
• Previous experience in yoga was not controlled, and interventions are supposed to be adapted to the individual, so there can be differences in interventions for group members.
• It is unclear if there were individual or group yoga sessions.

Yoga is a good recommendation for patients with breast cancer to manage menopausal symptoms and to decrease fatigue. Intervention is effective to improve quality of life. Yoga does not have serious adverse events, and minor adverse events could be related to other causes.