STUDY PURPOSE: The purpose of this systematic review of the literature was to evaluate the effectiveness of Qigong on symptom management in patients with cancer. Qigong is a complementary therapy with the goal of relaxation involving simple, repeated body posture or movements, breathing exercises, and meditation performed in synchrony.

TYPE OF STUDY: Systematic review

DATABASES USED: PubMed/MEDLINE, CINAHL, Cochrane Library, and PEDRO

YEARS INCLUDED: From 1995 through 12/2015

INCLUSION CRITERIA: RCTs, quasi-experimental with comparison group, and feasibility trials; adults ≥ 18 years of age; cancer diagnosis; receiving care in any healthcare setting; using Qigong during or after cancer treatment versus placebo, usual care, or other intervention to manage symptoms, including patient-reported physical-psychological symptoms reported as continuous or dichotomous and quality of life. 

EXCLUSION CRITERIA: Trials including patients receiving hospice care or were at the end-of-life

TOTAL REFERENCES RETRIEVED: N = 266

EVALUATION METHOD AND COMMENTS ON LITERATURE USED: Cochrane Collaboration’s Tool for Assessing Risk of Bias (Cochrane Collaboration, 2011) and strength of the evidence were evaluated using the Oxford Centre for Evidence-Based Medicine Levels of Evidence (Oxford Centre for Evidence-Based Medicine, 2009).

FINAL NUMBER STUDIES INCLUDED: N = 22

TOTAL PATIENTS INCLUDED IN REVIEW: 1,751

SAMPLE RANGE ACROSS STUDIES: 20-211

KEY SAMPLE CHARACTERISTICS: Studies were conducted in Hong Kong, China, Taiwan, Malaysia, South Korea, United States, Israel, and Australia. Various cancer diagnoses were included (i.e., breast, prostate, gynecologic, nasopharyngeal, hepatocellular, colon, non-Hodgkin lymphoma, lung cancer, and gastrointestinal cancers) from early in the treatment period through the recovery phase. Median intervention duration was 6 weeks (ranged from 3 to 24 weeks).

PHASE OF CARE: Multiple phases of care     

APPLICATIONS: Elder care

Of the 22 studies that met inclusion criteria, there were 14 RCTs and 8 controlled clinical trials. A high risk of bias was reported in 16 studies (73%) specifically in lack of blinding, allocation concealment, and incomplete outcome data. The efficacy of Qigong was examined for symptom management among patients with various cancers. Effects were described according to primary outcome measures, including physical (e.g., fatigue, sleep disturbances, pain, dyspnea) and psychological (e.g., depression, anxiety) symptoms, and quality of life. For example, 10 studies included a fatigue outcome whereas 3 studies included a sleep disturbance measure. In addition, 19 studies evaluated ≥ 2 outcomes. Results indicated that participants in Qigong groups were significantly improved postintervention compared with the control groups or there were positive trends from pre- to postintervention scores. Protocols used to deliver the interventions varied and included seven types or forms of Qigong. Interestingly, all seven styles of Qigong were effective for ≥ one outcome variable. Secondary outcomes found that Qigong was safe and feasible without unwanted side effects. The majority of outcomes were self-reported, but there were a few significant objective clinical outcomes: muscular strength, range of motion, six-minute walk test, and body mass index.

Results of this systematic review suggest that some of the symptoms were significantly improved in the Qigong group postintervention compared to controls. These somewhat promising results are tempered by some major limitations. There was a high risk of bias related to allocation concealment, lack of blinding, and incomplete outcome data. Limitations pertain to the potential incompleteness of the evidence reviewed. Conclusions regarding superiority of one form of Qigong over another were beyond the scope of this review.

Limited number of studies included

Mostly low quality or high risk of bias studies

High heterogeneity

Low sample sizes

Qigong for improving symptoms in patients with cancer are encouraging in some but not all reported studies in this review. For example, only one out of three studies that evaluated sleep quality reported significant improvement with Qigong. More research is needed before Qigong can be recommended for relief of cancer-related symptoms.

The purpose was to examine whether tai chi chih (TCC) is noninferior in effect to cognitive behavioral therapy (CBT-I) in reducing insomnia in breast cancer survivors.

Participants were randomly assigned to two groups: those receiving CBT-I and those receiving TCC. Prior to the intervention, participants were enrolled in a 2-month phase-in period to establish their degree of insomnia. CBT-I and TCC groups were comprised of 7-10 participants and consisted of weekly 120-minute sessions. Interventions were held over two months, with a third month of skill consolidation and adherence (three months total intervention exposure). Remission of insomnia was also measured by an interviewer blinded to intervention exposure who evaluated remission according to DSM-IV-TR criteria. Assessments  of insomnia, a daily sleep diary, polysomnography levels, levels of fatigue, sleepiness, depressive symptoms, body mass index, and physical activity levels were collected at month 2 (baseline data), month 3 (post intervention), and follow-up assessments at months 6 and 15.

• N: 90   
• AGE: Range = 42-83 years, Mean = 59.6
• FEMALES: 100%
• CURRENT TREATMENT: Not applicable
• KEY DISEASE CHARACTERISTICS: Breast cancer survivors met the DSM-IV-TR criteria for insomnia had reported sleep difficulties at least 3 times or more per week for at least three months or more; had finished surgical, radiation, or chemotherapy treatment at least 6 months prior; and did not have recurrence of cancer or a new tumor.

• SITE: Single site   
• SETTING TYPE: Not specified    
• LOCATION: Los Angeles, CA

PHASE OF CARE: Late effects and survivorship

Two groups were established in a randomized, partially blinded, noninferiority trial. Participants were blinded to the hypothesis and the alternate treatment group.

• Sleep quality was measured using the Pittsburgh Sleep Quality Index and Athens Insomnia Severity Index. 
• Objective sleep continuity was measured using polysomnography and subjectively with sleep diaries. 
• For secondary outcomes, insomnia remission was evaluated using DSM-IV-TR criteria and reviewed utilizing board-certified psychiatrists and psychologists. Fatigue was measured using the Multidimensional Fatigue Symptom Inventory, sleepiness was measured using the Epworth Sleepiness Scale, and depressive symptoms were measured using the Inventory of Depressive Symptoms. Body mass index and physical activity levels (Yale Physical Activity Survey) were also measured. A noninferiority margin of 50% was used.

Responsiveness to CBT-I or TCC treatment was comparable with a responsiveness rate of 43.6% and 46.7%, respectively. The noninferiority margin for this study’s purposes was set at 50%, and noninferiority of TCC was observed at month 3 (p = 0.02), month 6 (p =< 0.01), and month 15 (p = 0.02). Both treatments resulted in comparable insomnia remission rates at month 15 (46.2% and 37.9%, respectively). Differences in change of PSQI or AISI, as well as change in sleep time and wake after sleep onset, and effects on fatigue, sleepiness, or depression from baseline were not significant in comparing treatment groups (p > 0.3, p > 0.4, p > 0.5, respectively). PSG did not demonstrate treatment effects or differences across groups of significance.

CBT-I and TCC demonstrated high patient responsiveness and sustainable insomnia reduction at follow up yet yielded nonsignificant differences between treatment groups, thereby demonstrating noninferiority of TCC to CBT-I. Improvements in sleep quality, fatigue, sleepiness, and depressive symptoms were observed among both groups, but group differences were again not significant.

• Small sample (< 100)
• Findings were not generalizable.
• Intervention was expensive and impractical, and training was needed.
• Subject withdrawals ≥ 10%

Given not only the prevalence, but debilitative effect insomnia has on patients with cancer, alternative treatments to CBT-I, such as TCC, are important for nurses to assess and identify for patients, who may have variances in access to clinical CBT-I treatment.

The purpose was to evaluate the effect of therapeutic care (TC) with acupressure on fatigue in patients with breast cancer receiving chemotherapy.

Patients were randomized to the intervention or sham control arm. The intervention consisted of acupressure to three points related to energy in the human body (bilateral Hegu, Zusanli, & Sanyinjiao) administered 30 minutes per day, 10 minutes per point, 3 days a week for 12 weeks. Sham control included three points reported to have no relationship to alleviate cancer-related fatigue, first metacarpal head, patella, and inner ankle with same treatment administration, frequency, and duration. Fatigue, anxiety, depression, and sleep were measured at baseline, 6 weeks, and 12 weeks.

• N = 48 
• AGE: Mean age of the intervention group was 51.8 years (SD = 9.6) and control was 52.4 years (SD = 9.3).
• FEMALES: 100% 
• CURRENT TREATMENT: Chemotherapy
• KEY DISEASE CHARACTERISTICS: Breast cancer, actively receiving chemotherapy    
• OTHER KEY SAMPLE CHARACTERISTICS: s/p lumpectomy or mastectomy, did not take herbs or supplements, and did not report medication-related fatigue

• SITE: Single site
• SETTING TYPE: Not specified    
• LOCATION: China

PHASE OF CARE: Active antitumor treatment

Randomized control trial

Multidimensional fatigue inventory (MFI), Hospital Anxiety and Depression Scale (HADS), and Pittsburgh Sleep Quality Index (PSQI)

For those in the intervention group, fatigue improved statistically (p < 0.01) at 6 weeks and maintained improvement at 12 weeks (p < 0.01). Anxiety, depression, and sleep quality improved at 12 weeks (p < 0.01).

Acupressure may be an effective method or type of complementary and alternative therapy in improving fatigue, anxiety, depression, and sleep in patients with breast cancer receiving chemotherapy.

• Small sample (< 100)
• Subject withdrawals ≥ 10%  
• Other limitations or explanation: Single site, all Chinese patients

Acupressure focused on points known to help energy may be useful in treating cancer-related fatigue, anxiety, depression, and sleep quality.

A quality improvement project to educate caregivers on CL management and CLABSI prevention among children

The intervention consisted of nine in-person classes for education and practice on children and mannequins.

• N: 120   
• AGE: Not mentioned
• MALES: Not diversified  
• FEMALES: Not diversified
• CURRENT TREATMENT: Other
• KEY DISEASE CHARACTERISTICS: ALL, AML, CL, CLABSI, QI, Pediatric hemato-oncology
• OTHER KEY SAMPLE CHARACTERISTICS: Leukemia, caregivers

• SITE: Single site   
• SETTING TYPE: Multiple settings    
• LOCATION: Santobono-Pausilipon Children’s Hospital, Italy

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

QI project for in-person caregiver training classes; no ICF needed.

CLABSI rate per 1,000 CL days in children with acute leukemia. The baseline was calculated based on previous 12 months of the QI project between March 2012 and April 2013 and was compared with cumulative CLABSI rates computed with 95% confidence intervals (CI).

A total of 118 children were diagnosed with acute leukemia and included in the study. 120 caregivers of 118 children agreed to participate. Baseline CLABSI rate was 6.86 per 1,000 CL days; within 8 months, 3.7 per 1,000 CL days; 46.1% reduction attributable to intervention alone.

Implementing an education intervention for the reduction of CLABSI occurrences using evidence-based practices resulted in dramatic improvement of CLABSI rates and, in turn, survival rates of leukemic children.

Subject withdrawals 10% or greater

Nursing is synonymous for teaching and educating the patient population. Nurses would be at the forefront of this intervention creating a comprehensive explanation of the disease process in a palatable form for caregivers as well as reinforcement and encouragement.

To determine the appropriateness of vancomycin prescribing, based on consistency with guideline (IDSA and NCCN) recommendations before and after implementation of FN clinical pathway. Secondary endpoint was to determine influence of comorbidities with inconsistent vancomycin use based on guideline recommendations.

Using IDSA and NCCN guidelines for prescribing vancomycin in adults patients with cancer with FN and a risk assessment tool for adverse clinical outcomes a pathway was developed to increase compliance with guidelines. 337 patient records were analyzed to evaluate effectiveness of FN clinical pathway at academic medical center. Patients admitted with FN and no allergy to beta-lactam were included. Four groups were evaluated: pre-pathway vancomycin use consistent with guidelines, post-pathway vancomycin use consistent with guidelines, post-pathway vancomycin use inconsistent with guidelines and post-pathway vancomycin use inconsistent with guidelines. Vancomycin use was defined as use for at least 48 hours to exclude those receiving it for procedural prophylaxis.

• N = 337   
• AGE: Adults reported in mean and standard deviation for each group. Consistent vancomycin pre = 59 (SD = 13.3), consistent vancomycin post = 59.4 (SD = 15.6), inconsistent vancomycin pre = 55.5 (SD = 15.3), inconsistent vancomycin post = 51.3 (SD = 12.2)
• MALES: 59%  
• FEMALES: 41%
• CURRENT TREATMENT: Chemotherapy, other
• KEY DISEASE CHARACTERISTICS: Hematologic malignancy, solid tumor malignancy, stem cell transplantation autologous and stem cell transplantation allogeneic
• OTHER KEY SAMPLE CHARACTERISTICS: Patients with diagnosis of neutropenia ICD 9 codes 288.00, 288.02, 288.03, 288.04, 299.08, and ICD 9 for fever. Adult FN patients who received an appropriate anti-pseudomonal beta-lactam with or without vancomycin were included in the analysis. Patients transferred from outside facility or with documented penicillin or vancomycin allergy were excluded.

• SITE: Single site   
• SETTING TYPE: Not specified    
• LOCATION: University of Chicago Medical Center

• PHASE OF CARE: Active anti-tumor treatment
• APPLICATIONS: Elder care

Evaluate appropriate prescribing of vancomycin based on consistency with guideline recommendations pre- and post-implementation of a FN clinical pathway.

Antimicrobial usage report generated from electronic medical record. Hematopoietic Cell Transplantation Comorbidity Index (HCT CI)

The rate of vancomycin use, inconsistent with guideline recommendations in the pre-pathway implementation time frame, was significantly greater (n = 74, 35.9%) versus use in the post-pathway implementation time frame (n = 5, 11.4%; p = 0.001). No comorbidities or specific HCT CI scores were predictive of vancomycin without indication on multivariate analysis.

Implementation of a guideline-based pathway for FN in adult patients with cancer can significantly improve adherence to guideline recommendations for antimicrobial (vancomycin) use

• Findings not generalizable
• Other limitations/explanation: The use of HCT CI has not been validated in another malignancy except hematologic

Use of clinical pathways can improve compliance with guidelines for managing at-risk patients, leading to better outcomes.

Implement a pathway to achieve Time To Antibiotics (TTA) in less than 60 minutes form presentation for outpatient evaluation of FN in pediatric patients with cancer. Other endpoint was to improve bedside nurses’ understanding of fever, neutropenia, and importance of Rapid Time To Antibiotics (RTTA).

Implementation of Clinical Pathway for RTTA in less than 60 minutes

Inservice and poster board used to educate nurses about fever and neutropenia. Knowledge measured with pre- and post-tests.

• N: 25 patients and 12 nurses
• AGE: From birth to age 18 years
• MALES: Not reported  
• FEMALES: Not reported
• CURRENT TREATMENT: Combination radiation and chemotherapy
• KEY DISEASE CHARACTERISTICS: Pediatric oncology patients in the Ambulatory Infusion Center with fever and neutropenia receiving antibiotics.  Patients without implanted vascular access devices were excluded.

• SITE: Single site   
• SETTING TYPE: Outpatient    
• LOCATION: University of Chicago

• PHASE OF CARE: Active anti-tumor treatment
• APPLICATIONS: Pediatrics

TTA was tracked using retrospective chart review to determine pre-pathway metrics.

Retrospective chart review using electronic health record filters was used for pre-pathway data collection. A computerized spreadsheet was used for post-pathway data collection.

Nursing knowledge was tested using a 9-item Fever and Neutropenia Questionaire. A bulletin board with key FN concepts and an in-service by APNs were sources of education.

Nurses had a mean score of 7.5 correct answers for the pre-education questionnaire and an 8.92 mean score for post-education (p = 0.0002).

Improvement in nurses knowledge of FN was improved with education and TTA was improved with a clinical pathway. The study included a very small sample of pediatric patients and nurses from one cancer center, resulting in limited application to other settings.

• Small sample (< 30)
• Measurement validity/reliability questionable 
• Findings not generalizable

Based on literature review and limited findings of this QI project, clinical pathways and nursing education are successful ways to improve care of patients with FN. Recommendations for implementing in other settings will need larger studies demonstrating success with these interventions to demonstrate applicability.

To estimate the odds of FN, beginning with second chemotherapy cycle, among patients who received prophylactic pegfilgrastim in that cycle and all previous cycles versus those who received prophylactic pegfilgrastim in all previous cycles only.

This is a descriptive study using a retrospective matched-cohort design utilizing pooled data from two healthcare claims repositories, the MarketScan Database and LifeLink Database, spanning the period from January 1, 2010 through September 30, 2015. The study is not prospective, but rather completes a secondary analysis of existing data.

• N: 8,450 matched pairs of patients undergoing chemotherapy: comparison group received pegfilgrastim following first cycle only, source group received pegfilgrastim following each cycle
• AGE: Mean in comparison = 53.6 years, in pegfilgrastim = 53.9 years 
• MALES: Not identified, missing data 
• FEMALES: Not identified; study reports 89% of matched patients had breast cancer and 2% ovarian 
• CURRENT TREATMENT: Chemotherapy
• KEY DISEASE CHARACTERISTICS: 89% of matched had breast cancer, 7% had NHL, 2% lung, 2% ovarian, less than 1% colorectal
• OTHER KEY SAMPLE CHARACTERISTICS: 52% of the 89% of those with breast cancer received doxyrubicin and cyclophosphamide. The majority  of participants had surgery within the preceding 90 days

• SITE: Multi-site
• SETTING TYPE: Not specified; data obtained from larger number of participating private U.S. health plans. Appears to be primarily outpatients receiving chemotherapy with some hospital admissions    
• LOCATION: Varied throughout the United States

PHASE OF CARE: Active anti-tumor treatment

Retrospective matched-cohort design

Comparison of the incidence and odds ratios of FN were determined between comparison and pegfilgrastim patients. Data was evaluated using generalized estimating equation regression models. No standardized measurement or instrument used; data obtained from charts.

Second-cycle incidence of FN was greater is the comparison patients with an odds ratio of 1.7 and p < 0.001 (broad definition). Second-cycle incidence proportions for FN was greater in the comparison group (narrow definition), with an odds ratio of 4.3 and p < 0.001. All cycles from the third through course completions, the odds ratio for FN was 1.6 with p < 0.001 (broad definition).

In this retrospective, matched-cohort study, those who did not continue pegfilgrastim prophylaxis subsequent to the first cycle of chemotherapy had a higher risk for FN compared to those who continue pegfilgrastim prophylaxis after each cycle of chemotherapy. Therefore, the administration of pegfilgrastim following each chemotherapy cycle (as opposed to abbreviated use) appears to have a protective effective in reducing the incidence of FN.

• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• Risk of bias (no appropriate attentional control condition)
• Unintended interventions or applicable interventions not described that would influence results
• Selective outcomes reporting
• Key sample group differences that could influence results
• Measurement/methods not well described
• Measurement validity/reliability questionable 
• Findings not generalizable
• Other limitations/explanation: Cannot be generalized to the larger population due to the lack of rigor in the design. The non-experimental retrospective design cannot establish causal relationships, only show correlations. In addition, those whose who are publicly insured and older adults were poorly represented. Lastly, the study was funded by maker of pegfilgrastim and the authors are stockholders in Amgen.

This retrospective, matched-cohort study indicates that premature discontinuation of pegfilgrastim prophylaxis following chemotherapy is commonplace in U.S. practice and is associated with additional febrile neutropenia events. The decision to prematurely discontinue pegfilgrastim prophylaxis following chemotherapy should be carefully weighed against the associated risk of FN. Although this study was a retrospective design, the findings continue to support the importance of adhering to current standards of nursing care practice with pegfilgrastim prophylaxis for the prevention of FN. Additional independent research is necessary, particularly evaluating the risk of FN in the older adult and publicly insured populations, which are under-represented in this study.

To describe GCSF use and incidence of febrile neutropenia in patients aged 60 years or older with diffuse large B-cell lymphoma receiving initial CHOP or R-CHOP therapy.

Patients enrolled on the United States Intergroup Trial (CALGB 9793/ECOGSWOG 4494) were randomized to CHOP or RCHOP chemotherapy for the initial treatment of diffuse large B-cell lymphoma. The protocol did not allow CSF use for the first cycle.  

If day 1 ANC was less than 1,500 cells/mm³, treatment was delayed a week. If FN occurred in the prior treatment cycle, cyclophosphamide and doxorubicin doses were reduced by 50% in the next cycle. These doses could be increased by 25% if the subsequent cycle was well tolerated, with no grade 3/4 hematologic toxicities.
Colony stimulating factor (CSF) could be used starting with second cycle to maintain dose intensity in event of neutropenic fever or dose reduction/delay.

• N = 520   
• AGE: 60 years or older
• MALES: 50%  
• FEMALES: 50%
• CURRENT TREATMENT: Chemotherapy
• KEY DISEASE CHARACTERISTICS: Previously untreated diffuse large B-cell lymphoma
• OTHER KEY SAMPLE CHARACTERISTICS: Age greater than 60 years and receiving initial therapy with RCHOP or CHOP on the United States Intergroup Trial (CALGB 9793/ECOGSWOG 4494)

• SITE: Multi-site   
• SETTING TYPE: Outpatient    
• LOCATION: United States

• PHASE OF CARE: Active anti-tumor treatment
• APPLICATIONS: Elder care

Observational study

Data measured included the timeliness of chemotherapy administration (treatment delay), CSF use, reason for CSF use, febrile neutropenia, neutropenia, and chemotherapy dose reduction.

49% of patients received CSF during therapy. The median number of cycles for which CSF was used was three (range = 1-7) and the median duration of CSDF use was nine days. CSF was used to prevent chemotherapy dose reduction/dose delay in approximately 60% of patients, and for secondary prophylaxis in cycle(s) following FN hospitalization in one third of patients. Overall CSF was used during 16% of administered chemotherapy cycles. Significantly more patients were treated with CSF in later cycles of therapy. FN occurred in 41% of patients, and 38% of the episodes occurred in cycle 1.

For patients with diffuse large B-cell lymphoma who are 60 years of age and older who are receiving initial therapy with CHOP or RCHOP, CSFs helped maintain dose intensity and to prevent febrile neutropenia.

• Risk of bias (no control group)
• Risk of bias (no blinding)
• Risk of bias (no random assignment)

CSF is recommended for patients with diffuse large B-cell lymphoma who are 60 years of age and older who are receiving initial therapy with CHOP or RCHOP to prevent febrile neutropenia and maintain dose intensity. This is consistent with current standard practice.