• STUDY PURPOSE: To assess the effects of cytokines and growth factors for preventing oral mucositis in patients with cancer who are receiving treatment.
• TYPE OF STUDY: Systematic review

• DATABASES USED: Cochrane Oral Health’s information specialist searched the following databases: Cochrane Oral Health’s Trials Register (searched May 2017); the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 4) in the Cochrane Library (searched May 2017); MEDLINE Ovid (1946 to May 2017); Embase Ovid (December 2015 to May 2017); CINAHL EBSCO (Cumulative Index to Nursing and Allied Health Literature; 1937 to May 2017); and CANCERLIT PubMed (1950 to May 2017). The U.S. National Institutes of Health Ongoing Trials Register (ClinicalTrials.gov) and the World Health Organization International Clinical Trials Registry Platform were searched for ongoing trials. 
• YEARS INCLUDED: Through May 2017 
• INCLUSION CRITERIA: RCTs
• EXCLUSION CRITERIA:Not a RCT or unclear; stomatitis incidence reported in adverse events table; unclear if mucositis was oral or gastrointestinal; study stopped early with very few participants enrolled; oral mucositis not mentioned and unknown if measured; some participants had oral mucositis at baseline; crossover study with no reporting of first-period data; results reported by cycle assuming independence; survival/cure was primary outcome with mucositis (unclear if oral or gastrointestinal) as a toxicity

• TOTAL REFERENCES RETRIEVED: 3,145
• EVALUATION METHOD AND COMMENTS ON LITERATURE USED: Two review authors independently screened the results of electronic searches, extracted data, and assessed risk of bias. For dichotomous outcomes, they reported risk ratios (RR) and 95% confidence intervals (CI). For continuous outcomes, they reported mean differences (MD) and 95% CIs. They pooled similar studies in random-effects meta-analyses. 

• FINAL NUMBER STUDIES INCLUDED: 35 (published from 1993 to 2017) 
• TOTAL PATIENTS INCLUDED IN REVIEW: 3,102 
• SAMPLE RANGE ACROSS STUDIES: Fourteen studies enrolled participants with hematological cancers. Eighteen studies enrolled participants with solid cancers: head and neck, colorectal, breast, and sarcoma. The remaining three studies enrolled a mixture of participants with solid cancers and participants with hematological cancers, two of which were 80%-90% solid, and the other study only 3% solid.
• KEY SAMPLE CHARACTERISTICS: All patients being treated for cancer, aged 1 to 87 years old

PHASE OF CARE: Active anti-tumor treatment

• There might be a reduction in the risk of moderate to severe oral mucositis in adults receiving bone marrow/stem cell transplantation after conditioning therapy for hematological cancers (RR = 0.89, 95% CI [0.8, 0.99]; 6 studies; 852 participants; low-quality evidence).
• A possible reduction in the risk of severe oral mucositis in bone marrow/stem cell transplantation after conditioning therapy for hematological cancers, but there is also some possibility of an increase in risk (RR = 0.85, 95% CI [0.65, 1.11]; 6 studies; 852 participants; low-quality evidence).  
• Probably a reduction in the risk of moderate to severe oral mucositis in adults receiving radiotherapy to the head and neck with cisplatin or fluorouracil (RR = 0.91, 95% CI [0.83, 1]; 3 studies; 471 participants; moderate-quality evidence). 
• Likely that there is a reduction in the risk of severe oral mucositis in adults receiving radiotherapy to the head and neck (RR = 0.79, 95% CI [0.69, 0.9]; 3 studies; 471 participants; high-quality evidence)
• Likely that there is a reduction in the risk of moderate to severe oral mucositis in adults receiving chemotherapy alone for mixed solid and hematologic cancers (RR = 0.56, 95% CI [0.45, 0.7]; 4 studies; 344 participants; moderate-quality evidence)
• Might be a reduction in the risk of severe oral mucositis in this population (RR = 0.3, 95% CI [0.14, 0.65]; 3 studies; 263 participants; low-quality evidence)

Although authors concluded that KGF is beneficial in the prevention of oral mucositis in adults who are receiving (a) radiotherapy to the head and neck with cisplatin or fluorouracil, or (b) chemotherapy alone for mixed solid and hematologic cancers, the results are not conclusive. Could conclude likely effective but not established

• Low sample sizes
• 13 studies (37%) were at low overall risk of bias
• 12 studies (34%) were at unclear overall risk of bias.
• 10 studies (29%) were at high overall risk of bias

The analysis showed inconsistent effect of KGF (keratinocyte growth factor). Because of the concern of cost and benefit, this is not strong evidence enough to recommend.

To study the effects of oral bismuth in patients prior to autologous stem cell transplantation on reducing the adverse effects of high-dose chemotherapy, including mucositis, neutropenia, and bacteremia.

Randomized, double-blind controlled study either to intervention or placebo group. Bismuth or placebo was 1,000 mg × 2 orally daily for 5 days, followed by 10 days with a daily dose of 500 mg × 2 orally. The first 5 days of bismuth or placebo treatment were prior to the start of chemotherapy regimens, which started on day −3 (multiple myeloma) and day −7 (lymphoma) before ASCT (day 0). The 10 days on the lower dose of bismuth or placebo also started on day −3 (multiple myeloma) and day −7 (lymphoma). On day +4, all patients received 6 mg pegfilgrastim to reduce neutropenia.

• N = 50   
• AGE: 32-73 years
• MALES: 66%  
• FEMALES: 34%
• CURRENT TREATMENT: Chemotherapy
• KEY DISEASE CHARACTERISTICS: Diagnosis of multiple myeloma or lymphoma 
• OTHER KEY SAMPLE CHARACTERISTICS: Autologous stem cell transplantation candidates

• SITE: Single site   
• SETTING TYPE: Inpatient    
• LOCATION: Copenhagen, Denmark

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

• Randomized, double-blind study to one of two groups receiving oral bismuth or a placebo 

Laboratory results: Hemoglobin, leukocytes, differential count, thrombocytes, and reticulocytes. Stomatitis, diarrhea, fever, febrile neutropenia and documented infections based on the Common Criteria for Adverse Events, version 3.0.

Results showed a reduction in grade 2 stomatitis, febrile neutropenia, and infections caused by high-dose chemotherapy. Bismuth reduced significantly the incidence of grade 2 stomatitis, as it occurred only in 2 of 13 patients (15%, two-tailed p = 0.001)

Oral bismuth is shown to be effective in certain patient groups. Oral bismuth may be effective in reducing high-dose chemotherapy effects of mucositis, neutropenia, and infections. The study indicates that there may be a gender difference in side effects; therefore, more studies are warranted to determine the impact of gender differences of treatment and prevention of cytotoxic effects of the treatment.

Small sample (< 100)

First study to use this intervention in hematologic inpatients. More research is needed on the preventative properties of oral bismuth.

• STUDY PURPOSE: To evaluate effect of prophylactic and therapeutic low-level laser therapy (LLLT) in pediatric and young patients with cancer or undergoing HSCT.
• TYPE OF STUDY: Meta analysis and systematic review

• DATABASES USED: Cochrane Central Register of Controlled Trials, Embase, MEDLINE, Web of Science, China Biology Medicine (CBM), Wanfang Database, and China National Knowledge Infrastructure (CNKI)
• YEARS INCLUDED: (overall for all databases) Years searched was unclear. Included articles were as old as 2007. The newest study was from 2017.
• INCLUSION CRITERIA: The randomized controlled trials and clinical controlled trials. Study participants were younger than age 23 years at diagnosis of any type of childhood cancer or undergoing HSCT. Both prophylaxis and therapeutic use of LLLT were included.  
• EXCLUSION CRITERIA: Not specified, but can assume studies that do not fit inclusion criteria were excluded.

• TOTAL REFERENCES RETRIEVED: 202
• EVALUATION METHOD AND COMMENTS ON LITERATURE USED: The authors made reasonable effort to evaluate articles. The authors also used Cochrane Collaboration’s tool for assessing potential risk of bias for each article.

• FINAL NUMBER STUDIES INCLUDED: 8 
• TOTAL PATIENTS INCLUDED IN REVIEW: Occurrence of OM after prophylactic LLLT = 213 (ex, 106; con, 107);  grade 3 or higher OM after prophylactic LLLT = 173 (ex, 86; con, 87); OM severity after prophylactic LLLT = 96(ex, 44; con, 52); OM severity after therapeutic LLLT = 160 (ex, 79; con, 81); oral pain after therapeutic LLLT = 139 (ex, 70; con 69) 
• SAMPLE RANGE ACROSS STUDIES: 16-123 
• KEY SAMPLE CHARACTERISTICS: Patients with various solid tumors or lymphoma and leukemia who underwent HSCT

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

• After prophylactic LLLT, the OR for developing OM was significantly lower compared with placebo (OR = 0.5, 95% CI [0.29, 0.87], p = 0.01) 
• The OR for developing grade III OM or worse was statistically significantly lower compared with placebo (OR = 0.3, 95% CI [0.1, 0.9], p = 0.03) 
• The OM severity was statistically significantly lower compared with placebo (SMD = −0.56, 95% CI [−0.98, −0.14], p = 0.009) 
• For therapeutic LLLT, the OM severity was significantly reduced compared to routine care (SMD = −1.18, 95% CI [−1.52, −0.84], p < 0.00001) 
• Oral pain was also reduced after LLLT over routine care (MD = −0.73, 95% CI [−1.36, −0.11], p = 0.02)

• Prophylactic LLLT reduces mucositis and severe mucositis and decreases the average severity of oral mucositis in pediatric and young patients with cancer.
• Therapeutic LLLT also reduces the average severity of oral mucositis and oral pain.

Low sample sizes

LLLT is effective to reduce mucositis and associated pain in pediatric patients with cancer overall. Despite of the deliveries of LLLT vary among the studies, it has been consistent to show the reduction of mucositis in pediatric population.

• STUDY PURPOSE: To optimize the prophylactic treatment for radiotherapy-induced oral mucositis in patients with head and neck cancer receiving postoperative or definitive radiotherapy with or without chemotherapy
• TYPE OF STUDY: Network meta analysis and systematic review

• DATABASES USED: PubMed, Web of Science, Cochrane Library, and Chinese databases (WangFang, National Knowledge Infrastructure) 
• YEARS INCLUDED: (Overall for all databases) Authors stated the search was up to May 1, 2017. Supplemental material shows the oldest study included was 1989.  
• INCLUSION CRITERIA: Head and neck cancer or carcinoma or neoplasm, nasopharyngeal carcinoma or cancer or neoplasm, radiotherapy and mucositis 
• EXCLUSION CRITERIA: Not specified

TOTAL REFERENCES RETRIEVED: 112 randomized clinical trials were identified. 10 excluded that did not adopt the required criteria to evaluate oral mucositis, 28 studies or conference abstracts that did not provide a detailed number of responders and non-responders, 2 trials that recruited patients with previous chemotherapy, 5 studies that only evaluated mucositis-related pain, and 10 studies with the intention of treatment. 57 studies were eligible. 

EVALUATION METHOD AND COMMENTS ON LITERATURE USED: Randomization procedure, establishment of sample size, adoption of blinding in the study design, allocation of concealment if intention-to-treat analysis was followed, loss to follow-up, and dropout. Used the revised Jadad/Oxford quality scoring system to quantify study quality.

• FINAL NUMBER STUDIES INCLUDED: 57
• TOTAL PATIENTS INCLUDED IN REVIEW: 5,261 patients randomly assigned 
• SAMPLE RANGE ACROSS STUDIES: Not specified in this version of article.  
• KEY SAMPLE CHARACTERISTICS: Not specified in this version of article

PHASE OF CARE: Active anti-tumor treatment

• Direct meta analysis findings for grade 0–2 oral mucositis: Abs: SOC, AIS: PS, AVS: PS, CHS: PS, GFS: PS, GS: PS, GS: SOC, HS: SOC, LS: PS, LS: SOC, PS: SOC
• SOC and PS had worse effects and LS had better effects than most of the other treatments; details in supplementary materials
• In the network of 12 treatment arms, LS ranked as best and SOC as least effective in preventing grade 3 and 4 mucositis 

Abbreviations: SOC–standard oral care; ABS–antibiotics + SOC; AIS–anti-inflammatory + SOC; AVS–aloe vera + SOC, CAS–coating agents + SOC, CHS–Chinese herbs + SOC, GCS–granulocyte-macrophage colony–stimulating factor + SOC, GFS–growth factor + SOC, GS–glutamine + SOC, HS–honey + SOC, LS–laser + SOC, PS–placebo + SOC; NMT–non-medication treatment

Radiotherapy-induced oral mucositis in patients with head and neck cancer can be debilitating. This network meta-analysis compared prophylactic treatments in patients receiving postoperative radiation with or without chemotherapy. Low-level laser therapy in addition to standard of care may be more effective in reducing oral mucositis than standard care alone.

Limited information provided in the printed lack of control for or limit use of chemotherapy; not clear what constituted low-level laser therapy or the details regarding the other treatments.

Oral mucositis has been identified as a complex process; nurses should remain astute to changes in the oral cavity with the various treatments for cancer as well as changes over time. Interventions effective with a specific cancer treatment may not be universally effective. Study results should be read with a critical review process

This study aims to evaluate the time of onset and severity of mucositis in the treatment arm (aloe vera gel) versus the control arm in patients receiving head and neck radiation. Additionally, this study describes demographic variables that impact the severity of mucositis in patient undergoing radiation therapy of the head and neck. Secondary outcomes also included a comparison of hospitalization rates, need for analgesia, antifungals, and antibiotics, as well as nutritional support rates, rates of treatment interruption, and weight loss. Quality-of-life differences between groups was also assessed.

1. Using block randomization, subjects were assigned to a treatment or control arm
2. For patients in both groups, patients applied a thin layer of gel (presumably to the oral mucosa) three times daily throughout their radiation treatment. Patients were told not to drink/eat anything for 15 minutes. The treatment group applied 10% aloe vera, the control group gel was not specified other than a “base gel.”
3. The patients in both groups were assessed on day 1, 8, 15, 22, 29, 36, and “last day.”

• N = 100, 51 in treatment group, 49 in control group   
• AGE: Adult, 10  participants were younger than age 40 years, 28 participants were 41-50 years, 31 participants were 51-60 years, and 31 participants were older than age 60 years
• MALES: 85%  
• FEMALES: 15%
• CURRENT TREATMENT: Combination radiation therapy and chemotherapy
• KEY DISEASE CHARACTERISTICS: Patients with head and neck cancer undergoing radiation therapy or chemotherapy-radiation therapy
• OTHER KEY SAMPLE CHARACTERISTICS: Exclusion criteria included allergy to aloe vera, diabetes-mellitus, immune suppressants, and HIV-positive patients

• SITE: Single site   
• SETTING TYPE: Multiple settings    
• LOCATION: Mumbai, India

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

Randomized, double blind control study

• Data was collected using an interview schedule and an observational tool
• Primary outcomes: WHO grading of mucositis and VAS oral pain scores
• Secondary outcomes: Amount of antibiotic, antifungal, and analgesia used and on what day of treatment. Number of hospital admissions, nutritional support requirement, treatment interruption, weight loss, QOL: OMWQ-HN, and FACT-HN

Patients in the treatment group had later onset of mucositis (p < 0.05). The treatment group also had decreased severity of mucositis (p < 0.005). The treatment group had less weight loss and less need for supportive medications. The QOL measures were more favorable for the treatment group (p = 0.000 for OMWQ, p = 0.001 for FACT-HN). There was no difference between groups in hospitalization rates or the need for nutritional support. 

There is some discrepancy about oral pain results; the text says it was better in the treatment group but the p value listed is 0.243.

The author does not tell the reader anything about the statistical testing that was done, which limits the ability to interpret the results. The tables and charts are not completely labeled so they are hard to interpret as well.

• Measurement/methods not well described
• Measurement validity/reliability questionable
• Questionable protocol fidelity
• Other limitations/explanation: The statistical analysis is poorly described. Most of the data is reported as frequency and percent of occurrence. Although the onset of occurrence of mucositis is significant (p = 0.043), there is only a difference of either 0.7, but it does not state if this is 0.7 days or hours (the mean is 17.5 in the treatment group, 16.8 in the control group). The authors provide a z score of 1.7 and a df of 98). As far as analgesic requirements, the authors do not provide data. On grades of mucositis, the table only report on the grade on the last day of therapy, and the p value may be representative of all grades; however, grades 1 and 2 are worse in the experimental group and grade 3 is worse in the control group. It is difficult to interpret the data because the x and y axes are not labeled. There is no mention of how compliant patients were with the protocol; therefore, there is potential for poor protocol fidelity (Did the aloe vera feel good and the base solution not? Did it taste better/worse so people didn’t use it? All of this is unknown). It is very hard to delineate the magnitude of group differences across time. Seeing the raw data may help answer these questions.

Aloe vera gel may help decrease the time to development and severity of radiation-induced mucositis in patients with head and neck cancer.

The purpose of the study was to assess the effects of subcutaneous or IV fentanyl on dyspnea in patients with advanced cancer.

Subcutaneous or IV fentanyl for breathlessness at rest or with minimal exertion for patients with (a) decline in renal function and escalating doses transdermal fenatanyl/ or other opioid, and (b) alternative to transdermal fentanyl at discharge

• N = 72    
• AGE: 50% younger than 75 years old, 21% = 75-80 years old, 29% = 81 or older 
• MALES: 65%   
• FEMALES: 35% 
• CURRENT TREATMENT: Other
• KEY DISEASE CHARACTERISTICS: Mixed diagnoses 
• OTHER KEY SAMPLE CHARACTERISTICS: All patients with advanced cancer

• SITE: Single site   
• SETTING TYPE: Inpatient    
• LOCATION: Spain

PHASE OF CARE: End-of-life care
APPLICATIONS:  Pediatrics, elder care, palliative care

Retrospective cohort study

Breathlessness was measured on a 0-4 scale, other symptoms were measured with ESAS, MMSE/Pfeiffer, and Likert scales

Total percent of responders to fentanyl was 76%. Fentanyl efficacy was not statistically related to age, gender, cancer type, previous opioid treatment, steroid and midazolam doses, and PPS. The median fentanyl dose in responders was 25 mcg/h (interquartile range = 12–70). It was significantly related to age (37 versus 12 mcg/h, for ≤ 75 versus > 75 years, respectively; p = 0.02). There was not a significant difference between fentanyl doses of responders and non-responders. 36, 23, and 15 patients had sustained improvements in dyspnea over 48, 72, and 96 hours. Fentanyl had no significant toxicity.

Subcutaneous and IV fentanyl may be associated with dyspnea relief in patients with advanced cancer. No severe adverse effects were noted.

• Small sample (< 100)
• Risk of bias (no control group)
• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• Subject withdrawals ≥ 10%
• Other limitations/explanation: Single center experience

Subcutaneous and IV fentanyl may be related to dyspnea at rest relief in patients with advanced cancer. Additional research is need to confirm these results.

• STUDY PURPOSE: To examine the outcomes, experiences, and therapeutic components of holistic services. Definition of holistic services: “drawing on skills from multiple specialties and disciplines; using a holistic approach encompassing nonpharmacologic and pharmacologic interventions as indicated; and supporting self-management.”
• TYPE OF STUDY: Meta analysis and systematic review

• DATABASES USED: 9 
• YEARS INCLUDED: Database inception to June 2017
• INCLUSION CRITERIA: RCT, non-RCT, observational, and qualitative studies were included
• EXCLUSION CRITERIA: Grey literature

• TOTAL REFERENCES RETRIEVED: 3,239
• EVALUATION METHOD AND COMMENTS ON LITERATURE USED: Good methods, protocol registered in Prospero, and PRISMA methods followed.

• FINAL NUMBER STUDIES INCLUDED: 37 
• TOTAL PATIENTS INCLUDED IN REVIEW: Not reported as an aggregate, but individual studies described in tables
• SAMPLE RANGE ACROSS STUDIES: Described in tables
• KEY SAMPLE CHARACTERISTICS: Most patients had advanced cancer

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

Interventions represented 18 different services. Most services enrolled people with thoracic cancer, involved palliative care staff, and comprised 4–6 contacts over 4–6 weeks. Commonly used interventions included breathing techniques, psychological support, and relaxation techniques. Meta-analyses demonstrated reductions in Numeric Rating Scale distress due to breathlessness (n = 324; mean difference (MD) = −2.30, 95% CI [−4.43, −0.16], p = 0.03) and Hospital Anxiety and Depression Scale (HADS) depression scores (n = 408, MD = −1.67, 95% CI [−2.52, −0.81], p < 0.001). Statistically non-significant effects were observed for Chronic Respiratory Questionnaire (CRQ) mastery (n = 259, MD = 0.23, 95% CI [−0.1, 0.55], p = 0.17) and HADS anxiety scores (n = 552, MD = −1.59, 95% CI [−3.22, 0.05], p = 0.06). Patients and caregivers valued tailored education, self-management interventions, and expert staff providing person-centered, dignified care. There was no observable effect on health status or quality of life, and mixed evidence around physical function.

Evidence suggests an effect of integrative palliative care on the affective domain of breathlessness, and on psychological outcomes of anxiety and depression. Services were highly valued by patients and caregivers, who appreciated the education to help them understand their breathlessness, the provision of useful self-management interventions, and the provision of expert dignified care which centered on the person. No effect on overall health status or quality of life using generic measures and mixed evidence around any effect on physical function was identified

Integrative palliative care may provide a benefit to patients with advanced cancer.

To evaluate the effects of mediation group classes on patient and caregiver self-reported symptoms

This was an observational pilot that studied participants (patients and their caregivers) attending any of the three mediation group classes offered at a comprehensive cancer center. Classes were based on Tibetan mind-body mediation tradition, and spanned either 60 or 90 minutes in length, depending on type of class—power breath, sacred sounds, or movement and breath. Instructors of each mediation class consisted of mind-body therapists with at least five years of oncology experience. Participants completed a pre- and post-class Edmonton Symptom Assessment Scale (ESAS). Because participants could attend more than one meditation class, only data from the first visit of the 142 participants was examined. Data obtained from the ESAS was used to analyze symptoms individually and as subscales.

• N =142 (76 patients and 66 caregivers)   
• MEAN AGE: For patients: 57.5 years; for caregivers: 57.6 years
• MALES: Patients: 19.7%; caregivers: 22.7%  
• FEMALES: Patients: 80.3%; caregivers: 77.3%
• CURRENT TREATMENT: Participants spanned cancer continuum from prevention, active treatment, survivorship, or living with advanced cancer
• KEY DISEASE CHARACTERISTICS: Patient diagnoses included: breast (38.2%), hematologic (10.5%), skin (10.5%), thoracic/head and neck (9.2%), gastrointestinal (6.6%), gynecological (6.6%), and other (18.4%). Cancer staging included: local (56.6%), advanced (15.8%), and unstaged (27.6%)

• SITE: Single site   
• SETTING TYPE: Not specified    
• LOCATION: MD Anderson Cancer Center (Houston, Texas)

PHASE OF CARE: Multiple phases of care

Observational pilot that analyzed self-reported symptom information from patients and caregivers attending medication classes offered at a comprehensive cancer center between May and December 2015

ESAS was completed by participants before and after classes. Symptoms of the ESAS were analyzed both globally (subscales) and individually. ESAS subscales were scored as follows:

1. Global Distress Score (GDS) as sum of pain, fatigue, nausea, depression, anxiety, drowsiness, appetite, sense of well-being and shortness of breath (0-90)
2. Physical Distress Score (PHS) as sum of pain, fatigue, nausea, drowsiness, appetite, and shortness of breath (0-60)
3. Psychological Distress Score (PSS) as sum of depression and anxiety (0-20)

Clinically significant reduction of an individual symptom was defined as > 1; for ESAS global distress score (GDS) > 3; for physical distress score (PHS) > 2; for psychological distress score (PSS) > 2. Higher scores represented worse outcomes for the stated symptom or subscale.

For all participants there was a clinically and statistically significant decrease (improvement) in symptom of shortness of breath (mean = -1.2; p = 0.001), global distress (-5.17, p < 0.0001), fatigue (-1.34, p < 0.0001), anxiety (-1.26, p < 0.001). For patients, there was clinically significant improvement in dyspnea (mean = -1.12; p = 0.013). No clinically significant symptom change was observed when comparing class duration (60- versus 90-minute class). There was no clinically significant difference in participant symptom burden at baseline or in score reduction by group, or by attendance of one versus two or more classes.

Group mediation class, when used in conjunction to standard of therapy, shows a possible subjective improvement in shortness of breath, global distress, well-being, fatigue, and anxiety in the oncology population, but more research is warranted.

• Small sample (< 100)
• 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)
• Findings not generalizable
• Intervention expensive, impractical, or training needs
• Other limitations/explanation: A limitation to the use of mediation classes for symptom reduction in the oncology population is the need/cost for training such techniques as described in the study. The instructors of the meditation classes described in this study were mind-body practitioners with at least five years of oncology experience, and the institution already had a long-established integrative medicine program that was offered to patients on a rolling basis as part of standard of care by clinicians. Generalizability of the population is limited because of the fact that participants were self-selected and not randomized to meditation class. Also limiting generalizability was the fact that participants were of variable staging, cancer diagnoses, care spectrum, and caregivers. There was also no account for participants who may have attended a meditation class prior to the study period or engage in self-practice. For self-reported symptoms, the longitudinal effects of attending regular meditation class has not been examined. Assessments were immediately pre- and post-intervention, so it is unknown if there are any long-term benefits of meditation in this population.

Further research on the long-term effects and continued use of group meditation on shortness of breath is warranted.

• STUDY PURPOSE: To conduct a meta-analysis to establish the effect of exercise interventions on multiple physical symptoms, including fatigue, nausea/vomiting, pain, dyspnea, insomnia, loss of appetite, constipation, and diarrhea in patients with cancer
• TYPE OF STUDY: Systematic review

• DATABASES USED: Cochrane Library, the Center for Reviews and Dissemination, PubMed/MEDLINE, CINAHL, Scopus, PEDro, Health and Medical Collection, Psychology Database
• YEARS INCLUDED: Articles published before April 2017
• SEARCH TERMS: MeSH terms of cancer, tumor, randomized controlled trial, training, rehabilitation, and exercise, as well as outcome of physical symptoms
• INCLUSION CRITERIA: Included RCTs that evaluated the effects of exercise intervention by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 or the C15-PAL
• EXCLUSION CRITERIA: Excludes systematic reviews, editorials, cross-sectional studies, case reports, case series, and interventions that were not of high enough intensity (yoga, stretching, Pilates, and education). Also excluded shoulder exercise studies for breast patients and pelvic floor muscle training in gynecologic patients, as well was any trial that did not have a control group that received no major exercise intervention.

• TOTAL REFERENCES RETRIEVED: 743 (only 45 reviewed full-text after exclusion for study design)
• EVALUATION METHOD AND COMMENTS ON LITERATURE USED: Studies were evaluated for study design (RCT) and for data form, methodologic quality was evaluated with the PEDro scale

• FINAL NUMBER STUDIES INCLUDED: 10
• TOTAL PATIENTS INCLUDED IN REVIEW: 893 (434 in intervention groups)
• SAMPLE RANGE ACROSS STUDIES: Lists patients as having hematological malignancies (largest group), breast, prostate, and mixed cancer. Phases of care were heterogenous, although listed as “mainly postsurgery, posttransplantation (heme), and during chemotherapy
• KEY SAMPLE CHARACTERISTICS: Heme malignancy was most prevalent, states that the largest number of patients with lung cancer was 46 “at most”--total breakdown of cancer types was not provided.

• PHASE OF CARE: Varied
• APPLICATIONS:  Palliative care 

Results showed exercise positively affected the symptoms of fatigue (p = 0.0004), pain (p = 0.02), insomnia (p < 0.0001), dyspnea (p = 0.001), and no significant effect on nausea/vomiting, loss of appetite, constipation, or diarrhea. For dyspnea specifically, only within the mixed exercise program subgroup (as opposed to resistance alone or aerobic exercise alone) was an improvement effect in favor of the intervention group found.

This study concluded that it had confirmed that exercise interventions improve fatigue, pain, and insomnia in cancer, and that it had a novel finding of a benefit of exercise on dyspnea, but showed no effect on nausea/vomiting, loss of appetite, or constipation/diarrhea. The analysis did show significant results in the areas listed previously, although it is difficult to determine generalizability given the unknown sample characteristics. The effect of exercise on dyspnea was only seen with the mixed exercise groups, and it is difficult to understand who was included in that subgroup of patients; unclear, in particular, with cancer type and phase of case. The mechanism of dyspnea in a heme malignancy patient is very different, for example, than for a solid tumor patient, and there was a highly limited number of patients with lung cancer in this study. Not knowing phase of care also limits the ability to understand who this could be applied to. More exploration of the effect of exercise on dyspnea should be undertaken to reach solid conclusions, but this analysis does suggest that the exploration is warranted.

• Limited number of studies included
• Mostly low quality/high risk of bias studies
• It can be argued, also, that the search process itself had limitations by using only studies that measured outcomes from the two tools they chose and would limit a  number of high-quality studies using other tools.

With regard to dyspnea specifically, the nurse should be aware that there is a possibility that exercise may have an impact on dyspnea for some patients. It is unclear who these patients are, or what exercise regimens are most affected, so no clear recommendation can be provided to patients at this time based on this particular study.

• STUDY PURPOSE: Examine evidence on the effects of exercise interventions on fatigue, dyspnea, and depression.
• TYPE OF STUDY: Meta analysis and systematic review

• DATABASES USED: Using PRISMA guidelines, the databases CINAHL, MEDLINE, Embase, and Cochrane were accessed
• YEARS INCLUDED: 2000 to 2017
• INCLUSION CRITERIA: Lung cancer survivors, depression, fatigue, and dyspnea. 
• EXCLUSION CRITERIA: Patients undergoing therapy, duplicate studies, and participants aged 18 years or older, not primary research; fatigue, depression, and fatigue not outcome measures

• TOTAL REFERENCES: N = 852
• EVALUATION METHOD AND COMMENTS ON LITERATURE: Three researchers reviewed looking for dyspnea, fatigue, and depression as primary measures, looking for pre- and post-testing.

• STUDIES INCLUDED: 10  
• TOTAL PATIENTS INCLUDED: 516
• SAMPLE RANGE ACROSS STUDIES: 10 to 162.
• KEY SAMPLE CHARACTERISTICS: 58% were post-treatment for lung cancer

• PHASE OF CARE: Late effects and survivorship     
• APPLICATIONS: Elder care, palliative care 

Dimeo et al. (2004): After three weeks of exercises and relaxation, no significant results were noted for dyspnea, but were significant for fatigue (p = 0.67 and 0.54)

Glattki et al. (2012): In a study with pulmonary rehab measured using modified research council (MRC), the dyspnea scale was significant (p = 0.007, 0.26, SD = 0.61) for improvement in dyspnea.

Peddle-McIntyre et al. (2012): The MRC dyspnea scale was measured after 10 weeks and was not significant (pre = 1.6, SD = 0.6; post = 1.4, SD = 0.8).

Riesenberg and Lubbe (2010): The study showed significant improvements in dyspnea after four weeks of QLQ testing (p < 0.001) and also for fatigue (mean difference = -13.7).

Spruit et al. (2006): Using the BORG scale, no significant difference was found (p = 0.2969)

Overall, six studies reported statistically significant reductions in fatigue, two reported significant improvement in dyspnea, and one had significant reduction in depression.

Although there were some studies that showed that exercise interventions could possibly be effective for relief of symptoms such as dyspnea, the results were mixed, and there are unclear variations between programs and high dropout rates, so no recommendations can be made based on this particular analysis.

• Limited number of studies included
• Mostly low quality/high risk of bias studies

Nurses should be aware that there is the possibility that exercise may benefit some patients, and there is little risk of harm, but nurses should be aware that it is unclear what patients or what programs would be of benefit; therefore, no recommendations can be made at this time.