A uniform NCCN consensus determined that recommendations were appropriate (NCCN Category of Evidence and Consensus = 2A).

Some interventions that may be useful to improve or maintain cognitive function might not be included in these guidelines because this manuscript did not detail search strategies, inclusions and exclusions, or the number of articles included in the recommendations.

The NCCN cognitive function algorithm aids healthcare professionals considering the assessment and treatment of cancer-related cognitive function. Nonpharmacologic interventions should be recommended to oncology survivors experiencing cognitive issues. Pharmacologic interventions may be considered when medical conditions permit and potential contributing factors are ruled out or managed.

STUDY PURPOSE: To conduct a systematic review of the research evidence for the effects of Radix Astragali (RA)–based Chinese herbal medicine in the prevention and treatment of oxaliplatin-induced peripheral neuropathy (PN)

TYPE OF STUDY: Meta-analysis and systematic review

• FINAL NUMBER STUDIES INCLUDED = 24 
• TOTAL PATIENTS INCLUDED IN REVIEW = 1,552
• SAMPLE RANGE ACROSS STUDIES: 40–135; average size = 66
• KEY SAMPLE CHARACTERISTICS: 11 trials inpatients (n = 689); no setting identified for the other 13 trials (n = 863); 24 trials = 58.63% were male; colorectal cancer (n = 1,033); gastric cancer (n = 399); lung/breast/other cancers (n = 52), not specified (n = 68); range for total OXALI dose in all studies = 130 mg/m²–800 mg/m²; range for total OXALI dose in 11 trials 260–600 mg/m²

PHASE OF CARE: Not specified or not applicable; cannot determine if studies were in palliative care setting

APPLICATIONS: Elder care

• Fifteen RCTs comparing RA-based combined remedies to no intervention significantly reduced CIPN occurrence (n = 993 patients, odds ratio [OR] = 0.19, 95% CI confidence interval [0.14, 0.25], p < 0.01).
• One RCT comparing RA-based prescription to mecobalamin reduced CIPN occurrence (n = 42 patients, OR = 0.17, 95% CI [0.03, 0.94], p < 0.05).
• Two RCTs comparing RA-based prescription in addition to reduced glutathione versus calcium/magnesium infusions with the same conventional medications reduced CIPN occurrence (n = 120 patients, OR = 0.42, 95% CI [0.18, 0.97], p < 0.05).
• Fourteen RCTs comparing RA-based intervention versus no intervention significantly reduced the incidence of high-grade PN (11 trials used Levi’s grading) (n = 931 patients, OR = 0.17, 95% CI [0.09, 0.31], p < 0.01). No significant difference was found in the two trials comparing RA to mecobalamin or the two trials comparing RA to reduced glutathione or calcium/magnesium infusion with the same conventional medications. 
• Three RCTs comparing RA-based prescriptions and mecobalamin to mecobalamin alone found significant effect for RA-based prescription and mecobalamin in relieving CIPN (n = 213 patients, OR = 4.84, 95% CI [2.38, 9.83], p < 0.01).
• Six RCTs reported that the TA-based intervention significantly improved sensory nerve conduction velocity (MD = 4.42 m/s, 95% CI [3.27, 5.57], p < 0.01). No difference existed in motor nerve conduction velocity.
• No adverse events were reported in the 24 included studies for RA-based interventions. No consistent data was reported for quality of life, with only two trials including quality of life improvement after RA-based interventions.
• Funnel plots did not indicate publication bias.
• Effect sizes were not reported.

This meta-analysis indicated that RA-based interventions may provide potential benefit for oxaliplatin-induced PN. Although this meta-analysis did not show significant heterogeneity for different trial results, it did show considerable heterogeneity in the variables, treatments, and outcome measures studied. Studies included RA-based interventions with no reliable measures of drug composition, varied drug doses, self-made drug preparations, or RA combined with herbal compositions with variation in drug delivery methods. Therefore, it is premature to interpret these results as beneficial because of the substantial limitations for reliability and validity of the study results.

• Limited search
• High heterogeneity
• Low sample sizes
• Predominant yield of studies from only two databases: CNKI and Wanfang
• Safety, adverse event, or quality of life not used in search terms
• Twenty-four RCTs included three different CIPN grading scales.
• More than 50% of RA-based prescriptions included other herbal substances.
• No consistent reliable measure of drug composition
• Ten of the 24 RCTs had self-made prescriptions.
• Different RCT comparators (i.e., intervention, no intervention)
• More RCTs comparing RA-based prescription versus no intervention
• Doses/administration/duration of RA treatment different (oral = 10 RCTs, topical = 12 RCTs, IV = 1 RCT)
• Unclear phase of care or previous neurotoxic chemotherapy exposures
• Differences in duration of chemotherapy exposures and accumulated OXALI doses
• No multicenter large scale trials
• Effect sizes were not reported.

It remains unclear if RA provides benefit in alleviating oxaliplatin-induced PN. Additional RCTs are required to evaluate the reliable preparations of RA to investigate its full effects isolated in simple form versus its combined effect with other herbs. The effect of RA on the antitumor activity of oxaliplatin or other chemotherapeutic agents needs further study. Large multisite RCTs are needed to further evaluate drug safety in all phases of treatment and to identify the most effective dose, delivery method, duration of treatment, and quality of life.

Compare the immediate and long-term effects of true acupuncture versus sham acupuncture on hot flash frequency in women with breast cancer

The study included 72 women with breast cancer experiencing three or more hot flashes per day.

Patients were randomly assigned to receive either true or sham acupuncture.

The primary outcome measurement was hot flash frequency. Participants completed a hot flash diary for one day at days 7, 14, 21, 28, and 35.

The mean number of hot flashes per day was reduced from 8.7 to 6.2 in the true acupuncture group. The mean number of daily hot flashed was reduced from10.0 to 7.6 in the sham group. The true acupuncture was associated with 0.8 fewer hot flashes per day when compared to the sham at six weeks. This difference was not statistically significant. During the cross-over phase, participants in the sham group who received true acupuncture reported a further reduction in the frequency of hot flashes. The overall reduction in hot flash frequency persisted for up to 6 months after the completion of treatment.

The study was limited by a reliance on self-report instruments and recall. No physiologic measurements were used. The study may not have been of a sufficiently long duration and employed a modest sample size.

To determine if acupuncture reduced cancer-related fatigue (CRF) more effectively than did sham acupuncture.

Patients were randomized to an acupuncture or sham control group. Treatments were given once a week over six weeks. In the acupuncture group, a total of 14 needles were inserted at defined points during each session. The needles were stimulated manually and retained for 20 minutes. Sham needles, used in the control group, were blunt-tipped, moved up inside their handles when pressed against the skin, and did not penetrate the skin. In the control group, sham needles were applied in the same number and using the same technique as were the needles in the acupuncture group. Outcome measures were obtained at two weeks and at one week prior to the start of interventions and again at 42 and 49 days after completion.

• The study reported a sample of 74 patients (82% female, 18% male).
• Mean patient age was 53.5 years (range 45–59).
• Patients had multiple tumor types, and more than half had breast cancer.
• All had completed a course of chemotherapy at least 60 days prior to the study.

• Single site
• Outpatient
• Memorial Sloan Kettering Cancer Center, New York City, NY

Patients were undergoing the transition phase after initial treatment.

The study was a double-blind, randomized, sham-controlled trial.

• Brief Fatigue Inventory (BFI)
• Hospital Anxiety and Depression Scale (HADS)
• Functional Assessment of Cancer Therapy-General (FACT-G)

• At least 87% of participants completed all sessions.
• In both groups, total fatigue scores declined by approximately one point between baseline and follow-up.
• There were no differences between groups.
• Neither HADS nor FACT-G measures showed significant differences between groups.

The study showed that acupuncture had no effect on the symptoms of fatigue, anxiety, or depression.

• The study had a small sample size, with less than 100 participants.
• The drop-out rate was greater than 24%.
• The authors performed an intention-to-treat analysis, but they did not report their exact procedures.

The study did not demonstrate that acupuncture had an effect on fatigue, anxiety, or depression. The study contributes to a growing body of research that shows conflicting results regarding the effectiveness of this intervention for the management of fatigue. It has been shown that symptoms such as fatigue and anxiety tend to decline over time among patients with cancer. It is unclear if the timing in this study affected the results; symptoms may have declined with or without the intervention.

To compare, in thorascopy patients, the efficacy of intrapleural bupivacaine versus that of PCA fentanyl

All patients underwent a thorascopic operation during the study. Afterward, the F group received IV fentanyl (F) by means of patient-controlled analgesia (PCA). The IB group received intermittent intrapleural bolus delivery of bupivacaine plus fentanyl. The CB group received continuous intrapleural delivery of bupivacaine plus fentanyl.

PCA fentanyl was given as 40 mcg/hour basal rate with 30 mcg every 10 min as needed to a 160 mcg/hour maximum. Patients in the IB  group received an initial bolus of 0.25% bupivacaine and the same PCA fentanyl dosage as the fentanyl-only group. If the fentanyl escalation was insufficient, the patient was prescribed additional 50 mcg boluses as needed. Patients in the CB group received 5 ml/hour continuous infusion bupivacaine via chest tube as well as PCA fentanyl. In the CB group, if fentanyl escalation was insufficient, 15–30 mg ketorolac was administered intervenously.

Nurses obtained baseline pain measures at the first postoperative complaint of pain and request for additional analgesia. Pain was also measured at 6, 12, 18, and 24 hours after the operation.

• The sample was composed of 30 patients.
• In the F group, mean patient age was 56 years. In the IB group, mean patient age was 61 years. In the CB group, mean patient age was 60.
• Of all patients, 56.6% were female and 43.3% were male. All patients underwent, during the study, thorascopic operations to achieve nonanatomic lung resections. Of all patients, 80% had cancer.

• Single setting
• Inpatient
• Roswell Park Cancer Institute, Buffalo, New York

Nonblinded prospective randomized controlled trial

• Visual analog pain score (VAPS)
• Amount of fentanyl used

• During the first six hours, authors noted a statistically significant difference (p = 0.01) among groups in total fentanyl consumed. Patients in the intrapleural infusion groups had lower consumption.
• At six hours, three patients in the fentanyl-only group were not able to bring pain to an acceptable level (p = 0.04).
• Compared to the F group, more patients in both intrapleural groups required dose escalation. The continuous bupivacaine group contained the highest proportion of patients needing escalation (p = 0.08).
• Authors noted no differences in the proportion of patients whose pain improved from baseline, and the highest pain severity scores were similar across groups.

Administering local anesthetic through a chest tube catheter can reduce fentanyl consumption and pain after a thoracoscopy.

• The study had a small sample size, with fewer than 100 patients.
• Patients' relatively brief length of stay suggests that cases involved may have been carefully selected, subjecting the sample to bias.

Intrapleural bupivacaine can be used to reduce pain after a thoroscopy; however, this approach may require ongoing adjustment and dosage escalations to achieve sufficient pain control. Intrapleural infusion may reduce total opioid consumption and attendant side effects; however, the study evidenced no differences in terms of prevalence or severity of effects. The most appropriate and effective doses of intrapleural bupivacaine remain unclear. Authors note that the continuous intrapleural infusion approach is much more costly than the other interventions. Whether study findings warrant the increased cost is unclear.

The objective of the study was to compare tunneled pleural catheter drainage (TCD) to bedside talc pleurodesis (TP) via chest catheter for efficacy in controlling symptomatic unilateral malignant pleural effusions (MPE).

Randomized patients received one of two methods (TP or TCD) for pleural drainage then were followed up for 60 days. For the TP procedure, a single dose of 4–5 g of sterile talc slurry in 100 mL of saline was infused into the pleural space with a chest catheter. Placement was confirmed on a chest x-ray. Talc was administered within 36 hours of tube placement. The tube remained clamped for two hours for talc distribution. When the chest drainage decreased to 150 mL/24 hours, pleurodesis was assumed and the tube was removed. TP was performed on an inpatient basis. For TCD, catheters were drained daily with drainage bottles. No more than 1,000 mL were drained at a time, other than during the initial drainage. A chest x-ray was taken within 36 hours of initial drainage and the patient, a caregiver, or a visiting nurse drained the catheter daily after that. The catheter was removed when the drainage volume was less than 30 mL each day over three consecutive days. TCD is generally an outpatient procedure.

• The sample was comprised of 57 patients aged 60–67 years.
• Of the 57 patients, 45%–55% were males and 39%–61% were females.
• Patients had a performance status of 0 to 2 with no active pleural infection, talc allergy, or other indications to talc use.
• Lung cancer (62%) and breast cancer (12%) were the most common malignancies.
• The study originally planned 530 total patients for 90% power to detect differences in efficacy between the two methods of pleural drainage.
• Trapped lung was not recommended for randomized therapy, as TCD may be a better therapy option.

The study was conducted in 21 comprehensive cancer centers—17 cases were conducted at one instution, and 1–7 cases were conducted at each of the other institutions.

• Patients were undergoing multiple phases of care.
• The study has clinical applicability for elder care and palliative care.

The study was a prospective, randomized phase III trial.

• Lung re-expansion was determined by the treating physician using serial chest x-rays.
• Condensed Memorial Symptom Assessment Scale form (specific elements: performance status, dyspnea scale, physical function, social life, and overall quality of life) measured quality of life and specific symptoms or functionality.

• No statistical differences in lung expansion were noted between the two treatment arms, but it improved from baseline in both cases.
• The odds ratio for TCD success was five times higher than TP, and patients with good expansion experienced better success (odds ratio, 5; 95% CI, 1–25; P = .053).
• Pleurodesis occurred in 86.2% of patients treated with TP, compared with 68.0% of those treated with TCD (P = .1883).
• Therapy-related complications were low but were higher in the TCD arm.
• Recurrent dyspnea was seen only in TP cases, and dyspnea was statistically better in patients treated with TCD (8.7 vs. 5.9; P = .036) even after adjusting for baseline dyspnea score, initial drainage, gender, inpatient status, and performance status at baseline.
• No relationship was seen between baseline dyspnea score and lung expansion at any of the three points; however, 30-day dyspnea-free exercise and all quality-of-life measures correlated significantly with lung expansion.

• TCD is preferred for patients with complicated effusions or when the lung may be trapped.
• Although TCD prolongs therapy, this added duration may maintain lung expansion and improve quality-of-life parameters.
• Lung expansion may be an unreliable indicator of the benefits of pleural drainage.
• TCDs in this study may more predictably relieve dyspnea.
• The study had to be closed early because patients had a strong preference for treatment (inpatient vs. outpatient) and refused randomization.

• The study had a small sample size of less than 100 patients.
• The study had a risk of bias because of no blinding and its sample characteristics.
• Accrual was far less than anticipated due to patient preferences interfering with patient consent to randomization.
• Refusals to participate may have influenced the final study population, as evidenced by lower-than-anticipated success of talc pleurodesis intervention.
• The study does not describe that “malignant effusion” was validated cyopathologically.

• TCD and TP are both common strategies to manage malignant pleural effusion.
• Similar lung expansion appears to be able to be achieved with both techniques in patients with uncomplicated pleural effusion, and the selection of method may be based upon patient preference.
• Nurses should ensure that patients are thoroughly informed of therapeutic options to make the best decision for their circumstances.
• In cases in which patients experience distress form dyspnea at baseline, they may experience better symptom relief with the TCD method of managing malignant pleural effusions.

To test the feasibility of delivering problem-solving therapy via videophones

Videophones were installed for caregivers, and in an initial visit, caregivers were asked to review and prioritize common concerns. Three follow-up intervention calls were scheduled from days 5–16 of the hospice admission. Counseling via the videocalls was done to encourage caregivers to be creative and identify alternative solutions to stated problems, predicting consequences and developing an action plan, and trying out and evaluating the effect of the actions implemented. A final call was done to assess caregiver perceptions of the intervention. Calls were supervised to assure treatment fidelity.

• N = 42   
• MEAN AGE = 62 years
• MALES: 19%, FEMALES: 81%
• CURRENT TREATMENT: Not applicable
• KEY DISEASE CHARACTERISTICS: All were in hospice; no disease characteristics were reported.

• SITE: Single site   
• SETTING TYPE: Home    
• LOCATION: Washington

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

Quasiexperimental

• Caregiver Quality of Life Index (CQLI)
• Problem Solving Inventory (PSI)
• State-Trait Anxiety Inventory (STAI)
• Technical quality of video calls instrument

Caregivers reported lower anxiety scores after the intervention (p = 0.04). No significant changes occurred in other measures. Eighty-nine percent of attempted calls were successful, and the average technical quality was 48 out of a possible score of 50. Average call duration was 38 minutes (range = 18–84 minutes). Average usefulness of the intervention was rated as 4.8 by caregivers out of a possible score of 5.

The use of video calls to deliver psychoeducational interventions was generally feasible and well received by caregivers. The intervention was associated with a reduction in anxiety levels.

• Small sample (< 100)
• Risk of bias (no control group)
• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• Measurement/methods not well described
• Intervention expensive, impractical, or training needs
• Unclear how measurement instruments were completed
• Equipment for video calls may not be readily available.
• Type of patients and disease characteristics were not provided.

This study showed that the delivery of an intervention via video call was feasible and had benefit in terms of anxiety reduction for caregivers. Since the time of this study, technology has advanced, and it is more likely that video conferencing can be provided via the Internet. This can be a practical method for providing interventions to caregivers.

To compare the effectiveness of problem-solving therapy delivered via videophone versus face-to-face sessions

Caregivers were randomized to the experimental or face-to-face sessions for the intervention. Three videophone calls or sessions were done during 5–18 days after hospice admission. The intervention involved addressing problems initially identified by caregivers, visualization of effective problem solving, positive self-talk, brainstorming approaches to problems, setting goals and solutions, planning action, and evaluating effectiveness of actions taken. A final exit interview was conducted to elicit caregiver perceptions of the intervention. A manual for the intervention was used, all face-to-face visits and videophone calls were audio recorded, and a 10% random sample of recording was evaluated for treatment fidelity.

• N = 126   
• MEAN AGE = 59.6 years
• MALES: 25%, FEMALES: 75%
• OTHER KEY SAMPLE CHARACTERISTICS: Most were Caucasian and highly educated. Fifty-nine percent of caregivers were adult children of the patient and, in the majority of cases, the patient resided with the caregiver.

• SITE: Single site   
• SETTING TYPE: Multiple settings    
• LOCATION: Washington

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

Noninferiority, randomized, two-group trial

• Caregiver Quality of Life Index-Revised (CQLI-R)
• State-Trait Anxiety Inventory (STAIS); a six-point change was selected for measurement of noninferiority.
• Problem Solving Inventory (PSI)

Anxiety reduced significantly in both groups (p < 0.0001). The difference in the video group was not inferior to that in the face-to-face group, and the actual change in anxiety score was greater in the video group. No changes or differences occurred between groups in other study measures.

Delivery of problem-solving therapy, a cognitive behavioral therapy approach, by videophone was not inferior to delivery by face-to-face sessions.

• Risk of bias (no blinding)
• Subject withdrawals ≥ 10% 
• Participants mainly lost to follow-up because of patient death

The findings showed that a problem-solving intervention was effective to reduce stress in informal caregivers of patients in hospice, and the delivery of the intervention by videophone was not inferior to delivery by face-to-face sessions. Delivery of these types of interventions with technology can be a practical alternative to traditional methods of intervention.

To evaluate the use of transforming growth factor (TGF)-β2-enriched formula for amelioration of radiation-induced diarrhea for patients undergoing pelvic RT

There were three groups. Patients in group one were supported with TGF-β2-enriched formula from the first day of RT until at least one month after treatment completion. They used diphenoxylate-atropine tablets after the onset of diarrhea. Patients in group two started on diphenoxylate-atropine tablets and TGF-β2-enriched formula typically in the second week of  RT. They used TGF-β2-enriched formula for a period of at least one month after treatment completion. Patients in the third group received diphenoxylate-atropine tablets and feeding formulas (other TGF-β2-enriched formula) after onset of diarrhea, typically in the second week of  RT. They used TGF-β2-enriched formula for a period of at least one month after treatment completion. Diarrhea was measured weekly.

• N = 86  
• AGE RANGE: 35–77 years
• NUMBER OF MALES: 67  
• NUMBER OF FEMALES: 19
• KEY DISEASE CHARACTERISTICS: Malnourished patients undergoing RT for pelvic cancers

• SITE: Single site    
• SETTING TYPE: Outpatient    
• LOCATION: Gulhane Military Medical Academy, Ankara, Turkey

• PHASE OF CARE: Active antitumor treatment

• Retrospective analysis

• Common Terminology Criteria for Adverse Events (CTCAE) version 4

Patients receiving nutritional supplementation with TGR-β2-enriched formula (group one and two) experienced a lower median number of diarrhea episodes (p < 0.003) at all time points, and grade 2/3 diarrhea was also lower in these groups. Onset of diarrhea was typically the second week in all the groups. There was no statistical significance is diagnosis in the three groups. The number of patients with grade 2 diarrhea decreased after the second week of RT in groups one and two, and these patients did not experience grade 2 diarrhea one month after RT. However, the number of grade 2 diarrhea increased in group three after the second week of RT.

Patients receiving nutritional supplementation with TGF-β2-enriched formula had a decreased number of grade 2 and grade 3 diarrhea episodes compared to those receiving other nutritional supplements.

• Small sample (less than 100)
• Risk of bias (no control group)
• Risk of bias (no blinding)

Patients receiving nutritional supplementation with TGR-β2-enriched formula with diphenoxylate-atropine supplementation while receiving RT may reduce the incidence of diarrhea, but further studies are needed.