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Zimmer, P., Trebing, S., Timmers-Trebing, U., Schenk, A., Paust, R., Bloch, W., . . . Baumann, F.T. (2017). Eight-week, multimodal exercise counteracts a progress of chemotherapy-induced peripheral neuropathy and improves balance and strength in metastasized colorectal cancer patients: A randomized controlled trial. Supportive Care in Cancer, 26, 615–624.

Study Purpose

This study investigates the connection of providing an eight-week guided multimodal exercise class twice a week to patients with metastatic colorectal cancer in hopes of influencing their chemotherapy-induced peripheral neuropathy.

Intervention Characteristics/Basic Study Process

30 outpatients with metastatic colorectal cancer and with a history of chemotherapy treatment were recruited to participate in a randomized control trial. The intervention group participated in an eight-week supervised multimodal exercise class twice a week/60 min. This class included endurance, resistance, and balance training. The control group was given written recommendations to complete physical activity. Chemotherapy-induced peripheral neuropathy was measured using the FACT/COC-NTX questionnaire. Endurance capacity, strength, and balance were also measured at three separate intervals: before, after, and four weeks post-study.

Sample Characteristics

  • N: 30  (24 completed the study) 
  • AGE: The mean age of the intervention group was 68.53 years. The mean age of the control group was 70 years (NS)
  • MALES: 21 (70%) 
  • FEMALES: 9 (30%) 
  • CURRENT TREATMENT: Chemotherapy, other
  • KEY DISEASE CHARACTERISTICS: Metastatic colorectal cancer

Setting

  • SITE: Single site   
  • SETTING TYPE: Outpatient    
  • LOCATION: Germany

Phase of Care and Clinical Applications

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

Study Design

Randomized control trial

Measurement Instruments/Methods

  • FACT/GOG-NTX questionnaire for chemotherapy-induced peripheral neuropathy
  • 6MWT for endurance measurement
  • H1RM for strength measurement
  • GGT-Rehab for balance measure

Results

The study showed significant improvement in neuropathic symptoms in the intervention group compared to worsening symptoms in the control group (p = 0.023). Increase of balance was noted between groups (p = 0.048) along with static balance (TOI, p = 0.022; NXT, p = 0.006). The intervention group noted an increase in strength from baseline: bench press (p = 0.006), leg press (p = 0.002), and lat pull down (p < 0.001)

Conclusions

The implementation of a multimodal, supervised exercise program showed significance in counteracting the neuropathic symptoms related to chemotherapy, increasing muscle strength and increasing balance in patients with metastatic colorectal cancer.

Limitations

  • Small sample (< 30)
  • Subject withdrawals ≥ 10%
  • Other limitations/explanation: Unclear which exercise modality is responsible for the positive results.

Nursing Implications

Patients at risk for chemotherapy-induced peripheral neuropathy (CINP) could benefit from a supervised multimodality exercise class to counteract the worsening effects of CINP. Providing your patients with written instruction for exercise might not be enough of an intervention to combat the worsening of this side effect.

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Kumar, S.K., Laubach, J.P., Giove, T.J., Quick, M., Neuwirth, R., Yung, G., . . . Richardson, P.G. (2017). Impact of concomitant dexamethasone dosing schedule on bortezomib-induced peripheral neuropathy in multiple myeloma. British Journal of Haematology, 178, 756–763.

Purpose

STUDY PURPOSE: Evaluate different methods of dexamethasone dosing with bortezomib on severity of peripheral neuropathy

TYPE OF STUDY: Meta-analysis and systematic review

Search Strategy

DATABASES USED: PubMed from 2002 to June 14, 2015 and ASCO annual meeting abstracts from 2008 to June 14, 2015

YEARS INCLUDED: (Overall for all databases) as above

INCLUSION CRITERIA: (a) IV bortezomib, (b) at least 20 untreated participants with myeloma, and (c) reported grade of neuropathy

EXCLUSION CRITERIA: Not a clinical trial; studies focusing on bortezomib maintenance rather than initial treatment; retrospective studies

Literature Evaluated

TOTAL REFERENCES RETRIEVED: Not included

EVALUATION METHOD AND COMMENTS ON LITERATURE USED: Studies were categorized as dexamethasone partnered with bortezomib, weekly dosing, or other dosing schedule; only clinical trials used; no other evaluation of quality mentioned

Sample Characteristics

FINAL NUMBER STUDIES INCLUDED: 32

TOTAL PATIENTS INCLUDED IN REVIEW: 2,697

SAMPLE RANGE ACROSS STUDIES: Varying dexamethasone dosing schedules, 14 partnered, 6 weekly

KEY SAMPLE CHARACTERISTICS: All had multiple myeloma and were receiving initial treatment with bortezomib and dexamethasone.

Phase of Care and Clinical Applications

PHASE OF CARE: Active antitumor treatment     

APPLICATIONS: Palliative care

Results

Pooled grade 3 or higher PN for partnered, weekly, or other schedules were 5.3%, 11%, and 9.6%, respectively. Patients on weekly or other schedules had higher rates of grade 3 or higher PN. Overall, all grade PN for partnered, weekly, or other schedules were 45.5%, 63.9%, and 47.5%, respectively. When studies including thalidomide were omitted from the analysis, the lower incidence of grade 3 or higher PN in partnered dexamethasone dosing was still present.

Conclusions

Partnered dexamethasone dosing schedule (day of and day after) may result in less severe PN. There was consistently lower all grade and grade 3 or higher PN with partnered dosing when compared to other dosing schedules.

Limitations

  • Low sample sizes
  • Only multiple myeloma included; possible investigator bias

Nursing Implications

Nurses should be aware that, in patients undergoing initial treatment with bortezomib and dexamethasone, partnered dexamethasone may be preferred due to potentially less severe neuropathy.

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Hanai, A., Ishiguro, H., Sozu, T., Tsuda, M., Yano, I., Nakagawa, T., . . . Tsuboyama, T. (2018). Effects of cryotherapy on objective and subjective symptoms of paclitaxel-induced neuropathy: Prospective self-controlled trial. Journal of the National Cancer Institute, 110, 141–148.

Study Purpose

To investigate the effectiveness of cryotherapy to prevent paclitaxel-induced peripheral neuropathy.

Intervention Characteristics/Basic Study Process

Each patient wore frozen flexible gloves and socks on their dominant hand and foot (15 minutes before paclitaxel administration to 15 minutes after the infusion was complete: 90 minutes total). Gloves were replaced after the first 45 minutes.

Sample Characteristics

  • N = 36   
  • AGE: Mean age = 56 years, SD = 13.8
  • MALES (%): Not reported  
  • FEMALES (%): Not reported
  • CURRENT TREATMENT: Chemotherapy
  • KEY DISEASE CHARACTERISTICS: Patients with breast cancer undergoing paclitaxel therapy
  • OTHER KEY SAMPLE CHARACTERISTICS: Body mass index (BMI) mean score = 22.4

Setting

  • SITE: Single site   
  • SETTING TYPE: Outpatient    
  • LOCATION: Kyoto University Hospital, Japan

Phase of Care and Clinical Applications

PHASE OF CARE: Active antitumor treatment

Study Design

Controlled clinical trial where patients served as their own controls

Measurement Instruments/Methods

Symptoms were assessed before chemotherapy at baseline and before each subsequent cycle. Semmes-Weinstein monofilament test (PN, tactile disturbance), thermal simulator to measure thermosensory disturbance (objective symptoms), tuning form to measure vibration perception (objective symptoms), manipulative dexterity to measure performance speed (objective symptom), PROs (Japanese version of the PNQ a validated measure of neuropathy and activities of daily living), cryotherapy tolerability (ad hoc questions), electrophysiological signs (conduction velocity and action potential amplitude of the median nerve), and PKs36

Results

No patients dropped out due to cold intolerance. Pain was reported in 8.2%, and feeling cold was reported in 4.2%. The primary endpoint was tactile deterioration, which was clinically and statistically significantly lower for the intervention side (hand = 27.8% versus 80.6%, OR = 20, p < 0.001; foot = 25% versus 63.9%, OR = infinite, p < 0.001). For secondary endpoints, CIPN occurred faster on the control side than on the intervention side (hand HR = 0.13; foot HR = 0.13). Additional secondary endpoints also reported.

Conclusions

Cryotherapy appears to have efficacy for the prevention of CIPN. In this study, the development of subjective CIPN symptoms was almost completely prevented at a cumulative dose of 960 mg/m2.

Limitations

  • Small sample (< 100)
  • Risk of bias (no blinding)
  • Risk of bias (no random assignment)
  • Intervention expensive, impractical, or training needs
  • Other limitations/explanation: No information on gender or smoking history. No information was provided about the manufacturer of the gloves or socks and the cost. Unknown cost and workflow implications for patients and staff/institution.

Nursing Implications

Cryotherapy is a promising intervention to prevent CIPN. Additional studies are needed to determine the long-term effects of this therapy on the development of CIPN symptoms in patients treated with paclitaxel.

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Fu, X., Wu, H., Li, J., Wang, C., Li, M., Ma, Q., & Yang, W. (2017). Efficacy of drug interventions for chemotherapy-induced chronic peripheral neurotoxicity: A network meta-analysis. Frontiers in Neurology, 8, 223.

Purpose

STUDY PURPOSE: To evaluate status of research on pharmacologic interventions for CIPN

TYPE OF STUDY: Meta-analysis and systematic review

Search Strategy

DATABASES USED: Medline, Embase, and China National Knowledge Internet

YEARS INCLUDED: (Overall for all databases) Information for dates of search not provided, articles included were from 1995 to 2014

INCLUSION CRITERIA: The study (a) assessed CIPN in patients with cancer, (b) compared two or more drugs or placebo, (c) provided sufficient data to assess differences, and (c) assessed incidence or severity of CIPN

EXCLUSION CRITERIA: None listed

Literature Evaluated

TOTAL REFERENCES RETRIEVED: 1,839

EVALUATION METHOD AND COMMENTS ON LITERATURE USED: No description of quality evaluation

Sample Characteristics

FINAL NUMBER STUDIES INCLUDED: 23

TOTAL PATIENTS INCLUDED IN REVIEW: 2,298

SAMPLE RANGE ACROSS STUDIES: 20-732

KEY SAMPLE CHARACTERISTICS: All but one of the studies focused on patients getting platinum-based chemotherapy and 12 of 23 only included people with colorectal cancer.

Phase of Care and Clinical Applications

PHASE OF CARE: Active antitumor treatment

Results

Contrary to the title, this article does not include any commonly prescribed prescription drugs, including gabapentin, pregabalin, or duloxetine. This review included studies of amifostine, Vitamin E, calcium and magnesium infusions, and glutathione. Eighteen studies had a placebo control group and had no control group. Neither blinding nor control were needed for inclusion. Findings indicate that Vitamin E and amifostine reduce incidence of CIPN, while glutathione and amifostine reduced severity of CIPN. There was one study (n = 20) included that had patients getting amifostine who all had cervical cancer and were receiving cisplatin with radiation therapy. The authors of this original study (Gallardo et al., 1999) found no statistically significant difference in neurotoxicity between those getting amifostine and those who did not. It is therefore unclear how the authors of the meta-analysis found otherwise. There was also only a single study of glutathione versus placebo versus calcium/magnesium (n = 93, 33 of whom received glutathione) included. The original study (Dong et al., 2010) showed no significant differences in CIPN incidence or severity between the three groups. Four studies of Vitamin E, two which were placebo controlled and two with no control group.

Conclusions

The limitations, including lack of quality control, small sample sizes, focus on platinum use, and GI malignancies, limit the generalizability of the findings from this meta-analysis.

Limitations

  • Limited search
  • Limited number of studies included
  • No quality evaluation
  • Low sample sizes

Nursing Implications

Findings from this study suggest that amifostine, glutathione, and Vitamin E may be helpful for CIPN but no recommendations for practice can be made at this time due to limitations of this meta-analysis.

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Bernstein, L.J., McCreath, G.A., Nyhof-Young, J., Dissanayake, D., & Rich, J.B. (2018). A brief psychoeducational intervention improves memory contentment in breast cancer survivors with cognitive concerns: Results of a single-arm prospective study. Supportive Care in Cancer, 26, 2851–2859.

Study Purpose

To assess the impact of a brief, individualized, psychoeducational intervention on the self-management of cancer-related cognitive dysfunction (CRCD) for survivors of breast cancer. Primary endpoint: memory contentment; secondary endpoints: knowledge, attitudes, and behaviors related to CRCD.

Intervention Characteristics/Basic Study Process

Participants received a one-hour individualized psychoeducational intervention delivered by a clinical neuropsychologist that was tailored specifically to their level of knowledge and specific complaints related to CRCD. Content included information on CRCD, strategies to reduce frustration and normalize the experience, as well as specific strategies to improve memory. Strategies were not practiced during the session; however, participants selected one or two specific goals to regularly practice between assessment timepoints.

Sample Characteristics

  • N = 100   
  • AGE: 18 or older, mean age = 52.19 (range = 35-79)
  • FEMALES: 100%
  • CURRENT TREATMENT: Chemotherapy, radiation, combination radiation and chemotherapy, immunotherapy, and other
  • KEY DISEASE CHARACTERISTICS: Female patients diagnosed with breast cancer, not restricted by stage of disease, previous or current treatment. The majority had stage I or II disease and had completed chemotherapy and/or radiation. Half were currently receiving endocrine therapy. 
  • OTHER KEY SAMPLE CHARACTERISTICS: The majority were well educated at the college level or above and were currently employed.

Setting

  • SITE: Single site   
  • SETTING TYPE: Outpatient    
  • LOCATION: Princess Margaret Cancer Center

Phase of Care and Clinical Applications

PHASE OF CARE: Multiple phases of care

Study Design

Single-arm, prospective, longitudinal study

Measurement Instruments/Methods

  • Multifactorial Memory Questionnaire (MMQ)--contentment subscale
  • Researcher-developed instrument to measure CRCD knowledge (2 items), symptom distress (2 items), self-efficacy for CRCD management (3 items), satisfaction with the intervention (2 items), and effectiveness of compensatory strategies (3 items)

Results

Memory contentment improved from T1 to T2 (p < 0.001, Cohen’s d = 0.58) and T1 to T3 (p < 0.001, d = 0.77). 

Reliable Change Index (RCI) indicated statistically reliable change for 32% following the intervention. Reliable change was durable at six weeks postintervention for 38%. 

Participants’ statistically significant improvement in memory contentment after the intervention remained lower than published norms at six weeks follow-up (p < 0.001, d = -0.93). 

Lower baseline memory contentment predicted increased improvement postintervention (T1-T2: b = -0.18, p = 0.004; T1-T3: b = -0.18, p = -0.023). Change in memory contentment from baseline to six weeks postintervention was positively associated with compensatory strategy effectiveness (b = 3.73, p = 0.011).

Conclusions

The researchers concluded that the brief one-hour, individualized psychoeducational intervention appeared to be effective and durable in relieving distress from CRCD and improving memory contentment and self-efficacy for managing CRCD. They also concluded that the results supported generalizability of the intervention effectiveness to survivors currently on treatment.

Limitations

  • 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)
  • Subject withdrawals ≥ 10%
  • Other limitations/explanation: Subjective measures only

Nursing Implications

Individually tailored psychoeducational interventions for CRCD may be efficacious for facilitating self-efficacy in coping strategies and improvement of memory contentment for survivors of breast cancer. Future study with a randomized controlled design is needed for further validation and investigation of the intervention.

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Myers, J.S., Erickson, K.I., Sereika, S.M., & Bender, C.M. (2018). Exercise as an intervention to mitigate decreased cognitive function from cancer and cancer treatment: An integrative review. Cancer Nursing, 41, 327–343.

Purpose

STUDY PURPOSE: To determine the effectiveness of exercise for minimizing cognitive impairment related to cancer and/or cancer-treatment.

TYPE OF STUDY: Systematic integrative review

Search Strategy

DATABASES USED: PsycINFO, PubMed, CINAHL

YEARS INCLUDED: (Overall for all databases) though January 2016

INCLUSION CRITERIA: Quantitative studies evaluating effectiveness of exercise for maintaining cognitive functioning in adult patients with cancer with objective and/or subjective assessments 

EXCLUSION CRITERIA: Studies published in a language other than English.

Literature Evaluated

TOTAL REFERENCES RETRIEVED: 232 citations screened, but only 26 met study eligibility criteria.

EVALUATION METHOD AND COMMENTS ON LITERATURE USED: The Grading of Recommendations Assessment, Development and Evaluating tool was used to appraise the quality of evidence for study outcomes.

Sample Characteristics

FINAL NUMBER STUDIES INCLUDED: 26

TOTAL PATIENTS INCLUDED IN REVIEW: 2,145 

SAMPLE RANGE ACROSS STUDIES: 4 to 658 participants.

KEY SAMPLE CHARACTERISTICS: 85% of studies included breast cancer survivors, 77% of all participants received chemotherapy and 31% received radiation therapy.

Phase of Care and Clinical Applications

PHASE OF CARE: Late effects and survivorship

Results

Twenty-six studies evaluated the effectiveness of exercise on improving various cognitive functions (CF) (i.e., memory [M], attention/concentration [AC], executive function [EF], information processing speed [IPS], language [L]) or perceived cognitive function (PCF). Forty-two percent of the studies were randomized controlled trials (n = 11), 42% were quasiexperimental (n = 11), 11.5% were observational (n = 3), and one case study. Interventions included aerobic exercise (n = 4), resistance exercise (n = 3), combination of aerobic and resistance exercise (n = 7), aerobic exercise with another modality (e.g., methylphenidate, psycho-education, behavioral intervention) (n = 4), and mindfulness-based exercise (i.e., yoga, Tai chi, Qigong) (n = 8). Of note, 15% of studies did not have an intervention but, rather, relied on patient self-report regarding exercise.  

Eighty-one percent of studies used subjective measures, but only 35% included objective measures of CF. In addition, there was a great deal of variability between instruments used as well the frequency or timing of evaluation. Eighty-eight percent of studies were longitudinal and assessed patients at baseline until less than three months (26%), three months (52%), or six months (22%). While some studies found significant improvements in PCF and/or various cognitive domains (e.g., IPS, AC, EF, L, M), these results were not consistent across studies.

Conclusions

Findings from this study revealed that there is insufficient good quality evidence to determine whether exercise may improve cognitive functioning in cancer survivors.  Although exercise may be beneficial in improving cognitive functioning, there is insufficient evidence to determine the type of exercise, including duration and frequency, that would be recommended. Additional research, including multi-site studies with large sample sizes and higher quality evidence, are needed to determine the effectiveness that specific types of exercise might have a role in alleviating cognitive impairment.

Limitations

  • Limited search
  • Mostly low quality/high risk of bias studies

Nursing Implications

Study findings do not support recommending exercise for improving cognitive impairment in cancer survivors. However additional research using these interventions are recommended to further determine their effectiveness.

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Larkey, L.K., Roe, D.J., Smith, L., & Millstine, D. (2016). Exploratory outcome assessment of Qigong/Tai Chi Easy on breast cancer survivors. Complementary Therapies in Medicine, 29, 196–203.

Study Purpose

Explore whether meditative movement improves cognitive function, quality of life, physical activity, and body mass index (BMI) in postmenopausal women with breast cancer who report clinically significant fatigue.

Intervention Characteristics/Basic Study Process

The intervention included two groups: meditative movement (consisting of Qigong and Tai Chi Easy movements) versus sham Qigong (consisting of similar movements without meditative components), both of which were referred to as rejuvenating movement to blind participants. Participants completed 14 one-hour sessions over 12 weeks with interventionists and were asked to complete 30-minute DVD-guided sessions at home five days per week. Study assessments were done before groups began, at the end of the groups (i.e., 12 weeks post-baseline), and three months after the groups ended.

Sample Characteristics

  • N = 87   
  • AGE: mean = 58.8 years (SD = 8.94)
  • FEMALES: 100%
  • CURRENT TREATMENT: Other
  • KEY DISEASE CHARACTERISTICS: Initial diagnosis of nonmetastatic, invasive breast cancer
  • OTHER KEY SAMPLE CHARACTERISTICS: 91% White, 59% completed some college, stage 0-III, no recurrence or other cancers, 69% on endocrine therapy, completed adjuvant chemotherapy and/or radiation therapy six months to five years before enrollment, currently reporting clinically significant fatigue; excluded for moderately severe or greater depressive symptoms, BMI > 32, comorbidities and medications affecting fatigue and sleep, smoking/excessive alcohol consumption, and routine mind-body practices.

Setting

  • SITE: Single site   
  • SETTING TYPE: Outpatient    
  • LOCATION: Arizona

Phase of Care and Clinical Applications

PHASE OF CARE: Late effects and survivorship

Study Design

Double-blind randomized controlled trial of meditative movement versus sham control with repeated measures

Measurement Instruments/Methods

  • Cognitive impairment: Functional Assessment of Cancer Therapy-Cognitive Function (subjective); Digit Span and Letter-Number Sequencing (attention and working memory)
  • Other measures: SF-36 for quality of life, Brief Physical Activity Questionnaire

Results

Feasibility: 86% completed the study, adherence to intervention sessions and home practice not reported; no adverse events

Cognitive impairment: No group differences at baseline. Both groups improved in self-reported cognitive function and attention/working memory tests (time effects, p < 0.05), but no differences were found between the groups (no group by time effect).

Other outcomes: No group differences at baseline. BMI decreased in the meditative movement group but increased in the sham control group (p = 0.0048).  All other outcomes showed similar pattern to cognitive impairment (i.e., significant time effects for both groups, but no group by time effects).

Conclusions

This exploratory pilot study suggests that meditative movement does not improve cognitive function more than gentle movement without mindfulness. Although both types of movement may improve cognitive impairment, it is unclear if improvement was due simply to participating in groups.

Limitations

  • Small sample (< 100)
  • Measurement validity/reliability questionable 
  • Findings not generalizable
  • Subject withdrawals ≥ 10%
  • Other limitations/explanation: This secondary analysis used data from a larger study not designed to evaluate cognitive function comprehensively. The neuropsychological tests used did not capture all domains of cognitive function. The participants reported very few cognitive problems at baseline (potential floor effect). In addition, the sample size was determined based on primary outcome of fatigue, so whether there was sufficient statistical power to detect differences in cognitive outcomes is unclear. Therefore, definitive conclusions cannot be drawn about cognitive impairment. This single-site pilot study is not generalizable to all postmenopausal women with breast cancer.

Nursing Implications

Study findings do not support suggesting meditative movement exercises such as Qigong or Tai Chi over other types of gentle physical activity to improve cognitive impairment reported by postmenopausal women with breast cancer. The findings do support future well-powered studies using these types of interventions.

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Bray, V.J., Dhillon, H.M., Bell, M.L., Kabourakis, M., Fiero, M.H., Yip, D., . . . Vardy, J.L. (2017). Evaluation of a web-based cognitive rehabilitation program in cancer survivors reporting cognitive symptoms after chemotherapy. Journal of Clinical Oncology, 35, 217–225.

Study Purpose

The purpose was to compare results of a cognitive rehabilitation program to standard care in patients reporting cognitive symptoms.

Intervention Characteristics/Basic Study Process

All subjects participated in a 30-minute telephone consultation outlining cognitive compensatory strategies prior to study group assignment. Patients were randomly assigned to intervention and control groups. The intervention was a computerized neurocognitive program targeting visual precision, divided attention, working memory, and visual processing speed, which was provided as a CD. Patients were to use training for four 40-minute sessions per week for 15 weeks. The program had an automated measure of compliance. Study assessments were completed by patients at baseline, after 15 weeks, and 6 months later.

Sample Characteristics

  • N = 242 in ITT analysis   
  • AGE: Range 23-74 years, median 53
  • MALES: 5%  
  • FEMALES: 95%
  • KEY DISEASE CHARACTERISTICS: Solid tumors; had completed definitive treatment within a mean of 27 months reporting quite a bit of changes or greater in concentration or memory on the EORTC QLC–C30 cognitive function scale. The majority had breast cancer. About 70% were on hormone therapy.

Setting

  • SITE: Multisite   
  • SETTING TYPE: Outpatient    
  • LOCATION: Australia

Phase of Care and Clinical Applications

PHASE OF CARE: Late effects and survivorship

Study Design

Longitudinal randomized clinical trial

Measurement Instruments/Methods

  • FACT-COG questionnaire
  • Cogstate computerized testing
  • General Health Questionnaire (for anxiety and depression)
  • FACT-General 
  • FACT-Fatigue 
  • Perceived Stress Scale

Results

Only 86% of those in the intervention group used the program. Average total training time was 25 hours of the recommended 40 hours. Patients in the intervention group had better outcomes on the FACT-Cog compared to controls at 15 weeks on all subscales with better perceived cognitive abilities (p < 0.001), less perceived cognitive impairment (p < 0.001) with less impact on quality of life (p = 0.02), and less comments from others regarding cognitive functioning (p = 0.04). However, these differences were sustained at six months only for perceived cognitive impairment (p = 0.001) and perceived cognitive abilities (p < 0.001) but not for the other subscales. Similarly, those in the intervention group had less anxiety and depression (p = 0.02), fatigue (p = 0.03), and perceived stress (p = 0.03) at 15 months. Differences remained only for perceived stress (p = 0.01) at six months. There were no differences between groups in Cogstate measures of neuropsychological function. There was no evidence of dose response for training time and patient outcomes.

Conclusions

The computerized cognitive rehabilitation program tested here showed benefit in terms of patient-reported outcomes of cognitive function but no effect on objective measures of neuropsychological function. There were short-term improvements in anxiety, depression, and fatigue with the intervention that were not sustained.

Limitations

  • Risk of bias (no blinding)
  • Risk of bias (no appropriate attentional control condition)
  • Measurement validity/reliability questionable
  • Intervention expensive, impractical, or training needs
  • Other limitations/explanation: Single-scale scores were used for measurement of anxiety and depression outcomes. 14% of the intervention group never used the program, raising the question of overall usefulness for a variety of patients. There were varied numbers of patients lost to follow-up at various time points with different measures and it is not clear which participants and results were included in ITT analysis.

Nursing Implications

Findings suggest that computerized cognitive rehabilitation may improve patient perceptions of cognitive functioning; however, these findings were not consistent with objective measures. Actual benefit of computerized cognitive training for cancer treatment-related cognitive impairment remains unclear.

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Ercoli, L.M., Petersen, L., Hunter, A.M., Castellon, S.A., Kwan, L., Kahn-Mills, B.A., . . . Ganz, P.A. (2015). Cognitive rehabilitation group intervention for breast cancer survivors: Results of a randomized clinical trial. Psycho-Oncology, 24, 1360–1367.

Study Purpose

The purpose was to evaluate the efficacy of a cognitive rehabilitation intervention on self-report of cognitive dysfunction, performance on neuropsychological tests, and brain functioning.

Intervention Characteristics/Basic Study Process

Five weekly, manualized, two-hour sessions included two difficulty levels of in-class cognitive training and three levels of homework exercises that were designed to build skills in the targeted areas of attention, executive function, and memory. Participants were encouraged to do four 20-minute sessions of homework exercises per week. Participants received a training manual workbook, auditory exercises CDs, answer keys, and a stopwatch. In-class education also included instruction on coping strategies to minimize anxiety (e.g., deep breathing, relaxation, pacing, countering negative thoughts). Goal attainment was discussed during the group sessions to facilitate setting individual short-term and long-term goals. These specific intervention details were published in 2013 with the results of the single-arm pilot study and not iterated in the 2015 article. Neurocognitive testing, self-report instruments, and qEEG (substudy) were administered at baseline (T0), within one week (T1), and two (T2) and four (T3) months from completing the intervention.

Sample Characteristics

  • N = 48; 29 in EEG substudy   
  • AGE: mean = 53.8 years, SD = 8.2
  • FEMALES: 100%
  • CURRENT TREATMENT: Other
  • KEY DISEASE CHARACTERISTICS: Breast cancer survivors within 18 months to 5 years after initial treatment completion who reported persistent cognitive complaints that interfered with daily activities and scored at least one item on the memory scale of the PAOFI as moderately severe. Ongoing endocrine therapy was allowed. Inclusion requirements were within 21-75 years of age and stage 0-III breast cancer. 
  • OTHER KEY SAMPLE CHARACTERISTICS: Participants primarily were Caucasian (90%), married (79%), well educated (54% had postcollege degrees), status postchemotherapy (77%) and radiation therapy (75%), and were currently receiving endocrine therapy (71%). Exclusion criteria included uncontrolled depression, current psychiatric disorder, chronic concurrent use of psychoactive medications, central nervous system (CNS) disorders, previous intrathecal chemotherapy or cranial radiation, previous head trauma, seizures, or learning disability, or substance abuse disorder.

Setting

  • SITE: Single site   
  • SETTING TYPE: Outpatient    
  • LOCATION: UCLA, Los Angeles, CA

Phase of Care and Clinical Applications

PHASE OF CARE: Late effects and survivorship

Study Design

Randomized, wait-list controlled, interventional study. Powered on previous single-arm pilot study. Used block randomization (2:1). Intent-to-treat analyses

Measurement Instruments/Methods

CNS vital signs computerized testing platform

  •     Finger tapping dominant, finger tapping nondominant
  •     Shifting attention test
  •     Stroop reaction time
  •     Continuous performance test
  •     Symbol digit test

Rey Auditory Verbal Learning Test (RAVLT) 

Brief Visuospatial Memory Test, Revised

Verbal fluency test

Trail Making Tests A and B

Paced Auditory Serial Addition Test

Wechsler Test of Adult Reading (WTAR)

Patient’s Assessment of Own Functioning Inventory (PAOFI)

Beck Depression Inventory, 2nd edition (BDI-II)

Awake and resting state quantitative electroencephalography (qEEG)

Results

Improvement in PAOFI total scores and memory scale scores were significant for the intervention group (p = 0.01, Effect size (ES) 0.90 and 1.10 respectively). The intervention group improved on RAVLT total scores (trials I-V, p = 0.02, ES = 0.57) and delayed recall (p = 0.007, ES = 0.29). Both groups improved on BDI-II scores at T2 and T3 without significant group differences. The qEEG substudy demonstrated intervention group changes (T1 to T2) for global absolute delta power (p = 0.02) and absolute alpha power (AP, p = 0.04). Decreased delta power did not predict PAOFI improvement at T2 (p = 0.971), nor did increased AP (p = 0.137). However, increased AP predicted improved self-report of cognitive dysfunction at T3 (p = 0.012), even controlling for age and IQ (p = 0.011).

Conclusions

The intervention was associated with improved self-report of cognitive function and neuropsychological test performance sustained up to two months. The qEEG substudy demonstrated preliminary evidence of an overall decrease in delta power and increase in AP for the intervention group, suggesting qEEG may serve as a biomarker of intervention efficacy.

Limitations

  • Small sample (< 100)
  • Risk of bias (no appropriate attentional control condition)
  • Findings not generalizable

Nursing Implications

Study findings provided further evidence that cognitive rehabilitation is beneficial to improving perceived and actual cognitive function in breast cancer survivors. qEEG may be promising as an early biomarker of intervention effectiveness.

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