Day, J., Zienius, K., Gehring, K., Grosshans, D., Taphoorn, M., Grant, R., . . . Brown, P.D. (2014). Interventions for preventing and ameliorating cognitive deficits in adults treated with cranial irradiation. Cochrane Database of Systematic Reviews, 12, CD011335. 

DOI Link

Purpose

STUDY PURPOSE: To assess the efficacy of interventions aimed at preventing or managing cognitive impairment in adults who received cranial irradiation
 
TYPE OF STUDY: Systematic review

Search Strategy

DATABASES USED: For completed studies in database up to August 2014, Cochrane Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and PsychINFO; for ongoing studies: ClinicalTrials.gov, Physicians Data Query, abd Meta Register of Controlled Trails 
 
KEYWORDS: Cranial/skull, radiation/irradiation, brain neoplasm/tumor, glioma, cognitive disorders/impairment, mental processes/function, neurobehavioral manifestations, neuropsychological tests, memory, problem solving, attention, concentration, randomized control trial, randomized, control, placebo, clinical trials, and crossover
 
INCLUSION CRITERIA: Randomized, controlled trial (RCT) or non-RCT with control or comparison group; cranial irradiation (partial or whole); neuropsychological tests measuring cognitive function as primary outcome or as secondary outcome in a study where quality of life was primary outcome; measurements performed at baseline and at any intervention time point; intervention aimed at prevention or amelioration
 
EXCLUSION CRITERIA: Studies that used any form of radiation therapy as the primary intervention of interest such as hippocampal sparing, normal tissue sparing techniques such as intensity-modulated radiation therapy, chemotherapy administration with radiotherapy intervention

Literature Evaluated

TOTAL REFERENCES RETRIEVED: 16 
 
EVALUATION METHOD AND COMMENTS ON LITERATURE USED: The initial search yielded 3,422 records, which was reduced to 2,762 after the removal of duplicates. Sixteen studies were retrieved with six meeting final eligibility. Zero studies were included in the meta-analysis because of differences in interventions. Intervention foci were in two areas, the prevention of cognitive decline (n = 3) and the management of cognitive decline (n = 3). They included pharmacologic (n = 5) or nonpharmacologic interventions (n = 1). The authors used the Cochrane Handbook for Systematic Reviews of Interventions to abstract data (article details, methodology, population demographics, participant health status, intervention characteristics, primary and secondary outcomes, cognitive functioning results, additional outcome measures, and risk of bias). Efficacy was defined as (a) a statistically significant improvement in cognitive function or no change or decline in cognitive function from baseline measures for the prevention intervention, and (b) a statistically significant improvement in cognitive function or no change in function from baseline measures for the amelioration intervention.

Sample Characteristics

  • FINAL NUMBER STUDIES INCLUDED = 6
  • TOTAL PATIENTS INCLUDED IN REVIEW = 550 (prevention intervention); 169 (amelioration intervention)
  • KEY SAMPLE CHARACTERISTICS: In both intervention groups, adults aged ≥ 18 years, received radiotherapy for the treatment of brain metastasis, primary or secondary brain tumors, or prophylaxis for other cancer. For amelioration, intervention group documented cognitive impairment in at least one cognitive domain at baseline. At least 80% of the sample had to receive radiotherapy, and radiotherapy may have been provided during childhood, but the cognitive intervention performed in adulthood.

Phase of Care and Clinical Applications

PHASE OF CARE: Multiple phases of care

Results

Three cognitive interventions aimed at preventing cognitive decline during radiation therapy were reported. Two were pharmacologic. One tested memantine versus a placebo and found significant improvement in overall cognitive function, and one tested methylphenidate versus a placebo but failed to detect any significant differences between groups. The third study was nonpharmacologic and investigated the use of a rehabilitation program to prevent cognitive decline but did not statistically compare differences between groups. Three cognitive interventions aimed at ameliorating cognitive decline were reported. All three were pharmacologic studies. Two studies compared methylphenidate versus modafinil and one study examined donepezil versus a placebo. Both methylphenidate and modafinil interventions resulted in improved cognitive function. Combination therapy resulted in greater adverse events. Donepezil was found to improve the domain of memory after radiotherapy.

Conclusions

The authors reported that there was evidence for the use of memantine for preventing cognitive decline in patients receiving radiotherapy for brain metastasis. Likewise, there was supporting evidence for the use of donepezil in improving memory after radiotherapy for primary or metastatic brain tumors. There was limited evidence for cognitive behavioral or training interventions in preventing cognitive decline.

Limitations

  • Small sample sizes of less than 30 subjects
  • High risk of bias, particularly for nonpharmacologic interventions
  • Large number of patient withdrawals

Nursing Implications

Patients who receive cranial radiation therapy for primary brain tumors or metastatic lesions are at risk for declining cognitive function. The use of memantine during radiation therapy may aid in preventing cognitive decline. Those who develop cognitive decline after the completion of radiation therapy, even years afterwards, may benefit from donepezil administration. Additional exploration of interventions that may prevent or ameliorate cognitive decline related to cranial radiation therapy is warranted.

Legacy ID

5465