Chemotherapy-related cognitive impairment and non-pharmacological interventions targeting the nervous system: a systematic review.

Background: Chemotherapy-related cognitive impairment (CRCI) represents an increasingly recognized problem in the growing cancer survivor population within the US and worldwide. CRCI is characterized by deficits in memory, sustained attention, and executive function, which significantly worsens the cancer survivors' quality of life. An increasing number of studies have been conducted using novel intervention approaches aimed at mitigating CRCI. In this systematic review, we sought to summarize the current evidence of cognitive improvement in cancer survivors receiving non-pharmacological interventions with neurostimulatory effects following chemotherapy. Methods: We screened five databases (Embase, MEDLINE, PubMED, Scopus, and PsycINFO) for original articles reporting the administration of any type of brain stimulation or complementary/alternative therapies targeting the central and/or peripheral nervous system to improve cognitive outcomes in cancer survivors reporting CRCI. We systematically extracted information from each eligible study using participant, intervention, comparison, outcome(s), and study design (PICOS) framework according to Cochrane recommendations. We used the critical appraisal tool by Joanna Briggs Institute to assess the risk of bias. Results: After screening 2,708 manuscripts, we performed a full-text review of 77 papers and identified 17 studies that met our inclusion criteria: nine randomized controlled trials, four case reports, one case series, two quasi-experimental study, and one cohort study. We identified seven studies which focused on CRCI and 10 others where cognitive function was properly reported for inclusion. Subjective and objective cognitive outcome measures reflecting overall performance, attention, working memory, processing speed, and quality of life with separate cognitive function reporting were assessed in patient(s) treated with transcranial direct current stimulation, transcranial magnetic stimulation, multisensory stimulation, Flexyx neurotherapy system, acupuncture, and electroacupuncture. Mild improvements in some of the cognitive outcome measures were observed in all studies. The weaknesses of these studies can be attributed to insufficient statistical power and testing, lack of a control group, randomization, blinding, and incorrect statistical methods. Discussion and conclusion: We found only a handful of trials reporting cognitive outcomes in CRCI interventions, with small sample sizes and biased study designs limiting the validity of the statistically significant findings. Our systematic review provides rationale for assessing the impact of non-pharmacological neurostimulatory techniques on CRCI in large-scale randomized controlled trials.