Hippocampal avoidance in whole brain radiotherapy and prophylactic cranial irradiation: a systematic review and meta-analysis.

PURPOSE: We systematically reviewed the current landscape of hippocampal-avoidance radiotherapy, focusing specifically on rates of hippocampal tumor recurrence and changes in neurocognitive function. METHODS: PubMed was queried for studies involving hippocampal-avoidance radiation therapy and results were screened using PRISMA guidelines. Results were analyzed for median overall survival, progression-free survival, hippocampal relapse rates, and neurocognitive function testing. RESULTS: Of 3709 search results, 19 articles were included and a total of 1611 patients analyzed. Of these studies, 7 were randomized controlled trials, 4 prospective cohort studies, and 8 retrospective cohort studies. All studies evaluated hippocampal-avoidance whole brain radiation treatment (WBRT) and/or prophylactic cranial irradiation (PCI) in patients with brain metastases. Hippocampal relapse rates were low (overall effect size = 0.04; 95% confidence interval [0.03, 0.05]) and there was no significant difference in risk of relapse between the five studies that compared HA-WBRT/HA-PCI and WBRT/PCI groups (risk difference = 0.01; 95% confidence interval [- 0.02, 0.03]; p = 0.63). 11 out of 19 studies included neurocognitive function testing. Significant differences were reported in overall cognitive function and memory and verbal learning 3-24 months post-RT. Differences in executive function were reported by one study, Brown et al., at 4 months. No studies reported differences in verbal fluency, visual learning, concentration, processing speed, and psychomotor speed at any timepoint. CONCLUSION: Current studies in HA-WBRT/HA-PCI showed low hippocampal relapse or metastasis rates. Significant differences in neurocognitive testing were most prominent in overall cognitive function, memory, and verbal learning. Studies were hampered by loss to follow-up.

A neuropsychologically-based intervention with increased follow-up support for employed women with multiple sclerosis: a pilot randomized controlled trial.

OBJECTIVE: To evaluate feasibility and acceptability of a neuropsychologically-based vocational intervention with increased follow-up support for women with multiple sclerosis. DESIGN: Single-blinded parallel-group randomized controlled trial with 12-month follow-up. SETTING: Tertiary-care multiple sclerosis center. PARTICIPANTS: Forty-nine employed women with multiple sclerosis meeting criteria on measures of cognitive dysfunction (Symbol Digit Modalities Test), fatigue (Fatigue Severity Scale), and/or depression (Beck Depression Inventory/Patient Health Questionnaire). INTERVENTIONS: Participants received either neuropsychological testing and phone feedback regarding findings and tailored recommendations (standard-care treatment), or testing, in-person feedback, and two calls from a care-coordinator (experimental treatment). MEASURES: Feasibility measures included enrollment and attrition rates, and compliance to recommendations at 12-months between groups. Acceptability was evaluated by participants' report of benefit from interventions. Secondary analyses included evaluation of symptom changes (cognition, fatigue, depression) from baseline to 12-months. RESULTS: Of 49 women meeting screening measure thresholds, 44 were randomized to treatment groups (attrition: standard-care = 8, experimental = 6), and 30 completed the study (standard-care = 14, experimental = 16). Recommendation adherence rates did not significantly differ between standard-care and experimental groups (31% vs 49%). However, 16/16 experimental participants at least partially completed given recommendations as compared to 8/14 in the standard-care group. Participants across groups (97%) reported benefit from participation. No significant differences in symptom outcomes between groups at 12-months. CONCLUSION: In-person feedback and care-coordinator calls were feasible and acceptable additions to a neuropsychological intervention and may serve to increase recommendation adherence. Given high drop-out rate, particularly prior to testing, future research may explore avenues to improve completion rates and maximize benefits of such interventions.

Relationship Between Anxiety and Cognition in Multiple Sclerosis: Implications for Treatment.

BACKGROUND: Anxiety, which is very prevalent in multiple sclerosis (MS) but understudied, has been shown to negatively affect cognition in many different populations. Slowed information processing speed underlies most cognitive impairments in MS, including verbal learning. The aim of this study was to look at how anxiety influences cognition-specifically processing speed and verbal learning-in MS. METHODS: Eligibility criteria were adults (≥18 years) who had a diagnosis of clinically definite MS and had participated in neuropsychological research projects. A retrospective medical record review was conducted on the neuropsychological testing data. Two hierarchical multiple regressions were conducted to determine the unique contributions of processing speed and anxiety on verbal learning in MS, after adjusting for demographic and disability variables. Two separate mediation analyses were conducted to determine the relationship between processing speed, verbal learning, and anxiety. RESULTS: Participants (N = 141) ranged in age from 18-91 years. Based on the multiple regression analyses, processing speed (ß = 0.55, ΔR 2 = 0.27, P < .001) and anxiety (ß = -0.34, ΔR 2 = 0.11, P < .001) were uniquely significant predictors of verbal learning. Based on the mediation analyses, there was a significant indirect effect of anxiety on verbal learning through processing speed (ab = -0.31, 95% CI = -0.60 to -0.09). There was also a significant indirect effect of processing speed on verbal learning through anxiety (ab = -0.05, 95% CI = 0.01 to 0.12). CONCLUSIONS: Results suggest a bidirectional relationship of anxiety and processing speed on verbal learning in MS. Anxiety has a significant effect on cognition and should not be overlooked. Interventions targeting anxiety may improve cognition in MS.