Hippocampal neural stem-cell injury during whole-brain radiotherapy (WBRT) may play a role in memory decline. Intensity-modulated radiotherapy can be used to avoid conformally the hippocampal neural ...stem-cell compartment during WBRT (HA-WBRT). RTOG 0933 was a single-arm phase II study of HA-WBRT for brain metastases with prespecified comparison with a historical control of patients treated with WBRT without hippocampal avoidance.
Eligible adult patients with brain metastases received HA-WBRT to 30 Gy in 10 fractions. Standardized cognitive function and quality-of-life (QOL) assessments were performed at baseline and 2, 4, and 6 months. The primary end point was the Hopkins Verbal Learning Test-Revised Delayed Recall (HVLT-R DR) at 4 months. The historical control demonstrated a 30% mean relative decline in HVLT-R DR from baseline to 4 months. To detect a mean relative decline ≤ 15% in HVLT-R DR after HA-WBRT, 51 analyzable patients were required to ensure 80% statistical power with α = 0.05.
Of 113 patients accrued from March 2011 through November 2012, 42 patients were analyzable at 4 months. Mean relative decline in HVLT-R DR from baseline to 4 months was 7.0% (95% CI, -4.7% to 18.7%), significantly lower in comparison with the historical control (P < .001). No decline in QOL scores was observed. Two grade 3 toxicities and no grade 4 to 5 toxicities were reported. Median survival was 6.8 months.
Conformal avoidance of the hippocampus during WBRT is associated with preservation of memory and QOL as compared with historical series.
Whole brain radiotherapy (WBRT) is associated with memory dysfunction. As part of NRG Oncology RTOG 0933, a phase II study of WBRT for brain metastases that conformally avoided the hippocampal stem ...cell compartment (HA-WBRT), memory was assessed pre- and post-HA-WBRT using both traditional and computerized memory tests. We examined whether the computerized tests yielded similar findings and might serve as possible alternatives for assessment of memory in multi-institution clinical trials. Adult patients with brain metastases received HA-WBRT to 30 Gy in ten fractions and completed Hopkins Verbal Learning Test-Revised (HVLT-R), CogState International Shopping List Test (ISLT) and One Card Learning Test (OCLT), at baseline, 2 and 4 months. Tests’ completion rates were 52–53 % at 2 months and 34–42 % at 4 months. All baseline correlations between HVLT-R and CogState tests were significant (p ≤ 0.003). At baseline, both CogState tests and one component of HVLT-R differentiated those who were alive at 6 months and those who had died (p ≤ 0.01). At 4 months, mean relative decline was 7.0 % for HVLT-R Delayed Recall and 18.0 % for ISLT Delayed Recall. OCLT showed an 8.0 % increase. A reliable change index found no significant changes from baseline to 2 and 4 months for ISLT Delayed Recall (z = −0.40, p = 0.34; z = −0.68, p = 0.25) or OCLT (z = 0.15, p = 0.56; z = 0.41, p = 0.66). Study findings support the possibility that hippocampal avoidance may be associated with preservation of memory test performance, and that these computerized tests also may be useful and valid memory assessments in multi-institution adult brain tumor trials.
Background
: Children with heavy prenatal alcohol exposure have well documented deficits in overall cognitive ability. Recently, attention has turned to the executive function (EF) domain in this ...population. Until recently, comprehensive measures of EF have not been available within one test battery. This study used a battery of tests to assess four domains of EF in alcohol‐exposed children.
Methods
: The Delis‐Kaplan Executive Function Scale was used to evaluate EF in 18 children with heavy prenatal alcohol exposure, with and without a diagnosis of fetal alcohol syndrome (FAS), and 10 nonexposed controls. Children ranged in age from 8 to 15 years. Measures from four domains of executive functioning were analyzed: planning ability, cognitive flexibility, selective inhibition, and concept formation and reasoning. Tasks consisted of primary EF measures as well as measures of secondary component skills.
Results
: Alcohol‐exposed children were deficient on EF measures compared with nonexposed controls. Furthermore, in most cases, children with and without the FAS diagnosis did not differ from one another. These deficits were not entirely explainable by concomitant deficits on component skills. Specific impairments were identified within the domains of planning and response inhibition, with additional deficits in thinking and flexibility.
Conclusions
: Deficits in executive functioning were observed in alcohol‐exposed children with or without the diagnosis of FAS and in the absence of mental retardation. Performance on these EF tasks provides insight into the cognitive processes driving overall performance and has implications for adaptive and daily functions. These results arc consistent with anecdotal and empirical reports of deficits in behavioral control and with neuroanatomical evidence of volumetric reductions in structures within the frontal‐subcortical system in children with heavy prenatal alcohol exposure.
Neurocognitive function (NCF) impairment is an important component of primary and metastatic brain tumors and their therapeutic interventions. As a result, modern clinical trials of cranial ...irradiation for adult cancer patients have incorporated NCF testing as a primary or secondary end point. In doing so, these clinical trials have provided a novel insight into our understanding of the NCF effects of cranial irradiation and brain tumor progression. In this article, we review these clinical trials both in terms of the trial findings and in terms of the types of NCF tests used in these trials. We also provide an introduction to the strengths and limitations of these NCF tests, as well as expert commentary on the current status and future directions of NCF testing in brain tumor trials.
Abstract
Background
Cognitive function is an important outcome measure in many brain tumor clinical trials, and investigators are interested in employing the most efficient methods of cognitive ...assessment for this purpose. Computerized testing can be appealing because of the perceived ease of use and electronic data generated. Traditional tests may have the advantage of accumulated validity evidence and comparability across historic trials.
Methods
We evaluated feasibility of a Cogstate battery in 39 patients with high-grade glioma, and compared it with a commonly used paper-and-pencil battery.
Results
Both batteries were well tolerated and rated equally likeable. Correlations between the batteries were low to low-moderate. More patients showed impairment at baseline and decline across trials on traditional tests.
Conclusions
Both batteries were well tolerated, but the most complicated tasks (from both batteries) could not be completed by all subjects. Preliminary validity evidence for the Cogstate tasks was mixed, but a larger sample is needed.
The objective of this study was to acquire process information, clinician and client feedback during implementation of a routine suicide risk screening program for outpatients with serious mental ...disorders. We studied implementation of a suicide-screening tool in a large public mental health outpatient facility in New York City. Most clinical staff who provided an opinion indicated screening was useful, feasible and helpful; most clients did not mind screening. Facilitators to program implementation included administrative support and ease of use. Barriers included consent, misperceptions, and concerns regarding potential liability. It is feasible to implement a suicide-screening tool in a public outpatient clinic. However, even experienced clinicians harbor unfounded myths. Effective large scale use will require vigorous training and oversight.
To test feasibility of a routine screening tool and to examine factors associated with suicide and suicidal behaviors. Subjects included outpatients with serious mental disorders. One hundred and ...sixteen clinicians routinely screened randomly selected adult clients for suicide risk during a 6-month period. Forty-three (9%) clients reported thoughts to hurt/kill self (screened positive), which spurred enhanced clinical intervention. There was no increase in frequency of suicide attempts. A history of multiple suicide attempts, recent stressful events, and present hopelessness were associated with a positive risk screen, clinician rating of risk, or altered treatment plan. It is feasible to safely implement a brief routine screening process in psychiatric outpatient settings. Future research is needed to determine overall utility for routine screening.
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