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Background: Advances in radiation treatment (RT), specifically volumetric planning with detailed dose and volumetric data for specific brain structures, have provided new opportunities to study neurobehavioral outcomes of RT in children treated for brain tumor. The present study examined the relationship between biophysical and physical dose metrics and neurocognitive ability, namely learning and memory, 2 years post-RT in pediatric brain tumor patients., Procedure: The sample consisted of 26 pediatric patients with brain tumor, 14 of whom completed neuropsychological evaluations on average 24 months post-RT. Prescribed dose and dose-volume metrics for specific brain regions were calculated including physical metrics (i.e., mean dose and maximum dose) and biophysical metrics (i.e., integral biological effective dose and generalized equivalent uniform dose). We examined the associations between dose-volume metrics (whole brain, right and left hippocampus), and performance on measures of learning and memory (Children's Memory Scale)., Results: Biophysical dose metrics were highly correlated with the physical metric of mean dose but not with prescribed dose. Biophysical metrics and mean dose, but not prescribed dose, correlated with measures of learning and memory., Conclusions: These preliminary findings call into question the value of prescribed dose for characterizing treatment intensity; they also suggest that biophysical dose has only a limited advantage compared to physical dose when calculated for specific regions of the brain. We discuss the implications of the findings for evaluating and understanding the relation between RT and neurocognitive functioning., (© 2018 Wiley Periodicals, Inc.)

Our objectives were to (1) investigate the feasibility of the use of the Japanese version of the Hopkins Verbal Learning Test-Revised (HVLT-R); (2) identify the clinical factors influencing the HVLT-R scores of patients undergoing whole-brain radiation therapy (WBRT); and (3) compare the neurocognitive function (NCF) after WBRT in different dose fractionation schedules. We administered the HVLT-R (Japanese version) before (baseline) and at four and eight months after WBRT in 45 patients who received either therapeutic (35Gy-in-14, n = 16; 30Gy-in-10, n = 18) or prophylactic (25Gy-in-10, n = 11) WBRT. Sixteen patients dropped out before the eight-month examination, due mostly to death from cancer. The Karnofsky Performance Status (KPS) 80-100 group had significantly higher baseline total recall (TR) scores ( p = 0.0053), delayed recall (DR) scores ( p = 0.012), and delayed recognition (DRecog) scores ( p = 0.0078). The patients aged ≤65 years also had significantly higher TR scores ( p = 0.030) and DRecog scores ( p = 0.031). The patients who underwent two examinations (worse-prognosis group) had significantly decreased DR scores four months after WBRT compared to the baseline ( p = 0.0073), and they were significantly more likely to have declined individual TR scores ( p = 0.0017) and DR scores ( p = 0.035) at four months. The eight-month HVLT-R scores did not significantly decline regardless of the WBRT dose fractionation. The baseline NCF was determined by age and KPS, and the early decline in NCF is characteristic of the worse-prognosis group., Competing Interests: The authors declare no conflict of interest.

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.

Purpose: The primary objective of this study was to examine whether children with low-grade glioma (LGG) or craniopharyngioma had impaired learning and memory after conformal radiation therapy (CRT). A secondary objective was to determine whether children who received chemotherapy before CRT, a treatment often used to delay radiation therapy in younger children with LGG, received any protective benefit with respect to learning., Methods and Materials: Learning and memory in 57 children with LGG and 44 children with craniopharyngioma were assessed with the California Verbal Learning Test-Children's Version and the Visual-Auditory Learning tests. Learning measures were administered before CRT, 6 months later, and then yearly for a total of 5 years., Results: No decline in learning scores after CRT was observed when patients were grouped by diagnosis. For children with LGG, chemotherapy before CRT did not provide a protective effect on learning. Multiple regression analyses, which accounted for age and tumor volume and location, found that children treated with chemotherapy before CRT were at greater risk of decline on learning measures than those treated with CRT alone. Variables predictive of learning and memory decline included hydrocephalus, shunt insertion, younger age at time of treatment, female gender, and pre-CRT chemotherapy., Conclusions: This study did not reveal any impairment or decline in learning after CRT in overall aggregate learning scores. However, several important variables were found to have a significant effect on neurocognitive outcome. Specifically, chemotherapy before CRT was predictive of worse outcome on verbal learning in LGG patients. In addition, hydrocephalus and shunt insertion in craniopharyngioma were found to be predictive of worse neurocognitive outcome, suggesting a more aggressive natural history for those patients., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: It is unclear whether the benefit of adding whole-brain radiation therapy (WBRT) to stereotactic radiosurgery (SRS) for the control of brain-tumours outweighs the potential neurocognitive risks. We proposed that the learning and memory functions of patients who undergo SRS plus WBRT are worse than those of patients who undergo SRS alone. We did a randomised controlled trial to test our prediction., Methods: Patients with one to three newly diagnosed brain metastases were randomly assigned using a standard permutated block algorithm with random block sizes to SRS plus WBRT or SRS alone from Jan 2, 2001, to Sept 14, 2007. Patients were stratified by recursive partitioning analysis class, number of brain metastases, and radioresistant histology. The randomisation sequence was masked until assignation, at which point both clinicians and patients were made aware of the treatment allocation. The primary endpoint was neurocognitive function: objectively measured as a significant deterioration (5-point drop compared with baseline) in Hopkins Verbal Learning Test-Revised (HVLT-R) total recall at 4 months. An independent data monitoring committee monitored the trial using Bayesian statistical methods. Analysis was by intention-to-treat. This trial is registered at www.ClinicalTrials.gov, number NCT00548756., Findings: After 58 patients were recruited (n=30 in the SRS alone group, n=28 in the SRS plus WBRT group), the trial was stopped by the data monitoring committee according to early stopping rules on the basis that there was a high probability (96%) that patients randomly assigned to receive SRS plus WBRT were significantly more likely to show a decline in learning and memory function (mean posterior probability of decline 52%) at 4 months than patients assigned to receive SRS alone (mean posterior probability of decline 24%). At 4 months there were four deaths (13%) in the group that received SRS alone, and eight deaths (29%) in the group that received SRS plus WBRT. 73% of patients in the SRS plus WBRT group were free from CNS recurrence at 1 year, compared with 27% of patients who received SRS alone (p=0.0003). In the SRS plus WBRT group, one case of grade 3 toxicity (seizures, motor neuropathy, depressed level of consciousness) was attributed to radiation treatment. In the group that received SRS, one case of grade 3 toxicity (aphasia) was attributed to radiation treatment. Two cases of grade 4 toxicity in the group that received SRS alone were diagnosed as radiation necrosis., Interpretation: Patients treated with SRS plus WBRT were at a greater risk of a significant decline in learning and memory function by 4 months compared with the group that received SRS alone. Initial treatment with a combination of SRS and close clinical monitoring is recommended as the preferred treatment strategy to better preserve learning and memory in patients with newly diagnosed brain metastases.

Repetitive transcranial magnetic stimulation (rTMS) of human cortex may disrupt or facilitate cortical activity. The aim of the present study was to investigate the consequences of rTMS applied over different cortical areas during various memory tasks, measuring immediate, working and episodic verbal memory. The study was performed in 16 right-handed healthy men. A double-blind, cross-over, within-subject repeated measures design was used. There were five rTMS conditions: baseline without stimulation, high frequency (HF) rTMS over right and left dorsolateral prefrontal cortex (DLPFC) and over right cerebellum, and low frequency (LF) parameters over left DLPFC. Digits forwards and backwards and letter-number sequencing of the Wechsler Adults Intelligence Scale (WAIS) were used to assess immediate and working verbal memory, and logical memory of the Rivermead Behavioural Memory Test was used to assess episodic memory encoding. An analysis of variance (ANOVA) for repeated measures in the scores of each memory task according to rTMS conditions was used. Significantly lower scores in the number of memory units of the episodic memory task were observed when rTMS high frequency parameters were applied over left DLPFC (P=0.009). No significant differences were found in the other memory subtype tasks analysed during the different rTMS conditions. These findings provide evidence for the significant role of the left DLPFC in episodic verbal memory processes.