Dose–volume metrics and their relation to memory performance in pediatric brain tumor patients: A preliminary study

Raghubar, Kimberly P.; Lamba, Michael; Cecil, Kim M.; Yeates, Keith Owen; Mahone, E. Mark; Limke, Christina; Grosshans, David R.; Beckwith, Travis; Ris, M. Douglas

doi:10.1002/pbc.27245

Cited by 10 publications

(10 citation statements)

References 46 publications

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“…In particular, processing speed showed the greatest vulnerability post-PRT CSI, consistent with XRT outcomes research associating higher RT doses to larger volumes of brain with less favorable neurocognitive outcomes. 6,[28][29][30][31] Working memory vulnerability was also identified. The solidly stable performance in verbal and perceptual reasoning domains in this group suggests that the decline observed in FSIQ is likely driven by declines in processing speed and working memory.…”

Section: Discussionmentioning

confidence: 99%

Prospective, longitudinal comparison of neurocognitive change in pediatric brain tumor patients treated with proton radiotherapy versus surgery only

et al. 2019

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Background. Proton radiotherapy (PRT) reduces the volume of normal tissue receiving radiation dose, which may lead to better neurocognitive outcomes. We examined change in neurocognitive scores over time in pediatric brain tumor patients treated with proton craniospinal irradiation (CSI), proton focal RT, or surgery only. Methods. Patients received annual neurocognitive evaluations for up to 6 years. We examined Full Scale IQ (FSIQ), Verbal Comprehension Index (VCI), Perceptual Reasoning Index (PRI), Working Memory Index (WMI), and Processing Speed Index (PSI) scores. General linear mixed models examined change in scores over time by treatment group, adjusting for significant covariates. Results. Scores from 93 patients treated between 2012 and 2017 (22 proton CSI, 31 proton focal, and 40 surgery only) were examined. Treatment groups were similar on gender (51.6% male), age at treatment (median = 9.7 y), and length of follow-up (median = 2.9 y). The surgery only group had proportionately more gliomas (P < 0.001), and the proton CSI group had more infratentorial tumors (P = 0.001) and higher total RT dose (P = 0.004). The proton focal and surgery only groups exhibited stable neurocognitive scores over time across all indexes (all P > 0.05). In the proton CSI group, WMI, PSI, and FSIQ scores declined significantly (P = 0.036, 0.004, and 0.017, respectively), while VCI and PRI scores were stable (all P > 0.05). Conclusions. Focal PRT was associated with stable neurocognitive functioning into survivorship. Outcomes were similar whether patients received focal PRT or no radiotherapy, even in neurocognitive domains known to be particularly radiosensitive. Proton CSI emerged as a neurocognitive risk factor, consistent with photon outcomes research.

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Section: Discussionmentioning

confidence: 99%

Prospective, longitudinal comparison of neurocognitive change in pediatric brain tumor patients treated with proton radiotherapy versus surgery only

et al. 2019

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“… 26 Findings from a cohort of 14 pediatric patients with brain tumors treated with proton therapy with 2 years of follow-up suggested that word-pair delayed recall was associated with both left and right hippocampal doses. 27 There are also data suggesting that the hippocampal volume is reduced in survivors of pediatric brain tumors and that this volume reduction is associated with a decline in memory. 28 …”

Section: Discussionmentioning

confidence: 99%

Association between hippocampal dose and memory in survivors of childhood or adolescent low-grade glioma: a 10-year neurocognitive longitudinal study

Acharya

Ashford

et al. 2019

Neuro-Oncology

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Background Hippocampal avoidance has been suggested as a strategy to reduce short-term memory decline in adults receiving whole-brain radiation therapy (RT). The purpose of this study was to determine whether the hippocampal dose in children and adolescents undergoing RT for low-grade glioma was associated with memory, as measured by verbal recall. Methods Eighty patients aged at least 6 years but less than 21 years with low-grade glioma were treated with RT to 54 Gy on a phase II protocol. Patients underwent age-appropriate cognitive testing at baseline, 6 months posttreatment, yearly through 5 years posttreatment, year 7 or 8, and year 10 posttreatment. Random coefficient models were used to estimate the longitudinal trends in cognitive assessment scores. Results Median neurocognitive follow-up was 9.8 years. There was a significant decline in short-delay recall (slope = −0.01 standard deviation [SD]/year, P < 0.001), total recall (slope = −0.09 SD/y, P = 0.005), and long-delay recall (slope = −0.01 SD/y, P = 0.002). On multivariate regression, after accounting for hydrocephalus, decline in short-delay recall was associated with the volume of right (slope = −0.001 SD/y, P = 0.019) or left hippocampus (slope = −0.001 SD/y, P = 0.025) receiving 40 Gy (V40 Gy). On univariate regression, decline in total recall was only associated with right hippocampal dosimetry (V40 Gy slope = −0.002, P = 0.025). In children <12 years, on univariate regression, decline in long-delay recall was only associated with right (V40 Gy slope = −0.002, P = 0.013) and left (V40 Gy slope = −0.002, P = 0.014) hippocampal dosimetry. Conclusion In this 10-year longitudinal study, greater hippocampal dose was associated with a greater decline in delayed recall. Such findings might be informative for radiation therapy planning, warranting prospective evaluation.

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“…53 Additionally, CRT overlap with the hippocampus further portends a poorer neurocognitive prognosis in survivors, similar to anticipated toxic effects of chemotherapy on the hippocampus. 46,54,55 Proton-based CRT is one modifying factor that continues to undergo investigation as a means to decrease CRT-related neurocognitive injury. Proton CRT has less radiation scatter and ideally treats a more targeted volume with decreased radiation exposure to surrounding healthy tissue.…”

Section: Neurocognitive Injury In Relationship With Radiationmentioning

confidence: 99%

Neurocognitive Outcomes in Children with Brain Tumors

Kline

Mueller

2020

Semin Neurol

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Brain tumors are the most common solid tumor in childhood, and although survival outcomes continue to improve, survival is frequently offset by devastating late effects from tumor and treatment. The long-term effects of brain tumors and the therapy necessary to treat them range from sensory and neuroendocrine abnormalities to neurocognitive deficits leading to inferior quality of life. The multifactorial neurocognitive injury is one of the most broadly impacting and challenging late effects to predict and subsequently treat. Certain treatment modalities, such as intrathecal methotrexate and radiation, have been shown to be associated with poor neurocognition; however, long-term outcomes remain highly variable. There are efforts underway to investigate how to better predict, identify, and manage such neurocognitive injury in survivors of pediatric brain tumors. Herein, we focus on the current knowledge of neurocognitive outcomes and potential treatment strategies for this high-risk group.

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Dose–volume metrics and their relation to memory performance in pediatric brain tumor patients: A preliminary study

Cited by 10 publications

References 46 publications

Prospective, longitudinal comparison of neurocognitive change in pediatric brain tumor patients treated with proton radiotherapy versus surgery only

Prospective, longitudinal comparison of neurocognitive change in pediatric brain tumor patients treated with proton radiotherapy versus surgery only

Association between hippocampal dose and memory in survivors of childhood or adolescent low-grade glioma: a 10-year neurocognitive longitudinal study

Neurocognitive Outcomes in Children with Brain Tumors

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