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

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.

Long-term effects of radiation therapy on white matter of the corpus callosum: a diffusion tensor imaging study in children.

BACKGROUND: Despite improving survival rates, children are at risk for long-term cognitive and behavioral difficulties following the diagnosis and treatment of a brain tumor. Surgery, chemotherapy and radiation therapy have all been shown to impact the developing brain, especially the white matter. OBJECTIVE: The purpose of this study was to determine the long-term effects of radiation therapy on white matter integrity, as measured by diffusion tensor imaging, in pediatric brain tumor patients 2 years after the end of radiation treatment, while controlling for surgical interventions. MATERIALS AND METHODS: We evaluated diffusion tensor imaging performed at two time points: a baseline 3 to 12 months after surgery and a follow-up approximately 2 years later in pediatric brain tumor patients. A region of interest analysis was performed within three regions of the corpus callosum. Diffusion tensor metrics were determined for participants (n=22) who underwent surgical tumor resection and radiation therapy and demographically matched with participants (n=22) who received surgical tumor resection only. RESULTS: Analysis revealed that 2 years after treatment, the radiation treated group exhibited significantly lower fractional anisotropy and significantly higher radial diffusivity within the body of the corpus callosum compared to the group that did not receive radiation. CONCLUSION: The findings indicate that pediatric brain tumor patients treated with radiation therapy may be at greater risk of experiencing long-term damage to the body of the corpus callosum than those treated with surgery alone.

Dose response to melatonin treatment for disordered sleep rhythm in a blind child.

We assessed the effectiveness and safety of melatonin in normalizing sleep in a 7-year-old blind child with a longstanding sleep/wake cycle disorder, using a double-masked, randomized treatment trial of placebo, a physiological dose (0.14 mg) and a supraphysiological dose (2.2 mg) of melatonin. Sleep onset and sleep offset were erratic and inappropriately early with placebo and low dose melatonin, but improved significantly on high dose melatonin. This report confirms that melatonin may be effective in treatment of disordered sleep rhythm in blind children, and illustrates a protocol that enables dose adjustment for optimal treatment response.