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Background The objective of this study was to evaluate the contribution of radiation dose to different intracranial structures on changes in intellectual function for children with brain tumors. Methods We evaluated children with brain tumors treated from 2005-2017 who had longitudinal neuropsychological assessments and available photon dosimetric data (if RT given). Full scale intelligence quotient (FSIQ) and index scores were evaluated (perceptual reasoning [PRI], processing speed [PSI], verbal comprehension [VCI] and working memory [WMI]). Multivariable linear mixed effects models were used to model endpoints, with age at RT and dose to different brain regions as fixed effects and patient-specific random intercepts. P-values (p*) were adjusted for multiple comparisons. Results Sixty-nine patients were included, 56 of whom received RT. Median neuropsychological follow-up was 3.2 years. Right temporal lobe mean dose was strongly associated with decline in FSIQ (p* = 0.005); with each gray increase in mean dose, there was a decrease of 0.052 FSIQ points per year. Dose to 50% (D50) of the supratentorial brain was associated with decline in PSI (p* = 0.006) and WMI (p* = 0.001). Right and left hippocampus D50 were individually strongly associated with declines in VCI (p* = 0.009 for each). Presence of ventriculoperitoneal shunt decreased FSIQ by 10 points. Conclusions We reported associations between dosimetry to specific brain regions and intellectual outcomes, with suggested avoidance structures during RT planning. These models can help clinicians anticipate changes in neurocognition post-RT and guide selection of an optimal RT plan.

PURPOSE Hearing loss (HL) is a serious secondary effect of treatment for CNS and head-and-neck tumors in children. The goal of this study was to evaluate incidence and risk factors for HL in patients with multiple ototoxic exposures. PATIENTS AND METHODS We evaluated 340 ears from 171 patients with CNS or head-and-neck tumors treated with radiation, with or without chemotherapy, who had longitudinal audiologic evaluation. International Society of Pediatric Oncology-Boston grades were assigned to 2,420 hearing assessments. Multivariable weighted ordinal logistic regression was fitted to evaluate the effect of clinicopathologic features on HL. RESULTS Mean cochlea dose (odds ratio [OR] 1.04 per Gy, P < .001), time since radiotherapy (RT; OR 1.21 per year, P < .001), cisplatin dose (OR 1.48 per 100 mg/m2, P < .001), and carboplatin dose (OR 1.41 per 1,000 mg/m2, P = .002) were associated with increasing International Society of Pediatric Oncology-Boston grade of HL. There was no synergistic effect of RT and cisplatin (interaction term, P = .53) or RT and carboplatin (interaction term, P = .85). Cumulative incidence of high-frequency HL (> 4 kHz) was 50% or greater at 5 years after RT if mean cochlea dose was > 30 Gy, while incidence of HL across all frequencies continued to increase beyond 5 years after RT. CONCLUSION Children treated with radiation and chemotherapy experience a high incidence of HL over time, with associations found between more severe HL and cisplatin or carboplatin dose as well as mean cochlea dose. Mean cochlea dose of ≤ 30 Gy is proposed as a goal to reduce the risk of HL; a lower threshold (20-25 Gy) may be considered in patients receiving platinum chemotherapy to reduce cumulative HL burden.