Improved neuropsychological outcomes following proton therapy relative to X-ray therapy for pediatric brain tumor patients.

BACKGROUND: Survivors of pediatric brain tumors are at risk for impaired development in multiple neuropsychological domains. The purpose of this study was to compare neuropsychological outcomes of pediatric brain tumor patients who underwent X-ray radiotherapy (XRT) versus proton radiotherapy (PRT). METHODS: Pediatric patients who underwent either XRT or PRT and received posttreatment age-appropriate neuropsychological evaluation-including measures of intelligence (IQ), attention, memory, visuographic skills, academic skills, and parent-reported adaptive functioning-were identified. Multivariate analyses were performed to assess differences in neuropsychological outcomes and included tests for interaction between treatment cohort and follow-up time. RESULTS: Between 1998 and 2017, 125 patients with tumors located in the supratentorial (17.6%), midline (28.8%), or posterior fossa (53.6%) compartments received radiation and had posttreatment neuropsychological evaluation. Median age at treatment was 7.4 years. The PRT patient cohort had higher estimated SES and shorter median time from radiotherapy completion to last neuropsychological evaluation (6.7 vs 2.6 y, P < 0.001). On multivariable analysis, PRT was associated with higher full-scale IQ (ß = 10.6, P = 0.048) and processing speed (ß = 14.4, P = 0.007) relative to XRT, with trend toward higher verbal IQ (ß = 9.9, P = 0.06) and general adaptive functioning (ß = 11.4, P = 0.07). Planned sensitivity analyses truncating follow-up interval in the XRT cohort re-demonstrated higher verbal IQ (P = 0.01) and IQ (P = 0.04) following PRT, with trend toward improved processing speed (P = 0.09). CONCLUSIONS: PRT is associated with favorable outcomes for intelligence and processing speed. Combined with other strategies for treatment de-intensification, PRT may further reduce neuropsychological morbidity of brain tumor treatment.

Morning glory disc anomaly and ipsilateral sporadic optic pathway glioma.

PURPOSE: To present a rare case of morning glory disc anomaly in association with an ipsilateral low grade glioma. OBSERVATIONS: A 5 year old male presented with a unilateral morning glory disc anomaly and an ipsilateral sporadic optic pathway glioma with chiasmal involvement. After a strict patching regimen his vision improved from 20/400 to 20/80. CONCLUSIONS AND IMPORTANCE: This report strengthens the recommendation for brain magnetic resonance imaging in patients with morning glory disc anomaly. Patching of the contralateral eye should be attempted since the role of amblyopia may be significant.

Blood-brain barrier-adapted precision medicine therapy for pediatric brain tumors.

Targeted chemotherapeutics provide a promising new treatment option in neuro-oncology. The ability of these compounds to penetrate the blood-brain barrier is crucial for their successful incorporation into patient care. "CNS Targeted Agent Prediction" (CNS-TAP) is a multi-institutional and multidisciplinary translational program established at the University of Michigan for evaluating the central nervous system (CNS) activity of targeted therapies in neuro-oncology. In this report, we present the methodology of CNS-TAP in a series of pediatric and adolescent patients with high-risk brain tumors, for which molecular profiling (academic and commercial) was sought and targeted agents were incorporated. Four of five of the patients had potential clinical benefit (partial response or stable disease greater than 6 months on therapy). We further describe the specific drug properties of each agent chosen and discuss characteristics relevant in their evaluation for therapeutic suitability. Finally, we summarize both tumor and drug characteristics that impact the ability to successfully incorporate targeted therapies into CNS malignancy management.